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Sample records for juvenile onset diabetes

  1. Hypoglycemia and hemostatic parameters in juvenile-onset diabetes

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Nielsen, J D;

    1980-01-01

    Hypoglycemia was induced by intravenous infusion of insulin in six juvenile-onset diabetic subjects. Hemostatic parameters were assessed before insulin infusion and 0, 1, and 2 h after discontinuation of insulin infusion. The onset of hypoglycemia coincided with an enhancement of ADP-induced plat......Hypoglycemia was induced by intravenous infusion of insulin in six juvenile-onset diabetic subjects. Hemostatic parameters were assessed before insulin infusion and 0, 1, and 2 h after discontinuation of insulin infusion. The onset of hypoglycemia coincided with an enhancement of ADP...... potentially lead to intravascular coagulation in juvenile-onset diabetic patients....

  2. Genetic correlates of early accelerated infant growth associated with juvenile-onset type 1 diabetes

    NARCIS (Netherlands)

    Kharagjitsingh, A.V.; de Ridder, M.A.J.; Alizadeh, B.Z.; Veeze, H.J.; Bruining, G.J.; Roep, B.O.; Koeleman, Bobby P.C.

    2012-01-01

    Objective: We previously showed that accelerated growth predisposing to development of childhood-onset type 1 diabetes (T1D) is restricted to the first year after birth. We assessed whether this phenomenon of increased early growth is associated with variants of two genes, insulin-like growth factor

  3. Genetic correlates of early accelerated infant growth associated with juvenile-onset type 1 diabetes

    NARCIS (Netherlands)

    Kharagjitsingh, Av; de Ridder, Maj; Alizadeh, Bz; Veeze, Hj; Bruining, Gj; Roep, Bo; Koeleman, Bobby Pc

    2012-01-01

    OBJECTIVE: We previously showed that accelerated growth predisposing to development of childhood-onset type 1 diabetes (T1D) is restricted to the first year after birth. We assessed whether this phenomenon of increased early growth is associated with variants of two genes, insulin-like growth factor

  4. Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus

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    Khosla P

    1994-01-01

    Full Text Available Thirty-five patients of insulin-dependent diabetes mellitus (IDDM were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI levels and serum C-peptide radioimmunoreactivity (CPR as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM

  5. Late Onset Juvenile Xanthogranuloma

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    Punithwavathy K

    1999-01-01

    Full Text Available A 19 year old female was seen with multiple skin coloured and hyperpigmented macules, discrete as well as grouped papules and nodules of varying sizes distributed over the face, neck, extensor and flexor aspects of both upper and lower extremities including joints. The trunk was spared. Some of the lesions showed features of spontaneous regression. Investigations confirmed the diagnosis of juvenile xanthogranuloma. Lesions regressed satisfactorily with liquid nitrogen cryotherapy.

  6. Enhanced Apoptosis of Monocytes from Complication-Free Juvenile-Onset Diabetes Mellitus Type 1 May Be Ameliorated by TNF-α Inhibitors

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    Jolanta Myśliwska

    2014-01-01

    Full Text Available Diabetes mellitus type 1 is associated with an enhanced apoptosis of different cells and tissues, accelerating occurrence of diabetic microvascular complications. The aim of our study was to determine spontaneous apoptotic potential of the monocyte subsets in juvenile-onset complication-free diabetes mellitus type 1 and to compare them with the corresponding values of the healthy. Moreover, we wanted to assess effects of TNF-R1 blocking agents and those of general TNF-α blocker (Infliximab on spontaneous apoptosis of monocytes. Sixty randomly selected DM1 patients (14.5 ± 3.2 years and 30 healthy (13.5 ± 2.8 years volunteers were enrolled in the study. Our results indicate that three monocyte subsets are distinguishable in the groups of young diabetic patients and the healthy, similarly to in the blood of adults. DM1 patients were characterized by higher values of apoptotic monocytes than the healthy. The manipulation with drugs inhibiting TNF-R1 expression diminished the pool of CD16+ apoptotic monocytes. Infliximab reduced the apoptotic CD16− cells. In conclusion, diabetes mellitus type 1 is associated with greater apoptosis of three monocyte subsets which may contribute to the development of microvascular complications. TNF-α modifiers appear to ameliorate monocyte apoptosis. They may be useful for controlling excessive monocyte apoptosis in diabetic patients.

  7. Juvenile Diabetes and Rehabilitation Counseling.

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    Stone, J. Blair; Gregg, Charles H.

    1981-01-01

    Severe complications of diabetes are more likely to occur with the juvenile diabetic and problems of psychosocial adjustment are recurring and difficult. Implications for the rehabilitation counselor are discussed in terms of employment considerations, the effects of complications, genetic counseling, and cooperation with other professionals.…

  8. Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India

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    C Shivaprasad

    2014-01-01

    Full Text Available Introduction: Zinc transporter-8 (ZnT8 is an islet cell secretory granule membrane protein recently identified as an autoantigen in type 1 diabetes (T1D. The aim of this study was to estimate the prevalence of antibodies to ZnT8 (ZnT8A in juvenile onset T1D and to determine the utility of ZnT8A as an independent marker of autoimmunity either alone in antibody-negative subjects or in conjunction with glutamic acid decarboxylase (GAD and insulinoma-2 antigen antibodies (GADA and IA2A. Research Design: ZnT8A, GADA, and IA2A were measured in sera of consecutive T1D patients (n = 88, age range 2-18 years within 4 years of diagnosis and 88 sex-matched controls. Results: The prevalences of GADA, ZnT8a, and IA2A were 64.7%, 31.8% and 19.3%, respectively. In newly diagnosed patients, the frequency of ZnT8A was 45%. ZnT8A were positive in 26% of patients negative for both GADA and IA2A. IA2A were positive only in two patients who were negative for other two antibodies. Combined use of ZnT8A and GADA could detect 97% of antibody positive patients. In receiver operating characteristic (ROC analysis, the performances of GADA and ZnT8As were better than that of IA2A; and AUCs of GADA, ZnT8A, and IA2A for the prediction of T1D were 0.8, 0.65, and 0.59, respectively. Conclusions: ZnT8A complements GADA and increases the diagnostic sensitivity for detection of autoimmunity in juvenile-onset T1D. Inclusion of ZnT8A increases the proportion of patients with antibody positivity to nearly 80%. ZnT8A can replace IA2A as a serological marker for autoimmunity in Indian T1D patients without loss of sensitivity and specificity.

  9. Distinct synovial immunopathologic characteristics of juvenile-onset spondylarthritis and other forms of juvenile idiopathic arthritis

    NARCIS (Netherlands)

    E. Kruithof; V. van den Bossche; L. de Rycke; B. Vandooren; R. Joos; J.D. Canete; P.P. Tak; A.M.H. Boots; E.M. Veys; D. Baeten

    2006-01-01

    Objective. To characterize the synovial immunopathologic features of juvenile-onset spondylarthritis (SpA) in relation to adult SpA and other forms of juvenile idiopathic arthritis (JIA). Methods. Synovial biopsy samples were obtained from 10 patients with juvenile-onset SpA, 23 with adult SpA, 19 w

  10. Systemic-onset juvenile idiopathic arthritis.

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    Cimaz, Rolando

    2016-09-01

    Systemic-onset juvenile idiopathic arthritis (SoJIA) is a systemic inflammatory disease which has up to now been classified as a category of juvenile idiopathic arthritis. However, in this context, systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that it may rather be part of the spectrum of autoinflammatory disorders. The disease is in fact unique with regard to the other JIA categories, in terms of clinical manifestations, prognosis, and response to conventional immunosuppressant therapies. It is characterized clinically by fever, lymphadenopathy, arthritis, rash, and serositis. IL-1 and IL-6 play a major role in the pathogenesis of SoJIA, and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. However, complications of SoJIA, including macrophage activation syndrome, limitations in functional outcome by arthritis and long-term damage from chronic inflammation continue to be a major issue in patients' care. Recent advances on the pathogenesis and treatment have revolutionized the care and prognosis of this potentially life-threatening pediatric condition.

  11. Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep

    OpenAIRE

    Bloor, Ian D.; Sébert, Sylvain P.; Saroha, Vivek; Gardner, David S.; Keisler, Duane H.; Budge, Helen; Symonds, Michael E.; Mahajan, Ravi P.

    2013-01-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissu...

  12. Metabolic responses to hypoglycemia in juvenile diabetics

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Krarup, T;

    1980-01-01

    Glucagon and metabolic responses to insulin-induced hypoglycemia were studied in seven juvenile diabetics, age 31 +/- 2 years (mean and S.E.M.), duration of diabetes 17 +/- 3 years, with diabetic autonomic neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation and...... in both patient groups. Metabolic responses to hypoglycemia were also similar in the two patient groups. In conclusion, diabetic autonomic neuropathy has no effect on glucagon and metabolic responses to hypoglycemia in juvenile, insulin-treated diabetics....

  13. AA amyloidosis associated with systemic-onset juvenile idiopathic arthritis.

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    Saha, Abhijeet; Chopra, Yogiraj; Theis, Jason D; Vrana, Julie A; Sethi, Sanjeev

    2013-10-01

    We report a 12-year-old boy with nephrotic syndrome due to renal AA amyloidosis. The AA amyloidosis was associated with a 3-year history of systemic-onset juvenile idiopathic arthritis. The presence of serum amyloid A protein was confirmed by laser microdissection of Congo Red-positive glomeruli and vessels followed by liquid chromatography and tandem mass spectrometry; this analysis excluded hereditary and familial amyloidosis. Aggressive management of the systemic-onset juvenile idiopathic arthritis resulted in improvement in clinical and laboratory parameters. The case represents an unusual cause of nephrotic syndrome in children. Early diagnosis of renal amyloidosis and management of systemic-onset juvenile idiopathic arthritis is paramount to preventing progression of kidney disease.

  14. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

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    Mirian S. Tamashiro

    2011-01-01

    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

  15. Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

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    Bloor, Ian D; Sébert, Sylvain P; Saroha, Vivek; Gardner, David S; Keisler, Duane H; Budge, Helen; Symonds, Michael E; Mahajan, Ravi P

    2013-10-01

    Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

  16. Mucormycosis associated with juvenile diabetes

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    SVSG Nirmala

    2011-01-01

    Full Text Available Mucormycosis is one of the most rapidly progressing and lethal form of fungal infections in humans which usually begins in the nose and paranasal sinuses. The fungus assaults the arteries, leading to thrombosis that subsequently causes necrosis of hard and soft tissues. The purpose of this article is to describe a rare case of maxillary necrosis due to mucormycosis in a 12-year-old diabetic patient and emphasizes on early diagnosis and timely management of this potentially fatal fungal infection.

  17. Juvenile onset ankylosing spondylitis with ankylosing tarsitis: a rare combination.

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    Siddiq, A B; Hasan, S A; Abdullah, A M; Azad, S A; Khan, E H; Khasru, M R

    2012-01-01

    Ankylosing spondylitis is the most common whereas ankylosing tarsitis is the least common subgroup of juvenile onset spondyloarthritides. In our recent study a male presented with ankle joint pain and swelling with limited movements and characteristic radiological changes including; periarticular swelling, thickened heel pad, hyperostosis and reduced ankle, calcaneo-cuboid and talo-navicular joint space for ankylosing tarsitis. He also had persistent inflammatory low back pain with radiological sacroilitis satisfying the clinical features for ankylosing spondylitis. The patient was treated with different anti-inflammatory agents including intra-articular methyl-prednisolone with short-term relief. Associated back pain was improved with spine mobilizing exercise.

  18. Infantile onset diabetes mellitus in developing countries - India

    OpenAIRE

    Varadarajan, Poovazhagi

    2016-01-01

    Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes...

  19. Complicated uveitis in late onset juvenile idiopathic psoriatic arthritis.

    Science.gov (United States)

    Bravo Ljubetic, L; Peralta Calvo, J; Larrañaga Fragoso, P

    2016-04-01

    A 6 year-old girl with juvenile psoriatic arthritis (JPsA) and bilateral complicated anterior uveitis developed several ocular complications that required 5 surgical procedures. Despite the aggressive course of ocular inflammation, her visual acuity remained good. Arthritis (main criterion for the diagnosis of JPsA) appeared years after ocular involvement. She showed a good anti-tumour necrosis factor initial response. The definitive diagnosis of JPsA was established years after the onset of symptoms. In addition, the patient maintained a good visual acuity, despite its complicated disease course. Finally, she showed a good clinical response to adalimumab. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  20. A case of adult onset disseminated juvenile xanthogranuloma

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    Havva Hilal Ayvaz

    2016-01-01

    Full Text Available Juvenile xanthogranuloma (JX is a rare, benign, non-Langerhans histiocytic proliferative disease that etiology is unknown. It is usually seen in children and infants. JX in adult is very rare. A 41-year-old female patient was admitted to our clinic with papules on her face, torso and extremities. A few lesions had occured 3 years ago on her face, they disseminated all over her body after having a traffic accident one year ago which for she had operations and she also concurrently was diagnosed asdiabetes mellitus (DM. Based on clinical and histopathological findings, the diagnosis of JX was made. There is no systemic involvement of JX detected. JX seen in adults are very rare and usually associated with hematological malignancy. The present case is a rare adult onset disseminated JX case without malignancy

  1. Prospective Prediction of Juvenile Homicide/Attempted Homicide among Early-Onset Juvenile Offenders

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    Baglivio, Michael T.; Wolff, Kevin T.

    2017-01-01

    While homicide perpetrated by juveniles is a relatively rare occurrence, between 2010 and 2014, approximately 7%–8% of all murders involved a juvenile offender. Unfortunately, few studies have prospectively examined the predictors of homicide offending, with none examining first-time murder among a sample of adjudicated male and female youth. The current study employed data on 5908 juvenile offenders (70% male, 45% Black) first arrested at the age of 12 or younger to prospectively examine predictors of an arrest for homicide/attempted homicide by the age of 18. Among these early-onset offenders, males, Black youth, those living in households with family members with a history of mental illness, those engaging in self-mutilation, and those with elevated levels of anger/aggression (all measured by age 13) were more likely to be arrested for homicide/attempted homicide by age 18. These findings add to the scant scientific literature on the predictors of homicide, and illustrate potential avenues for intervention. PMID:28212340

  2. Prospective Prediction of Juvenile Homicide/Attempted Homicide among Early-Onset Juvenile Offenders

    Directory of Open Access Journals (Sweden)

    Michael T. Baglivio

    2017-02-01

    Full Text Available While homicide perpetrated by juveniles is a relatively rare occurrence, between 2010 and 2014, approximately 7%–8% of all murders involved a juvenile offender. Unfortunately, few studies have prospectively examined the predictors of homicide offending, with none examining first-time murder among a sample of adjudicated male and female youth. The current study employed data on 5908 juvenile offenders (70% male, 45% Black first arrested at the age of 12 or younger to prospectively examine predictors of an arrest for homicide/attempted homicide by the age of 18. Among these early-onset offenders, males, Black youth, those living in households with family members with a history of mental illness, those engaging in self-mutilation, and those with elevated levels of anger/aggression (all measured by age 13 were more likely to be arrested for homicide/attempted homicide by age 18. These findings add to the scant scientific literature on the predictors of homicide, and illustrate potential avenues for intervention.

  3. Diabetic Retinopathy: Nature and Extent.

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    Coughlin, W. Ronald; Patz, Arnall

    1978-01-01

    The authors discuss the incidence and prevalence of diabetic retinopathy in juvenile and maturity onset diabetics, background and proliferative retinopathy, and current modalities of treatment. (Author)

  4. Age of crime onset and psychopathic traits in female juvenile delinquents.

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    Pechorro, Pedro; Gonçalves, Rui Abrunhosa; Marôco, João; Nunes, Cristina; Jesus, Saul Neves

    2014-09-01

    The aim of this study was to analyze the role of psychopathic traits in the age of crime onset of female juvenile delinquents. Using a sample of 132 young females from the Juvenile Detention Centers of the Portuguese Ministry of Justice and from schools in the Lisbon region, a group of early crime onset (n = 44), a group of late crime onset (n = 44), and a nondelinquent school group (n = 44) were formed. Results showed that early crime onset participants score higher on psychopathy measures, self-reported delinquency, and crime seriousness than late crime onset participants and school participants. Psychopathic-traits scores were significantly associated with age of crime onset, age at first trouble with the law, and frequency and seriousness of crime.

  5. New-onset diabetes mellitus after kidney transplantation in Denmark

    DEFF Research Database (Denmark)

    Hornum, Mads; Jørgensen, Kaj Anker; Hansen, Jesper Melchior;

    2010-01-01

    This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients.......This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients....

  6. Norwegian Childhood Diabetes Registry: Childhood onset diabetes in Norway 1973-2012

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    Torild Skrivarhaug

    2013-06-01

    Full Text Available The Norwegian Childhood Diabetes Registry (NCDR is a prospective, population-based, nationwide registry which systematically register all incident cases of childhood diabetes, and systematically monitors the outcome of diabetes care in children and adolescents. NCDR includes data on childhood onset diabetes since 1973, and diabetes care outcome since 2001. NCDR was founded with the following objectives: To improve the diagnostics, classifications and treatment of childhood-onset diabetes, surveillance of incidence of diabetes in children and adolescents, surveillance of quality of diabetes care in Norwegian paediatric departments, and to stimulate to research in diabetes.

  7. Self-control with urinalysis in juvenile diabetes.

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    Ludvigsson, J; Svensson, P G

    1979-11-01

    Urinary glucose excretion reflects the blood glucose levels and is therefore recommended and used as a relevant and practical method for self-control in juvenile diabetes. The purpose of this study was to estimate the attitudes of diabetic children and their parents towards such daily urinalysis. In 1975 69 juvenile diabetics 6--18 years old and their parents were studied and three years later another 69 patients were added. Standardized interviews and questionnaires were used. Only 3 out of 138 patients refused to test their urine regularly and to write down their results in the diary. The results indicate that a great majority of the patients and the parents easily accept the self-testing method and regard it as a valuable tool in the management of the disease. Almost nobody experienced the urine tests as a psychological problem.

  8. Clinical and genetic study of a juvenile-onset Huntington disease

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    HAO Ying

    2012-06-01

    Full Text Available Background Huntington's disease (HD is an autosomal dominant hereditary progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dementia, cognitive and affective impairment. There are selective neural cell loss and atrophy in the caudate and putamen. Dr. George Huntington firstly described the disease accurately and insightfully, which led to a widespread recognition of the inherited chorea that now bears his name. Huntington disease gene (IT15 locus on chromosome 4p16.3, and encompasses 67 exons with a trinucleotide repeat (CAG in the first exon. The CAG repeat length is highly polymorphic in the population and expanded on at least one chromosome of individuals with HD. Clinically, patient with HD are often onset in adulthood. Juvenile-onset HD is relatively rare. Adult-onset HD patients usually have a CAG expansion from 40 to 55 whereas those with juvenile-onset greater than 60 which are often inherited from the father. We investigated the clinical features of a juvenile-onset case with Huntington disease and dynamic mutation of his family. Methods The CAG repeats of IT15 gene were detected using polymerase chain reaction and capillary electrophoresis in 115 individuals with preliminary diagnosis as Huntington disease. The repeat numbers of some samples carried expanded or intermediate alleles were verified by the pMD18-T vector clone sequencing. Results Fragment analysis showed that one juvenile-onset case presenting with cognitive dysfunction and hypokinesis carried 15/68 CAG repeats of IT15. His father carried 17/37 and mother carried 15/17. Conclusion 1 The juvenile-onset case of HD presented with different clinical features compared with adult-onset cases. The typical signs of adult-onset cases include progressive chorea, rigidity and dementia. The most common sign of juvenile-onset Huntington disease is cognitive decline. 2 The dynamic mutation of IT15 gene expansion of the CAG repeats in the

  9. Registry of Youth Onset Diabetes in India (YDR)

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    Praveen, Pradeep A.; Madhu, Sri Venkata; Mohan, Viswanathan; Das, Siddhartha; Kakati, Sanjeeb; Shah, Nalini; Chaddha, Manoj; Bhadada, Sanjay Kumar; Das, Ashok Kumar; Shukla, Deepak Kumar; Kaur, Tanvir; Tandon, Nikhil

    2016-01-01

    Background: With the aim of addressing the relative scarcity of information on youth-onset diabetes in India, the Indian Council of Medical Research (ICMR) decided to establish the Registry of People with Diabetes with Young Age at Onset (YDR) in 2006. The major objectives of YDR are to generate information on disease pattern or types of youth-onset diabetes including their geographical variations within India and to estimate the burden of diabetes complications. Methods: YDR is an observational multicenter clinic based registry enlisting physician diagnosed diabetes in individuals below 25 years of age. Diabetes was classified using symptom based clinical criteria. YDR data collection is coordinated through regional collaborating centers and their interacting reporting centers across India. A baseline and an annual follow-up proformas are used to obtain information on sociodemographic details, clinical profile, and anthropometric and laboratory measurements of the patients. Results: In phase 1, the registry has enrolled 5546 patients, in which type 1 diabetes mellitus (T1DM) was the most prevalent (63.9%), followed by youth-onset type 2 diabetes mellitus (T2DM) (25.3%). Conclusion: This registry provides a unique opportunity to study the natural history of youth-onset diabetes in India. PMID:27179010

  10. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis

    DEFF Research Database (Denmark)

    Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta

    2015-01-01

    OBJECTIVE: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. METHODS: Data collected between June 2004 and April 2013 were examined with focus...

  11. Infantile onset diabetes mellitus in developing countries-India

    Institute of Scientific and Technical Information of China (English)

    Poovazhagi; Varadarajan

    2016-01-01

    Infantile onset diabetes mellitus(IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus(DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes(67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India.

  12. Infantile onset diabetes mellitus in developing countries - India.

    Science.gov (United States)

    Varadarajan, Poovazhagi

    2016-03-25

    Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes (67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India.

  13. Macrophage activation syndrome in a patient with systemic onset of the juvenile idiopathic arthritis.

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    Jain, Deepak; Aggarwal, Hari K; Rao, Avinash; Mittal, Anshul; Jain, Promil

    2016-01-01

    Systemic onset juvenile idiopathic arthritis (sJIA) is defined as arthritis affecting one or more joint usually in the juvenile age group (< 16 years of age) with or preceded by fever of at least 2 weeks duration that is documented to be daily ("quotidian") for at least 3 days which may be associated with evanescent (non-fixed) erythematous rash or generalized lymph node enlargement or hepatomegaly/splenomegaly/both or serositis. Macrophage activation syndrome (MAS) is a life-threatening complication of sJIA marked by sudden onset of non-remitting high fever, profound depression in all three blood cell lines (i.e. leukopenia, anemia, and thrombocytopenia), hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels. In children with systemic juvenile idiopathic arthritis, the clinical picture may mimic sepsis or an exacerbation of the underlying disease. We report a case of a 16-year-old female patient presenting with high grade fever with joint pains and generalized weakness which proved to be systemic onset juvenile idiopathic arthritis with macrophage activation syndrome after ruling out all other differential diagnoses and responded well to intravenous steroids.

  14. Fever of unknown origin in a patient of systemic onset juvenile idiopathic arthritis

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    Vinod Kolar Vishwanath

    2010-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis is a potentially fatal condition characterized by pathologic immune activation, which can complicate infections, childhood systemic rheumatologic diseases and malignancies. Here we report a case of reactive hemophagocytic lymphohistiocytosis [macrophage activation syndrome] complicating systemic onset juvenile idiopathic arthritis, which was treated successfully with dexamethasone and cyclosporine. Reactive hemophagocytic lymphohistiocytosis or macrophage activation syndrome should be considered in patients of juvenile idiopathic arthritis with prolonged fever of unknown origin and cytopenias. Early diagnosis with high index of suspicion and prompt, aggressive treatment are needed for successful outcomes.

  15. Risk of new-onset diabetes associated with statin use

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    Robert D Beckett

    2015-09-01

    Full Text Available Objective: To identify and assess studies investigating the association between statins and new-onset diabetes and determine the clinical significance of this risk. Data sources: A MEDLINE (1977–April 2015, Google Scholar (1997–April 2015, and International Pharmaceutical Abstracts (1977–April 2015 search was performed using the search terms hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects, statins, adverse effects, diabetes mellitus, diabetes mellitus/etiology, and drug-induced. Citations of identified articles and clinical practice guidelines were also reviewed. Study selection and data extraction: Articles describing results from original investigations or meta-analyses specifically designed to assess the association between statins and new-onset diabetes and published in English were included. Data synthesis: A total of 13 cohort studies and seven meta-analyses were included. In all, 11 were retrospective cohort studies and reported some degree of increased risk of new-onset diabetes associated with statins. The two prospective cohort studies differed. One identified increased risk of new-onset diabetes, but the other did not. Increased risk was not identified when any statin was compared to placebo alone, individual statins were compared, or in the single meta-analysis that included observational studies. Overall, the meta-analyses suggest that statin therapy is associated with an increased risk of new-onset diabetes when compared to placebo or active control, and when intensive therapy is compared to moderate therapy. Conclusion: Statins have been associated with a small, but statistically significant risk of new-onset diabetes. Patients with risk factors for developing diabetes mellitus may be at higher risk. This risk is likely outweighed by the benefits of reducing cardiovascular risk.

  16. Juvenile systemic lupus erythematosus onset patterns in Vietnamese children

    DEFF Research Database (Denmark)

    Dung, Nguyen Thi Ngoc; Loan, Huynh Thoai; Nielsen, Susan

    2013-01-01

    UNLABELLED: BACKGROUND: Incidence and disease pattern of childhood-onset SLE is reported to differ among ethnic groups. METHODS: To describe disease pattern and 6 month follow-up in a referral based cohort of 45 Vietnamese children with SLE. Forty-five children who were subsequently diagnosed...... sedimentation rate was 83.6 (SD 37.4). The patient age at diagnosis was positively correlated to the SLEDAI (p = 0.034) and ECLAM (p = 0.022). At 6 month follow-up of the 45 children, 15 patients were in complete remission, 5 were in partial remission, 6 had stable disease, 3 had relapsed, 3 had evolving...... disease, 2 had ongoing resistant disease and 4 had died. Seven patients were lost to follow-up. A second renal biopsy showed an improved ISN class in 13 of 15; in 2 cases the ISN class remained unchanged. CONCLUSIONS: Forty-five Vietnamese children with SLE were referred to Ho Chi Minh Children's Hospital...

  17. Antihypertensive therapy, new-onset diabetes, and cardiovascular disease

    Science.gov (United States)

    Basile, J N

    2009-01-01

    Type 2 diabetes mellitus is a worldwide epidemic with considerable health and economic consequences. Diabetes is an important risk factor for cardiovascular disease, which is the leading cause of death in diabetic patients, and decreasing the incidence of diabetes may potentially reduce the burden of cardiovascular disease. This article discusses the clinical trial evidence for modalities associated with a reduction in the risk of new-onset diabetes, with a focus on the role of antihypertensive agents that block the renin–angiotensin system. Lifestyle interventions and the use of antidiabetic, anti-obesity, and lipid-lowering drugs are also reviewed. An unresolved question is whether decreasing the incidence of new-onset diabetes with non-pharmacologic or pharmacologic intervention will also lower the risk of cardiovascular disease. A large ongoing study is investigating whether the treatment with an oral antidiabetic drug or an angiotensin-receptor blocker will reduce the incidence of new-onset diabetes and cardiovascular disease in patients at high risk for developing diabetes. PMID:19220522

  18. Onset of type 1 diabetes mellitus in two patients with maturity onset diabetes of the young.

    Science.gov (United States)

    Maltoni, Giulio; Zucchini, Stefano; Scipione, Mirella; Mantovani, Vilma; Salardi, Silvana; Cicognani, Alessandro

    2012-03-01

    The association between maturity onset diabetes of the young (MODY) and type 1 diabetes mellitus (T1DM) has been rarely described. We report two patients affected by MODY who developed T1DM. Case 1: a 4-yr-old girl referred for glycosuria presented hemoglobin A1c (HbA1c) of 6.6%. Islet cell antibodies (ICA) and anti-glutamic acid decarboxylase (GADA) were initially negative. As her father, uncle and grandmother showed mild hyperglycemia, they were screened for MODY 2. A novel mutation in glucokinase gene was found in the family. Few months later, her glycemic control worsened consistently and she required insulin treatment. A high titer of GADA and ICA was then detected. Six years afterwards insulin requirement is 0.8 U/kg and HbA1c 6.7%. Case 2: a 15-yr-old boy treated for growth hormone deficiency was found with a blood glucose level of 106 mg/dL. HbA1c was 7.2%, ICA and GADA were negative. Family history was positive for autoimmune diseases and type 2 diabetes mellitus. The patient was investigated for MODY 2 and MODY 3, and a mutation of hepatocyte nuclear factor-1 alpha gene was found. The same mutation was found in the mother who had never been referred for hyperglycemia. After 1 yr, due to an unjustified worsening of the metabolic control, autoimmunity was again investigated and a mild positivity was found. He then required insulin therapy and after 5 yr current HbA1c was 8.2%. The diagnosis of MODY does not exclude the risk of developing T1DM. Therefore autoimmunity should be investigated when ordinary treatments fail and metabolic control unexpectedly worsens. © 2011 John Wiley & Sons A/S.

  19. Disease activity, severity, and damage in the UK Juvenile-Onset Systemic Lupus Erythematosus Cohort.

    Science.gov (United States)

    Watson, Louise; Leone, Valentina; Pilkington, Clarissa; Tullus, Kjell; Rangaraj, Satyapal; McDonagh, Janet E; Gardner-Medwin, Janet; Wilkinson, Nick; Riley, Phil; Tizard, Jane; Armon, Kate; Sinha, Manish D; Ioannou, Yiannis; Archer, Neil; Bailey, Kathryn; Davidson, Joyce; Baildam, Eileen M; Cleary, Gavin; McCann, Liza J; Beresford, Michael W

    2012-07-01

    The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort. Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE. Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (PLupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1. The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen. Copyright © 2012 by the American College of Rheumatology.

  20. Total care for juvenile diabetics--a Swedish experiment.

    Science.gov (United States)

    Larsson, Y

    1983-01-01

    A Swedish Study Group for Childhood Diabetes has recently prepared a national treatment and care programme for diabetes in children and adolescents, which is briefly presented in this paper. The programme is based on the working hypothesis that long-term vascular and neurological complications - still the most serious threats to the well-being and survival of juvenile diabetics - may be prevented by continuously maintaining a normal or near-normal blood glucose level. Four levels (I--IV) of metabolic control are being defined, of which level I is the optimal goal and level II acceptable, while levels III and IV are regarded as inadequate. To achieve a satisfactory therapeutic result great efforts are required by both patients and the diabetic health teams at the pediatric clinics. In addition to insulin, diet and exercise, great emphasis should be laid on home-monitoring of blood glucose and glycosuria, on patient education and on psychological support both to the children and to their families. The therapeutic team should understand the psychological problems which frequently occur in diabetic families and be able to guide them through the different stages of the disease until the patients reach psychosocial maturity. The programme thus aims at providing a total - biological, functional, emotional and social - care for diabetic children and adolescents, and at thereby improving their quality of life on a long-term basis.

  1. Do adolescent drug users fare the worst? Onset type, juvenile delinquency, and criminal careers.

    Science.gov (United States)

    DeLisi, Matt; Angton, Alexia; Behnken, Monic P; Kusow, Abdi M

    2015-02-01

    Although substance abuse often accompanies delinquency and other forms of antisocial behavior, there is less scholarly agreement about the timing of substance use vis-à-vis an individual's antisocial trajectory. Similarly, although there is extraordinary evidence that onset is inversely related to the severity of the criminal career, there is surprisingly little research on the offense type of onset or the type of antisocial behavior that was displayed when an individual initiated his or her offending career. Drawing on data from a sample of serious adult criminal offenders (N = 500), the current study examined 12 forms of juvenile delinquency (murder, rape, robbery, aggravated assault, burglary, larceny, auto theft, arson, weapons, sexual offense, drug sales, and drug use) in addition to age at arrest onset, age, sex, race to explore their association with chronicity (total arrests), extreme chronicity (1 SD above the mean which was equivalent to 90 career arrests), and lambda (offending per year). The only onset offense type that was significantly associated with all criminal career outcomes was juvenile drug use. Additional research on the offense type of delinquent onset is needed to understand launching points of serious antisocial careers.

  2. Psoriasis and New-Onset Diabetes

    DEFF Research Database (Denmark)

    Khalid, Usman; Hansen, Peter Riis; Gislason, Gunnar Hilmar

    2013-01-01

    OBJECTIVE Psoriasis is associated with increased risk of cardiovascular events and increased prevalence of cardiovascular risk factors. Diabetes mellitus (DM) is a major contributor to cardiovascular morbidity and mortality that may be associated with psoriasis, but conflicting results have been...

  3. Attitudes towards self-control with urinalysis in juvenile diabetes.

    Science.gov (United States)

    Ludvigsson, J; Svensson, P G

    1980-01-01

    Urinary glucose excretion reflects the blood glucose levels and is therefore recommended and used as a relevant and practical method for self-control in juvenile diabetes. The purpose of this study was to estimate the attitudes of of diabetic children and their parents towards such daily urinalysis. In 1975 69 juvenile diabetics 6-18 years old and their parents were studied and three years later another 69 patients were added. Still a year later 31 of the children were studied again. Standardized interviews, questionnaires and a special attitude test were used. The results indicate that a great majority of the patients and the parents accept the self-testing method and regard it as a valuable tool in the management of the disease. Almost nobody experienced the urine tests as a psychological problem. As urinalysis has become established as a self-evident part of the treatment, the attitudes have become even more positive among a growing number of patients. Parallel to this feeling of usefulness the patients are honest and the urine tests thus give reliable information.

  4. The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset.

    Science.gov (United States)

    Andresen, J Michael; Gayán, Javier; Djoussé, Luc; Roberts, Simone; Brocklebank, Denise; Cherny, Stacey S; Cardon, Lon R; Gusella, James F; MacDonald, Marcy E; Myers, Richard H; Housman, David E; Wexler, Nancy S

    2007-05-01

    Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 x 10(-5)] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 x 10(-16)]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range.

  5. Maturity onset diabetes of the young: Diagnosis and treatment options

    Directory of Open Access Journals (Sweden)

    Serghei Covanțev

    2016-12-01

    Full Text Available Diabetes is a complicated disease, so multiple factors are involved in its development. Nevertheless some of the patients with type 1 and 2 diabetes mellitus have a monogenic form of this disease which has different treatment options and usually fewer complications. It is estimated that about 5% of patients with type 2 diabetes melitus (T2DM and about 10% of type 1 diabetes melitus (T1DM are misdiagnosed and have maturity onset diabetes of the young (MODY. We present a review study of the management of most frequent monogenic forms of diabetes such as MODY 1, 2 and 3 and the possibilities of their diagnosis including in resource limited situations.

  6. Interleukin-1 antagonism in type 1 diabetes of recent onset

    DEFF Research Database (Denmark)

    Moran, Antoinette; Bundy, Brian; Becker, Dorothy J

    2013-01-01

    Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomised, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. We aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1...... antibody, or anakinra, a human interleukin-1 receptor antagonist, improved β-cell function in recent-onset type 1 diabetes....

  7. Intervening before the onset of Type 1 diabetes

    DEFF Research Database (Denmark)

    Reimers, Jesper Irving

    2003-01-01

    AIMS/HYPOTHESIS: To set up a clinical trial to establish whether nicotinamide can prevent or delay clinical onset of Type 1 diabetes. METHOD: The European Nicotinamide Diabetes Intervention Trial is a randomised, double-blind, placebo-controlled intervention trial undertaken in 18 European...... countries, Canada and the USA. Entry criteria were a first-degree family history of Type 1 diabetes, age 3-40 years, confirmed islet cell antibody (ICA) levels greater than or equal to 20 JDF units, and a non-diabetic OGTT; the study group was further characterised by intravenous glucose tolerance testing....../INTERPRETATION: ENDIT has shown that a trial of an intervention designed to halt or delay progression to Type 1 diabetes can be carried out on a multinational collaborative basis, as and when potentially safe and effective forms of intervention become available. Primary screening with biochemically defined...

  8. Ovulatory patterns in women with juvenile and late-onset/persistent acne vulgaris.

    Science.gov (United States)

    Noto, G; Pravatà, G; Aricò, M; Maneschi, F; Palisi, F

    1990-01-01

    The ovulatory patterns in women with acne vulgaris were evaluated in order to understand their relationship with androgenic levels. Ovulation disturbances were found in 58.3% of patients with prevalence of anovulation in the juvenile acne and of luteal insufficiency in the late-onset/persistent acne. Significant negative correlation was found between T free and P in the late-onset/persistent group (r: -0.629; p = 0.016): This may be interpreted as a rather steady endocrine status in which the raised androgenic levels, probably due to peripheral conversion, are concomitant to absent or insufficient ovulations. In the younger patients both the androgen excess and the ovulation disturbances could be due to an abnormal or delayed maturation of the hypothalamus-pituitary ovarian axis. The evaluation of the ovarian function in women with acne vulgaris may be useful to detect ovulatory disturbances in view of a possible resolution of both the problems by specific endocrine management.

  9. Juvenile versus adult-onset ankylosing spondylitis -- clinical, radiographic, and social outcomes. a systematic review.

    Science.gov (United States)

    Jadon, Deepak R; Ramanan, Athimalaipet V; Sengupta, Raj

    2013-11-01

    Ankylosing spondylitis (AS) has 2 main modes of onset: juvenile-onset AS (JoAS) and adult-onset AS (AoAS). It is not known whether JoAS is a subtype of AS, or AS modulated by early age of onset and longer disease duration. We performed a systematic review of the literature, identifying 12 articles and 1 abstract directly comparing JoAS and AoAS cohorts, with observational study design. Patients with JoAS appear to have more peripheral joint involvement both clinically and radiographically (especially knees and ankles) and more root joint involvement (hips and shoulders); they are more likely to proceed to hip arthroplasty and often initially present with peripheral rather than axial symptoms. Patients with AoAS appear to have more axial symptoms and radiographic disease, particularly in the lumbar spine, and worse axial metrology. In terms of other characteristics, more evidence is needed to confidently state whether JoAS and AoAS are different.

  10. Clinical Features in Juvenile-Onset Ankylosing Spondylitis Patients Carrying Different B27 Subtypes

    Directory of Open Access Journals (Sweden)

    Yikun Mou

    2015-01-01

    Full Text Available Background. Ankylosing spondylitis (AS is a common rheumatic disease and is characterized by inflammation of the axial skeleton. HLA-B27 is strongly associated with AS. Juvenile-onset AS (JAS with disease onset before 16 years of age differs from adult-onset AS (AAS in many respects. Objective. To compare the clinical features in JAS with different B27 subtypes and analyze the differences between JAS and AAS. Methods. 145 JAS and 360 AAS patients were included. The demographic data, clinical manifestations, laboratory markers, Bath AS indices, and B27 subtypes were recorded. Results. Peripheral arthritis, enthesitis, BASDAI, ESR, and CRP were significantly higher in JAS patients with HLA-B*2704 than those with B27-negative. Enthesitis and ESR were significantly higher in patients with HLA-B*2705 than those with B27-negative. The onset age of HLA-B*2715 group was much earlier than the other groups. The peripheral arthritis, enthesitis, and hip joint involvement in JAS with HLA-B*2704 were significantly higher than those in AAS with HLA-B*2704. Conclusion. JAS with different B27 subtypes had similar features in most of manifestations; JAS and AAS patients with the same subtype could have distinctive courses. Early diagnosis, hip detection, and control of systemic active inflammation in JAS patients will be helpful for improving the prognosis.

  11. New-onset diabetes mellitus after kidney transplantation in Denmark

    DEFF Research Database (Denmark)

    Hornum, Mads; Jørgensen, Kaj Anker; Hansen, Jesper Melchior;

    2010-01-01

    Background and objectives: This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients. Design, setting, participants, & measurements: Included were 57 kidney recipients (Tx group, age 39 13 years) and 40 uremic...... patients remaining on the waiting list for kidney transplantation (uremic controls, age 47 11 years). All were examined at baseline before possible transplantation and after 12 months. The prevalence of diabetes, prediabetes, insulin sensitivity index (ISI), and insulin secretion index (Isecr) were...

  12. Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype

    DEFF Research Database (Denmark)

    Hawa, Mohammed I; Kolb, Hubert; Schloot, Nanette

    2013-01-01

    OBJECTIVESSpecific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non-insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes.RESEARCH DESIGN AND METHODSWe c...

  13. Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-Onset Diabetes of the Young

    Science.gov (United States)

    ... Diabetes Monogenic Forms of Diabetes Monogenic Forms of Diabetes The most common forms of diabetes, type 1 ... is inherited from each parent. Monogenic Forms of Diabetes Some rare forms of diabetes result from mutations ...

  14. Lipemic Serum in a Toddler with New-Onset Diabetes Mellitus Presenting with Diabetic Ketoacidosis

    Directory of Open Access Journals (Sweden)

    Muhammad Waseem

    2012-01-01

    Full Text Available Context Significant hyperlipidemia causing lipemic serum in patients with poorly controlled diabetes is under-reported in children. The recognition of the severe hyperlipidemia is important for proper management and to prevent associated morbidities. Severe hyperlipidemia in patients with diabetic ketoacidosis should be considered. Case report In this case we report a 2-year-old girl with new onset type 1 diabetes mellitus, who presented with severe diabetic ketoacidosis and hyperlipidemia. Hyperlipidemia was resolved with hydration and insulin therapy. Conclusion It is important to diagnose hyperlipidemia by checking serum lipid profile for all pediatric patients presenting with hyperglycemic crisis to prevent morbidities

  15. Coblation plus photodynamic therapy (PDT) for the treatment of juvenile onset laryngeal papillomatosis: case reports.

    Science.gov (United States)

    Zhou, Chengyong; Sun, Baochun; Wang, Feng; Dai, Zhiyao; Han, Zeli; Han, Jiahong; Chen, Maomao; Shen, Yao

    2014-08-29

    In treating juvenile-onset laryngeal papillomatosis, the most difficult aspect is preventing recurrence. After a single treatment, recurrence can begin after as soon as 20 days and the recurrent rate can be higher than 90%. The causes of recurrence include the presence of mucosal cells infected with papilloma virus, which are undetectable with the naked eyes, and surgery-induced infection. Photodynamic therapy (PDT) could effectively solve this problem. Virus-infected cells have a very high metabolic energy for capturing and internalizing the photosensitizer, which, after light stimulation, subsequently induces active oxygen species inside the nucleus, which kill infected cells. The second generation of photosensitizer agents (PA) are locally applied to avoid the intravenous systemic damage caused by first-generation PAs, and this method is widely used for the treatment of genital warts to very good effect. We used the photodynamic method to treat laryngeal papillomatosis in children and obtained significant efficacy. We followed three juvenile subjects with recurrent laryngeal papillomatosis through a course of treatment (each course includes three PDT sessions), with a follow-up after 6 months. The characteristic procedures involve exposing the larynx with a laryngoscope and using low-temperature plasma technology to visualize the tumor resection, as the effects of plasma technology can reduce postoperative laryngeal edema and reduce intraoperative metastasis. PDT was performed during the first surgery, 20 days after and 30 days after surgery. At the 6-month follow-ups, there was no recurrence. This was the world's first successful reported case of the use of PDT treatment for juvenile laryngeal papillomatosis.

  16. The role of heme oxygenase-1 in systemic-onset juvenile idiopathic arthritis.

    Science.gov (United States)

    Takahashi, Akitaka; Mori, Masaaki; Naruto, Takuya; Nakajima, Shoko; Miyamae, Takako; Imagawa, Tomoyuki; Yokota, Shumpei

    2009-01-01

    We have determined the serum levels of heme oxygenase-1 (HO-1) in 56 patients with systemic-onset juvenile idiopathic arthritis (s-JIA) and compared these with serum HO-1 levels in healthy controls and patients with other pediatric rheumatic diseases. Serum HO-1 levels were measured by the sandwich enzyme-linked immunosorbent assay. The mean serum HO-1 level in s-JIA patients during the active phase was 123.6 +/- 13.83 ng/ml, which was significantly higher than that in patients with polyarticular juvenile idiopathic arthritis (p-JIA), Kawasaki disease, systemic lupus erythematosus or mixed connective tissue disease (P < 0.0005). The serum levels of HO-1, cytokines and cytokine receptors in patients with s-JIA were also assessed at both the active and inactive phases. The serum HO-1 level in patients with s-JIA in the active phase was found to be significantly greater than that in patients with the disease in the inactive phase (P < 0.0001). An assessment of the relationships between serum HO-1 levels and other laboratory parameters or cytokines in patients with s-JIA did not reveal any strong correlations. These results suggest that the serum level of HO-1 may be a useful marker for the differential diagnosis of s-JIA. Further study will be necessary to elucidate the mechanism of HO-1 production and to clarify the role of HO-1 in the disease process.

  17. Association between new onset diabetic retinopathy and monocyte chemoattractant protein-1 (MCP-1) polymorphism in Japanese type 2 diabetes.

    Science.gov (United States)

    Ninomiya, Hiroyo; Katakami, Naoto; Osonoi, Takeshi; Saitou, Miyoko; Yamamoto, Yuichi; Takahara, Mitsuyoshi; Kawamori, Dan; Matsuoka, Taka-aki; Yamasaki, Yoshimitsu; Shimomura, Iichiro

    2015-06-01

    We longitudinally evaluated the association between monocyte chemoattractant protein-1 (MCP-1) A-2518G polymorphism and new onset of diabetic retinopathy in 758 type 2 diabetic patients. The new onset of retinopathy increased with the increase of the number of G alleles, even after adjustment for age, HbA1c levels, and duration of diabetes.

  18. Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis

    DEFF Research Database (Denmark)

    Silverberg, Michael J.; Thorsen, Poul; Lindeberg, Henning

    2003-01-01

    OBJECTIVE: To assess the risk of juvenile-onset recurrent respiratory papillomatosis conferred by a maternal history of genital warts in pregnancy, and to identify additional cofactors such as the method of delivery (cesarean versus vaginal) and procedures or complications during pregnancy. METHODS......: A retrospective cohort design was used to evaluate maternal and infant characteristics associated with respiratory papillomatosis among Danish births between 1974 and 1993. Using data from Danish registries, we identified 3033 births with a maternal history of genital warts during pregnancy. Fifty......-seven respiratory papillomatosis cases were identified by review of medical records from ear, nose, and throat departments. RESULTS: Seven of every 1000 births with a maternal history of genital warts resulted in disease in the offspring, corresponding to a 231.4 (95% confidence interval 135.3, 395.9) times higher...

  19. Accommodative lag and juvenile-onset myopia progression in children wearing refractive correction.

    Science.gov (United States)

    Berntsen, David A; Sinnott, Loraine T; Mutti, Donald O; Zadnik, Karla

    2011-05-11

    The relationship between accommodative lag and annual myopia progression was investigated using linear models in 592 myopic children wearing a full refractive correction in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. The mean (± SD) age and spherical equivalent refractive error at baseline were 10.4 ± 1.8 years and -2.13 ± 1.24 D, respectively. The mean annual progression of myopia was -0.45 ± 0.32 D, and the mean accommodative lag (for a 4-D Badal stimulus) was 1.59 ± 0.63 D. Neither lag at the beginning nor at the end of a yearly progression interval was associated with annual myopia progression (all p ≥ 0.12). These data suggest that foveal hyperopic retinal blur during near viewing may not drive juvenile-onset myopia progression.

  20. A Case Report on Juvenile Neuromyelitis Optica: Early Onset, Long Remission Period, and Atypical Treatment Response.

    Science.gov (United States)

    Elpers, Christiane; Gross, Catharina C; Fiedler, Barbara; Meuth, Sven G; Kurlemann, Gerhard

    2015-08-01

    Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the central nervous system and preferentially targets the optic nerves and spinal cord. NMO is rare in children and clinical course of the disease is highly variable as described in studies. Here, we present a case report of a young girl presenting with a rare course of pediatric NMO with an early disease onset at the age of 12 years, a relapse free interval of 4 years, evidence of NMO immunoglobulin G (IgG) and an unusual response against immunosuppressive therapy. The aim of this report is to highlight the potentially long remission period between relapses complicating proper diagnosis despite well defined diagnostic criteria. In addition, we want to encourage the use of rituximab in pediatric NMO, although larger cohorts are warranted to establish B cell depleting therapies in juvenile NMO.

  1. Maturity-onset diabetes of the young (MODY): an update.

    Science.gov (United States)

    Anık, Ahmet; Çatlı, Gönül; Abacı, Ayhan; Böber, Ece

    2015-03-01

    Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes classically presenting in adolescence or young adults before the age of 25 years. MODY is a rare cause of diabetes (1% of all cases) and is frequently misdiagnosed as Type 1 diabetes (T1DM) or Type 2 diabetes (T2DM). A precise molecular diagnosis is essential because it leads to optimal treatment of the patients and allows early diagnosis for their asymptomatic family members. Mutations in the glucokinase (GCK) (MODY 2) and hepatocyte nuclear factor (HNF)1A/4A (MODY 3 and MODY 1) genes are the most common causes of MODY. GCK mutations cause a mild, asymptomatic, and stable fasting hyperglycemia usually requiring no specific treatment. However, mutations in the HNF1A and HNF4A cause a progressive pancreatic β-cell dysfunction and hyperglycemia that can result in microvascular complications. Sulfonylureas are effective in these patients by acting on adenosine triphosphate (ATP)-sensitive potassium channels, although insulin therapy may be required later in life. Mutations in the HNF1B (MODY 5) is associated with pancreatic agenesis, renal abnormalities, genital tract malformations, and liver dysfunction. Compared to MODY 1, 2, 3, and 5, the remaining subtypes of MODY have a much lower prevalence. In this review, we summarize the main clinical and laboratory characteristics of the common and rarer causes of MODY.

  2. HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

    Directory of Open Access Journals (Sweden)

    B.L. Liphaus

    2007-04-01

    Full Text Available Human leukocyte antigens (HLA DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

  3. Interleukin-1 receptor antagonist in neonates, children and adults, and in patients with pauci- and polyarticular onset juvenile chronic arthritis

    DEFF Research Database (Denmark)

    Müller, K; Zak, M; Nielsen, S;

    2011-01-01

    patients with juvenile chronic arthritis (JCA) of the pauci- or polyarticular onset type. RESULTS: IL-1ra serum levels were found to differ significantly between the three age groups, being higher in neonates (569 pg/ml) than in children (70 pg/ml) and adults (177 pg/ml). IL-1ra production in E. coli...

  4. Evaluation of New-Onset Diabetes in Patients Presenting Emergency Service with a Diabetic Ketoacidosis Attack

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    Yavuz Yiğit

    2013-12-01

    Full Text Available Aim: The aim of this study was to investigate the rate of new-onset diabetes mellitus (DM in patients presenting to our emergency department with diabetic ketoacidosis. Methods: We retrospectively evaluated hospital records of patients who presented to the Emergency Department at Istanbul Goztepe Research and Training Hospital between 01 April 2009 and 01 April 2011 and were diagnosed with diabetic ketoacidosis. 57 patients having complete clinical data were included in the study. Results: 45.6%of patients had type 1 DM, 33.3%- type 2 DM, and 21%of them were with new-onset DM. No statistically significant difference was found between type 1 DM, type 2 DM and new-onset DM patients with respect to arterial blood pH and HCO3 levels and serum sodium, potassium and plasma glucose levels at presentation as well as time of presentation (p>0.05, while HbA1c levels showed statistically significant difference in new-onset DM patients. Conclusion: No statistically significant difference was found between types of DM in patients diagnosed with diabetic ketoacidosis except for precipitating factors, age and HbA1c. Detecting high blood glucose levels in patients presenting to emergency room for reasons other than DM is not a rare condition. Cautious evaluation and recognition of these patients in emergency room for the possibility of undiagnosed DM is important for prevention of future diabetic ketoacidosis episodes. (The Medical Bulletin of Haseki 2013; 51: 168-72

  5. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  6. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  7. Maturity-onset diabetes of the young--MODY. Molekylaergenetiske, patofysiologiske og kliniske karakteristika

    DEFF Research Database (Denmark)

    Hansen, Torben; Urhammer, Søren A; Pedersen, Oluf Borbye

    2002-01-01

    Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous subtype of type 2 diabetes characterised by an early onset, an autosomal dominant inheritance, and a primary defect in insulin secretion. MODY comprises 2-5% of cases of type 2 diabetes. So far, six MODY gen...

  8. Association of Family History of Epilepsy with Earlier Age Onset of Juvenile Myoclonic Epilepsy

    Science.gov (United States)

    NAJAFI, Mohammad Reza; NAJAFI, Mohammad Amin; SAFAEI, Ali

    2016-01-01

    Objective Juvenile myoclonic epilepsy (JME) is supposedly the most frequent subtype of idiopathic generalized epilepsies (IGE). The aim of this study was to determine the prevalence of JME and comparison of patients’ demographics as well as timeline of the disease between positive family history epileptic patients (PFHE) and negative family history epileptic patients (NFHE) among sample of Iranian epileptic patients. Materials & Methods From Feb. 2006 to Oct. 2009, 1915 definite epileptic patients (873 females) referred to epilepsy clinics in Isfahan, central Iran, were surveyed and among them, 194 JME patients were diagnosed. JME was diagnosed by its specific clinical and EEG criteria. Patients were divided into two groups as PFHE and NFHE and data were compared between them. Results JME was responsible for 10% (194 patients) of all types of epilepsies. Of JME patients, 53% were female. In terms of family history of epilepsy, 40% were positive. No significant differences was found between PFHE and NFHE groups as for gender (P>0.05). Age of epilepsy onset was significantly earlier in PFHE patients (15 vs. 22 yr, P<0.001). Occurrence of JME before 18 yr old among PFHE patients was significantly higher (OR=2.356, P=0.007). Conclusion A family history of epilepsy might be associated with an earlier age of onset in patients with JME. PMID:27247579

  9. Association of Family History of Epilepsy with Earlier Age Onset of Juvenile Myoclonic Epilepsy.

    Science.gov (United States)

    Najafi, Mohammad Reza; Najafi, Mohammad Amin; Safaei, Ali

    2016-01-01

    Juvenile myoclonic epilepsy (JME) is supposedly the most frequent subtype of idiopathic generalized epilepsies (IGE). The aim of this study was to determine the prevalence of JME and comparison of patients' demographics as well as timeline of the disease between positive family history epileptic patients (PFHE) and negative family history epileptic patients (NFHE) among sample of Iranian epileptic patients. From Feb. 2006 to Oct. 2009, 1915 definite epileptic patients (873 females) referred to epilepsy clinics in Isfahan, central Iran, were surveyed and among them, 194 JME patients were diagnosed. JME was diagnosed by its specific clinical and EEG criteria. Patients were divided into two groups as PFHE and NFHE and data were compared between them. JME was responsible for 10% (194 patients) of all types of epilepsies. Of JME patients, 53% were female. In terms of family history of epilepsy, 40% were positive. No significant differences was found between PFHE and NFHE groups as for gender (P>0.05). Age of epilepsy onset was significantly earlier in PFHE patients (15 vs. 22 yr, P<0.001). Occurrence of JME before 18 yr old among PFHE patients was significantly higher (OR=2.356, P=0.007). A family history of epilepsy might be associated with an earlier age of onset in patients with JME.

  10. Estimativa da herdabilidade do diabetes juvenil em uma população brasileira An estimate of the inheritability of juvenile diabetes in a Brazilian population

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    Calógeras A. de A. Barbosa

    1984-10-01

    Full Text Available A herdabilidade da suscetibilidade do diabetes juvenil em uma população brasileira é estimada baseando-se em informações da prevalência da doença na população em geral e entre os pais de afetados. A estimativa de 90%, então obtida, sugere uma alta participação de fatores genéticos na determinação da moléstia. Exemplifica-se a aplicação desse resultado no cálculo de risco de recorrência do diabetes em familiares de indivíduos afetados.The inheritability of liability to juvenile diabetes in a Brazilian population is estimated from parent-offspring correlation. The high value of the estimate, 0.9, suggests that genetic factors are the most important causative agents of the disease in this population.

  11. Diabetes and onset of natural menopause : Results from the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Brand, J. S.; Onland-Moret, N. C.; Eijkemans, M. J C; Tjønneland, A.; Roswall, N.; Overvad, K.; Fagherazzi, G.; Clavel-Chapelon, F.; Dossus, L.; Lukanova, A.; Grote, V.; Bergmann, M. M.; Boeing, H.; Trichopoulou, A.; Tzivoglou, M.; Trichopoulos, D.; Grioni, S.; Mattiello, A.; Masala, G.; Tumino, R.; Vineis, P.; Bueno-De-Mesquita, H. B.; Weiderpass, E.; Redondo, M. L.; Sánchez, M. J.; Castaño, J. M Huerta; Arriola, L.; Ardanaz, E.; Duell, E. J.; Rolandsson, O.; Franks, P. W.; Butt, S.; Nilsson, P.; Khaw, K. T.; Wareham, N.; Travis, R.; Romieu, I.; Gunter, M. J.; Riboli, E.; Van Der Schouw, Y. T.

    2015-01-01

    STUDY QUESTION Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate

  12. Diabetes and onset of natural menopause : Results from the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Brand, J. S.; Onland-Moret, N. C.; Eijkemans, M. J C; Tjønneland, A.; Roswall, N.; Overvad, K.; Fagherazzi, G.; Clavel-Chapelon, F.; Dossus, L.; Lukanova, A.; Grote, V.; Bergmann, M. M.; Boeing, H.; Trichopoulou, A.; Tzivoglou, M.; Trichopoulos, D.; Grioni, S.; Mattiello, A.; Masala, G.; Tumino, R.; Vineis, P.; Bueno-De-Mesquita, H. B.; Weiderpass, E.; Redondo, M. L.; Sánchez, M. J.; Castaño, J. M Huerta; Arriola, L.; Ardanaz, E.; Duell, E. J.; Rolandsson, O.; Franks, P. W.; Butt, S.; Nilsson, P.; Khaw, K. T.; Wareham, N.; Travis, R.; Romieu, I.; Gunter, M. J.; Riboli, E.; Van Der Schouw, Y. T.

    2015-01-01

    STUDY QUESTION Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopaus

  13. Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors.

    Science.gov (United States)

    Senf, Philine; Schmitz, Bettina; Holtkamp, Martin; Janz, Dieter

    2013-12-10

    Juvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy subsyndrome, contributing to approximately 3% to 11% of adolescent and adult cases of epilepsy. However, little is known about the long-term medical evolution of this clinical entity. The aim of this study was to analyze long-term outcome in a clinically well-defined series of patients with JME for seizure evolution and predictors of seizure outcome. In this retrospective cohort study, we analyzed seizure outcome in 66 patients who had JME, were treated at the Department of Neurology, Charité-Universitätsmedizin Berlin, and were initially diagnosed by a single senior epileptologist. After a mean follow-up time of 44.6 years (20-69 years), 59.1% of patients remained free of seizures for at least 5 years before the last contact. Among the seizure-free patients, 28 (71.8%) were still taking antiepileptic drugs and 11 (28.2%) were off medication for at least the last 5 years. We identified manifestation of additional absence seizures at onset of JME as an independent predictor of an unfavorable outcome regarding seizure freedom. A significant proportion of patients with JME were seizure-free and off antiepileptic drug therapy in the later course of their disorder. Patients with JME and additional absence seizures might represent a different JME subtype with a worse outcome.

  14. Coronary artery abnormalities in children with systemic-onset juvenile idiopathic arthritis.

    Science.gov (United States)

    Lefèvre-Utile, Alain; Galeotti, Caroline; Koné-Paut, Isabelle

    2014-05-01

    Still's disease (Systemic-onset Juvenile Idiopathic Arthritis: SoJIA) is characterised by high-spiking daily fevers, arthritis and evanescent rashes. Diagnosis of Still's disease is often challenging. Infectious diseases and other inflammatory conditions, especially in young children, Kawasaki disease may look similar. Clinicians often rely on echocardiographic evidence of coronary artery abnormalities to differentiate between Kawasaki disease and Still's disease. Coronary artery dilation would typically favour the diagnosis of Kawasaki disease. We present four children with Still's disease and coronary artery abnormalities who were initially misdiagnosed as Kawasaki disease. The first patient had pericarditis and an irregular wall of the left coronary artery, without dilation on echocardiography. The second patient had a left coronary artery dilatation and a pericarditis. The third patient had thickened left coronary artery walls, and the fourth patient had a hyperechogenicity of the left and right coronary arteries. They received IVIG without success. The diagnosis of Still's disease was made secondary with evidence of persistent arthritis. All but one patient finally needed biologic treatments. Coronary abnormalities may be observed during various febrile conditions and do not exclude the diagnosis of Still's disease. Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  15. IL12RB2 gene is associated with the age of type 1 diabetes onset in Croatian family Trios.

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    Marina Pehlić

    Full Text Available BACKGROUND: Common complex diseases are influenced by both genetic and environmental factors. Many genetic factors overlap between various autoimmune diseases. The aim of the present study is to determine whether four genetic variants known to be risk variants for several autoimmune diseases could be associated with an increased susceptibility to type 1 diabetes mellitus. METHODS AND FINDINGS: We genotyped four genetic variants (rs2358817, rs1049550, rs6679356, rs9865818 within VTCN1, ANXA11, IL12RB2 and LPP genes respectively, in 265 T1DM family trios in Croatian population. We did not detect association of these polymorphisms with T1DM. However, quantitative transmission disequilibrium test (QTDT, orthogonal model revealed a significant association between the age of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was associated with the rs6679356 minor dominant allele C (p = 0.005. The association remained significant even after the Bonferroni correction for multiple testing and permutation. CONCLUSIONS: Variants originally associated with juvenile idiopathic arthritis (VTCN1 gene, sarcoidosis (ANXA11 gene, primary biliary cirrhosis (IL12RB2 gene and celiac disease (LPP gene were not associated with type 1 diabetes in our dataset. Nevertheless, association of IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene plays a role in defining the time of disease onset.

  16. Macrophage activation syndrome associated with hepatitis a virus in a child with systemic onset juvenile idiopathic arthritis: A case report

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    Mohammad Imnul Islam

    2016-07-01

    Full Text Available Macrophage Activation Syndrome (MAS is a rare but a grave complication of systemic onset juvenile idiopathic arthritis (SOJIA. It occurs as a result of immune dysfunction of macrophages and T lymphocyte. A twelve-year old boy diagnosed case of SOJIA presented with high grade fever, diffuse abdominal pain, vomiting and jaundice. He had high ALT, abnormal coagulation profile and Anti HA V IgM was positive. He had also high ferritin and triglyceride level which were very much suggestive for MAS. Infection especially Epstein Barr Virus, Herpes viruses and drugs are the common triggers for the development of MAS in association with SOJIA patients. MAS associated with hepatitis A virus are very rare. Only a few case reports are available in the literature. Considering its rarity and grave prognosis we are reporting a case of hepatitis A associated Macrophages Activation Syndrome in a systemic onset juvenile idiopathic arthritis.

  17. Incidence and severity of ketoacidosis in childhood-onset diabetes in Kuwait. Kuwait Diabetes Study Group.

    Science.gov (United States)

    al Khawari, M; Shaltout, A; Qabazard, M; Abdella, N; al Moemen, J; al-Mazidi, Z; Mandani, F; Moussa, M A

    1997-03-01

    In 1992, the diabetes registry was started in Kuwait, as part of DiaMond, a WHO multinational collaborative project on the incidence of childhood-onset diabetes. Children (243) aged below 15 years, were identified between 1 January 1992 and 31 December 1995. Children (203) were Kuwaiti and 40 were non-Kuwaiti children but resident of Kuwait. For the years 1992, 1993, the annual incidence of childhood onset diabetes for Kuwaiti children was 15.4 per 100,000 (95% confidence interval 12.9-19), and the degree of ascertainment was 92%. Polyuria, polydypsia, weight loss and nocturia were the most frequently reported symptoms; four children were in coma and one in shock at presentation. Nearly half of the children (49%) presented ketoacidosis (venous pH < 7.3 and/or plasma bicarbonate level < 18 mmol/l). and in 53 children (23.5%) it was severe (venous pH < 7.1 and/or plasma bicarbonate level < 10 mmol/l). In 62 children (25.5%) it was mild to moderate (venous pH 7.1-7.3 and/or plasma bicarbonate level 10.1-18 mmol/l). The incidence of severe ketoacidosis was similar in all age groups and sexes. All children recovered completely without major complications and no deaths were recorded. We conclude that diabetic ketoacidosis is a common presentation at the onset of diabetes in childhood in Kuwait and attests to the lack of awareness of general practitioners and parents to the symptoms and signs of diabetes in childhood.

  18. Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.

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    Margaret Maheandiran

    Full Text Available It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM. Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ administered intraperitoneally (IP. Insulin IP (15 U/kg, in rats fasted (14-16 hours, induced hypoglycemia, defined as <3.5 mM blood glucose (BG, in 68% of diabetic (STZ and 86% of control rats (CON. Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4 ± 1.3 mM than in CON rodents (6.3 ± 0.3 mM, resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8 ± 0.2 mM and CON animals (1.6 ± 0.1 mM as well as between those that survived (S+S and those that died (S+M post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of

  19. Vitamin D status in Egyptian patients with juvenile-onset systemic lupus erythematosus.

    Science.gov (United States)

    Garf, Kamal El; Marzouk, Huda; Farag, Yomna; Rasheed, Laila; Garf, Ayman El

    2015-09-01

    There are scanty data on the prevalence of vitamin D deficiency and its relation to disease activity among patients with juvenile-onset systemic lupus erythematosus (JoSLE) in the Middle East and North Africa, an area known to be endemic for vitamin D deficiency and insufficiency. The aim of this study was, therefore, to study vitamin D status and its relation to disease activity and parameters in Egyptian patients with JoSLE. Serum levels of 25(OH) D3 in 70 JoSLE patients were compared to 40 age-, sex-, and body mass index-matched healthy controls. The 25(OH) D3 was determined by enzyme-linked immunosorbent assay. Information regarding the medical history, clinical symptoms, and signs was registered at the time of serum sampling. Disease activity of SLE was evaluated according to the SLEDAI score. The mean level of serum 25(OH) D3 was 12 ± 3.7 in JoSLE patients compared to 21 ± 3.5 ng/mL in normal controls (p 30 ng/mL. There was no significant correlation between serum levels of 25(OH) D3 and the demographic data, medication used, and some laboratory data of patients with JoSLE. Disease activity score in our patients was insignificantly correlated with serum levels of 25(OH) D3. In spite of vitamin D supplementation in Egyptian JoSLE patients and the presence of vitamin D insufficiency in the control group, there are still significantly lower levels of vitamin D in JoSLE compared to normal controls.

  20. Adult-onset autoimmune diabetes: current knowledge and implications for management.

    Science.gov (United States)

    Buzzetti, Raffaella; Zampetti, Simona; Maddaloni, Ernesto

    2017-09-08

    Adult-onset autoimmune diabetes is a heterogeneous disease that is characterized by a reduced genetic load, a less intensive autoimmune process and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus (T1DM). The majority of patients with adult-onset autoimmune diabetes do not require insulin treatment for at least 6 months after diagnosis. Such patients are defined as having latent autoimmune diabetes in adults (LADA), which is distinct from classic adult-onset T1DM. The extensive heterogeneity of adult-onset autoimmune diabetes is apparent beyond the distinction between classic adult-onset T1DM and LADA. LADA is characterized by genetic, phenotypic and humoral heterogeneity, encompassing different degrees of insulin resistance and autoimmunity; this heterogeneity is probably a result of different pathological mechanisms, which have implications for treatment. The existence of heterogeneous phenotypes in LADA makes it difficult to establish an a priori treatment algorithm, and therefore, a personalized medicine approach is required. In this Review, we discuss the current understanding and gaps in knowledge regarding the pathophysiology and clinical features of adult-onset autoimmune diabetes and highlight the similarities and differences with classic T1DM and type 2 diabetes mellitus.

  1. [Maturity onset diabetes of the young (MODY) - screening, diagnostic and therapy].

    Science.gov (United States)

    Kaser, Susanne; Resl, Michael

    2016-04-01

    Maturity onset diabetes of the young (MODY) is a group of monogenetic diabetes types affecting up to 2% all known diabetics. Transcription factor MODY (HNF1α, HNF4α), the most frequent forms of MODY, allow treatment with sulfonylureas, mutations of glucokinase (GCK-MODY) usually do not require any therapy. Especially in younger patients correct diagnosis of MODY often results in discontinuation of insulin therapy and initiation of a sulfonylurea. Accordingly, in patients with diabetes onset below age of 25 years, with a positive family history for diabetes and negative autoantibodies screening for MODY is recommended.

  2. Adult-Onset Type 1 Diabetes and Pregnancy: Three Case Reports

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    Barbara Bonsembiante

    2013-01-01

    Full Text Available From 5% to 10% of diabetic patients have type 1 diabetes. Here we describe three cases of adult-onset type 1 diabetes in pregnancy treated at our clinic between 2009 and 2012. Two patients came for specialist examination during pregnancy, the third after pregnancy. These women had no prior overt diabetes and shared certain characteristics, that is, no family diabetes history, age over 35, normal prepregnancy BMI, need for insulin therapy as of the early weeks of pregnancy, and high-titer anti-GAD antibody positivity. The patients had persistent diabetes after delivery, suggesting that they developed adult-onset type 1 diabetes during pregnancy. About 10% of GDM patients become pancreatic autoantibody positive and the risk of developing overt diabetes is higher when two or more autoantibodies are present (particularly GAD and ICA. GAD-Ab shows the highest sensitivity for type 1 diabetes prediction. We need to bear in mind that older patients might conceivably develop an adult-onset type 1 diabetes during or after pregnancy. So we suggest that women with GDM showing the described clinical features shall be preferably tested for autoimmunity. Pregnant patients at risk of type 1 diabetes should be identified to avoid the maternal and fetal complications and the acute onset of diabetes afterwards.

  3. Aberrant gut microbiota composition at the onset of type 1 diabetes in young children

    NARCIS (Netherlands)

    Goffau, de M.C.; Fuentes, S.; Bogert, van den B.; Honkanen, H.; Vos, de W.M.; Welling, G.W.; Hyöty, H.; Harmsen, H.J.

    2014-01-01

    Aims/hypothesis Recent studies indicate that an aberrant gut microbiota is associated with the development of type 1 diabetes, yet little is known about the microbiota in children who have diabetes at an early age. To this end, the microbiota of children aged 1–5 years with new-onset type 1 diabetes

  4. Aberrant gut microbiota composition at the onset of type 1 diabetes in young children

    NARCIS (Netherlands)

    de Goffau, Marcus C.; Fuentes, Susana; van den Bogert, Bartholomeus; Honkanen, Hanna; de Vos, Willem M.; Welling, Gjalt; Hyoty, Heikki; Harmsen, Hermie J. M.

    2014-01-01

    Aims/hypothesis Recent studies indicate that an aberrant gut microbiota is associated with the development of type 1 diabetes, yet little is known about the microbiota in children who have diabetes at an early age. To this end, the microbiota of children aged 1-5 years with new-onset type 1 diabetes

  5. CD28⁻ CD8⁺ T cells are significantly reduced and correlate with disease duration in juveniles with type 1 diabetes.

    Science.gov (United States)

    Yarde, Danielle N; Lorenzo-Arteaga, Kristina; Corley, Kevin P; Cabrera, Monina; Sarvetnick, Nora E

    2014-10-01

    Type 1 diabetes (T1D) is a chronic disease caused by autoimmune destruction of insulin-producing pancreatic β-cells. T1D is typically diagnosed in children, but information regarding immune cell subsets in juveniles with T1D is scarce. Therefore, we studied various lymphocytic populations found in the peripheral blood of juveniles with T1D compared to age-matched controls (ages 2-17). One population of interest is the CD28(-) CD8(+) T cell subset, which are late-differentiated cells also described as suppressors. These cells are altered in a number of disease states and have been shown to be reduced in adults with T1D. We found that the proportion of CD28(-) cells within the CD8(+) T cell population is significantly reduced in juvenile type 1 diabetics. Furthermore, this reduction is not correlated with age in T1D juveniles, although a significant negative correlation between proportion CD28(-) CD8(+) T cells and age was observed in the healthy controls. Finally, correlation analysis revealed a significant and negative correlation between the proportion of CD28(-) CD8(+) T cells and T1D disease duration. These findings show that the CD28(-) CD8(+) T cell population is perturbed following onset of disease and may prove to be a valuable marker for monitoring the progression of T1D.

  6. Incretin hormones and maturity onset diabetes of the young - pathophysiological implications and anti-diabetic treatment potential

    DEFF Research Database (Denmark)

    Østoft, Signe Harring

    2015-01-01

    Maturity onset diabetes of the young (MODY) designates monogenic forms of non-autoimmune diabetes characterised by autosomal dominant inheritance, non-insulin dependent diabetes at onset and diagnosis often before 25 years of age. MODY constitutes genetically and clinically heterogeneous forms of...... insignificant, but at the expense of a higher risk of hypoglycaemia (predominantly mild). GLP-1RAs may have a place in treatment of patients with HNF1A-diabetes, especially when hypoglycaemia is a problem. Future studies are required to clarify this....

  7. Validity of a three-variable Juvenile Arthritis Disease Activity Score in children with new-onset juvenile idiopathic arthritis

    Science.gov (United States)

    Mcerlane, Flora; Beresford, Michael W; Baildam, Eileen M; Chieng, S E Alice; Davidson, Joyce E; Foster, Helen E; Gardner-Medwin, Janet; Lunt, Mark; Wedderburn, Lucy R; Thomson, Wendy; Hyrich, Kimme L

    2013-01-01

    Objectives To investigate the validity and feasibility of the Juvenile Arthritis Disease Activity Score (JADAS) in the routine clinical setting for all juvenile idiopathic arthritis (JIA) disease categories and explore whether exclusion of the erythrocyte sedimentation rate (ESR) from JADAS (the ‘JADAS3’) influences correlation with single markers of disease activity. Methods JADAS-71, JADAS-27 and JADAS-10 were determined at baseline for an inception cohort of children with JIA in the Childhood Arthritis Prospective Study. JADAS3-71, JADAS3-27 and JADAS3-10 were determined using an identical formula but with exclusion of ESR. Correlation of JADAS with JADAS3 and single measures of disease activity/severity were determined by category. Results Of 956 eligible children, sufficient data were available to calculate JADAS-71, JADAS-27 and JADAS-10 at baseline in 352 (37%) and JADAS3 in 551 (58%). The median (IQR) JADAS-71, JADAS-27 and JADAS-10 for all 352 children was 11 (5.9–18), 10.4 (5.7–17) and 11 (5.9–17.3), respectively. Median JADAS and JADAS3 varied significantly with the category (Kruskal–Wallis p=0.0001), with the highest values in children with polyarticular disease patterns. Correlation of JADAS and JADAS3 across all categories was excellent. Correlation of JADAS71 with single markers of disease activity/severity was good to moderate, with some variation across the categories. With the exception of ESR, correlation of JADAS3-71 was similar to correlation of JADAS-71 with the same indices. Conclusions This study is the first to apply JADAS to all categories of JIA in a routine clinical setting in the UK, adding further information about the feasibility and construct validity of JADAS. For the majority of categories, clinical applicability would be improved by exclusion of the ESR. PMID:23256951

  8. Different familial association patterns of autoimmune diseases between juvenile-onset systemic lupus erythematosus and juvenile rheumatoid arthritis.

    Science.gov (United States)

    Huang, Chun-Mei; Yang, Yao-Hsu; Chiang, Bor-Luen

    2004-04-01

    The aim of this study was to determine if the prevalence of autoimmune disorders in the relatives of patients with systemic lupus erythematosus (SLE) is greater than that of relatives of patients with juvenile rheumatoid arthritis (JRA). Interviews were used to obtain histories of the following autoimmune disorders among living or deceased first-, second-, and third-degree relatives of 91 SLE and 110 JRA families: ankylosing spondylitis, SLE, rheumatoid arthritis (RA), JRA, multiple sclerosis, juvenile dermatomyositis, Sjögren's syndrome, myasthenia gravis, psoriasis, and thyroid diseases. There were statistically significant differences between the SLE and JRA probands in mean age and gender ratio (19.1 +/- 4.8 vs 14.0 +/- 5.5 years; M (male)/F (female): 17/74 vs 62/48, pJRA families (11.8%), but not statistically significantly so. The mean age (18.0 +/- 5.3 vs 14.0 +/- 4.3 years), mean age at diagnosis (13.4 +/- 4.3 vs 7.9 +/- 3.9 years) and gender ratio (F/M, 16/3 vs 5/8) of the patients with affected relatives between these 2 groups all had statistically significant differences. A higher prevalence of SLE in relatives was found in SLE families than in JRA cases. Furthermore, this study revealed a higher incidence of autoimmune disorders among second- and third-degree relatives of SLE or JRA probands versus first-degree ones, especially sisters (including 1 pair of twins) and the maternal aunt in SLE families. These data demonstrate that the prevalence of autoimmune disorders in the relatives of patients with SLE is greater than those of relatives of patients with JRA. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.

  9. Maturity-onset diabetes of the young with end-stage nephropathy

    DEFF Research Database (Denmark)

    Saudek, Frantisek; Pruhová, Stepánka; Boucek, Peter;

    2004-01-01

    -onset diabetes of the young (MODY). SPK was performed in a 47-year old man who has MODY3 because of a Arg272His mutation in the hepatocyte nuclear factor-1alphagene. He developed overt diabetes mellitus at 19 years and end-stage diabetic nephropathy 26 years thereafter. Before SPK, the patient had measurable....... CONCLUSION: Identification of MODY3 among all C-peptide-positive patients with advanced diabetic nephropathy might help to select a specific group profiting from SPK....

  10. Long-term results after Boston brace treatment in late-onset juvenile and adolescent idiopathic scoliosis

    Directory of Open Access Journals (Sweden)

    Gunderson Ragnhild

    2011-08-01

    Full Text Available Abstract Background It is recommended that research in patients with idiopathic scoliosis should focus on short- and long-term patient-centred outcome. The aim of the present study was to evaluate outcome in patients with late-onset juvenile or adolescent idiopathic scoliosis 16 years or more after Boston brace treatment. Methods 272 (78% of 360 patients, 251 (92% women, responded to follow-up examination at a mean of 24.7 (range 16 - 32 years after Boston brace treatment. Fifty-eight (21% patients had late-onset juvenile and 214 had adolescent idiopathic scoliosis. All patients had clinical and radiological examination and answered a standardised questionnaire including work status, demographics, General Function Score (GFS (100 - worst possible and Oswestry Disability Index (ODI (100 - worst possible, EuroQol (EQ-5D (1 - best possible, EQ-VAS (100 - best possible, and Scoliosis Research Society - 22 (SRS - 22 (5 - best possible. Results The mean age at follow-up was 40.4 (31-48 years. The prebrace major curve was in average 33.2 (20 - 57°. At weaning and at the last follow-up the corresponding values were 28.3 (1 - 58° and 32.5 (7 - 80°, respectively. Curve development was similar in patients with late-onset juvenile and adolescent start. The prebrace curve increased > 5° in 31% and decreased > 5° in 26%. Twenty-five patients had surgery. Those who did not attend follow-up (n = 88 had a lower mean curve at weaning: 25.4 (6-53°. Work status was 76% full-time and 10% part-time. Eighty-seven percent had delivered a baby, 50% had pain in pregnancy. The mean (SD GFS was 7.4 (10.8, ODI 9.3 (11.0, EQ-5D 0.82 (0.2, EQ-VAS 77.6 (17.8, SRS-22: pain 4.1 (0.8, mental health 4.1 (0.6, self-image 3.7 (0.7, function 4.0 (0.6, satisfaction with treatment 3.7 (1.0. Surgical patients had significantly reduced scores for SRS-physical function and self-image, and patients with curves ≥ 45° had reduced self-image. Conclusion Long-term results were

  11. Long-term results after Boston brace treatment in late-onset juvenile and adolescent idiopathic scoliosis

    OpenAIRE

    Lange, Johan Emil; Steen, Harald; Gunderson, Ragnhild; Brox, Jens Ivar

    2011-01-01

    Background It is recommended that research in patients with idiopathic scoliosis should focus on short- and long-term patient-centred outcome. The aim of the present study was to evaluate outcome in patients with late-onset juvenile or adolescent idiopathic scoliosis 16 years or more after Boston brace treatment. Methods 272 (78%) of 360 patients, 251 (92%) women, responded to follow-up examination at a mean of 24.7 (range 16 - 32) years after Boston brace treatment. Fifty-eight (21%) patient...

  12. Long-term results after Boston brace treatment in late-onset juvenile and adolescent idiopathic scoliosis

    OpenAIRE

    Gunderson Ragnhild; Steen Harald; Lange Johan; Brox Jens

    2011-01-01

    Abstract Background It is recommended that research in patients with idiopathic scoliosis should focus on short- and long-term patient-centred outcome. The aim of the present study was to evaluate outcome in patients with late-onset juvenile or adolescent idiopathic scoliosis 16 years or more after Boston brace treatment. Methods 272 (78%) of 360 patients, 251 (92%) women, responded to follow-up examination at a mean of 24.7 (range 16 - 32) years after Boston brace treatment. Fifty-eight (21%...

  13. Long-term results after Boston brace treatment in late-onset juvenile and adolescent idiopathic scoliosis.

    Science.gov (United States)

    Lange, Johan Emil; Steen, Harald; Gunderson, Ragnhild; Brox, Jens Ivar

    2011-08-31

    It is recommended that research in patients with idiopathic scoliosis should focus on short- and long-term patient-centred outcome. The aim of the present study was to evaluate outcome in patients with late-onset juvenile or adolescent idiopathic scoliosis 16 years or more after Boston brace treatment. 272 (78%) of 360 patients, 251 (92%) women, responded to follow-up examination at a mean of 24.7 (range 16 - 32) years after Boston brace treatment. Fifty-eight (21%) patients had late-onset juvenile and 214 had adolescent idiopathic scoliosis. All patients had clinical and radiological examination and answered a standardised questionnaire including work status, demographics, General Function Score (GFS) (100 - worst possible) and Oswestry Disability Index (ODI) (100 - worst possible), EuroQol (EQ-5D) (1 - best possible), EQ-VAS (100 - best possible), and Scoliosis Research Society - 22 (SRS - 22) (5 - best possible). The mean age at follow-up was 40.4 (31-48) years. The prebrace major curve was in average 33.2 (20 - 57)°. At weaning and at the last follow-up the corresponding values were 28.3 (1 - 58)° and 32.5 (7 - 80)°, respectively. Curve development was similar in patients with late-onset juvenile and adolescent start. The prebrace curve increased > 5° in 31% and decreased > 5° in 26%. Twenty-five patients had surgery. Those who did not attend follow-up (n = 88) had a lower mean curve at weaning: 25.4 (6-53)°. Work status was 76% full-time and 10% part-time. Eighty-seven percent had delivered a baby, 50% had pain in pregnancy. The mean (SD) GFS was 7.4 (10.8), ODI 9.3 (11.0), EQ-5D 0.82 (0.2), EQ-VAS 77.6 (17.8), SRS-22: pain 4.1 (0.8), mental health 4.1 (0.6), self-image 3.7 (0.7), function 4.0 (0.6), satisfaction with treatment 3.7 (1.0). Surgical patients had significantly reduced scores for SRS-physical function and self-image, and patients with curves ≥ 45° had reduced self-image. Long-term results were satisfactory in most braced patients and

  14. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  15. Molecular diagnosis of maturity onset diabetes of the young in India

    Directory of Open Access Journals (Sweden)

    Veena V Nair

    2013-01-01

    Full Text Available Diabetes is highly prevalent in India and the proportion of younger patients developing diabetes is on the increase. Apart from the more universally known type 1 diabetes and obesity related type 2 diabetes, monogenic forms of diabetes are also suspected to be prevalent in many young diabetic patients. The identification of the genetic basis of the disease not only guides in therapeutic decision making, but also aids in genetic counselling and prognostication. Genetic testing may establish the occurrence and frequency of early diabetes in our population. This review attempts to explore the utilities and horizons of molecular genetics in the field of maturity onset diabetes of the young (MODY, which include the commoner forms of monogenic diabetes.

  16. Cardiovascular, hormonal and metabolic responses to graded exercise in juvenile diabetics with and without autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Galbo, H; Christensen, N J

    1980-01-01

    Thirteen juvenile diabetics were studied in order to determine if decreased beat-to-beat variation during deep respiration, indicating abnormal autonomic nerve function, imply that cardiovascular, hormonal and metabolic responses are impaired. Patients with decreased beat-to-beat variation had to...... to be more heavily stressed during exercise to reach a certain heart rate or catecholamine level. The relation between other metabolic and hormonal response is discussed....

  17. Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis

    DEFF Research Database (Denmark)

    Ødum, Niels; Morling, Niels; Friis, J;

    1986-01-01

    Thirty-six unrelated Danish patients with pauciarticular Juvenile Chronic Arthritis (PJCA) and 120 controls were typed for HLA-DPw1-w6 and the local specificity CDPHEI with bulk-expanded Primed Lymphocyte Typing (PLT) cells. The frequency of HLA-DPw2 was 52.8% in PJCA patients and 16.7% in contro...

  18. The onset of type 2 diabetes: Proposal for a multi-scale model

    NARCIS (Netherlands)

    Castiglione, F.; Tieri, P.; Graaf, A. de; Franceschi, C.; Liò, P.; Ommen, B. van; Mazzà, C.; Tuchel, A.; Bernaschi, M.; Samson, C.; Colombo, T.; Castellani, G.C.; Capri, M.; Garagnani, P.; Salvioli, S.; Nguyen, V.A.; Bobeldijk-Pastorova, I.; Krishnan, S.; Cappozzo, A.; Sacchetti, M.; Morettini, M.; Ernst, M.

    2013-01-01

    Background: Type 2 diabetes mellitus (T2D) is a common age-related disease, and is a major health concern, particularly in developed countries where the population is aging, including Europe. The multi-scale immune system simulator for the onset of type 2 diabetes (MISSION-T2D) is a European Union-f

  19. The onset of type 2 diabetes: Proposal for a multi-scale model

    NARCIS (Netherlands)

    Castiglione, F.; Tieri, P.; Graaf, A. de; Franceschi, C.; Liò, P.; Ommen, B. van; Mazzà, C.; Tuchel, A.; Bernaschi, M.; Samson, C.; Colombo, T.; Castellani, G.C.; Capri, M.; Garagnani, P.; Salvioli, S.; Nguyen, V.A.; Bobeldijk-Pastorova, I.; Krishnan, S.; Cappozzo, A.; Sacchetti, M.; Morettini, M.; Ernst, M.

    2013-01-01

    Background: Type 2 diabetes mellitus (T2D) is a common age-related disease, and is a major health concern, particularly in developed countries where the population is aging, including Europe. The multi-scale immune system simulator for the onset of type 2 diabetes (MISSION-T2D) is a European

  20. Maturity onset diabetes of the young : Seek and you will find

    NARCIS (Netherlands)

    Heuvel-Borsboom, H; de Valk, H W; Losekoot, M; Westerink, J

    2016-01-01

    Maturity onset diabetes of the young (MODY) is a monogenic, autosomal dominant form of diabetes characterised by mutations in genes resulting in dysfunction of pancreatic β-cells and subsequent insulin production. We present a family with HNF1A-MODY due to a likely pathogenic mutation in HNF1A (c.59

  1. Maturity onset diabetes of the young : Seek and you will find

    NARCIS (Netherlands)

    Heuvel-Borsboom, H; de Valk, H W; Losekoot, M; Westerink, J

    2016-01-01

    Maturity onset diabetes of the young (MODY) is a monogenic, autosomal dominant form of diabetes characterised by mutations in genes resulting in dysfunction of pancreatic β-cells and subsequent insulin production. We present a family with HNF1A-MODY due to a likely pathogenic mutation in HNF1A (c.59

  2. Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Andersen, Gitte; Wegner, Lise; Rose, Christian Schack;

    2004-01-01

    candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His......223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant...... was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes....

  3. Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know?

    Directory of Open Access Journals (Sweden)

    Sung-Hoon Kim

    2015-12-01

    Full Text Available Maturity-onset diabetes of the young (MODY is a monogenic form of diabetes that is characterized by an early onset, autosomal dominant mode of inheritance and a primary defect in pancreatic β-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus. At least 13 MODY subtypes with distinct genetic etiologies have been identified to date. A correct genetic diagnosis is important as it often leads to personalized treatment for those with diabetes and enables predictive genetic testing for their asymptomatic relatives. Next-generation sequencing may provide an efficient method for screening mutations in this form of diabetes as well as identifying new MODY genes. In this review, I discuss a current update on MODY in the literatures and cover the studies that have been performed in Korea.

  4. Skin microvascular function in patients with type 1 diabetes: An observational study from the onset of diabetes.

    Science.gov (United States)

    Santesson, Pia; Lins, Per-Eric; Kalani, Majid; Adamson, Ulf; Lelic, Isak; von Wendt, Gunvor; Fagrell, Bengt; Jörneskog, Gun

    2017-05-01

    The development of disturbances in skin microcirculation in type 1 diabetes is not well characterised. We assessed skin microcirculation longitudinally from the onset of diabetes up to 29 years of duration to investigate when such disturbances start. Seventeen adult patients with type 1 diabetes participated. Skin microvascular function in digit IV of the left hand was investigated by laser Doppler fluxmetry (LDF, arbitrary units [AU]). LDF was carried out at rest and following one-min arterial occlusion. Time to peak LDF (s) and percentage increase of LDF (post-occlusive reactive hyperaemia, PRH%) were determined. Retinopathy was assessed from fundus photographs or ophthalmoscopic recordings. Skin microvascular function remained normal during the first five years. Compared with baseline and a non-diabetic reference group, time to peak LDF was prolonged after 7-9 years of diabetes ( p type 1 diabetes and preceded diabetic complications such as retinopathy.

  5. Mortality in childhood-onset type 1 diabetes: Nationwide population based data from Norway

    Directory of Open Access Journals (Sweden)

    Torild Skrivarhaug

    2013-06-01

    Full Text Available Type 1 diabetes with onset in childhood (0-14.9 years represents one of the most frequent chronic diseases in children and young adults. Norway has one of the highest incidences of childhood onset type 1 diabetes in the world. Before introduction of insulin therapy in 1922, few children survived more than one to two years after clinical onset. When insulin came available, a major shift occurred in the distribution of causes of death in type 1 diabetic patients away from diabetic coma, which dominated the pre-insulin era, to renal and cardiac diseases. The disease is related to a significant burden to society and patients because most cases require lifelong treatment with insulin as well as day-to-day monitoring. Type 1 diabetes also confers increased risk of severe late complications such as renal failure, blindness, amputations, heart disease and stroke. Despite advances in diabetes treatment, type 1 diabetes is still associated with considerable premature mortality resulting from acute and chronic complications of diabetes and an increase in mortality at every age. Although the main cause of death in type 1 diabetes is long-term complications, an excess death rate has also been reported in subjects with short duration without signs of long-term complications.

  6. An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs.

    Directory of Open Access Journals (Sweden)

    Kari J Ekenstedt

    2014-10-01

    Full Text Available An inherited polyneuropathy (PN observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10-10, Pgenome, corrected = 0.006 utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3'-end of exon 17 and six nucleotides from the 5'-end of intron 17 (c.1955_1958+6delCACGGTGAGC. This eliminates the 3'-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species.

  7. Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels

    DEFF Research Database (Denmark)

    Fredheim, Siri; Johannesen, J; Johansen, A

    2013-01-01

    AIMS/HYPOTHESIS: We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes. METHODS: The study is based on data from DanDiabKids, a Danish national diabetes register for children....... The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996-2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods. RESULTS: The study population comprised 2,964 children...

  8. Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes.

    Science.gov (United States)

    Mathews, Clayton E; Xue, Song; Posgai, Amanda; Lightfoot, Yaima L; Li, Xia; Lin, Andrea; Wasserfall, Clive; Haller, Michael J; Schatz, Desmond; Atkinson, Mark A

    2015-11-01

    Most natural history models for type 1 diabetes (T1D) propose that overt hyperglycemia results after a progressive loss of insulin-secreting β-cell mass and/or function. To experimentally address this concept, we prospectively determined morning blood glucose measurements every other day in multiple cohorts (total n = 660) of female NOD/ShiLtJ mice starting at 8 weeks of age until diabetes onset or 26 weeks of age. Consistent with this notion, a majority of mice that developed diabetes (354 of 489 [72%]) displayed a progressive increase in blood glucose with transient excursions >200 mg/dL, followed by acute and persistent hyperglycemia at diabetes onset. However, 135 of the 489 (28%) diabetic animals demonstrated normal glucose values followed by acute (i.e., sudden) hyperglycemia. Interestingly, diabetes onset occurred earlier in mice with acute versus progressive disease onset (15.37 ± 0.3207 vs. 17.44 ± 0.2073 weeks of age, P reversal of T1D by immunotherapeutic intervention, with increased effectiveness observed in situations of a progressive deterioration in euglycemia. These studies highlight a novel natural history aspect in this animal model, one that may provide important guidance for the selection of subjects participating in human trials seeking disease reversal.

  9. Breast-feeding and childhood-onset type 1 diabetes

    DEFF Research Database (Denmark)

    Cardwell, Chris R; Stene, Lars C; Ludvigsson, Johnny

    2012-01-01

    To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders.......To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders....

  10. The blood-retinal barrier permeability to fluorescein in normal subjects and in juvenile diabetics without retinopathy

    DEFF Research Database (Denmark)

    Krogsaa, B; Lund-Andersen, H; Mehlsen, J;

    1986-01-01

    The blood-retinal barrier permeability to fluorescein was determined in 20 eyes from 17 normal volunteers (mean age 31 years) and in 20 eyes from 19 juvenile diabetics without apparent retinopathy (mean age 35 years - mean duration of diabetes 6 years). The permeability was in normal subjects (1...... coefficient in the vitreous body was determined and juvenile diabetics without apparent retinopathy showed a diffusion coefficient of (0.80 +/- 0.25) X 10(-5) cm2/sec (mean +/- 2 X SD), which was the same as in normals where the diffusion coefficient was (0.69 +/- 0.46) X 10(-5) cm2/sec (mean +/- 2 X SD)....

  11. Predictive genetic testing in minors for Myocilin juvenile onset open angle glaucoma.

    Science.gov (United States)

    Souzeau, E; Glading, J; Ridge, B; Wechsler, D; Chehade, M; Dubowsky, A; Burdon, K P; Craig, J E

    2015-12-01

    Myocilin glaucoma is an autosomal dominant disorder leading to irreversible blindness, but early intervention can minimize vision loss and delay disease progression. The purpose of this study was to discuss the benefits of predictive genetic testing in minors for Myocilin mutations associated with childhood onset glaucoma. Three families with Myocilin mutations associated with an age of onset before 18 years and six unaffected at-risk children were identified. Predictive genetic testing was discussed with the parents and offered for at-risk minors. Parents opted for genetic testing in half of the cases. None carried the familial mutation. The age of disease onset in the family, the severity of the condition, and the age of the child are all factors that appear to influence the decision of the parent to test their children. Predictive genetic testing for early onset Myocilin glaucoma can facilitate early detection of disease or discharge from routine ophthalmic examinations.

  12. Acute-Onset Type 1 Diabetes that Developed During the Administration of Olanzapine

    Science.gov (United States)

    Iwaku, Kenji; Otuka, Fumiko; Taniyama, Matsuo

    2017-01-01

    The patient was 32-year-old man, who received olanzapine for schizophrenia and developed polyuria and thirst without drinking soft-drinks after 4 months. Five months after the initiation of treatment, he developed diabetic ketoacidosis (blood glucose: 490 mg/dL, HbA1c: 15.5%). He was diagnosed with type 1 diabetes (glutamic acid decarboxylase (GAD)-Ab: 5.6 U/mL, IA-2 Ab: 5.9 U/mL, fasting C-peptide: 0.12 ng/mL) and was put on intensive insulin therapy. At four months after the onset of 1A diabetes, he experienced a honeymoon phase that was sustained until the 40th month of treatment. We hypothesize that the administration of olanzapine to a patient with pre-type 1A diabetes induced marked hyperglycemia and accelerated the onset of type 1A diabetes. PMID:28154279

  13. Adult-onset juvenile xanthogranuloma of the external auditory canal: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Hur, Joon Ho; Kim, Jae Kyun; Seo, Gi Young; Choi, Woo Sun; Byun, Jun Soo; Lee, Woong Jae; Lee, Tae Jin [Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul (Korea, Republic of); Kim, Na Ra [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

    2016-05-15

    Juvenile xanthogranuloma (JXG) is a benign, spontaneously regressing lesion that usually occurs during the first year of life, but may also occur in adulthood. Although the most common presentation of JXG is the cutaneous lesion, it can also manifest in various visceral organs. JXG of the external auditory canal is extremely rare, and there have been only a few reports of those cases in the English literature. In this study, we present a case of pathologically proven JXG that occurred in the external auditory canal with a symptomatic clinical presentation.

  14. Prophylactic fenbendazole therapy does not affect the incidence and onset of type 1 diabetes in non-obese diabetic mice.

    Science.gov (United States)

    Franke, Deanna D H; Shirwan, Haval

    2006-03-01

    Fenbendazole (FBZ) is a common, highly efficacious broad-spectrum anthelmintic drug used to treat and limit rodent pinworm infections. However, the effect of its prophylactic use on the immune response of rodents is largely undefined. The non-obese diabetic (NOD) mouse is a model commonly used to study type 1 diabetes (T1D). Parasitic infections will inhibit diabetes development in NOD mice; thus, in the presence of contamination, prophylactic treatment with anthelmintics must be considered to maintain experimental research. Herein, we investigated the prophylactic use of FBZ in NOD mice to determine its effect on the incidence and onset of diabetes, lymphocyte sub-populations and T cell proliferative responses. NOD mice were separated into control and treatment groups. The treatment group received a diet containing FBZ. Animals were monitored for the incidence and onset of T1D. At matched time points, diabetic and non-diabetic mice were killed and splenic lymphocytes analyzed for various cell sub-populations and mitogen-induced proliferative responses using flow cytometry. Treated and control mice were monitored >23 weeks with no detectable effects on the incidence or onset of diabetes. Moreover, no significant differences were detected in lymphocyte sub-populations and mitogen-induced CD4(+) and CD8(+) proliferative responses between control and treatment groups. These results suggest that prophylactic FBZ treatment does not significantly alter the incidence or onset of diabetes in NOD mice. The prophylactic use of FBZ, therefore, presents a viable approach for the prevention of pinworm infection in precious experimental animals with substantial scientific and economic benefits.

  15. Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case-control study.

    Science.gov (United States)

    Bukulmez, Hulya; Fife, Mark; Tsoras, Monica; Thompson, Susan D; Twine, Natalie A; Woo, Patricia; Olson, Jane M; Elston, Robert C; Glass, David N; Colbert, Robert A

    2005-01-01

    Juvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic inflammatory disorders that primarily affect joints and can cause long-term disability. JRA is likely to be a complex genetic trait, or a series of such traits, with both genetic and environmental factors contributing to the risk for developing the disease and to its progression. The HLA region on the short arm of chromosome 6 has been intensively evaluated for genetic contributors to JRA, and multiple associations, and more recently linkage, has been detected. Other genes involved in innate and acquired immunity also map to near the HLA cluster on 6p, and it is possible that variation within these genes also confers risk for developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic reticulum chaperone that is involved in antigen processing, to elucidate its involvement, if any, in JRA. We employed both a case-control approach and the transmission disequilibrium test, and found linkage and association between the TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati Children's Hospital Medical Center (82 simplex families) and one collected by the British Paediatric Rheumatology Group in London, England (74 simplex families). The transmission disequilibrium test for these cohorts combined was statistically significant (chi2 = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium testing between the HLA alleles that are known to be associated with systemic onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals. These results suggest that there is a weak association between systemic onset JRA and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet unknown susceptibility allele in the centromeric part of chromosome 6.

  16. Changes in platelet function, blood coagulation and fibrinolysis during insulin-induced hypoglycaemia in juvenile diabetics and normal subjects

    DEFF Research Database (Denmark)

    Dalsgaard-Nielsen, J; Madsbad, S; Hilsted, J

    1982-01-01

    in the diabetics after hypoglycaemia, whereas no changes were seen in the control group. The activated partial thromboplastin time (APTT) was reduced in both groups and significantly lower in the diabetics than in the controls 120 min after insulin infusion. Fibrinogen and factor VIII R:Ag increased after insulin......Haemostatic parameters were assessed before insulin induced hypoglycaemia and 0, 1 and 2 hr after discontinuation of insulin infusion in 7 non-diabetics, aged 28 (22-31) years (mean and range), and 8 juvenile diabetics, aged 31 (27-35) years, with a mean duration of diabetes of 4 years...

  17. Direct diabetes-related costs in young patients with early-onset, long-lasting type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Christina Bächle

    Full Text Available OBJECTIVE: To estimate diabetes-related direct health care costs in pediatric patients with early-onset type 1 diabetes of long duration in Germany. RESEARCH DESIGN AND METHODS: Data of a population-based cohort of 1,473 subjects with type 1 diabetes onset at 0-4 years of age within the years 1993-1999 were included (mean age 13.9 (SD 2.2 years, mean diabetes duration 10.9 (SD 1.9 years, as of 31.12.2007. Diabetes-related health care services utilized in 2007 were derived from a nationwide prospective documentation system (DPV. Health care utilization was valued in monetary terms based on inpatient and outpatient medical fees and retail prices (perspective of statutory health insurance. Multiple regression models were applied to assess associations between direct diabetes-related health care costs per patient-year and demographic and clinical predictors. RESULTS: Mean direct diabetes-related health care costs per patient-year were €3,745 (inter-quartile range: 1,943-4,881. Costs for glucose self-monitoring were the main cost category (28.5%, followed by costs for continuous subcutaneous insulin infusion (25.0%, diabetes-related hospitalizations (22.1% and insulin (18.4%. Female gender, pubertal age and poor glycemic control were associated with higher and migration background with lower total costs. CONCLUSIONS: Main cost categories in patients with on average 11 years of diabetes duration were costs for glucose self-monitoring, insulin pump therapy, hospitalization and insulin. Optimization of glycemic control in particular in pubertal age through intensified care with improved diabetes education and tailored insulin regimen, can contribute to the reduction of direct diabetes-related costs in this patient group.

  18. Type 2 diabetes mellitus as a risk factor for the onset of depression

    DEFF Research Database (Denmark)

    Nouwen, Arie; Winkley, Kirsty; Twisk, Jos W R

    2010-01-01

    examined the association of diabetes and the onset of depression by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. METHODS: EMBASE, MEDLINE and PsycInfo were searched for articles published up to September 2009. All studies that examined the relationship......AIMS/HYPOTHESIS: An earlier meta-analysis showed that diabetes is a risk factor for the development and/or recurrence of depression. Yet whether this risk is different for studies using questionnaires than for those relying on diagnostic criteria for depression has not been examined. This study...... between type 2 diabetes and the onset of depression were included. Pooled relative risks were calculated using fixed and random effects models. RESULTS: Eleven studies met our inclusion criteria for this meta-analysis. Based on the pooled data, including 48,808 cases of type 2 diabetes without depression...

  19. Acute-onset opioid-induced hyperalgesia in a child with juvenile idiopathic arthritis.

    Science.gov (United States)

    Vijayan, Vini; Moran, Ryan; Elder, Melissa E; Sukumaran, Sukesh

    2012-10-01

    We describe a child with polyarticular juvenile idiopathic arthritis (JIA) presenting with severe diffuse pain refractory to nonsteroidal anti-inflammatory agents and high-dose opioids. Her JIA involved her knees and ankles and was mildly active on etanercept and nonsteroidal anti-inflammatory agents. At presentation, she complained of hip pain progressing to severe diffuse pain and allodynia involving her extremities. No abnormalities were seen in her laboratory parameters and imaging of her lower extremities. After appreciating no substantial benefit by increasing her opioids, her opioids were tapered and discontinued, and this was followed by significant alleviation in her pain, and a diagnosis of opioid-induced hyperalgesia (OIH) was made. Despite reports in adults, the phenomenon of OIH has been reported infrequently in children. To our knowledge, OIH has not been described in children with rheumatologic conditions. We recommend investigating the possibility of OIH when treating a child with JIA and severe refractory pain.

  20. Increased Fas and Bcl-2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile-Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Bernadete L. Liphaus

    2006-01-01

    Full Text Available Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE, juvenile rheumatoid arthritis (JRA and juvenile dermatomyositis (JDM. Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.

  1. Increased Fas and Bcl-2 expression on peripheral blood T and B lymphocytes from juvenile-onset systemic lupus erythematosus, but not from juvenile rheumatoid arthritis and juvenile dermatomyositis.

    Science.gov (United States)

    Liphaus, Bernadete L; Kiss, Maria H B; Carrasco, Solange; Goldenstein-Schainberg, Claudia

    2006-01-01

    Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal-Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.

  2. Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.

    Science.gov (United States)

    Surapolchai, Pacharapan; Ha, Shau-Yin; Chan, Godfrey Chi-Fung; Lukito, Johannes B; Wan, Thomas S K; So, Chi-Chiu; Chiang, Alan Kwok-Shing

    2013-03-01

    Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

  3. HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Berntson, Lillemor; Damgård, Michael; Andersson-Gäre, Boel

    2008-01-01

    OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous condition with very few clinical and laboratory signs that can help predict the course and severity of the disease in the individual patient. The cell-surface antigen HLA-B27 is well known to be associated with spondyloarthropathies...... to a population-based study as possible. METHODS: We studied an incidence-based cohort of 305 patients collected prospectively in 3 Nordic countries (Sweden, Norway, Denmark). Clinical and serological data of the first 3 years of the disease were collected. RESULTS: HLA-B27 was found to be positive in 25.......5% of the patients, and we found a higher proportion of HLA-B27-positive boys with older age at disease onset (p=0.034). Regression analysis showed a correlation of 0.7 in the HLA-B27-positive boys, pointing to a higher risk of more joint involvement with older age at disease onset. By Fisher's exact test...

  4. Novel views on new-onset diabetes after transplantation: development, prevention and treatment

    OpenAIRE

    Hecking, Manfred; Werzowa, Johannes; Haidinger, Michael; Walter H. Hörl; Pascual, Julio; Budde, Klemens; Luan, Fu L.; Ojo, Akinlolu; de Vries, Aiko P. J.; Porrini, Esteban; Pacini, Giovanni; Port, Friedrich K.; Sharif, Adnan; Säemann, Marcus D.

    2013-01-01

    New-onset diabetes after transplantation (NODAT) is associated with increased risk of allograft failure, cardiovascular disease and mortality, and therefore, jeopardizes the success of renal transplantation. Increased awareness of NODAT and the prediabetic states (impaired fasting glucose and impaired glucose tolerance, IGT) has fostered previous and present recommendations, based on the management of type 2 diabetes mellitus (T2DM). Unfortunately, the idea that NODAT merely resembles T2DM is...

  5. Diabetes distress in adult type 1 diabetes mellitus men and women with disease onset in childhood and in adulthood.

    Science.gov (United States)

    Lašaitė, Lina; Ostrauskas, Rytas; Žalinkevičius, Rimantas; Jurgevičienė, Nijolė; Radzevičienė, Lina

    2016-01-01

    To determine whether or not diabetes distress varies by age of type 1 diabetes mellitus (T1DM) onset and/or gender. A total of 700 adult T1DM patients were randomly selected from the Lithuanian Diabetes Registry; 214 of them (30.6%) agreed to participate and were recruited for the study. Diabetes distress (emotional burden, physician-related distress, regimen-related distress, interpersonal distress) was compared in 105 (42 men and 63 women) patients with T1DM diagnosed during 0-18years of life, and in 109 (61 men and 48 women) with T1DM diagnosed in adulthood, using Diabetes Distress Scale (DDS). Adult childhood-onset T1DM women have higher regimen-related distress (36.3±21.3 vs 26.6±16.2, p=0.016) than adulthood-onset women. Adult childhood-onset T1DM women experience higher diabetes distress (higher emotional burden (27.0±22.0 vs 15.6±16.4, p=0.006), physician-related distress (34.4±33.9 vs 20.7±29.4, p=0.024), total diabetes distress (41.2±13.6 vs 34.8±10.9, p=0.011)) than childhood-onset men. Adulthood-onset T1DM women experience higher physician-related distress (39.2±37.6 vs 23.4±32.5, p=0.013), but lower regimen-related distress (26.6±16.2 vs 35.8±21.6, p=0.014) than adulthood-onset men. In conclusion our findings reinforce the interdependence of psychological and biomedical factors in influencing health outcomes and support the need to provide psychological assessment and support to patients with T1DM. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Effect of repeated stress in early childhood on the onset of diabetes mellitus in male Spontaneously Diabetic Torii rats.

    Science.gov (United States)

    Ookawa, Katumasa; Mochizuki, Kazuo; Yokogoshi, Hidehiko

    2008-02-01

    Spontaneously Diabetic Torii (SDT) rats were discovered from SD rats and represent a confirmed spontaneous type 2 diabetes mellitus model. We investigated the effect of repeated stress in early childhood on SDT rats fed a high-fat diet, on locomotor activity and on the onset of diabetes mellitus. Regarding stress, a water immersion-restraint stress (WIRS) burden was applied 10 times every other day from 4 weeks of age. The results of the study showed, that the locomotor activity of the young SDT rats was clearly lower than that of the SD rats, and their locomotor activity was inferred to be congenitally low. In addition, the stress-burdened SDT rats showed delayed onset of diabetes mellitus and impaired glucose tolerance compared with the rats not receiving stress burden. The locomotor activity of SDT rats is less than that of SD rats, and they SDT rats are thought to have poor at spontaneous energy expenditure. On the other hand, the feeding efficiency of the WIRS-burdened SDT rats was reduced, and in comparison with the SDT rats with no WIRS burden, energy expenditure was increased; this is suggested to influence the onset of diabetes mellitus.

  7. Geographical Clustering of Juvenile Onset Systemic Lupus Erythematosus within the Sultanate of Oman

    Directory of Open Access Journals (Sweden)

    Ibrahim Al-Zakwani

    2013-05-01

    Full Text Available Objective: While SLE is found worldwide, there is diversity in clinical presentation of the disease according to geographical variations. The aim of this study is to describe geographical distributions of childhood onset SLE within Oman to identify geographical clustering and to compare the demographic, clinical, and immunological characteristics of this cluster against the rest of Oman.Methods: We retrospectively reviewed the hospital charts of 104 consecutive children with childhood onset SLE who were seen in pediatric rheumatology centers in the Sultanate of Oman over a 15-year period between 1995 and 2010.Results: Geographical clustering of childhood onset SLE was identified in Sharqiya region, which constituted 41% (n=43 of all cases in Oman. This cohort of patients had characteristic disease features which consisted of significantly more boys affected with SLE compared to the rest of the country (42% versus 15%; p=0.002. These children also tended to be younger (10.3 versus 16.5 years; p=0.001, diagnosed at an earlier age (6.4 versus 9.4 years; p<0.001 with a stronger family history of SLE (58% versus 33%; p=0.010. These children also had increased incidence of mucocutanous changes (81% versus 62%; p=0.036 and decreased hematological abnormalities (30% versus 51%; p=0.036.Conclusion: We identified geographical clustering of childhood onset SLE to Sharqiya region in Oman which is associated with unique demographical and clinical features. Whether increased prevalence of disease in this region is due to geographical, environmental, ethnic or genetic factors is yet to be determined. However, it is likely to be interplay of known and other unrecognized factors.

  8. Osteoprotegerin is up-regulated in pancreatic cancers and correlates with cancer-associated new-onset diabetes.

    Science.gov (United States)

    Shi, Wanchun; Qiu, Wei; Wang, Wenhua; Zhou, Xiaohui; Zhong, Xiaojing; Tian, Gang; Deng, Anmei

    2014-12-01

    New-onset diabetes might help to yield biomarkers for the early diagnosis of pancreatic cancer (PaC). In this study, we computationally predicted and experimentally validated osteoprotegerin (OPG) being associated with pancreatic cancer related new-onset diabetes. We first performed a meta-analysis on microarray datasets to search for genes specifically highly expressed in PaC, and then filtered for cytokines involved in islet dysfunction. The expression of OPG in PaC and normal pancreas were validated by immunohistochemistry. Serum OPG levels in healthy controls, non-cancerous diabetes and PaC patients with or without diabetes were detected by enzyme-linked immunosorbent assay (ELISA). In silico assay found that OPG up-regulated in PaC tissues in comparison to normal pancreas. Immunohistochemical data further confirmed that OPG was overexpressed in PaC samples. Furthermore, increased expression of OPG in PaC tissues correlated to the occurrence of new-onset diabetes, and adversely affected the patients' overall survival in both univariate and multivariate analysis. In addition, the serum levels of OPG were significantly higher in pancreatic cancer patients with new-onset diabetes than other groups including pancreatic patients without diabetes, new-onset type 2 diabetes and healthy controls. In conclusion, there is a close association between OPG and pancreatic cancer related new-onset diabetes, and OPG might serve as a potential biomarker for the early diagnosis of pancreatic cancer from populations with new-onset diabetes.

  9. Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.

    Science.gov (United States)

    Mayoral, María; Merchán-Naranjo, Jessica; Rapado, Marta; Leiva, Marta; Moreno, Carmen; Giráldez, Marisa; Arango, Celso; Parellada, Mara

    2010-11-01

    The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls. NSS were assessed by means of the Neurological Evaluation Scale in a sample of 29 patients with Asperger syndrome (mean age = 12.86 ± 2.58 years), 30 patients with first-episode early-onset psychoses (mean age 14.17 ± 1.02 years) and 30 healthy controls (mean age 12.33 ± 2.69 years). Significant group differences were found between Asperger syndrome patients and healthy controls both in all the Neurological Evaluation Scale subscales and in the Neurological Evaluation Scale total score. There were no significant differences between both groups of patients in any of the Neurological Evaluation Scale scores. NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses. © 2010 Blackwell Publishing Asia Pty Ltd.

  10. New-Onset Diabetes Mellitus After Heart Transplantation - Incidence, Risk Factors and Impact on Clinical Outcome.

    Science.gov (United States)

    Kim, Ho Jin; Jung, Sung-Ho; Kim, Jae-Joong; Yun, Tae-Jin; Kim, Joon Bum; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won

    2017-05-25

    New-onset diabetes mellitus (DM) can occur as a serious complication after heart transplantation, but the comparative data on its clinical impact on survival and on transplant-related adverse events are limited.Methods and Results:We reviewed a total of consecutive 391 patients aged ≥17 years undergoing isolated orthotopic heart transplantation at the present institution from 1992 to 2013. The entire cohort was divided into 3 groups: (1) no diabetes (n=257); (2) pre-existing DM (n=46); and (3) new-onset DM (n=88). Early and long-term clinical outcomes were compared across the 3 groups. Early death occurred in 8 patients (2.0%). Of the 345 non-diabetic patients before transplantation, 88 (25.5%) developed new-onset DM postoperatively. During follow-up, 83 (21.2%) died. On time-varying Cox analysis, new-onset DM was associated with increased risk for overall death (HR, 2.11; 95% CI: 1.26-3.55) and tended to have a greater risk for severe chronic kidney disease (HR, 1.77; 95% CI: 0.94-3.44). Compared with the no-diabetes group, the new-onset DM group had a worse survival rate (P=0.035), but a similar survival rate to that of the pre-existing DM group (P=0.364). New-onset DM has a negative effect on long-term survival and kidney function after heart transplantation. Further studies are warranted to evaluate the relevance of early diagnosis and timely control of new-onset DM to improve long-term survival.

  11. Hepatitis C virus antibodies in high risk juvenile onset systemic lupus erythematosus.

    Science.gov (United States)

    Aikawa, Nádia E; Nascimento, Ana P; Hayata, André L S; Bonfá, Eloisa; Goldenstein-Schainberg, Cláudia

    2016-01-01

    To evaluate the prevalence of hepatitis C virus (HCV) infection in high risk juvenile systemic lupus erythematosus (JSLE). Forty low income JSLE patients (6M:34F; mean age 19±4.4 yrs; mean disease duration 6±3.2 yrs) were studied. Twenty healthy children and adolescents matched for social economical level were included as controls. Anti-HCV tests were performed using a third generation microparticle enzyme immunoassay. Inclusion criterion was low social economical level. The frequencies of anti-HCV antibody were low and comparable between JSLE and control group (2.5% vs. 0, p=1.0). JSLE patients had significantly more risk factors for HCV infection compared to the control group, including immunosuppressive treatment (90% vs. 0, p<0.0001), hospitalization (50% vs. 12.5%, p=0.0006) and invasive procedures (47.5% vs. 12.5%, p=0.001). The observed low frequency of anti-HCV antibodies in high risk JSLE suggests that this virus does not seem to have a relevant role in the pathogenesis of this disease. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  12. Extremely elevated IL-18 levels may help distinguish systemic-onset juvenile idiopathic arthritis from other febrile diseases

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    Y. Xia

    Full Text Available The aim of this research was to explore whether IL-18 can be a serological marker for the diagnosis of systemic-onset juvenile idiopathic arthritis (sJIA. A total of 23 sJIA patients (13 males, median age 8.2, 20 acute lymphoblastic leukemia (ALL patients, 18 patients with severe infections (SIF, 26 Kawasaki disease (KD patients, 18 juvenile idiopathic arthritis (JIA patients, and 25 healthy control patients were selected for this study. Enzyme-linked immunosorbent assays (ELISAs were used to determine the serum concentrations of the S100A8, S100A9, and IL-6 proteins. The serum IL-18 levels were detected by a cytometric bead array (CBA. The serum IL-6 concentrations in various disease groups were significantly higher than that in the healthy control group. The IL-6 concentrations exhibited no significant difference between disease groups. The S100A8 level in the sJIA group was significantly higher than those of the ALL, JIA, and healthy control groups but showed no significant difference compared to the SIF and KD groups. The S100A9 serum concentration in the sJIA group was significantly higher than those in the ALL and healthy control groups and exhibited no significant difference from the SIF, KD, and JIA groups. The IL-18 level of the sJIA group was significantly higher than that of the other febrile disease groups. The IL-18 serum concentration may be used as a biological serum marker to distinguish sJIA from other febrile diseases.

  13. Extremely elevated IL-18 levels may help distinguish systemic-onset juvenile idiopathic arthritis from other febrile diseases

    Science.gov (United States)

    Xia, Y.; Cui, P.; Li, Q.; Liang, F.; Li, C.; Yang, J.

    2017-01-01

    The aim of this research was to explore whether IL-18 can be a serological marker for the diagnosis of systemic-onset juvenile idiopathic arthritis (sJIA). A total of 23 sJIA patients (13 males, median age 8.2), 20 acute lymphoblastic leukemia (ALL) patients, 18 patients with severe infections (SIF), 26 Kawasaki disease (KD) patients, 18 juvenile idiopathic arthritis (JIA) patients, and 25 healthy control patients were selected for this study. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum concentrations of the S100A8, S100A9, and IL-6 proteins. The serum IL-18 levels were detected by a cytometric bead array (CBA). The serum IL-6 concentrations in various disease groups were significantly higher than that in the healthy control group. The IL-6 concentrations exhibited no significant difference between disease groups. The S100A8 level in the sJIA group was significantly higher than those of the ALL, JIA, and healthy control groups but showed no significant difference compared to the SIF and KD groups. The S100A9 serum concentration in the sJIA group was significantly higher than those in the ALL and healthy control groups and exhibited no significant difference from the SIF, KD, and JIA groups. The IL-18 level of the sJIA group was significantly higher than that of the other febrile disease groups. The IL-18 serum concentration may be used as a biological serum marker to distinguish sJIA from other febrile diseases. PMID:28225869

  14. Validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes : a systematic review

    NARCIS (Netherlands)

    Hellemons, M. E.; Kerschbaum, J.; Bakker, S. J. L.; Neuwirt, H.; Mayer, B.; Mayer, G.; de Zeeuw, D.; Lambers Heerspink, H. J.; Rudnicki, M.

    2012-01-01

    Novel biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes have been recently identified. We performed a systematic review to assess the validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes in longitudinal studie

  15. Clinical features and treatment of maturity onset diabetes of the young (MODY

    Directory of Open Access Journals (Sweden)

    Gardner DS,Tai ES

    2012-05-01

    Full Text Available Daphne SL Gardner1, E Shyong Tai21Department of Endocrinology, Singapore General Hospital, 2Department of Endocrinology, National University Hospital, SingaporeAbstract: Maturity onset diabetes of the young (MODY is a heterogeneous group of disorders that result in ß-cell dysfunction. It is rare, accounting for just 1%–2% of all diabetes. It is often misdiagnosed as type 1 or type 2 diabetes, as it is often difficult to distinguish MODY from these two forms. However, diagnosis allows appropriate individualized care, depending on the genetic etiology, and allows prognostication in family members. In this review, we discuss features of the common causes of MODY, as well as the treatment and diagnosis of MODY.Keywords: type 1 diabetes, type 2 diabetes, HNF1A, HNF4A, HNF1B, GCK

  16. The epidemiology of childhood-onset Type I diabetes mellitus in Romania

    DEFF Research Database (Denmark)

    Serban, V.; Timar, R.; Dabelea, D.

    2001-01-01

    The ONROCAD Study group was established to provide descriptive epidemiological information on type 1 diabetes mellitus (DM) in Romania. Data on all new patients with type 1 DM with onset before age 15 years during the four-year period 1992-1995 in Romania were submitted from all members...

  17. Demographic and Clinical Characteristics of youth onset Diabetes Mellitus in Kashmir India

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    Riyaz Daga

    2015-07-01

    Full Text Available Diabetes mellitus (DM is a major public health problem. Objective of current study was to know the demography, clinical characteristics and etiology of youth Diabetes mellitus (DM in Kashmir, North India. METHODS: A prospective hospital based study, carried out in the Department of Endocrinology, SKIMS Srinagar, Kashmir India over the period from 2008 July - September 2010. Setting: A teaching, Research and tertiary care hospital at Srinagar Kashmir North India. PARTICIPANTS: All the new youth onset diabetes patients whose age were less than 25 years and were admitted in endocrinology ward for various reasons over the period from 2008 July - September 2010. PROCEDURE: All children with diabetes mellitus less than twenty five years of age were enrolled in this study. Variables recorded were demographics, clinical presentation, laboratory tests. RESULTS: A total of seventy two patients of youth onset diabetes mellitus were studied, Forty six were less than 20 years and twenty six more than 20 years of age. There were 33 males (45.8% and 39 females (54.2%. Family history of diabetes was present in nineteen (26.4%, fourteen were less than 20 yrs and five more than 20 yrs. Fifty nine (81.9% presented with osmotic symptoms, Thirteen (18.1% with DKA. Hypoglycemic episodes were present in forty one patients. Sixteen patients had nephropathy and nine had Retinopathy. CONCLUSION: Diabetes mellitus is a major public health problem. Type 2 diabetes mellitus is emerging as the form of diabetes in young diabetic patients, due to epidemic of childhood obesity.

  18. Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    Hui Yu; Li-Fang Xie; Kang Chen; Gang-Yi Yang; Xiao-Yan Xing; Jia-Jun Zhao; Tian-Pei Hong

    2016-01-01

    Background:Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly;however,the age at diagnosis has gradually reduced in recent years.Although the incidence of young-onset T2DM is increasing,it is still not fully clear the onset characteristics and risk factors of early-onset T2DM.The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.Methods:This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China.A total of 1545 patients with T2DM with an age at onset of<40 years were included,and the control group consisted of subjects aged <40 years with normal blood glucose level.Results:In patients with young-onset T2DM,the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%,respectively.Most of the patients were obese,followed irregular diet pattern and sedentary lifestyle,had life or work pressure,and had a family history of diabetes mellitus.Compared with subjects with normal blood glucose level,logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99,95% confidence interval [CI] 42.37-4714.87),family history of diabetes mellitus (OR 23.46,CI14.47-38.03),dyslipidemia (OR 2.65,CI 1.54-4.56),diastolic blood pressure (OR 1.02,CI 1.00-1.04),and body mass index (OR 0.95,CI 0.92-0.99) are independent factors for early-onset T2DM.Conclusions:We observed that abdominal obesity,family history of diabetes mellitus,and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM.It is,therefore,necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.

  19. Childhood-onset (Juvenile Huntington′s disease: A rare case report

    Directory of Open Access Journals (Sweden)

    Kailash Chandra Patra

    2015-01-01

    Full Text Available Huntington′s disease (HD is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions.

  20. Early-onset type 2 diabetes in a Mexican survey. Results from the National Health and Nutrition Survey 2006

    OpenAIRE

    Aída Jiménez-Corona; Rosalba Rojas; Francisco J Gómez-Pérez; Aguilar-Salinas, Carlos A

    2010-01-01

    OBJECTIVE: To describe the characteristics of patients with type 2 diabetes diagnosed before age 40 (early-onset type 2 diabetes) identified in a nation-wide, population-based study. MATERIALS AND METHODS: The survey was done in Mexico during 2006. Medical history, anthropometric and biochemical measurements were obtained in every subject. RESULTS: Cases diagnosed before (n=181) and after age 40 (n=659) were included. Early-onset type 2 diabetes was present in 13.1% of the previously diagnose...

  1. Nitrosative Stress in the Rat Retina at the Onset of Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Hernández-Ramírez, Ernesto; Sánchez-Chávez, Gustavo; Estrella-Salazar, Luis A; Salceda, Rocío

    2017-08-18

    Nitric oxide is a multifunctional molecule that can modify proteins via nitrosylation; it can also initiate signaling cascades through the activation of soluble guanylate cyclase. Diabetic retinopathy is the leading cause of blindness, but its pathogenesis is unknown. Multiple mechanisms including oxidative-nitrosative stress have been implicated. Our main goal was to find significant changes in nitric oxide (NO) levels and determine their association with nitrosative stress in the rat retina at the onset of diabetes. Diabetes was induced by a single intraperitoneal administration of streptozotocin. The possible nitric oxide effects on the rat retina were evaluated by the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a specific marker for NO-producing neurons, detected by histochemistry performed on whole retinas and retina sections. Immunohistochemistry was also performed on retina sections for iNOS, 3-nitrotyrosine (3-NT) and glial fibrillary acidic protein (GFAP). Retinal nitric oxide levels were assessed by measuring total nitrate/nitrite concentrations. Retinal cGMP levels were determined by radioimmunoassay. Western blots for nitrotyrosine (3-NT) and oxidized proteins were performed. In the present study, we found increased activity of NADPH-diaphorase and iNOS immunoreactivity in the rat retina at the onset of diabetes; this increase correlated with a remarkable increase in NO levels as early as 7 days after the onset of diabetes. However, cGMP levels were not modified by diabetes, suggesting that NO did not activate its signaling cascade. Even so, Western blots revealed a progressive increase in nitrated proteins at 7 days after diabetes induction. Likewise, positive nitrotyrosine immunolabeling was observed in the photoreceptor layer, ganglion cell layer, inner nuclear layer and some Müller cell processes in the retinas of diabetic rats. In addition, levels of oxidized proteins were increased in the retina early after

  2. Revision of the ADA-classification of diabetes mellitus type 2 (DMT2): the importance of maturity onset diabetes (MOD), and senile diabetes (DS).

    Science.gov (United States)

    Vacante, Marco; Malaguarnera, Michele; Motta, Massimo

    2011-01-01

    The changing social and economic conditions and the increase of the life span induced a progressive increase of the general prevalence of DMT2, particularly in the elderly population of the highly evoluted countries. Up to now 18 genetic loci have been identified, each of them consisting of several single nucleotide polymorphisms (SNPs). The evidence that the DMT2 is regulated by a high number of genes, demonstrate the pathogenetic complexity of this disease. The onset of diabetes mellitus (DM) in medium age is a consequence of the breakdown of the glycemic homeostasis in correlation with the genetic factors, such as the variants of the TCF7L2, obesity, etc., and the environmental factors, such as the life-style, the evolution of chronic-degenerative diseases, etc. In case of DM that onsets in old age we have to add the deterioration of the anti-aging defense mechanisms, characterized by the antagonistic action of the genes of longevity and aging. One can observe several clinical and therapeutic differences; therefore, the authors of this review propose the reinsertion of three forms into the DMT2 correlated with the age of onset and with the actual age of the subjects: the maturity onset diabetes (MOD), the maturity onset diabetes in elderly (MODE), and the senile diabetes (DS).

  3. Pyridoxal 5'-phosphate (PLP) deficiency might contribute to the onset of type I diabetes.

    Science.gov (United States)

    Rubí, B

    2012-01-01

    The incidence of type I diabetes is rising worldwide, particularly in young children. Type I diabetes is considered a multifactorial disease with genetic predisposition and environmental factors participating. Currently, despite years of research, there is no consensus regarding the factors that initiate the autoimmune response. Type I diabetes is preceded by autoimmunity to islet antigens, among them the protein glutamic acid decarboxylase, GAD-65. Pyridoxal 5'-phosphate (PLP) is formed from vitamin B6 by the action of pyridoxal kinase. Interaction of GAD65 with PLP is necessary for GAD65-mediated synthesis of the neurotransmitter γ-aminobutyric acid (GABA). PLP is also a required cofactor for dopamine synthesis by L-aromatic decarboxylase (L-AADC). Both GAD65 and L-AADC are expressed in pancreatic islets. Here it is proposed that lack of the vitamin B6 derivative pyridoxal 5'-phosphate might contribute to the appearance of pancreatic islet autoimmunity and type I diabetes onset.

  4. Reduction in IgG galactose in juvenile and adult onset rheumatoid arthritis measured by a lectin binding method and its relation to rheumatoid factor.

    OpenAIRE

    1991-01-01

    Glycosylation changes in patients with juvenile chronic and adult onset rheumatoid arthritis have been studied using a novel binding method. Both these major types of arthritis showed decreased galactosylation of serum IgG, which confirms earlier studies using a different, more complex chemical method. No significant correlation between serum IgG, IgM, and IgA rheumatoid factors and age corrected G(o) (percentage of oligosaccharide chains lacking galactose) was found. The possibility that the...

  5. Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a descriptive study of 45 children

    Directory of Open Access Journals (Sweden)

    Dung Nguyen Thi Ngoc

    2012-11-01

    Full Text Available Abstract Background Incidence and disease pattern of childhood-onset SLE is reported to differ among ethnic groups. Methods To describe disease pattern and 6 month follow-up in a referral based cohort of 45 Vietnamese children with SLE. Forty-five children who were subsequently diagnosed to have systemic lupus erythematosus (f/m = 4/1 were referred to the Ho Chi Minh City Children’s Hospital No.1 during a 12-month period in 2009. Results The mean age at diagnosis was 12.8 years (SD = 2.5. Thirty-seven (82% fulfilled criteria for lupus nephritis (LN. At diagnosis, impressively high SLEDAI and ECLAM scores were recorded (mean and SD, 23.8 (11.6 and 6 (2.3, respectively. The mean renal SLEDAI score was 8.2. The mean haemoglobin (g/dL, SD was 8.5 (2.1. The Coombs test was positive in 30 of 36 children (83%. The mean plasma creatinine was 0.98 (SD 1.2 and mean Westergren sedimentation rate was 83.6 (SD 37.4. The patient age at diagnosis was positively correlated to the SLEDAI (p = 0.034 and ECLAM (p = 0.022. At 6 month follow-up of the 45 children, 15 patients were in complete remission, 5 were in partial remission, 6 had stable disease, 3 had relapsed, 3 had evolving disease, 2 had ongoing resistant disease and 4 had died. Seven patients were lost to follow-up. A second renal biopsy showed an improved ISN class in 13 of 15; in 2 cases the ISN class remained unchanged. Conclusions Forty-five Vietnamese children with SLE were referred to Ho Chi Minh Children’s Hospital No. 1 during a16 month period from 2008–2009. These patients had a strikingly high prevalence of Coombs positive anaemia, a high prevalence of lupus nephritis, and very high SLEDAI and ECLAM scores at the time of diagnosis. While there may be referral biases, our Vietnamese SLE patients appear to have severe disease upon presentation but do reasonably well in the short-term.

  6. Maturity onset diabetes of the young (MODY)--history, first case reports and recent advances.

    Science.gov (United States)

    Siddiqui, Khalid; Musambil, Mohthash; Nazir, Nyla

    2015-01-15

    The world is seemingly facing a global increase in people suffering from diabetes especially in developing countries. The worldwide occurrence of diabetes for all age groups in year 2000 was estimated to be 2.8% and this number is most certainly expected to rise to 4.4% by 2030. Maturity-onset of diabetes of the young, or MODY, is a form of monogenic diabetes that is caused by mutations occurring in a number of different genes. Mutations in different genes tend to cause a slightly different variant of diabetes. MODY is typically diagnosed during late childhood, adolescence, or early adulthood and is usually observed to develop in adults during their late 50's. One of the main drawbacks in its diagnosis is that many people with MODY are misdiagnosed as having type 1 or type 2 diabetes. However, a molecular and genetic diagnosis can result in a better treatment and could also help in identifying other family members with MODY. This article explores the historical prospect and the genetic background of MODY, a brief summary of the first case reported and the significant factors that differentiate it from type 1 and type 2 diabetes.

  7. Severe diabetic ketoacidosis in combination with starvation and anorexia nervosa at onset of type 1 diabetes: a case report.

    Science.gov (United States)

    Espes, Daniel; Engström, Joakim; Reinius, Henrik; Carlsson, Per-Ola

    2013-05-01

    We here report a case of diabetic ketoacidosis at onset of type 1 diabetes after a prolonged period of starvation due to anorexia nervosa. A 53-year-old female with a history of anorexia nervosa was admitted to the psychiatric clinic due to psychotic behaviour and inability to take care of herself. Twenty-four hours after admission she was transferred to the clinic of internal medicine due to altered mental status, and laboratory screening revealed a pH of 6.895 and blood glucose concentration of 40 mmol/L. Due to the unusual combination of prolonged starvation and diabetic ketoacidosis we implemented some modifications of existing treatment guidelines and some special considerations regarding nutrition in order to prevent a re-feeding syndrome.

  8. Diabetes mellitus is associated with late-onset post-stroke depression.

    Science.gov (United States)

    Zhang, Yu; He, Ji-Rong; Liang, Huai-Bin; Lu, Wen-Jing; Yang, Guo-Yuan; Liu, Jian-Rong; Zeng, Li-Li

    2017-10-15

    To explore the associated factors of late-onset post-stroke depression (PSD). A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors. 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%. The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke. The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials

    Science.gov (United States)

    Moran, Antoinette; Bundy, Brian; Becker, Dorothy J; DiMeglio, Linda A; Gitelman, Stephen E; Goland, Robin; Greenbaum, Carla J; Herold, Kevan C; Marks, Jennifer B; Raskin, Philip; Sanda, Srinath; Schatz, Desmond; Wherrett, Diane K; Wilson, Darrell M; Krischer, Jeffrey P; Skyler, Jay S; Pickersgill, Linda; de Koning, Eelco; Ziegler, Anette-G; Böehm, Bernhard; Badenhoop, Klaus; Schloot, Nanette; Bak, Jens Friis; Pozzilli, Paolo; Mauricio, Didac; Donath, Marc Y; Castaño, Luis; Wägner, Ana; Lervang, Hans Henrik; Perrild, Hans; Poulsen, Thomas Mandrup

    2013-01-01

    and 25 anakinra-treated and 26 placebo-treated patients in the anakinra trial were included in the primary analyses. The difference in C peptide area under curve between the canakinumab and placebo groups at 12 months was 0·01 nmol/L (95% CI −0·11 to 0·14; p=0·86), and between the anakinra and the placebo groups at 9 months was 0·02 nmol/L (−0·09 to 0·15; p=0·71). The number and severity of adverse events did not differ between groups in the canakinumab trial. In the anakinra trial, patients in the anakinra group had significantly higher grades of adverse events than the placebo group (p=0·018), which was mainly because of a higher number of injection site reactions in the anakinra group. Interpretation Canakinumab and anakinra were safe but were not effective as single immunomodulatory drugs in recent-onset type 1 diabetes. Interleukin-1 blockade might be more effective in combination with treatments that target adaptive immunity in organ-specific autoimmune disorders. Funding National Institutes of Health and Juvenile Diabetes Research Foundation. PMID:23562090

  10. Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Andersen, Gitte; Wegner, Lise; Rose, Christian Schack;

    2004-01-01

    Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positiona...

  11. A genome-wide scan in families with maturity-onset diabetes of the young

    DEFF Research Database (Denmark)

    Frayling, Timothy M; Lindgren, Cecilia M; Chevre, Jean Claude;

    2003-01-01

    Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15-20% of families fitting MODY criteria do...... not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of beta-cell dysfunction. To facilitate the identification of novel...... MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage...

  12. Diabetic microangiopathy in capillaroscopic examination of juveniles with diabetes type 1

    Directory of Open Access Journals (Sweden)

    Grażyna Kaminska-Winciorek

    2012-01-01

    Full Text Available Introduction:The aim of this work was a quantitative and qualitative assessment of a selected part of the microcirculation in children with diabetes type 1 using videocapillaroscopy technique.Material/Methods:The authors tested a group consisting of 145 children (70 boys, 75 girls diagnosed and treated for diabetes type 1 in the Diabetic Clinic of GCZD in Katowice for at least one year. The study included history, clinical examination (including dermatological examination and videocapillaroscopy. Capillaroscopy, a non-invasive, painless and easily repeatable test, was performed using videocapillaroscopy with digital storage of the obtained images. All nailfolds were examined in all children using videocapillaroscopy, and the obtained images were assessed quantitatively and qualitatively for changes in capillary loops in the tested children according to the defined diagnostic procedure.Results:The analysis of capillaroscopic images described selected quantitative and qualitative characteristics. The conducted analysis showed an increase in the number of capillaries and their elongation, the presence of megacapillaries and Raynaud loops, which were accompanied by an intensive red background, indicating possible neoangiogenesis. The increase in the number of capillaries, disturbances in distribution of capillaries and the presence of abnormal capillaries were correlated with the longer duration of diabetes. Raynaud loops were more frequently found in the cases of increased mean values of HbA1c. Higher values of HbA1c influenced the capillaroscopic images, mainly the number of vessels, including Raynaud loops.Conclusions:Videocapillaroscopy technique could be a useful tool to detect the early changes of microangiopathy in children with diabetes type 1.

  13. Primary Pancreatic Lymphoma in a Patient with Maturity Onset Diabetes of the Young type 3

    Directory of Open Access Journals (Sweden)

    Valentina Bozzoli

    2012-01-01

    Full Text Available Primary pancreatic lymphoma (PPL is an extremely rare disease which occurs in pancreas, accounts for less than 1% of extra-nodal malignant lymphomas and 0,5% of cases of pancreatic masses. We report the case of PPL in a 15 year-old boy suffering from Maturity onset Diabetes of the young type 3 (MODY3 diagnosed at the age of 1 year

  14. EULAR/PReS standards and recommendations for the transitional care of young people with juvenile-onset rheumatic diseases.

    Science.gov (United States)

    Foster, Helen E; Minden, Kirsten; Clemente, Daniel; Leon, Leticia; McDonagh, Janet E; Kamphuis, Sylvia; Berggren, Karin; van Pelt, Philomine; Wouters, Carine; Waite-Jones, Jennifer; Tattersall, Rachel; Wyllie, Ruth; Stones, Simon R; Martini, Alberto; Constantin, Tamas; Schalm, Susanne; Fidanci, Berna; Erer, Burak; Dermikaya, Erkan; Ozen, Seza; Carmona, Loreto

    2017-04-01

    To develop standards and recommendations for transitional care for young people (YP) with juvenile-onset rheumatic and musculoskeletal diseases (jRMD). The consensus process involved the following: (1) establishing an international expert panel to include patients and representatives from multidisciplinary teams in adult and paediatric rheumatology; (2) a systematic review of published models of transitional care in jRMDs, potential standards and recommendations, strategies for implementation and tools to evaluate services and outcomes; (3) setting the framework, developing the process map and generating a first draft of standards and recommendations; (4) further iteration of recommendations; (5) establishing consensus recommendations with Delphi methodology and (6) establishing standards and quality indicators. The final consensus derived 12 specific recommendations for YP with jRMD focused on transitional care. These included: high-quality, multidisciplinary care starting in early adolescence; the integral role of a transition co-ordinator; transition policies and protocols; efficient communications; transfer documentation; an open electronic-based platform to access resources; appropriate training for paediatric and adult healthcare teams; secure funding to continue treatments and services into adult rheumatology and the need for increased evidence to inform best practice. These consensus-based recommendations inform strategies to reach optimal outcomes in transitional care for YP with jRMD based on available evidence and expert opinion. They need to be implemented in the context of individual countries, healthcare systems and regulatory frameworks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Hepatocyte nuclear factor 1-alpha mutation in normal glucose-tolerant subjects and early-onset type 2 diabetic patients.

    Science.gov (United States)

    Lim, Dong Mee; Huh, Nam; Park, Keun Yong

    2008-12-01

    The prevalence of diabetes in Korea is reported to be approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are rare in Korea. A diagnostic technique for autosomal dominant MODY is being actively sought. In this regard, we used a DNA chip to investigate the frequency of mutations of the MODY3 gene (hepatocyte nuclear factor-1alpha) in Korean patients with early-onset type 2 diabetes. The genomic DNA of 30 normal individuals [age, 24.9+/-8.6 years] and 25 patients with early-onset type 2 diabetes (age, 27+/-5.9 years) was extracted, and the MODY3 gene was amplified. The amplified DNA was hybridized onto a MODY3 chip, which has oligonucleotides of 15-25 bases, representing wild-type and mutant MODY3 sequences in both forward and reverse orientations, immobilized on its surface. Among the normal subjects, there was no mutation of MODY3. Among those with early-onset type 2 diabetes, there was one case of MODY3 mutation. Our results indicate that MODY3 mutations are not rare in Korean early-onset type 2 diabetes patients in Korea and suggest that MODY3 mutations in patients with early-onset type 2 diabetes need to be further evaluated.

  16. [Identifying different susceptibility loci associated with early onset diabetes and cardiovascular disease in Mexican families].

    Science.gov (United States)

    Canizales-Quinteros, Samuel; Huertas-Vázquez, Adriana; Riba-Ramírez, Laura; Monroy-Guzmán, Adriana; Domínguez-López, Aarón; Romero-Hidalgo, Sandra; Aguilar-Salinas, Carlos; Rodríguez-Torres, Maribel; Ramírez-Jiménez, Salvador; Tusié-Luna, María Teresa

    2005-01-01

    Coronary artery disease and diabetes mellitus are among the primary mortality and morbidity causes in Mexico. Genetic factors play a fundamental role in the development of these entities. In the past few years due to the recognition and study of families with monogenic forms of diabetes and dislipidemias associated with development of atherosclerosis, several genes and loci have been associated with these conditions through genetic linkage studies. These studies have provided evidence of the genetic heterogeneity that exists and the type of genes involved in different ethnic groups. The study of Mexican families with early-onset diabetes and combined familial hyperlipidemia showed the participation of different genetic loci associated with these conditions in the Mexican population. These findings show the value of gene mapping strategies in the identification of the genetic component in these entities in our population.

  17. Age of Childhood Onset in Type 1 Diabetes and Functional Brain Connectivity in Midlife.

    Science.gov (United States)

    Ryan, John P; Aizenstein, Howard J; Orchard, Trevor J; Ryan, Christopher M; Saxton, Judith A; Fine, David F; Nunley, Karen A; Rosano, Caterina

    2015-01-01

    The development of Type 1 diabetes mellitus (T1DM) within the first 7 years of life has been linked to poorer cognitive performance. Adults with T1DM have altered functional brain connectivity, but no studies have examined whether earlier age of T1DM onset is associated with functional connectivity later in life. Accordingly, we tested the relationship between age of onset and resting state functional connectivity in a cohort of middle-aged adults with childhood-onset T1DM. Participants were from a subsample of the Pittsburgh Epidemiology of Diabetes Complications cohort and included 66 adults (mean age = 47.54 years, 32 men). Resting state blood oxygen level-dependent activity was used to calculate mean connectivity for eight functional brain networks. A multivariate analysis of variance examined associations between age of onset and network connectivity. Diffusion tensor and fluid-attenuated inversion recovery images were analyzed to identify microstructural alterations and white-matter hyperintensity volumes. Later childhood onset of T1DM was associated with lower connectivity (F(8,57) = 2.40, p = .026). A significant interaction was present for current age such that an inverse association with age of onset for functional connectivity was present in older individuals (F(8,55) = 2.88, p = .035). Lower connectivity was associated with older age, increased white-matter hyperintensity volume, and lower microstructural integrity. Diagnosis of T1DM later in childhood may be associated with lower brain functional connectivity, particularly in those surviving into older ages. These alterations may be an early marker for subsequent cognitive decrements. Future studies are warranted to understand the pathways underlying these associations.

  18. Incretin hormones and maturity onset diabetes of the young--pathophysiological implications and anti-diabetic treatment potential.

    Science.gov (United States)

    Østoft, Signe Harring

    2015-09-01

    Maturity onset diabetes of the young (MODY) designates monogenic forms of non-autoimmune diabetes characterised by autosomal dominant inheritance, non-insulin dependent diabetes at onset and diagnosis often before 25 years of age. MODY constitutes genetically and clinically heterogeneous forms of diabetes. More than 8 different genes are known to cause MODY, among which hepatocyte nuclear factor 1 alpha (HNF1A) (MODY3) and glucokinase (GCK) (MODY2) mutations are the most common. Both forms of MODY are characterised by specific beta cell dysfunction, with patients with HNF1A-diabetes having a reduced insulin secretory capacity, while patients with GCK-diabetes have a glucose-sensing defect, but preserved insulin secretory capacity. Patients with MODY are effectively treated with sulphonylurea (SU) due to very high sensitivity to these drugs, but they are also prone to develop hypoglycaemia. The objectives of this thesis were to study the pathophysiology of GCK-diabetes and HNF1A-diabetes by investigating the incretin effect, the physiological response to food ingestion and to estimate the treatment potential of a glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with HNF1A-diabetes. In Study I we investigated the incretin effect and the responses of islet hormones and incretin hormones to oral glucose tolerance test (OGTT) and isoglycaemic IV glucose infusion (IIGI) in patients with GCK-diabetes, in patients with HNF1A-diabetes, and in BMI and age matched healthy individuals (CTRLs). In Study II we investigated responses of islet hormones and incretin hormones to a more physiological stimulus consisting of a standardised meal test in patients with GCK-diabetes, in patients with HNF1A--diabetes, and in BMI and age matched CTRLs. In Study III we conducted a randomised, double-blind, crossover trial investigating the glucose lowering effect and risk of hypoglycaemia during 6 weeks of treatment with the GLP-1RA, liraglutide compared to the SU, glimepiride

  19. Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy.

    Science.gov (United States)

    Kadian, Supriya; Mahadevan, Nanjaian; Balakumar, Pitchai

    2013-01-05

    We have previously shown that low-dose fenofibrate treatment has an ability to prevent diabetes-induced nephropathy in rats. We investigated here the comparative pre- and post-treatment effects of low-dose fenofibrate (30 mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55 mg/kg i.p.). The development of diabetic nephropathy was assessed biochemically and histologically. Moreover, lipid profile and renal oxidative stress were assessed. Diabetic rats after 8 weeks of STZ-administration developed apparent nephropathy by elevating serum creatinine, blood urea nitrogen and microproteinuria, and inducing glomerular-capsular wall distortion, mesangial expansion and tubular damage and renal oxidative stress. Fenofibrate (30 mg/kg/day p.o., 4 weeks) pretreatment (4 weeks after STZ-administration) markedly prevented diabetes-induced onset of diabetic nephropathy, while the fenofibrate (30 mg/kg/day p.o., 4 weeks) post-treatment (8 weeks after STZ-administration) was less-effective. However, both pre-and post fenofibrate treatments were effective in preventing diabetes-induced renal oxidative stress and lipid alteration in diabetic rats though the pretreatment was slightly more effective. Conversely, both pre-and post fenofibrate treatments did not alter elevated glucose levels in diabetic rats. It may be concluded that diabetes-induced oxidative stress and lipid alteration, in addition to a marked glucose elevation, play a detrimental role in the onset of nephropathy in diabetic rats. The pretreatment with low-dose fenofibrate might be a potential therapeutic approach in preventing the onset of nephropathy in diabetic subjects under the risk of renal disease induction. However, low-dose fenofibrate treatment might not be effective in treating the established nephropathy in diabetic subjects.

  20. Diabetes mellitus juvenil: a experiência de familiares de adolescentes e pré-adolescentes Juvenile diabetes: the family's experience with diabetic adolescents and pre-adolescents

    Directory of Open Access Journals (Sweden)

    Thaís Basso de Brito

    2009-06-01

    Full Text Available Este estudo foi desenvolvido com o objetivo de investigar a experiência de cuidar de adolescentes e pré-adolescentes portadores de diabetes tipo I, na perspectiva dos seus familiares. Foi utilizada a abordagem fenomenológica, modalidade de pesquisa qualitativa que se propõe a compreender os significados das experiências vividas. Foram entrevistados dez pais (9 mães e 1 pai em hospital de ensino do interior paulista. A experiência de cuidar do filho com diabetes emerge das convergências das descrições dos participantes, sendo descrita em três temas principais: o universo da doença; relação com as pessoas; reflexão sobre a experiência vivida. Os participantes descrevem suas dificuldades e estratégias para manterem a família unida e ainda oferecer suporte aos filhos. Eles acreditam que têm que aceitar e enfrentar os desafios, além de estimularem os filhos para sua segurança e qualidade de vida. Os dados mostraram a necessidade de um suporte profissional, além de um espaço para a discussão de temas tanto para as crianças com diabetes como para seus familiares.This study aimed at investigating the experience of taking care of adolescents and pre-adolescents with type 1 diabetes from the standpoint of their family members. A phenomenological approach, i.e. a type of qualitative analysis aimed at understanding the meaning of life experiences, was used. Ten parents (9 mothers and 1 father were interviewed at a teaching hospital in the interior of São Paulo state. The experience of taking care of a child with diabetes emerged from the converging points reported under 3 main themes: the universe of the disease; personal relationships; reflections on the experience. The participants described their difficulties and the strategies they use for keeping the family together besides providing support to the children. They believe they have to accept and face the challenges, besides motivating their children in order to ensure their

  1. Metabolic profiling in Maturity-onset diabetes of the young (MODY and young onset type 2 diabetes fails to detect robust urinary biomarkers.

    Directory of Open Access Journals (Sweden)

    Anna L Gloyn

    Full Text Available It is important to identify patients with Maturity-onset diabetes of the young (MODY as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK or hepatocyte nuclear factor 1 alpha (HNF1A, type 2 diabetes (T2D and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS was performed in a Discovery set of subjects with HNF1A-MODY (n = 14, GCK-MODY (n = 17, T2D (n = 14 and normoglycaemic controls (n = 34. Data were used to build a valid partial least squares discriminate analysis (PLS-DA model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic

  2. Metabolic profiling in Maturity-onset diabetes of the young (MODY) and young onset type 2 diabetes fails to detect robust urinary biomarkers.

    Science.gov (United States)

    Gloyn, Anna L; Faber, Johan H; Malmodin, Daniel; Thanabalasingham, Gaya; Lam, Francis; Ueland, Per Magne; McCarthy, Mark I; Owen, Katharine R; Baunsgaard, Dorrit

    2012-01-01

    It is important to identify patients with Maturity-onset diabetes of the young (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14), GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were used to build a valid partial least squares discriminate analysis (PLS-DA) model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic subtypes

  3. Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis.

    Directory of Open Access Journals (Sweden)

    Christian Ulrich Huebbers

    Full Text Available Juvenile-onset recurrent respiratory papillomatosis (RRP is associated with low risk human papillomavirus (HPV types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2-4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16(INK4A, p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR showed integration in the aldo-keto reductase 1C3 gene (AKR1C3 on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related malignancies.

  4. Juvenile Onset HD

    Science.gov (United States)

    ... Staff Directory Annual Convention Board of Trustees National Youth Alliance Advocacy Support Groups Social Workers Scientific Advisory Board News Financials Strategic Plan Careers Shop Locate Resources Media Center What is HD? What is HD? Stages ...

  5. A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians

    DEFF Research Database (Denmark)

    Anuradha, Shekher; Radha, Venkatesan; Deepa, Raj

    2005-01-01

    Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. ....... The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians....

  6. Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to Interventions for Diabetes Prevention.

    Science.gov (United States)

    Billings, Liana K; Jablonski, Kathleen A; Warner, A Sofia; Cheng, Yu-Chien; McAteer, Jarred B; Tipton, Laura; Shuldiner, Alan R; Ehrmann, David A; Manning, Alisa K; Dabelea, Dana; Franks, Paul W; Kahn, Steven E; Pollin, Toni I; Knowler, William C; Altshuler, David; Florez, Jose C

    2017-08-01

    Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits. This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP. The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944). Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism × treatment interaction (Pint < 0.05). Sequence kernel association tests examined the association between an aggregate of rare missense variants and insulinogenic traits. After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups. These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions.

  7. Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors

    Directory of Open Access Journals (Sweden)

    Jalal Taneera

    2014-01-01

    Full Text Available Although several molecular pathways have been linked to type 2 diabetes (T2D pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia n=20 and normoglycemia n=58 were subjected to Gene Set Enrichment Analysis (GSEA. About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM and maturity onset diabetes of the young (MODY pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis.

  8. The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Noer, Ivan; Deckert, Toke

    1976-01-01

    of albumin (TER), glomerular filtration rate (GFR), capillary filtration coefficient (CFC), and capillary diffusion capacity (CDC). The urinary albumin and beta2-microglobulin concentration were measured by sensitive radioimmunoassays; TER was detemined from the initial disappearance of intravenously......The microvascular permeability to small and large molecules was studied during good and poor metabolic regulation in ten short duration juvenile diabetics. The following variables were measured; daily urinary albumin and beta2-microglobulin-excretion rates, whole body transcapillary escape rate...

  9. Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset

    DEFF Research Database (Denmark)

    Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang

    2016-01-01

    It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured...

  10. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice

    DEFF Research Database (Denmark)

    Krych, Lukasz; Nielsen, Dennis Sandris; Hansen, Axel Kornerup;

    2015-01-01

    between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations...

  11. Is childhood-onset type I diabetes a wealth-related disease?

    DEFF Research Database (Denmark)

    Patterson, C.C.; Dahlquist, G.; Soltész, G.

    2001-01-01

    AIMS/HYPOTHESIS: To describe the epidemiology of childhood-onset Type I (insulin-dependent) diabetes mellitus in Europe, the EURODIAB collaborative group established prospective, geographically-defined registers of children diagnosed under 15 years of age. A total of 16,362 cases were registered ...... could reflect differences in environmental risk factors such as nutrition or lifestyle that are important in determining a country's incidence rate.......AIMS/HYPOTHESIS: To describe the epidemiology of childhood-onset Type I (insulin-dependent) diabetes mellitus in Europe, the EURODIAB collaborative group established prospective, geographically-defined registers of children diagnosed under 15 years of age. A total of 16,362 cases were registered......-reported associations with milk consumption (r = 0.58), coffee consumption (r = 0.51) and latitude (r = 0.40) were also observed. CONCLUSION/INTERPRETATION: The wide variation in childhood Type I diabetes incidence rates within Europe could be partially explained by indicators of national prosperity. These indicators...

  12. New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

    Science.gov (United States)

    Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

    2015-08-01

    A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

  13. New-onset diabetes after liver transplantation: a national report from China Liver Transplant Registry.

    Science.gov (United States)

    Ling, Qi; Xu, Xiao; Xie, Haiyang; Wang, Kai; Xiang, Penghui; Zhuang, Runzhou; Shen, Tian; Wu, Jian; Wang, Weilin; Zheng, Shusen

    2016-05-01

    New-onset diabetes after transplantation (NODAT) is a serious complication of liver transplantation (LT). The present study aimed to investigate the risk factors of NODAT by a national survey using the China Liver Transplant Registry database. A total of 10 204 non-pre-existing diabetic patients undergone primary LT between January 2000 and December 2013 were included. Risk factors were identified by logistic regression analysis. NODAT occurred in 24.3% of liver recipients with a median follow-up time of 2.6 years, and was associated with a significantly lower patient survival. NODAT increased not only diabetes related complications (e.g., infection, kidney failure) but also biliary stricture and cholangitis. NODAT patients who received hypoglycaemic treatment had a worse prognosis and a higher hepatocellular carcinoma recurrence compared with those without treatment. New-onset hyperglycaemia (9 h, recipient age >50 years, body mass index >25 kg/m(2) , other hepatitis (mainly hepatitis C), post-transplant intensive care unit stay >15 days, cytomegalovirus infection and corticosteroid at discharge. The incidence of NODAT in China is similar to that in Western countries. However, the NODAT-related complications are more common and severer in China compared with those in Western countries. The major risk factors are different. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus

    NARCIS (Netherlands)

    Heida, Karst Y.; Franx, Arie; Van Rijn, Bas B.; Eijkemans, Marinus J C; Boer, Jolanda M A; Verschuren, W.M. Monique; Oudijk, Martijn A.; Bots, Michiel L.; Van Der Schouw, Yvonne T.

    2015-01-01

    A prospective cohort study was conducted to assess the impact of a history of hypertensive disorder of pregnancy (HDP) or gestational diabetes mellitus (GDM) on the risk and age of onset of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease (CVD) later in life, independent of

  15. Long-Term Blood Pressure Variability, New-Onset Diabetes Mellitus, and New-Onset Chronic Kidney Disease in the Japanese General Population.

    Science.gov (United States)

    Yano, Yuichiro; Fujimoto, Shouichi; Kramer, Holly; Sato, Yuji; Konta, Tsuneo; Iseki, Kunitoshi; Iseki, Chiho; Moriyama, Toshiki; Yamagata, Kunihiro; Tsuruya, Kazuhiko; Narita, Ichiei; Kondo, Masahide; Kimura, Kenjiro; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi

    2015-07-01

    Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate diabetes mellitus, long-term BP variability during 3 years was associated with new-onset CKD risk, independently of mean or cumulative exposure to BP and metabolic profile changes during follow-up.

  16. Superior oblique tendon (Brown’s syndrome as the presenting finding in childhood onset HLA-B27-related enthesitis and juvenile idiopathic oligoarticular arthritis

    Directory of Open Access Journals (Sweden)

    C. Pham

    2014-11-01

    Full Text Available We report two patients who presented with Brown’s syndrome. The first is a 7-year-old boy who at the time of his diagnosis was also found to have enthesitis and HLA-B27 positivity. The second patient was diagnosed with bilateral Brown’s syndrome at 13 months of age. At age 7 she developed a persistent oligoarticular arthritis and unilateral anterior iritis consistent with the oligoarticular Juvenile Idiopatic Arthritis (JIA phenotype. These cases highlight ophthalmologic findings and diagnostic considerations with respect to Brown’s syndrome and associated childhood onset rheumatologic disease.

  17. Reduction in IgG galactose in juvenile and adult onset rheumatoid arthritis measured by a lectin binding method and its relation to rheumatoid factor.

    Science.gov (United States)

    Sumar, N; Isenberg, D A; Bodman, K B; Soltys, A; Young, A; Leak, A M; Round, J; Hay, F C; Roitt, I M

    1991-09-01

    Glycosylation changes in patients with juvenile chronic and adult onset rheumatoid arthritis have been studied using a novel binding method. Both these major types of arthritis showed decreased galactosylation of serum IgG, which confirms earlier studies using a different, more complex chemical method. No significant correlation between serum IgG, IgM, and IgA rheumatoid factors and age corrected G(o) (percentage of oligosaccharide chains lacking galactose) was found. The possibility that the less glycosylated IgG is preferentially confined to circulating IgM/IgG immune complexes cannot be excluded, however.

  18. Pathogenic Variant in ACTB, p.Arg183Trp, Causes Juvenile-Onset Dystonia, Hearing Loss, and Developmental Delay without Midline Malformation

    Directory of Open Access Journals (Sweden)

    Erin Conboy

    2017-01-01

    Full Text Available ACTB encodes the β-actin, and pathogenic variations in this gene have typically been associated with Baraitser-Winter cerebrofrontofacial syndrome, a congenital malformation syndrome characterized by short stature, craniofacial anomalies, and cerebral anomalies. Here, we describe the third case with the p.Arg183Trp variant in ACTB causing juvenile-onset dystonia. Our patient has severe, intractable dystonia, developmental delay, and sensorineural hearing loss, besides hyperintensities in the caudate nuclei and putamen on the brain MRI, which is a distinct but overlapping phenotype with the previously reported case of identical twins with the same alteration in ACTB.

  19. Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India

    Science.gov (United States)

    Hesarghatta Shyamasunder, Asha; Varghese, Deny; Varshney, Manika; Paul, Johan; Inbakumari, Mercy; Christina, Flory; Varghese, Ron Thomas; Kuruvilla, Kurien Anil; V. Paul, Thomas; Jose, Ruby; Regi, Annie; Lionel, Jessie; Jeyaseelan, L.; Mathew, Jiji; Thomas, Nihal

    2017-01-01

    Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with HNF1A Ser3Cys, two PDX1 Glu224Lys, His94Gln, two NEUROD1 Glu59Gln, Phe318Ser, one INS Gly44Arg, one GCK, one ABCC8 Arg620Cys and one BLK Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding PMID:28095440

  20. IDENTIFICATION OF NOVEL VARIANTS IN THE HEPATOCYTE NUCLEAR FACTOR 1 ALPHA GENE IN SOUTH INDIAN PATIENTS WITH MATURITY ONSET DIABETES OF YOUNG

    DEFF Research Database (Denmark)

    Radha, V; Ek, J; Anuradha, S

    2009-01-01

    Context: Mutations in the HNF 1A gene are the commonest cause of maturity-onset diabetes of the young (MODY) in most populations. India currently has the largest number of people with diabetes in the world and onset of type 2 diabetes occurs at a younger age with possible overlap with MODY. There...

  1. A DEEPER LOOK INTO TYPE 1 DIABETES – IMAGING IMMUNE RESPONES DURING ONSET OF DISEASE

    Directory of Open Access Journals (Sweden)

    Gustaf Christoffersson

    2016-08-01

    Full Text Available Cytotoxic T lymphocytes execute the killing of insulin-producing beta cells during onset of type 1 diabetes mellitus (T1D. The research community has come far in dissecting the major events in the development of this disease, but still the trigger and high-resolved information of the immunological events leading up to beta cell loss are missing. During the past decades, intravital imaging of immune responses has led to significant scientific breakthroughs in diverse models of disease, including T1D. Dynamic imaging of immune cells at the pancreatic islets during T1D onset has been made possible through the development of both advanced microscopes, and animal models that allow long-term immobilization of the pancreas. The use of these modalities has revealed a milling microenvironment at the pancreatic islets during disease onset with a plethora of active players. Clues to answering the remaining questions in this disease may lie in intravital imaging, including how key immune cells traffic to and from the pancreas, and how cells interact at this target tissue. This review highlights and discusses recent studies, models, and techniques focused to understand the immune responses during T1D onset through intravital imaging.

  2. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus

    DEFF Research Database (Denmark)

    Colombo, Carlo; Porzio, Ottavia; Liu, Ming;

    2008-01-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation...... in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset...... of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM....

  3. Prevention and management of new-onset diabetes mellitus in kidney transplantation.

    Science.gov (United States)

    Juan Khong, M; Ping Chong, Ch

    2014-04-01

    New-onset diabetes mellitus after transplantation (NODAT) is one of the complications that is increasingly occurring among kidney transplanted patients. It is associated with the risk of cardiovascular disease, graft failure and mortality. The risk of NODAT development increases with time from transplantation. Therefore, early detection and prompt action are essential in reducing the risk of NODAT and its complications. This paper aims to review the screening parameters, prevention and management strategies for NODAT in both pre- and post-transplantation conditions. The pre-transplant patient should be screened for diabetes and cardiometabolic risk factors. Blood glucose evaluation for the pre-transplantation period is important for early detection of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which are highly associated with the incidence of NODAT. Post-kidney transplant patients should have periodical blood glucose monitoring with more frequent assessment in the initial phase. As early hyperglycaemia development is a strong predictor for NODAT, prompt intervention is needed. When NODAT develops, monitoring and control of blood glucose profile, lipid profile, microalbuminuria, diabetic complications and comorbid conditions is recommended. Immunosuppressive regimen modification may be considered as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) guideline to reverse or to improve the diabetes after weighing the risk of rejection and other potential adverse effects. Strategies for modifying immunosuppressive agents include dose reduction, discontinuation, and selection of calcineurin inhibitor (CNI), anti-metabolite agents, mammalian target of rapamycin inhibitors (mTORi), belatacept and corticosteroids. Lifestyle modification and a conventional anti-diabetic approach, as in the type 2 diabetes mellitus guidelines, are also recommended in NODAT management.

  4. High Levels of Perfluorooctane Sulfonate in Children at the Onset of Diabetes

    Directory of Open Access Journals (Sweden)

    Barbara Predieri

    2015-01-01

    Full Text Available Background. Impairments of endocrine system may be associated with exposure to perfluorinated compounds that are able to bind nuclear receptors, including the peroxisome proliferator-activating receptors. Aim of this study was to assess perfluorooctane sulfonate and perfluorooctanoic acid concentrations in children and adolescents at the onset of type 1 diabetes compared to healthy controls. Methods. Forty-four children and adolescents were recruited and subdivided into two groups: (A 25 subjects with type 1 diabetes and (B 19 healthy controls. Perfluorinated compounds were measured using high performance liquid chromatography with electrospray ionization tandem mass spectrometry. Nonparametric statistical analysis was performed. Results. Perfluorooctane sulfonate concentrations were significantly higher in patients with type 1 diabetes compared to controls (1.53 ± 1.50 versus 0.55 ± 0.15 ng/mL, resp.; p<0.001. Multivariate linear regression analysis identified lipid levels as significant predictive factors for perfluorooctane sulfonate levels. Conclusions. Our data suggests that higher serum levels of perfluorooctane sulfonate may be considered a biomarker of exposure and susceptibility to develop type 1 diabetes.

  5. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders.

    Science.gov (United States)

    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita

    2012-01-01

    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose regulation, Lipid metabolism and nerve signaling. Emphasis is laid on BCHE's diverse functions whose impediment affects the above mentioned metabolic pathways. Insilco techniques were employed to analyze the sequence, structural and functional similarities of the two proteins. A point mutation is focused which is common to both BCHE and Neuroligin. The mutation occurs at the homologous position in both the proteins making them deficient. This affects the three metabolic pathways leading to the respective disorders. The work describes the pathway that describes the role of BCHE in the onset of obesity mediated diabetes. The pathway further explains the association between Diabetes, Obesity and neurological disturbances.

  6. Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats.

    Science.gov (United States)

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber; Haj, Fawaz G; Havel, Peter J

    2014-04-01

    There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset.

  7. Guidelines for the Child with Diabetes in the Classroom.

    Science.gov (United States)

    Maryland State Dept. of Health and Mental Hygiene, Baltimore.

    These guidelines are intended to aid Maryland teachers in managing the child with diabetes in the classroom. After a brief description of juvenile onset diabetes, information is provided on signs and symptoms of diabetes, general management, recognition and treatment of hypoglycemia, treatment, other recommendations, recognition and treatment of…

  8. Cortisol Levels in Children With Diabetic Ketoacidosis Associated With New-Onset Type 1 Diabetes Mellitus: A Retrospective Review

    Science.gov (United States)

    Williams, Kristen M.; Fazzio, Pamela; Oberfield, Sharon E.; Gallagher, Mary P.; Aranoff, Gaya S.

    2017-01-01

    There is little data documenting cortisol levels in children with diabetic ketoacidosis (DKA), despite the fact that untreated adrenal insufficiency (AI) could worsen the outcome of DKA. In this cross-sectional study, we assessed serum cortisol levels in 28 children with DKA and new onset type 1 diabetes mellitus evaluated at our center over a 5-year period. Average duration of diabetes-related symptoms was positively associated with age (P = .002), and significantly lower hemoglobin A1c levels were observed in the youngest children. The mean cortisol level was 40.9 mg/dL, with a range of 7.8 to 119 mg/dL. Cortisol levels were found to be inversely associated with serum pH (P = .007). There was no difference in the clinical outcome of the 4 patients who had cortisol levels less than 18 mg/dL. Overall, we did not find clinical or laboratory evidence of diminished cortisol reserve; however, the possibility of AI must be kept in mind when treating children with DKA. PMID:28145127

  9. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis

    DEFF Research Database (Denmark)

    Knol, M J; Twisk, Jos W R; Beekman, Aartjan T F

    2006-01-01

    AIMS/HYPOTHESIS: Evidence strongly suggests that depression and type 2 diabetes are associated, but the direction of the association is still unclear. Depression may occur as a consequence of having diabetes, but may also be a risk factor for the onset of type 2 diabetes. This study examined the ...... study is needed to test whether effective prevention or treatment of depression can reduce the incidence of type 2 diabetes and its health consequences.......AIMS/HYPOTHESIS: Evidence strongly suggests that depression and type 2 diabetes are associated, but the direction of the association is still unclear. Depression may occur as a consequence of having diabetes, but may also be a risk factor for the onset of type 2 diabetes. This study examined...... the latter association by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. METHODS: Medline and PsycInfo were searched for articles published up to January 2005. All studies that examined the relationship between depression and the onset of type 2 diabetes were...

  10. Juvenile onset systemic lupus erythematosus: a possible role for vitamin D in disease status and bone health.

    Science.gov (United States)

    Casella, C B; Seguro, L P C; Takayama, L; Medeiros, D; Bonfa, E; Pereira, R M R

    2012-10-01

    In juvenile onset systemic lupus erythematosus (JoSLE), evidence for the association between vitamin D status, lupus activity, and bone health is very limited and not conclusive. The aim of this study was, therefore, to assess in JoSLE patients the possible relevance of vitamin D deficiency in disease and bone parameters. Fifty-seven JoSLE patients were initially compared to 37 age, race and body mass index (BMI) -matched healthy controls. The serum concentration of 25 hydroxyvitamin D (25OHD) was determined by radioimmunoassay. Patients with 25OHD deficiency (≤20 ng/mL) were compared to those with levels >20 ng/mL. Disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Bone mineral density (BMD) and body composition (BC) were measured using dual-energy X-ray absorptiometry (DXA). 25OHD levels were similar in patients and controls (21.44 ± 7.91 vs 22.54 ± 8.25 ng/mL, p = 0.519), regardless of supplementation (65% of patients and none in controls). Thirty-one patients with 25OHD deficiency (≤20 ng/mL) were further compared to the 26 JoSLE patients with levels >20 ng/mL. These two groups were well-balanced regarding vitamin D confounding variables: age (p = 0.100), ethnicity (p = 1.000), BMI (p = 0.911), season (p = 0.502), frequency of vitamin D supplementation (p = 0.587), creatinine (p = 0.751), renal involvement (p = 0.597), fat mass (p = 0.764), lean mass (p = 0.549), previous/current use of glucocorticoids(GC) (p = 1.0), immunosuppressors (p = 0.765), and mean current daily dose of GC (p = 0.345). Patients with vitamin D deficiency had higher SLEDAI (3.35 ± 4.35 vs 1.00 ± 2.48, p = 0.018), lower C4 levels (12.79 ± 6.78 vs 18.38 ± 12.24 mg/dL, p = 0.038), lower spine BMD (0.798 ± 0.148 vs 0.880 ± 0.127 g/cm(2), p = 0.037) and whole body BMD (0.962 ± 0.109 vs 1.027 ± 0.098 g/cm(2), p = 0.024). JoSLE vitamin D

  11. Studio genetico del Diabete MODY (Maturity Onset Diabetes of the Young): approcci diagnostici in fenotipi diversi

    OpenAIRE

    Incani, Michela

    2010-01-01

    Il MODY è la forma più comune di diabete monogenico. Mutazioni nel gene GCK (MODY2) e nel gene HNF1α (MODY3) sono responsabili da sole del 70% di tutti i casi MODY. OBIETTIVO: validare in modo prospettico l’utilizzo di linee guida recentemente proposte, usando i criteri di inclusione per la selezione dei soggetti da sottoporre allo screening. METODI: Criteri di inclusione: Per GCK, iperglicemia persistente a digiuno >100 mg/dl, lieve aumento dell’HbA1c e della glicemia dopo OGTT < 54 mg/dl. ...

  12. The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut?

    Science.gov (United States)

    Ling, Qi; Xu, Xiao; Wang, Baohong; Li, Lanjuan; Zheng, Shusen

    2016-04-01

    New-onset diabetes is a frequent complication after solid organ transplantation. Although a number of common factors are associated with the disease, including recipient age, body mass index, hepatitis C infection, and use of immunosuppressive drugs, new-onset diabetes after liver transplantation (NODALT) has the following unique aspects and thus needs to be considered its own entity. First, a liver graft becomes the patient's primary metabolic regulator after liver transplantation, but this would not be the case for kidney or other grafts. The metabolic states, as well as the genetics of the graft, play crucial roles in the development of NODALT. Second, dysfunction of the islets of Langerhans is common in cirrhotic patients and would be exacerbated by immunosuppressive agents, particularly calcineurin inhibitors. On the other hand, minimized immunosuppressive protocols have been widely advocated in liver transplantation because of liver tolerance (immune privilege). Third and last, through the "gut-liver axis," graft function is closely linked to gut microbiota, which is now considered an important metabolic organ and known to independently influence the host's metabolic homeostasis. Liver transplant recipients present with specific gut microbiota that may be prone to trigger metabolic disorders. In this review, we proposed 3 possible sites for the origin of NODALT, which are liver, islets, and gut, to help elucidate the underlying mechanism of NODALT.

  13. Novel glucokinase mutation in a boy with maturity-onset diabetes of the young

    Directory of Open Access Journals (Sweden)

    Milenković Tatjana

    2008-01-01

    Full Text Available INTRODUCTION Maturity-onset diabetes of the young (MODY is a heterogenous group of disorders characterized by an early onset of insulin-independent diabetes mellitus, an autosomal dominant mode of inheritance and a primary defect in beta-cell. There are six subtypes of MODY. MODY2 and MODY3 are the most frequent. CASE OUTLINE We present a nine-year-old boy with intermittent hyperglycaemia. According to family history, the diagnosis of MODY2 was suspected. Molecular analysis revealed novel missense mutation R250c in exon 7 of glucokinase gene. Mutation (c.748 C>T is the result of substitution of aminoacid cysteine by arginine (p.Arg250Cys. This is the first pediatric patient with MODY2 in Serbia whose diagnosis is established at molecular level. CONCLUSION Molecular diagnosis of MODY has important consequences in terms of prognosis, therapy and family screening of the disorder. Investigation of other patients with MODY2 in our country is important to establish prevalence and nature of mutations in glucokinase gene.

  14. Mutations in MODY Genes Are not Common Cause of Early-Onset Type 2 Diabetes in Mexican Families

    Directory of Open Access Journals (Sweden)

    Bravo-Ríos LE

    2005-05-01

    Full Text Available CONTEXT: Maturity-onset diabetes of the young (MODY is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes. OBJECTIVE: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance. PATIENTS: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied. DESIGN: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines. MAIN OUTCOME MEASURES: MODY gene mutation screening and P379H mutant protein transactivation assay. RESULTS: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter. CONCLUSIONS: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.

  15. Lower urinary pH is useful for predicting renovascular disorder onset in patients with diabetes.

    Science.gov (United States)

    Ogawa, Susumu; Nako, Kazuhiro; Okamura, Masashi; Ito, Sadayoshi

    2015-01-01

    A lower urinary pH (UpH) is closely linked to diabetes. However, its relation to diabetic renovascular damage is unclear. This study aimed to identify the relationship between UpH and the exacerbation of diabetic renovascular disorders. This is a 10-year observational study targeting 400 outpatients with diabetes who registered in 2003. We investigated the relationship between UpH in 2003 and renovascular damage from 2003 to 2013. A total of 350 participants were eligible for the analysis. During their 10-year outpatient treatment, a decrease was seen in glycated hemoglobin levels, blood pressure, and estimated glomerular filtration rates (eGFRs), and an increase was seen in their urinary albumin-creatinine ratios (ACRs), uric acid (UA) levels, and intima-media thickness (IMT). UpH negatively correlated with urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), body mass index, UA, and ACR, and positively correlated with eGFR. The results of a multiple regression analysis showed that the independent risk factors for UpH were 8-OHdG, UA, eGFR, and ACR. UpH also negatively correlated with the percent change in IMT (%IMT), the percent change in pulse wave velocity (%PWV), and the change in log ACR (Δlog ACR), and positively correlated with the percent change in eGFR. A multiple regression analysis revealed that UpH was an independent risk factor for the %IMT, %PWV and Δlog ACR. Obese patients with low UpH values frequently suffered from sleep apnea syndrome. These results suggest that UpH is a useful marker for predicting the onset of renovascular disorder in patients with diabetes.

  16. Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis : a randomised trial

    NARCIS (Netherlands)

    Ruperto, Nicolino; Pistorio, Angela; Oliveira, Sheila; Zulian, Francesco; Cuttica, Ruben; Ravelli, Angelo; Fischbach, Michel; Magnusson, Bo; Sterba, Gary; Avcin, Tadej; Brochard, Karine; Corona, Fabrizia; Dressler, Frank; Gerloni, Valeria; Apaz, Maria T; Bracaglia, Claudia; Cespedes-Cruz, Adriana; Cimaz, Rolando; Couillault, Gerard; Joos, Rik; Quartier, Pierre; Russo, Ricardo; Tardieu, Marc; Wulffraat, Nico; Bica, Blanca; Dolezalova, Pavla; Ferriani, Virginia; Flato, Berit; Bernard-Medina, Ana G; Herlin, Troels; Trachana, Maria; Meini, Antonella; Allain-Launay, Emma; Pilkington, Clarissa; Vargova, Veronika; Wouters, Carine; Angioloni, Simona; Martini, Alberto

    2016-01-01

    BACKGROUND: Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with

  17. Clinical and genetic study of a juvenile-onset Huntington disease%少年型亨廷顿病临床与基因突变分析

    Institute of Scientific and Technical Information of China (English)

    郝莹; 陈园园; 顾卫红; 王国相; 马惠姿; 李丽林; 王康; 金淼; 段晓慧

    2012-01-01

    Background Huntington's disease (HD) is an autosomal dominant hereditary progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dementia, cognitive and affective impairment. There are selective neural cell loss and atrophy in the caudate and putamen. Dr. George Huntington firstly described the disease accurately and insightfully, which led to a widespread recognition of the inherited chorea that now bears his name. Huntington disease gene (1T15) locus on chromosome 4p16.3, and encompasses 67 exons with a trinucleotide repeat (CAG) in the first exon.The CAG repeat length is highly polymorphic in the population and expanded on at least one chromosome of individuals with HD. Clinically, patient with HD are often onset in adulthood. Juvenile - onset HD is relatively rare. Adult-onset HD patients usually have a CAG expansion from 40 to 55 whereas those with juvenile - onset greater than 60 which are often inherited from the father. We investigated the clinical features of a juvenile-onset case with Huntington disease and dynamic mutation of his family. Methods The CAG repeats of 1T15 gene were detected using polymerase chain reaction and capillary electrophoresis in 115 individuals with preliminary diagnosis as Huntington disease. The repeat numbers of some samples carried expanded or intermediate alleles were verified by the pMD18-T vector clone sequencing. Results Fragment analysis showed that one juvenile - onset case presenting with cognitive dysfunction and hypokinesis carried 15/68 CAG repeats of 1T15. His father carried 17/37 and mother carried 15/17. Conclusion 1) The juvenile-onset case of HD presented with different clinical features compared with adult-onset cases. The typical signs of adult-onset cases include progressive chorea, rigidity and dementia. The most common sign of juvenile-onset Huntington disease is cognitive decline. 2) The dynamic mutation of IT15 gene expansion of the CAG repeats in the intergenerational

  18. Profiling of circulating microRNAs in children with recent onset of type 1 diabetes

    Science.gov (United States)

    Erener, Suheda; Marwaha, Ashish; Tan, Rusung; Kieffer, Timothy J.

    2017-01-01

    Type 1 diabetes (T1D) is an autoimmune disease that is clinically silent until the majority of β cells are destroyed. There is an unmet need for reliable and cost-effective biomarkers to predict and diagnose diabetes at an early stage. A number of stable microRNAs (miRNAs) have been reported in serum and plasma and are now being investigated as biomarkers of different diseases. We measured the levels of 745 miRNAs in sera of children with recent-onset T1D and age-matched controls using locked nucleic acid–enhanced (LNA-enhanced) quantitative PCR profiling. Thirty-five miRNAs were significantly different between the groups, and 27 miRNAs were elevated in T1D. Good discriminating power was obtained for 6 miRNAs (miR-454-3p, miR-222-3p, miR-144-5p, miR-345-5p, miR-24-3p, and miR-140-5p), which were not elevated at later stages of diabetes. In silico pathway analysis, based on inferred miRNA target genes, associated glycosaminoglycan biosynthesis as well as PI3K/Akt, MAPK, and Wnt signaling pathways with early stages of T1D. Among the 27 upregulated miRNAs in T1D, 2 miRNAs significantly correlated with hemoglobin A1c (HbA1c), as did 5 of 8 downregulated miRNAs. A total of 134 miRNAs significantly correlated with HbA1c when stratifying hyperglycemia-induced miRNAs from T1D-specific miRNAs. In conclusion, we have identified a serum miRNA pattern of recent-onset T1D and signaling pathways that may be involved in its pathogenesis.

  19. Diabetes and Insulin Injection Modalities: Effects on Hepatic and Hippocampal Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Juvenile Diabetic Male Rats.

    Science.gov (United States)

    Rougeon, Véronica; Moisan, Marie-Pierre; Barthe, Nicole; Beauvieux, Marie-Christine; Helbling, Jean-Christophe; Pallet, Véronique; Marissal-Arvy, Nathalie; Barat, Pascal

    2017-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is often encountered in diabetes, leading to several clinical complications. Our recent results showing an elevated tetrahydrocortisol/tetrahydrocorticosterone ratio in morning urine of diabetic children compared to that of controls suggest an increased nocturnal activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the former. We hypothesized that these observations could be explained by a reduced inhibition of hepatic 11β-HSD1 activity by exogenous insulin owing to its subcutaneous (SC) administration and absence of first hepatic passage. Additionally, we hypothesized that hippocampal 11β-HSD1 activity might also be impaired by diabetes. We therefore measured HPA axis activity and 11β-HSD1 expression and activity in liver and hippocampus in streptozotocin-induced diabetic juvenile rats treated with SC or intraperitoneal (IP) insulin. Plasma corticosterone levels were elevated in untreated diabetic rats during the resting phase and restored by both types of insulin treatment. The mRNA expression and activity of 11β-HSD1 were increased in the untreated diabetic group in liver. Although diabetes was controlled equally whatever the route of insulin administration, liver 11β-HSD1 gene expression and activity was decreased only in the IP group, suggesting that a first hepatic pass is needed for 11β-HSD1 hepatic inhibition. In hippocampus, 11β-HSD1 activity was elevated in the untreated diabetic group but restored by both types of insulin treatment. Thus, these data extend our findings in diabetic children by showing impairment of hippocampal 11β-HSD1 in diabetes and by demonstrating that IP is preferable to SC insulin administration to restore 11β-HSD1 activity in liver.

  20. A hyper-ferritinemia syndrome evolving in recurrent macrophage activation syndrome, as an onset of amyopathic juvenile dermatomyositis: a challenging clinical case in light of the current diagnostic criteria.

    Science.gov (United States)

    Poddighe, Dimitri; Cavagna, Lorenzo; Brazzelli, Valeria; Bruni, Paola; Marseglia, Gian Luigi

    2014-11-01

    Juvenile dermatomyositis is an immune-mediated inflammatory multi-system disease involving mainly striated muscles and skin. Typical dermatological features are fundamental to establish the diagnosis, especially whenever the myopathy is very mild or absent, as it occurs in the form called as amyopathic juvenile dermatomyositis. Sometimes, systemic rheumatic diseases can develop a hyperferritinemia syndrome characterized by hemophagocytosis, namely macrophage activation syndrome, which represents a severe and life-threatening complication. Here, we describe a complex clinical history characterized by a hyper-ferritinemia syndrome after infectious mononucleosis, leading to recurrent episodes of macrophage activation syndrome. Finally, the late onset of several skin changes brought to a diagnosis of amyopathic juvenile dermatomyositis.

  1. Duodenal neuroendocrine tumor and the onset of severe diabetes mellitus in a US veteran

    Directory of Open Access Journals (Sweden)

    Lauren Murray

    2016-01-01

    Full Text Available Objective: Neuroendocrine tumors are neoplasms derived from endocrine cells, most commonly occurring in the gastrointestinal tract. Duodenal neuroendocrine tumors are rare tumors averaging 1.2–1.5 cm, and most are asymptomatic. Common presentation is abdominal pain, upper gastrointestinal bleed, constipation, anemia, and jaundice. Methods: An adult, Black, male patient with newly diagnosed diabetes mellitus presented to the emergency department with elevated liver function test and fatigue. Results: Magnetic resonance cholangiopancreatography demonstrated a large obstructing mass (3.6 cm × 4.4 cm × 3 cm within the second and third portions of the duodenum at the ampulla. Esophagogastroduodenoscopy demonstrated an ulcerated duodenal mass that was biopsied. Immunohistochemical stains were positive for synaptophysin, chromogranin B, and CK7. Chromogranin A was in normal range. Post-Whipple procedure demonstrated a 5.5 cm × 4.1 cm × 2.9 cm duodenal mass with invasion of the subserosal tissue of the small intestine, a mitotic rate of 2 per high-power field, and antigen Ki-67 of 2%–5%. Conclusion: This case raises the question as to if the patient developed diabetes mellitus due to the tumor size and location or if the new onset of diabetes was coincidental. This case also demonstrates the importance of a proficient history and physical.

  2. Relationship between inpatient hyperglycemia and insulin treatment after kidney transplantation and future new onset diabetes mellitus.

    Science.gov (United States)

    Chakkera, Harini A; Knowler, William C; Devarapalli, Yugandhara; Weil, E Jennifer; Heilman, Raymond L; Dueck, Amylou; Mulligan, David C; Reddy, Kunam S; Moss, Adyr A; Mekeel, Kristin L; Mazur, Marek J; Hamawi, Khaled; Castro, Janna C; Cook, Curtiss B

    2010-09-01

    Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose > or = 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C > or = 6.5%, fasting venous serum glucose > or = 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT.

  3. New-onset diabetes mellitus after kidney transplantation:Current status and future directions

    Institute of Scientific and Technical Information of China (English)

    Sneha Palepu; G V Ramesh Prasad

    2015-01-01

    A diagnosis of new-onset diabetes after transplantation(NODAT) carries with it a threat to the renal allograft,as well as the same short- and long-term implicationsof type 2 diabetes seen in the general population.NODAT usually occurs early after transplantation, andis usually diagnosed according to general populationguidelines. Non-modifiable risk factors for NODATinclude advancing age, African American, Hispanic, orSouth Asian ethnicity, genetic background, a positive family history for diabetes mellitus, polycystic kidney disease, and previously diagnosed glucose intolerance. Modifiable risk factors for NODAT include obesity and the metabolic syndrome, hepatitis C virus and cytomegalovirus infection, corticosteroids, calcineurin inhibitor drugs (especially tacrolimus), and sirolimus. NODAT affects graft and patient survival, and increases the incidence of post-transplant cardiovascular disease. The incidence and impact of NODAT can be minimized through pre- and post-transplant screening to identify patients at higher risk, including by oral glucose tolerance tests, as well as multi-disciplinary care, lifestyle modification, and the use of modified immunosuppressive regimens coupled with glucose-lowering therapies including oral hypoglycemic agents and insulin. Since NODAT is a major cause of post-transplant morbidity and mortality, measures to reduce its incidence and impact have the potential to greatly improve overall transplant success.

  4. Diabetes - resources

    Science.gov (United States)

    Resources - diabetes ... The following sites provide further information on diabetes: American Diabetes Association -- www.diabetes.org Juvenile Diabetes Research Foundation International -- www.jdrf.org National Center for Chronic Disease Prevention and Health Promotion -- ...

  5. The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, L. B.; Porksen, S.; Andersen, M. L. M.;

    2011-01-01

    Background: The protein tyrosine phosphatase nonreceptor type 2 (PTPN22) has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients......-2A, GADA, ICA, ZnT8Ab) in children during the first year after diagnosis of type 1 diabetes. Methods: The C1858T variant was genotyped in an international cohort of children (n = 257 patients) with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association...... with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA(1c)), glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA) and diabetes-related autoantibodies (IA...

  6. Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis

    Science.gov (United States)

    Hinks, Anne; Martin, Paul; Flynn, Edward; Eyre, Steve; Packham, Jon; Barton, Anne; Worthington, Jane; Thomson, Wendy

    2010-01-01

    Background There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. Objective To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. Methods Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane–Armitage trend test implemented in PLINK. Results One SNP in the LPP gene, rs1464510, showed significant association with JIA (ptrend=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (ptrend=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (ptrend=0.005, OR=1.88, 95% CI 1.2 to 2.94). Conclusions Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts. PMID:20647273

  7. The Effects of 12 Weeks Regular Aerobic Exercise on Brain-derived Neurotrophic Factor and Inflammatory Factors in Juvenile Obesity and Type 2 Diabetes Mellitus

    OpenAIRE

    Lee, Sung Soo; Yoo, Jae Ho; Kang, Sung; Woo, Jin Hee; Shin, Ki Ok; Kim, Kwi Beak; Cho, Su Youn; Roh, Hee Tae; Kim, Young Il

    2014-01-01

    [Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enroll...

  8. Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies

    OpenAIRE

    Gang Zhao; Gitanjali Dharmadhikari; Kathrin Maedler; Michael Meyer-Hermann

    2014-01-01

    Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from in vitro experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting gluco...

  9. Body composition in adults with Type 1 diabetes at onset and during the first year of insulin therapy

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Almdal, Thomas Peter; Hilsted, J

    2002-01-01

    . RESULTS: During the first year after onset of diabetes body weight (BW) increased 4.3 +/- 2.9 (0.1-8.3) kg (P = 0.0012) distributed as a 13.3% (1.6 kg) increase in total fat mass (FM) and 4.9% (2.5 kg) increase in lean body soft tissue mass (LBM). The self-reported weight loss at onset was 6.3 +/- 2.5 kg......AIMS: To describe body composition in patients with Type 1 diabetes at diagnosis and during the first year after initiation of insulin therapy. RESEARCH DESIGN AND METHODS: In 10 (eight male and two female) newly onset Type 1 patients, age 31.5 +/- 3.2 years (27-37 years) (sd and range), body mass...... was within the expected range. CONCLUSIONS: During the first year after onset of Type 1 diabetes the mean increase in BW is 6.5% with a 13.3% increase in FM and a 4.9% increase in LBM. Self-reported data on premorbid BW suggest an approximately 10% reduction in BW at onset of Type 1 diabetes. Compared...

  10. Meta-Analysis of Impact of Different Types and Doses of Statins on New-Onset Diabetes Mellitus

    OpenAIRE

    Navarese, Eliano Pio; Buffon, Antonino; Andreotti, Felicita; Koziński, Marek; Welton, Nicky; Fabiszak, Tomasz; Caputo, Salvatore; GRZEŚK, GRZEGORZ; Kubica, Aldona; Świątkiewicz, Iwona; Sukiennik, Adam; Kelm, Malte; De Servi, Stefano; Kubica, Jacek

    2013-01-01

    Recent reports indicate that statins are associated with an increased risk for new-onset diabetes mellitus (DM) compared with placebo and that this relation is dose dependent. The aim of this study was to perform a comprehensive network meta-analysis of randomized controlled trials (RCTs) investigating the impact of different types and doses of statins on new-onset DM. RCTs comparing different types and doses of statins with placebo were searched for using the MEDLINE, Embase, ...

  11. Protection against myocardial ischemia-reperfusion injury at onset of type 2 diabetes in Zucker diabetic fatty rats is associated with altered glucose oxidation.

    Directory of Open Access Journals (Sweden)

    Jonas Agerlund Povlsen

    Full Text Available BACKGROUND: Inhibition of glucose oxidation during initial reperfusion confers protection against ischemia-reperfusion (IR injury in the heart. Mitochondrial metabolism is altered with progression of type 2 diabetes (T2DM. We hypothesized that the metabolic alterations present at onset of T2DM induce cardioprotection by metabolic shutdown during IR, and that chronic alterations seen in late T2DM cause increased IR injury. METHODS: Isolated perfused hearts from 6 (prediabetic, 12 (onset of T2DM and 24 (late T2DM weeks old male Zucker diabetic fatty rats (ZDF and their age-matched heterozygote controls were subjected to 40 min ischemia/120 min reperfusion. IR injury was assessed by TTC-staining. Myocardial glucose metabolism was evaluated by glucose tracer kinetics (glucose uptake-, glycolysis- and glucose oxidation rates, myocardial microdialysis (metabolomics and tissue glycogen measurements. RESULTS: T2DM altered the development in sensitivity towards IR injury compared to controls. At late diabetes ZDF hearts suffered increased damage, while injury was decreased at onset of T2DM. Coincident with cardioprotection, oxidation of exogenous glucose was decreased during the initial and normalized after 5 minutes of reperfusion. Metabolomic analysis of citric acid cycle intermediates demonstrated that cardioprotection was associated with a reversible shutdown of mitochondrial glucose metabolism during ischemia and early reperfusion at onset of but not at late type 2 diabetes. CONCLUSIONS: The metabolic alterations of type 2 diabetes are associated with protection against IR injury at onset but detrimental effects in late diabetes mellitus consistent with progressive dysfunction of glucose oxidation. These findings may explain the variable efficacy of cardioprotective interventions in individuals with type 2 diabetes.

  12. Impact of Statin Use on Development of New-Onset Diabetes Mellitus in Asian Population.

    Science.gov (United States)

    Rha, Seung-Woon; Choi, Byoung Geol; Seo, Hong Seog; Park, Sang-Ho; Park, Ji Young; Chen, Kang-Yin; Park, Yoonjee; Choi, Se Yeon; Shim, Min-Suk; Kim, Ji Bak; Park, Taeshik; Park, Joonhyung; Lee, Jae Joong; Park, Eun Jin; Park, Sung Hun; Choi, Jah Yeon; Lee, Sunki; Na, Jin Oh; Choi, Cheol Ung; Lim, Hong Euy; Kim, Jin Won; Kim, Eung Ju; Park, Chang Gyu; Oh, Dong Joo

    2016-02-01

    There have been several reports showing that the statin use is associated with new-onset diabetes mellitus (DM). The aim of the present study was to evaluate the impact of chronic statin use on development of new-onset DM in a series of Asian population. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2010. A total of 10,994 patients without a history of diabetes were analyzed. Baseline lipid profiles, fasting glucose, Hemoglobin (Hb) A1c, and glucose tolerance tests were measured in all patients before statin treatment. Included patients had HbA1c ≤ 5.7% and fasting glucose level ≤ 100 (mg/dl). The patients were divided into 2 groups according to the use of statins (the statin group, n = 2,324 patients and the nonstatin group, n = 8,670 patients). To adjust baseline potential confounders, a propensity score-matched analysis was performed using logistic regression model. After propensity score matching, 2 propensity-matched groups (1,699 pairs, n = 3,398, C statistic = 0.859) were generated and analyzed. After propensity score matching, baseline characteristics of both groups were balanced except that the statin group was older and had higher rate of coronary artery disease compared with the nonstatin group. During a 3-year follow-up, the statin group had higher incidence of new-onset DM compared with the nonstatin group (hazard ratio 1.99, 95% CI 1.36 to 2.92, p <0.001), but the statin group showed lower incidence of major adverse cerebral-cardiovascular events compared with the nonstatin group (hazard ratio 0.40, 95% CI 0.19 to 0.85, p <0.001). In the present study, although the use of statins was associated with higher rate of new-onset DM, it markedly improved 3-year cardiovascular outcomes in Asian population.

  13. The incidence of new onset diabetes after transplantation and related factors: Single center experience.

    Science.gov (United States)

    Sinangil, Ayse; Celik, Vedat; Barlas, Soykan; Koc, Yener; Basturk, Taner; Sakaci, Tamer; Akin, Emin Baris; Ecder, Tevfik

    New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication and is considered a risk factor for patients undergoing renal transplant. The aim of this study was to evaluate the incidence and developing duration of new-onset diabetes after transplant (NODAT) and influencing factors. All patients' data was investigated retrospectively. Diabetics, follow-up period<6 months, age<18years were excluded. Demographic, clinical and laboratory data was recorded. Patients were divided into two groups: with/without NODAT. NODAT group was divided into four subgroups according to the time of developing NODAT, which were 0-3, 3-6, 6-12 and 12 months later. Two groups were compared, to investigate the incidence of NODAT and risk factors associated with the occurrence of NODAT. We retrospectively analyzed the records of 570 patients, of which 420 patients were included. Seventy (16.6%) patients had NODAT (36 female, mean age 51.7±8.2 years, mean follow-up 41.6±21.5 months), 52.8% of patients developed NODAT within the first three months of being diagnosed. 350 patients (116 female, mean age 43.2±12.5 years, mean follow-up 41.6±21.5 months) were without NODAT. The incidence of impaired fasting glucose (IFG) during the first week after transplant was found to be higher in the patients with NODAT (p<0.001). There was positive correlation between NODAT and older age, obesity, family history of diabetes, presence of IFG, fasting plasma glucose, total and LDL-cholesterol, triglycerides, parathormone. Old age, obesity, presence of IFG, pretransplant hypertriglyceridemia and hyperparathyroidism were predictors of development of NODAT. Incidence of NODAT, especially the first six months, was high. All patients should be screened for IFG within the first week. Patients with dyslipidemia, elderly and obese patients should be closely monitored for the risk of development of NODAT. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S

  14. Impact of Antiinflammatory Treatment on the Onset of Uveitis in Juvenile Idiopathic Arthritis: Longitudinal Analysis From a Nationwide Pediatric Rheumatology Database

    Science.gov (United States)

    Schenck, Sandra; Niewerth, Martina; Heiligenhaus, Arnd; Minden, Kirsten; Klotsche, Jens

    2015-01-01

    Objective Based on a nationwide database, this study analyzed the influence of methotrexate (MTX), tumor necrosis factor (TNF) inhibitors, and a combination of the 2 medications on uveitis occurrence in juvenile idiopathic arthritis (JIA) patients. Methods Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating pediatric rheumatologic sites. Patients with a JIA disease duration of uveitis was evaluated by discrete‐time survival analysis. Results A total of 3,512 JIA patients (mean ± SD age 8.3 ± 4.8 years, 65.7% female, 53.2% antinuclear antibody positive, and mean ± SD age at arthritis onset 7.8 ± 4.8 years) fulfilled the inclusion criteria. Mean ± SD total followup time was 3.6 ± 2.4 years. Uveitis developed in a total of 180 patients (5.1%) within 1 year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). Disease‐modifying antirheumatic drug (DMARD) treatment in the year before uveitis onset significantly reduced the risk for uveitis as follows: MTX: hazard ratio (HR) 0.63, P = 0.022; TNF inhibitors: HR 0.56, P uveitis risk (HR 0.29, P uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. PMID:26212111

  15. Serum Concentrations of Transforming Growth Factor-Beta 1 in Predicting the Occurrence of Diabetic Retinopathy in Juvenile Patients with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Katarzyna Zorena

    2013-01-01

    Full Text Available In the present study, we have decided to evaluate if serum transforming growth factor-beta 1 (TGF-β1 concentrations may have diagnostic value in predicting the occurrence of diabetic retinopathy (DR in juvenile patients with type 1 diabetes mellitus (T1DM. The study included 81 children and adolescents with T1DM and 19 control subjects. All study participants had biochemical parameters examined, underwent an eye examination, and 24-hour blood pressure monitoring. Moreover, serum concentrations of TGF-β1 were measured. The group of patients with T1DM and nonproliferative diabetic retinopathy (NPDR had statistically significant higher serum levels of TGF-β1 (P=0.001 as compared to T1DM patients without retinopathy as well as the healthy control subject. The threshold serum TGF-β1 concentrations which had a discriminative ability to predict the presence of DR were calculated using the receiver operating characteristic (ROC curves analysis and amounted to 443 pg/ml. The area under the ROC curve (AUCROC was 0.80, and its population value was in the range of 0.66 to 0.94. The sensitivity and specificity were calculated to be 72% and 88%, respectively. Our results suggest that TGF-β1 serum concentrations may be an additional parameter in predicting the occurrence of DR in juvenile patients with T1DM.

  16. A pruritic linear urticarial rash, fever, and systemic inflammatory disease in five adolescents: adult-onset still disease or systemic juvenile idiopathic arthritis sine arthritis?

    Science.gov (United States)

    Prendiville, Julie S; Tucker, Lori B; Cabral, David A; Crawford, Richard I

    2004-01-01

    The characteristic rash of systemic juvenile idiopathic arthritis is a transient erythematous eruption associated with a quotidian spiking fever. Usually asymptomatic, it can be pruritic, with dermatographism at sites of scratching or pressure. An illness similar to this entity in adults is designated adult-onset Still disease. The relationship between the pediatric and adult disease is uncertain and differences in case definition have evolved. Specifically, a sustained arthritis for at least 6 weeks is required for a diagnosis of systemic juvenile idiopathic arthritis, whereas transient arthritis and arthralgia are accepted criteria in adult-onset Still disease. We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. Intense pruritus and linear erythematous lesions flared with a spiking fever, usually in the late afternoon and evening. Periorbital edema/erythema and nonlinear urticarial lesions were also seen. Two children had splinter hemorrhages of the nail beds and one girl developed a fixed, scaling, pigmented, linear eruption. Severe malaise, myalgia, arthralgia, and leukocytosis were present in every patient. Other systemic manifestations included sore throat, transient arthritis, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No patient had a sustained arthritis. The course of the disease was variable. One patient, diagnosed with macrophage activation syndrome, recovered on oral naproxen. Two patients responded to systemic corticosteroid therapy. One girl developed status epilepticus and died from aspiration and asphyxia. A boy with severe hepatitis developed renal failure and thrombotic thrombocytopenic purpura and was treated with plasmapheresis, dialysis, and systemic corticosteroids; he had recurrent episodes of rash and fever into adult life. These children did not fulfill the case definition of systemic

  17. New-Onset Diabetes Mellitus With Exposure to Ledipasvir and Sofosbuvir

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    Resmi Premji MD

    2015-12-01

    Full Text Available The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. Hence, clinicians should be cautious about worsening of glucose intolerance, and more studies are warranted to explore the underlying mechanism.

  18. The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

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    Vanelli Maurizio

    2011-03-01

    Full Text Available Abstract Background The protein tyrosine phosphatase nonreceptor type 2 (PTPN22 has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c, glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab in children during the first year after diagnosis of type 1 diabetes. Methods The C1858T variant was genotyped in an international cohort of children (n = 257 patients with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association of this variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset. Results A repeated measurement model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03 for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002, which did not influence the association between PTPN22 and proinsulin (est.: 1.28, p = 0.03. Conclusions The T allele of the C1858T variant is positively associated with proinsulin levels during the first 12 months in newly diagnosed type 1 diabetes children.

  19. New-Onset Diabetes Mellitus Among Parkinsonian Patients Treated with Long-term Quetiapine

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    Hubert H. Fernandez

    2008-01-01

    Full Text Available Atypical antipsychotics (AA are commonly used to manage drug-induced psychosis (DIP in parkinsonian patients. In the treatment of schizophrenia, AA’s have been associated with increasing reports of new-onset diabetes mellitus (DM. This study examined the risk of developing new-onset DM among parkinsonian patients on long-term, low dose quetiapine. Fifty-three parkinsonian subjects (mean age: 71.3 years taking an average quetiapine dose of 70.5 mg/day (range: 12.5–350 mg/day for a mean duration of 21.3 months (range 3–61 months were reviewed. Eight out of 53 subjects carried a diagnosis of DM prior to quetiapine treatment. Four out of 45 patients (8.9% met criteria for new diagnosis of DM, giving a total prevalence rate of 22.6% (12 out of 53. This prevalence rate of 22.6% was slightly higher than that reported in the aged-matched general population (year 2003 DM prevalence = 17.3% for 65–74 years but methodological differences could explain the difference. Larger epidemiologic studies will be needed to confirm these results as they could potentially impact a significant number of patients.

  20. Use of Serum Bicarbonate to Substitute for Venous pH in New-Onset Diabetes.

    Science.gov (United States)

    von Oettingen, Julia; Wolfsdorf, Joseph; Feldman, Henry A; Rhodes, Erinn T

    2015-08-01

    To investigate whether serum bicarbonate (HCO3) levels can be used to accurately diagnose diabetic ketoacidosis (DKA) and classify its severity in children with new-onset diabetes mellitus (NODM). Retrospective study of all patients with NODM presenting to Boston Children's Hospital from October 1, 2007, to July 1, 2013. DKA was defined as blood glucose ≥200 mg/dL, venous pH (vpH) vpH vpH, and logistic regression to evaluate serum HCO3 as a predictor of DKA and severe DKA. Of 690 study cohort subjects (47% girls, age 10.8 ± 4.3 years, 76.7% white), 19.4% presented with DKA. The relationship between serum HCO3 and vpH was log-linear (r = 0.87, 95% CI 0.85-0.89, P vpH (R(2) 0.75, P vpH = 6.81301 + (0.17823*ln[HCO3]) and DKA and severe DKA (c-statistic 0.97 [95% CI 0.96-0.99, P vpH to diagnose DKA and classify severity in children with NODM. It is suggested as an alternative to reliance on vpH, especially in settings in which access to vpH measurement is limited. Copyright © 2015 by the American Academy of Pediatrics.

  1. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus.

    Science.gov (United States)

    Colombo, Carlo; Porzio, Ottavia; Liu, Ming; Massa, Ornella; Vasta, Mario; Salardi, Silvana; Beccaria, Luciano; Monciotti, Carla; Toni, Sonia; Pedersen, Oluf; Hansen, Torben; Federici, Luca; Pesavento, Roberta; Cadario, Francesco; Federici, Giorgio; Ghirri, Paolo; Arvan, Peter; Iafusco, Dario; Barbetti, Fabrizio

    2008-06-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.

  2. Heart Disease, Hypertension, Gestational Diabetes Mellitus, and Preeclampsia/Eclampsia in Mothers With Juvenile Arthritis: A Nested Case-Control Study.

    Science.gov (United States)

    Feldman, Debbie E; Vinet, Évelyne; Bérard, Anick; Duffy, Ciarán; Hazel, Beth; Meshefedjian, Garbis; Sylvestre, Marie-Pierre; Bernatsky, Sasha

    2017-02-01

    To determine whether women with a history of juvenile arthritis are at higher risk for heart disease and hypertension and for developing adverse maternal outcomes: gestational diabetes mellitus, maternal hypertension, and preeclampsia/eclampsia. We designed a nested case-control study from a cohort of first-time mothers with prior physician billing codes suggesting juvenile arthritis, and a matched comparison group without juvenile arthritis. For the nested case-control design, we selected 3 controls for each case for the outcomes of heart disease (n = 403), prepregnancy hypertension (n = 66), gestational diabetes mellitus (n = 285), maternal hypertension (n = 561), and preeclampsia/eclampsia (n = 236). We used conditional logistic regression, adjusting for maternal age and education. Having juvenile arthritis was associated with heart disease (odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.15-5.15]) but not with gestational hypertension, diabetes mellitus, or preeclampsia/eclampsia. All 66 cases of prepregnancy hypertension had juvenile arthritis. Having prepregnancy hypertension was strongly associated with preeclampsia/eclampsia (OR 8.05 [95% CI 2.69-24.07]). Women with a history of juvenile arthritis had a higher risk of heart disease. This risk signals the potential importance of cardiac prevention strategies in juvenile arthritis. As this was a retrospective study, it was not possible to correct for some relevant potential confounders. Further studies should assess the impact of medications, disease severity, and other factors (e.g., obesity) on cardiac outcomes in juvenile arthritis. © 2016, American College of Rheumatology.

  3. Effect of calcitriol on bone turnover and osteocalcin in recent-onset type 1 diabetes.

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    Nicola Napoli

    Full Text Available BACKGROUND: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D. Moreover, the association between osteocalcin and parameters of β-cell function and metabolic control was examined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve β-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 µg calcitriol per day or placebo (1:1 and followed up for one year. Changes in bone formation (osteoclacin and resorption (beta-CrossLaps markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P<0.01 while no other metabolic parameters as HbA1c and C-peptide differed between gender. No significant correlations were found in relation to HbA1c, insulin requirement and C-peptide. At 1 year follow-up, no significant differences were observed between calcitriol and placebo groups for osteocalcin and β-CrossLaps. In the placebo group osteocalcin levels were unrelated with parameters of metabolic control, such as C-peptide, insulin requirement or HbA1c. Changes of C-peptide, insulin requirement and HbA1c were not related to osteocalcin levels. CONCLUSIONS: Supplementation with 0.25 µg calcitriol per day to patients with new-onset T1D does not affect circulating markers of bone turnover. OC levels were unrelated to β-cell function and other metabolic parameters suggesting that OC is ineffective to control pancreatic function in presence of aggressive autoimmune destruction.

  4. Circulating Ribonucleic Acids and Metabolic Stress Parameters May Reflect Progression of Autoimmune or Inflammatory Conditions in Juvenile Type 1 Diabetes

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    Gordana Kocic

    2011-01-01

    Full Text Available The sensing of ribonucleic acids (RNAs by the monocyte/macrophage system occurs through the TLR7/8 Toll-like receptor family, the retinoic acidi–nducible protein I (RIG-I, and the melanoma differentiation–associated protein-5 (MDA-5. The aim of the present study was to evaluate the effect of circulating RNAs, isolated from juvenile type 1 diabetic patients and healthy control children, on the inflammatory, apoptotic, and antiviral response in human peripheral blood mononuclear cells (PBMCs isolated from a healthy donor. Obtained effects were compared to the effects of metabolic stress parameters (hyperglycemia, oxidative and nitrosative stress. Forty-eight patients with juvenile type 1 diabetes and control children were included in the study. By performing the chromatographic analysis of circulating RNAs, the peak at the retention time 0.645 min for diabetic and control RNA samples was identified. To determine whether circulating RNAs have an agonistic or antagonistic effect on the signaling pathways involved in inflammatory, apoptotic, and antiviral cascade, their effect on TLR8, RIG-I, MDA-5, MyD88, NF-κB, IRF-3, phosphoIRF-3, IRF-7, RIP, and p38 was evaluated. A significantly lower level was achieved by cultivating PBMCs with circulating RNAs isolated from type 1 diabetic children, compared to the intact PBMCs, in relation to TLR-8, MDA-5, NF-κB, phospho IRF-3, and RIP, while it was higher for Bax. All the metabolic stress conditions up-regulated NF-κB, Bcl-2, and Bax. The NF-κB, determination seems to be the most sensitive parameter that may reflect disease processes associated with the progression of autoimmune or inflammatory conditions, while the IRF3/phosphoIRF3 ratio may suggest an insufficient antiviral response.

  5. Circulating ribonucleic acids and metabolic stress parameters may reflect progression of autoimmune or inflammatory conditions in juvenile type 1 diabetes.

    Science.gov (United States)

    Kocic, Gordana; Pavlovic, Radmila; Najman, Stevo; Nikolic, Goran; Sokolovic, Dusan; Jevtovic-Stoimenov, Tatjana; Musovic, Dijana; Veljkovic, Andrej; Kocic, Radivoj; Djindjic, Natasa

    2011-07-28

    The sensing of ribonucleic acids (RNAs) by the monocyte/macrophage system occurs through the TLR7/8 Toll-like receptor family, the retinoic acid-inducible protein I (RIG-I), and the melanoma differentiation-associated protein-5 (MDA-5). The aim of the present study was to evaluate the effect of circulating RNAs, isolated from juvenile type 1 diabetic patients and healthy control children, on the inflammatory, apoptotic, and antiviral response in human peripheral blood mononuclear cells (PBMCs) isolated from a healthy donor. Obtained effects were compared to the effects of metabolic stress parameters (hyperglycemia, oxidative and nitrosative stress). Forty-eight patients with juvenile type 1 diabetes and control children were included in the study. By performing the chromatographic analysis of circulating RNAs, the peak at the retention time 0.645 min for diabetic and control RNA samples was identified. To determine whether circulating RNAs have an agonistic or antagonistic effect on the signaling pathways involved in inflammatory, apoptotic, and antiviral cascade, their effect on TLR8, RIG-I, MDA-5, MyD88, NF-KB, IRF-3, phosphoIRF-3, IRF-7, RIP, and p38 was evaluated. A significantly lower level was achieved by cultivating PBMCs with circulating RNAs isolated from type 1 diabetic children, compared to the intact PBMCs, in relation to TLR-8, MDA-5, NF-KB, phospho IRF-3, and RIP, while it was higher for Bax. All the metabolic stress conditions up-regulated NF-KB, Bcl-2, and Bax. The NF-êB determination seems to be the most sensitive parameter that may reflect disease processes associated with the progression of autoimmune or inflammatory conditions, while the IRF3/phosphoIRF3 ratio may suggest an insufficient antiviral response.

  6. Serum uric acid is associated with new-onset diabetes in hypertensive patients with left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Wiik, Benedicte P; Larstorp, Anne C K; Høieggen, Aud

    2010-01-01

    It is unclear whether serum uric acid (SUA) is associated with development of new-onset diabetes (NOD) in patients with hypertension and left ventricular hypertrophy (LVH). The aim of the present investigation was to test the hypothesis that SUA predicts development of NOD in these patients....

  7. Comparison between New-Onset and Old-Diagnosed Type 2 Diabetes with Ketosis in Rural Regions of China.

    Science.gov (United States)

    Du, Shichun; Yang, Xia; Shi, Degang; Su, Qing

    2016-01-01

    Objectives. Type 2 diabetes (T2D) with ketosis was common because of late diagnosis and lacking adequate treatment in rural regions of China. This study aimed to provide the data of T2D with ketosis among inpatients in a south-west border city of China. Methods. Data of 371 patients of T2D with ketosis who were hospitalized between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan, China, were analyzed. New-onset and old-diagnosed T2D patients presenting with ketosis were compared according to clinical characteristics, laboratory results, and chronic diabetic complications. Results. Overall, the blood glucose control was poor in our study subjects. Male predominated in both groups (male prevalence was 68% in new-onset and 64% in old-diagnosed groups). Overweight and obesity accounted for 50% in new-onset and 46% in old-diagnosed cases. Inducements of ketosis were 13.8% in new-onset and 38.7% in old-diagnosed patients. Infections were the first inducements in both groups. The prevalence of chronic complications of diabetes was common in both groups. Conclusions. More medical supports were needed for the early detection and adequate treatment of diabetes in rural areas of China.

  8. Study of relation between the onset age of type 1 diabetes and celiac disease in children andadole scents

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    robabe Ghergherehchi

    2010-02-01

    Full Text Available Celiac disease (CD is a chronic enteropathy caused by hypersensitivity to gluten. Most studies have showed more prevalence of CD in the patients with diabetes mellitus type 1. Both diseases are autoimmune and their incidence is related to inheritance and environmental factors. The aim of this research is the study of relation between CD prevalence and diabetic age onset. Materials and Methods: In this descriptive cross-sectional study, 135 children with diabetes mellitus type 1 referring to Tabriz children hospital endocrine department and clinic between 2006-2008 were selected. After filling individual identity of the patients and the measurement of weight and height, the serumic level of anti-tissue Trans glutaminase IgA antibody (A-tTG-A-IgA, anti endomisial IgA antibody (AEA-IgA and anti-gliadin IgG antibody (AGA-IgG were measured. In the case that A-tTG-A either AEA alone or with AGA was high, small intestinal biopsy was preformed. The data was analysed using SPSS ver 16 software. Results: 28 of 135 patients with diabetes mellitus type 1, were serologically positive for celiac. Confirmed celiac prevalence based on biopsy was 6. 8%. From diabetic age onset and celiac incidence point of view there was not any significant relation (P=0. 996. Conclusion: Celiac disease in type1 diabetic patients dose not have correlation with the onset age of type 1 diabetes and diabetic patients should be followed up from celiac point of view during treatment and prevention.

  9. The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis.

    NARCIS (Netherlands)

    Holzinger, D.; Frosch, M.; Kastrup, A.; Prince, F.H.; Otten, M.H.; Suijlekom-Smit, L.W. van; Cate, R. ten; Hoppenreijs, E.P.A.H.; Hansmann, S.; Moncrieffe, H.; Ursu, S.; Wedderburn, L.R.; Roth, J.; Foell, D.; Wittkowski, H.

    2012-01-01

    BACKGROUND: Analysis of myeloid-related protein 8 and 14 complex (MRP8/14) serum concentrations is a potential new tool to support the diagnosis of systemic-onset juvenile idiopathic arthritis (SJIA) in the presence of fever of unknown origin. OBJECTIVE: To test the ability of MRP8/14 serum concentr

  10. Polymorphism on chromosome 9p21.3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; PENG Wen-hui; LU Lin; ZHANG Rui-yan; ZHANG Qi; WANG Ling-jie; CHEN Qiu-jing; SHEN Wei-feng

    2011-01-01

    Background Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways.Methods Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A1c (HbA1c), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype.Results The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR:1.270,P=0.044) and non-diabetic (OR: 1.369, P=0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P=0.019), but not in non-diabetics (P=0.126). Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD (OR:. 2.367, P=0.008)and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80±17.20 vs.23.09±21.63, P=0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA1c, or inflammatory cytokines for diabetic or non-diabetic patients with CAD.Conclusions This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or

  11. Obesity, islet cell autoimmunity, and cardiovascular risk factors in youth at onset of type 1 autoimmune diabetes.

    Science.gov (United States)

    Cedillo, Maribel; Libman, Ingrid M; Arena, Vincent C; Zhou, Lei; Trucco, Massimo; Ize-Ludlow, Diego; Pietropaolo, Massimo; Becker, Dorothy J

    2015-01-01

    The current increase in childhood type 1 diabetes (T1D) and obesity has led to two conflicting hypotheses and conflicting reports regarding the effects of overweight on initiation and spreading of islet cell autoimmunity vs earlier clinical manifestation of preexisting autoimmune β-cell damage driven by excess weight. The objective of the study was to address the question of whether the degree of β-cell autoimmunity and age are related to overweight at diabetes onset in a large cohort of T1D youth. This was a prospective cross-sectional study of youth with autoimmune T1D consecutively recruited at diabetes onset. The study was conducted at a regional academic pediatric diabetes center. Two hundred sixty-three consecutive children younger than 19 years at onset of T1D participated in the study. Relationships between body mass index and central obesity (waist circumference and waist to height ratio) and antigen spreading (islet cell autoantibody number), age, and cardiovascular (CVD) risk factors examined at onset and/or 3 months after the diagnosis were measured. There were no significant associations between number of autoantibodies with measures of adiposity. Age relationships revealed that a greater proportion of those with central obesity (21%) were in the youngest age group (0-4 y) compared with those without central obesity (6%) (P = .001). PATIENTS with central obesity had increased CVD risk factors and higher onset C-peptide levels (P obesity accelerates progression of autoantibody spreading once autoimmunity, marked by standard islet cell autoantibody assays, is present. Central obesity was present in almost one-third of the subjects and was associated with early CVD risk markers already at onset.

  12. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention

    DEFF Research Database (Denmark)

    Meur, Gargi; Simon, Albane; Harun, Nasret

    2009-01-01

    the molecular mechanisms involved. RESEARCH DESIGN AND METHODS: The INS gene was sequenced in 16 French probands with unexplained MODY, 95 patients with nonautoimmune early-onset diabetes (diagnosed at ... quantitated by real-time PCR. RESULTS: A novel coding mutation, L30M, potentially affecting insulin multimerization, was identified in five diabetic individuals (diabetes onset 17-36 years) in a single family. L30M preproinsulin-GFP fluorescence largely associated with the endoplasmic reticulum (ER) in MIN6...

  13. Frequency and genetic spectrum of maturity-onset diabetes of the young (MODY) in southern New Zealand.

    Science.gov (United States)

    Wheeler, Benjamin J; Patterson, Nicola; Love, Donald R; Prosser, Debbie; Tomlinson, Paul; Taylor, Barry J; Manning, Patrick

    2013-12-19

    Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes, consisting of a heterogeneous group of autosomal dominant inherited disorders. Typical onset is in individuals prior to twenty five years, and presentation can mimic type 1 or 2 diabetes. Molecular genetic testing can allow precise identification of the different MODY sub-types. Making a specific diagnosis of MODY can have important implications for the guidance of appropriate treatment, prognosis and genetic counselling.We present the cases of three children and their families diagnosed with MODY over the past two years. These families highlight the features of three of the more common MODY subtypes, including two with novel mutations, one of which segregates in a kindred that is strongly affected by both MODY and classic autoimmune mediated diabetes. To date, we have identified a prevalence of MODY in the paediatric diabetes population of the lower South Island, New Zealand, of approximately 2.5%. This prevalence, along with increasing access to molecular genetic testing, highlights the importance of consideration of MODY in atypical diabetes presentations in the paediatric/adolescent population.

  14. Impact of sex and age at onset of diabetes on mortality from ischemic heart disease in patients with type 1 diabetes.

    Science.gov (United States)

    Harjutsalo, Valma; Maric-Bilkan, Christine; Forsblom, Carol; Groop, Per-Henrik

    2014-01-01

    OBJECTIVE To study whether ischemic heart disease (IHD) mortality among patients with type 1 diabetes (T1D) depends on the age at onset of diabetes and whether this effect is sex specific. RESEARCH DESIGN AND METHODS The study examined long-term IHD-specific mortality in a Finnish population-based cohort of patients with early-onset (0-14 years) and late-onset (15-29 years) T1D (n = 17,306). RESULTS During 433,782 person-years of follow-up, 478 deaths from IHD were observed. Within the early-onset cohort, the average crude mortality rate in women was 33.3% lower than in men, whereas in the late-onset cohort, mortality was only one-half that in men. In contrast, the standardized mortality ratio (SMR) was higher in women than in men (21.6 [95% CI 17.2-27.0] vs. 5.8 [5.1-6.6]). The difference in SMR between sexes was more striking in the early-onset cohort (women 52.8 [36.3-74.5], men 12.1 [9.2-15.8]). The SMR was also greater in women in the late-onset cohort (15.8 [11.8-20.7]) compared with men (5.0 [4.3-5.8]). The relative risk of dying from IHD was greatest in women aged early- and late-onset cohorts, respectively. CONCLUSIONS The risk of mortality from IHD is exceptionally high in women with early-onset T1D compared with women in the background population. These observations underscore the importance of identifying risk factors early in women and delivering more-aggressive treatment after diagnosis.

  15. Experimental periodontitis induced by Porphyromonas gingivalis does not alter the onset or severity of diabetes in mice.

    Science.gov (United States)

    Li, H; Yang, H; Ding, Y; Aprecio, R; Zhang, W; Wang, Q; Li, Y

    2013-10-01

    Diabetes mellitus is believed to increase the risk and severity of periodontitis. However, less evidence is available on the converse effects of periodontitis on diabetes. The objective of the study was to investigate to what degree experimental periodontitis induced by Porphyromonas gingivalis might influence the onset and severity of diabetes in different mouse models. Twenty-eight male Tallyho/JngJ mice (type 2 diabetes), 20 male streptozotocin-induced diabetes C57BL/6J mice (type 1 diabetes) and 20 male C57BL/6J mice at 4 wks of age were evenly divided into two groups: periodontal infection and sham infection. Periodontitis was induced by Porphyromonas gingivalis W50 (P. gingivalis) oral inoculation before the development of diabetes. Sham-infected mice received vehicle as control. P. gingivalis in the oral cavity were identified by quantitative polymerase chain reaction. Fasting glucose, body weight and food intake levels were monitored and glucose tolerance tests were performed to assess glucose homeostasis for the onset and progression of diabetes. The level of alveolar bone loss and tumor necrosis factor-alpha were determined in week 20 when mice were killed. Mice in the infection groups developed more alveolar bone loss than those in sham-infection groups (Tallyho p = 0.021; C57-STZ p = 0.014; C57 p = 0.035). Hyperglycemic mice exhibited significantly more bone loss compared to those normal glucose mice (Tallyho vs. C57 p = 0.029; C57-STZ vs. C57 p = 0.024). The level of tumor necrosis factor-alpha was consistent with that of periodontal bone loss and hyperglycemia. There was no significant effect of mouse species on the amount of bone loss at the same level of blood glucose. No statistically significant difference or trend in glucose metabolism was found between the infection and sham-infection group. Diabetes enhanced the risk for periodontal disease induced by P. gingivalis. However, no converse impact was found between this periodontal

  16. Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation

    Science.gov (United States)

    Song, Jiu-Lin; Gao, Wei; Zhong, Yan; Yan, Lu-Nan; Yang, Jia-Yin; Wen, Tian-Fu; Li, Bo; Wang, Wen-Tao; Wu, Hong; Xu, Ming-Qing; Chen, Zhe-Yu; Wei, Yong-Gang; Jiang, Li; Yang, Jian

    2016-01-01

    AIM: To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT). METHODS: We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ2 test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression. RESULTS: Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22 ng/mL, P 50 years), hypertension pre-LT, and high mean cTAC (≥ 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy. CONCLUSION: A minimal TAC regimen can decrease the risk of long

  17. Stress increases the risk of type 2 diabetes onset in women: A 12-year longitudinal study using causal modelling

    Science.gov (United States)

    Oldmeadow, Christopher; Hure, Alexis; Luu, Judy; Loxton, Deborah

    2017-01-01

    Background Type 2 diabetes is associated with significant morbidity and mortality. Modifiable risk factors have been found to contribute up to 60% of type 2 diabetes risk. However, type 2 diabetes continues to rise despite implementation of interventions based on traditional risk factors. There is a clear need to identify additional risk factors for chronic disease prevention. The aim of this study was to examine the relationship between perceived stress and type 2 diabetes onset, and partition the estimates into direct and indirect effects. Methods and findings Women born in 1946–1951 (n = 12,844) completed surveys for the Australian Longitudinal Study on Women’s Health in 1998, 2001, 2004, 2007 and 2010. The total causal effect was estimated using logistic regression and marginal structural modelling. Controlled direct effects were estimated through conditioning in the regression model. A graded association was found between perceived stress and all mediators in the multivariate time lag analyses. A significant association was found between hypertension, as well as physical activity and body mass index, and diabetes, but not smoking or diet quality. Moderate/high stress levels were associated with a 2.3-fold increase in the odds of diabetes three years later, for the total estimated effect. Results were only slightly attenuated when the direct and indirect effects of perceived stress on diabetes were partitioned, with the mediators only explaining 10–20% of the excess variation in diabetes. Conclusions Perceived stress is a strong risk factor for type 2 diabetes. The majority of the effect estimate of stress on diabetes risk is not mediated by the traditional risk factors of hypertension, physical activity, smoking, diet quality, and body mass index. This gives a new pathway for diabetes prevention trials and clinical practice. PMID:28222165

  18. [Proportion of low insulin responders to glucose among the offspring of maturity-onset diabetics (author's transl)].

    Science.gov (United States)

    Vague, P; Ramahandridona, G; Vague, J

    1975-03-01

    The insensitivity of B cells to glucose, a characteristic of mild essential glucose intolerance may be estimated in a given individual by the comparison of the immediate plasma insulin response to glucose (0 to 10' plasma insulin area or iG) with that to Tolbutamide (iT). It was shown that iG/iT clearly differentiates between nondiabetics and diabetics, whatever their body weight. All the diabetics had an iT/iT lower than 0,65. A high proportion of the offspring of diabetics had an iG/iT ratio in the diabetic range, whether or not they were diabetic. Among these subjects aged from 10 to 49 and weighing between 90 and 144% of their ideal body weight, the iG/iT ratio was not correlated with age nor with relative body weight while the K value was negatively correlated with age. We were thus able to look for the frequency of a "diabetic" iG/iT ratio in the offspring of diabetics, For this in sibships in which all the sibs had been tested, one subject was selected by randomisation. A "diabetic" iG/iT ratio was observed in 7 of 41 subjects with no family history of diabetes, in 27 of 50 with one parent having clinical, maturity-onset diabetes melitus, and in 15 of 19 subjects with two diabetic parents. These results are not compatible with the hypothesis of recessive transmission of the "low insulin response to glucose" characteristic.

  19. Novel views on new-onset diabetes after transplantation: development, prevention and treatment.

    Science.gov (United States)

    Hecking, Manfred; Werzowa, Johannes; Haidinger, Michael; Hörl, Walter H; Pascual, Julio; Budde, Klemens; Luan, Fu L; Ojo, Akinlolu; de Vries, Aiko P J; Porrini, Esteban; Pacini, Giovanni; Port, Friedrich K; Sharif, Adnan; Säemann, Marcus D

    2013-03-01

    New-onset diabetes after transplantation (NODAT) is associated with increased risk of allograft failure, cardiovascular disease and mortality, and therefore, jeopardizes the success of renal transplantation. Increased awareness of NODAT and the prediabetic states (impaired fasting glucose and impaired glucose tolerance, IGT) has fostered previous and present recommendations, based on the management of type 2 diabetes mellitus (T2DM). Unfortunately, the idea that NODAT merely resembles T2DM is potentially misleading, because the opportunity to initiate adequate anti-hyperglycaemic treatment early after transplantation might be given away for 'tailored' immunosuppression in patients who have developed NODAT or carry personal risk factors. Risk factor-independent mechanisms, however, seem to render postoperative hyperglycaemia with subsequent development of overt or 'full-blown' NODAT, the unavoidable consequence of the transplant and immunosuppressive process itself, at least in many cases. A proof of the concept that timely preventive intervention with exogenous insulin against post-transplant hyperglycaemia may decrease NODAT was recently provided by a small clinical trial, which is awaiting confirmation from a multicentre study. However, because early insulin therapy aimed at beta-cell protection seems to contrast the currently recommended, stepwise approach of 'watchful waiting' prior to pancreatic decompensation, we here aim at reviewing recent concepts regarding the development, prevention and treatment of NODAT, some of which seem to challenge the traditional view on T2DM and NODAT. In summary, we suggest a novel, risk factor-independent management approach to NODAT, which includes glycaemic monitoring and anti-hyperglycaemic treatment in virtually everybody after transplantation. This approach has widespread implications for future research and is intended to tackle NODAT and also ultimately cardiovascular disease.

  20. Association of Metabolic Syndrome with Development of New Onset Diabetes After Transplantation

    Science.gov (United States)

    Bayer, Nathaniel D.; Cochetti, Philip T.; Anil Kumar, Mysore S.; Teal, Valerie; Huan, Yonghong; Doria, Cataldo; Bloom, Roy D.; Rosas, Sylvia E.

    2010-01-01

    Background New-onset diabetes after transplantation (NODAT) is a major post-transplant complication associated with lower allograft and recipient survival. Our objective was to determine if metabolic syndrome pre-transplant is independently associated with NODAT development. Methods We recruited 640 consecutive incident non-diabetic renal transplant recipients from 3 academic centers between 1999 and 2004. NODAT was defined as use of hypoglycemic medication, a random plasma glucose >200 mg/dL, or 2 fasting glucose levels ≥126 mg/dL beyond 30 days post-transplant. Results Metabolic syndrome was common pre-transplant (57.2 %). NODAT developed in 31.4% of recipients one year post-transplant. Participants with metabolic syndrome were more likely to develop NODAT compared to recipients without metabolic syndrome (34.4% v. 27.4%, p=0.057). Recipients with increasing number of positive metabolic syndrome components were more likely to develop NODAT (metabolic syndrome score-prevalence at 1 year: 0-0.0%, 1-24.2, 2-29.3%, 3-31.0%, 4-34.8%, and 5-73.7%, p=0.001). After adjustment for demographics, age by decade (HR-1.34 (1.20-1.50), psyndrome (HR-1.34 (1.00-1.79), p=0.047) were independent predictors of development of NODAT at 1 year post-transplant. In a multivariable analysis incorporating the individual metabolic syndrome components themselves as covariates, the only pre-transplant metabolic syndrome component to remain an independent predictor of NODAT was low HDL (HR-1.37 (1.01-1.85), p=0.042). Conclusions Metabolic syndrome is an independent predictor for NODAT and is a possible target for intervention to prevent NODAT. Future studies to evaluate if modification of metabolic syndrome factors pre-transplant reduces NODAT development are needed. PMID:20724958

  1. Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease

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    Spires Tara L

    2008-04-01

    Full Text Available Abstract Background Huntington's disease (HD is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line, expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit. Results We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks, with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running. Conclusion These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment

  2. Juvenile rheumatoid arthritis and asthma, but not childhood-onset systemic lupus erythematosus are associated with FCRL3 polymorphisms in Mexicans.

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    Ramírez-Bello, J; Jiménez-Morales, S; Espinosa-Rosales, F; Gómez-Vera, J; Gutiérrez, A; Velázquez Cruz, R; Baca, V; Orozco, L

    2013-04-01

    A regulatory single nucleotide polymorphism located in the 5' region (-169T/C) of the Fc receptor-like 3 (FCRL3_3) gene has been associated with both susceptibility and protection in immune diseases. This case-control study aimed to evaluate the association between FCRL3 polymorphisms and juvenile rheumatoid arthritis (JRA), asthma, and childhood-onset systemic lupus erythematosus (SLE) in a Mexican population. We performed PCR-based genotyping to identify four FCRL3 single nucleotide polymorphisms (FCRL3_3 to FCRL3_6) in patients with JRA (n=202), asthma (n=239), or childhood-onset SLE (n=377), and healthy controls (n=400). The case-control analysis showed a male-gender dependent association between the FCRL3_3C, FCRL3_5C, and FCRL3_6A alleles and either JRA (OR=0.57, p=0.003; OR=0.55, p=0.002; OR=0.53, p=0.0007, respectively) or asthma (OR=0.72, p=0.04; OR=0.74, p=0.05; OR=0.70, p=0.02, respectively). As expected, minor alleles of these SNPs with the CGCA haplotype were also significantly associated with JRA (OR=0.35, p=0.00005) and asthma (OR=0.61, p=0.007). We found no association between FCRL3 SNPs or haplotypes and childhood-onset SLE. These results supported the notion that FCRL3 is involved in the etiology of several immune diseases. Our results also suggested that SNPs located in the FCRL3 gene were protective against JRA and asthma in male Mexican patients.

  3. Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome.

    Science.gov (United States)

    Villanueva, Joyce; Lee, Susan; Giannini, Edward H; Graham, Thomas B; Passo, Murray H; Filipovich, Alexandra; Grom, Alexei A

    2005-01-01

    Macrophage activation syndrome (MAS) has been reported in association with many rheumatic diseases, most commonly in systemic juvenile rheumatoid arthritis (sJRA). Clinically, MAS is similar to hemophagocytic lymphohistiocytosis (HLH), a genetic disorder with absent or depressed natural killer (NK) function. We have previously reported that, as in HLH, patients with MAS have profoundly decreased NK activity, suggesting that this abnormality might be relevant to the pathogenesis of the syndrome. Here we examined the extent of NK dysfunction across the spectrum of diseases that comprise juvenile rheumatoid arthritis (JRA). Peripheral blood mononuclear cells (PBMC) were collected from patients with pauciarticular (n = 4), polyarticular (n = 16), and systemic (n = 20) forms of JRA. NK cytolytic activity was measured after co-incubation of PBMC with the NK-sensitive K562 cell line. NK cells (CD56+/T cell receptor [TCR]-alphabeta-), NK T cells (CD56+/TCR-alphabeta+), and CD8+ T cells were also assessed for perforin and granzyme B expression by flow cytometry. Overall, NK cytolytic activity was significantly lower in patients with sJRA than in other JRA patients and controls. In a subgroup of patients with predominantly sJRA, NK cell activity was profoundly decreased: in 10 of 20 patients with sJRA and in only 1 of 20 patients with other JRA, levels of NK activity were below two standard deviations of pediatric controls (P = 0.002). Some decrease in perforin expression in NK cells and cytotoxic T lymphocytes was seen in patients within each of the JRA groups with no statistically significant differences. There was a profound decrease in the proportion of circulating CD56bright NK cells in three sJRA patients, a pattern similar to that previously observed in MAS and HLH. In conclusion, a subgroup of patients with JRA who have not yet had an episode of MAS showed decreased NK function and an absence of circulating CD56bright population, similar to the abnormalities observed

  4. Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY

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    Pisinger Charlotta

    2010-03-01

    Full Text Available Abstract Background Insulin gene (INS mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM and a rare cause of diabetes diagnosed in childhood or adulthood. Methods INS was sequenced in 116 maturity-onset diabetes of the young (MODYX patients (n = 48 Danish and n = 68 Czech, 83 patients with gestational diabetes mellitus (GDM, 34 type 1 diabetic patients screened negative for glutamic acid decarboxylase (GAD, and 96 glucose tolerant individuals. The control group was randomly selected from the population-based sampled Inter99 study. Results One novel heterozygous mutation c.17G>A, R6H, was identified in the pre-proinsulin gene (INS in a Danish MODYX family. The proband was diagnosed at 20 years of age with mild diabetes and treated with diet and oral hypoglycaemic agent. Two other family members who carried the INS R6H were diagnosed with diabetes when 51 years old and with GDM when 27 years old, respectively. A fourth mutation carrier had normal glucose tolerance when 20 years old. Two carriers of INS R6H were also examined twice with an oral glucose tolerance test (OGTT with 5 years interval. They both had a ~30% reduction in beta-cell function measured as insulinogenic index. In a Czech MODYX family a previously described R46Q mutation was found. The proband was diagnosed at 13 years of age and had been treated with insulin since onset of diabetes. Her mother and grandmother were diagnosed at 14 and 35 years of age, respectively, and were treated with oral hypoglycaemic agents and/or insulin. Conclusion Mutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.

  5. Geometric phase transition in the cellular network of the pancreatic islets may underlie the onset of type 1diabetes

    Science.gov (United States)

    Wang, Xujing

    Living systems are characterized by complexity in structure and emergent dynamic orders. In many aspects the onset of a chronic disease resembles phase transition in a dynamic system: quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. In this study we investigate this idea in a real example, the insulin-producing pancreatic islet β-cells and the onset of type 1 diabetes. Within each islet, the β-cells are electrically coupled to each other, and function as a network with synchronized actions. Using percolation theory we show how normal islet function is intrinsically linked to network connectivity, and the critical point where the islet cellular network loses site percolation, is consistent with laboratory and clinical observations of the threshold β-cell loss that causes islet functional failure. Numerical simulations confirm that the islet cellular network needs to be percolated for β-cells to synchronize. Furthermore, the interplay between site percolation and bond strength predicts the existence of a transient phase of islet functional recovery after disease onset and introduction of treatment, potentially explaining a long time mystery in the clinical study of type 1 diabetes: the honeymoon phenomenon. Based on these results, we hypothesized that the onset of T1D may be the result of a phase transition of the islet β-cell network. We further discuss the potential applications in identifying disease-driving factors, and the critical parameters that are predictive of disease onset.

  6. A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

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    Saima Siddiqi

    Full Text Available The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A in the ALS2 gene (NM_020919.3 encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS, one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

  7. A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

    Science.gov (United States)

    Siddiqi, Saima; Foo, Jia Nee; Vu, Anthony; Azim, Saad; Silver, David L; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E Shyong; Yeo, Gene W; Khor, Chiea Chuen

    2014-01-01

    The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

  8. Possible role of interleukin-1β in type 2 diabetes onset and implications for anti-inflammatory therapy strategies.

    Directory of Open Access Journals (Sweden)

    Gang Zhao

    2014-08-01

    Full Text Available Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from in vitro experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting glucose bear the potential of stopping progression from pre-diabetes to overt type 2 diabetes. However, once in overt type 2 diabetes, these treatments have to be complemented by adjuvant anti-inflammatory therapies in order to stop or decelerate disease progression. Moreover, the model suggests that while glucose-lowering therapy needs to be continued all the way, dose and duration of the anti-inflammatory therapy needs to be specifically controlled. The model proposes a framework for the discussion of clinical trial outcomes.

  9. Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies

    Science.gov (United States)

    Zhao, Gang; Dharmadhikari, Gitanjali; Maedler, Kathrin; Meyer-Hermann, Michael

    2014-01-01

    Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from in vitro experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting glucose bear the potential of stopping progression from pre-diabetes to overt type 2 diabetes. However, once in overt type 2 diabetes, these treatments have to be complemented by adjuvant anti-inflammatory therapies in order to stop or decelerate disease progression. Moreover, the model suggests that while glucose-lowering therapy needs to be continued all the way, dose and duration of the anti-inflammatory therapy needs to be specifically controlled. The model proposes a framework for the discussion of clinical trial outcomes. PMID:25167060

  10. Lipoprotein(a) predicts a new onset of chronic kidney disease in people with Type 2 diabetes mellitus.

    Science.gov (United States)

    Yun, J-S; Ahn, Y-B; Song, K-H; Yoo, K-D; Park, Y-M; Kim, H-W; Ko, S-H

    2016-05-01

    We investigated the association between lipoprotein(a) [Lp(a)] level and new-onset chronic kidney disease (CKD) in patients with Type 2 diabetes. We conducted a prospective cohort study from March 2003 to December 2004 with a median follow-up time of 10.1 years. Patients aged 25-75 years with Type 2 diabetes and without CKD [estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m(2) ) were consecutively enrolled. The eGFR was measured at least twice every year , and new-onset CKD was defined as a decreased eGFR status of diabetes were 53.3 ± 9.6 and 7.5 ± 6.0 years, respectively. The baseline eGFR was 101.8 ± 11.3 ml/min/1.73 m(2) . After adjusting for multiple confounding factors, a Cox hazard regression analysis revealed that the third tertile of Lp(a) was significantly associated with the development of CKD during the observation period when compared with the first tertile [hazard ratio 2.12 (95% confidence interval 1.33-3.36); P = 0.001). In this prospective, longitudinal, observational cohort study, we demonstrated that the Lp(a) level was an independent prognostic factor for the future development of CKD in patients with Type 2 diabetes. © 2015 Diabetes UK.

  11. Impaired metabolic control and socio-demographic status in immigrant children at onset of Type 1 diabetes

    OpenAIRE

    Soderstrom, U.; Samuelsson, Ulf; Sahlqvist, L.; Aman, J

    2014-01-01

    AimThe aim of the present study was to compare clinical and socio-demographic conditions at the onset of Type1 diabetes in children born to immigrant families and children born to Swedish families, and to assess whether those conditions had an impact on metabolic status. Methods and designThis was an observational nationwide population-based matched cohort study on prospectively recorded registry data of all children with diabetes in Sweden and their families during 2000-2010. Out of a total ...

  12. Angiotensin converting enzyme inhibitors for prevention of new-onset type 2 diabetes mellitus: a meta-analysis of 72,128 patients.

    Science.gov (United States)

    Geng, Deng-feng; Jin, Dong-mei; Wu, Wei; Liang, Yong-de; Wang, Jing-feng

    2013-09-10

    Angiotensin converting enzyme inhibitors (ACEIs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. The aim of this study was to evaluate the effect of ACEIs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ACEIs and new-onset diabetes were identified by electronic and manual searches. Nine RCTs with 92,404 patients (72,128 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in the ACEIs group [OR 0.80, (0.71, 0.91)], irrespective of achieved blood pressure levels at the follow-up. ACEIs therapy was associated with significant reduction in the risk of new-onset diabetes compared with beta-blockers/diuretics [OR 0.78, (0.65, 0.93)], placebo [OR 0.79, (0.64, 0.96)], or calcium channel blockers [OR 0.85, (0.73, 0.99)]. ACEIs treatment was associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.80, (0.68, 0.93)], coronary artery disease (CAD) or cardiovascular disease [OR 0.83, (0.68, 1.00)], or heart failure [OR 0.22, (0.10, 0.47)]. Among patients with impaired glucose tolerance or impaired fasting glucose, ramipril did not significantly reduce the incidence of diabetes [OR 0.91, (0.79, 1.05)], but significantly increased regression to normoglycemia. ACEIs have beneficial effects in preventing new-onset diabetes. ACEIs provide additional benefits of lowering the risk of new-onset diabetes in patients with hypertension, CAD or other cardiovascular disease. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor.

    Science.gov (United States)

    Tian, Lei; Gao, Jie; Hao, Jianqiang; Zhang, Yu; Yi, Huimin; O'Brien, Timothy D; Sorenson, Robert; Luo, Jian; Guo, Zhiguang

    2010-07-01

    Inhibition of dipeptidyl peptidase IV (DPP-IV) activity by NVP-DPP728, a DPP-IV inhibitor, improves the therapeutic efficacy of glucagon-like peptide-1 (GLP-1). CD26 is a membrane-associated glycoprotein with DPP-IV activity and is expressed on lymphocytes. We investigated the effect of NVP-DPP728 on reversing new-onset diabetes in nonobese diabetic (NOD) mice and modulating the inflammatory response and stimulating beta-cell regeneration. New-onset diabetic NOD mice were treated with NVP-DPP728 for 2, 4, and 6 wk. Blood glucose level was monitored. Regulatory T cells in thymus and secondary lymph nodes, TGF-beta1 and GLP-1 in plasma, and the insulin content in the pancreas were measured. Immunostaining for insulin and bromodeoxyuridine (BrdU) were performed. The correlation of beta-cell replication with inflammation was determined. In NVP-DPP728-treated NOD mice, diabetes could be reversed in 57, 74, and 73% of mice after 2, 4, and 6 wk treatment, respectively. Insulitis was reduced and the percentage of CD4(+)CD25(+)FoxP3(+) regulatory T cells was increased in treated NOD mice with remission. Plasma TGF-beta1 and GLP-1, the insulin content, and both insulin(+) and BrdU(+) beta-cells in pancreas were also significantly increased. No significant correlations were found between numbers of both insulin(+) and BrdU(+) beta-cells in islets and beta-cell area or islets with different insulitis score in NOD mice with remission of diabetes. In conclusion, NVP-DPP728 treatment can reverse new-onset diabetes in NOD mice by reducing insulitis, increasing CD4(+)CD25(+)FoxP3(+) regulatory T cells, and stimulating beta-cell replication. beta-Cell replication is not associated with the degree of inflammation in NVP-DPP728-treated NOD mice.

  14. Maturity-onset diabetes of the young type 5 in a family with diabetes and mild kidney disease diagnosed by whole exome sequencing.

    Science.gov (United States)

    Wentworth, J M; Lukic, V; Bahlo, M; Finlay, M; Nguyen, C; Morahan, G; Harrison, L C

    2014-11-01

    Exome sequencing is being increasingly used to identify disease-associated gene mutations. We used whole exome sequencing to determine the genetic basis of a syndrome of diabetes and renal disease affecting a mother and her son. We identified a mutation in the hepatocyte nuclear factor 1-b (HNF1B) gene that encoded a methionine to valine amino acid change (M160V) in the HNF1B protein. This leads us to the previously unappreciated diagnosis of maturity-onset diabetes of the young type 5 and provided a basis for genetic counselling of other family members. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  15. TNF-alpha promoter gene polymorphisms in Spanish children with persistent oligoarticular and systemic-onset juvenile idiopathic arthritis.

    Science.gov (United States)

    Modesto, C; Patiño-García, A; Sotillo-Piñeiro, E; Merino, J; García-Consuegra, J; Merino, R; Rua, M J; Sierrasesúmaga, L; Arnal, C

    2005-01-01

    To explore the possible association/s of the first reported tumour necrosis factor (TNF-alphaTNF-) alpha promoter gene polymorphisms -308, -238, -376 and -163 (G-->A) with systemic (SoJIA) and oligoarticular subtypes of juvenile idiopathic arthritis (JIA); and to test the association between these polymorphisms and the class I/class II HLA alleles in our population. The patient group comprised 29 oligoarticular and 26 systemic Caucasian Spanish children with JIA; 68 healthy volunteers from the same ethnic group and geographical region served as controls. HLA alleles were determined using low-resolution polymerase chain reaction (PCR). TNF-alpha promoter gene polymorphisms were screened using PCR denaturing gradient gel electrophoresis (PCR-DGGE), followed, if positive, by restriction fragment length polymorphism (RFLP) analysis for identification. No statistical association was found between the four polymorphisms studied and JIA. However, the -308 G-->A polymorphism (TNF A2) tended to be more frequent in patients with SoJIA than in the oligoarticular group. TNF A2 was strongly associated with the extended haplotype A1B8DR3 (p = 0.003), and the tandem polymorphism -238/-376 in the presence of B18 and DR3. The TNF A2 allele was more frequent in SoJIA than in the oligoarticular group. TNF A2 can help to create a more inflammatory milieu in this JIA subtype, in combination with other polymorphisms involved in regulatory sequences of key molecules in the inflammatory response. The association of the -308 and -238/-376 polymorphisms with specific alleles of the HLA is reconfirmed.

  16. 幼年发病型脊柱关节病的临床特征%Clinical characters of juvenile onset spondyloarthropathies

    Institute of Scientific and Technical Information of China (English)

    张江林; 黄烽

    2001-01-01

    目的 提高对幼年发病型脊柱关节病(JSpA)的认识。方法 分析190例JSpA患者的临床、实验室及放射学资料,并对幼年发病关节炎的诊断、分类和鉴别进行讨论。结果 190例JSpA中,男性163例,女性27例,男女之比为6∶1,发病年龄3~16岁,平均(12±3)岁,8岁后发病175例,占92.1%;157例(82.6%)患者首先出现的是外周关节炎,23例(12.1%)以腰背痛为第一症状,病程中共有187例(98.4%)的患者出现了外周关节炎,123例(64.7%)患者有或有过腰背疼痛史,外周关节炎与腰背疼痛出现的时间间隔,从同时发生到间隔20年,平均3.2年。67例(35.3%)有肌腱端炎的表现,20例(10.5%)腊肠指(趾),9例虹膜炎。HLA-B27的阳性率为87.9%,76.0%有X线证实的骶髂关节炎。在190例患者中,106例患者确诊幼年强直性脊柱炎(JAS),此组患者平均病程6.3年,明显长于JSpA组(P<0.01)。结论 JSpA的概念有助于提高对儿童关节炎的认识,半数以上JSpA患者约在发病6.3年后发展为幼年强直性脊柱炎。%Objective To better understand the clinical characters of juvenile onset spondyloarthropa-thies (JSpA).Methods The clinical and laboratory data of 190 in-patients with JSpA were analyzed and the diagnosis,classification and differentiation of juvenile onset arthritis were discussed.Results Among these 190 patients,163 were male,with a male to female ratio 6∶1.Of them 92.1% had the disease after the age of 8.Peak of age at onset was 12 to 15 years;157(82.6%) patients had peripheral arthritis and only 23(12.1%) patients felt low back pain at onset.During the disease course, peripheral arthritis was found in 187(98.4%) patients and the history of low back pain or buttock pain was recorded in 123(64.7%).The interval between peripheral arthritis and low back pain was from 0 to 20 years,with an average of (3.2±4.5)years.Extra-articular features including enthesitis in 67

  17. New-onset diabetes mellitus after shock wave lithotripsy for urinary stone: a systematic review and meta-analysis.

    Science.gov (United States)

    Deng, Tuo; Liao, Banghua; Tian, Ye; Luo, Deyi; Liu, Jiaming; Jin, Tao; Wang, Kunjie

    2015-06-01

    The purpose of the study was to evaluate the association between shock wave lithotripsy (SWL) for urinary stone and new-onset diabetes mellitus (DM). A comprehensive data collection was performed in the Pubmed database, Embase database, Chinese Biomedical database, Chinese National Knowledge Infrastructure database and VIP database. Difference in incidence of new-onset DM after SWL between cases and controls was evaluated by odds ratio (OR) with its 95% confidence interval (CI). And summary adjusted risk ratios (RRs) and 95% CIs were calculated to assess the strength of association between SWL and new-onset DM, and then subgroup analyses were conducted. Five studies were included in this meta-analysis. The incidence of new-onset DM after SWL is not higher than that in the population who do not receive SWL [OR = 1.59, 95% CI (0.92, 2.74), P = 0.10]. And statistical association between SWL and new-onset DM could not be found significantly [RR = 1.33, 95% CI (0.83, 2.13), P = 0.24], either. However, body mass index (BMI) [RR = 1.09, 95% CI (1.04, 1.14), P urinary stone and new-onset DM.

  18. Assessing the likelihood of new-onset inflammatory bowel disease following tumor necrosis factor-alpha inhibitor therapy for rheumatoid arthritis and juvenile rheumatoid arthritis.

    Science.gov (United States)

    Krishnan, Asha; Stobaugh, Derrick J; Deepak, Parakkal

    2015-04-01

    The association between inhibition of tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and the onset of inflammatory bowel disease (IBD) is unclear. We sought to evaluate this association by analyzing adverse events (AEs) reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) with a standardized scoring tool for drug-induced AEs. A search of the FAERS for RA or JRA (January 2003-December 2011) reported with adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab was performed. This dataset was then queried for cases indicating IBD. Full-length reports were accessed using the Freedom of Information Act and organized by age, sex, concomitant medications, co-morbidities, type of TNF-α inhibitor used, and diagnosis/treatment details. The Naranjo score was used to determine whether the drug-induced AEs were definite, probable, possible, or doubtful. There were 158 cases of IBD after TNF-α inhibitor exposure in RA or JRA patients. Use of the Naranjo score revealed that, in a majority of the cases (71.5 %), TNF-α inhibitor exposure was considered a 'possible' cause. A majority of the 'probable cases' in JRA were reported with etanercept (40 patients, 90.91 %). There were no 'definite' cases of anti-TNF-induced IBD. After applying the Naranjo scale, a weak association between new-onset IBD and TNF-α inhibitor therapy in RA patients and a moderately strong association especially with etanercept exposure in JRA patients was observed. However, causality cannot be determined due to limitations of the FAERS and the Naranjo score.

  19. Preliminary analysis of immune activation in early onset type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Julia D. Rempel

    2013-08-01

    Full Text Available Introduction. First Nations and other Aboriginal children are disproportionately affected by cardiometabolic diseases, including type 2 diabetes (T2D. In T2D, the disruption of insulin signalling can be driven by pro-inflammatory immunity. Pro-inflammatory responses can be fueled by toll-like receptors (TLR on immune cells such as peripheral blood mononuclear cells (PBMC, a white blood cell population. TLR4 can bind to lipids from bacteria and food sources activating PBMC to produce cytokines tumour necrosis factor (TNF-α and interleukin (IL-1β. These cytokines can interfere with insulin signalling. Here, we seek to understand how TLR4 activation may be involved in early onset T2D. We hypothesized that immune cells from youth with T2D (n=8 would be more reactive upon TLR4 stimulation relative to cells from age and body mass index (BMI-matched controls without T2D (n=8. Methods. Serum samples were assayed for adipokines (adiponectin and leptin, as well as cytokines. Freshly isolated PBMC were examined for immune reactivity upon culture with TLR4 ligands bacterial lipopolysaccharide (LPS, 2 and 0.2 ng/ml and the fatty acid palmitate (200 µM. Culture supernatants were evaluated for the amount of TNF-α and IL-1β produced by PBMC. Results. Youth with T2D displayed lower median serum adiponectin levels compared to controls (395 vs. 904 ng/ml, p<0.05. PBMC isolated from youth with and without T2D produced similar levels of TNF-α and IL-1β after exposure to the higher LPS concentration. However, at the low LPS dose the T2D cohort exhibited enhanced IL-1β synthesis relative to the control cohort. Additionally, exposure to palmitate resulted in greater IL-1β synthesis in PBMCs isolated from youth with T2D versus controls (p<0.05. These differences in cytokine production corresponded to greater monocyte activation in the T2D cohort. Conclusion. These preliminary results suggest that cellular immune responses are exaggerated in T2D, particularly

  20. Loss of autoregulation of blood flow in subcutaneous tissue in juvenile diabetes

    DEFF Research Database (Denmark)

    Henriksen, O; Kastrup, J; Parving, H H;

    1984-01-01

    and retinopathy. The blood flow remained constant in all normal subjects, when the arterial perfusion pressure was varied between 70 and 150 mm Hg. All diabetics had impaired or reduced autoregulation of the subcutaneous blood flow. The blood flow increased and decreased almost linearly with the changes...... in arterial perfusion pressure. The mechanism underlying the defect autoregulation of blood flow in diabetics is uncertain; possibilities include structural changes of the arterioles and/or alterations of local metabolic factors.......The autoregulation of blood flow in subcutaneous tissue was investigated at the level of the lateral malleolus by the local 133Xenon washout technique. We have investigated eight long-term insulin-dependent diabetics and seven healthy controls. All diabetics had moderate diabetic nephropathy...

  1. Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial.

    Science.gov (United States)

    Hermida, Ramón C; Ayala, Diana E; Mojón, Artemio; Fernández, José R

    2016-02-01

    We investigated whether therapy with the entire daily dose of ≥ 1 hypertension medications at bedtime exerts greater reduction in the risk of new-onset diabetes than therapy with all medications upon awakening. We conducted a prospective, randomised, open-label, blinded endpoint trial of 2,012 hypertensive patients without diabetes, 976 men and 1,036 women, 52.7 ± 13.6 years of age. Patients were randomised, using a computer-generated allocation table, to ingest all their prescribed hypertension medications upon awakening or the entire daily dose of ≥ 1 of them at bedtime. Investigators blinded to the hypertension treatment scheme of the patients assessed the development of new-onset diabetes. During a 5.9-year median follow-up, 171 participants developed type 2 diabetes. Patients of the bedtime, compared with the morning-treatment group, showed: (1) significantly lower asleep BP mean, greater sleep-time relative BP decline and attenuated prevalence of non-dipping at the final evaluation (32% vs 52%, p Ciencia e Innovación (SAF2006-6254-FEDER; SAF2009-7028-FEDER); Xunta de Galicia (PGIDIT03-PXIB-32201PR; INCITE07-PXI-322003ES; INCITE08-E1R-322063ES; INCITE09-E2R-322099ES; 09CSA018322PR); and Vicerrectorado de Investigación, University of Vigo.

  2. Ketosis Onset Type 2 Diabetes Had Better Islet β-Cell Function and More Serious Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hongyun Lu

    2014-01-01

    Full Text Available Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM, but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases and nonketotic onset group (78 cases. After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β and insulin resistance (HOMA-IR. Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD than nonketotic group (P=0.04. Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC0–0.5, AUC0–1, AUC0–3 (P<0.05. Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P<0.05. From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM.

  3. Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease.

    Science.gov (United States)

    Anheim, Mathieu; Lagha-Boukbiza, Ouhaïd; Fleury-Lesaunier, Marie-Céline; Valenti-Hirsch, Maria-Paola; Hirsch, Edouard; Gervais-Bernard, Hélène; Broussolle, Emmanuel; Thobois, Stéphane; Vanier, Marie T; Latour, Philippe; Tranchant, Christine

    2014-01-01

    Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.

  4. Study of Tripterygium Associated with Nicotinamide in Treating Late-onset Autoimmune Diabetes Mellitus in Adults

    Institute of Scientific and Technical Information of China (English)

    刘江华; 段世芳; 刘志文; 刘宗汉; 曹仁贤; 文芳; 文格波

    2004-01-01

    Objective: To explore the effect of Tripterygium polyglycoside (TP) associated with nicotinamide on the islet cell function, immune parameters and lipoperoxide (LPO) in adult patients with late-onset autoimmune diabetes mellitus (LADA) Methods: Thirty-six cases of LADA were randomly divided into three groups: TP group (n= 12), treated with TP plus orally taken metformin; combined treatment group (n =12), treated with TP combined with nicotinamide and metformin, and control group (n = 12) treated with metformin alone. They were followed-up for 18 months. Results: (1) Compared with the control group after 9months of treatment, postprandial plasma glucose and LPO in combined treatment group were decreased (P <0.05), and the postprandial C-peptide was higher (P<0.05). At the 18th month, the value of postprandial C-peptide in the TP and combined treatment group was higher than that in the control group. The slL-2R level of both TP and combined treatment groups were lowered (P<0.01); (2) Islet cell antibody (ICA) positive of 5 cases in the TP group and 6 cases in the combined treatment group got converted to the negative respectively, while only one in the control group at the time (P<0.05) ; (3) The level of LPO in the combined treatment group was significantly lower than that in the TP group at the 18th month of treatment (P<0.05).Conclusion: TP combined with nicotinamide played a role in immunity regulation, decreasing the titer of islet cell antibody and slL-2R, which also reduced the production of LPO and had a tendency to improve islet cell function in early LADA patients.

  5. Mediterranean style diet is associated with low risk of new-onset diabetes after renal transplantation

    Science.gov (United States)

    Osté, Maryse C J; Corpeleijn, Eva; Navis, Gerjan J; Keyzer, Charlotte A; Soedamah-Muthu, Sabita S; van den Berg, Else; Postmus, Douwe; de Borst, Martin H; Kromhout, Daan; Bakker, Stephan J L

    2017-01-01

    Objective The incidence of new-onset diabetes after transplantation (NODAT) and premature mortality is high in renal transplant recipients (RTR). We hypothesized that a Mediterranean Style diet protects against NODAT and premature mortality in RTR. Research design and methods A prospective cohort study of adult RTR with a functioning graft for >1 year. Dietary intake was assessed with a 177-item validated food frequency questionnaire. Patients were divided based on a 9-point Mediterranean Style Diet Score (MDS): low MDS (0–4 points) versus high MDS (5–9 points). A total of 468 RTR were eligible for analyses. Logistic multivariable regression analyses were used to study the association of MDS with NODAT and Cox multivariable regression models for the association with all-cause mortality. Results Mean±SD age was 51.3±13.2 years and 56.6% were men. About 50% of the patients had a high MDS. During median follow-up of 4.0 (IQR, 0.4–5.4) years, 22 (5%) RTR developed NODAT and 50 (11%) died. High MDS was significantly associated with both a lower risk of NODAT (HR=0.23; 95% CI 0.09 to 0.64; p=0.004) and all-cause mortality (HR=0.51; 95% CI 0.29 to 0.89, p=0.02) compared to low MDS, independent of age and sex. Adjustment for other potential confounders, including total energy intake, physical activity and smoking status, did not materially change the results of the analyses. Conclusions Dietary habits leading to high MDS were associated with lower risk of NODAT. These results suggest that healthy dietary habits are of paramount importance for RTR. PMID:28123752

  6. Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q

    Energy Technology Data Exchange (ETDEWEB)

    Bell, G.I.; Xiang, Kunsan; Newman, M.V.; Wu, Songhua; Cox, N.J. (Univ. of Chicago, IL (United States)); Wright, L.G.; Spielman, R.S. (Univ. of Pennsylvania, Philadelphia (United States)); Fajans, S.S. (Univ. of Michigan, Ann Arbor (United States))

    1991-02-15

    Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. The largest and best-studies MODY pedigree is the TW family. The majority of the diabetic subjects in this pedigree has a reduced and delayed insulin-secretory response to glucose, and it has been proposed that this abnormal response is the manifestation of the basic genetic defect that leads to diabetes. Using DNA from members of the TW family, the authors tested more than 75 DNA markers for linkage with MODY. A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. The maximum logarithm of adds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. These results indicate that the odds are {gt}178,000:1 that the gene responsible for MODY is this family is tightly linked to the ADA gene on chromosome 20q.

  7. Incretin Effect and Glucagon Responses to Oral and Intravenous Glucose in Patients with Maturity Onset Diabetes of the Young - Type 2 and Type 3

    DEFF Research Database (Denmark)

    Ostoft, Signe H; Bagger, Jonatan I; Hansen, Torben

    2014-01-01

    Maturity onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of non-autoimmune diabetes, constituting 1-2% of all diabetes. Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and...... incretin effect and inappropriate glucagon responses, whereas incretin effect and glucagon response to oral glucose remain unaffected in GCK-diabetes, reflecting important pathogenetic differences between the two MODY forms.......-diabetes), but only patients with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon responses to OGTT. Both groups of patients with diabetes showed normal suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes, similar to type 2 diabetes, is characterized by an impaired...

  8. Heritability, parental transmission and environment correlation of pediatric-onset type 2 diabetes mellitus and metabolic syndrome-related traits.

    Science.gov (United States)

    Miranda-Lora, América L; Vilchis-Gil, Jenny; Molina-Díaz, Mario; Flores-Huerta, Samuel; Klünder-Klünder, Miguel

    2017-04-01

    To estimate the heritability, parental transmission and environmental contributions to the phenotypic variation in type 2 diabetes mellitus and metabolic syndrome-related traits in families of Mexican children and adolescents. We performed a cross-sectional study of 184 tri-generational pedigrees with a total of 1160 individuals (99 families with a type 2 diabetes mellitus proband before age 19). The family history of type 2 diabetes mellitus in three generations was obtained by interview. Demographic, anthropometric, biochemical and lifestyle information was corroborated in parents and offspring. We obtained correlations for metabolic traits between relative pairs, and variance component methods were used to determine the heritability and environmental components. The heritability of early-onset of type 2 diabetes mellitus was 0.50 (p0.50) for blood pressure, HbA1c and HDL-cholesterol after multivariate adjustment (pdiabetes mellitus and insulin resistance, were significantly correlated only through the mother and others, such as hypertriglyceridemia, were significantly correlated only through the father. This study demonstrates that type 2 diabetes mellitus and metabolic syndrome-related traits are highly heritable among Mexican children and adolescents. Furthermore, several cardiometabolic factors have strong heritability and/or high environmental contributions that highlight the complex architecture of these alterations. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Islet autoantibodies in Latvian subjects with non-insulin-dependent diabetes mellitus: slow-onset type 1 diabetes or polyendocrine autoimmunity?

    Science.gov (United States)

    Shtauvere-Brameus, A; Falorni, A; Rumba, I; Sanjeevi, C B

    2002-04-01

    In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria; assays for the detection of autoantibodies are not available, and hence slowly progressive autoimmune diabetes is likely to be missed. Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. The aim of this study was to estimate the risk of polyendocrine autoimmunity among clinically diagnosed NIDDM patients from Latvia. One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. Age at onset was >or= 30 years, and duration of disease less than 5 years. Of 100 patients, 85 were on oral hypoglycemic agents and 15 were on insulin. Body mass index (BMI) under 19 was recorded in 1% (1 of 100 cases), while overweight (BMI > 25.5 in females and 27 in males) was documented in 45% (45 of 100 cases). GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). None of the patients carried antibodies against 21-OH and only 1 of 100 (1%) carried antibodies against TTG. From the results obtained in our study we conclude that in Latvian adult NIDDM subjects, islet autoantibodies identify groups of slow-onset type 1 diabetes but not polyendocrine autoimmunity.

  10. E-selectina soluble en una población infanto-juvenil con diabetes tipo 1 Soluble E- selectin in children and adolescents with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Teresita del R. Carrizo

    2008-06-01

    Full Text Available El estado de hiperglucemia crónica en los pacientes diabéticos produce una agresión al endotelio vascular, conduciendo al desarrollo prematuro de ateroesclerosis. El objetivo de este trabajo fue determinar niveles de E-selectina soluble (sE-S en una población infanto-juvenil con diabetes tipo1 (DT1 y su relación con el control glucémico y el perfil lipídico. Se estudiaron 30 pacientes con DT1 (16 mujeres y 14 varones, de edades comprendidas entre 6 y 15 años, comparados con 20 sujetos controles. Se determinaron: sE-S, glucemia en ayunas, hemoglobina glicosilada (HbA1c, colesterol total (CT, HDL-C, LDL-C, no HDL-C y triglicéridos (TG. Los niveles de sE-S fueron 66% más altos en los diabéticos que en los sujetos controles (p = 0.0001. Los pacientes fueron agrupados en: diabéticos con buen control glucémico (DBCG, HbA1c 8%. La concentración de sE-S en DPCG y en DBCG fue: 111.3 ± 40.5 vs. 68.0 ± 11.3 ng/ml, respectivamente p = 0.02. En los diabéticos la incidencia de valores no deseables en el perfil lipídico fue: CT: 50%; HDL-C 14%; LDL-C 52%, no HDL-C 26.7% y TG 14%. La sE-S se correlacionó mejor con HbA1c (r = 0.53, p = 0.0001 que con la glucemia en ayunas (r = 0.36, p = 0.008 y CT (r = 0.36, p = 0.009. De los resultados obtenidos se sugiere que la sE-S es un marcador temprano de disfunción endotelial y de probable riesgo de aterosclerosis en pacientes infanto-juveniles con DT1.The chronic hyperglycemic state in diabetic patients produces an aggression to the vascular endothelium leading to a premature development of atherosclerosis. The objective of this paper was to determine the soluble E-selectin (sE-S levels in children with type 1 diabetes (DT1 and its relationship with glycemic control and lipid profile. Thirty patients with DT1, (16 girls and 14 boys, age between 6 and 15 years were studied, whose data were compared with 20 control subjects. In both groups sE-S was determined as well as fasting glycemia, glycosylated

  11. Two novel RFX6 variants in siblings with Mitchell-Riley syndrome with later diabetes onset and heterotopic gastric mucosa.

    Science.gov (United States)

    Skopkova, Martina; Ciljakova, Miriam; Havlicekova, Zuzana; Vojtkova, Jarmila; Valentinova, Lucia; Danis, Daniel; Murgas, Dalibor; Szepeova, Renata; Stanik, Juraj; Banovcin, Peter; Klimes, Iwar; Gasperikova, Daniela

    2016-09-01

    Mitchell-Riley syndrome, an autosomal recessive disorder caused by mutations in the RFX6 gene, is defined as a combination of neonatal diabetes mellitus and serious congenital gastrointestinal defects. We describe Mitchell-Riley syndrome in two sisters with two novel compound heterozygous variants in the RFX6 gene: c.1154G > A, p.(Arg385Gln), and c.1316_1319delTCTA, p.(Ile439Thrfs*13). Both sisters present milder forms of the syndrome, likely due to possible residual activity of the p.Arg385Gln variant, which is localized in a dimerization domain of the RFX6 transcription factor. We propose that the prognosis is dependent on patient RFX6 genotype and possible residual activity of RFX6 transcription factor. Both sisters had atypical later onset of diabetes, at 2 years and 10 months and 2 years and 7 months, respectively. This supports the need of extending the definition of diabetes in Mitchell-Riley syndrome from neonatal to childhood onset and regular glyceamia check in patients with gastrointestinal tract malformations typical for Mitchell-Riley syndrome. The clinical course in both sisters improved significantly after surgical removal of parts of the small intestine with heterotopic gastric mucosa. We suggest that gastric mucosa heterotopy is an important actionable part of Mitchell-Riley syndrome and could have been responsible for the malabsorption, failure to thrive and severe anemia present in previously reported patients with Mitchell-Riley syndrome.

  12. The burden of type 2 diabetes: strategies to prevent or delay onset

    Directory of Open Access Journals (Sweden)

    Nayyar Iqbal

    2007-09-01

    Full Text Available Nayyar IqbalDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia VA Medical Center, PA, USAAbstract: Type 2 diabetes is widespread and its prevalence is increasing rapidly. In the US alone, approximately 41 million individuals have prediabetes, placing them at high risk for the development of diabetes. The pathogenesis of type 2 diabetes involves inadequate insulin secretion and resistance to the action of insulin. Suggestive data link insulin resistance and accompanying hyperglycemia to an excess of abdominal adipose tissue, a link that appears to be mediated partially by adipocyte secretion of multiple adipokines that mediate inflammation, thrombosis, atherogenesis, hypertension, and insulin resistance. The adipokine adiponectin has reduced expression in obesity and appears to be protective against the development of type 2 diabetes. Current recommendations to prevent type 2 diabetes center on lifestyle modifications, such as diet and exercise. Clinical trials have established the efficacy of lifestyle intervention, as well as pharmacologic interventions that target glycemic control or fat metabolism. However, diabetes did develop in a substantial percentage of individuals who received intensive intervention in these trials. Thus there is an unmet need for additional strategies in high-risk individuals. Recent data suggest thiazolidinediones and blockade of the endocannabinoid system represent novel therapeutic approaches that may be used for the prevention of diabetes.Keywords: cardiometabolic risk, abdominal obesity, dyslipidemia, diabetes, insulin resistance, endocannabinoid system

  13. Juvenile angiofibroma

    Science.gov (United States)

    Nasal tumor; Angiofibroma - juvenile; Benign nasal tumor; Juvenile nasal angiofibroma; JNA ... Juvenile angiofibroma is not very common. It is most often found in adolescent boys. The tumor contains ...

  14. Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.

    Science.gov (United States)

    Pruul, K; Kisand, K; Alnek, K; Metsküla, K; Reimand, K; Heilman, K; Peet, A; Varik, K; Peetsalu, M; Einberg, Ü; Tillmann, V; Uibo, R

    2015-09-05

    Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-β, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-β in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-β and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-β production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D.

  15. Increased metabolic turnover rate and transcapillary escape rate of albumin in long-term juvenile diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, N; Sander, E

    1975-01-01

    smaller than 0.05). The previously reported decrease in the intravascular albumin mass in long-term diabetics was thus confirmed by an average of 59.0 g/m2 surface area, compared with a normal value of 71.7 g/m2-(minus18%) (P smaller than 0.005). The albumin metabolic rate was increased, the fractional...

  16. Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes.

    Science.gov (United States)

    Leete, Pia; Willcox, Abby; Krogvold, Lars; Dahl-Jørgensen, Knut; Foulis, Alan K; Richardson, Sarah J; Morgan, Noel G

    2016-05-01

    Type 1 diabetes (T1D) results from a T cell-mediated destruction of pancreatic β-cells following the infiltration of leukocytes (including CD8(+), CD4(+), and CD20(+) cells) into and around pancreatic islets (insulitis). Recently, we reported that two distinct patterns of insulitis occur in patients with recent-onset T1D from the U.K. and that these differ principally in the proportion of infiltrating CD20(+) B cells (designated CD20Hi and CD20Lo, respectively). We have now extended this analysis to include patients from the Network for Pancreatic Organ Donors with Diabetes (U.S.) and Diabetes Virus Detection (DiViD) study (Norway) cohorts and confirm that the two profiles of insulitis occur more widely. Moreover, we show that patients can be directly stratified according to their insulitic profile and that those receiving a diagnosis before the age of 7 years always display the CD20Hi profile. By contrast, individuals who received a diagnosis beyond the age of 13 years are uniformly defined as CD20Lo. This implies that the two forms of insulitis are differentially aggressive and that patients with a CD20Hi profile lose their β-cells at a more rapid rate. In support of this, we also find that the proportion of residual insulin-containing islets (ICIs) increases in parallel with age at the onset of T1D. Importantly, those receiving a diagnosis in, or beyond, their teenage years retain ∼40% ICIs at diagnosis, implying that a functional deficit rather than an absolute β-cell loss may be causal for disease onset in these patients. We conclude that appropriate patient stratification will be critical for correct interpretation of the outcomes of intervention therapies targeted to islet-infiltrating immune cells in T1D.

  17. Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes

    Science.gov (United States)

    With the rise of type 2 diabetes in youth, it is critical to investigate factors such as physical activity (PA) and time spent sedentary that may be contributing to this public health problem. This article describes PA and sedentary time in a large cohort of youth with type 2 diabetes and compares t...

  18. Troubleshooting methods for microarray gene expression analysis in the onset of diabetic kidney disease

    NARCIS (Netherlands)

    Mazagova, Magdalena; Henning, Robert H.; Duin, Marry; van Buiten, Azuwerus; Buikema, Hendrik; Deelman, Leo E.

    2013-01-01

    Introduction: Microarrays have become the standard technique for discovering new genes involved in the development of (kidney) disease. Diabetic nephropathy is a frequent complication of diabetes and is characterized by renal fibrosis. As the pathways leading to fibrosis are initiated early in diabe

  19. Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

    Science.gov (United States)

    Chakkera, H.A.; Hanson, R.L.; Raza, S.M.; DiStefano, J.K.; Millis, M.P.; Heilman, R.L.; Mulligan, D.C.; Reddy, K.S.; Mazur, M.J.; Hamawi, K.; Moss, A.A.; Mekeel, K.L.; Cerhan, J.R.

    2012-01-01

    Introduction New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are “tipped over” to develop diabetes mellitus in the posttransplant milieu. Methods We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. Results The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. Conclusions These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT. PMID:20005362

  20. Association of New-Onset Diabetes Mellitus in Older People and Mortality in Taiwan: A 10-Year Nationwide Population-Based Study.

    Science.gov (United States)

    Chi, M-J; Liang, C-K; Lee, W-J; Peng, L-N; Chou, M-Y; Chen, L-K

    2017-01-01

    Older patients with diabetes mellitus are at a higher risk of developing diabetic macro- and micro-vascular complications and cardiovascular diseases than younger diabetes mellitus patients. However, older diabetes mellitus patients are very heterogeneous in their clinical characteristics, diabetes mellitus-related complications and age at disease onset. This study aimed to evaluate the all-cause mortality rates and adverse health outcomes among older adults with new-onset diabetes mellitus through a nationwide population-based study. A retrospective cohort study. 2001-2011 data of the National Health Insurance database. Nationally representative sample of Taiwanese adults aged 65 years and older with propensity score-matched controls. All-cause mortality and adverse health outcomes. During the study period, 45.3% of patients in the diabetes mellitus cohort and 38.8% in the non-diabetes mellitus cohort died. The adjusted relative risk for mortality in the diabetes mellitus cohort compared to the non-diabetes mellitus cohort was 1.23 (95% Confidence Interval [CI]=1.16-1.30) for males and 1.27 (95%CI=1.19-1.35) for females. During the follow-up period, 8.9% of the diabetes mellitus cohort and 5.8% of the non-diabetes mellitus cohort developed cardiovascular diseases; the diabetes mellitus cohort had an adjusted relative risk of cardiovascular complications compared to the non-diabetes mellitus cohort of 1.54 (95%CI=1.36-1.75) for men and 1.70 (95%CI=1.43-2.02) for women. The adjusted relative risk of mortality in the patients with hypoglycemia compared to non-hypoglycemia patients in the diabetes mellitus cohort was 2.33 (95%CI=1.81-3.01) for men and 2.73 (95%CI=2.10-3.52) for women after adjustment for age, Charlson comorbidity index, acute coronary syndrome, respiratory disease, cancer, infectious disease and nervous system disease at baseline. New-onset diabetes in older adults is associated with an increased risk of mortality, and hypoglycemia is an important

  1. Bone marrow transplantation reverses new-onset immunoinflammatory diabetes in a mouse model.

    Science.gov (United States)

    Lv, Cheng-Lan; Wang, Jing; Xie, Ting; Ouyang, Jian

    2014-01-01

    Bone marrow transplantation might be an effective method to cure type 1 diabetes mellitus. This study aimed to investigate whether bone marrow transplantation could reverse hyperglycemia in diabetic mice and whether high-dose total body irradiation followed by high-dose bone marrow mononuclear cell infusion could improve the efficiency of bone marrow transplantation in treating diabetic mice. Diabetic mice after multiple low doses of streptozotocin injection were irradiated followed by infusion with approximately 1×10(7) bone marrow mononuclear cells intravenously. Before and after bone marrow transplantation, fasting blood glucose, intraperitoneal glucose tolerance test, serum insulin, pancreatic histology, and the examination of insulin and glucagon in islets were processed. All recipients returned to near euglycemic within 1 week after undergoing bone marrow transplantation. No mice became hyperglycemia again during investigation period. The change of serum insulin, glucose tolerance test, pancreatic histology and the expression of insulin and glucagon in recipient islets after bone marrow transplantation all revealed islets regeneration and significant amelioration when compared respectively with those of diabetic mice without bone marrow transplantation. Bone marrow transplantation contributed to reduce blood glucose, prevent further blood glucose hike in diabetic recipients, and promote islets regeneration. High-dose total body irradiation in combination with high-dose bone marrow monoclear cell infusion could improve the efficiency of bone marrow transplantation in treating streptozotocin-induced diabetes.

  2. Chicken Embryos as a Potential New Model for Early Onset Type I Diabetes

    Directory of Open Access Journals (Sweden)

    Liheng Shi

    2014-01-01

    Full Text Available Diabetic retinopathy (DR is the leading cause of blindness among the American working population. The purpose of this study is to establish a new diabetic animal model using a cone-dominant avian species to address the distorted color vision and altered cone pathway responses in prediabetic and early diabetic patients. Chicken embryos were injected with either streptozotocin (STZ, high concentration of glucose (high-glucose, or vehicle at embryonic day 11. Cataracts occurred in varying degrees in both STZ- and high glucose-induced diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had decreased levels of blood insulin, glucose transporter 4 (Glut4, and phosphorylated protein kinase B (pAKT. In STZ-injected E20 embryos, the ERG amplitudes of both a- and b-waves were significantly decreased, the implicit time of the a-wave was delayed, while that of the b-wave was significantly increased. Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease in L-type voltage-gated calcium channel (L-VGCC currents, which was reflected in the decreased level of L-VGCCα1D subunit in the STZ-diabetic retinas. Through these independent lines of evidence, STZ-injection was able to induce pathological conditions in the chicken embryonic retina, and it is promising to use chickens as a potential new animal model for type I diabetes.

  3. Quality of Life in Patients with Early-onset and Late-onset Type 2 Diabetes Mellitus%早发和迟发2型糖尿病患者生存质量对比研究

    Institute of Scientific and Technical Information of China (English)

    郭员志; 李俊玲

    2016-01-01

    with early-onset and late-onset type 2 diabetes by using comparative analysis method, and to investigate the influencing factors for QoL.Methods By using purposive sampling method, 99 cases with early-onset type 2 diabetes and 99 cases with late-onset type 2 diabetes who were treated in Department of Endocrinology in Second Affiliated Hospital of Zhengzhou University from August 2015 to February 2016, were selected as study subjects.The general data of the patients including gender, age of onset, height, body weight, marital status, education level, occupation, payment of medical expenses, insulin use, family history of diabetes, diabetes duration, smoking or not after onset, and exercise frequency per week were recorded.The QoL was assessed using the Chinese normal audit of diabetes dependent quality of life ( CN-ADDQoL) .The QoL was compared between early-onset type 2 diabetes patients and late-onset type 2 diabetes patients, and the influencing factors for QoL were analyzed. Results A total of 198 questionnaires were distributed in this study, and 186 effective questionnaires were returned, the effective return rate was 93.9%.93 effective questionnaires were completed by early-onset type 2 diabetes patients, and 93 effective questionnaires were completed by late-onset type 2 diabetes patients.There were no statistically significant difference in CN-ADDQoL score of family life dimension and diet status dimension between early-onset and late-onset type 2 diabetes patients (P >0.05).The CN-ADDQoL score of sports and leisure dimension, emotion status dimension, psychological feeling dimension, and CN-ADDQoL total score among early-onset type 2 diabetes patients were significantly lower than those among late-onset type 2 diabetes patients respectively (P<0.05).The scores of willingness to work, short distance or long distance trips, holidays, friends and social relationships, close personal relationships, sexual life, self -confidence, feelings about the future, economic

  4. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders

    OpenAIRE

    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita

    2012-01-01

    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose r...

  5. Incretin hormones and maturity onset diabetes of the young - pathophysiological implications and anti-diabetic treatment potential

    DEFF Research Database (Denmark)

    Østoft, Signe Harring

    2015-01-01

    demonstrated according to insulin and glucagon responses and gastric emptying, and counter-regulatory responses were preserved during both treatments. No effect of either treatment was seen on fructosamine or HbA1c. In conclusion, patients with GCK-diabetes show normal incretin and glucagon physiology, thus...

  6. Early-onset diabetic E1-DN mice develop albuminuria and glomerular injury typical of diabetic nephropathy.

    Science.gov (United States)

    Hyvönen, Mervi E; Dumont, Vincent; Tienari, Jukka; Lehtonen, Eero; Ustinov, Jarkko; Havana, Marika; Jalanko, Hannu; Otonkoski, Timo; Miettinen, Päivi J; Lehtonen, Sanna

    2015-01-01

    The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER) at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

  7. Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Mervi E. Hyvönen

    2015-01-01

    Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

  8. Reversal of New-Onset Type 1 Diabetes With an Agonistic TLR4/MD-2 Monoclonal Antibody.

    Science.gov (United States)

    Bednar, Kyle J; Tsukamoto, Hiroki; Kachapati, Kritika; Ohta, Shoichiro; Wu, Yuehong; Katz, Jonathan D; Ascherman, Dana P; Ridgway, William M

    2015-10-01

    Type 1 diabetes (T1D) is currently an incurable disease, characterized by a silent prodromal phase followed by an acute clinical phase, reflecting progressive autoimmune destruction of insulin-producing pancreatic β-cells. Autoreactive T cells play a major role in β-cell destruction, but innate immune cell cytokines and costimulatory molecules critically affect T-cell functional status. We show that an agonistic monoclonal antibody to TLR4/MD-2 (TLR4-Ab) reverses new-onset diabetes in a high percentage of NOD mice. TLR4-Ab induces antigen-presenting cell (APC) tolerance in vitro and in vivo, resulting in an altered cytokine profile, decreased costimulatory molecule expression, and decreased T-cell proliferation in APC:T-cell assays. TLR4-Ab treatment increases T-regulatory cell (Treg) numbers in both the periphery and the pancreatic islet, predominantly expanding the Helios(+)Nrp-1(+)Foxp3(+) Treg subset. TLR4-Ab treatment in the absence of B cells in NOD.scid mice prevents subsequent T cell-mediated disease, further suggesting a major role for APC tolerization in disease protection. Specific stimulation of the innate immune system through TLR4/MD-2, therefore, can restore tolerance in the aberrant adaptive immune system and reverse new-onset T1D, suggesting a novel immunological approach to treatment of T1D in humans.

  9. Use of an artificial pancreas as a tool to determine subcutaneous insulin doses in juvenile diabetes.

    Science.gov (United States)

    Lambert, A E; Buysschaert, M; Lambotte, L

    1979-01-01

    The present study was undertaken to examine the feasibility of determining the most appropriate subcutaneous insulin treatment in unstable diabetes on the basis of the circadian hormonal profile delivered by an artificial pancreas. The metabolic control of 11 brittle diabetic subjects, as assessed by the M value and the MAGE index (used as indexes of blood glucose control and of glycemic fluctuations, respectively), was compared during a 5-day period before and after a 24-h connection to the artificial pancreas. The usual insulin treatment was continued to that day. Examination of the insulin pattern revealed by the artificial pancreas suggested that a valid scheme for subsequent treatment should consist of two daily injections of a mixture of short-acting and intermediate-acting insulins, which was administered to the patients beginning with the injection given after the artificial pancreas onwards. The new insulin regimen was characterized by a total daily dose that increased from 0.93 +/- 0.10 to 1.20 +/- 0.10 U/kg body weight (mean +/- SEM; P less than 0.005) as well as by a higher proportion of the dose given as regular insulin (37.1 +/- 6.9% before vs. 56.0 +/- 2.1% after; P less than 0.05). These changes led to a better control of blood glucose in 10 patients, as evidenced by a decrease of both the M value and the mean of all blood glucose levels. The mean MAGE index was not decreased, however, by the new insulin program, thereby suggesting that the lability of the disease remained unabated. These results indicate that subcutaneous treatment consisting of two daily injections of regular and intermediate-acting insulins and comprising 50 to 60% of the former could improve the metabolic control in unstable diabetes. The artifical pancreas provided a rapid and simple means to determine the appropriate doses for each type of insulin.

  10. Diabetic nephropathy. Pathogenesis and prevention.

    Science.gov (United States)

    Westberg, N G

    1980-01-01

    Already at the time of diagnosis of juvenile onset diabetes mellitus, there are morphological and functional changes in the kidney. The kidneys and the individual glomeruli are considerably enlarged, and the glomerular filtration increased. In experimental diabetes mellitus the metabolism of the glomerular basement membrane is increased. These abnormalities are reversible by meticulous metabolic control. Their relationship to the diabetic glomerulosclerosis that causes uremia twenty to thirty years later is not clear. Carefully analyzed extensive clinical experience confirms that good metabolic control delays the onset of symptomatic diabetic renal disease, as expected from experimental studies. Normalization of even a slightly elevated blood pressure may be important to slow the progression of the renal insufficiency. Better methods for the management of the diabetic state and better education of the patients may be important to postpone the heroic endeavours of renal or pancreatic transplantation or dialysis.

  11. 15-year incidence of diabetic ketoacidosis at onset of type 1 diabetes in children from a regional setting (Auckland, New Zealand).

    Science.gov (United States)

    Jefferies, Craig; Cutfield, Samuel W; Derraik, José G B; Bhagvandas, Jignal; Albert, Benjamin B; Hofman, Paul L; Gunn, Alistair J; Cutfield, Wayne S

    2015-05-19

    We assessed the incidence of diabetic ketoacidosis (DKA) in children aged <15 years with newly diagnosed type 1 diabetes mellitus (T1DM) in the Auckland Region (New Zealand) in 1999-2013, in a retrospective review of a complete regional cohort. DKA and its severity were classified according to ISPAD 2014 guidelines. Of 730 children presenting with new-onset T1DM over the 15-year time period, 195 cases had DKA of any severity (27%). There was no change in the incidence of DKA or the proportion of children with severe DKA at presentation. The incidence of DKA among children aged <2.0 years (n = 40) was 53% compared to 25% for those aged 2-14 years (n = 690; p = 0.005). In children aged 2-14 years, increasing age at diagnosis was associated with greater likelihood of DKA at presentation (p = 0.025), with the odds of DKA increasing 1.06 times with each year increase in age. Non-Europeans were more likely to present in DKA than New Zealand Europeans (OR 1.52; p = 0.048). Despite a consistent secular trend of increasing incidence of T1DM, there was no reduction in the incidence of DKA in new-onset T1DM in the Auckland Region over time. Thus, it is important to explore ways to reduce DKA risk.

  12. Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese.

    Directory of Open Access Journals (Sweden)

    Ronald Ching Wan Ma

    Full Text Available In Asia, young-onset type 2 diabetes (YOD is characterized by obesity and increased risk for cardiovascular disease (CVD. In a genome-wide association study (GWAS of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1 was associated with an odds ratio (OR of 2.49(95% confidence intervals:1.57-3.96, P = 8.4 × 10(-5. Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC from 63 cases compared to 65 controls (P = 0.02. In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802 with an OR of 1.07(1.02-1.12, P(meta  = 0.012. In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953, rs1408888 was associated with an OR of 1.54(1.07-2.22, P = 0.019 for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19-9.19, P = 0.0214 and 3.27(1.25-11.07, P = 0.0184 for coronary heart disease (CHD and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese.

  13. Relative size of the eye and orbit: an evolutionary and craniofacial constraint model for examining the etiology and disparate incidence of juvenile-onset myopia in humans.

    Science.gov (United States)

    Masters, Michael P

    2012-05-01

    within the confines of the orbital walls. The results of this study indicate that future research examining the etiology of juvenile-onset myopia, and particularly its correlation with ancestry, sex, age, and intelligence, should consider how the eye interacts with the matrix of structural and functional components of the skull during both ontogenetic and evolutionary morphogenesis.

  14. Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist.

    Science.gov (United States)

    Damond, Nicolas; Thorel, Fabrizio; Moyers, Julie S; Charron, Maureen J; Vuguin, Patricia M; Powers, Alvin C; Herrera, Pedro L

    2016-04-19

    Glucagon secretion dysregulation in diabetes fosters hyperglycemia. Recent studies report that mice lacking glucagon receptor (Gcgr(-/-)) do not develop diabetes following streptozotocin (STZ)-mediated ablation of insulin-producing β-cells. Here, we show that diabetes prevention in STZ-treated Gcgr(-/-) animals requires remnant insulin action originating from spared residual β-cells: these mice indeed became hyperglycemic after insulin receptor blockade. Accordingly, Gcgr(-/-) mice developed hyperglycemia after induction of a more complete, diphtheria toxin (DT)-induced β-cell loss, a situation of near-absolute insulin deficiency similar to type 1 diabetes. In addition, glucagon deficiency did not impair the natural capacity of α-cells to reprogram into insulin production after extreme β-cell loss. α-to-β-cell conversion was improved in Gcgr(-/-) mice as a consequence of α-cell hyperplasia. Collectively, these results indicate that glucagon antagonism could i) be a useful adjuvant therapy in diabetes only when residual insulin action persists, and ii) help devising future β-cell regeneration therapies relying upon α-cell reprogramming.

  15. Infant Growth and Risk of Childhood-Onset Type 1 Diabetes in Children From 2 Scandinavian Birth Cohorts

    DEFF Research Database (Denmark)

    Magnus, Maria C; Olsen, Sjurdur F; Granström, Charlotta

    2015-01-01

    -onset type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study using information from 2 population-based cohort studies in Norway and Denmark, the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC), of children born between February 1998 and July 2009...... proportional hazards regression. RESULTS: A total of 99,832 children were included in the study, with 59,221 in MoBa (51.2% boys and 48.8% girls; mean age at end of follow-up, 8.6 years [range, 4.6-14.2 years]) and 40,611 in DNBC (50.6% boys and 49.4% girls; mean age at end of follow-up, 13.0 years [range, 10.......4-15.7 years]). The incidence rate of type 1 diabetes from age 12 months to the end of follow-up was 25 cases per 100,000 person-years in DNBC and 31 cases per 100,000 person-years in MoBa. The change in weight from birth to 12 months was positively associated with type 1 diabetes (pooled unadjusted HR = 1...

  16. Effects of pregnancy on the onset and progression of diabetic nephropathy and of diabetic nephropathy on pregnancy outcomes.

    Science.gov (United States)

    Young, Esther Cytrynbaum; Pires, Maria Lucia Elias; Marques, Luiz Paulo José; de Oliveira, José Egídio Paulo; Zajdenverg, Lenita

    2011-01-01

    Controversy exists regarding the effect of pregnancy on the development and course of diabetic nephropathy. This study followed 43 pregnant women with previous diabetes mellitus, 32 without nephropathy (Group I) and 11 with nephropathy (Group II). Urinary albumin excretion (UAE), serum creatinine (Cr) and creatinine clearance (CCr) in the pre-pregnancy (Pre-P), first trimester (1T), third trimester (3T) and 1 year postpartum (PP) were evaluated. In both groups there were an increase in 3T compared to Pre-P of CCr (137 vs. 98 ml/min and 110 vs. 81 ml/min, p=0.0001, respectively) and UAE (7.78 vs. 3.15 mg/24 h and 592 vs. 119 mg/24 h, p=0.0001, respectively). Increase of Cr in the PP compared to 1T in Group II (0.88 vs. 0.70 mg/dL, p=0.031) was observed. There were no difference in UAE, CCr and Cr in the PP when compared to pre-P as well variance over time between groups. Group II showed higher prevalence of chronic hypertension (72.7 vs. 21.9%, p=0.004), preeclampsia (63.6 vs. 6.3%, p=0.0003) and lower gestational age at birth (36 vs. 38 weeks, p=0.003). We conclude that pregnancy was not associated with development and progression of diabetic nephropathy in women with or without mild renal dysfunction. The presence of diabetic nephropathy was associated with increased risk of perinatal complications.

  17. Delay between Onset of Symptoms and Seeking Physician Intervention Increases Risk of Diabetic Foot Complications: Results of a Cross-Sectional Population-Based Survey

    Directory of Open Access Journals (Sweden)

    Norina A. Gavan

    2016-01-01

    Full Text Available We present a post hoc analysis of 17,530 questionnaires collected as part of the 2012 screening for neuropathy using Norfolk Quality of Life tool in patients with diabetes in Romania, to assess the impact on foot complications of time between the onset of symptoms of diabetes/its complications and the physician visit. Odds ratios (ORs for self-reporting neuropathy increased from 1.16 (95% CI: 1.07–1.25 in those who sought medical care in 1–6 months from symptoms of diabetes/its complications onset to 2.27 in those who sought medical care >2 years after symptoms onset. The ORs for having a history of foot ulcers were 1.43 (95% CI: 1.26–1.63 in those who sought medical care in 1–6 months and increased to 3.08 (95% CI: 2.59–3.66 in those who sought medical care after >2 years from symptoms of diabetes/its complications onset. The highest ORs for a history of gangrene (2.49 [95% CI: 1.90–3.26] and amputations (2.18 [95% CI: 1.60–2.97] were observed in those who sought medical care after >2 years following symptoms onset. In conclusion, we showed that waiting for >1 month after symptoms onset dramatically increases the risk of diabetic foot complications. These results show the need for accessible educational programs on diabetes and its chronic complications and the need to avoid delays in reporting.

  18. 青少年开角型青光眼临床表型及遗传学特征%Clinical and genetic characteristics of primary juvenile-onset open-angle glaucoma

    Institute of Scientific and Technical Information of China (English)

    刘铁城

    2014-01-01

    青少年开角型青光眼(juvenile-onset open-angle glaucoma,JOAG)是常染色体显性遗传性疾病,具有发病年龄早、眼压高和进展快等特点.本文回顾了JOAG的临床表型、相关基因及功能,为建立基因型和表型之间的联系,为探讨青光眼的发病机制提供帮助.

  19. The Effects of 12 Weeks Regular Aerobic Exercise on Brain-derived Neurotrophic Factor and Inflammatory Factors in Juvenile Obesity and Type 2 Diabetes Mellitus

    Science.gov (United States)

    Lee, Sung Soo; Yoo, Jae Ho; Kang, Sung; Woo, Jin Hee; Shin, Ki Ok; Kim, Kwi Beak; Cho, Su Youn; Roh, Hee Tae; Kim, Young Il

    2014-01-01

    [Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enrolled 26 juveniles (boys = 15, girls = 9) who were assigned to a control group (CG, n = 11), obesity group (OG, n = 8), or T2DM group (TG, n = 7). [Methods] The outcome of a 40–60-minute aerobic exercise session that took place three times per week for 12 weeks at a maximum oxygen intake (VO2max) of 50~60% was investigated. [Results] The exercise resulted in a significant reduction in the resting serum BDNF and TrkB levels (baseline) among juveniles in the OG and TG as compared to those in the CG. Additionally, the 12 weeks of regular aerobic exercise led to significant reductions in body weight, body fat percentage, and body mass index in the OG and a significant increase of VO2max in the OG and TG. However, no significant differences in serum NGF or inflammatory factors were found among the three groups. There was a significant increase in resting serum BDNF levels following the 12 weeks regular exercise only in the OG. [Conclusion] While 12 weeks of regular aerobic exercise had a positive effect on body composition, and increased BDNF levels of juveniles in the OG, it did not affect the inflammatory factor levels and had no effect on the TG. PMID:25202180

  20. The Effects of 12 Weeks Regular Aerobic Exercise on Brain-derived Neurotrophic Factor and Inflammatory Factors in Juvenile Obesity and Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Lee, Sung Soo; Yoo, Jae Ho; Kang, Sung; Woo, Jin Hee; Shin, Ki Ok; Kim, Kwi Beak; Cho, Su Youn; Roh, Hee Tae; Kim, Young Il

    2014-08-01

    [Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enrolled 26 juveniles (boys = 15, girls = 9) who were assigned to a control group (CG, n = 11), obesity group (OG, n = 8), or T2DM group (TG, n = 7). [Methods] The outcome of a 40-60-minute aerobic exercise session that took place three times per week for 12 weeks at a maximum oxygen intake (VO2max) of 50~60% was investigated. [Results] The exercise resulted in a significant reduction in the resting serum BDNF and TrkB levels (baseline) among juveniles in the OG and TG as compared to those in the CG. Additionally, the 12 weeks of regular aerobic exercise led to significant reductions in body weight, body fat percentage, and body mass index in the OG and a significant increase of VO2max in the OG and TG. However, no significant differences in serum NGF or inflammatory factors were found among the three groups. There was a significant increase in resting serum BDNF levels following the 12 weeks regular exercise only in the OG. [Conclusion] While 12 weeks of regular aerobic exercise had a positive effect on body composition, and increased BDNF levels of juveniles in the OG, it did not affect the inflammatory factor levels and had no effect on the TG.

  1. Apoptosis of Purified CD4+ T Cell Subsets Is Dominated by Cytokine Deprivation and Absence of Other Cells in New Onset Diabetic NOD Mice

    OpenAIRE

    Ayelet Kaminitz; Askenasy, Enosh M.; Isaac Yaniv; Jerry Stein; Nadir Askenasy

    2010-01-01

    BACKGROUND: Regulatory T cells (Treg) play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. PRINCIPAL FINDINGS: Apopto...

  2. The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial.

    Directory of Open Access Journals (Sweden)

    Hubert Kolb

    Full Text Available BACKGROUND: The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics. METHODS AND FINDINGS: All patients (n = 89, 40% female of the Diabetes and Atorvastatin (DIATOR Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25-0.72, i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI. There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex. CONCLUSIONS: In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and

  3. The Systemic Immune Network in Recent Onset Type 1 Diabetes: Central Role of Interleukin-1 Receptor Antagonist (DIATOR Trial)

    Science.gov (United States)

    Kolb, Hubert; Lückemeyer, Kathrin; Heise, Tim; Herder, Christian; Schloot, Nanette C.; Koenig, Wolfgang; Heinemann, Lutz; Martin, Stephan

    2013-01-01

    Background The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics. Methods and Findings All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18–39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25–0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex. Conclusions In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only

  4. Effect of Extended-Release Niacin on New-Onset Diabetes Among Hyperlipidemic Patients Treated With Ezetimibe/Simvastatin in a Randomized Controlled Trial

    Science.gov (United States)

    Guyton, John R.; Fazio, Sergio; Adewale, Adeniyi J.; Jensen, Erin; Tomassini, Joanne E.; Shah, Arvind; Tershakovec, Andrew M.

    2012-01-01

    OBJECTIVE To determine the effect of niacin on fasting glucose (FG) and new-onset diabetes in statin/ezetimibe-treated patients. RESEARCH DESIGN AND METHODS This was a prespecified secondary analysis among 942 hyperlipidemic patients randomized to ezetimibe/simvastatin (E/S; 10/20 mg) or E/S + extended-release niacin (N; titrated to 2 g) over 64 weeks. RESULTS FG levels peaked by 8–12 weeks, then declined even without antidiabetic medication. At 64 weeks, 3.5% taking E/S+N versus 2.6% taking E/S met criteria for new-onset diabetes (P = 0.66). An additional 1.4% taking E/S+N versus 0.4% taking E/S transiently met criteria for diabetes and then remitted (P = 0.46). Of 28 new-diabetes diagnoses in the E/S+N group, 25 occurred by 24 weeks. Among patients with baseline diabetes, 13.9% taking E/S+N and 11.6% taking E/S underwent antidiabetic treatment modification. CONCLUSIONS Increased FG and new-onset diabetes with E/S+N occurred mainly around the time of initial uptitration of N and often improved or remitted without specific treatment. PMID:22338103

  5. Body composition in adults with Type 1 diabetes at onset and during the first year of insulin therapy

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Almdal, Thomas Peter; Hilsted, J

    2002-01-01

    index (BMI) 20.8 +/- 1.6 (19.2-23.4) kg/m2, body composition was estimated by means of dual-energy X-ray absorptiometry (DXA) whole body scanning supplemented by estimation of total body water (TBW) (isotope dilution technique with 3H2O) at diagnosis and after 1, 3, 6 and 12 months of insulin therapy......AIMS: To describe body composition in patients with Type 1 diabetes at diagnosis and during the first year after initiation of insulin therapy. RESEARCH DESIGN AND METHODS: In 10 (eight male and two female) newly onset Type 1 patients, age 31.5 +/- 3.2 years (27-37 years) (sd and range), body mass...

  6. Body composition in adults with Type 1 diabetes at onset and during the first year of insulin therapy

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Almdal, Thomas Peter; Hilsted, J;

    2002-01-01

    index (BMI) 20.8 +/- 1.6 (19.2-23.4) kg/m2, body composition was estimated by means of dual-energy X-ray absorptiometry (DXA) whole body scanning supplemented by estimation of total body water (TBW) (isotope dilution technique with 3H2O) at diagnosis and after 1, 3, 6 and 12 months of insulin therapy......AIMS: To describe body composition in patients with Type 1 diabetes at diagnosis and during the first year after initiation of insulin therapy. RESEARCH DESIGN AND METHODS: In 10 (eight male and two female) newly onset Type 1 patients, age 31.5 +/- 3.2 years (27-37 years) (sd and range), body mass...

  7. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    Directory of Open Access Journals (Sweden)

    Siri Fredheim

    2011-01-01

    Full Text Available Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule causing permanent neonatal diabetes. All three were diagnosed before 29 weeks of age, were born at term with near-normal birth weight, and were negative for GAD, ICA, IA-2, and IAA autoantibodies. The daily insulin requirement the first six months after diagnosis was <0.5 U kg−1 day−1 for both children. The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated for mutations of INS gene.

  8. Is childhood-onset type I diabetes a wealth-related disease?

    DEFF Research Database (Denmark)

    Patterson, C.C.; Dahlquist, G.; Soltész, G.

    2001-01-01

    -reported associations with milk consumption (r = 0.58), coffee consumption (r = 0.51) and latitude (r = 0.40) were also observed. CONCLUSION/INTERPRETATION: The wide variation in childhood Type I diabetes incidence rates within Europe could be partially explained by indicators of national prosperity. These indicators...... could reflect differences in environmental risk factors such as nutrition or lifestyle that are important in determining a country's incidence rate....

  9. New-onset diabetes mellitus after heart transplantation in children - Incidence and risk factors.

    Science.gov (United States)

    Sehgal, Swati; Bock, Matthew J; Louks Palac, Hannah; Brickman, Wendy J; Gossett, Jeffrey G; Marino, Bradley S; Backer, Carl L; Pahl, Elfriede

    2016-11-01

    Diabetes mellitus is a recognized complication of SOT in adults and is associated with decreased graft and patient survival. Little is known about NOD in pediatric HT recipients. We aimed to characterize the incidence and describe risk factors for development of NOD after HT in children. Children who developed diabetes after HT were identified from the OPTN database. Demographic and clinical data before and after transplant were compared between patients with and without NOD. A total of 2056 children were included, 56% were male, 54% were Caucasian, and 62% had cardiomyopathy prior to HT. NOD developed in 219 children (11%) after HT. The incidence of NOD was 2.4, 9.0, and 10.4% at one, five, and 10 yr after HT, respectively. Obesity (HR: 4.32), dialysis prior to transplant (HR: 2.38), African American race (HR: 1.86), transplant before year 2000 (HR: 1.82), female gender (HR: 1.68), and older age at transplant (HR: 1.28) were independent predictors of NOD. The major modifiable risk factor for NOD is obesity, imparting the maximum hazard. Improved surveillance for diabetes in high-risk patients and specific prevention and intervention strategies are imperative in this population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Early Treatment With Olmesartan Prevents Juxtamedullary Glomerular Podocyte Injury and the Onset of Microalbuminuria in Type 2 Diabetic Rats

    Science.gov (United States)

    Sofue, Tadashi; Kiyomoto, Hideyasu; Kobori, Hiroyuki; Urushihara, Maki; Nishijima, Yoko; Kaifu, Kumiko; Hara, Taiga; Matsumoto, Sachiko; Ichimura, Atsuhiko; Ohsaki, Hiroyuki; Hitomi, Hirofumi; Kawachi, Hiroshi; Hayden, Melvin R.; Whaley-Connell, Adam; Sowers, James R.; Ito, Sadayoshi; Kohno, Masakazu; Nishiyama, Akira

    2012-01-01

    Background Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus. Methods OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7–25 weeks. Results OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters. Conclusions This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes. PMID:22318512

  11. The Leu7Pro polymorphism of neuropeptide Y is associated with younger age of onset of type 2 diabetes mellitus and increased risk for nephropathy in subjects with diabetic retinopathy.

    Science.gov (United States)

    Jaakkola, U; Pesonen, U; Vainio-Jylhä, E; Koulu, M; Pöllönen, M; Kallio, J

    2006-04-01

    Several studies have shown genetic predisposition for diabetic complications. The leucine7 to proline7 (Leu7Pro) polymorphism of preproNPY has been shown to be a risk factor for diabetic retinopathy in type 1 diabetes. In the current study we examined the contribution of this polymorphism on the progression of retinopathy in Caucasian type 1 and type 2 diabetes patients. Patients with type 2 diabetes and the Leu7Pro polymorphism developed retinopathy at younger age because of markedly earlier disease onset of diabetes (RC- 6.8, 95% CI-12.2 - [- 1.5]), but no association of the Leu7Pro polymorphism with the current severity of retinopathy was detected. A strong association of the polymorphism with proteinuria in type 2 diabetes patients with retinopathy could be detected (OR 3.1, 95% CI 1.1-8.8); 31% of subjects having both retinopathy and proteinuria had the polymorphism compared to only 13% of retinopathy patents without concomitant proteinuria (p = 0.032). Plasma concentrations of NPY were increased in subjects with proteinuria (79.2+/-28.4 and 64.7+/-26.2 pmol/l, p = 0.001). These results suggest that the Leu7Pro polymorphism could be used to predict earlier onset of type 2 diabetes and retinopathy, and increased risk for diabetic nephropathy.

  12. Dermatomyositis (Juvenile)

    Science.gov (United States)

    ... Am A Patient / Caregiver Diseases & Conditions Dermatomyositis (Juvenile) Dermatomyositis (Juvenile) Fast Facts Patients with JDM have varying ... What are common signs and symptoms of juvenile dermatomyositis? The most common signs and symptoms of JDM ...

  13. Retinoschisis (Juvenile)

    Science.gov (United States)

    ... here Home › Eye Conditions Listen Retinoschisis What is Juvenile Retinoschisis? Juvenile retinoschisis is an inherited disease diagnosed in childhood ... degeneration of the retina. What are the symptoms? Juvenile retinoschisis, also known as X-linked retinoschisis, occurs ...

  14. Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus.

    Science.gov (United States)

    Heida, Karst Y; Franx, Arie; van Rijn, Bas B; Eijkemans, Marinus J C; Boer, Jolanda M A; Verschuren, Monique W M; Oudijk, Martijn A; Bots, Michiel L; van der Schouw, Yvonne T

    2015-12-01

    A prospective cohort study was conducted to assess the impact of a history of hypertensive disorder of pregnancy (HDP) or gestational diabetes mellitus (GDM) on the risk and age of onset of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease (CVD) later in life, independent of hypertension and T2D. Between 1993 and 1997, 22 265 ever-pregnant women were included from the European Prospective Investigation into Cancer and Nutrition-NL study, aged 20 to 70 years at baseline. Details on complications of pregnancy and known hypertension were obtained by questionnaire. Blood pressure was measured at enrollment. Participants were followed for the occurrence of CVD events. Data were analyzed using ANCOVA, multivariable logistic regression, and Cox proportional hazard (with HDP and GDM as time-dependent variables for T2D and CVD) models. At enrollment, women with a HDP reported diagnosis of hypertension 7.7 years earlier (95% confidence interval [CI] 6.9-8.5) and women with GDM reported diagnosis of T2D 7.7 years earlier (95% CI 5.8-9.6) than women without pregnancy complications. After adjustment for potential confounders, HDP was associated with presence of hypertension at enrollment (odds ratio 2.12, 95% CI 1.98-2.28) and onset of CVD later in life (hazard ratio 1.21, 95% CI 1.10-1.32). After including the intermediates hypertension and T2D in the model, the risk of CVD later in life decreased (hazard ratio 1.09, 95% CI 1.00-1.20). GDM was associated with an increased risk of developing T2D later in life (hazard ratio 3.68, 95% CI 2.77-4.90), but not with risk of CVD. HDP and GDM have a substantial impact on the risk of CVD and are potentially important indicators for preventive cardiovascular risk management. © 2015 American Heart Association, Inc.

  15. New Onset Diabetes Mellitus in Living Donor versus Deceased Donor Liver Transplant Recipients: Analysis of the UNOS/OPTN Database

    Directory of Open Access Journals (Sweden)

    Anitha D. Yadav

    2013-01-01

    Full Text Available New onset diabetes after transplantation (NODAT occurs less frequently in living donor liver transplant (LDLT recipients than in deceased donor liver transplant (DDLT recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75, P<0.001. Predictors for NODAT in LDLT recipients were hepatitis C (HCV and treated acute cellular rejection (ACR. Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.

  16. Glucagon/insulin ratio as a potential biomarker for pancreatic cancer in patients with new-onset diabetes mellitus.

    Science.gov (United States)

    Kolb, Armin; Rieder, Simon; Born, Diana; Giese, Nathalia A; Giese, Thomas; Rudofsky, Gottfried; Werner, Jens; Büchler, Markus W; Friess, Helmut; Esposito, Irene; Kleeff, Jörg

    2009-08-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with an overall 5-year survival rate of less than 5%. This dismal prognosis is largely due to the advanced stage of the disease at presentation, i.e., the late diagnosis. Therefore, early detection would have the potential to significantly improve the overall prognosis of PDAC patients. Diabetes mellitus (DM) has a high prevalence in PDAC patients and is frequently of new onset. The aim of this study was to analyze whether DM can be utilized as an early disease marker in PDAC. Quantitative RT-PCR analysis and immunohistochemistry for insulin and glucagon was performed in 22 PDAC and 16 normal pancreas tissues. Blood samples of 66 patients suffering from PDAC, 35 DM type 2 patients, and 29 healthy donors were analyzed for insulin, glucagon, C-peptide and glucose levels. Quantitative RT-PCR showed a two-fold increase of the glucagon/insulin ratio in pancreatic cancer tissues in comparison to the normal pancreas. By immunohistochemistry a shift in the expression pattern of glucagon and insulin, i.e., a higher glucagon/insulin ratio was found in PDAC associated islets compared to islets in the normal pancreas. Fasting insulin levels in PDAC patients were lower compared to DM patients. The calculated serum glucagon/insulin ratio was significantly different between PDAC and DM patients. At a cut-off of 7.4 ng/mU glucagon/insulin, pancreatic cancer induced new-onset DM could be discriminated from type 2 DM with 77% sensitivity and 69% specificity. In conclusion, the suggested serum glucagon/insulin ratio showed significant differences in patients with PDAC related DM and type 2 DM. Therefore, this analysis might help to identify PDAC in patients with new-onset DM in the age group at risk. Larger clinical trials have to confirm these findings.

  17. Plasma COOH-Terminal Proendothelin-1 A marker of fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in type 2 diabetes? (ZODIAC-29)

    NARCIS (Netherlands)

    Drion, Iefke; Kleefstra, Nanne; Landman, Gijs W. D.; Alkhalaf, Alaa; Struck, Joachim; Groenier, Klaas H.; Bakker, Stephan J. L.; Bilo, Henk J. G.

    2012-01-01

    OBJECTIVE-The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 1,225 patients with ty

  18. Population-based cohort study of anti-infective medication use before and after the onset of type 1 diabetes in children and adolescents

    NARCIS (Netherlands)

    Fazeli Farsani, Soulmaz; Souverein, Patrick C; van der Vorst, Marja M J; Knibbe, Catherijne A J; de Boer, Anthonius; Mantel-Teeuwisse, Aukje K

    2014-01-01

    A population-based cohort study was conducted in the Dutch PHARMO database to investigate prevalence and patterns of anti-infective medication use in children and adolescents with type 1 diabetes (T1D) before and after the onset of this disease. All patients <19 years with at least 2 insulin prescri

  19. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients

    DEFF Research Database (Denmark)

    Brorsson, Caroline A.; Nielsen, Lotte B.; Andersen, Marie Louise;

    2016-01-01

    1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we...

  20. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation.

    Science.gov (United States)

    Fredheim, Siri; Svensson, Jannet; Pørksen, Sven; Hansen, Lars; Hansen, Torben; Pedersen, Oluf Borbye; Mortensen, Henrik Bindesbøl; Barbetti, Fabrizio; Nielsen, Lotte Brøndum

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule causing permanent neonatal diabetes. All three were diagnosed before 29 weeks of age, were born at term with near-normal birth weight, and were negative for GAD, ICA, IA-2, and IAA autoantibodies. The daily insulin requirement the first six months after diagnosis was INS gene.

  1. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    DEFF Research Database (Denmark)

    Fredheim, Siri; Svensson, Jannet; Pörksen, Sven

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule....... The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated for mutations...... of INS gene....

  2. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    DEFF Research Database (Denmark)

    Fredheim, Siri; Svensson, Jannet; Pørksen, Sven

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule...... children. The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated...... for mutations of INS gene....

  3. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

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    de Beaufort Carine

    2010-09-01

    Full Text Available Abstract Background To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative for pancreatic autoantibodies [islet cell autoantibodies(ICA, glutamic acid decarboxylase antibodies (GADA and insulinoma-associated antigen-2 antibodies (IA-2A]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. Materials and methods In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation. Results Twenty-four patients (9.1% tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual β-cell function (P = 0.002, lower blood glucose (P = 0.004, received less insulin (P = 0.05 and had lower HbA1c (P = 0.02 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8 by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide. Conclusion GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes.

  4. Familial Young-Onset Diabetes, Pre-Diabetes and Cardiovascular Disease Are Associated with Genetic Variants of DACH1 in Chinese

    Science.gov (United States)

    Tam, Claudia Ha Ting; Ho, Janice Siu Ka; Zhao, Hai-Lu; Guan, Jing; Kong, Alice Pik Shan; Lau, Eric; Zhang, Guozhi; Luk, Andrea; Wang, Ying; Tsui, Stephen Kwok Wing; Chan, Ting Fung; Hu, Cheng; Jia, Wei Ping; Park, Kyong Soo; Lee, Hong Kyu; Furuta, Hiroto; Nanjo, Kishio; Tai, E. Shyong; Ng, Daniel Peng-Keat; Tang, Nelson Leung Sang; Woo, Jean; Leung, Ping Chung; Xue, Hong; Wong, Jeffrey; Leung, Po Sing; Lau, Terrence C. K.; Tong, Peter Chun Yip; Xu, Gang; Ng, Maggie Chor Yin; So, Wing Yee; Chan, Juliana Chung Ngor

    2014-01-01

    In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57–3.96, P = 8.4×10−5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02–1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07–2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19–9.19, P = 0.0214) and 3.27(1.25–11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese. PMID:24465431

  5. Effects of Diabetic Ketoacidosis on Visual and Verbal Neurocognitive Function in Young Patients Presenting with New-Onset Type 1 Diabetes.

    Science.gov (United States)

    Jessup, Ashley B; Grimley, Mary Beth; Meyer, Echo; Passmore, Gregory P; Belger, Ayşenil; Hoffman, William H; Çalıkoğlu, Ali S

    2015-09-01

    To evaluate the effects of diabetic ketoacidosis (DKA) on neurocognitive functions in children and adolescents presenting with new-onset type 1 diabetes. Newly diagnosed patients were divided into two groups: those with DKA and those without DKA (non-DKA). Following metabolic stabilization, the patients took a mini-mental status exam prior to undergoing a baseline battery of cognitive tests that evaluated visual and verbal cognitive tasks. Follow-up testing was performed 8-12 weeks after diagnosis. Patients completed an IQ test at follow-up. There was no statistical difference between the DKA and non-DKA groups neither in alertness at baseline testing nor in an IQ test at follow-up. The DKA group had significantly lower baseline scores than the non-DKA group for the visual cognitive tasks of design recognition, design memory and the composite visual memory index (VMI). At follow-up, Design Recognition remained statistically lower in the DKA group, but the design memory and the VMI tasks returned to statistical parity between the two groups. No significant differences were found in verbal cognitive tasks at baseline or follow-up between the two groups. Direct correlations were present for the admission CO2 and the visual cognitive tasks of VMI, design memory and design recognition. Direct correlations were also present for admission pH and VMI, design memory and picture memory. Pediatric patients presenting with newly diagnosed type 1 diabetes and severe but uncomplicated DKA showed a definite trend for lower cognitive functioning when compared to the age-matched patients without DKA.

  6. Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi-zhi; GAO Qing; ZHAO Xue-zhi; CHEN Ying-zhang; Craig L Bennett; XIONG Xi-shan; MEI Chang-lin; SHI Yong-quan; CHEN Xiang-mei

    2010-01-01

    Objective There is a paucity of published works that systematically evaluate gene anomalies or clinical features of patients with renal cysts and diabetes syndrome (RCAD)/maturity onset diabetes of the young type 5 (MODY5). The purpose of this review was to systematically assess the detection rate, genetic and phenotypic implications of heterozygous autosomal dominant TCF2 anomalies.Data sources MEDLINE database was searched to select articles recorded in English from 1997 to 2008. The focus was monoallelic germline TCF2 gene mutations/deletions. Biallelic inactivation, polymorphisms, DNA modification (hypomethylation and hypermethylation), loci associated with cancer risk, and somatic TCF2 anomalies were all excluded.Study selection After searching the literature, 50 articles were selected.Results The detection rate of TCF2 anomalies was 9.7% and varied considerably among MODY (1.4%), renal structure anomalies (RSA) (21.4%) and RSA with MODY (41.2%) subgroups. Mutations were strikingly located within the DNA binding domain and varied among exons of the DNA binding domain: exons 2 and 4 were the hottest spots, while mutations were sporadically distributed in exon 3. The consistent phenotypes were RSA (89.6%) and diabetes mellitus (DM) (45.0%). However, the concurrence of RSA and DM was relatively low (27.5%), which hinders the optimal performance of genetic testing and obtainment of timely diagnosis. Other organ involvements were complementary and necessary for the early identification of patients with TCF2 anomalies. Analysis of phenotypes of TCF2 point mutations showed significant differences in the detection rates of RSA, impaired renal function (IRF) and DM according to mutation type but not utation location.Conclusion These valuable features of TCF2 anomalies that previously did not receive sufficient attention should not be neglected.

  7. Impact of the PPAR-gamma2 Pro12Ala polymorphism and ACE inhibitor therapy on new-onset microalbuminuria in type 2 diabetes: evidence from BENEDICT.

    Science.gov (United States)

    De Cosmo, Salvatore; Motterlini, Nicola; Prudente, Sabrina; Pellegrini, Fabio; Trevisan, Roberto; Bossi, Antonio; Remuzzi, Giuseppe; Trischitta, Vincenzo; Ruggenenti, Piero

    2009-12-01

    Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria. Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo NEphrologic DIabetic Complications Trial (BENEDICT)-a prospective, randomized trial evaluating ACE inhibition effect on new-onset microalbuminuria (albuminuria 20-200 microg/min in at least two of three consecutive overnight urine collections in two consecutive visits) in hypertensive type 2 diabetes with albuminuria Pro12Ala polymorphism may help identifying patients at risk who may benefit the most from early renoprotective therapy.

  8. Identification of four novel mutations in the HNF-1A gene in Chinese early-onset and/or multiplex diabetes pedigrees

    Institute of Scientific and Technical Information of China (English)

    YANG Zhen; WU Song-hua; ZHENG Tai-shan; LU Hui-juan; XIANG Kun-san

    2006-01-01

    Background Mutations in the hepatocyte nuclear factor-1A gene cause the type 3 form of maturity-onset diabetes of the young (MODY3). This study was undertaken to determine mutations and sequence variations of the HNF-1A gene in Chinese with familial early-onset and/or multiplex diabetes mellitus.Methods We screened all ten exons of the HNF- 1A gene, including exon/intron junctions, by direct sequencing in 272 unrelated Chinese, including 80 healthy controls and 192 probands of early-onset and/or multiplex diabetes pedigrees.Results In addition to one silent mutation of c.864 G >C [p. G288G] in exon4 at codon 288, which had been reported previously, a total of four novel mutations including two missense mutations (c.245C>T [p.T82M] and c.390 G > T [p. Q130H]) and one frameshift mutation P353fsdelACGGGCCTGGAGC and one silent mutation c.759 G > T [p. G253G] were identified. Moreover, eleven substitutions were identified in 192 probands. Of these,three variants (-8 G>A, -128 T>G and IVS2+21 G>A) were not observed in 80 healthy controls and one of them (-8 G>A) was not reported previously and the two promoter variants co-segregated with diabetes. The genotype and allele frequencies of the other eight variants in the diabetic patients were not significantly different from those in the healthy controls. No significant relationships were observed between the eight variants of the HNF-1A gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile).Conclusion The prevalence of structural mutations in the HNF-1A gene responsible for familial early-onset and/or multiplex diabetes appears to be rare among Chinese patients.

  9. Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie de Preux Charles

    Full Text Available While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG] or the glial (endoneurium compartments of the peripheral nerve. We used Ins2(Akita/+ mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM. Weight, blood glucose and motor nerve conduction velocity (MNCV were measured in Ins2(Akita/+ and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2(Akita/+ mice and sex-matched littermate controls. Our phenotypic analysis of Ins2(Akita/+ mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM.

  10. Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus.

    Science.gov (United States)

    Sommese, Linda; Zullo, Alberto; Mancini, Francesco Paolo; Fabbricini, Rossella; Soricelli, Andrea; Napoli, Claudio

    2017-06-03

    Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

  11. Metabolic control in patients with type 1 diabetes mellitus at the onset of primary adrenal insufficiency

    Directory of Open Access Journals (Sweden)

    A A Larina

    2013-06-01

    Full Text Available Primary adrenal insufficiency is a rare disorder but it is more common in patients with type 1 diabetes mellitus (T1DM or autoimmune thyroid diseases than in the general population. T1DM may precede the development of adrenocortical insufficiency. Addison’s disease can influence the glycemic control in patients with T1DM worsening glucose metabolism. It causes the decrease of gluconeogenesis, reduction in total insulin requirement and rather often «unexplained» recurrent hypoglycemia. Glucocorticoid replacement therapy in patients with primary adrenal insufficiency and T1DM increases the insulin requirement. The article presents the development of primary adrenal insufficiency in a patient with type 1 DM and autoimmune hypothyroidism, accompanied with incidents of recurrent hypoglycemia.

  12. Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes.

    Science.gov (United States)

    Shah, Amy S; Dolan, Lawrence M; Dabelea, Dana; Stafford, Jeanette M; D'Agostino, Ralph B; Mayer-Davis, Elizabeth J; Marcovina, Santica; Imperatore, Giuseppina; Wadwa, R Paul; Daniels, Stephen R; Reynolds, Kristi; Hamman, Richard F; Bowlby, Deborah A; Maahs, David M

    2015-06-01

    Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D. We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 ± 3.9 yr, BMIz = 0.55 ± 0.97, T1D duration = 10.7 ± 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c). We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz. Our data suggest that weight loss may be an effective, but limited, therapeutic approach for dyslipidemia in youth with T1D. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Frameshift mutations in the insulin gene leading to prolonged molecule of insulin in two families with Maturity-Onset Diabetes of the Young.

    Science.gov (United States)

    Dusatkova, Lenka; Dusatkova, Petra; Vosahlo, Jan; Vesela, Klara; Cinek, Ondrej; Lebl, Jan; Pruhova, Stepanka

    2015-04-01

    Mutations in the insulin (INS) gene rarely occur in patients with Maturity-Onset Diabetes of the Young (MODY). We aimed to describe in detail two MODY families with INS mutations. The INS gene was screened by direct sequencing. The probands and their affected relatives underwent a mixed-meal test. Mutation predictions were modeled using I-TASSER and were visualized by Swiss-PdbViewer. A novel heterozygous frameshift mutation p.Gln78fs in the INS gene was found in three generations of patients with clinically distinct diabetes. The single nucleotide deletion (c.233delA) is predicted to change and prolong amino acid sequence, resulting in aberrant proinsulin without native structures of C-peptide and A-chain. In the second family, the heterozygous mutation c.188-31G>A within the terminal intron was detected. The mother and her daughter were misdiagnosed as having type 1 diabetes since the ages of 6 and 2 years, respectively. This result is in contrast to the previously described carrier of the same mutation who was diagnosed with permanent neonatal diabetes. We identified a novel coding frameshift mutation and an intronic mutation in the INS gene leading to childhood-onset diabetes. INS mutations may result in various phenotypes, suggesting that additional mechanisms may be involved in the pathogenesis and clinical manifestation of diabetes.

  14. Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

    Directory of Open Access Journals (Sweden)

    A. Vigo

    2007-07-01

    Full Text Available To efficiently examine the association of glutamic acid decarboxylase antibody (GADA positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65 were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (³1 U/mL was 7.3%. Baseline risk factors, with the exception of smoking and interleukin-6 (P £ 0.02, were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95%CI = 0.55, 1.96 proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95%CI = 0.58, 2.88 was seen for those in the highest tertile (³2.38 U/mL of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95%CI = 3.4, 28.5. In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

  15. Temporary Efficacy of Pyrimethamine in Juvenile-Onset Tay-Sachs Disease Caused by 2 Unreported HEXA Mutations in the Indian Population.

    Science.gov (United States)

    Udwadia-Hegde, Anaita; Hajirnis, Omkar

    2017-01-01

    Juvenile Tay-Sachs disease is rarer than other forms of Tay-Sachs disease and is usually seen in children between the age of 2 and 10 years. Pyrimethamine as a pharmacological chaperone was used to increase β-hexosaminidase A activity in this patient. We describe a patient with Tay-Sachs disease from the Indian population, a juvenile case who presented with developmental regression starting at the age of three, initially with motor followed by language regression. She is currently incapacitated with severe behavioral issues. This brief communication gives an insight into the efficacy of pharmacological chaperones. It also describes two unreported mutations in hexosaminidase A gene from the Indian population. After commencing Pyrimethamine, though initial benefits with increase in levels corresponded with briefly halting the motor regression, the observed increase was only transient and not associated with discernible beneficial neurological or psychiatric effects.

  16. The changes in the hypothalamo-pituitary-gonadal axis of streptozotocin-treated male rats depend from age at diabetes onset.

    Science.gov (United States)

    Pitton, I; Bestetti, G E; Rossi, G L

    1987-01-01

    The influence of age at diabetes onset and of capillary microangiopathy on the severity and evolution of hypothalamo-pituitary-gonadal changes was studied morphologically and morphometrically in male rats 4 and 8 months after streptozotocin injection. At each time period we studied 2 groups of rats, one made diabetic before (age 1 month), the other after puberty (age 3 months), and compared them with corresponding controls. The size of hypothalamic axons, numerical density and size of pituitary gonadotrophs, size of testicular tubules, and basement membrane thickness of retinal capillaries were measured. Major differences were found at 8 months. Changes of pituitary glands (i.e. small and numerous gonadotrophs) and testes (i.e. small tubular size) were more important in pre- than in postpubertal diabetic rats. This was a consequence of the aggravating prepubertal diabetes between 4 and 8 months. On the contrary, these changes partially regressed in postpubertal diabetic animals. Pituitary and testicular changes were correlated. Other lesions, such as swollen axonal processes in the hypothalamus, increased thickness of seminiferous epithelium and of capillary basement membranes, though very evident in diabetics, were independent from age at induction. Neither microangiopathy nor glycemia were correlated with any other change which confirmed their secondary role in diabetic neuroendocrine disorders. Thus, two types of diabetic disorders of the hypothalamo-pituitary-gonadal axis could be distinguished: 1) those with irreversible effects on immature yet partially reversible effects on mature structures; and 2) those independent from age at induction.

  17. Metabolic syndrome in hemodialysis patients as a risk factor for new-onset diabetes mellitus after renal transplant: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Bonet J

    2013-09-01

    Full Text Available Josep Bonet1, Albert Martinez-Castelao2, Beatriz Bayés11Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 2Department of Nephrology, Hospital Universitari de Bellvitge, IDIBELL, Hospitalet de Llobregat, Barcelona, SpainPurpose: Metabolic syndrome is a cluster of biochemical abnormalities including cardiovascular and diabetes risk factors. The development of diabetes mellitus after renal transplant represents a major posttransplant complication that may adversely affect graft/patient survival. The aim of this study was to assess the role of metabolic syndrome in patients on hemodialysis as a risk factor for the incidence of new-onset diabetes mellitus after renal transplant.Patients and methods: This was a prospective observational epidemiologic study carried out in adult nondiabetic patients undergoing chronic hemodialysis and on the renal transplant waiting list between November 2008 and April 2009. Patients were followed up from Visit 1 (baseline to 6 months after the renal transplant. The analysis of the role of metabolic syndrome in hemodialysis patients as a risk factor for the incidence of new-onset diabetes mellitus after renal transplant included the estimation of relative risk and its 95% confidence interval (CI.Results: A total of 383 evaluable patients were entered into the study (mean age, 52.7 years; male, 57.7%; Caucasian, 90.1%. The prevalence of metabolic syndrome on hemodialysis was 30.4% (95% CI, 25.8%–35.4%. Hypertension was the most prevalent criterion for metabolic syndrome (65.0%, followed by low levels of high-density lipoprotein cholesterol (52.7%, abdominal obesity (36.2%, hypertriglyceridemia (32.4%, and impaired glucose (8.9%. After the renal transplant, the prevalence of metabolic syndrome was still 25.8%. During the posttransplant period, the incidence of new-onset diabetes mellitus reached 13.0% (95% CI, 7.8%–20.6% and patients with pretransplant metabolic syndrome were 2

  18. Juvenile idiopathic arthritis

    NARCIS (Netherlands)

    Prakken, Berent; Albani, Salvatore; Martini, Alberto

    2011-01-01

    Juvenile idiopathic arthritis is a heterogeneous group of diseases characterised by arthritis of unknown origin with onset before age of 16 years. Pivotal studies in the past 5 years have led to substantial progress in various areas, ranging from disease classification to new treatments. Gene expres

  19. Effect of Demographic and Clinical Factors on New- Onset Diabetes Mellitus after Liver Transplantation in Iranian Patients

    Directory of Open Access Journals (Sweden)

    Soha Namazi

    2017-03-01

    Full Text Available BACKGROUNDS: New- onset diabetes after transplantation (NODAT is a serious complication which runs the risk of infections, morbidity and mortality. Older age, male sex, immunosuppressive agents and hepatitis C are reported as risk factors. The focus of this research is evaluating some demographic and clinical factors in development of NODAT in hepatic transplanted patients. This study aims to help identifying high risk recipients in order to prevent NODAT and improve transplantation prognosis.METHODS: In this study 134 liver recipients without pre- transplantation diabetes were investigated; 70 euglycemic and 64 with NODAT within 2 years after transplantation. All the patients were on tacrolimus- based immunosuppressive regimen. The role of recipients’ age, sex, body mass index (BMI, model for end- stage liver disease (MELD score, blood group, diseases leading to transplantation, tacrolimus dose and serum level, mycophenolate mofetil (MMF and prednisolone dose in the incidence of NODAT were assessed.RESULTS: The prevalence of NODAT in this study was 17.92%. The means of duration after transplantation that NODAT occurred, was 98.36± 21.62 days. The mean age of all patients was 37.83±16.26 years and 60.40% were females. Two groups were similar in terms of pre- transplantation fasting blood sugar (FBS (P=0.091. Age (P=0.001,OR=1.063,CI:1.025-1.102 and prednisolone dose (P<0.0001,OR=1.270,CI:1.163-1.388 the only independent predictors of NODAT, while tacrolimus daily dose and plasma level, MMF daily dose, sex, BMI and underlying diseases were not risk factors for NODAT.CONCLUSIONS: Recipients with older age and higher prednisolone dose are more prone to NODAT and need more accurate monitoring.

  20. The immune marker soluble urokinase plasminogen activator receptor is associated with new-onset diabetes in non-smoking women and men

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Hansen, T W

    2012-01-01

    Aim: To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive...... International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. Methods: The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy...... individuals). The soluble urokinase plasminogen activator receptor was measured by the ELISA method. To fulfil model assumptions, outcome analyses were stratified by age, and further by smoking, owing to the interaction between the soluble urokinase plasminogen activator receptor and smoking on new...

  1. Life Course Socioeconomic Transition and its Association with Early Onset Type 2 Diabetes: Protocol for a Sequential Exploratory Mixed Method Study

    Science.gov (United States)

    Raman, V Kutty; Nochikattil, Santhosh Kumar

    2016-01-01

    Introduction The prevalence of early onset type 2 diabetes (Diabetes below the age of 45 years) is increasing worldwide. Transition in socio-economic position–i.e. Life Course Socio-Economic Transition (LSET) - may contribute to the development of early onset T2D through complex processes involving economic and occupational opportunities as well as individual life style choices. Aim To develop and validate the life course socioeconomic transition questionnaire and to know the association between life courses socioeconomic transition and early onset type 2 diabetes. Materials and Methods This study follows sequential exploratory mixed method study design. It consists of one qualitative strand followed by two quantitative strands. Qualitative strand consist of in- depth interview among the community dwellers to develop a tool for measuring LSET. Two quantitative strands consist of the validation of the questionnaire by conducting cross-sectional survey among 200 randomly selected community dwellers and a hospital based case control study using the same questionnaire. Results Those who have a history of lower SEP during his childhood period and enjoying higher SEP during his adulthood period have an increased risk for developing type 2 diabetes at their younger age (18-45 years). Conclusion This study will help to develop a validated life course socioeconomic transition questionnaire and application of that tool in an epidemiological study. PMID:27504317

  2. The importance of general self-efficacy for the quality of life of adolescents with diabetes or juvenile rheumatoid arthritis over time: a longitudinal study among adolescents and parents

    NARCIS (Netherlands)

    J.M. Cramm (Jane); M.M.H. Strating (Mathilde); A.P. Nieboer (Anna)

    2013-01-01

    markdownabstractPurpose: To (i) investigate the influence of general self-efficacy on quality of life outcomesover time among adolescents with type I diabetes or juvenile rheumatoid arthritis (JRA), (ii)investigate parents’ perceptions of general self-efficacy and quality of life of adolescentswith

  3. Early Onset of Type 1 Diabetes and Educational Field at Upper Secondary and University Level: Is Own Experience an Asset for a Health Care Career?

    Directory of Open Access Journals (Sweden)

    Ida Lovén

    2017-06-01

    Full Text Available Ill health in early life has a significant negative impact on school grades, grade repetition, educational level, and labor market outcomes. However, less is known about qualitative socio-economic consequences of a health shock in childhood or adolescence. We investigate the relationship between onset of type 1 diabetes up to age 15 and the probability of choosing and completing a health-oriented path at upper secondary and university level of education. We analyze the Swedish Childhood Diabetes Register, the National Educational Register, and other population registers in Sweden for 2756 people with type 1 diabetes and 10,020 matched population controls. Educational decisions are modeled as unsorted series of binary choices to assess the choice of educational field as a potential mechanism linking early life health to adult outcomes. The analyses reject the hypothesis of no systematic differences in choice of educational field between people with and without type 1 diabetes at both levels. The results are robust to selection on ability proxies and across sensitivity analysis. We conclude that the observed pro health-oriented educational choices among people with type 1 diabetes in our data are consistent with disease onset in childhood and adolescence having qualitative impact on life-course choices.

  4. Frequent loss of genome gap region in 4p16.3 subtelomere in early-onset type 2 diabetes mellitus.

    Science.gov (United States)

    Kudo, Hirohito; Emi, Mitsuru; Ishigaki, Yasushi; Tsunoda, Uiko; Hinokio, Yoshinori; Ishii, Miho; Sato, Hidenori; Yamada, Tetsuya; Katagiri, Hideki; Oka, Yoshitomo

    2011-01-01

    A small portion of Type 2 diabetes mellitus (T2DM) is familial, but the majority occurs as sporadic disease. Although causative genes are found in some rare forms, the genetic basis for sporadic T2DM is largely unknown. We searched for a copy number abnormality in 100 early-onset Japanese T2DM patients (onset age experiments verified the copy number losses and delineated structural changes in the 1.3-Mb region. The results suggested that copy number losses of the genes in the deleted region around the genome gap in 4p16.3 may play significant roles in the etiology of T2DM.

  5. Onset of polyarticular juvenile idiopathic arthritis with both anti-cyclic citrullinated peptide antibodies and rheumatoid factor in a 3-year-old girl

    Directory of Open Access Journals (Sweden)

    Yasui Kozo

    2012-12-01

    Full Text Available Abstract This report describes 3 year old girl with the unusual presentation of polyarticular juvenile idiopathic arthritis (JIA with anti-cyclic citrullinated peptide (anti-CCP antibodies and a positive rheumatoid factor (RF. She was initially treated with a nonsteroidal anti-inflammatory drug (NSAID; ibuprofen followed by methotrexate (MTX, 10 mg/m2/week and prednisolone (0.25 mg/kg/day, but these treatments were ineffective. Administration of tocilizumab, a humanized antihuman interleukin-6 receptor monoclonal antibody, promptly improved her clinical manifestations, and she has been in complete remission (DAS28

  6. Reactive species, cellular repair and risk factors in the onset of type 2 diabetes mellitus: review and hypothesis.

    Science.gov (United States)

    Fridlyand, Leonid E; Philipson, Louis H

    2006-05-01

    Insulin resistance (IRe) and a failure of insulin secretion are the major features of the early pathophysiology of type-2 diabetes mellitus (T2D) but the etiology is still not well understood. We suggest that: 1. The cellular mechanisms that protect against oxidative stress per se are capable of creating a reactive species-dependent IRe. 2. Reactive species-induced mitochondrial dysfunction can lead to disruption of lipid metabolism, increased intracellular lipid content, and can also contribute to lipid-dependent IRe in myocytes and adipocytes. 3. Metabolic secretagogues that stimulate insulin secretion by the activation of initial steps in the glucose-stimulated insulin secretion pathway can also lead to increased reactive species production and cellular destruction contributing to beta-cell damage and apoptosis. These events that underlie the repair mechanisms in beta-cells, muscle and adipocytes, are important factors in the early etiology of T2D, leading to both IRe and decreased insulin secretion. This hypothesis is supported by data from multiple disciplines and includes aging, obesity and genetic factors in promoting multiple failures in this system leading to the onset of T2D. On the basis of this hypothesis therapeutic strategies should be directed towards increasing insulin secretion and reducing IRe without increasing reactive species production or concentration. Pharmacological or other approaches that result in the activation of mitochondrial biogenesis could be beneficial for both IRe and T2D.

  7. Transplantation of Aire-overexpressing bone marrow-derived dendritic cells delays the onset of type 1 diabetes.

    Science.gov (United States)

    Li, Dongbei; Zhao, Bo; Luo, Yadong; Limbara, Steven; Zhao, Bingjie; Zou, Xueyang; Yang, Wei; Li, Yi

    2017-08-01

    Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance. We attempted to transplant Aire-overexpressing bone marrow-derived DCs (Aire-BMDCs) to treat type 1 diabetes (T1D) and to explore a new strategy for autoimmune disease treatment. We observed that the onset of T1D in recipient mice was delayed; insulin autoantibody (IAA) production was significantly decreased; the structure of islets was protected; and the degree of inflammatory infiltration was lower. Furthermore, we found that Aire-BMDCs can promote apoptosis and induce autoreactive CD4(+) T cell clonal anergy, inhibit Th1 and Th17 production, and induce Treg production. These results suggest that transplantation of Aire-BMDCs will be a manipulation and effective method for preventing or treating T1D. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. A Retrospective Longitudinal Cohort Study of Antihypertensive Drug Use and New-Onset Diabetes in Taiwanese Patients

    Directory of Open Access Journals (Sweden)

    Ching-Ya Huang

    2013-01-01

    Full Text Available Antihypertensive drugs have been linked to new-onset diabetes (NOD; however, data on the effect of these drugs on the development of NOD in hypertensive patients has not been well determined in a clinical setting. The aim was to investigate the association between antihypertensive drugs and NOD in Taiwan. We conducted a retrospective study of hypertensive Taiwanese patients receiving antihypertensive drugs treatment between January 2006 and December 2011. Clinical information and laboratory parameters were collected by reviewing the medical records. We estimated the odds ratios (ORs of NOD associated with antihypertensive drug use; nondiabetic subjects served as the reference group. A total of 120 NOD cases were identified in 1001 hypertensive patients during the study period. The risk of NOD after adjusting sex, age, baseline characteristics, and lipid profiles was higher among users of thiazide diuretics (OR, 1.65; 95% confidence interval (CI, 1.12–2.45 and nondihydropyridine (non-DHP calcium channel blockers (CCBs (OR, 1.96; 95% CI, 1.01–3.75 than among nonusers. Other antihypertensive drug classes were not associated with risk of NOD. Our results show that patients with hypertension who take thiazide diuretics and non-DHP CCBs are at higher risk of developing NOD than those who take other classes of antihypertensive drugs in Taiwan.

  9. Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications.

    Directory of Open Access Journals (Sweden)

    Vivekanandhan Aravindhan

    Full Text Available Lipopolysaccharide (LPS/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM and its complications. Endotoxin core antibodies (EndoCAb, LPS binding protein (LBP and soluble CD14 (sCD14 act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF.A total of 197 subjects (64 normal glucose tolerance (NGT subjects, 97 T1DM subjects without MVC and 36 with MVC were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays.Compared to NGT, T1DM subjects (both with and without MVC had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1β, IL-6, TNF-α and GM-CSF (p<0.05. No significant change was seen in the levels of these biomarkers between T1DM subjects with and without MVC.Decreased levels of EndoCAb and LBP suggest sustained endotoxin activity in T1DM subjects even before the onset of microvascular complications.

  10. A novel deletion partly removing the AVP gene causes autosomal recessive inheritance of early-onset neurohypophyseal diabetes insipidus.

    Science.gov (United States)

    Christensen, J H; Kvistgaard, H; Knudsen, J; Shaikh, G; Tolmie, J; Cooke, S; Pedersen, S; Corydon, T J; Gregersen, N; Rittig, S

    2013-01-01

    Familial neurohypophyseal diabetes insipidus (FNDI) typically presents with age-dependent penetrance and autosomal dominant inheritance caused by missense variations in one allele of the AVP gene encoding the arginine vasopressin (AVP) prohormone. We present the molecular genetic characteristics underlying an unusual form of FNDI occurring with very early onset and seemingly autosomal recessive inheritance. By DNA amplification and sequencing, we identified a novel variant allele of the AVP gene carrying a 10,396 base pair deletion involving the majority of the AVP gene as well as its regulatory sequences in the intergenic region between the AVP and the OXT gene, encoding the oxytocin prohormone. We found two chromosomes carrying the deletion in affected family members and one in unaffected family members suspected to transmit the deleted allele. Whole-genome array analysis confirmed the results and excluded the presence of any additional major pathogenic abnormalities. The deletion is predicted to abolish the transcription of the AVP gene, thus the fact that family members heterozygous for the deletion remain healthy argues, in general, against haploinsufficiency as the pathogenic mechanism FNDI. Accordingly, our data is strong support to the prevailing idea that dominant inheritance of FNDI is due to a dominant-negative effect exerted by variant AVP prohormone.

  11. Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammation.

    Science.gov (United States)

    Askenasy, Nadir

    2016-04-01

    The mechanisms of autoimmune reactivity onset in type 1 diabetes (T1D) remain elusive despite extensive experimentation and discussion. We reconsider several key aspects of the early stages of autoimmunity at four levels: islets, pancreatic lymph nodes, thymic function and peripheral immune homeostasis. Antigen presentation is the islets and has the capacity to provoke immune sensitization, either in the process of physiological neonatal β cell apoptosis or as a consequence of cytolytic activity of self-reactive thymocytes that escaped negative regulation. Diabetogenic effectors are efficiently expanded in both the islets and the lymph nodes under conditions of empty lymphoid niches during a period of time coinciding with a synchronized wave of β cell apoptosis surrounding weaning. A major drive of effector cell activation and expansion is inherent peripheral lymphopenia characteristic of neonates, though it remains unclear when is autoimmunity triggered in subjects displaying hyperglycemia in late adolescence. Our analysis suggests that T1D evolves through coordinated activity of multiple physiological mechanisms of stimulation within specific characteristics of the neonate immune system.

  12. Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a known INS gene mutation.

    Science.gov (United States)

    Wasserman, Halley; Hufnagel, Robert B; Miraldi Utz, Virginia; Zhang, Kejian; Valencia, C Alexander; Leslie, Nancy D; Crimmins, Nancy A

    2016-11-01

    The prevalence of diabetes-related cataracts during childhood is less than 1%. When cataracts occur, it is often in adolescent females with prolonged symptoms and significant hyperglycemia. Cataracts are not a classic feature of monogenic diabetes. We report a case of a 6-yr-old, previously healthy Caucasian male, who presented with bilateral acquired cataracts and was subsequently diagnosed with new onset diabetes. Additional symptoms at presentation included a several year history of polyuria and polydipsia, mild hepatomegaly, and short stature. Pertinent negatives include acanthosis nigricans, lipoatrophy, deafness, muscle weakness, or neuropathy. HbA1c was significantly elevated at diagnosis (>14%, 129.5 mmol/mol) without evidence of ketosis. Autoantibody testing was negative. Features of Mauriac syndrome (short stature, hepatomegaly) as well as acquired cataracts indicated long-standing hyperglycemia with sufficient insulin production to prevent ketone production and development of diabetic ketoacidosis. Whole exome sequencing was conducted and a de novo heterozygous mutation in the INS gene (c.94G>A; p.Gly32Ser) was identified. INS gene mutations are common causes of permanent neonatal diabetes but rare causes of antibody-negative diabetes in children. Importantly, INS gene mutations have not been previously associated with acquired cataracts. Knowledge of a monogenic cause of diabetes allows clinicians to tailor counseling and screening of diabetes-related comorbidities. In summary, this case highlights the need to consider testing for monogenic diabetes, specifically INS gene mutations, in pediatric patients with antibody-negative diabetes, especially if complications of prolonged hyperglycemia are present at diagnosis.

  13. Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY)

    DEFF Research Database (Denmark)

    Boesgaard, Trine W; Pruhova, Stepanka; Andersson, Ehm A

    2010-01-01

    Insulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood.......Insulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood....

  14. 成人起病的青少年糖尿病研究进展%Research Progress of Maturity Onset Diabetes in Young

    Institute of Scientific and Technical Information of China (English)

    彭辉; 周太成; 杨莹

    2014-01-01

    成人起病的青少年糖尿病(maturity-onset diabetes of the young,MODY)是一种常染色体显性遗传的单基因遗传病.它的发生与基因突变相关联.随着科学技术的发展,MODY的研究得到了很大进步,就MODY及研究进展进行综述.

  15. Molecular Mechanisms and Clinical Pathophysiology of Maturity Onset Diabetes Mellitus in youth%MODY发病的分子和临床病理生理机理

    Institute of Scientific and Technical Information of China (English)

    曹旭; 田浩明

    2006-01-01

    青年起病的成人型糖尿病(maturity onset diabetes mellitus in youth,MODY)主要是由于胰岛B细胞功能缺陷所致,临床上多表现为不易发生酮症的糖尿病;遵循常染色体显性遗传模式;常在25岁前发病。

  16. The effect of glucagon infusion on kidney function in short-term insulin-dependent juvenile diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Christiansen, J S; Noer, I;

    1980-01-01

    with the high dose (p reversible elevation of glomerular filtration rate typically found in poorly regulated insulin-dependent diabetics, but not to the moderate......Kidney function was studied in nine, metabolically well controlled, short-term insulin-dependent male diabetics before and during glucagon infusion of 4 to 5 and 8 to 10 ng/kg/min. Glomerular filtration rate, effective renal plasma flow (steady-state infusion technique, with urinary collections...... elevation found in well controlled diabetics....

  17. Modification and Validation of the Triglyceride-to-HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus

    DEFF Research Database (Denmark)

    Paulmichl, Katharina; Hatunic, Mensud; Højlund, Kurt

    2016-01-01

    but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS: Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes...... sensitivity indices using area under the ROC curve (aROC) analysis and χ(2) test. RESULTS: The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C(0.185)/(TG(0.2) × BMI(1.338)), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m(2)). A cutoff value of 6...

  18. Multiscale Immune System Simulator for the Onset of Type-2 Diabetes for use in online decision support and coaching tools

    Directory of Open Access Journals (Sweden)

    Albert De Graaf

    2015-10-01

    intensity; 5 IMMUNE SYSTEM simulates Th differentiation and macrophage MA1/MA2 differentiation as a function of (and influencing cytokine concentrations. The integrated model generates simulations of the integrated effects of physical activity and nutrition on metabolism and inflammation with 15 min time resolution and a maximum 6 months total time span. Conclusions: An integrated immune system-metabolism model relevant for simulation of the onset of type-2 diabetes was developed. This model combined with a personal health tracking system and other sources of data (personal health records, wearables, apps should find application in mobile-based self management and diagnosis support tools.

  19. Juvenile Scleroderma

    Science.gov (United States)

    Juvenile Scleroderma INTRODUCTION Every parent will experience a moment of panic when told their child has scleroderma. ... in all their family members as well. CONCLUSION Juvenile scleroderma can be unsettling for the child and ...

  20. Identification and functional characterisation of novel glucokinase mutations causing maturity-onset diabetes of the young in Slovakia.

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    Lucia Valentínová

    Full Text Available Heterozygous glucokinase (GCK mutations cause a subtype of maturity-onset diabetes of the young (GCK-MODY. Over 600 GCK mutations have been reported of which ∼65% are missense. In many cases co-segregation has not been established and despite the importance of functional studies in ascribing pathogenicity for missense variants these have only been performed for C, c.1113-1114delGC were novel. Parental DNA was available for 22 probands (covering 14/22 mutations and co-segregation established in all cases. Bioinformatic analysis predicted all missense mutations to be damaging. Nine (I110N, V200A, N204D, G223S, G258R, F419S, V244G, L315H, I436N mutations were functionally evaluated. Basic kinetic analysis explained pathogenicity for 7 mutants which showed reduced glucokinase activity with relative activity indices (RAI between 0.6 to <0.001 compared to wild-type GCK (1.0. For the remaining 2 mutants additional molecular mechanisms were investigated. Differences in glucokinase regulatory protein (GKRP -mediated-inhibition of GCK were observed for both L315H & I436N when compared to wild type (IC(50 14.6±0.1 mM & 20.3±1.6 mM vs.13.3±0.1 mM respectively [p<0.03]. Protein instability as assessed by thermal lability studies demonstrated that both L315H and I436N show marked thermal instability compared to wild-type GCK (RAI at 55°C 8.8±0.8% & 3.1±0.4% vs. 42.5±3.9% respectively [p<0.001]. The minimum prevalence of GCK-MODY amongst Slovakian patients with diabetes was 0.03%. In conclusion, we have identified 22 GCK mutations in 36 Slovakian probands and demonstrate that combining family, bioinformatic and functional studies can aid the interpretation of variants identified by molecular diagnostic screening.

  1. The Serum Level of KL-6 is Associated with the Risk of Insulin Resistance and New-onset Diabetes Mellitus: The Tanno-Sobetsu Study.

    Science.gov (United States)

    Akasaka, Hiroshi; Ohnishi, Hirofumi; Narita, Yoshifumi; Kameda, Masami; Miki, Takayuki; Takahashi, Hiroki; Yamamoto, Wari; Sohma, Hitoshi; Masumori, Naoya; Miura, Tetsuji

    2017-09-25

    Objective Inflammatory cytokines generated in visceral fat have been shown to contribute to the development of insulin resistance. The involvement of pulmonary inflammation in insulin resistance remains unclear, but smoking is known to be a risk factor for diabetes as well as chronic obstructive pulmonary disease. We herein examined the hypothesis that increased serum levels of lung interstitial injury biomarkers (SP-A, SP-D and KL-6) are associated with the risk of diabetes development. Methods For cross-sectional and longitudinal analyses, we enrolled 750 apparently healthy non-diabetic subjects who received annual examinations in 2011 or 2012 in the Tanno-Sobetsu cohort. Results A cross-sectional analysis showed that distinct clinical parameters were associated with SP-A, SP-D and KL-6. In a multiple regression analysis, independent explanatory variables were Brinkman index and brain natriuretic peptide (BNP) for SP-A, sex (women), BNP and body mass index (BMI) for SP-D, and age and BMI for KL-6. A longitudinal analysis of 415 subjects who received annual examinations in both 2011 and 2014 showed that 13 (3.1%) of the patients developed type 2 diabetes during the 3-year follow-up. A multiple logistic regression analysis showed the KL-6 levels, systolic blood pressure and homeostasis model assessment of insulin resistance (HOMA-IR) in 2011 to be independently associated with new-onset diabetes. In a multiple regression analysis for HOMA-IR in 2014, the KL-6 level and BMI in 2011 were selected as explanatory variables. Conclusion A modest elevation of the serum KL-6 level is therefore considered to be associated with the risk for insulin resistance development and new-onset diabetes mellitus in a general population.

  2. Population-based cohort study of anti-infective medication use before and after the onset of type 1 diabetes in children and adolescents.

    Science.gov (United States)

    Fazeli Farsani, Soulmaz; Souverein, Patrick C; van der Vorst, Marja M J; Knibbe, Catherijne A J; de Boer, Anthonius; Mantel-Teeuwisse, Aukje K

    2014-08-01

    A population-based cohort study was conducted in the Dutch PHARMO database to investigate prevalence and patterns of anti-infective medication use in children and adolescents with type 1 diabetes (T1D) before and after the onset of this disease. All patients <19 years with at least 2 insulin prescriptions (1999 to 2009) were identified (T1D cohort) and compared with an age- and sex-matched (ratio: 1 up to 4) diabetes-free reference group. The prevalence and average number of anti-infective use was studied from (up to) 8 years before until a maximum of 4 years after the onset of T1D. A total of 925 patients with T1D and 3,591 children and adolescents in the reference cohort (51% boys, mean age of 10.1 [standard deviation, 4.5] years) were included. The overall prevalence of anti-infective use (62.6 compared to 52.6%, P < 0.001) and average number of prescriptions (2.71 compared to 1.42 per child, P < 0.001) in the T1D cohort were significantly higher than those in the reference cohort after the onset of diabetes. This pattern was consistent across sex and age categories and already observed in the year before the onset of type 1 diabetes. Patients in the T1D cohort received more antibacterials (49.8 compared to 40%, P < 0.001), antimycotics (4.0 compared to 1.3%, P < 0.001), antivirals (2.5 compared to 0.4%, P < 0.001), and second-line antibiotics, such as aminoglycosides, quinolones, and third-generation cephalosporins and carbapenems. Our findings that elevated anti-infective use in the T1D cohort exists in the period before the onset of type 1 diabetes and the consumption of more second-line anti-infective compounds in this time period warrant further research.

  3. GCK gene mutations are a common cause of childhood‐onset MODY (maturity‐onset diabetes of the young) in Turkey

    OpenAIRE

    Haliloglu, Belma; Hysenaj, Gerald; Atay, Zeynep; Guran, Tulay; Abalı, Saygın; Turan, Serap; Bereket, Abdullah; Ellard, Sian

    2016-01-01

    Summary Objective Inactivating heterozygous mutations in the GCK gene are a common cause of MODY and result in mild fasting hyperglycaemia, which does not require treatment. We aimed to identify the frequency, clinical and molecular features of GCK mutations in a Turkish paediatric cohort. Design and Patients Fifty‐four unrelated probands were selected based on the following criteria: age of diagnosis ≤17 years, family history of diabetes in at least two generations, anti‐GAD/ICA negative, BM...

  4. Early-onset type 2 diabetes in a Mexican survey: results from the National Health and Nutrition Survey 2006 Diabetes tipo 2 de inicio temprano en una encuesta nacional: resultados de la Encuesta Nacional de Salud y Nutrición 2006

    OpenAIRE

    Aída Jiménez-Corona; Rosalba Rojas; Francisco J Gómez-Pérez; Aguilar-Salinas, Carlos A.

    2010-01-01

    OBJECTIVE: To describe the characteristics of patients with type 2 diabetes diagnosed before age 40 (early-onset type 2 diabetes) identified in a nation-wide, population-based study. MATERIALS AND METHODS: The survey was done in Mexico during 2006. Medical history, anthropometric and biochemical measurements were obtained in every subject. RESULTS: Cases diagnosed before (n=181) and after age 40 (n=659) were included. Early-onset type 2 diabetes was present in 13.1% of the previously diagnose...

  5. Epidemiology of diabetes mellitus in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Blackard, W.G.; Omori, Yoshiaki; Freedman, L.R.

    1964-03-12

    The clinical and epidemiological features of diabetes mellitus in Japan have been compiled and compared with data from other countries. Diabetes is basically the same in Japan as elsewhere: however, consideration of important differences has led to the following conclusions: The rarity of ketoacidosis in Japan is due to the mild carbohydrate defect present in most diabetics. The mild carbohydrate intolerance in diabetics is probably in part due to a high carbohydrate intake. Diabetic retinopathy is more common in women than in men in Japan; there are limited and conflicting data from the West on this point, but retinopathy, nephropathy and neuropathy occur about as frequently in Japan as in the West. Because of marked dietary differences between Japan and Western countries, these findings suggest that dietary fat has no significance in the pathogenesis of these lesions. Peripheral gangrene is distinctly unusual in Japanese diabetics. This suggests that either: the responsible vascular lesions are different from those responsible for nephropathy and retinopathy; or that small vessel lesions are the same but the lack of large vessel atherosclerosis in the population accounts for the decreased incidence of gangrene. Men have diabetes 2 or 3 times as commonly as women in Japan. If sex-limited inheritance is discarded as a possible reason, it is likely that adult-onset diabetes is more common in men than women except in those countries (the West) where women gain relatively large amounts of weight. The rarity of juvenile diabetes in Japan is best explained by the infrequency of responsible genetic factors. As a consequence, it is likely that juvenile diabetes is caused by different or additional genetic factors which are not significant in adult-onset diabetes. Diabetes prevalance varies sufficiently between different localities in the same country to render the concept of national prevalance of doubtful usefulness. 55 references, 3 figures, 3 tables.

  6. A Single Nucleotide Variant in HNF-1β is associated with Ma¬turity-Onset Diabetes of the Young in a Large Chinese Family

    Directory of Open Access Journals (Sweden)

    Peng ZHOU

    2016-02-01

    Full Text Available Background: Maturity-onset diabetes of the young (MODY is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported. Methods: To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations.DNA was extracted from the periphery blood samples of (i 9 affected members, (ii 17 unaffected members, and (iii 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity ofDNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants.Results: Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P<0.001 between the affected vs. unaffected members and the affected vs. healthy controls, but not between the unaffected members vs. healthy controls. MODY5-related gene, hepatocyte nuclear factor-1β (HNF-1β on 17q12 near D17S798 became the candidate gene. A single nucleotide variant (SNV of C77T in the non-coding area of exon 1 of HNF-1β was found to be related to MODY5. Conclusion: This novel SNV of HNF-1β contributes to the diabetes development in the family through regulating gene expression most likely. The findings help presymptomatic diagnosis, and imply that mutations in the non-coding areas, as well as in the exons, play roles in the etiology of MODY. Keywords: Maturity-onset diabetes of the young (MODY, Maturity-onset diabetes of the young type 5 (MODY5, Hepatic nuclear factor 1 beta (HNF1β

  7. Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA).

    Science.gov (United States)

    Berntson, Lillemor; Nordal, Ellen; Fasth, Anders; Aalto, Kristiina; Herlin, Troels; Nielsen, Susan; Rygg, Marite; Zak, Marek; Rönnelid, Johan

    2014-01-01

    Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied.

  8. Studies of genetic variability of the hepatocyte nuclear factor-1α gene in an Indian maturity-onset diabetes of the young family.

    Science.gov (United States)

    Yang, Jing; Jiang, Feng; Guo, Hui; Soniya, Thadimacca; Yan, Chun-Xia; Tian, Zhu-Fang; Shi, Bing-Yin

    2016-01-01

    Maturity-onset diabetes of the young (MODY), one of the specific types of diabetes mellitus, is a monogenetic disorder characterized by an autosomal dominant (AD) inheritance and β-cell dysfunction. To study an Indian family with clinical diagnosis of MODY and detect the genetic mutations in the aspect of molecular mechanism, seven blood samples were obtained from the diabetic patients of this pedigree and genomic DNA was extracted from peripheral leukocytes. The exon1, exon2 and exon4 of hepatocyte nuclear factor-1α (HNF-1α) gene were amplified by polymerase chain reaction. Then the products were sequenced and compared with standard sequences on gene bank. As a result, two mutations were detected in exon1. That was CTC → CTG (Leu → Leu) in codon17 and ATC → CTC (Ile → Leu) in codon27. I27L was speculated to have a close relationship with the glycometabolism and the pathogenesis of diabetes mellitus together with the putative novel mutation existed in this Indian pedigree. Meanwhile, one mutation of GGG → GGC (Gly → Gly) in codon288 of exon4 was detected in the proband. No mutations were found in exon2 but a G → T base substitution in the intron4 region among all seven samples was detected. It may have some potential effects on the onset of diabetes in this family, but we do not have any evidence right now. Although it requires further investigation on the function of mutations found in the intron region, our research may provide some clue for this issue and it deserves more attention.

  9. Cardiovascular risk factors, micro and macrovascular complications at diagnosis in patients with young onset type 2 diabetes in India: CINDI 2

    Directory of Open Access Journals (Sweden)

    Bhavana Sosale

    2016-01-01

    Full Text Available Context: Type 2 diabetes mellitus (T2DM in young adults is increasing in India. Data on the prevalence of cardiovascular (CV risk factors and complications associated with young-onset T2DM (YOD at the time of diagnosis of diabetes are limited. This data can aid in aggressive diabetes management, CV risk reduction, and prevention of complications. Aim: To determine the prevalence of CV risk factors, micro and macrovascular complications in patients with newly diagnosed YOD. To assess the percentage of patients who require statin therapy based on current American Diabetes Association (ADA guidelines. Settings and Design: This was a retrospective cross-sectional study of 1500 patients with newly detected YOD across seven centers from 2013 to 2015. Designs and Methods: Patients were evaluated for complications of diabetes and CV risk factors such as body mass index (BMI, hypertension, dyslipidemia, and smoking. Statistical Analysis: Measurements have been presented as mean ± standard deviation; results on categorical measurements have been presented in percentages. Results: The mean age, glycated hemoglobin and BMI were 34.7 ± 4.2 years, 9.9 ± 2.4%, and 26.8 ± 4.7 kg/m2. Hypertension, dyslipidemia, BMI >23 kg/m2, and smoking were presented in 27.6%, 62.4%, 84.2%, and 24%. Diabetic retinopathy, neuropathy, and nephropathy were seen in 5.1%, 13.2%, and 0.9%. Ischemic heart disease, peripheral vascular disease, and stroke were presented in 0.7%, 2%, and 0.1%. As per current guidelines, 95.33% needed statin therapy. Conclusion: This study demonstrates that patients with YOD have micro and macrovascular complications at diagnosis. Nearly, every patient required a statin to reduce CV risk. This highlights the importance of screening patients with YOD for CV risk factors and complications of diabetes at the time of diagnosis.

  10. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    Energy Technology Data Exchange (ETDEWEB)

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E. [Kings College Hospital, London (United Kingdom)

    1995-05-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  11. Syphacia muris infection delays the onset of hyperglycemia in WBN/Kob-Leprfa rats, a new type 2 diabetes mellitus model

    Directory of Open Access Journals (Sweden)

    Taira K.

    2015-02-01

    Full Text Available Diabetes mellitus is one of the most common endocrine disorders and its continuous global increase is due to factors as population growth, urbanization, aging, and increasing prevalence of obesity and physical inactivity. The effect of pinworm infection on the development of hyperglycemia was examined in WBN/K-Lepf (fa/fa rats, a new model of the obese type 2 diabetes mellitus (T2DM with pancreatitis. The rats were orally administered Syphacia muris eggs (infected group and distilled water (control group. Hyperglycemia onset in the infected group was significantly delayed compared to the control group. Neither body weight nor intake of food and water were affected by S. muris infection. This study demonstrated that S. muris infection delayed the onset of T2DM in fa/fa rats and suggested that elucidation of the underlying mechanism and relevant pathways in the helminth-mediated protection may lead to the development of a new strategy to prevent diabetes mellitus.

  12. Association of TCF7L2 and GCG Gene Variants with Insulin Secretion, Insulin Resistance, and Obesity in New-onset Diabetes.

    Science.gov (United States)

    Zhang, Lu; Zhang, Ming; Wang, Jin Jin; Wang, Chong Jian; Ren, Yong Cheng; Wang, Bing Yuan; Zhang, Hong Yan; Yang, Xiang Yu; Zhao, Yang; Han, Cheng Yi; Zhou, Jun Mei; Pang, Chao; Yin, Lei; Zhao, Jing Zhi; Luo, Xin Ping; Hu, Dong Sheng

    2016-11-01

    This cohort study was designed to evaluate the association of transcription factor 7-like 2 (TCF7L2) and proglucagon gene (GCG) variants with disordered glucose metabolism and the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. A total of 7,751 non-T2DM participants ⋝18 years old genotyped at baseline were recruited. The same questionnaire interview and physical and blood biochemical examinations were performed at both baseline and follow-up. During a median 6 years of follow-up, T2DM developed in 227 participants. After adjustment for potential contributory factors, nominally significant associations were seen between TT genotype and the recessive model of TCF7L2 rs7903146 and increased risk of T2DM [hazard ratio (HR)=4.068, 95% confidence interval (CI): 1.270-13.026; HR=4.051, 95% CI: 1.268-12.946, respectively]. The TT genotype of rs7903146 was also significantly associated with higher fasting plasma insulin level and the homeostasis model assessment of insulin resistance in case of new-onset diabetes. In addition, the TCF7L2 rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  13. Type D personality and diabetes predict the onset of depressive symptoms in patients after percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Ong, Andrew T L; Sonnenschein, Karel

    2006-01-01

    Depression is common in cardiac patients and has been associated with adverse clinical outcome. However, little is known about predictors of the onset of depressive symptoms. We examined predictors of the onset of depressive symptoms at 12 months post-percutaneous coronary intervention (PCI...

  14. Juvenile Judge

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    SHANG Xiuyun was among the first sitting judges when the juvenile court was set up in Beijing 10 years ago. With enriched experience she has altered the way judges ask questions in court. She began the practice of inviting juvenile offenders, their parents, relatives, friends and teachers to the juvenile court to work hand in hand in dealing with cases: Facing their relatives and friends and hearing their heartfelt words, juvenile offenders would often be touched, thus bringing forth a positive attitude toward life.

  15. The Risk of Hepatotoxicity, New Onset Diabetes and Rhabdomyolysis in the Era of High-Intensity Statin Therapy: Does Statin Type Matter?

    Science.gov (United States)

    Benes, Lane B; Bassi, Nikhil S; Davidson, Michael H

    The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management have placed greater emphasis on high-intensity statin dosing for those with known cardiovascular disease or diabetes mellitus. Differences in risk of hepatotoxicity, new onset diabetes and rhabdomyolysis specifically between the high-intensity statins and the most common moderate-intensity statin, simvastatin, were not found to a significant degree in this review. Rather, baseline characteristics and drug-drug interactions (DDIs) appear to be more important regarding the risk of these adverse effects. Pharmacogenetic differences in statin metabolism may explain individual susceptibility, however genetic testing is not felt to be cost effective at this time. More importantly, statin choice should consider concomitant use of the many prevalent CYP3A4 inhibitors or inducers, and when present, rosuvastatin selection is recommended to reduce DDIs and risk of statin-induced adverse effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Longitudinal associations between changes in physical activity and onset of type 2 diabetes in older British men: the influence of adiposity.

    Science.gov (United States)

    Jefferis, Barbara J; Whincup, Peter H; Lennon, Lucy; Wannamethee, S Goya

    2012-09-01

    To determine how much physical activity (PA) is needed to protect against diabetes onset in older adults, whether protection is greater among overweight individuals, and whether taking up moderate activity in later life is beneficial. Men (4,252) from a U.K. population-based cohort self-reported usual PA (regular walking and cycling, recreational activity, and sport) in 1996 and in 1998-2000, alongside other health behaviors and medical history. Fasting blood lipids were measured. Median follow-up was 7.1 years, during which 135 cases of type 2 diabetes (validated self-report) occurred. Among 3,012 men free from cardiovascular disease and diabetes in 1998-2000, 9% reported no usual leisure-time PA, 23% occasional PA, and 15% vigorous PA. Compared with men reporting no activity, men reporting occasional, light, moderate, moderately vigorous, and vigorous PA had lower diabetes risks: hazard ratio (HR) 0.58 (95% CI 0.33-1.02), 0.39 (0.20-0.74), 0.38 (0.19-0.73), 0.39 (0.20-0.77), and 0.33 (0.16-0.70), respectively; P (trend) = 0.002, adjusted for age, social class, tobacco, alcohol, diet, and blood lipids. Adjustment for BMI, waist circumference, or fasting insulin attenuated HRs. HRs were stronger in men with BMI ≥28 vs. activity or less in 1996 and 2000, men who became at least moderately active by 2000 or remained at least moderately active at both times had adjusted HRs of 0.62 (0.34-1.12) and 0.51 (0.31-0.82), respectively. Even light PA markedly reduced diabetes risk in older men, especially among the overweight or obese. Taking up or maintaining at least moderate PA in older adulthood strongly protected against diabetes.

  17. 幼年特发性关节炎全身型血清铁蛋白的水平变化及临床意义%The Change and Clinical Significance of Serum Ferritin in Systemic Onset Juvenile Rheumatoid

    Institute of Scientific and Technical Information of China (English)

    叶春风; 刘洋; 刘燕玲; 李国林; 宋小华

    2010-01-01

    目的 探讨血清铁蛋白(serum ferritin,SF)在幼年特发性关节炎全身型(system onset juvenile idiopathic arthritis,SoJIA)的水平变化及临床意义.方法 采用化学发光法检测SoJIA组患儿(n=30) 在治疗前活动期和治疗后病情缓解期SF水平的变化;同时检测感染性疾病组(n=30) 、肿瘤组(n=30)及其他结缔组织病组(n=30)患儿的SF水平.结果 SoJIA组、感染性疾病组、肿瘤组及其他结缔组织病组患儿的血清SF水均升高;SoJIA组活动期血清SF水平显著高于其他3组(均P<0.01);SoJIA组活动期SF水平明显高于缓解期(P<0.01).结论 SF是诊断SoJIA有价值的实验室指标,并可为病情活动期及疗效观察提供依据.

  18. Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients

    Science.gov (United States)

    Dotta, Francesco; Censini, Stefano; van Halteren, Astrid G. S.; Marselli, Lorella; Masini, Matilde; Dionisi, Sabrina; Mosca, Franco; Boggi, Ugo; Muda, Andrea Onetti; Prato, Stefano Del; Elliott, John F.; Covacci, Antonello; Rappuoli, Rino; Roep, Bart O.; Marchetti, Piero

    2007-01-01

    Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic β cells. Several studies have suggested an association between Coxsackie enterovirus seroconversion and onset of disease. However, a direct link between β cell viral infection and islet inflammation has not been established. We analyzed pancreatic tissue from six type 1 diabetic and 26 control organ donors. Immunohistochemical, electron microscopy, whole-genome ex vivo nucleotide sequencing, cell culture, and immunological studies demonstrated Coxsackie B4 enterovirus in specimens from three of the six diabetic patients. Infection was specific of β cells, which showed nondestructive islet inflammation mediated mainly by natural killer cells. Islets from enterovirus-positive samples displayed reduced insulin secretion in response to glucose and other secretagogues. In addition, virus extracted from positive islets was able to infect β cells from human islets of nondiabetic donors, causing viral inclusions and signs of pyknosis. None of the control organ donors showed signs of viral infection. These studies provide direct evidence that enterovirus can infect β cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment. PMID:17360338

  19. A polymorphism within the fructosamine-3-kinase gene is associated with HbA1c Levels and the onset of type 2 diabetes mellitus.

    Science.gov (United States)

    Mohás, M; Kisfali, P; Baricza, E; Mérei, A; Maász, A; Cseh, J; Mikolás, E; Szijártó, I A; Melegh, B; Wittmann, I

    2010-03-01

    Non-enzymatic glycation is a process, which leads to the formation of advanced glycation endproducts. These compounds are involved in the development of diabetic microvascular complications. Fructosamine-3-kinase (FN3K) is an intracellular enzyme that phosphorylates fructosamines resulting in fructosamine-3-phosphate, which subsequently decomposes to inorganic phosphate, 3-deoxyglucasone and the unmodified amine. Recently, the G900C (rs1056534) single nucleotide polymorpism (SNP) of the FN3K gene was found to be associated with the enzyme activity. The aim of the study was to investigate the impact of the SNP on clinical and biochemical features and microvascular complications of type 2 diabetes. A total of 859 type 2 diabetic subjects and 265 healthy controls were enrolled in the study and were genotyped with PCR-RFLP method. Genotype frequencies were as follows, CC: 5%, GC: 54%, GG: 41% in subjects with type 2 diabetes and CC: 6%, GC: 51%, GG: 43% in the controls. Diabetic subjects with the CC variant had lower HbA (1c) levels compared with the others (CC: 6.48+/-0.05%; GC: 7.66+/-0.09%; GG: 7.68+/-0.09%; p<0.001). Furthermore, in case of the CC allelic variant type 2 diabetes was diagnosed at a later age than in case of GC or GG variants (CC: 56.0+/-1.90 years; GC: 52.0+/-0.62 years; GG: 50.1+/-0.71 years; p<0.05). Logistic regression analysis did not reveal association between CC genotype and diabetic complications, such as diabetic nephropathy, neuropathy and retinopathy (OR=1.036, CI 95% 0.652-1.647, p=0.880; OR=0.985, CI 95% 0.564-1.721 p=0.958; OR=1.213, CI 95% 0.470-3.132, p=0.690, respectively). We conclude that the G900C polymorphism associates with the level of HbA (1c) and the onset of the disease, but not with either of the diabetic microvascular complications. J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart * New York.

  20. The Effect of Resting Heart Rate on the New Onset of Microalbuminuria in Patients With Type 2 Diabetes: A Subanalysis of the ROADMAP Study.

    Science.gov (United States)

    Schmieder, Roland E; Bramlage, Peter; Haller, Hermann; Ruilope, Luis M; Böhm, Michael

    2016-04-01

    The association between resting heart rate and new-onset microalbuminuria in patients with type 2 diabetes is not clear. The objective of the current analysis was to assess the relationship between heart rate and incidence of microalbuminuria in patients with type 2 diabetes. Data from the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study were retrospectively analyzed. New-onset microalbuminuria was documented and related to heart rate as recorded at baseline and last assessment, and the mean of the measurements taken during the double-blind part of the ROADMAP trial. Patients (n = 4299) had a mean age of 57.8 ± 8.7 years and 46.3% were male. Characteristics were not different between the olmesartan and the placebo groups, except for a higher systolic blood pressure (136.7 vs 135.7 mm Hg; P = 0.04) and albumin creatinine ratio (5.9 vs 5.5; P = 0.03). Increased risk of microalbuminuria was found with increasing heart rate, independent of whether baseline [highest vs lowest quartile odds ratio (OR) 1.39; 95% confidence interval (95% CI) 1.03-1.87; P = 0.032], last assessment (OR 1.71; 95% CI 1.26-2.31; P = 0.001), or mean heart rate was considered (OR: 1.77; 95% CI: 1.30-2.41; P = 0.0003). The greater risk of new-onset microalbuminuria with a high baseline heart rate was also found when data were adjusted for mean systolic blood pressure (OR: 1.35; 95% CI: 1.00-1.82; P = 0.0496; interaction P microalbuminuria was less frequent in patients receiving olmesartan in the low heart rate quartiles (P = 0.002 for trend). A low heart rate reduces the risk of patients with type 2 diabetes developing microalbuminuria, independent of blood pressure. The data demonstrate potential benefits of reducing the heart rate of type 2 diabetes patients, and indicate that olmesartan could, in particular, reduce the risk of microalbuminuria in patients with low heart rate.

  1. Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF rat

    Directory of Open Access Journals (Sweden)

    Al-Jarrah Muhammed

    2010-09-01

    Full Text Available Abstract Background Early markers of diabetic autonomic neuropathy (DAN in an electrocardiogram (ECG include elevated R wave amplitudes, widening of QTc intervals and decreased heart rate variability (HRV. The severity of DAN has a direct relationship with mortality risk. Aerobic exercise training is a common recommendation for the delay and possible reversal of cardiac dysfunction. Limited research exists on ECG measures for the evaluation of aerobic exercise training in Zucker Diabetic Fatty (ZDF rat, a model of type 2 diabetes. The objective of this study was to assess whether aerobic exercise training may attenuate diabetes induced ECG changes. Methods Male ZDF (obese fa/fa and control Zucker (lean fa/+ rats were assigned to 4 groups: sedentary control (SC, sedentary diabetic (SD, exercised control (EC and exercised diabetic (ED. The exercised groups began 7 weeks of treadmill training after the development of diabetes in the ED group. Baseline (prior to the training and termination measurements included body weight, heart weight, blood glucose and glycated hemoglobin levels and ECG parameters. One way repeated measures ANOVA (group analyzed within and between subject differences and interactions. Pearson coefficients and descriptive statistics described variable relationships and animal characteristics. Results Diabetes caused crucial changes in R wave amplitudes (p c intervals (p c interval prolongation nor restored decreases in HRV in diabetic rats. Conclusion This study revealed alterations in R wave amplitudes, HRV, QT and QTc intervals in ZDF rats. Of these changes, aerobic exercise training was able to correct R wave amplitude changes. In addition, exercise has beneficial effect in this diabetic rat model in regards to ECG correlates of left ventricular mass.

  2. Self-reported dietary intake of youth with recent onset of type 2 diabetes: results from the TODAY study.

    Science.gov (United States)

    Delahanty, Linda; Kriska, Andrea; Edelstein, Sharon; Amodei, Nancy; Chadwick, Jennifer; Copeland, Kenneth; Galvin, Bryan; El Ghormli, Laure; Haymond, Morey; Kelsey, Megan M; Lassiter, Chad; Milaszewski, Kerry; Syme, Amy; Mayer-Davis, Elizabeth

    2013-03-01

    Despite the widely recognized importance of diet in managing diabetes, few studies have documented usual dietary intake in young people with type 2 diabetes. The objectives of our study were to assess dietary intake among a large, ethnically diverse cohort of young people with type 2 diabetes and compare intake to current recommendations. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is a multicenter randomized clinical trial of 699 youth aged 10 to 17 years. At baseline, following a run-in period that included standard diabetes education, diet was assessed using a food frequency questionnaire between 2004 and 2009. Analysis of variance and nonparametric tests were used to compare mean and median nutrient intakes; logistic regression was used to compare the odds of meeting predefined dietary intake recommendation cutpoints between subgroups of age, sex, and race-ethnicity. Percent of energy from saturated fat was consistently 13% to 14% across all subgroups-substantially exceeding national recommendations. Overall, only 12% of youth met Healthy People 2010 guidelines for intake of Diabetes Association recommendations for intake of fruit consumption goals, 5% met vegetable consumption goals, and 67% met grain intake goals. Overall, dietary intake in this large cohort of young people with type 2 diabetes fell substantially short of recommendations, in ways that were consistent by sex, age, and race-ethnicity. The data suggest a critical need for better approaches to improve dietary intake of these young people.

  3. Levels of adiponectin and leptin at onset of type 1 diabetes have changed over time in children and adolescents

    DEFF Research Database (Denmark)

    Safai, Narges; Eising, Stefanie; Hougaard, David Michael

    2015-01-01

    in children with type 1 diabetes mellitus (T1D) in relation to the increasing incidence of T1D, and studied the impact of patient status, age, gender and body mass index (BMI). Data were derived from a population-based registry of diabetic children (DanDiabKids) from 1997 to 2005. Children with newly......Adiponectin and leptin are proteins secreted by the adipose tissue and have an influence on insulin sensitivity and on inflammatory markers. Altered levels could play a part in the pathogenesis of type 1 diabetes mellitus. We determined adiponectin and leptin levels over a nine-year period...

  4. Intergeneration CAG expansion in a Wuhan juvenile-onset Huntingto ndisease family%武汉地区CAG扩增突变致青少年发病的亨廷顿舞蹈病的家系分析

    Institute of Scientific and Technical Information of China (English)

    刘媛; 沈滟; 李和; 王慧; 杨真荣; 陈燕; 唐艳平

    2007-01-01

    目的 对青少年发病的亨廷顿舞蹈病(Huntington disease)家系进行致病IT15基因早期诊断分析,为家系成员提供遗传咨询,并为后续的HD发病机制及实验治疗研究提供依据.方法 按照知情同意原则抽取家系成员外周血,提取基因组DNA,采用改良的降落PCR方法扩增IT15基因致病区域,DNA测序检测异常等位基因(CAG)n三核苷酸重复次数.结果 在该家系三代25名成员中,共发现8名致病IT15基因携带者,其中,Ⅲ10、Ⅲ12、Ⅲ14、Ⅳ3和Ⅴ2 CAG三核苷酸的拷贝数均为48,Ⅳ11和Ⅳ12均为(CAG)67,Ⅳ14为(CAG)63,而对照组35名正常人的CAG三核苷酸的拷贝数为8-25,两者之间没有重叠.结论 家系中第四代致病基因携带者Ⅳ14与第三代患者Ⅲ10比较,CAG三核苷酸重复次数增加15次,即本家系IT15基因在传递过程中发生了扩增突变.同时,扩增突变导致该家系出现青少年发病及遗传早现现象.%Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease (HD)family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. Methods According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. Results Eight of twenty-five family members carried abnormal allele: Ⅲ10, Ⅲ12, Ⅲ14, Ⅳ3,and Ⅴ2 carried (CAG) 48, Ⅳ11 and Ⅳ12 carried (CAG) 67, and Ⅳ14 carried (CAG) 63, in contrast with the 8-25 CAG trinucleotides in the members of control group. Ⅳ14 carried 15 more CAG trinucleotides than her father Ⅲ10. Conclusion The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family.In addition, CAG expansion results in juvenile-onset and anticipation (characterized

  5. The analysis of the risk factors for sacroiliac joint damage in juvenile-onset spondyloarthropathy%212例少年脊柱关节病骶髂关节损害相关危险因素分析

    Institute of Scientific and Technical Information of China (English)

    单鸣凤; 郭君; 陈鸿健

    2012-01-01

    目的:探讨少年脊柱关节病(juvenile-onset spondyloarthropathy,JSpA)患者出现骶髂关节损害的相关危险因素,为选择恰当的治疗方案提供依据.方法:对212例JSpA患者的人口学因素、遗传学因素、受累部位、各个实验室指标等进行分析.将患者按照年龄段(≤11岁及12~16岁)分为两组.分别采用Logistic回归的方法进行分析,筛选出JSpA出现骶髂关节损害的相关发病因素.结果:本组212例患者中有骶髂关节损害者124例,占58.5%.单因素分析显示多个因素在骶髂关节损害中有统计学意义;多因素Logistic逐步回归分析显示病程、起病时外周关节炎尤其是下肢大关节、持续肌腱端炎、HLA-B27阳性、家族史是JSpA并发骶髂关节损害的相关危险因素.结论:JSpA患者出现骶髂关节损害的发生率较高,与多种因素有关,当患者出现这些危险因素时,应早期积极干预治疗,定期检查骶髂关节MRI,减轻或延缓病情的进展.%Objective:To investigate the risk factors of sacroiliac joint damage in patients with juvenile-onset spondyloarthropathy (JSpA),and to provide reference for the selection of appropriate treatment strategy. Methods:To analysis the clinical data of 212 cases of JSpA,including demographic factors(sex,age) .genetic factors,the affected area,laboratories indicators. Patients were divided into two groups according to age (≤ 11 years old and 12~16 years old). Using the Logistic regression to filter out the risk factors of sacroiliac joint damage in patients with JSpA. Results:Out of the 212 cases, 124 (58.5%) patients suffered from sacroiliac joint damage. Single factor analysis showed that a number of factors were related to sacroiliac joint damage. Logistic regression analysis showed that the course of disease, at the onset of peripheral arthritis, particularly the large joints of lower limbs, tendon-sustained inflammation and HLA-B27-positive, family history were the risk

  6. Juvenile Arthritis

    Science.gov (United States)

    Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but ... of JA that children get is juvenile idiopathic arthritis. There are several other forms of arthritis affecting ...

  7. [Juvenile scleroderma].

    Science.gov (United States)

    de Mâcedo, Patrícia Andrade; Shinjo, Samuel Katsuyuki; Goldenstein-Schainberg, Cláudia

    2008-01-01

    Juvenile scleroderma is a rare childhood condition characterized by fibrosis of the skin and internal organs. Clinical manifestations of childhood scleroderma are different from adult disease and early recognition, correct classification and treatment can improve long-term outcome. This review explores the most recent actualizations on clinical manifestations, classification criteria, treatment options and prognosis of juvenile scleroderma. There are two main forms of the disease: localized scleroderma and systemic sclerosis. Localized scleroderma is the most common form in children and mostly restricted to the skin. Juvenile diffuse systemic sclerosis is related to visceral involvement and cardiac disease which is the main cause of death in these patients. The outcome of juvenile systemic sclerosis is better compared with the adult form. Treatment remains a medical challenge and the EULAR task force proposed an approach to juvenile scleroderma treatment based on expert's opinion and guidelines used for the treatment of adults. Larger studies on childhood scleroderma are warranted.

  8. TyG Index Change Is More Determinant for Forecasting Type 2 Diabetes Onset Than Weight Gain

    National Research Council Canada - National Science Library

    Navarro-González, David; Sánchez-Íñigo, Laura; Fernández-Montero, Alejandro; Pastrana-Delgado, Juan; Martinez, Jose Alfredo

    2016-01-01

    The risk of type 2 diabetes associated with obesity appears to be influenced by other metabolic abnormalities, and there is controversy about the harmless condition of the metabolically healthy obese (MHO) state...

  9. Changes in the redox state in the retina and brain during the onset of diabetes in rats.

    Science.gov (United States)

    Salceda, R; Vilchis, C; Coffe, V; Hernández-Muñoz, R

    1998-06-01

    Diabetic retinopathy is thought to result from chronic changes in the metabolic pathways of the retina. Hyperglycemia leads to increased intracellular glucose concentrations, alterations in glucose degradation and an increase in lactate/pyruvate ratio. We measured lactate content in retina and other ocular and non-ocular tissues from normal and diabetic rats in the early stages of streptozotocin-induced diabetes. The intracellular redox state was calculated from the cytoplasmic [lactate]/[pyruvate] ratio. Elevated lactate concentration were found in retina and cerebral cortex from diabetic rats. These concentrations led to a significant and progressive decrease in the NAD+/NADH ratio, suggesting that altered glucose metabolism is an initial step of retinopathy. It is thus possible that tissues such as cerebral cortex have mechanisms that prevent the damaging effect of lactate produced by hyperglycemia and/or alterations of the intracellular redox state.

  10. Alcohol consumption, new onset of diabetes after transplantation, and all-cause mortality in renal transplant recipients

    NARCIS (Netherlands)

    Zelle, Dorien M.; Agarwal, Pramod K.; Ramirez, Jessica L. Pinto; van der Heide, Jaap J. Homan; Corpeleijn, Eva; Gans, Reinold O. B.; Navis, Gerjan; Bakker, Stephan J. L.

    2011-01-01

    Background. Renal transplant recipients (RTR) are often advised to refrain from alcohol because of possible interaction with their immunosuppressive medication. Although moderate alcohol consumption is associated with reduced risk of diabetes and mortality in the general population, this is unknown

  11. JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    I N Sartika

    2012-11-01

    Full Text Available Juvenile rheumatoid arthritis (JRA is the most common rheumatic condition in children. JRA is defined as persistent arthritis in 1 or more joints for at least 6 weeks, with the onset before age 16 years. The etiology of JRA is unknown. Antigen activated CD4+ T cell stimulate monocytes, macrophages, and synovial fibroblasts to produce the cytokines Interleukin-1 (IL-1, IL-6, and tumor necrosis factor ? (TNF-? and to secrete matrix metalloproteinases, which lead to chronic inflammation due to infiltration of inflammatory cell, angiogenesis, destruction of cartilage and bone with pannus formation. The 3 major subtypes of JRA are based on the symptoms at disease onset and are designated systemic onset, pauciarticular onset, and polyarticular onset. For all patients, the goals of therapy are to decrease chronic joint pain and suppress the inflammatory process. Poor prognostic have been observed in patients with polyarticular onset, rheumatoid factor, persistent morning stiffness, tenosynovitis, involvement of the small joints, rapid appearance of erosions, active late onset childhood, subcutaneous nodules, or antinuclear antibody.

  12. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment.

    Science.gov (United States)

    Amar, Jacques; Chabo, Chantal; Waget, Aurélie; Klopp, Pascale; Vachoux, Christelle; Bermúdez-Humarán, Luis G; Smirnova, Natalia; Bergé, Mathieu; Sulpice, Thierry; Lahtinen, Sampo; Ouwehand, Arthur; Langella, Philippe; Rautonen, Nina; Sansonetti, Philippe J; Burcelin, Rémy

    2011-09-01

    A fat-enriched diet modifies intestinal microbiota and initiates a low-grade inflammation, insulin resistance and type-2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high-fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This 'metabolic bacteremia' is characterized by an increased co-localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non-pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD-induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.

  13. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

    DEFF Research Database (Denmark)

    Pörksen, Sven; Laborie, Lene Bjerke; Nielsen, Lotte

    2010-01-01

    BACKGROUND: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (...

  14. Comparing risk of new onset diabetes mellitus in chronic kidney disease patients receiving peritoneal dialysis and hemodialysis using propensity score matching.

    Directory of Open Access Journals (Sweden)

    Che-Yi Chou

    Full Text Available Chronic kidney disease (CKD patients are at risk for developing new-onset diabetes mellitus (NODM even after hemodialysis (HD and peritoneal dialysis (PD treatment. It is not clear if the incidence for NODM is different in CKD patients receiving HD and PD. This study compared the risk of NODM in PD patients and HD patients.All HD and PD patients in Taiwan Renal Registry Database from 1997 to 2005 were included and all patients were followed to December 31, 2008. The risk of NODM was analyzed in PD patients and propensity score matched HD patients using logistic regression for early type NODM (6 months after dialysis.A total of 2548 PD patients and 10192 HD patients who had no diabetes on the initiation of dialysis were analyzed. The incidence for NODM was 3.7 per 100 patient/year for HD and 2.4 for PD patients. HD patients are more at risk for developing early type NODM (p<0.001 with an adjusted odds ratio of 1.41 [95% confidence interval (CI 1.12-1.78]. HD patients are more at risk for late type NODM (p<0.001 with an adjusted hazard ratio of 2.01 (95% CI: 1.77-2.29. Patient's age was negatively associated with risk of early type of NODM (p<0.001 but positively associated with risk of late type NODM (p<0.001.Chronic kidney disease patients receiving hemodialysis are more at risk for developing new-onset diabetes mellitus compared to those receiving peritoneal dialysis.

  15. The glycated albumin to HbA1c ratio is elevated in patients with fulminant type 1 diabetes mellitus with onset during pregnancy.

    Science.gov (United States)

    Koga, Masafumi; Shimizu, Ikki; Murai, Jun; Saito, Hiroshi; Kasayama, Soji; Kobayashi, Tetsuro; Imagawa, Akihisa; Hanafusa, Toshiaki

    2013-01-01

    Fulminant type 1 diabetes mellitus (FT1DM) develops as a result of very rapid and almost complete destruction of pancreatic β cell. The most common form of type 1 diabetes mellitus with onset during pregnancy has been shown to be FT1DM at least in Japan. We previously reported that the ratio of glycated albumin (GA) to HbA1c (GA/HbA1c ratio) is elevated in FT1DM patients at the diagnosis. In the present study, we investigated whether the GA/HbA1c ratio is also elevated in FT1DM with onset during pregnancy (P-FT1DM). The study subjects consisted of 7 patients with P-FT1DM. Ten patients with untreated type 2 diabetes mellitus (T2DM) discovered during pregnancy (P-T2DM) and 9 non-pregnant women with untreated T2DM (NP-T2DM) were used as controls. All study patients satisfied HbA1c < 8.7%, the diagnostic criteria for FT1DM. The GA/HbA1c ratio in the P-FT1DM patients at the diagnosis was significantly higher than that in the P-T2DM patients and the NP-T2DM patients. The GA/HbA1c ratio was ≥ 3.0 in all P-FT1DM patients, whereas it was < 3.0 in 8 of 10 P-T2DM patients and all NP-T2DM patients. The GA/HbA1c ratio was also elevated in P-FT1DM patients at the diagnosis compared with T2DM with or without pregnancy.

  16. Frequent Loss of Genome Gap Region in 4p16.3 Subtelomere in Early-Onset Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Hirohito Kudo

    2011-01-01

    Full Text Available A small portion of Type 2 diabetes mellitus (T2DM is familial, but the majority occurs as sporadic disease. Although causative genes are found in some rare forms, the genetic basis for sporadic T2DM is largely unknown. We searched for a copy number abnormality in 100 early-onset Japanese T2DM patients (onset age <35 years by whole-genome screening with a copy number variation BeadChip. Within the 1.3-Mb subtelomeric region on chromosome 4p16.3, we found copy number losses in early-onset T2DM (13 of 100 T2DM versus one of 100 controls. This region surrounds a genome gap, which is rich in multiple low copy repeats. Subsequent region-targeted high-density custom-made oligonucleotide microarray experiments verified the copy number losses and delineated structural changes in the 1.3-Mb region. The results suggested that copy number losses of the genes in the deleted region around the genome gap in 4p16.3 may play significant roles in the etiology of T2DM.

  17. No Contribution of GAD-65 and IA-2 Autoantibodies around Time of Diagnosis to the Increasing Incidence of Juvenile Type 1 Diabetes: A 9-Year Nationwide Danish Study

    Directory of Open Access Journals (Sweden)

    Steffen U. Thorsen

    2016-01-01

    Full Text Available Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65 (GADA and insulinoma associated antigen-2A (IA-2A mirrored the 3.4% annual increase in incidence of T1D. Methods. From the Danish Childhood Diabetes Register, we randomly selected 500 patients and 500 siblings for GADA and IA-2A analysis (1997 through 2005. Blood samples were taken within three months after onset. A robust log-normal regression model was used. Nine hundred children and adolescents had complete records and were included in the analysis. Cochran-Armitage test for trend was used to evaluate changes in prevalence of autoantibody positivity by period. Results. No significant changes in levels of GADA and IA-2A were found over our 9-year study period. No trends in autoantibody positivity—in either patients or siblings—were found. Levels of GADA and IA-2A were significantly associated with HLA risk groups and GADA with age. Conclusion. The prevalence of positivity and the levels of GADA and IA-2A have not changed between 1997 and 2005 in newly diagnosed patients with T1D and their siblings without T1D.

  18. High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Johan F Paulsson

    Full Text Available AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP is a beta cell hormone secreted together with insulin upon glucose stimulation. IAPP participates in normal glucose regulation, but IAPP is also known for its ability to misfold and form islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and deposited amyloid disrupts normal islet architecture. Even though IAPP and amyloid formation are much discussed in type 2 diabetes, our aim was to study the significance of IAPP in type 1 diabetes. RESULTS: Plasma IAPP levels in children and adolescents with newly diagnosed type 1 diabetes (n = 224 were analysed and concentrations exceeding 100 pmol/L (127.2-888.7 pmol/L were found in 11% (25/224. The IAPP increase did not correlate with C-peptide levels. CONCLUSIONS/INTERPRETATION: Plasma levels of IAPP and insulin deviate in a subpopulation of young with newly-diagnosed type 1 diabetes. The determined elevated levels of IAPP might increase the risk for IAPP misfolding and formation of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the list over putative pathological factors causing type 1 diabetes.

  19. Characteristics of children and adolescents at onset of type 2 diabetes in a Tertiary Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    Bedowra Zabeen

    2016-01-01

    Full Text Available Introduction: Recent data show that the prevalence of diabetes among children and adolescents is increasing in some ethnic groups. The worldwide epidemic of childhood obesity has been accompanied by an increase in the incidence of type 2 diabetes (T2D in youth. Methods: The aim of this study was to describe the baseline characteristics of children and adolescents diagnosed ≤18 years who had features of T2D and presented at  Changing Diabetes in Children, Paediatric Diabetes Clinic at Bangladesh Institute of Research and Rehabilitation of Diabetes, Endocrine, and Metabolic Disorders. All patients who were newly diagnosed and came to the clinic from March 2011 to March 2015 were included. Results: Among 939 newly registered patients, 77 (8% had a diagnosis of T2D. The age at diagnosis was 9-10 years in 11 patients (14%, 11-14 years in 46 (60% and 15-17 years in other 20 patients (26%. Majority of the children had a positive family history of T2D (94% and 58% were obese. Median fasting insulin (27.9 [17.3-99.3] was high in 76% patients. Insulin was started initially along with metformin in 40 patients and could be stopped in six patients in 3 months. Conclusion: Our study reflects that T2D is emerging as a problem in children and adolescents in Bangladesh.

  20. Characteristics of children and adolescents at onset of type 2 diabetes in a Tertiary Hospital in Bangladesh

    Science.gov (United States)

    Zabeen, Bedowra; Nahar, Jebun; Tayyeb, Samin; Mohsin, Fauzia; Nahar, Nazmun; Azad, Kishwar

    2016-01-01

    Introduction: Recent data show that the prevalence of diabetes among children and adolescents is increasing in some ethnic groups. The worldwide epidemic of childhood obesity has been accompanied by an increase in the incidence of type 2 diabetes (T2D) in youth. Methods: The aim of this study was to describe the baseline characteristics of children and adolescents diagnosed ≤18 years who had features of T2D and presented at Changing Diabetes in Children, Paediatric Diabetes Clinic at Bangladesh Institute of Research and Rehabilitation of Diabetes, Endocrine, and Metabolic Disorders. All patients who were newly diagnosed and came to the clinic from March 2011 to March 2015 were included. Results: Among 939 newly registered patients, 77 (8%) had a diagnosis of T2D. The age at diagnosis was 9–10 years in 11 patients (14%), 11–14 years in 46 (60%) and 15–17 years in other 20 patients (26%). Majority of the children had a positive family history of T2D (94%) and 58% were obese. Median fasting insulin (27.9 [17.3–99.3]) was high in 76% patients. Insulin was started initially along with metformin in 40 patients and could be stopped in six patients in 3 months. Conclusion: Our study reflects that T2D is emerging as a problem in children and adolescents in Bangladesh. PMID:27730073

  1. Effect of Histone Modifications in the Onset of Diabetes%组蛋白修饰在糖尿病发病中的作用

    Institute of Scientific and Technical Information of China (English)

    冯田田

    2013-01-01

    Histone modification is an important epigenetic phenomenon of gene expression which plays an important regulatory function. Diabetes is a metabolic disease caused by environmental factors,genetic factors and immune factors together and the pathogenesis is closely related to insulin resistance, insufficient insulin secretion,and immune inflammation. The pathogenesis of diabetes is not yet entirely clear,and there are some limitations in the treatment. However,some studies have shown that histone modification is closely related to the onset of diabetes.%组蛋白修饰是一种重要的表观遗传学现象,对基因表达调控发挥着至关重要的作用.一般认为糖尿病是一种由环境因素、遗传因素及免疫因素等共同作用的代谢性疾病,其发病机制主要与胰岛素抵抗、胰岛素分泌不足及免疫炎症等密切相关.目前,糖尿病的发病机制尚未完全清楚,治疗中也有一定局限性.但有研究表明组蛋白修饰与糖尿病的发病有密切关系.

  2. Hemodynamics in diabetic orthostatic hypotension

    DEFF Research Database (Denmark)

    Hilsted, J; Parving, H H; Christensen, N J

    1981-01-01

    in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously...... than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due...... to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy....

  3. Case Report: Juvenile Tophaceous Gout

    Directory of Open Access Journals (Sweden)

    Seyma Gunes

    2016-01-01

    Full Text Available Gout is a metabolic disease that manifests as recurrent arthritis. Its incidance increases with age. Clinical findings include recurrent acute arthritis, tophus at joints and tissues, uricacid stones and gouty nephropathy. Tophi is a late period complication of arthritis. In this casereport we presented  a patient with early-onset juvenile tophaceous gout.

  4. Increasing incidence of early onset type 1 (insulin-dependent) diabetes mellitus: a study of Danish male birth cohorts

    DEFF Research Database (Denmark)

    Green, A; Andersen, P K; Svendsen, Anders Jørgen

    1992-01-01

    To provide information of the incidence trends of Type 1 (insulin-dependent) diabetes mellitus we performed a cohort study of a series of Danish male birth cohorts. All male livebirths in Denmark between 1 January 1949 and 31 December 1964, were investigated regarding the development of Type 1...... diabetes during the first 20 years of life using the files of the Danish Conscript Board, supplemented by a search in the Danish National Registry of Deaths. Diagnosis was verified and clinical information obtained from medical records. The material is estimated to be more than 95% complete. A total...

  5. Lipid profiles of adipose and muscle tissues in mouse models of juvenile onset of obesity without high fat diet induction: a Fourier transform infrared (FT-IR) spectroscopic study.

    Science.gov (United States)

    Sen, Ilke; Bozkurt, Ozlem; Aras, Ebru; Heise, Sebastian; Brockmann, Gudrun Anni; Severcan, Feride

    2015-06-01

    The current study aims to determine lipid profiles in terms of the content and structure of skeletal muscle and adipose tissues to better understand the characteristics of juvenile-onset spontaneous obesity without high fat diet induction. For the purposes of this study, muscle (longissimus, quadriceps) and adipose (inguinal, gonadal) tissues of 10-week-old male DBA/2J and Berlin fat mouse inbred (BFMI) lines (BFMI856, BFMI860, BFMI861) fed with a standard breeding diet were used. Biomolecular structure and composition was determined using attenuated total reflection Fourier transform (ATR FT-IR) spectroscopy, and muscle triglyceride content was further quantified using high-performance liquid chromatography (HPLC) coupled with an evaporative light scattering detector (ELSD). The results revealed a loss of unsaturation in BFMI860 and BFMI861 lines in both muscles and inguinal adipose tissue, together with a decrease in the hydrocarbon chain length of lipids, especially in the BFMI860 line in muscles, suggesting an increased lipid peroxidation. There was an increase in saturated lipid and triglyceride content in all tissues of BFMI lines, more profoundly in longissimus muscle, where the increased triglyceride content was quantitatively confirmed by HPLC-ELSD. Moreover, an increase in the metabolic turnover of carbohydrates in muscles of the BFMI860 line was observed. The results demonstrated that subcutaneous (inguinal) fat also displayed considerable obesity-induced alterations. Taken together, the results revealed differences in lipid structure and content of BFMI lines, which may originate from different insulin sensitivity levels of the lines, making them promising animal models for spontaneous obesity. The results will contribute to the understanding of the generation of insulin resistance in obesity without high fat diet induction.

  6. History of Juvenile Arrests and Vocational Career Outcomes for At-Risk Young Men

    Science.gov (United States)

    Wiesner, Margit; Kim, Hyoun K.; Capaldi, Deborah M.

    2010-01-01

    This study uses longitudinal data from the Oregon Youth Study (OYS) to examine prospective effects of juvenile arrests and of early versus late onset of juvenile offending on two labor market outcomes by age 29 or 30 years. It was expected that those with more juvenile arrests and those with an early onset of offending would show poorer outcomes…

  7. How to make an early and accurate diagnosis of systemic onset juvenile idiopathic arthritis%幼年特发性关节炎全身型早期诊断标准探讨

    Institute of Scientific and Technical Information of China (English)

    殷蕾; 周纬; 金燕樑; 李怀远; 周征宇; 黄华

    2013-01-01

    目的 通过回顾性分析与比较幼年特发性关节炎全身型(systemic onset juvenile idiopathic arthritis,SOJIA)与其他疾病引起的发热待查患儿的临床特点及实验室检查结果,来获得鉴别诊断的临界值,以提高早期诊断SOJIA的准确性.方法 收集不明原因发热患儿共124例,记录患儿持续发热达2~4周时的临床特点和实验室检查结果,并随访1年以上.对资料完整的病例采用SPSS16.0软件进行单因素分析,对有统计学意义的单因素进行受试者工作特征曲线(ROC)分析,然后对有意义的临床特点和实验室检查结果进行联合分析.结果 诊断明确且资料完整者共96例,其中33例为SOJIA,19例为其他自身免疫性疾病,25例为血液/肿瘤疾病,19例为感染性疾病.当血清铁蛋白(SF)≥545.75 ng/ml时,可以将SOJIA与其他自身免疫性疾病区分的灵敏度为97.0%,特异度为100%,若以出现皮疹或关节肿/痛加上血小板计数≥217×109/L或C3≥1.275 g/L作为标准,其区分SOJIA和血液肿瘤疾病的灵敏度为100%,特异度为96%.若以SF≥441.7ng/ml加上出现皮疹或关节肿/痛,那么其区分SOJIA和感染性疾病的灵敏度和特异度均可达到100%.结论 结合发热待查患儿的临床特点及实验室检查结果可提高早期诊断SOJIA的准确性.%Objective To identify the cut-off points for differential diagnosis to increase the accuracy of early diagnosis for systemic onset juvenile idiopathic arthritis (SOJIA) by retrospectively analysis on the patients with SOJIA and the patients with fever of unknown origin. Methods One hundred and twenty-four patients with fever of unknown origin were enrolled in this study. The clinical features and the results of laboratory tests of the patients with persistent fever for 2 to 4 weeks were recorded completely and they were then followed up for more than one year. The data were analysed by single factor analysis using SPSS16.0. The areas under

  8. Juvenile Prostitution.

    Science.gov (United States)

    Csapo, Marg

    1986-01-01

    Recent research and Canadian government committee reports concerning juvenile prostitution are reviewed. Proposals are made in the realms of law and social policy; and existing programs are described. (DB)

  9. Juvenile Prostitution.

    Science.gov (United States)

    Csapo, Marg

    1986-01-01

    Recent research and Canadian government committee reports concerning juvenile prostitution are reviewed. Proposals are made in the realms of law and social policy; and existing programs are described. (DB)

  10. Diabetes MODY tipo 5: a propósito de un caso Maturity-onset diabetes of the young type 5: a case report

    OpenAIRE

    Junquera, S.; M. J. Goñi; J. Lafita

    2011-01-01

    La diabetes MODY-5 es un tipo de diabetes monogénica infrecuente, causada por mutación en el gen del factor de transcripción nuclear hepático 1-beta (HNF-1β). Esta mutación puede ser de tipo puntual o bien corresponder a delecciones grandes, y a su vez, puede aparecer de novo por mutación espontánea o bien ser transmitida de forma hereditaria con carácter autosómico dominante. Está asociada con un alto riesgo de complicaciones microvasculares de aparición temprana en las personas afectas...

  11. Juvenile myasthenia

    Directory of Open Access Journals (Sweden)

    Knežević-Pogančev Marija

    2011-01-01

    Full Text Available Introduction. Juvenile myasthenia is a chronic autoimmune neuromuscular disease characterized by varying degrees of fluctuating, painless muscle weakness and rapid fatigue of any muscles under voluntary control. Juvenile myasthenia is a form of myasthenia appearing in adolescent age, representing 10% to 15% of all cases of myasthenia gravis. Juvenile myasthenia is presented by a defect in the transmission of nerve impulses to muscles, resulting from a breakdown in the normal communication between nerves and muscles. In myasthenia, antibodies produced by the body’s own immune system block, alter, or destroy the receptors for acetylcholine. Juvenile myasthenia is neither directly inherited nor is it contagious. Signs and Symptoms. The first noticeable symptoms may be eye muscle weakness, difficulty in swallowing, or slurred speech. Juvenile myasthenia usually affects muscles innervated by the cranial nerves (face, lips, tongue, neck and throat, but it can affect any muscle group. Symptoms vary in type and severity with typical periods of exacerbation interspersed with periods of remission. When the muscles necessary for breathing are affected, a patient is said to be in a myasthenic crisis, which is a life-threatening situation. Disease Outcome and Treatment. Juvenile myasthenia produces sporadic but progressive weakness and abnormal fatigability of striated (skeletal muscles, exacerbated by exercise and repeated movement, but improved by rest and anticholinesterase drugs. Juvenile myasthenia follows an unpredictable course of recurring exacerbations and periodic remissions. With current therapies, however, most cases of juvenile myasthenia are not as serious as the name implies. Although there is no known cure, drug treatment has improved prognosis and allows patients to lead relatively normal lives, except during exacerbations.

  12. AB096. Pharmaco-genetic guided personalized medicine: discovery of a maturity onset diabetes of the young (MODY2) novel mutation [S441W in glucose kinase (GCK) gene] by next generation sequencing (NGS)

    Science.gov (United States)

    Clara, Tan Si Hua; Fen, Ang Su; Jessie, Fong Choi Wan; Ester, Yeoh Chai Kheng; Subramaniam, Tavintharan; Fang, Sum Chee; Chi, Lim Su

    2015-01-01

    Background and objective Monogenic diabetes or maturity onset diabetes of the young (MODY) is characterized by young-onset (G, p.Ser441Trp) in the GCK gene, which was confirmed by bi-directional Sanger’s sequencing. The mutation is predicted to be functionally deleterious using multiple bioinformatics tools (e.g., SIFT and PolyPhen-2). In accordance with clinical practice guideline, insulin replacement was successfully discontinued with no deterioration of glycemic control. Conclusions The successful treatment-conversion based on genotype exemplifies how pharmaco-genetics can improve disease-stratify to inform diagnosis and treatment. This can translate into improved clinical outcome and quality of life.

  13. ANAEROBIC GLYCOSIS IS THE CENTRE OF DIFFERENT BIOCH EMICAL DISARRAYS ASSOCIATED WITH THE ONSET OF DIABETIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Lakshmi Kanta

    2013-04-01

    Full Text Available ABSTRACT: BACKGROUND: Despite almost similar hyperglycemic status and dura tion of the disease, some patients of type-2 diabetes mellitus de velop microangiopathy within few years where as some individuals avoid this complication fo r a considerable period. It is assumed that some subjects of type 2 diabetes mellitus show hyper glycemia induced faster rate of anaerobic glycolytic pathway which liberate excessive intermed iates of glycolysis responsible for increased intracellular Ca + and increased extracellular glutamate and lactate, the end product of this metabolic pathway causing apoptosis of pericytes and dysfunction of endothelium of retinal capillaries. This retinal background created by exce ssive lactate may invite excessive secretion of vascular endothelial growth factor ( VEGF and its receptor-2 ( VEGFR2 in an attempt to avoid the resultant irritating and destructive cell ular condition. Associated increased activity of matrix metalloproteinases ( MMP2 and MMP9 may caus e degradation of extracellular matrix ( ECM and disruption of basal membrane of retinal ca pillaries. Aim : This longitudinal study was undertaken to assess the association of anaerobic g lycolysis with lipid peroxidation, NO secretion, VEGF, VEGFR2, MMP2 and MMP9 at the time of development of earliest stage of diabetic retinopathy. METHODS: 142 patients of type-2 diabetes mellitus of 5 to 10 years duration having no retinopathy were recruited in thi s longitudinal study. Molecules like lactate, nitric oxide ( NO , malondialdehyde ( MDA , VEGF, VEGFR2, MMP2 and MMP9 were measured at the interval of one year for three years followi ng standard methods of estimation. Detailed fundus examination and digital fundus photography we re done in each patient to document appearance of microaneurysm. RESULTS : Surrogate markers of anaerobic glycolysis, oxidati ve stress, lipid peroxidation and consequently growth fa ctor VEGF, it’s receptor VEGFR2, MMP2 and MMP9 were

  14. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

    DEFF Research Database (Denmark)

    Pörksen, Sven; Laborie, Lene; Nielsen, Lotte

    2010-01-01

    BACKGROUND:To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (I...

  15. Identification of novel variants in HNF1-alpha gene in maturity onset diabetes in young adults (MODY subjects of Eastern India

    Directory of Open Access Journals (Sweden)

    Chaitry Ghosal

    2013-01-01

    Full Text Available Background: The disorder, Maturity Onset of Diabetes of the young (MODY is a monogenic form of Non-Insulin dependent Diabetes Mellitus (NIDDM, characterized by autosomal dominant mode of inheritance and onset is usually before 25 years of age. Clinical studies of the subjects with the different forms of MODY indicate that each is associated with a different defect in the normal pattern of glucose stimulated insulin secretion. MODY can result from mutations in any one of the six different genes as of now, one of which encodes the glycolytic enzyme Glucokinase, associated with MODY2 and the other five encode transcription factors HNF4alpha associated with MODY1,HNF1alpha associated with MODY3, IPF with MODY4, HNF1Beta with MODY5 and NeuroD1 with MODY6.Studies related to mutations in the MODY genes have led to a better understanding of the genetic causes of the Beta cell dysfunction as genetic factors play a great role in this disorder. Objective: To investigate the mutation pattern/patterns in the different transcription factor genes with special reference to HNF1alpha gene which are highly penetrant with 63% mutation carriers manifesting clinical diabetes by the age of 25 years. Hence study of mutation pattern in this gene is essential in our population i.e. Eastern Indian population. Our study is focused on HNF1alpha related to MODY3, which is the most common one. Methods: In our study, the enzyme amplification (PCR of the10 target exons of the said gene with simultaneous mutation detection in them by PCR-SSCP (Polymerase chain reaction followed by single strand conformational polymorphism reaction analysis method was attempted by screening of exon1-10 with respect to normal healthy controls without Diabetes Mellitus. The nature of the specific mutations was also determined by sequencing. Result: It was observed in our study that there were sequence variants existing in exon7 and exon 8 of HNF1-alpha gene, revealed by PCR-SSCP study in our

  16. Diabetes MODY tipo 5: a propósito de un caso Maturity-onset diabetes of the young type 5: a case report

    Directory of Open Access Journals (Sweden)

    S. Junquera

    2011-12-01

    Full Text Available La diabetes MODY-5 es un tipo de diabetes monogénica infrecuente, causada por mutación en el gen del factor de transcripción nuclear hepático 1-beta (HNF-1β. Esta mutación puede ser de tipo puntual o bien corresponder a delecciones grandes, y a su vez, puede aparecer de novo por mutación espontánea o bien ser transmitida de forma hereditaria con carácter autosómico dominante. Está asociada con un alto riesgo de complicaciones microvasculares de aparición temprana en las personas afectas, así como con alteraciones renales características del tipo quistes y anomalías del tracto genital, que están presentes incluso antes del nacimiento. Por ello, está justificado hacer pruebas de detección para las mutaciones de HNF-1β en diabéticos no obesos, sobre todo, cuando existen alteraciones renales o genitales asociadas, sin tener en cuenta los antecedentes familiares.MODY-5 diabetes is an infrequent type of monogenic diabetes, caused by mutation in the gene of the nuclear hepatic transcription factor 1-beta (HNF-1β. This mutation can be of a momentary type or it might correspond to big deletions, and, in its turn, it can appear due to spontaneous de novo mutation or it can be transmitted by hereditary with an autosomal dominant character. It is associated with a high risk of microvascular complications that appear early in affected people, as well as with characteristic renal alterations of the cyst type, and anomalies of the genital tract, which are present even before birth. That is why it is justified to carry out detection tests for HNF-1β mutations in non-obese diabetics, above all when there are associated renal or genital alterations, without consideration of family antecedents.

  17. The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes

    DEFF Research Database (Denmark)

    Fredheim, Siri; Andersen, Marie-Louise M; Pörksen, Sven

    2015-01-01

    AIMS/HYPOTHESIS: The influence of glucagon on glycaemic control in type 1 diabetes is debated. We investigated the relationship between postprandial glucagon levels and HbA1c during a period up to 60 months after diagnosis of childhood type 1 diabetes. METHODS: The Danish remission phase cohort......), C-peptide, total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and HbA1c were analysed. Multivariate regression (repeated measurements with all five visits included) was applied and results expressed as relative change (95% CI). RESULTS: Postprandial glucagon...... associated negatively with postprandial C-peptide (p = 0.017). A doubling in postprandial glucagon corresponded to a 3% relative increase in HbA1c levels (p = 0.0045). CONCLUSIONS/INTERPRETATION: Postprandial glucagon levels were associated with deterioration of glycaemic control and declining beta cell...

  18. Juvenile idiopathic arthritis

    Science.gov (United States)

    Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ... The cause of juvenile idiopathic arthritis (JIA) is not known. It ... illness . This means the body attacks and destroys healthy body ...

  19. Juvenile Polyposis Syndrome

    Science.gov (United States)

    ... Types of Cancer > Juvenile Polyposis Syndrome Request Permissions Juvenile Polyposis Syndrome Approved by the Cancer.Net Editorial Board , 12/2015 What is juvenile polyposis syndrome? Juvenile polyposis syndrome (JPS) is a ...

  20. Adult onset pityriasis rubra pilaris

    Directory of Open Access Journals (Sweden)

    Sehgal Virendra

    2008-01-01

    Full Text Available Pityriasis rubra pilaris (PRP has always been an intriguing topic ever since its inception. It is a group of chronic disorders characterized by reddish orange plaques with pityriasiform scaling showing follicular keratoses, palmoplantar keratoderma, and sometimes, erythroderma. It occurs all over the world but with racial variations. Its incidence might vary and the age at onset, behavior, clinical appearance, and prognosis are considered to be very important for its classification. It may manifest either as Type I classical adult onset PRP, Type II atypical adult (onset PRP, or Type VI PRP (HIV-associated PRP pityriasis rubra pilaris in contrast to classical juvenile (Type III and circumscribed juvenile (Type IV encountered among children. Its diagnosis is largely clinical with microscopic pathology being a useful supplement, but it continues to be a therapeutic dilemma. We review the epidemiology of adult onset PRP here and take stock of the prevalent treatment options.

  1. Juvenile hyaline fibromatosis.

    Science.gov (United States)

    Larralde, M; Santos-Muñoz, A; Calb, I; Magariños, C

    2001-01-01

    Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease with onset in infancy or early childhood. It is characterized by papulonodular skin lesions, soft tissue masses, gingival hypertrophy, and flexion contractures of the large joints. The light and electron microscopic features are very distinctive. Here we report an 8-month-old boy with characteristic stiffness of the knees and elbows and pink confluent papules on the paranasal folds, and periauricular and perianal regions. He also had hard nodules all over the scalp and around the mouth, and severe gingival hypertrophy. Histologic and ultrastructural features were typical of JHF. Clinical features, pathology, and physiology are discussed.

  2. Gene expression in term placentas is regulated more by spinal or epidural anesthesia than by late-onset preeclampsia or gestational diabetes mellitus

    Science.gov (United States)

    Lekva, Tove; Lyle, Robert; Roland, Marie Cecilie Paasche; Friis, Camilla; Bianchi, Diana W.; Jaffe, Iris Z.; Norwitz, Errol R.; Bollerslev, Jens; Henriksen, Tore; Ueland, Thor

    2016-01-01

    Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are common complications of pregnancy, but the mechanisms underlying these disorders remain unclear. The aim was to identify the extent of altered gene expression in term placentas from pregnant women with late-onset PE and GDM compared to controls. RNAseq identified few significantly differentially regulated genes in placental biopsies between PE, GDM, or uncomplicated pregnancy (n = 10 each group). Five genes were altered in placentas from PE including 4 non-coding genes and Angiopoietin 2 (ANGPT2). No genes were significantly regulated by GDM. In contrast, many genes were significantly regulated by fetal, maternal and delivery-specific variables, particularly spinal and epidural anesthesia. We selected ANGPT2 and Chemokine (C-X-C motif) ligand 14 (CXCL14) to test with qPCR in a larger set of placentas (n = 475) and found no differences between the groups. However, regression analysis revealed a stronger association between placental ANGPT2 and CXCL14 mRNA expression and fetal, maternal and delivery-specific variables than diagnostic group. To conclude, the gene expression in term placentas are highly affected by fetal, maternal and delivery specific variables. Few regulated genes were found in late-onset PE and GDM placentas, which may suggest that these conditions could be more affected by maternal factors. PMID:27405415

  3. Streptozotocin-induced type-1-diabetes disease onset in Sprague-Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity.

    Science.gov (United States)

    Patterson, Elaine; Marques, Tatiana M; O'Sullivan, Orla; Fitzgerald, Patrick; Fitzgerald, Gerald F; Cotter, Paul D; Dinan, Timothy G; Cryan, John F; Stanton, Catherine; Ross, R Paul

    2015-01-01

    There is a growing appreciation that microbiota composition can significantly affect host health and play a role in disease onset and progression. This study assessed the impact of streptozotocin (STZ)-induced type-1-diabetes (T1D) on intestinal microbiota composition and diversity in Sprague-Dawley rats, compared with healthy controls over time. T1D was induced by injection of a single dose (60 mg STZ kg(-1)) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 4 and from caecal content at week 5 from both healthy and T1D groups. High-throughput 16S rRNA sequencing was employed to investigate intestinal microbiota composition. The data revealed that although intestinal microbiota composition between the groups was similar at week 0, a dramatic impact of T1D development on the microbiota was apparent post-STZ injection and for up to 5 weeks. Most notably, T1D onset was associated with a shift in the Bacteroidetes : Firmicutes ratio (Pmicrobiota composition and reduced microbial diversity over time.

  4. Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young

    Directory of Open Access Journals (Sweden)

    Tavakolafshari Jalil

    2009-12-01

    Full Text Available Abstract Hepatocyte nuclear factor 4α (HNF4α is a nuclear receptor involved in glucose homeostasis and is required for normal β cell function. Mutations in the HNF4α gene are associated with maturity onset diabetes of the young type 1 (MODY1. The aim of the present study was to determine the prevalence and nature of mutations in HNF4α gene in Iranian patients with a clinical diagnosis of MODY and their family members. Twelve families including 30 patients with clinically MODY diagnosis and 21 members of their family were examined using PCR-RFLP method and in case of mutation confirmed by sequencing techniques. Fifty age and sex matched subjects with normal fasting blood sugar (FBS and Glucose tolerance test (GTT were constituted the control group and investigated in the similar pattern. Single mutation of V255M in the HNF4α gene was detected. This known mutation was found in 8 of 30 patients and 3 of 21 individuals in relatives. Fifty healthy control subjects did not show any mutation. Here, it is indicated that the prevalence of HNF4α mutation among Iranian patients with clinical MODY is considerable. This mutation was present in 26.6% of our patients, but nothing was found in control group. In the family members, 3 subjects with the age of ≤25 years old carried this mutation. Therefore, holding this mutation in this range of age could be a predisposing factor for developing diabetes in future.

  5. Advances on research of early-onset type 2 diabetes%早发型糖尿病的研究进展

    Institute of Scientific and Technical Information of China (English)

    翁建平; 黄知敏

    2003-01-01

    @@ 以往多认为早发型糖尿病的主要类型是1型糖尿病,但近年随着糖尿病分子遗传学研究的深入,越来越多的证据显示,在早发型糖尿病患者中,2型糖尿病及一些特殊类型糖尿病如年青的成年发病型糖尿病(maturity-onset diabetes of the young, MODY)及线粒体基因突变糖尿病(mitochondrial diabetes mellitus, MDM)等所占比例并不低,说明糖尿病发病年龄的提前,既有免疫及遗传方面的原因,也有环境、生活方式等多种因素的作用.本文对早发型糖尿病近年研究作一简要的综述,并探讨其病因学及临床表现的多样性.

  6. Effect of intensive multifactorial treatment on the intima-media thickness of large arteries in patients with new-onset type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Xiao-hong ZHAO; Zhe-rong XU; Qin ZHANG; Hai-feng GU; Yun-mei YANG

    2012-01-01

    Objective:To quantify the changes in blood glucose,blood lipids,blood pressure,and the intima-media thickness (IMT) of large arteries in patients with new-onset type 2 diabetes mellitus who received either intensive multifactorial treatment or conventional treatment.Methods:Two-hundred and ten patients with new-onset type 2 diabetes mellitus were randomly assigned to two groups:an intensive treatment group (n=110) and a conventional treatment group (n=100).Fasting blood glucose (FBG),glycosylated hemoglobin A1c (HbA1c),blood pressure,blood lipids [total cholesterol (TC),triolyceride (TG),low-density lipoprotein C (LDL-C),and high-density lipoprotein C (HDL-C)],and IMTs of large arteries (carotid,iliac,and femoral arteries) were determined before and at one and two years after starting treatment.The patients in the conventional treatment group received routine diabetes management in our outpatient department.Targets were established for patients in the intensive treatment group.Their blood glucose,blood lipids,and blood pressure levels were regularly monitored and therapeutic regimens were adjusted for those whose measurements did not meet the target values until all the parameters met the established targets.Within-group and between-group differences were evaluated.Results:A significantly greater percentage of patients in the intensive treatment group had LDL-C levels that reached the target value one year after starting treatment than those in the conventional treatment group (52.04% vs.33.33%,P<0.05).No significant differences were found between groups for FBG,HbA1c,blood pressure,TG,TC,or HDL-C.The percentages of patients with TG (51.02% vs.34.48%),TC (52.04% vs.33.33%),and LDL-C (61.22% vs.43.67%) who met the respective target values in the intensive treatment group were all significantly higher than the corresponding percentages in the conventional treatment group two years after starting treatment (P<0.05).There were no significant

  7. Impact of birth weight on adult-onset diabetes mellitus in relation to current body mass index: The Japan Nurses' Health Study.

    Science.gov (United States)

    Katanoda, Kota; Noda, Mitsuhiko; Goto, Atsushi; Mizunuma, Hideki; Lee, Jung Su; Hayashi, Kunihiko

    2017-09-01

    Although birth weight is considered as a fetal determinant of the development of adult-onset diabetes mellitus (DM), its public health importance relative to adult body mass index (BMI) remains unclear. We aimed to examine the association between adult-onset DM and birth weight in relation to adult BMI. We conducted a self-administered questionnaire as a baseline survey of the Japanese Nurses' Health Study cohort between 2001 and 2007. Exclusion criteria were applied to the volunteer sample of 49,927 female nurses (age <30 years or unknown, current pregnancy, development of DM before the age of 30 years, unknown core variables), and data from 26,949 female nurses aged 30 years or older were used. The association between history of DM diagnosis and birth weight was analyzed using logistic regression. A linear inverse association was observed between birth weight and DM, after adjustment for age, BMI, and parental history of DM. The odds ratio for developing DM per 100 g increase in birth weight was 0.93 (95% confidence interval [CI], 0.90-0.96). The association was unchanged when birth weight was converted to percentile for gestational age. In the BMI-stratified analysis, the odds ratio for DM in the <2500 g birth weight group reached 4.75 (95% CI, 1.22-18.44, compared to the reference 3000-3499 g group) among women with normal low BMI (18.5-20.9). Birth weight and its percentile for gestational age were associated with adult-onset DM. Attention should be paid to the risk of DM among women born with low weight, even when their current BMI is normal. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  8. Huntington's disease does not appear to increase the risk of diabetes mellitus

    DEFF Research Database (Denmark)

    Boesgaard, T W; Nielsen, T T; Josefsen, K;

    2009-01-01

    . This challenges the assumption of an increased risk of diabetes among HD patients, although our results do not exclude a changed glucose tolerance in end-stage HD patients or in patients with juvenile onset HD. It also raises the question of which extent transgenic mice models reflect the pathology of human HD......, the severity of the diabetic phenotype appears to correlate with the length of a polyglutamine expansion in the protein huntingtin. In the present study, we investigated the association between diabetes mellitus and HD by performing an oral glucose-tolerance test (OGTT) to evaluate the glucose-tolerance status...

  9. A three-step programmed method for the identification of causative gene mutations of maturity onset diabetes of the young (MODY).

    Science.gov (United States)

    Li, Qian; Cao, Xi; Qiu, Hai-Yan; Lu, Jing; Gao, Rui; Liu, Chao; Yuan, Ming-Xia; Yang, Guang-Ran; Yang, Jin-Kui

    2016-08-22

    To establish a three-step programmed method to find gene mutations related to maturity onset diabetes of the young (MODY). Target region capture and next-generation sequencing (NGS) were performed using customized oligonucleotide probes designed to capture suspected genes for MODY in 11 probands with clinically diagnosed MODY. The suspected associations of certain genes with MODY were then confirmed by Sanger sequencing in the probands and their family members. Finally, to validate variants of one of the genes of interest (glucokinase, GCK) as pathogenic mutations, protein function editing by the variant genes was assessed. In the target region capture and NGS phase, a total of nine variants of seven genes (GCK, WFS1, SLC19A2, SH2B1, SERPINB4, RFX6, and GATA6) were identified in eight probands. Two heterozygous GCK mutations located on the same allele (p.Leu77Arg and p.Val101Met) were identified in a MODY family. Sanger sequencing was used to confirm the variants identified by NGS to be present in probands and their diabetic family members, but not in non-diabetic family members. Finally, enzyme kinetic and thermal stability analyses revealed that the p.Leu77Arg mutation or the p.Leu77Arg mutation in combination with the p.Val101Met mutation inactivates GCK function and stability, while mutation of p.Val101Met alone does not. The p.Leu77Arg but not p.Val101Met GCK mutation is therefore considered a pathogenic mutation associated with MODY. Genetic screening coupled with gene-editing protein function testing is an effective and reliable method by which causative gene mutations of MODY can be identified.

  10. Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control.

    Directory of Open Access Journals (Sweden)

    Christina Bächle

    Full Text Available This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control.In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9 for symptoms of depression and severity of depressive symptoms (PHQ-9 score. Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c.A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation was 5.3 (4.4 among women and 3.9 (3.6 among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (βwomen 3.8, p<0.001. However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (βmen 0.14, p=0.006.Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes.

  11. A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity.

    Science.gov (United States)

    Mencarelli, Monica; Zulian, Alessandra; Cancello, Raffaella; Alberti, Luisella; Gilardini, Luisa; Di Blasio, Anna Maria; Invitti, Cecilia

    2012-12-01

    Rare mutations in several genes have a critical role in the control of homeostatic mechanisms such as food-intake, energy balance and glucose metabolism. In this study, we performed a mutational screening in a 58-year-old woman presenting early-onset type 2 diabetes and central obesity. The entire coding regions of MC4R, MC3R, HNF1A, GCK and POMC (pro-opiomelanocortin) genes were analyzed by direct sequencing. A new missense mutation was identified within the POMC gene signal peptide sequence, resulting in a heterozygous substitution of an arginine for a glycine at codon 15 (p.A15G) that was excluded in 300 healthy normal weight controls. The mutation segregated in the family and was associated with overweight, type 2 diabetes, hypertension and coronary heart disease in the carriers. Functional studies demonstrated that POMC protein was not detectable in β-TC3 cells transfected with A15G-POMC vector as well as in their culture media, despite POMC mRNA levels were comparable for amount and stability to those of wild-type-transfected cells. In silico RNA folding prediction indicated that the mutation gives rise to a different RNA secondary structure, suggesting that it might affect translation and protein synthesis. To the best of our knowledge, this is the first report addressing the functional consequences of a mutation in the signal peptide of POMC. These findings further support the hypothesis that POMC-derived peptides might have a role in the control of peripheral glucose metabolism and suggest that disruption of central POMC secretion might represent an additional link between type 2 diabetes and obesity.

  12. Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin Therapy for Chronic Hepatitis C Virus Infection

    Science.gov (United States)

    Ranganathan, Raghini; Janarthanan, Krishnaveni; Rajasekaran, Senthilkumar

    2012-01-01

    A 16-year-old female was treated with pegylated-interferon (PEG-IFN) alfa (a)-2b and ribavirin combination therapy for chronic hepatitis C virus (HCV) infection. She attained rapid virological response. She presented with diabetic ketoacidosis after 41 weeks of therapy. Anti-glutamic acid decarboxylase antibodies and islet cell antibodies were negative. Her fasting serum C-peptide level was <0.1 ng/mL, and the treatment course was completed. This case underlines the importance of periodic plasma glucose monitoring in patients during and after PEG-IFN and ribavirin therapy. PMID:25755410

  13. Change of glutamic acid decarboxylase antibody and protein tyrosine phosphatase antibody in Chinese patients with acute-onset type 1 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    CHAO Chen; HUANG Gan; LI Xia; YANG Lin; LIN Jian; JIN Ping; LUO Shuo-ming

    2013-01-01

    Background Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies,which exert important roles in the process of type 1 diabetes mellitus (T1D).Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.Methods Two hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited.GADA and IA-2A were detected at the time of diagnosis,one year later,3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well.Results During the course of acute-onset T1D,the majority of patients remained stable for GADA or IA-2A,however,a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity.The prevalence of GADA was 56.3% at diagnosis,decreasing to 50.5% one year later,and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%,31.0% and 23.3%,respectively.The median GADA titers were 0.0825 at diagnosis,declining to 0.0585 one year later and 0.0383 3-5 years later (P <0.001),while the corresponding median titers were 0.0016,0.0010,0.0014 for IA-2A,respectively.Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h)levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P <0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of β cell function.Conclusion Our data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the β cell function in Chinese patients.

  14. Predictive value of non-fasting remnant cholesterol for short-term outcome of diabetics with new-onset stable coronary artery disease.

    Science.gov (United States)

    Hong, Li-Feng; Yan, Xiao-Ni; Lu, Zhen-Hua; Fan, Ying; Ye, Fei; Wu, Qiong; Luo, Song-Hui; Yang, Bo; Li, Jian-Jun

    2017-01-13

    The relationship between non-fasting remnant cholesterol and cardiovascular outcome in the era of potent statin therapy remained to be elucidated. A cohort study of three hundred and twenty eight diabetics diagnosed with new-onset stable coronary artery disease (CAD) by coronary angiography were enrolled. All cases were followed up for an average duration of twelve months. The association between baseline remnant cholesterol levels and major cardiovascular outcomes were evaluated using the receivers operating characteristic (ROC) curves and Cox proportional hazards regression analysis. During a period of 12-month's follow-up, 14.3% patients (47/328) underwent pre-specified adverse outcomes. The remnant cholesterol associated with high sensitivity C-reactive protein, neutrophil count and fibrinogen (R (2) = 0.20, 0.12 and 0.14; P = 0.000, 0.036 and 0.010 respectively). Area under the ROC curves (AUC) indicated discriminatory power of the remnant cholesterol to predict the adverse outcomes for this population (AUC = 0.64, P cholesterol showed relatively lower cardiac events for diabetic patients with stable CAD (Log rank X (2) = 8.94, P = 0.04). However, according to multivariate Cox proportional hazards regression, apart from hemoglobin A1C (Hazard ratio [H.R.] =1.38, 95% CI: 1.14-1.66, P = 0.001) and Gensini scores (H.R. = 1.00, 95% CI: 1.00-1.02; P = 0.035), remnant cholesterol did not qualify as an independent predictor of adverse prognosis in these settings (H.R. = 1.05, 95% CI: 0.46-2.37, P = 0.909). Non-fasting remnant cholesterol was associated with inflammatory biomarkers and high incidence of revascularization, but not qualified as an independent predictor for short-term prognosis of diabetics with new-onset stable coronary artery disease.

  15. Long-Term Glycemic Control as a Result of Initial Education for Children With New Onset Type 1 Diabetes

    Science.gov (United States)

    Cabrera, Susanne M.; Srivastava, Nayan T.; Behzadi, Jennifer M.; Pottorff, Tina M.; DiMeglio, Linda A.; Walvoord, Emily C.

    2016-01-01

    Purpose The purpose of this study was to examine the role of initial diabetes education delivery at an academic medical center (AMC) versus non-AMCs on long-term glycemic control. Methods We performed a retrospective study of children with type 1 diabetes referred to an AMC after being educated at non-AMCs. These children were matched to a group of children diagnosed and educated as inpatients at an AMC. The A1C levels at 2, 3, and 5 years from diagnosis were compared between the 2 groups of children. Results Records were identified from 138 children. Glycemic control was comparable in the non-AMC-educated versus AMC-educated patients at 2, 3, and 5 years from diagnosis. The A1C was also highly consistent in each patient over time. Conclusions Long-term glycemic control was independent of whether initial education was delivered at an AMC or non-AMC. Formal education and location at time of diagnosis do not appear to play a significant role in long-term glycemic control. Novel educational constructs, focusing on developmental stages of childhood and reeducation over time, are likely more important than education at time of diagnosis. PMID:23427241

  16. Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia

    Institute of Scientific and Technical Information of China (English)

    Fulvia; Gloria-Bottini; Patrizia; Saccucci; Gian; Franco; Meloni; Maria; Luisa; Manca-Bitti; Luca; Coppeta; Anna; Neri; Andrea; Magrini; Bottini; Egidio

    2014-01-01

    AIM:To investigate the role of protein tyrosin phosphatase 22(PTPN22),maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes(T1D)in Continental Italy and Sardinian populations.METHODS:Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia.PTPN22 genotype was determined by DNA analysis.Maternal age at conception and age at onset of disease were obtained from clinical records.χ2 test of independence,student t test for differences between means and odds ratio analysis were carried out by SPSS programs.Three way contingency table analysis was carried out according to Sokal and Rohlf.RESULTS:The pattern of association between PTPN22and T1D is similar in Continental Italy and Sardinia:the proportion of*T allele carriers is 13.6%in T1D vs6.7%in controls in Continental Italy while in Sardinia is 7.3%in T1D vs 4.4%in controls.The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy:the proportion of newborn from mother aging more than 32 years is89.3%in T1D vs 32.7%in consecutive newborn in Sardinia(P<10-6)while in Continental Italy is 32.2%in T1D vs 19.1%in consecutive newborns(P=0.005).This points to an important role of ethnicity.A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia.PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia.Maternal age does not influence significantly age at onset in Italy(8.2 years in T1D infants from mothers aging32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years:P=0.824)while in Sardinia a border line effect is observed(5.75 years in T1D infants from mothers aging 32 years or less vs7.54 years in T1D infants from

  17. Presence of antibodies to cyclic citrullinated peptides in juvenile-onset systemic lupus erythematosus%儿童系统性红斑狼疮抗环瓜氨酸肽抗体检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    刘海英; 刘云锋; 关启鸿; 钟艳玲; 皮蕾; 张白杜; 郭彩娇; 曾华松

    2010-01-01

    Objective To determine the prevalence of antibodies to cyclic citrullinated peptides (antiCCP) in patients with juvenile-onset systemic lupus erythematosus (JSLE) and its potential clinical significance. Methods Anti-CCP was measured in sera from patients with JSLE (n=47), juvenile idiopathic arthritis (JIA, n=54) and the sera from age-matched healthy children (n=40) using the third generation of anti-CCP ELISA commercial kit. The association of anti-CCP with other laboratory parameters and clinical features, especially arthritic symptoms in JSLE was also analyzed. T-test, Mann-Whitney U test, Chi-square and Fisher's exact test were used for statistical analysis. Results Out of the 47 JSLE patients, 6 (13%) were anti-CCP positive, which was significantly higher than that of the healthy controls( 13% vs 0, P<0.05 ), but not different from that of the JIA group (26%, P=0.098). RF was more prevalent in JSLE patients with anti-CCP than patients without (83% vs 15%, P<0.01 ), but there was no difference in other laboratory parameters and the clinical features ineluding the occurrence of arthritis (67% vs 51%, P>0.05). As one of the initial symptoms, arthritis was observed in 25 of 47 JSLE patients and no one had developed deforming arthropathy.There was no statistical difference in anti-CCP positivity between JSLE patients with and without articular involvement ( 16% vs 9%, P>0.05 ). Anti-CCP was not detected in any of the 3 patients with JSLE who had experienced joint pain and limited activity during 3 years follow-up. Conclusion Anti-CCP could be detected in patients with JSLE. It is noteworthy when differentiate from juvenile idiopathic arthritis, but the presence of anti-CCP does not relate with the occurrence of arthritis at presentation and persistence of arthritis in JSLE.%目的 检测儿童系统性红斑狼疮(JSLE)患者血清抗环瓜氨酸肽(CCP)抗体水平,了解抗CCP抗体在该病中的阳性检出率以及探讨其与

  18. Juvenile Spondyloarthritis

    Science.gov (United States)

    Gmuca, Sabrina; Weiss, Pamela F.

    2015-01-01

    Purpose of review To provide a comprehensive update of the pathogenesis, diagnostic imaging, treatments, and disease activity measurements of juvenile spondyloarthritis (JSpA). Recent findings Genetic and microbiome studies have provided new information regarding possible pathogenesis of JSpA. Recent work suggests that children with JSpA have decreased thresholds for pain in comparison to healthy children. Additionally, pain on physical examination and abnormalities on ultrasound of the entheses are not well correlated. Treatment guidelines for juvenile arthritis, including JSpA, were published by the American College of Rheumatology and are based on active joint count and presence of sacroiliitis. Recent studies have established the efficacy of tumor necrosis factor inhibitors in the symptomatic treatment of axial disease, though their efficacy for halting progression of structural damage is less clear. Newly developed disease activity measures for JSpA include the Juvenile Arthritis Disease Activity Score and the JSpA Disease Activity index. In comparison to other categories of juvenile arthritis, children with JSpA are less likely to attain and sustain inactive disease. Summary Further microbiome and genetic research may help elucidate JSpA pathogenesis. More randomized therapeutic trials are needed and the advent of new composite disease activity measurement tools will hopefully allow for the design of these greatly needed trials. PMID:26002028

  19. Clinical efficacy of mycophenolate mofetil in the treatment of systemic-onset juvenile idiopathic arthritis%麦考酚酸酯治疗幼年特发性关节炎全身型的疗效分析

    Institute of Scientific and Technical Information of China (English)

    韩彤昕; 李彩凤; 王江; 邝伟英; 周怡芳; 邓江红

    2013-01-01

    Objective To evaluate the clinical efficacy of mycophenolate mofetil (MMF) in the treatment of systemic-onset juvenile idiopathic arthritis (SoJIA).Methods Thirty-five patients with a confirmed diagnosis of SoJIA who had received initial treatment were randomly divided into control (n=15),MMF1 (n=7) and MMF2 groups (n=13).The control group received conventional treatment,the MMF1 group received MMF after 2 weeks of conventional treatment that had not led to remission,and the MMF2 group received combination therapy with non-steroidal antiinflammatory drugs,prednisone and MMF.Symptoms,signs,laboratory indices,and adverse events were observed after 2,4,and 12 weeks of treatment,and follow-up was performed for 3-6 months.Results Before treatment,the MMF2 group had a significantly longer disease course than the control group (P<0.05).After 2 weeks of treatment,the MMF1 and MMF2 groups had a significantly lower prednisone dose and erythrocyte sedimentation rate (ESR) than the control group (P<0.05).The MMF1 group had significantly higher body temperature than the other two groups (P<0.05).After 4 weeks of treatment,the MMF1 group had a significantly lower prednisone dose and ESR than the control group (P<0.05).The MMF2 group had a significantly lower prednisone dose,body temperature (recovery to normal),white blood cell count,ESR and serum ferritin concentration than the control group (P<0.05).Body temperature was significantly lower in the MMF2 group than in the MMF1 group (P<0.05).No adverse events were observed in either the MMF1 or MMF2 groups during treatment.Conclusions Combination therapy with MMF can lead to better control of the patient's condition,more rapid relief of clinical symptoms and reduced glucocorticoid dose.The therapy with MMF is safe in children.%目的 评价麦考酚酸酯(mycophenolate mofetil,MMF)治疗幼年特发性关节炎全身型(system onset juvenile idiopathic arthritis,SoJIA)的临床疗效.方法 35例确诊为SoJIA并初

  20. Juvenile arthritis and uveitis.

    Science.gov (United States)

    Kanski, J J

    1990-01-01

    The association between juvenile arthritis and uveitis is reviewed. Some children with the HLA-B27 related spondyloarthropathies develop anterior uveitis. About 20% of patients with juvenile rheumatoid arthritis (JRA) who are negative for IgM rheumatoid factor develop a frequently bilateral, nongranulomatous chronic anterior uveitis. Risk factors for uveitis in JRA patients are: female gender, pauciarticular onset of arthritis, presence of circulating antinuclear antibodies, and the antigens HLA-DW5 and HLA-DPw2. Uveitis is rare after seven years or more have elapsed from the onset of arthritis. The visual prognosis in patients with uveitis is good in 25% and fair in 50%. The remaining 25% develop visual impairment from complicated cataract and/or secondary inflammatory glaucoma. The potential benefit of cytotoxic agents in the treatment of intractable uveitis is outweighed by the risk of serious side effects. The management of secondary inflammatory glaucoma is unsatisfactory, but the results of treatment of complicated cataracts by lensectomy-vitrectomy are good.

  1. A Relentless Illness—Fighting Diabetes

    Science.gov (United States)

    ... Current Issue Past Issues A Relentless Illness— Fighting Diabetes Past Issues / Fall 2006 Table of Contents For ... the fight to control and cure type 1 diabetes. As international chairman of the Juvenile Diabetes Research ...

  2. Absence of diabetes and pancreatic exocrine dysfunction in a transgenic model of carboxyl-ester lipase-MODY (maturity-onset diabetes of the young.

    Directory of Open Access Journals (Sweden)

    Helge Ræder

    Full Text Available CEL-MODY is a monogenic form of diabetes with exocrine pancreatic insufficiency caused by mutations in CARBOXYL-ESTER LIPASE (CEL. The pathogenic processes underlying CEL-MODY are poorly understood, and the global knockout mouse model of the CEL gene (CELKO did not recapitulate the disease. We therefore aimed to create and phenotype a mouse model specifically over-expressing mutated CEL in the pancreas.We established a monotransgenic floxed (flanking LOX sequences mouse line carrying the human CEL mutation c.1686delT and crossed it with an elastase-Cre mouse to derive a bitransgenic mouse line with pancreas-specific over-expression of CEL carrying this disease-associated mutation (TgCEL. Following confirmation of murine pancreatic expression of the human transgene by real-time quantitative PCR, we phenotyped the mouse model fed a normal chow and compared it with mice fed a 60% high fat diet (HFD as well as the effects of short-term and long-term cerulein exposure.Pancreatic exocrine function was normal in TgCEL mice on normal chow as assessed by serum lipid and lipid-soluble vitamin levels, fecal elastase and fecal fat absorption, and the normoglycemic mice exhibited normal pancreatic morphology. On 60% HFD, the mice gained weight to the same extent as controls, had normal pancreatic exocrine function and comparable glucose tolerance even after resuming normal diet and follow up up to 22 months of age. The cerulein-exposed TgCEL mice gained weight and remained glucose tolerant, and there were no detectable mutation-specific differences in serum amylase, islet hormones or the extent of pancreatic tissue inflammation.In this murine model of human CEL-MODY diabetes, we did not detect mutation-specific endocrine or exocrine pancreatic phenotypes, in response to altered diets or exposure to cerulein.

  3. Diabetes

    OpenAIRE

    Smith, Paul

    2003-01-01

    Derbyshire general practitioner Stuart Bootle has had diabetes for 20 years. He speaks to Paul Smith, who has type 1 diabetes himself, about the trials and tribulations of being on the receiving end of NHS care

  4. Differential impact of statin on new-onset diabetes in different age groups: a population-based case-control study in women from an asian country.

    Directory of Open Access Journals (Sweden)

    Chih-Wei Chen

    Full Text Available BACKGROUND: Statins reduce cardiovascular risks but increase the risk of new-onset diabetes (NOD. The aim of this study is to determine what effect, if any, statins have on the risk of NOD events in a population-based case-control study. An evaluation of the relationship between age and statin-exposure on NOD risks was further examined in a female Asian population. METHOD: In a nationwide case-controlled study, the authors assessed 1065 female NOD patients and 10650 controls with matching ages, genders and physician visit dates. The impact of statin-exposure on NOD was examined through multiple logistic regression models. Subgroup analysis for exploring the risk of NOD and statin-exposure in different age groups was performed. RESULTS: Statin-exposure was statistically significantly associated with increased new-onset diabetes risks using multivariate analysis. Interaction effect between age and statin-exposure on NOD risk was noted. For atorvastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted odds ratio [OR], 8.0; 95% confidence interval [CI], 2.57-24.90. For rosuvastatin, the risk of cDDDs>60 was highest among the 40-54 year-olds (adjusted OR, 14.8; 95% CI, 2.27-96.15. For simvastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted OR, 15.8; 95% CI, 5.77-43.26. For pravastatin, the risk of cDDDs>60 was highest among the 55-64 year-olds (adjusted OR, 14.0; 95% CI, 1.56-125.18. CONCLUSIONS: This population-based study found that statin use is associated with an increased risk of NOD in women. The risk of statin-related NOD was more evident for women aged 40-64 years compared to women aged 65 or more, and was cumulative-dose dependent. The use of statins should always be determined by weighing the clinical benefits and potential risks for NOD, and the patients should be continuously monitored for adverse effects.

  5. Dietary Intervention for Glucose Tolerance In Teens (DIG IT): Protocol of a randomized controlled trial using health coaching to prevent youth-onset type 2 diabetes.

    Science.gov (United States)

    Wagner, Kelly A; Braun, Ethan; Armah, Seth M; Horan, Diarmuid; Smith, Lisa G; Pike, Julie; Tu, Wanzhu; Hamilton, Marc T; Delp, Edward J; Campbell, Wayne W; Boushey, Carol J; Hannon, Tamara S; Gletsu-Miller, Nana

    2017-02-01

    Youth-onset type 2 diabetes (T2D) is a disease that is newly emerging and behavioral strategies for its prevention are limited. Interventions that target the lifestyle behaviors of adolescents, to improve poor dietary quality and reduce excessive sedentariness, promise to reduce the risk of developing T2D. Health coaching is effective for promoting healthy behaviors in patients who have chronic disease, but few experimental studies are in adolescents. This randomized controlled trial, in adolescents with prediabetes, will determine the effectiveness of a health coaching intervention to facilitate adoption of healthy diet and activity behaviors that delay or prevent development of T2D. The Dietary Intervention for Glucose Tolerance In Teens (DIG IT) trial will involve an evaluation of a health coaching intervention in adolescents with prediabetes. Eligible participants will be randomized to receive 6months of health coaching or a single dietary consultation that is standard-of-care. The primary outcome will be 2-hour oral glucose tolerance test concentration. Secondary outcomes will include measures of glycemia and insulin action as well as dietary, physical activity and sedentary behaviors measured using an electronic food record, and by inclinometer. Data will be collected before and after the intervention (at 6months) and at 12months (to assess sustainability). This trial will determine whether a health coaching intervention, a personalized and low-cost approach to modify dietary and activity behaviors, is effective and sustainable for prevention of youth-onset T2D, relative to standard-of-care. Health coaching has the potential to be widely implemented in clinical or community settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Structural and functional study of the GlnB22-insulin mutant responsible for maturity-onset diabetes of the young.

    Directory of Open Access Journals (Sweden)

    Květoslava Křížková

    Full Text Available The insulin gene mutation c.137G>A (R46Q, which changes an arginine at the B22 position of the mature hormone to glutamine, causes the monogenic diabetes variant maturity-onset diabetes of the young (MODY. In MODY patients, this mutation is heterozygous, and both mutant and wild-type (WT human insulin are produced simultaneously. However, the patients often depend on administration of exogenous insulin. In this study, we chemically synthesized the MODY mutant [GlnB22]-insulin and characterized its biological and structural properties. The chemical synthesis of this insulin analogue revealed that its folding ability is severely impaired. In vitro and in vivo tests showed that its binding affinity and biological activity are reduced (both approximately 20% that of human insulin. Comparison of the solution structure of [GlnB22]-insulin with the solution structure of native human insulin revealed that the most significant structural effect of the mutation is distortion of the B20-B23 β-turn, leading to liberation of the B chain C-terminus from the protein core. The distortion of the B20-B23 β-turn is caused by the extended conformational freedom of the GlnB22 side chain, which is no longer anchored in a hydrogen bonding network like the native ArgB22. The partially disordered [GlnB22]-insulin structure appears to be one reason for the reduced binding potency of this mutant and may also be responsible for its low folding efficiency in vivo. The altered orientation and flexibility of the B20-B23 β-turn may interfere with the formation of disulfide bonds in proinsulin bearing the R46Q (GlnB22 mutation. This may also have a negative effect on the WT proinsulin simultaneously biosynthesized in β-cells and therefore play a major role in the development of MODY in patients producing [GlnB22]-insulin.

  7. Apoptosis of purified CD4+ T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Ayelet Kaminitz

    Full Text Available BACKGROUND: Regulatory T cells (Treg play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. PRINCIPAL FINDINGS: Apoptotic cells are short lived in vivo and death occurs primarily during isolation, manipulation and culture. Excessive susceptibility of CD25(+ T cells to spontaneous apoptosis is characteristic of isolated subsets, however disappears when death is measured in mixed splenocyte cultures. In variance, CD25(- T cells display balanced sensitivity to apoptosis under both conditions. The isolation procedure removes soluble factors, IL-2 playing a significant role in sustaining Treg viability. In addition, pro- and anti-apoptotic signals are transduced by cell-to-cell interactions: CD3 and CD28 protect CD25(+ T cells from apoptosis, and in parallel sensitize naïve effector cells to apoptosis. Treg viability is modulated both by other T cells and other subsets within mixed splenocyte cultures. Variations in sensitivity to apoptosis are often hindered by fast proliferation of viable cells, therefore cycling rates are mandatory to adequate interpretation of cell death assays. CONCLUSIONS: The sensitivity of purified Treg to apoptosis is dominated by cytokine deprivation and absence of cell-to-cell interactions, and deviate significantly from measurements in mixed populations. Balanced sensitivity of naïve/effector and regulatory T cells to apoptosis in NOD mice argues against the concept that differential susceptibility affects disease evolution and progression.

  8. Juvenile Justice in Milwaukee

    Science.gov (United States)

    Williams, Gary L.; Greer, Lanetta

    2010-01-01

    Historically, there have been several attempts made to address issues surrounding juvenile delinquency. The Wisconsin Legislature outlines the objectives of the juvenile justice system in the Juvenile Justice Code in s. 939.01, ?to promote a juvenile justice system capable of dealing with the problem of juvenile delinquency, a system which will…

  9. Juvenile xanthogranuloma.

    Science.gov (United States)

    Singh, R; Ghazali, W

    1992-05-01

    Juvenile xanthogranuloma is a benign cutaneous growth presenting as papules or nodules. It is characterized by an intradermal collection of lipid-laden macrophages and varying degrees of fibroblastic proliferation. We have recently observed two patients with xanthogranulomas: one was found to have a papular type and the second patient had multiple nodular growths. We present these cases, which should be considered in the differential diagnosis of skin nodules.

  10. Uveitis in juvenile chronic arthritis.

    Science.gov (United States)

    Kanski, J J

    1990-01-01

    About 20% of patients with juvenile chronic arthritis develop uveitis which is frequently bilateral. Risk factors for uveitis are: female gender, pauciarticular onset of arthritis, presence of circulating antinuclear antibodies, and the antigens HLA-DW5 and HLA-DPw2. The visual prognosis in patients with uveitis is good in 25% and fair in 50%. The remaining 25% develop cataract and/or glaucoma. The management of glaucoma is unsatisfactory, but the results of cataract surgery by lensectomy are good.

  11. Dipeptidyl peptidase-IV inhibitors are efficient adjunct therapy in HNF1A maturity-onset diabetes of the young patients--report of two cases.

    Science.gov (United States)

    Katra, Barbara; Klupa, Tomasz; Skupien, Jan; Szopa, Magdalena; Nowak, Natalia; Borowiec, Maciej; Kozek, Elzbieta; Malecki, Maciej T

    2010-04-01

    In HNF1A maturity-onset diabetes of the young (MODY), sulfonylurea (SU) is the first-line treatment. Over time, such therapy fails, and additional treatment is required. Dipeptidyl peptidase IV (DPP-IV) inhibitors are new agents that lower blood glucose by prolonging the activity of circulating incretins. We applied DPP-IV inhibitors in two HNF1A MODY patients whose earlier therapeutic regimen included SU. Case 1, a 39-year-old woman, a carrier of the ArgR171X HNF1A mutation, with a 7-year history of diabetes was on 160 mg of gliclazide and 2,000 mg of metformin. Her initial hemoglobin A1c (HbA1c) level was 7.2%, while the mean glucose level on the CGMS((R)) (Medtronic, Northridge, CA) record was 162 mg/dL. Sitagliptine, in a dose of 100 mg/day, was added to the previous treatment. Case 2, a 62-year-old woman, a carrier of the IVS7nt-6G>A mutation, with a 41-year history of diabetes was treated with 240 mg/day gliclazide and 6 IU of insulin/day. Her initial HbA1c was 8.8%, and average glycemia reached 172 mg/dL. In her case, we started the combined therapy with 50 mg of vildagliptine twice daily. Patients were reexamined after 3 months, and HbA1c fell to 6.3% in both subjects. Similarly, significant improvement in glycemic control on CGMS was observed as the average glycemia decreased to 114 mg/dL and 134 mg/dL in Case 1 and Case 2, respectively. No episodes of hypoglycemia or other side effects were recorded. As intravenous glucose tolerance tests (IVGTTs) were performed before and after DPP-IV implementation, we were able to assess their impact on insulin secretion under fasting conditions. We saw a substantial rise in insulin level increment during IVGTT (by 9.8 and13.4 mIU/L in Case 1 and Case 2, respectively). DPP-IV inhibitors may be an effective tool of combined therapy in HNF1A MODY, and they seem to improve beta-cell function under fasting conditions.

  12. Functional defect of truncated hepatocyte nuclear factor-1{alpha} (G554fsX556) associated with maturity-onset diabetes of the young

    Energy Technology Data Exchange (ETDEWEB)

    Kooptiwut, Suwattanee, E-mail: S_kooptiwut@hotmail.com [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Sujjitjoon, Jatuporn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Plengvidhya, Nattachet [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Semprasert, Namoiy [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Furuta, Hiroto; Nanjo, Kishio [The First Department, Wakayama Medical University (Japan); Banchuin, Napatawn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai [Division of Medical Molecular Biology, Medicine Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Bangkok (Thailand)

    2009-05-22

    A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1{alpha} (HNF-1{alpha}) encoding a truncated HNF-1{alpha} (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1{alpha} proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1{alpha} could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1{alpha} on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1{alpha} (G554fsX556) on the transactivation of its target-gene promoters would account for the {beta}-cell dysfunction associated with the pathogenesis of MODY.

  13. Cholecalciferol supplementation improves suppressive capacity of regulatory T-cells in young patients with new-onset type 1 diabetes mellitus - A randomized clinical trial.

    Science.gov (United States)

    Treiber, Gerlies; Prietl, Barbara; Fröhlich-Reiterer, Elke; Lechner, Evelyne; Ribitsch, Anja; Fritsch, Maria; Rami-Merhar, Birgit; Steigleder-Schweiger, Claudia; Graninger, Winfried; Borkenstein, Martin; Pieber, Thomas R

    2015-12-01

    It is unknown if cholecalciferol is able to modify defects in regulatory T cells (Tregs) in type 1 diabetes (T1D). In this randomized, double-blind, placebo controlled trial 30 young patients with new-onset T1D were assigned to cholecalciferol (70IU/kgbodyweight/day) or placebo for 12months. Tregs were determined by FACS-analysis and functional tests were assessed with ex vivo suppression co-cultures at months 0, 3, 6 and 12. Suppressive capacity of Tregs increased (pcholecalciferol from baseline (-1.59±25.6%) to 3 (30.5±39.4%), 6 (44.6±23.8%) and 12months (37.2±25.0%) and change of suppression capacity from baseline to 12months was significantly higher (pcholecalciferol (22.2±47.2%) than placebo (-16.6±21.1%). Serum calcium and parathormone stayed within normal range. This is the first study, which showed that cholecalciferol improved suppressor function of Tregs in patients with T1D and vitamin D could serve as one possible agent in the development of immunomodulatory combination therapies for T1D.

  14. Long-term follow-up after conversion from tacrolimus to cyclosporin in renal transplant patients with new-onset diabetes mellitus after transplantation.

    Science.gov (United States)

    Batista, F; Auyanet, I; Torregrosa, J-V; Oppenheimer, F

    2012-11-01

    The relationship between anticalcineurin (CNI) drugs and the development new-onset diabetes mellitus after kidney transplantation (NODAT) is well established. Among these agents cyclosporine shows lesser diabetogenicity than tacrolimus. It has been described that conversion from tacrolimus to cyclosporine improves glycemic control; however, there are no studies showing whether this reduced risk is maintained upon long-term follow-up. To evaluate whether CNI drugs conversion from tacrolimus to cyclosporine helps to maintain better glycemic control. We retrospectively evaluated the evolution of glucose metabolism at 5 years after conversion from tacrolimus to cyclosporine in eight patients (six men) with NODAT. Mean age was 42.8 ± 15 years, and time after transplantation to conversion 128 ± 40 months. We analyzed fasting serum glucose, lipid metabolism, renal function, and cyclosporine levels at 0, 6, 12, 24, 36, 48, and 60 months after conversion. At 6 months after conversion, improved glucose metabolism was observed (268 ± 161 versus 121 ± 31 mg/dL; P Cyclosporine levels remained stable during the follow-up. Conversion of renal transplant patients with NODAT from tacrolimus to cyclosporine improves glucose metabolism in the short term but glycemia increases thereafter. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands Clinic, Harare, Zimbabwe: retrospective cohort analysis.

    Science.gov (United States)

    Chimbetete, Cleophas; Mugglin, Catrina; Shamu, Tinei; Kalesan, Bindu; Bertisch, Barbara; Egger, Matthias; Keiser, Olivia

    2017-07-01

    To assess the incidence and associated factors of Type 2 Diabetes Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. We analysed data of all HIV-infected patients older than 16 years who attended Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers patients whose random blood sugar is higher than 11.1 mmol/l and which is confirmed by a fasting blood sugar higher than 7.0 mmol/l to have T2DM. T2DM is also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors for developing T2DM were identified using Cox proportional hazard models adjusted for confounding. Missing baseline BMI data were multiply imputed. Results are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). Data for 4,110 participants were included: 67.2% were women; median age was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337) cells/mm(3) . The proportion of participants with hypertension at baseline was 15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57 patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per 1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR: 1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30 kg/m(2) ) (aHR=2.26, 95% CI: 1.17-4.36), age >40 years (aHR=2.16, 95% CI: 1.22-3.83) and male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO clinical stage) were not independent risk factors for developing T2DM. Although the incidence of T2DM in this HIV cohort was lower than that has been observed in others, our results show that risk factors for developing T2DM among HIV-infected people are similar to those of the general population. HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care that includes better health services for prevention, early

  16. Genetic Variations in the Kir6.2 Subunit (KCNJ11 of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan

    Directory of Open Access Journals (Sweden)

    Yi-Der Jiang

    2014-01-01

    Full Text Available To investigate the role of E23K polymorphism of the KCNJ11 gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4 and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0 from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of the KCNJ11 gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism of KCNJ11 gene than control subjects (P = 0.044. After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P = 0.047. K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of the KCNJ11 gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading.

  17. Clinical heterogeneity of type 1 diabetes mellitus at onset%1型糖尿病起病过程的临床异质性分析

    Institute of Scientific and Technical Information of China (English)

    黄知敏; 黎凤珍; 陈月英; 李延兵

    2011-01-01

    Objective To investigate the clinical heterogeneity of type 1 diabetes mellitus (T1 DM) at onset.Method A total of 205 newly diagnosed T1 DM patients discharged from the hospital between January 1999 and December 2009 were retrospectively reviewed.Clinical characteristics and laboratory data at onset were compared among fulminant type 1 diabetes ( FT1 DM ) and those with duration of symptoms before diagnosis shorter (acute-onset) or longer (slow-onset) than 3 months.Antibodies to glutamic acid decarboxylase (GADA) were determined by enzyme-linked immunosorbent assay (ELISA), while islet cell antibodies (ICA) ,insulin autoantibody(IAA) and serum C-peptide were detected using radioimmunoassay (RIA).Statistical analyses were performed using One-way ANOVA and two independent samples t-test for measurement data, multivariate Chi-square and Fisher's exact probability test were used for enumeration data.Results The proportions of FT1 DM, acute-onset and slow-onset T1 DM were 8.8%, 66.8%, 24.4% respectively.The onset of FT1 DM was so abrupt that the concentration of plasma glucose was prominently elevated ((31±12) vs (25 ±10), (24 ±8) mmol/L, F=4.462, P<0.05), whereas HbA1c was disproportionately near normal ( (6.8±1.1 ) % vs ( 12.3 ± 2.4 ) %, ( 13.9 t 2.7 ) %, F = 54.661, P <0.05).Ketoacidosis was almost inevitable at diagnosis ( 93.8% vs 45.3%, 8.0%, F = 44.943, P =0.000) and the accompanied metabolic derangement.Hyponatremia, hyperkalemia, acidosis, association with liver and kidney dysfunction was more severe in FT1 DM group.Association with pregnancy was more frequent as compared to the other 2 groups ( 22.2% vs 0, 0, X2 = 20.982, P = 0.000).Patients with slowonset type were relatively older and had greater BMI but lost more weight at diagnosis.The post-load C-peptides were relatively higher( (0.40 ±0.36) vs (0.10 ±0.13), (0.34 ±0.26) nmol/L, F=8.752,P < 0.05 ) in this group.Children and adolescents constituted a greater proportion in the acute-onset T1

  18. Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Salem, K A; Adrian, T E; Qureshi, M A; Parekh, K; Oz, M; Howarth, F C

    2012-12-01

    There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0

  19. Dermatomiositis juvenil

    OpenAIRE

    Goldaracena, Pablo; Pérez, Federico

    2008-01-01

    La dermatomiositis juvenil (DMJ) es una enfermedad multi sistémica de etiología desconocida, caracterizada por una vasculitis que ocasiona una inflamación no supurativa del músculo estriado y lesiones cutáneas distintivas. La cobertura de los criterios de Bohan y Peter establece el diagnóstico: exantema patognomónico junto a debilidad muscular proximal simétrica, elevación sérica de enzimas musculares, s...

  20. Heteroplasmy Level of the Mitochondrial tRNALeu(UUR) A3243G Mutation in a Chinese Family Is Positively Associated with Earlier Age-of-onset and Increasing Severity of Diabetes

    Institute of Scientific and Technical Information of China (English)

    Shi Zhang; An-li Tong; Yun Zhang; Min Nie; Yu-xiu Li; Heng Wang

    2009-01-01

    Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNALeu(UUR) A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980 (P = 0.02). Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNALeu(UUR) A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNALeu(UUR) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

  1. Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

    Science.gov (United States)

    Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

    2016-07-01

    New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

  2. Antihypertensive Drug Use and New-Onset Diabetes in Female Patients with Coronary Artery Disease: A Population-based Longitudinal Cohort Study.

    Science.gov (United States)

    Liou, Yi-Sheng; Chen, Hung-Yi; Tien, Lyun; Gu, Yi-Sian; Jong, Gwo-Ping

    2015-09-01

    Antihypertensives have been linked to new-onset diabetes (NOD) and different classes of antihypertensives may alter the risk for the development of NOD; however, the effect of different antihypertensives on the development of NOD in women with hypertension and coronary artery disease (CAD) has not been well studied. The purpose of this study is to investigate the association between usage of different antihypertensive drugs and the development of NOD in female patients with hypertension and CAD.Data in this retrospective cohort study were obtained from claim forms submitted to the Taiwan Bureau of National Health Insurance in central Taiwan during the period 2006-2011. We estimated the odds ratios (OR) to approximate the relative risk of NOD development associated with antihypertensive drug use.Of the 20,108 female patients with CAD at baseline, 2288 patients developed NOD during the 6-year follow-up. Subjects treated with angiotensin-converting enzyme (ACE) inhibitors (OR, 0.92; 95% confidence interval [CI], 0.84-1.00), angiotensin receptor blockers (OR, 0.92; 95% CI, 0.82-0.99), and alpha-blockers (OR, 0.88; 95% CI, 0.79-0.98) in the adjusted analyses had greater reductions of the risk than among nonusers. Patients who took diuretics (OR, 1.10; 95% CI, 1.01-1.20), beta-blockers (OR, 1.12; 95% CI, 1.04-1.21), and calcium channel blockers (OR, 1.10; 95% CI, 1.02-1.18) were at high risk of developing NOD than nonusers. Vasodilators were not associated with risk of NOD.We conclude that women with hypertension who take ACE inhibitors, angiotensin receptor blockers, and alpha-blockers are at lower risk of NOD and that use of diuretics, beta-blockers, and calcium channel blockers was associated with a significantly increased risk of developing NOD during the 6-year follow-up.

  3. Social relationships among young adults with insulin-dependent diabetes mellitus: ten-year follow-up of an onset cohort.

    Science.gov (United States)

    Jacobson, A M; Hauser, S T; Cole, C; Willett, J B; Wolfsdorf, J I; Dvorak, R; Wolpert, H; Herman, L; de Groot, M

    1997-01-01

    Past cross-sectional studies have suggested that young adults with insulin-dependent (Type 1) diabetes mellitus (IDDM) may experience problems in their close peer relationships. For 10 years, we have followed an onset cohort of children and adolescents with IDDM (n = 57) and an age-matched group who were originally recruited after an acute illness, accident, or injury (n = 54). Now aged 19-26 years, these two groups were compared in terms of their friendship patterns, dating and love experiences, and sense of loneliness. All subjects in both groups had at least one friend. However, the IDDM group reported fewer friendships overall. The difference was accounted for by the number of less intimate friends. The two groups had similar frequencies of current romantic partners (IDDM = 63%; comparison group = 64%). While dating attitude and dating assertiveness did not differ between groups, some differences were found in terms of experiences of a primary love relationship. IDDM patients experienced less trust and sense of intimate friendship in these love relationships. No differences in loneliness were found. The preponderance of our findings indicate that the two groups had similar patterns and experiences of close peer relationships. Thus, the study does not suggest that IDDM leads to serious problems in forming social relationships for these patients during the transition to young adulthood. On the other hand, the IDDM patients' lower level of trust and intimacy within love relationships are consistent with other findings from this study suggesting specific areas of lowered self-worth that appear in social relationships.

  4. Diabetes.

    Science.gov (United States)

    Lomberk, Gwen

    2009-01-01

    Pancreatologists have often divided research of the pancreas based upon the origin of the function or disease, namely the endocrine or exocrine pancreas. In fact, as a result, many of our meetings and conferences have followed separate paths. Interestingly, among patients with chronic pancreatitis and pancreatic cancer, both disorders of the exocrine pancreas, diabetes is common. However, the clinical features of the diabetes associated with these two differ. Peripheral insulin resistance and hyperinsulinemia are the predominant diabetic traits in pancreatic cancer, while reduced islet cell mass and impaired insulin secretion are observed more often in chronic pancreatitis. The causal relationship between diabetes and pancreatic cancer remains an intriguing but unanswered question. Since diabetes often precedes pancreatic cancer, it is regarded as a potential risk factor for malignancy. On the other hand, there remains the possibility that pancreatic cancer secretes diabetogenic factors. Regardless of how the science ultimately illuminates this issue, there is increasing interest in utilizing screening for diabetes to aid early detection of pancreatic tumor lesions. Therefore, in this issue of Pancreatology and the Web, we explore the topic of diabetes to keep us alert to this very important association, even if we study diseases of the exocrine pancreas.

  5. Diabetes, Glycemic Control, and New-Onset Heart Failure in Patients With Stable Coronary Artery Disease Data from the Heart and Soul Study

    NARCIS (Netherlands)

    van Melle, Joost P.; Bot, Marisica; De Jonge, Peter; De Boer, Rudolf A.; van Veldhuisen, Dirk J.; Whooley, Mary A.

    2010-01-01

    OBJECTIVE- Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS- We evaluated the association of diabetes and

  6. Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease : data from the heart and soul study

    NARCIS (Netherlands)

    van Melle, J.P.; Bot, M.; de Jonge, P.; de Boer, R.A.; van Veldhuisen, D.J.; Whooley, M.A.

    2010-01-01

    OBJECTIVE Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS We evaluated the association of diabetes and A

  7. Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease : data from the heart and soul study

    NARCIS (Netherlands)

    van Melle, J.P.; Bot, M.; de Jonge, P.; de Boer, R.A.; van Veldhuisen, D.J.; Whooley, M.A.

    2010-01-01

    OBJECTIVE Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS We evaluated the association of diabetes and

  8. Juvenile Huntington disease in Argentina.

    Science.gov (United States)

    Gatto, Emilia Mabel; Parisi, Virginia; Etcheverry, José Luis; Sanguinetti, Ana; Cordi, Lorena; Binelli, Adrian; Persi, Gabriel; Squitieri, Ferdinando

    2016-01-01

    We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors.

  9. Clinical presentation of juvenile Huntington disease

    Directory of Open Access Journals (Sweden)

    Ruocco Heloísa H.

    2006-01-01

    Full Text Available OBJECTIVE: To describe the clinical presentation a group of patients with juvenile onset of Huntington disease. METHOD: All patients were interviewed following a structured clinical questioner. Patients were genotyped for the trinucleotide cytosine-adenine-guanine (CAG repeat in the Huntington Disease gene. High resolution brain MRI was performed in all patients. RESULTS: We identified 4 patients with juvenile onset of disease among 50 patients with Huntington disease followed prospectively in our Neurogenetics clinic. Age at onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal inheritance of the disease. Expanded Huntington disease allele sizes varied from 41 to 69 trinucleotide repeats. The early onset patients presented with rigidity, bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume loss of caudate and putamen nuclei (p=0.001 and reduced cerebral and cerebellum volumes (p=0.01. CONCLUSION: 8% of Huntington disease patients seen in our clinic had juvenile onset of the disease. They did not present with typical chorea as seen in adult onset Huntington disease. There was a predominance of rigidity and bradykinesia. Two other important clinical features were seizures and ataxia, which related with the imaging findings of early cortical atrophy and cerebellum volume loss.

  10. Diabetes

    DEFF Research Database (Denmark)

    Damm, Peter; Mathiesen, Elisabeth R

    2015-01-01

    For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women with gestat......For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women...... with gestational diabetes mellitus is highly relevant....

  11. Antineutrophil cytoplasmic antibodies in juvenile chronic arthritis

    NARCIS (Netherlands)

    Mulder, L; Horst, G; Limburg, P; deGraeffMeeder, ER; Kuis, W; Kallenberg, C

    1997-01-01

    Objective, To evaluate the diagnostic significance of antineutrophil cytoplasmic antibodies (ANCA) by assessing the prevalence of ANCA in juvenile chronic arthritis (JCA) (n = 93) of either oligoarticular, polyarticular, or systemic onset. To investigate the prevalence of ANCA in other diseases of c

  12. A Practical Approach to Juvenile Dermatomyositis and Juvenile Scleroderma.

    Science.gov (United States)

    McCann, Liza J; Pain, Clare E

    2016-02-01

    Juvenile dermatomyositis and juvenile scleroderma are rare multisystem autoimmune disorders. Although they share some pathognomonic hallmarks with adult onset myositis or scleroderma, there are significant differences in presentation, characteristics and associated features when the diseases present in childhood. In view of this, and the rarity of the conditions, it is important for care to be led by teams with expertise in pediatric rheumatology conditions. Prognosis has improved significantly in the West; likely due to early diagnosis and aggressive treatment with immunosuppressive medications. However, this trend is not replicated in the developing world. Early recognition of these diseases is crucial to achieve rapid and sustained remission and prevent disease or medication associated complications. This article aims to provide a practical overview for recognition, diagnosis and treatment of these conditions.

  13. Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2016-01-01

    Full Text Available Maturity-onset diabetes of the young (MODY is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I and two HNF1A polymorphisms (p.I27L and p.S487N were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

  14. Diabetes

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for diabetes. The data is provided by three managed care organizations in Allegheny County (Gateway Health Plan,...

  15. The importance of general self-efficacy for the quality of life of adolescents with diabetes or juvenile rheumatoid arthritis over time: a longitudinal study among adolescents and parents

    Directory of Open Access Journals (Sweden)

    Jane Murray Cramm

    2013-11-01

    Full Text Available Purpose: To (i investigate the influence of general self-efficacy on quality of life outcomes over time among adolescents with type I diabetes or juvenile rheumatoid arthritis (JRA, (ii investigate parents’ perceptions of general self-efficacy and quality of life of adolescents with diabetes or JRA over time, and (iii identify possible differences in the evaluations of adolescents and parents. Methods: This study included adolescents aged 12–25 years with type I diabetes or JRA and their parents. At T1, 171/573 (30% response rate adolescents with diabetes or JRA and 229/563 (41% response rate parents completed the questionnaire. At T2, 230/551 (42% response rate adolescents and 220/559 (39% response rate parents still participating in the study completed the questionnaire. A total of 112 adolescents and 143 parents filled in the questionnaires at both T1 and T2.Results: Adolescents perceived significant improvement in their general self-efficacy and reduced quality of life over time, whereas parents’ perceptions did not change. According to adolescents and parents, physical functioning was better among adolescents with diabetes than among those with JRA. Regression analyses of adolescents’ data showed that general self-efficacy at T1 (β = 0.13; p ≤ 0.10 and changes in general self-efficacy (β = 0.22; p ≤ 0.01 predicted quality of life at T2. Parents’ responses revealed that adolescents’ general self-efficacy at T1 (β = 0.16; p ≤ 0.05 and changes in adolescents’ general self-efficacy (β = 0.18; p ≤ 0.05 predicted adolescents’ quality of life at T2. Conclusions: General self-efficacy and changes therein positively affected quality of life in adolescents with diabetes or JRA over time, as perceived by adolescents and parents. These findings emphasise the need for the implementation of interventions aiming to improve general self-efficacy in these populations.

  16. Discussion of Deficiency of Liver-YIN in Type 2 Diabetes Mellitus Onset%论肝阴虚在2型糖尿病发病中的地位

    Institute of Scientific and Technical Information of China (English)

    谢斌; 俞大军

    2011-01-01

    根据糖尿病的病机特点,结合现代中西医学研究成果,探讨肝阴虚致毒邪胶结与2型糖尿病肝内炎症的相互关系,提出肝阴虚致2型糖尿病肝内炎症的可能途径,阐述肝阴虚在2型糖尿病发病中的地位,为丰富和发展2型糖尿病中医防治理论提供有益的借鉴.%According to the pathogenesis characteristic of diabetes, combining with modem research achievement of Chinese medicine and Western medicine, the article approached interrelation between inflammation in liver of type 2 diabetes mellitus and cementation of toxin pathogen induced by deficiency of liver - YIN, proposed possible path of inflammation in liver of type 2 diabetes mellitus induced by deficiency of liver - YIN .discussed the position of deficiency of liver - YIN in type 2 diabetes mellitus onset, provided beneficial referencein for affluencing and developing and traditional Chinese medicine control theory for type 2 diabetes mellitus.

  17. Early-onset type 2 diabetes in a Mexican survey: results from the National Health and Nutrition Survey 2006 Diabetes tipo 2 de inicio temprano en una encuesta nacional: resultados de la Encuesta Nacional de Salud y Nutrición 2006

    Directory of Open Access Journals (Sweden)

    Aída Jiménez-Corona

    2010-01-01

    Full Text Available OBJECTIVE: To describe the characteristics of patients with type 2 diabetes diagnosed before age 40 (early-onset type 2 diabetes identified in a nation-wide, population-based study. MATERIALS AND METHODS: The survey was done in Mexico during 2006. Medical history, anthropometric and biochemical measurements were obtained in every subject. RESULTS: Cases diagnosed before (n=181 and after age 40 (n=659 were included. Early-onset type 2 diabetes was present in 13.1% of the previously diagnosed, 30.3% of the cases identified during the survey and 21.5% of the whole population with diabetes. These individuals had a greater prevalence of obesity and hypertriglyceridemia compared to the cases diagnosed after age 40. CONCLUSIONS: Early-onset type 2 diabetes was present in 21.5 % of patients with type 2 diabetes in Mexico. Close to 70% of them were obese or overweight and had the clinical profile of the metabolic syndrome.OBJETIVO: Describir las características de los pacientes con diabetes diagnosticados antes de los 40 años en una encuesta representativa de la población mexicana. MATERIAL Y MÉTODOS: La encuesta fue realizada en México durante 2006. Se registró la historia médica, mediciones antropométricas y bioquímicas de los participantes. RESULTADOS: Se incluyeron casos diagnosticados antes (n=181 y después (n=659 de los 40 años. La diabetes tipo 2 de inicio temprano está presente en 13.1% de los casos previamente diagnosticados, 30.3% de los identificados durante la encuesta y en 21.5% de la población total con diabetes. En los casos diagnosticados antes de los 40 años hay una prevalencia mayor de obesidad e hipertrigliceridemia que en los diagnosticados después de los 40. CONCLUSIONES: La diabetes de aparición temprana está presente en 21.5% de los casos con diabetes en México. Setenta por ciento de ellos tenían un peso mayor al saludable y tenían el perfil clínico del síndrome metabólico.

  18. Preliminary study of alleviating new onset diabetic NOD mice by a DPP-Ⅳ inhibitor%二肽基肽酶Ⅳ抑制剂治疗NOD小鼠新发糖尿病初步研究

    Institute of Scientific and Technical Information of China (English)

    田磊; 周燕; 覃新干; 顾永耀; 吴向华; 李杰华; 桂小龙

    2010-01-01

    观察二肽基肽酶Ⅳ(dipeptidyl peptidase Ⅳ,DPP-Ⅳ)抑制剂NVP-DPF728对雌性非肥胖性糖尿病(non-obese diabetic,NOD)小鼠发病早期治疗作用.结果 显示,给药组20只小鼠中15只血糖逆转,逆转率为75%;血糖逆转的NOD小鼠,血清中转化生长因子β1、胰升糖素样肽1浓度显著升高,胰岛炎的程度显著减轻,腹腔淋巴结、胸腺中Tregs占总T细胞百分比显著升高(P<0.05).NVP-DPP728能够缓解胰岛炎和调节自身免疫反应,有效治疗NOD小鼠新发糖尿病.%To investigate the effect of NVP-DPP728, a DPP-Ⅳ inhibitor on new-onset diabetes and the autoimmune response in non-obese diabetic ( NOD ) mice. Diabetes could be reversed in 75% of NVP-DPP728 treated 20 NOD mice. In these 15 mice with remission, insulitis scores were significantly lower than those of the control group. The percentage of Tregs was increased in the thymus and celiac lymph nodes, plasma TGF-β1 and GLP-1 were also significantly increased ( P<0. 01 ). NVP-DPP728 treatment may reverse new-onset diabetes in NOD mice by reducing insulitis and increasing Tregs.

  19. Urinary proteomics predict onset of microalbuminuria in normoalbuminuric type 2 diabetic patients, a sub-study of the DIRECT-Protect 2 study

    DEFF Research Database (Denmark)

    Lindhardt, Morten; Persson, Frederik; Zürbig, Petra

    2016-01-01

    BACKGROUND: Early prevention of diabetic nephropathy is not successful as early interventions have shown conflicting results, partly because of a lack of early and precise indicators of disease development. Urinary proteomics has shown promise in this regard and could identify those at high risk...... who might benefit from treatment. In this study we investigate its utility in a large type 2 diabetic cohort with normoalbuminuria. METHODS: We performed a post hoc analysis in the Diabetic Retinopathy Candesartan Trials (DIRECT-Protect 2 study), a multi centric randomized clinical controlled trial...... strategies for diabetic nephropathy....

  20. Thrombocytopenia-associated multiorgan failure occurring in an infant at the onset of type 1 diabetes successfully treated with fresh frozen plasma.

    Science.gov (United States)

    Kumar, Revati; McSharry, Brent; Bradbeer, Peter; Wiltshire, Esko; Jefferies, Craig

    2016-07-01

    TAMOF is a devastating microangiopathy that can occur in association with the new onset of T1DM, and should be considered with the onset of thrombocytopenia, renal failure, and raised LDH. Treatment with fresh frozen plasma should be considered as a first-line option in such cases prior to plasma exchange.

  1. [Juvenile monomelic amyotrophy: Hirayama disease].

    Science.gov (United States)

    Drozdowski, W; Baniukiewicz, E; Lewonowska, M

    1998-01-01

    We present three patients with unilateral upper limb weakness (with muscular atrophy)-two of them with distal and one with proximal localization. The disease onset was between 18th end 35-th year of life; the disease course was biphasic (i.e. progressive within first 1 to 3 years, and stabilized during following 4-24 years). The laboratory investigations permitted to diagnose juvenile monomelic amyotrophy, an entity that is very rare outside Japan. Electromyography revealed neurogenic involvement with spinal features also in clinically unaffected muscles. We suggest that these results may support the hypothesis of this disease being a benign variant of spinal muscular atrophy.

  2. Pro12Ala gene polymorphism in the peroxisome proliferator-activated receptor gamma as a risk factor for the onset of type 2 diabetes mellitus in the Serbian population

    Directory of Open Access Journals (Sweden)

    Šoškić Sanja

    2010-01-01

    Full Text Available The peroxisome proliferator-activated receptor gamma (PPARγ is a gene candidate for the onset of type 2 diabetes mellitus (T2DM. We investigated the association of the PPARγ Pro12Ala gene with the onset of T2DM for the first time in the Serbian population. The study population consisted of 197 controls and 163 T2DM patients. The 12Ala allele tended to be more frequent in the group of T2DM patients (0.11 compared to the control subjects (0.09. The results from this study indicate that the PPARγ2 12Ala allele presents a non-significant risk factor for T2DM development in the Serbian population.

  3. Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young

    DEFF Research Database (Denmark)

    Østoft, Signe Harring; Bagger, Jonatan Ising; Hansen, Torben;

    2015-01-01

    )), and dipeptidyl-peptidase 4 (DPP-4) enzymatic activity in patients with glucokinase (GCK)-diabetes (MODY2), hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), and in matched healthy individuals (CTRLs). Subjects and methods: Ten patients with GCK-diabetes (age: 43±5 years; BMI: 24±2 kg/m2; FPG: 7.1±0.3 mmol...... with a liquid test meal. Results: All groups exhibited similar baseline values of glucagon (7±1 (GCK-diabetes), 6±1 pmol/l (HNF1A-diabetes), 8±2 (CTRLs), P=0.787), but patients with HNF1A-diabetes exhibited postprandial hyperglucagonaemia (area under curve (AUC): 838±108 min×pmol/l) compared to CTRLs (182......±176 min×pmol/l, P=0.005) and tended to have a greater response than patients with GCK-diabetes (410±154 min×pmol/l, P=0.063). Similar peak concentrations and AUCs for plasma GIP and plasma GLP-1 were observed across the groups. Increased fasting DPP-4-activity was seen in patients with HNF1A-diabetes (17...

  4. TYPE 1 DIABETES AND ITS LONG DURATION EFFECT ON COGNITIVE FUNCTIONS: AN ASSESSMENT IN ALLOXAN INDUCED DIABETIC RATS

    Directory of Open Access Journals (Sweden)

    Mahaboob Basha P

    2013-10-01

    Full Text Available Despite the enormous research in the field of Diabetology, its prevalence and complications are raising. Studies made on diabetic subjects showed deficits in cognition and memory in children suffering from long term diabetes. The relationship between cognitive dysfunction and type-1 diabetes of early onset has not been addressed properly. Hence, this study was made to investigate the effect of different duration diabetes onset on cognitive dysfunction. Using alloxan (200 mg/kg bw induced diabetic rats learning and memory assessments were made, in addition oxidative stress indices studied. The results indicate that the duration of diabetes has significant contribution in learning and memory deficits, which were irreversible and the activity levels of CAT (P < 0.05, SOD, GST (P < 0.05, and GPx (P < 0.05 showed greater impact of free radical damage on hippocampal circuitry. The atrophic changes observed in hippocampal region corroborates the difficulties in learning and memory, and the degenerative changes were most striking in the cells of CA-1 and CA-3 hippocampal regions which could be linked to deficits in certain cognitive domains, such as memory, information processing speed, executive function, attention and motor speed. It is evident from data that brain tissue is not spared by diabetes and diabetic encephalopathy occurs due to metabolic perturbations by hyperglycaemia, insulin deficiency. The findings of this study strongly advocate that learning ability and memory have a direct relation to the duration of the diabetes. The clinical implication of the study highlights the importance of early diagnosis and treatment of juvenile diabetes induced cognitive deficits among children.

  5. The time has come to test the beta cell preserving effects of exercise in patients with new onset type 1 diabetes

    DEFF Research Database (Denmark)

    Narendran, Parth; Solomon, Thomas; Kennedy, Amy

    2015-01-01

    Type 1 diabetes is characterised by immune-mediated destruction of insulin-producing beta cells. Significant beta cell function is usually present at the time of diagnosis with type 1 diabetes, and preservation of this function has important clinical benefits. The last 30 years have seen a number...... for physical exercise as a therapy for the preservation of beta cell function in patients with newly diagnosed type 1 diabetes. We highlight possible mechanisms by which exercise could preserve beta cell function and then present evidence from other models of diabetes that demonstrate that exercise preserves...... beta cell function. We conclude by proposing that there is now a need for studies to explore whether exercise can preserve beta cell in patients newly diagnosed with type 1 diabetes....

  6. A genetic map of chromosome 20q12-q13.1: Multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the young (MODY) locus

    OpenAIRE

    1993-01-01

    Multiple highly polymorphic markers have been used to construct a genetic map of the q12-q13.1 region of chromosome 20 and to map the location of the maturity-onset diabetes of the young (MODY) locus. The genetic map encompasses 23 cM and includes 11 loci with PIC values >.50, seven of which have PICs >.70. New dinucleotide repeat polymorphisms associated with the D20S17, PPGB, and ADA loci have been identified and mapped. The dinucleotide repeat polymorphisms have increased the PIC of the AD...

  7. Circulating preproinsulin signal peptide-specific CD8 T cells restricted by the susceptibility molecule HLA-A24 are expanded at onset of type 1 diabetes and kill β-cells.

    Science.gov (United States)

    Kronenberg, Deborah; Knight, Robin R; Estorninho, Megan; Ellis, Richard J; Kester, Michel G; de Ru, Arnoud; Eichmann, Martin; Huang, Guo C; Powrie, Jake; Dayan, Colin M; Skowera, Ania; van Veelen, Peter A; Peakman, Mark

    2012-07-01

    Type 1 diabetes results from T cell-mediated β-cell destruction. The HLA-A*24 class I gene confers significant risk of disease and early onset. We tested the hypothesis that HLA-A24 molecules on islet cells present preproinsulin (PPI) peptide epitopes to CD8 cytotoxic T cells (CTLs). Surrogate β-cell lines secreting proinsulin and expressing HLA-A24 were generated and their peptide ligandome examined by mass spectrometry to discover naturally processed and HLA-A24-presented PPI epitopes. A novel PPI epitope was identified and used to generate HLA-A24 tetramers and examine the frequency of PPI-specific T cells in new-onset HLA-A*24(+) patients and control subjects. We identified a novel naturally processed and HLA-A24-presented PPI signal peptide epitope (PPI(3-11); LWMRLLPLL). HLA-A24 tetramer analysis reveals a significant expansion of PPI(3-11)-specific CD8 T cells in the blood of HLA-A*24(+) recent-onset patients compared with HLA-matched control subjects. Moreover, a patient-derived PPI(3-11)-specific CD8 T-cell clone shows a proinflammatory phenotype and kills surrogate β-cells and human HLA-A*24(+) islet cells in vitro. These results indicate that the type 1 diabetes susceptibility molecule HLA-A24 presents a naturally processed PPI signal peptide epitope. PPI-specific, HLA-A24-restricted CD8 T cells are expanded in patients with recent-onset disease. Human islet cells process and present PPI(3-11), rendering themselves targets for CTL-mediated killing.

  8. A family with a novel termination mutation in hepatic nuclear factor 1α in maturity-onset diabetes of the young type 3 which is unresponsive to sulphonylurea therapy.

    Science.gov (United States)

    Demol, S; Lebenthal, Y; Bar-Meisels, M; Phillip, M; Gat-Yablonski, G; Gozlan, Y

    2014-01-01

    Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus. To identify the genetic basis in a family with 3 generations of diabetes and to assess the concordance between the genotype and phenotype. A molecular analysis was performed on genomic DNA using polymerase chain reaction, denaturing gradient gel electrophoresis, and sequencing. A mixed-meal tolerance test (MMTT) was performed with/without glibenclamide. Abdominal ultrasonography was performed on all family members with diabetes due to the location of the mutation. A novel c.618G>A, p.W206X termination mutation was identified in the hepatic nuclear factor 1α (HNF1α) gene. The mutation was identified in the proband and 8 of the 14 family members tested. An MMTT stimulus (±2.5 and 5 mg glibenclamide) produced a similar glucose profile and C-peptide graph in both the obese proband and her nonobese mother, showing no effect of the glibenclamide. No evidence of liver adenomas was found in the abdominal ultrasonography. We described a novel c.618G>A, p.W206X mutation in HNF1α associated with MODY 3 but not with hepatocellular adenoma. In contradistinction to most MODY 3 mutations, treatment with sulphonylurea was found to be a clinically ineffective alternative to insulin therapy.

  9. What Is Juvenile Arthritis?

    Science.gov (United States)

    ... Analgesics for Osteoarthritis (Report from AHRQ) Joint Replacement Surgery: Health Information Basics for You and Your Family NIH Pediatric Rheumatology Clinic Health Information Juvenile Arthritis Find a Clinical Trial Journal Articles Juvenile Arthritis PDF Version Size: 123 KB ...

  10. Juvenile Delinquency: An Introduction

    Science.gov (United States)

    Smith, Carolyn A.

    2008-01-01

    Juvenile Delinquency is a term which is often inaccurately used. This article clarifies definitions, looks at prevalence, and explores the relationship between juvenile delinquency and mental health. Throughout, differences between males and females are explored. (Contains 1 table.)

  11. Parenting and juvenile delinquency

    NARCIS (Netherlands)

    Hoeve, Machteld

    2008-01-01

    Juvenile delinquency is a noteworthy problem. This thesis addressed the association between parenting and juvenile delinquency by analyzing the concepts of parenting adopted in family research in relation to criminological concepts and measures of delinquent behavior. Four studies were conducted.

  12. No Contribution of GAD-65 and IA-2 Autoantibodies around Time of Diagnosis to the Increasing Incidence of Juvenile Type 1 Diabetes

    DEFF Research Database (Denmark)

    Thorsen, Steffen U.; Pipper, Christian B.; Mortensen, Henrik B.;

    2016-01-01

    Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D) has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinom...

  13. Juvenile Arrests, 2007. Juvenile Justice Bulletin

    Science.gov (United States)

    Puzzanchera, Charles

    2009-01-01

    This Bulletin summarizes 2007 juvenile crime and arrest data reported by local law enforcement agencies across the country and cited in the FBI report, "Crime in the United States 2007." The Bulletin describes the extent and nature of juvenile crime that comes to the attention of the justice system. It serves as a baseline for comparison for…

  14. Juvenile polyposis syndrome

    NARCIS (Netherlands)

    L.A.A. Brosens; D. Langeveld; W.A. van Hattem; F.M. Giardiello; G.J.A. Offerhaus

    2011-01-01

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a

  15. SUBTYPES OF JUVENILE SYSTEMIC SCLERODERMA

    Directory of Open Access Journals (Sweden)

    M N Slarovoitova

    2001-01-01

    Full Text Available Aim: to allot clinical forms of juvenile systemic scleroderma (JSSD. Material and methods: investigation and dynamic observation of 60 patients aged 14-54 (mean age 25.1 ±7.2 with onset of disease in child's and adolescent’s ages from 1 to 16 years old ( in average 11. 4±3.8 year old and disease duration from 1 to 39 years (in average 13.1 ±7.9. Results: 55% of patients demonstrated JSSD subtype with focal cutaneous lesion of different localization. The possibility of overlap-syndrome development in JSSD patients with onset in adolescent age typical for SSD-rheumatoid arthritis, SSD-polymvositis should be underlined. Conclusion: knowledge of different clinical forms and courses of the disease, modern diagnostics and early beginning of differential JSSD treatment will enable us to improve the prognosis and disease outcome.

  16. Obesity and diabetes epidemics: cancer repercussions.

    Science.gov (United States)

    Hjartåker, Anette; Langseth, Hilde; Weiderpass, Elisabete

    2008-01-01

    The prevalence of overweight (body mass index, BMI, between 25 and 30 kg/m2) and obesity (BMI of 30 kg/m2 or higher) is increasing rapidly worldwide, especially in developing countries and countries undergoing economic transition to a market economy. One consequence of obesity is an increased risk of developing type II diabetes. Overall, there is considerable evidence that overweight and obesity are associated with risk for some of the most common cancers. There is convincing evidence of a positive association between overweight/obesity and risk for adenocarcinoma of the oesophagus and the gastric cardia, colorectal cancer, postmenopausal breast cancer, endometrial cancer and kidney cancer (renal-cell). Premenopausal breast cancer seems to be inversely related to obesity. For all other cancer sites the evidence of an association between overweight/obesity and cancer is inadequate, although there are studies suggesting an increased risk of cancers of the liver, gallbladder, pancreas, thyroid gland and in lymphoid and haematopoietic tissue. Far less is known about the association between diabetes mellitus type I (also called insulin dependent diabetes mellitus or juvenile diabetes), type II diabetes (called non-insulin dependent diabetes mellitus or adult onset diabetes mellitus) and cancer risk. The most common type of diabetes mellitus, type II, seems to be associated with liver and pancreas cancer and probably with colorectal cancer. Some studies suggest an association with endometrial and postmenopausal breast cancer. Studies reporting on the association between type I diabetes mellitus, which is relatively rare in most populations and cancer risk are scanty, but suggest a possible association with endometrial cancer. Overweight and obesity, as well as type II diabetes mellitus are largely preventable through changes in lifestyle. The fundamental causes of the obesity epidemic-and consequently the diabetes type II epidemic-are societal, resulting from an