Light-intensity physical activity is associated with insulin resistance in elderly Japanese women independent of moderate-to vigorous-intensity physical activity.

Science.gov (United States)

Gando, Yuko; Murakami, Haruka; Kawakami, Ryoko; Tanaka, Noriko; Sanada, Kiyoshi; Tabata, Izumi; Higuchi, Mitsuru; Miyachi, Motohiko

2014-02-01

It is unclear whether light physical activity is beneficially associated with insulin resistance, similar to moderate and/or vigorous physical activity. This cross-sectional study was performed to determine the relationship between the amount of light physical activity, as determined with a triaxial accelerometer, and insulin resistance. A total of 807 healthy men and women participated in this study. Physical activity was measured using a triaxial accelerometer worn for 28 days and summarized as light intensity (1.1-2.9 METs) or moderate to vigorous intensity (≥ 3.0 METs). Insulin resistance was evaluated by HOMA_R (FPG [mg/dL] × IRI [μU/mL]/405). The daily time spent in light physical activity was inversely associated with HOMA_R (r = -0.173, P physical activity and HOMA_R remained statistically significant (β = -0.119, P physical activity remained significantly associated with HOMA_R following further adjustment for moderate to vigorous intensity activity (β = -0.125, P physical activity was modeled as quartiles, especially in elderly women. These cross-sectional data suggest that light-intensity physical activity is beneficially associated with insulin resistance in elderly Japanese women.

A periodic-type dose effect of insulin in the blood glucose level of a ...

African Journals Online (AJOL)

We investigated in this paper the effect of a periodic-type insulin dose on a diabetic patient. An appropriate matching condition is introduced in our problem by expressing the insulin dose using a Fourier series expansion. Our result gives insight to the state of the patient over a period of administration. Clearly, there is the ...

How and why do patients with Type 1 diabetes sustain their use of flexible intensive insulin therapy? A qualitative longitudinal investigation of patients' self-management practices following attendance at a Dose Adjustment for Normal Eating (DAFNE) course.

Science.gov (United States)

Rankin, D; Cooke, D D; Clark, M; Heller, S; Elliott, J; Lawton, J

2011-05-01

Conventional insulin therapy requires patients with Type 1 diabetes to adhere to rigid dietary and insulin injection practices. Recent trends towards flexible intensive insulin therapy enable patients to match insulin to dietary intake and lifestyle; however, little work has examined patients' experiences of incorporating these practices into real-life contexts. This qualitative longitudinal study explored patients' experiences of using flexible intensive insulin therapy to help inform the development of effective long-term support. Semi-structured interviews were conducted with 30 adult patients with Type 1 diabetes following participation in a structured education programme on using flexible intensive insulin therapy, and 6 and 12 months post-course. Longitudinal data analysis used an inductive, thematic approach. Patients consistently reported feeling committed to and wanting to sustain flexible intensive insulin therapy. This regimen was seen as a logical and effective method of self-management, as patients experienced improved blood glucose readings and/or reported feeling better. Implementing and sustaining flexible intensive insulin therapy was enhanced when patients had stable routines, with more challenges reported by those working irregular hours and during weekends/holidays. Some patients re-crafted their lives to make this approach work for them; for instance, by creating dietary routines or adjusting dietary choices. Clinical data have shown that flexible intensive insulin therapy can lead to improvement in glycaemic control. This study, drawing on patients' perspectives, provides further endorsement for flexible intensive insulin therapy by demonstrating patients' liking of, and their motivation to sustain, this approach over time. To help patients implement and sustain flexible intensive insulin therapy, follow-up support should encourage them to identify routines to better integrate this regimen into their lives. © 2011 The Authors. Diabetic

Social, Organizational, and Contextual Characteristics of Clinical Decision Support Systems for Intensive Insulin Therapy: A Literature Review and Case Study

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Campion, Thomas R.; Waitman, Lemuel R.; May, Addison K.; Ozdas, Asli; Lorenzi, Nancy M.; Gadd, Cynthia S.

2009-01-01

Introduction: Evaluations of computerized clinical decision support systems (CDSS) typically focus on clinical performance changes and do not include social, organizational, and contextual characteristics explaining use and effectiveness. Studies of CDSS for intensive insulin therapy (IIT) are no exception, and the literature lacks an understanding of effective computer-based IIT implementation and operation. Results: This paper presents (1) a literature review of computer-based IIT evaluations through the lens of institutional theory, a discipline from sociology and organization studies, to demonstrate the inconsistent reporting of workflow and care process execution and (2) a single-site case study to illustrate how computer-based IIT requires substantial organizational change and creates additional complexity with unintended consequences including error. Discussion: Computer-based IIT requires organizational commitment and attention to site-specific technology, workflow, and care processes to achieve intensive insulin therapy goals. The complex interaction between clinicians, blood glucose testing devices, and CDSS may contribute to workflow inefficiency and error. Evaluations rarely focus on the perspective of nurses, the primary users of computer-based IIT whose knowledge can potentially lead to process and care improvements. Conclusion: This paper addresses a gap in the literature concerning the social, organizational, and contextual characteristics of CDSS in general and for intensive insulin therapy specifically. Additionally, this paper identifies areas for future research to define optimal computer-based IIT process execution: the frequency and effect of manual data entry error of blood glucose values, the frequency and effect of nurse overrides of CDSS insulin dosing recommendations, and comprehensive ethnographic study of CDSS for IIT. PMID:19815452

Social, organizational, and contextual characteristics of clinical decision support systems for intensive insulin therapy: a literature review and case study.

Science.gov (United States)

Campion, Thomas R; Waitman, Lemuel R; May, Addison K; Ozdas, Asli; Lorenzi, Nancy M; Gadd, Cynthia S

2010-01-01

Evaluations of computerized clinical decision support systems (CDSS) typically focus on clinical performance changes and do not include social, organizational, and contextual characteristics explaining use and effectiveness. Studies of CDSS for intensive insulin therapy (IIT) are no exception, and the literature lacks an understanding of effective computer-based IIT implementation and operation. This paper presents (1) a literature review of computer-based IIT evaluations through the lens of institutional theory, a discipline from sociology and organization studies, to demonstrate the inconsistent reporting of workflow and care process execution and (2) a single-site case study to illustrate how computer-based IIT requires substantial organizational change and creates additional complexity with unintended consequences including error. Computer-based IIT requires organizational commitment and attention to site-specific technology, workflow, and care processes to achieve intensive insulin therapy goals. The complex interaction between clinicians, blood glucose testing devices, and CDSS may contribute to workflow inefficiency and error. Evaluations rarely focus on the perspective of nurses, the primary users of computer-based IIT whose knowledge can potentially lead to process and care improvements. This paper addresses a gap in the literature concerning the social, organizational, and contextual characteristics of CDSS in general and for intensive insulin therapy specifically. Additionally, this paper identifies areas for future research to define optimal computer-based IIT process execution: the frequency and effect of manual data entry error of blood glucose values, the frequency and effect of nurse overrides of CDSS insulin dosing recommendations, and comprehensive ethnographic study of CDSS for IIT. Copyright (c) 2009. Published by Elsevier Ireland Ltd.

The Comparison of Two Methods of Exercise (intense interval training and concurrent resistance- endurance training on Fasting Sugar, Insulin and Insulin Resistance in Women with Mellitus Diabetes

Directory of Open Access Journals (Sweden)

F Bazyar

2016-05-01

Full Text Available Background & aim: Exercise is an important component of health and an integral approach to the management of diabetes mellitus. The purpose of this study was to compare the effects of intense interval training and concurrent resistance- endurance training on fasting sugar, insulin and insulin resistance in women with mellitus diabetes.   Methods: Fifty-two overweight female diabetic type 2 patients (aged 45-60 years old with fasting blood glucose≥ 126 mg/dl were selected to participate in the present study. Participants were assigned to intense interval training group (N=17, concurrent resistance- endurance training group (N=17 and control group (N=18. The exercises incorporated 10 weeks of concurrent resistance- endurance training and intense interval training. Fasting blood sugar, serum insulin concentrations levels were measured. Concurrent training group trained eight weeks, three times a week of endurance training at 60% of maximum heart rate (MHR and two resistance training sessions per week with 70% of one repetition maximum (1-RM. Intense interval training group trained for eight weeks, three sessions per week for 4 to 10 repeats Wingate test on the ergometer 30s performed with maximum effort. The control group did no systematic exercise. At the end of experiment 42 subjects were succeed and completed the study period, and 10 subjects were removed due to illness and absence in the exercise sessions. Fasting blood sugar and insulin levels 24 hours before and 48 hours after the last training session was measured.   Results: The findings indicated that in periodic fasting, the blood sugar in intensive training group had a marked decrease (p= 0.000 however, the fasting blood sugar of exercise and power stamina groups reduced significantly (p=0.062. The results showed no significant difference between the groups (171/0 p =0.171. Fasting insulin (p <0.001 and insulin resistance (0001/0 = p=0.001 in periodic intensive training group were

High intensity interval training improves liver and adipose tissue insulin sensitivity

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Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

Evaluation of Total Daily Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the Hospital

Science.gov (United States)

2016-05-20

regular insulin has significantly increased in recent years. These patients are severely insulin resistant requiring high doses of insulin to achieve...on U-500 Insulin Admitted to the Hospital presented at SURF Conference, San Antonio, TX 20 May 201 6 with MDWI 41-108, and has been assigned local...59th CSPG/SGVU) C.201 4 . I 52d PROTOCOL TITLE Evaluation of Total Dai ly Dose and Glycemic Control for Patients on U-500 Insulin Admitted to the

Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Schmidt, S; Madsbad, Sten

2016-01-01

AIM: To investigate the dose-response relationship of subcutaneous glucagon administration on plasma glucose and on counterregulatory hormone responses during subcutaneous insulin induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. MATERIALS AND METHODS: Eight...... hypoglycaemia in patients with type 1 diabetes....... insulin pump treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by a subcutaneous insulin bolus and when plasma glucose reached 3.4 mmol/l (95%CI 3.2-3.5), a subcutaneous bolus of either 100, 200, 300 µg glucagon or saline...

Smartphone apps for calculating insulin dose: a systematic assessment.

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Huckvale, Kit; Adomaviciute, Samanta; Prieto, José Tomás; Leow, Melvin Khee-Shing; Car, Josip

2015-05-06

Medical apps are widely available, increasingly used by patients and clinicians, and are being actively promoted for use in routine care. However, there is little systematic evidence exploring possible risks associated with apps intended for patient use. Because self-medication errors are a recognized source of avoidable harm, apps that affect medication use, such as dose calculators, deserve particular scrutiny. We explored the accuracy and clinical suitability of apps for calculating medication doses, focusing on insulin calculators for patients with diabetes as a representative use for a prevalent long-term condition. We performed a systematic assessment of all English-language rapid/short-acting insulin dose calculators available for iOS and Android. Searches identified 46 calculators that performed simple mathematical operations using planned carbohydrate intake and measured blood glucose. While 59% (n = 27/46) of apps included a clinical disclaimer, only 30% (n = 14/46) documented the calculation formula. 91% (n = 42/46) lacked numeric input validation, 59% (n = 27/46) allowed calculation when one or more values were missing, 48% (n = 22/46) used ambiguous terminology, 9% (n = 4/46) did not use adequate numeric precision and 4% (n = 2/46) did not store parameters faithfully. 67% (n = 31/46) of apps carried a risk of inappropriate output dose recommendation that either violated basic clinical assumptions (48%, n = 22/46) or did not match a stated formula (14%, n = 3/21) or correctly update in response to changing user inputs (37%, n = 17/46). Only one app, for iOS, was issue-free according to our criteria. No significant differences were observed in issue prevalence by payment model or platform. The majority of insulin dose calculator apps provide no protection against, and may actively contribute to, incorrect or inappropriate dose recommendations that put current users at risk of both catastrophic overdose and more

Changes of β-cell function after short-term transient intensive insulin treatment in newly diagnosed type 2 diabetes patients

International Nuclear Information System (INIS)

Tian Xiaoping; Zhuang Huiqin; Su Cainu; Xu Ning; Yin Dong; Hui Yuan; Wu Yan

2007-01-01

To evaluate the effect of short-term intensive insulin treatment on β-cell function in newly diagnosed type 2 diabetes patients with apparently hyperglycemia, twenty-four newly diagnosed type 2 diabetes patients with FPG more than 12.0 mmol/L were treated by short-term transient intensive insulin in average 9.04-4.8 days. Their β-cell function was assessed by oral glucose tolerance test. The FPG, HbAlc and HOMA IR of patients were significantly decreased (P<0.01), while the insulin, the Area Under Curve (AUC) of insulin and HOMA β were significantly increased (P<0.01) after the treatment with insulin. Improvement of β-cell function can be induced by short-term intensive insulin treatment for newly diagnosed type 2 diabetes patients with apparently hyperglycemia. (authors)

Dosing Accuracy of Insulin Aspart FlexPens After Transport Through the Pneumatic Tube System.

Science.gov (United States)

Ward, Leah G; Heckman, Michael G; Warren, Amy I; Tran, Kimberly

2013-01-01

The purpose of this study was to evaluate whether transporting insulin aspart FlexPens via a pneumatic tube system affects the dosing accuracy of the pens. A total of 115 Novo Nordisk FlexPens containing insulin aspart were randomly assigned to be transported via a pneumatic tube system (n = 92) or to serve as the control (n = 23). Each pen was then randomized to 10 international unit (IU) doses (n = 25) or 30 IU doses (n = 67), providing 600 and 603 doses, respectively, for the pneumatic tube group. The control group also received random assignment to 10 IU doses (n = 6) or 30 IU doses (n = 17), providing 144 and 153 doses, respectively. Each dose was expelled using manufacturer instructions. Weights were recorded, corrected for specific gravity, and evaluated based on acceptable International Organization for Standardization (ISO) dosing limits. In the group of pens transported through the pneumatic tube system, none of the 600 doses of 10 IU (0.0%; 95% CI, 0.0 to 0.6) and none of the 603 doses of 30 IU (0.0%; 95% CI, 0.0 to 0.6) fell outside of the range of acceptable weights. Correspondingly, in the control group, none of the 144 doses at 10 IU (0.0%; 95% CI, 0.0 to 2.5) and none of the 153 doses at 30 IU (0.0%; 95% CI, 0.0 to 2.4) were outside of acceptable ISO limits. Transportation via pneumatic tube system does not appear to compromise dosing accuracy. Hospital pharmacies may rely on the pneumatic tube system for timely and accurate transport of insulin aspart FlexPens.

Islet oxygen consumption rate (OCR) dose predicts insulin independence for first clinical islet allotransplants

Science.gov (United States)

Kitzmann, JP; O’Gorman, D; Kin, T; Gruessner, AC; Senior, P; Imes, S; Gruessner, RW; Shapiro, AMJ; Papas, KK

2014-01-01

Human islet allotransplant (ITx) for the treatment of type 1 diabetes is in phase III clinical registration trials in the US and standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose stimulated insulin release (GSIR), and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following one transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. In this paper we report on the assessment of clinical islet allograft preparations using islet oxygen consumption rate (OCR) dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results showed that OCR dose was most predictive of CTO. IE dose was also highly predictive, while GSIR and membrane integrity stains were not. In conclusion, OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical ITx. PMID:25131089

Evaluation of Total Daily Dose and Glycemic Control for Patients Taking U-500 Insulin Admitted to the Hospital

Science.gov (United States)

2016-04-27

mail:jack.e.lewi.mil@mail.mil Key Words: U-500 regular insulin , inpatient diabetes mellitus, insulin resistance Conflict of Interest Statements...500 regular insulin are severely insulin resistant requiring high doses of insulin . It has been observed that a patient’s insulin requirements may...concentrated than U-100 regular insulin and is generally used in patients with severe insulin resistance requiring greater than 200 units of insulin

Conversion from insulin glargine U-100 to insulin glargine U-300 or insulin degludec and the impact on dosage requirements.

Science.gov (United States)

Pearson, Scott M; Trujillo, Jennifer M

2018-04-01

We wanted to determine whether basal insulin requirements change when patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or insulin degludec. This study involved subjects seen in the University of Colorado Health Endocrine Clinic who were transitioned from Gla-100 to either Gla-300 ( n = 95) or insulin degludec ( n = 39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-300 or insulin degludec prescribed after first follow-up visit within 1-12 months. Secondary outcomes included changes in glycemic control and empiric dose conversion from Gla-100 to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated changes in insulin doses, and paired t tests assessed changes in glycemic control using GraphPad statistical software. Median daily basal insulin dose increased for individuals transitioned from Gla-100 to Gla-300 from 30 [19-60 interquartile range (IQR)] units at baseline to 34.5 (19-70 IQR) units after follow up ( p = 0.01). For patients transitioned to insulin degludec, dose changes from baseline to follow up were not significantly different ( p = 0.56). At the time of transition, the prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous dose of Gla-100 ( p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments were not routinely prescribed. Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin requirements between visits, while basal insulin requirements for those transitioned from Gla-100 to insulin degludec were not significantly different.

In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control.

Science.gov (United States)

McCarty, Mark F

2016-10-01

In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive. Alternatively, administration of high-dose biotin has potential for modulating hepatic enzyme expression in a favorable way. Studies in rodents and in cultured hepatocytes demonstrate that, in the context of low insulin exposure, supra-physiological levels of biotin induce increased expression of GK while suppressing that of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects may be a downstream consequence of the fact that biotin down-regulates mRNA expression of FOXO1; insulin's antagonism of the activity of this transcription factor is largely responsible for its modulatory impact on hepatic glycolysis and gluconeogenesis. Hence, high-dose biotin may compensate for subnormal insulin exposure by suppressing FOXO1 levels. High-dose biotin also has the potential to oppose hepatic steatosis by down-regulating SREBP-1 expression. Two pilot trials of high-dose biotin (16 or 2mg per day) in type 1 diabetics have yielded promising results. There is also some reason to suspect that high-dose biotin could aid control of diabetic neuropathy and nephropathy via its stimulatory effect on cGMP production. Owing to the safety, good tolerance, moderate expense, and current availability of high-dose biotin, this strategy merits more

Insulin is essential for in vitro chondrogenesis of mesenchymal progenitor cells and influences chondrogenesis in a dose-dependent manner.

Science.gov (United States)

Mueller, Michael B; Blunk, Torsten; Appel, Bernhard; Maschke, Angelika; Goepferich, Achim; Zellner, Johannes; Englert, Carsten; Prantl, Lukas; Kujat, Richard; Nerlich, Michael; Angele, Peter

2013-01-01

Insulin is a commonly used additive in chondrogenic media for differentiating mesenchymal stem cells (MSCs). The indispensability of other bioactive factors like TGF-β or dexamethasone in these medium formulations has been shown, but the role of insulin is unclear. The purpose of this study was to investigate whether insulin is essential for MSC chondrogenesis and if there is a dose-dependent effect of insulin on MSC chondrogenesis. We cultivated human MSCs in pellet culture in serum-free chondrogenic medium with insulin concentrations between 0 and 50 μg/ml and assessed the grade of chondrogenic differentiation by histological evaluation and determination of glycosaminoglycan (GAG), total collagen and DNA content. We further tested whether insulin can be delivered in an amount sufficient for MSC chondrogenesis via a drug delivery system in insulin-free medium. Chondrogenesis was not induced by standard chondrogenic medium without insulin and the expression of cartilage differentiation markers was dose-dependent at insulin concentrations between 0 and 10 μg/ml. An insulin concentration of 50 μg/ml had no additional effect compared with 10 μg/ml. Insulin was delivered by a release system into the cell culture under insulin-free conditions in an amount sufficient to induce chondrogenesis. Insulin is essential for MSC chondrogenesis in this system and chondrogenic differentiation is influenced by insulin in a dose-dependent manner. Insulin can be provided in a sufficient amount by a drug delivery system. Therefore, insulin is a suitable and inexpensive indicator substance for testing drug release systems in vitro.

The automatic regulation of the basal dose on the insulin pump for the treatment of patients that have Diabetes type 1.

Science.gov (United States)

Mehanović, Sifet; Mujić, Midhat

2010-05-01

Diabetes mellitus type 1 is a chronic metabolic disorder, and its main characteristic is Hyperglycemia. It usually occurs in the early years because of the absolute or relative absence of the active insulin that is caused by the autoimmune disease of the beta cells of the pancreas. Despite the numerous researches and efforts of the scientists, the therapy for Diabetes type 1 is based on the substitution of insulin. Even though the principles of the therapy have not changed so much, still some important changes have occurred in the production and usage of insulin. Lately, the insulin pumps are more frequent in the therapy for Diabetes type 1. The functioning of the pump is based on the continuing delivery of insulin in a small dose ("the basal dose"), that keeps the level of glycemia in the blood constant. The increase of glycemia during the meal is reduced with the additional dose of insulin ("the bolus dose"). The use of the insulin pumps and the continuing glucose sensors has provided an easier and more efficient monitoring of the diabetes, a better metabolic control and a better life quality for the patient and his/her family. This work presents the way of automatic regulation of the basal dose of insulin through the synthesis of the functions of the insulin pump and the continuing glucose sensor. The aim is to give a contribution to the development of the controlling algorithm on the insulin pump for the automatic regulation of the glucose concentration in the blood. This could be a step further which is closer to the delivery of the dose of insulin that is really needed for the basic needs of the organism, and a significant contribution is given to the development of the artificial pancreas.

Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis.

Science.gov (United States)

Kramer, Caroline Kaercher; Zinman, Bernard; Retnakaran, Ravi

2013-09-01

Studies have shown that, when implemented early in the course of type 2 diabetes mellitus, treatment with intensive insulin therapy for 2-3 weeks can induce a glycaemic remission, wherein patients are able to maintain normoglycaemia without any anti-diabetic medication. We thus did a systematic review and meta-analysis of interventional studies to assess the effect of short-term intensive insulin therapy on the pathophysiological defects underlying type 2 diabetes mellitus (pancreatic β-cell dysfunction and insulin resistance) and identify clinical predictors of remission. We identified studies published between 1950 and Nov 19, 2012, which assessed the effect of intensive insulin therapy on β-cell function or insulin resistance, or both, or assessed long-term drug-free glycaemic remission in adults aged 18 years or older with newly diagnosed type 2 diabetes mellitus. We calculated pooled estimates by random-effects model. This study is registered with International Prospective Register of Systematic Reviews, number CRD42012002829. We identified 1645 studies of which seven fulfilled inclusion criteria (n=839 participants). Five studies were non-randomised. A pooled analysis of the seven studies showed a post-intensive insulin therapy increase in Homeostasis Model Assessment of β-cell function as compared with baseline (1·13, 95% CI 1·02 to 1·25) and a decrease in Homeostasis Model Assessment of Insulin Resistance (-0·57, -0·84 to -0·29). In the four studies that assessed glycaemic remission (n=559 participants), the proportion of participants in drug-free remission was about 66·2% (292 of 441 patients) after 3 months of follow-up, about 58·9% (222 of 377 patients) after 6 months, about 46·3% (229 of 495 patients) after 12 months, and about 42·1% (53 of 126 patients) after 24 months. Patients who achieved remission had higher body-mass index than those who did not achieve remission (1·06 kg/m(2), 95% CI 0·55 to 1·58) and lower fasting plasma glucose

Influence of dietary protein on postprandial blood glucose levels in individuals with Type 1 diabetes mellitus using intensive insulin therapy.

Science.gov (United States)

Paterson, M A; Smart, C E M; Lopez, P E; McElduff, P; Attia, J; Morbey, C; King, B R

2016-05-01

To determine the effects of protein alone (independent of fat and carbohydrate) on postprandial glycaemia in individuals with Type 1 diabetes mellitus using intensive insulin therapy. Participants with Type 1 diabetes mellitus aged 7-40 years consumed six 150 ml whey isolate protein drinks [0 g (control), 12.5, 25, 50, 75 and 100] and two 150 ml glucose drinks (10 and 20 g) without insulin, in randomized order over 8 days, 4 h after the evening meal. Continuous glucose monitoring was used to assess postprandial glycaemia. Data were collected from 27 participants. Protein loads of 12.5 and 50 g did not result in significant postprandial glycaemic excursions compared with control (water) throughout the 300 min study period (P > 0.05). Protein loads of 75 and 100 g resulted in lower glycaemic excursions than control in the 60-120 min postprandial interval, but higher excursions in the 180-300 min interval. In comparison with 20 g glucose, the large protein loads resulted in significantly delayed and sustained glucose excursions, commencing at 180 min and continuing to 5 h. Seventy-five grams or more of protein alone significantly increases postprandial glycaemia from 3 to 5 h in people with Type 1 diabetes mellitus using intensive insulin therapy. The glycaemic profiles resulting from high protein loads differ significantly from the excursion from glucose in terms of time to peak glucose and duration of the glycaemic excursion. This research supports recommendations for insulin dosing for large amounts of protein. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Relationship between Optimum Mini-doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes - A Simulation Study

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Wendt, Sabrina Lyngbye; Schmidt, Signe

2017-01-01

-treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba-insulin), insulin on board...... (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre-defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin...... levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin...

Concentrated insulins: the new basal insulins

Directory of Open Access Journals (Sweden)

Lamos EM

2016-03-01

Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

Optimal dose and timing of insulin Aspart to mimic first phase insulin response in patients with recently onset type 2 diabetes

DEFF Research Database (Denmark)

Gredal, C.; Rosenfalck, A.; Dejgaard, A.

2008-01-01

OBJECTIVE: To assess the optimal dose and timing of subcutaneous injection of insulin Aspart (IAsp) in relation to meal to mimic first phase insulin response in patients with recently diagnosed type 2 diabetes. DESIGN AND METHODS: Twenty patients were randomised in a double blind, double dummy...... design to four standard meal tests with pre-meal injection of insulin Aspart 0.08 IU/kg BW 30 min before the meal, insulin Aspart 0.04 IU/kg BW 30 or 15 min before the meal and placebo. RESULTS: All three insulin regimes significantly reduced postprandial glucose increment (area under the curve AUC(-30...... injection of IAsp 0.08 IU/kg BW. No difference in postprandial glucose profile was demonstrated whether IAsp 0.04 IU/kg BW was administrated 15 or 30 min before mealtime. CONCLUSIONS: IAsp 0.04IU/kg BW injected subcutaneously 15 or 30 min before meal reduced the postprandial blood glucose increment without...

[Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

Science.gov (United States)

Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

2016-01-01

To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Low-volume high-intensity swim training is superior to high-volume low-intensity training in relation to insulin sensitivity and glucose control in inactive middle-aged women.

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Connolly, Luke J; Nordsborg, Nikolai B; Nyberg, Michael; Weihe, Pál; Krustrup, Peter; Mohr, Magni

2016-10-01

We tested the hypothesis that low-volume high-intensity swimming has a larger impact on insulin sensitivity and glucose control than high-volume low-intensity swimming in inactive premenopausal women with mild hypertension. Sixty-two untrained premenopausal women were randomised to an inactive control (n = 20; CON), a high-intensity low-volume (n = 21; HIT) or a low-intensity high-volume (n = 21; LIT) training group. During the 15-week intervention period, HIT performed 3 weekly 6-10 × 30-s all-out swimming intervals (average heart rate (HR) = 86 ± 3 % HRmax) interspersed by 2-min recovery periods and LIT swam continuously for 1 h at low intensity (average HR = 73 ± 3 % HRmax). Fasting blood samples were taken and an oral glucose tolerance test (OGTT) was conducted pre- and post-intervention. After HIT, resting plasma [insulin] was lowered (17 ± 34 %; P high-intensity intermittent swimming is an effective and time-efficient training strategy for improving insulin sensitivity, glucose control and biomarkers of vascular function in inactive, middle-aged mildly hypertensive women.

Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

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Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

2014-09-01

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence

Self-Tuning Insulin Adjustment Algorithm for Type 1 Diabetic Patients based on Multi-Doses Regime

Directory of Open Access Journals (Sweden)

D. U. Campos-Delgado

2005-01-01

Full Text Available A self-tuning algorithm is presented for on-line insulin dosage adjustment in type 1 diabetic patients (chronic stage. The algorithm suggested does not need information of the patient insulin–glucose dynamics (model-free. Three doses are programmed daily, where a combination of two types of insulin: rapid/short and intermediate/long acting is injected into the patient through a subcutaneous route. The doses adaptation is performed by reducing the error in the blood glucose level from euglycemics. In this way, a total of five doses are tuned per day: three rapid/short and two intermediate/long, where there is large penalty to avoid hypoglycemic scenarios. Closed-loop simulation results are illustrated using a detailed nonlinear model of the subcutaneous insulin–glucose dynamics in a type 1 diabetic patient with meal intake.

The Automatic Regulation of the Basal Dose on the Insulin Pump for the Treatment of Patients that have Diabetes Type 1

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Sifet Mehanović

2010-05-01

Full Text Available Diabetes mellitus type 1 is a chronic metabolic disorder, and its main characteristic is Hyperglycemia. It usually occurs in the early years because of the absolute or relative absence of the active insulin that is caused by the autoimmune disease of the β cells of the pancreas. Despite the numerous researches and efforts of the scientists, the therapy for Diabetes type 1 is based on the substitution of insulin. Even though the principles of the therapy have not changed so much, still some important changes have occurred in the production and usage of insulin. Lately, the insulin pumps are more frequent in the therapy for Diabetes type 1. The functioning of the pump is based on the continuing delivery of insulin in a small dose (“the basal dose”, that keeps the level of glycemia in the blood constant. The increase of glycemia during the meal is reduced with the additional dose of insulin (“the bolus dose”. The use of the insulin pumps and the continuing glucose sensors has provided an easier and more efficient monitoring of the diabetes, a better metabolic control and a better life quality for the patient and his/her family.This work presents the way of automatic regulation of the basal dose of insulin through the synthesis of the functions of the insulin pump and the continuing glucose sensor. The aim is to give a contribution to the development of the controlling algorithm on the insulin pump for the automatic regulation of the glucose concentration in the blood. This could be a step further which is closer to the delivery of the dose of insulin that is really needed for the basic needs of the organism, and a significant contribution is given to the development of the artificial pancreas.

A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock.

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Cole, J B; Stellpflug, S J; Ellsworth, H; Anderson, C P; Adams, A B; Engebretsen, K M; Holger, J S

2013-05-01

High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.

Design and clinical pilot testing of the model-based dynamic insulin sensitivity and secretion test (DISST).

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Lotz, Thomas F; Chase, J Geoffrey; McAuley, Kirsten A; Shaw, Geoffrey M; Docherty, Paul D; Berkeley, Juliet E; Williams, Sheila M; Hann, Christopher E; Mann, Jim I

2010-11-01

Insulin resistance is a significant risk factor in the pathogenesis of type 2 diabetes. This article presents pilot study results of the dynamic insulin sensitivity and secretion test (DISST), a high-resolution, low-intensity test to diagnose insulin sensitivity (IS) and characterize pancreatic insulin secretion in response to a (small) glucose challenge. This pilot study examines the effect of glucose and insulin dose on the DISST, and tests its repeatability. DISST tests were performed on 16 subjects randomly allocated to low (5 g glucose, 0.5 U insulin), medium (10 g glucose, 1 U insulin) and high dose (20 g glucose, 2 U insulin) protocols. Two or three tests were performed on each subject a few days apart. Average variability in IS between low and medium dose was 10.3% (p=.50) and between medium and high dose 6.0% (p=.87). Geometric mean variability between tests was 6.0% (multiplicative standard deviation (MSD) 4.9%). Geometric mean variability in first phase endogenous insulin response was 6.8% (MSD 2.2%). Results were most consistent in subjects with low IS. These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS. © 2010 Diabetes Technology Society.

Comparison of Two Intensities of Aerobic Training (low intensity and High Intensity on Expression of Perlipin 2 Skeletal Muscle, Serum Glucose and Insulin levels in Streptozotocin-Diabetic Rats

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M Ghafari

2017-06-01

Full Text Available Abstract   Background & aim: Lipid metabolism disorder plays an important role in insulin resistance in skeletal muscle and lipid drop proteins such as perlipine 2 (PLIN2 are effective in regulating intracellular fat metabolism. One of the suggested pathways for the effects of endurance activity in metabolic diseases is the effect of physical activity on intramuscular. Therefore, the purpose of this study was compare the intensity of aerobic exercise intensity (low intensity and high intensity on expression of PLIN2 skeletal muscle, serum glucose and insulin levels in streptozotocin-diabetic rats.   Methods: In this experimental study, 24 male Wistar rats were randomly divided into three groups of 8, including two intervention groups (low intensity endurance training group and high intensity continuous exercise group and one control group. After induction of diabetic rats by injection streptozotocin (55 mg / kg body weight, Intraperitoneally, endurance training was applied for eight weeks, three sessions per week in diabetic rats. Exercise intensity in the low-intensity group was equal to 5-8 m / min (equivalent to 50-60% Vo2max, the intensity of training in a high intensity training group was equivalent to a speed of 22-25 m / min (equivalent to 80% Vo2max and the control group did not receive intervene in this time. Relative protein expression of PLIN2 was performed using western blot technique. Data were analyzed by one-way ANOVA and Tukey's post hoc test.   Results: The results of the intergroup comparison revealed a significant difference among three groups in the PLIN2 variables (p = 0.037. The results of post hoc test showed a significant increase in PLIN2 in high intensity training diabetic group compared to the control group (p = 0.033 However, there was no significant difference in PLIN2 level in the low exercise group compared to the control group (p = 0.18. Also, there was no significant difference between the low intensity and

An overview of insulin pump therapy: appropriate use of an ...

African Journals Online (AJOL)

2012-06-13

Jun 13, 2012 ... Careful assessment of patients is vital, as pump therapy is an expensive treatment option and can be ... Intensive education of patients who meet the criteria is essential. .... to keep a food, blood glucose and insulin dose diary,.

Effects of menopause and high-intensity training on insulin sensitivity and muscle metabolism.

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Mandrup, Camilla M; Egelund, Jon; Nyberg, Michael; Enevoldsen, Lotte Hahn; Kjær, Andreas; Clemmensen, Andreas E; Christensen, Anders Nymark; Suetta, Charlotte; Frikke-Schmidt, Ruth; Steenberg, Dorte Enggaard; Wojtaszewski, Jørgen F P; Hellsten, Ylva; Stallknecht, Bente M

2018-02-01

To investigate peripheral insulin sensitivity and skeletal muscle glucose metabolism in premenopausal and postmenopausal women, and evaluate whether exercise training benefits are maintained after menopause. Sedentary, healthy, normal-weight, late premenopausal (n = 21), and early postmenopausal (n = 20) women were included in a 3-month high-intensity exercise training intervention. Body composition was assessed by magnetic resonance imaging and dual-energy x-ray absorptiometry, whole body glucose disposal rate (GDR) by hyperinsulinemic euglycemic clamp (40 mU/m/min), and femoral muscle glucose uptake by positron emission tomography/computed tomography, using the glucose analog fluorodeoxyglucose, expressed as estimated metabolic rate (eMR). Insulin signaling was investigated in muscle biopsies. Age difference between groups was 4.5 years, and no difference was observed in body composition. Training increased lean body mass (estimate [95% confidence interval] 0.5 [0.2-0.9] kg, P training (eMR vastus lateralis muscle: 27.8 [19.6-36.0] μmol/min/kg, P training-induced increases in insulin sensitivity included increased expression of hexokinase (19.2 [5.0-24.7] AU, P = 0.02) and glycogen synthase (32.4 [15.0-49.8] AU, P high-intensity exercise training.

Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients

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Guillaume Marquis-Gravel

2015-01-01

Conclusion: Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects.

Effect of Eight Weeks High Intensity Interval Training and Medium Intensity Interval Training and Aloe vera Intake on Serum Vaspin and Insulin Resistance in Diabetic Male Rats

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Darya Asgari Hazaveh

2018-02-01

Full Text Available Abstract Background: The use of herbal supplements and exercise training for the treatment of diabetic has increased.The purpose of this study was to investigate the effect of eight weeks high intensity interval training and moderate intensity interval training and Aloe vera intake on serum vaspin and insulin resistance in diabetic male rats. Materials and Methods: During this experimental study, 32 diabetic rats with STZ Wistar were randomly divided into four groups including the control, high intensity interval training +supplement, moderate intensity interval training + supplement and supplement. Training program was planned for 8 weeks and 3 sessions per week. Each session consisted of 6 to 12 periods of 2-minute activity with the intensity of 90% and 60% with one minute rest (speed: 10m/min. In the supplement groups, 300milligrams Aloe vera solution per kilogram of body weight Gavage was given 5 sessions per week for 8 weeks. The data were analyzed using one-way analysis of variance (ANOVA. Results: The results showed that high and moderate intensity interval training with supplement has no significant effect on the of serum vaspin (p=0.112. High intensity interval training with supplement had significant effects on insulin in diabetic male rats (0.000. Conclusion: .Based on the findings of this study, it seems that supplementation of Aloe vera with high intensity interval training can have better effects on serum insulin in diabetic rats.

Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice.

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Jafari, M R; Zarrindast, M R; Djahanguiri, B

2004-10-01

Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice. The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured. Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions. Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.

Design of spray dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose.

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Ung, Keith T; Rao, Nagaraja; Weers, Jeffry G; Huang, Daniel; Chan, Hak-Kim

2016-09-25

Inhaled drugs all too often deliver only a fraction of the emitted dose to the target lung site due to deposition in the extrathoracic region (i.e., mouth and throat), which can lead to increased variation in lung exposure, and in some instances increases in local and systemic side effects. For aerosol medications, improved targeting to the lungs may be achieved by tailoring the micromeritic properties of the particles (e.g., size, density, rugosity) to minimize deposition in the mouth-throat and maximize the total lung dose. This study evaluated a co-solvent spray drying approach to modulate particle morphology and dose delivery characteristics of engineered powder formulations of insulin microparticles. The binary co-solvent system studied included water as the primary solvent mixed with an organic co-solvent, e.g., ethanol. Factors such as the relative rate of evaporation of each component of a binary co-solvent mixture, and insulin solubility in each component were considered in selecting feedstock compositions. A water-ethanol co-solvent mixture with a composition range considered suitable for modulating particle shell formation during drying was selected for experimental investigation. An Alberta Idealized Throat model was used to evaluate the in vitro total lung dose of a series of spray dried insulin formulations engineered with different bulk powder properties and delivered with two prototype inhalers that fluidize and disperse powder using different principles. The in vitro total lung dose of insulin microparticles was improved and favored for powders with low bulk density and small primary particle size, with reduction of deposition in the extrathoracic region. The results demonstrated that a total lung dose >95% of the delivered dose can be achieved with engineered particles, indicating a high degree of lung targeting, almost completely bypassing deposition in the mouth-throat. Copyright © 2016 Elsevier B.V. All rights reserved.

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

Science.gov (United States)

2014-01-01

Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention

Science.gov (United States)

Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

2016-01-01

Abstract Background: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. Methods: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. Results: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. Conclusion: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID:27684837

Low-Active Male Adolescents: A Dose Response to High-Intensity Interval Training.

Science.gov (United States)

Logan, Greig Robert Melrose; Harris, Nigel; Duncan, Scott; Plank, Lindsay D; Merien, Fabrice; Schofield, Grant

2016-03-01

High-intensity interval training (HIIT) is a potential alternative to traditionally recommended steady state exercise for providing health benefits in adolescents, yet its dose-response relationship in this cohort remains unclear, as does its translatability to real-world, nonclinical settings. The present study adopts a novel dose-response design to investigate the effects of undertaking 8 wk of HIIT on the cardiometabolic health of low-active male adolescents. Twenty-six male adolescents (age 16 ± 1 yr), identified as low active by nonparticipation in structured sport and physical education classes, were randomly assigned to one of five treatment groups. Corresponding with their group numbers (1-5), participants completed a number of HIIT "sets," which consisted of 4 repeated bouts of 20-s near-maximal exertion interspersed with 10-s passive recovery. Participants performed two HIIT sessions and one resistance training session each week for 8 wk. Baseline and follow-up health measures consisted of peak oxygen uptake (V˙O2peak) with an incremental ramp test to volitional exhaustion; body composition (including visceral fat mass, body fat, and lean tissue mass) with dual-energy x-ray absorptiometry; and lipid profile, glucose, insulin, and interleukin-6 from blood analysis. All health outcomes were analyzed as percentage changes, and data were modeled using a quadratic function to explore dose-response relationships. Significant improvements were observed for V˙O2peak (∼6%), body fat percentage (∼4%), visceral fat mass (∼10%), and waist circumference-to-height ratio (∼3%), but there was no clear effect of dose across groups. Low-active adolescent males performing a single HIIT set twice weekly, in addition to one resistance training session, gained meaningful improvements in fitness and body composition. Performing additional HIIT sets provided no additional improvements to those of the lowest dose in this study.

Evaluation of vildagliptin and fixed dose combination of vildagliptin and metformin on glycemic control and insulin dose over 3 months in patients with type 2 diabetes mellitus

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Paresh Ved

2012-01-01

Full Text Available Objective: Addition of vildagliptin to ongoing insulin therapy may help in terms of overall glycemic control as well as reduction in dose of insulin and weight. This study sought to evaluate the effect of vildagliptin and fixed dose combination (FDC of vildagliptin and metformin in patients in ongoing insulin therapy for Type 2 diabetes mellitus. Materials and Methods: This was an open label, prospective, non-randomised, multicentric observational study. In this study 400 patients with T2DM on insulin were enrolled and allocated with the treatment of vildagliptin 50 mg in monotherapy and FDC of vildagliptin 50 mg and metformin strengths as 500/ 850 / 1000 mg. Baseline investigations included fasting blood glucose (FBG and post prandial plasma glucose (PPPG Estimation and glycosylated haemoglobin (HbA1c. Results: The combined analysis was carried out on 300 completed patients in this study, who were treated with vildagliptin or FDC of vildagliptin and metformin. The difference in mean value of insulin dose (MID showed a highly significant decrease (P <0.0001 from baseline to end of the treatment i.e. from 36.26 ± 18.21 to 26.87 ± 16.49 IU. A highly significant decrease (P <0.0001 in FBG from 194.94 ± 56.19 to 124.93 ± 30.11 mg/dl was observed. Similarly PPPG showed a highly significant (P <0.0001 decrease from baseline to end of the treatment i.e. from 287.60 mg/dl to 172.05 mg/dl and there was highly significant (P <0.0001 decrease in HbA1c i.e. from 9.01% to 7.65% respectively. At the same time, highly significant decrease (P <0.0001 in mean weight also observed from baseline to end of the treatment i.e. from 71.23 ± 11.06 kg to 70.06 ± 10.62 Kg. Conclusion: Addition of vildagliptin and FDC of vildagliptin and metformin is an effective strategy in glycemic control, reduction in dose of insulin and weight of patients suffering with T2DM.

Beam intensity scanner system for three dimensional dose verification of IMRT

International Nuclear Information System (INIS)

Vahc, Young W.; Kwon, Ohyun; Park, Kwangyl; Park, Kyung R.; Yi, Byung Y.; Kim, Keun M.

2003-01-01

Patient dose verification is clinically one of the most important parts in the treatment delivery of radiation therapy. The three dimensional (3D) reconstruction of dose distribution delivered to target volume helps to verify patient dose and determine the physical characteristics of beams used in IMRT. Here we present beam intensity scanner (BInS) system for the pre-treatment dosimetric verification of two dimensional photon intensity. The BInS is a radiation detector with a custom-made software for dose conversion of fluorescence signals from scintillator. The scintillator is used to produce fluorescence from the irradiation of 6 MV photons on a Varian Clinac 21EX. The digitized fluoroscopic signals obtained by digital video camera-based scintillator (DVCS) will be processed by our custom made software to reproduce 3D- relative dose distribution. For the intensity modulated beam (IMB), the BInS calculates absorbed dose in absolute beam fluence which is used for the patient dose distribution. Using BInS, we performed various measurements related to IMRT and found the following: (1) The 3D-dose profiles of the IMBs measured by the BInS demonstrate good agreement with radiographic film, pin type ionization chamber and Monte Carlo simulation. (2) The delivered beam intensity is altered by the mechanical and dosimetric properties of the collimation of dynamic and/or step MLC system. This is mostly due to leaf transmission, leaf penumbra scattered photons from the round edges of leaves, and geometry of leaf. (3) The delivered dose depends on the operational detail of how to make multi leaf opening. These phenomena result in a fluence distribution that can be substantially different from the initial and calculated intensity modulation and therefore, should be taken into account by the treatment planning for accurate dose calculations delivered to the target volume in IMRT. (author)

Patient safety and minimizing risk with insulin administration - role of insulin degludec.

Science.gov (United States)

Aye, Myint M; Atkin, Stephen L

2014-01-01

Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long

Dosing of U-100 insulin and associated outcomes among Medicare enrollees with type 1 or type 2 diabetes

Directory of Open Access Journals (Sweden)

Eby EL

2015-06-01

Full Text Available Elizabeth L Eby,1 Kate Van Brunt,2 Cynthia Brusko,3 Bradley Curtis,4 Maureen J Lage5 1Global Patient Outcomes and Real World Evidence, Eli Lilly and Co., Indianapolis IN USA; 2Eli Lilly and Co., Windlesham, UK; 3Lilly USA, LLC, Indianapolis, IN, USA; 4Eli Lilly and Co., Indianapolis, IN, USA; 5HealthMetrics Outcomes Research, LLC, Bonita Springs, FL, USA Objective: To examine costs, resource utilization, adherence, and hypoglycemic events among various doses of U-100 insulin regimens among elderly patients (age ≥65 years diagnosed with diabetes.Methods: Truven Health Analytics Medicare databases from January 1, 2008 through December 31, 2011 were utilized. General linear models with a gamma distribution and log link were used to examine costs, while logistic and negative binomial regressions were used to examine resource utilization and hypoglycemic events. Analyses controlled for patient characteristics, pre-period comorbidities, general health, and use of antidiabetic medications as well as index dose of insulin.Results: All-cause inpatient, emergency room, and outpatients costs, as well as diabetes-related inpatient costs, were highest among individuals who were treated with an index dose of 10–100 units/day followed by >300 units/day, while drug costs and total costs generally increased as index dosage increased. Resource utilization generally followed the same pattern as costs, with number of office visits increasing as the dose increased and the highest hospital length of stay, number of hospitalizations, number of emergency room visits, and number of diabetes-related hospitalizations were generally highest among those in the lowest and highest index dose cohorts. Compared to patients who initiated with an index dose of 10–100 units/day, all other patients were significantly less likely to achieve an adherence threshold of 80% based upon index dose range, and while those with an index dose of >100–150 units/day were

Comparison of standard (self-directed) versus intensive patient training for the human insulin inhalation powder (HIIP) delivery system in patients with type 2 diabetes: efficacy, safety, and training measures.

Science.gov (United States)

Rosenstock, Julio; Nakano, Masako; Silverman, Bernard L; Sun, Bin; de la Peña, Amparo; Suri, Ajit; Muchmore, Douglas B

2007-02-01

The Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system [AIR (a registered trademark of Alkermes, Inc., Cambridge, MA) Inhaled Insulin System] was designed to be easy to use. Training methods were compared in insulin-naive patients with type 2 diabetes. Patients (n = 102) were randomized to standard or intensive training. With standard training, patients learned how to use the HIIP delivery system by reading directions for use (DFU) and trying on their own. Intensive training included orientation to the HIIP delivery system with individual coaching and inspiratory flow rate training. Both groups received preprandial HIIP + metformin with or without a thiazolidinedione for 4 weeks. Overall 2-h postprandial blood glucose (PPBG) excursion was the primary measure. Noninferiority was defined as the upper limit of the two-sided 95% confidence interval of the mean difference between groups being 1.2 training) and 0.23 +/- 0.36 (intensive training) mmol/L. The mean difference (standard minus intensive training) and two-sided 95% confidence interval were -0.35 (-1.02, 0.33) mmol/L. No statistically or clinically significant differences were observed between training methods in premeal, postmeal, or bedtime blood glucose values, HIIP doses at endpoint, or blood glucose values after a test meal. No discontinuations occurred because of difficulty of use or dislike of the HIIP system. DFU compliance was >90% in both training groups. There were no significant differences between training methods in safety measures. The HIIP delivery system is easy to use, and most patients can learn to use it by reading the DFU without assistance from health care professionals.

Insulin signaling displayed a differential tissue-specific response to low-dose dihydrotestosterone in female mice.

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Andrisse, Stanley; Billings, Katelyn; Xue, Ping; Wu, Sheng

2018-04-01

Hyperandrogenemia and hyperinsulinemia are believed to play prominent roles in polycystic ovarian syndrome (PCOS). We explored the effects of low-dose dihydrotestosterone (DHT), a model of PCOS, on insulin signaling in metabolic and reproductive tissues in a female mouse model. Insulin resistance in the energy storage tissues is associated with type 2 diabetes. Insulin signaling in the ovaries and pituitary either directly or indirectly stimulates androgen production. Energy storage and reproductive tissues were isolated and molecular assays were performed. Livers and white adipose tissue (WAT) from DHT mice displayed lower mRNA and protein expression of insulin signaling intermediates. However, ovaries and pituitaries of DHT mice exhibited higher expression levels of insulin signaling genes/proteins. Insulin-stimulated p-AKT levels were blunted in the livers and WAT of the DHT mice but increased or remained the same in the ovaries and pituitaries compared with controls. Glucose uptake decreased in liver and WAT but was unchanged in pituitary and ovary of DHT mice. Plasma membrane GLUTs were decreased in liver and WAT but increased in ovary and pituitary of DHT mice. Skeletal muscle insulin-signaling genes were not lowered in DHT mice compared with control. DHT mice did not display skeletal muscle insulin resistance. Insulin-stimulated glucose transport increased in skeletal muscles of DHT mice compared with controls. DHT mice were hyperinsulinemic. However, the differential mRNA and protein expression pattern was independent of hyperinsulinemia in cultured hepatocytes and pituitary cells. These findings demonstrate a differential effect of DHT on the insulin-signaling pathway in energy storage vs. reproductive tissues independent of hyperinsulinemia.

Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function

DEFF Research Database (Denmark)

Kielgast, Urd; Krarup, Thure; Holst, Jens Juul

2011-01-01

OBJECTIVE To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual ß-cell function. RESEARCH DESIGN AND METHODS Ten type 1 diabetic patients with residual ß-cell function (C-peptide positive) and 19.......1]; P Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control....... activity was performed before (week 0) and during (week 4) treatment. Differences in insulin dose; HbA(1c); time spent with blood glucose 10, and 3.9-9.9 mmol/L; and body weight were evaluated. RESULTS Insulin dose decreased from 0.50 ± 0.06 to 0.31 ± 0.08 units/kg per day (P

The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy.

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Soheilykhah, Sedigheh; Mojibian, Mahdieh; Moghadam, Maryam Jannati; Shojaoddiny-Ardekani, Ahmad

2013-04-01

Low serum vitamin D levels are correlated with insulin resistance during pregnancy. We have assessed the effects of different doses of vitamin D on insulin resistance during pregnancy. A randomized clinical trial was done on 120 women with a gestational age of less than 12 weeks. The women were divided into three groups randomly. Group A received 200 IU vitamin D daily, group B 50,000 IU vitamin D monthly and group C 50,000 IU vitamin D every 2 weeks from 12 weeks of pregnancy until delivery. The serum levels of fasting blood sugar (FBS), insulin, calcium and 25-hydroxyvitamin D were measured before and after intervention. We used the homeostatic model assessment of insulin resistance (HOMA-IR) as a surrogate measure of insulin resistance. The mean ± standard deviation of serum 25-hydroxyvitamin D increased in group C from 7.3 ± 5.9 to 34.1 ± 11.5 ng/ml and in group B it increased from 7.3 ± 5.3 to 27.23 ± 10.7 ng/ml, but the level of vitamin D in group A increased from 8.3 ± 7.8 to 17.7 ± 9.3 ng/ml (p insulin and HOMA-IR before and after intervention in groups A and C were significant (p = 0.01, p = 0.02). This study has shown that supplementation of pregnant women with 50 000 IU vitamin D every 2 weeks improved insulin resistance significantly.

NovoPen Echo® insulin delivery device

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Hyllested-Winge J

2016-01-01

Full Text Available Jacob Hyllested-Winge,1 Thomas Sparre,2 Line Kynemund Pedersen2 1Novo Nordisk Pharma Ltd, Tokyo, Japan; 2Novo Nordisk A/S, Søborg, Denmark Abstract: The introduction of insulin pen devices has provided easier, well-tolerated, and more convenient treatment regimens for patients with diabetes mellitus. When compared with vial and syringe regimens, insulin pens offer a greater clinical efficacy, improved quality of life, and increased dosing accuracy, particularly at low doses. The portable and discreet nature of pen devices reduces the burden on the patient, facilitates adherence, and subsequently contributes to the improvement in glycemic control. NovoPen Echo® is one of the latest members of the NovoPen® family that has been specifically designed for the pediatric population and is the first to combine half-unit increment (=0.5 U of insulin dosing with a simple memory function. The half-unit increment dosing amendments and accurate injection of 0.5 U of insulin are particularly beneficial for children (and insulin-sensitive adults/elders, who often require small insulin doses. The memory function can be used to record the time and amount of the last dose, reducing the fear of double dosing or missing a dose. The memory function also provides parents with extra confidence and security that their child is taking insulin at the correct doses and times. NovoPen Echo is a lightweight, durable insulin delivery pen; it is available in two different colors, which may help to distinguish between different types of insulin, providing more confidence for both users and caregivers. Studies have demonstrated a high level of patient satisfaction, with 80% of users preferring NovoPen Echo to other pediatric insulin pens. Keywords: NovoPen Echo®, memory function, half-unit increment dosing, adherence, children, adolescents 

Physical characteristics that predict final basal insulin dose in type 2 diabetes mellitus, with a special focus on BMI

NARCIS (Netherlands)

Simon, A. C. R.; Bolli, G. B.; Dain, M.-P.; Wang, E.; Holleman, F.

2014-01-01

The possibility to predict final insulin dose based on patient's characteristics would allow for efficient titration for patients with higher dose needs. The primary aim of this post-hoc analysis of the L2T3 study was to determine predictors for final dose. Specifically, we focused on the

Pitfalls of Insulin Pump Clocks

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Reed, Amy J.

2014-01-01

The objective was to raise awareness about the importance of ensuring that insulin pumps internal clocks are set up correctly at all times. This is a very important safety issue because all commercially available insulin pumps are not GPS-enabled (though this is controversial), nor equipped with automatically adjusting internal clocks. Special attention is paid to how basal and bolus dose errors can be introduced by daylight savings time changes, travel across time zones, and am-pm clock errors. Correct setting of insulin pump internal clock is crucial for appropriate insulin delivery. A comprehensive literature review is provided, as are illustrative cases. Incorrect setting can potentially result in incorrect insulin delivery, with potential harmful consequences, if too much or too little insulin is delivered. Daylight saving time changes may not significantly affect basal insulin delivery, given the triviality of the time difference. However, bolus insulin doses can be dramatically affected. Such problems may occur when pump wearers have large variations in their insulin to carb ratio, especially if they forget to change their pump clock in the spring. More worrisome than daylight saving time change is the am-pm clock setting. If this setting is set up incorrectly, both basal rates and bolus doses will be affected. Appropriate insulin delivery through insulin pumps requires correct correlation between dose settings and internal clock time settings. Because insulin pumps are not GPS-enabled or automatically time-adjusting, extra caution should be practiced by patients to ensure correct time settings at all times. Clinicians and diabetes educators should verify the date/time of insulin pumps during patients’ visits, and should remind their patients to always verify these settings. PMID:25355713

The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.

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Ibrahim, Moustafa Ibrahim; Hamdy, Ahmed; Shafik, Adel; Taha, Salah; Anwar, Mohammed; Faris, Mohammed

2014-05-01

The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus. The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes. A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20-42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21-34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily

High-Intensity Interval Training Attenuates Insulin Resistance Induced by Sleep Deprivation in Healthy Males

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Jorge F. T. de Souza

2017-12-01

Full Text Available Introduction: Sleep deprivation can impair several physiological systems and recently, new evidence has pointed to the relationship between a lack of sleep and carbohydrate metabolism, consequently resulting in insulin resistance. To minimize this effect, High-Intensity Interval Training (HIIT is emerging as a potential strategy.Objective: The aim of this study was to investigate the effects of HIIT on insulin resistance induced by sleep deprivation.Method: Eleven healthy male volunteers were recruited, aged 18–35 years, who declared taking 7–8 h sleep per night. All volunteers were submitted to four different conditions: a single night of regular sleep (RS condition, 24 h of total sleep deprivation (SD condition, HIIT training followed by regular sleep (HIIT+RS condition, and HIIT training followed by 24 h of total sleep deprivation (HIIT+SD condition. They performed six training sessions over 2 weeks and each session consisted of 8–12 × 60 s intervals at 100% of peak power output. In each experimental condition, tests for glucose, insulin, cortisol, free fatty acids, and insulin sensitivity, measured by oral glucose tolerance test (OGTT, were performed.Results: Sleep deprivation increased glycaemia and insulin levels, as well as the area under the curve. Furthermore, an increase in free fatty acids concentrations and basal metabolism was observed. There were no differences in the concentrations of cortisol. However, HIIT before 24 h of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids.Conclusion: Twenty-four hours of sleep deprivation resulted in acute insulin resistance. However, HIIT is an effective strategy to minimize the deleterious effects promoted by this condition.

High-Intensity Interval Training Attenuates Insulin Resistance Induced by Sleep Deprivation in Healthy Males.

Science.gov (United States)

de Souza, Jorge F T; Dáttilo, Murilo; de Mello, Marco T; Tufik, Sergio; Antunes, Hanna K M

2017-01-01

Introduction: Sleep deprivation can impair several physiological systems and recently, new evidence has pointed to the relationship between a lack of sleep and carbohydrate metabolism, consequently resulting in insulin resistance. To minimize this effect, High-Intensity Interval Training (HIIT) is emerging as a potential strategy. Objective: The aim of this study was to investigate the effects of HIIT on insulin resistance induced by sleep deprivation. Method: Eleven healthy male volunteers were recruited, aged 18-35 years, who declared taking 7-8 h sleep per night. All volunteers were submitted to four different conditions: a single night of regular sleep (RS condition), 24 h of total sleep deprivation ( SD condition), HIIT training followed by regular sleep (HIIT+RS condition), and HIIT training followed by 24 h of total sleep deprivation (HIIT+ SD condition). They performed six training sessions over 2 weeks and each session consisted of 8-12 × 60 s intervals at 100% of peak power output. In each experimental condition, tests for glucose, insulin, cortisol, free fatty acids, and insulin sensitivity, measured by oral glucose tolerance test (OGTT), were performed. Results: Sleep deprivation increased glycaemia and insulin levels, as well as the area under the curve. Furthermore, an increase in free fatty acids concentrations and basal metabolism was observed. There were no differences in the concentrations of cortisol. However, HIIT before 24 h of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids. Conclusion: Twenty-four hours of sleep deprivation resulted in acute insulin resistance. However, HIIT is an effective strategy to minimize the deleterious effects promoted by this condition.

High-Intensity Interval Training Attenuates Insulin Resistance Induced by Sleep Deprivation in Healthy Males

Science.gov (United States)

de Souza, Jorge F. T.; Dáttilo, Murilo; de Mello, Marco T.; Tufik, Sergio; Antunes, Hanna K. M.

2017-01-01

Introduction: Sleep deprivation can impair several physiological systems and recently, new evidence has pointed to the relationship between a lack of sleep and carbohydrate metabolism, consequently resulting in insulin resistance. To minimize this effect, High-Intensity Interval Training (HIIT) is emerging as a potential strategy. Objective: The aim of this study was to investigate the effects of HIIT on insulin resistance induced by sleep deprivation. Method: Eleven healthy male volunteers were recruited, aged 18–35 years, who declared taking 7–8 h sleep per night. All volunteers were submitted to four different conditions: a single night of regular sleep (RS condition), 24 h of total sleep deprivation (SD condition), HIIT training followed by regular sleep (HIIT+RS condition), and HIIT training followed by 24 h of total sleep deprivation (HIIT+SD condition). They performed six training sessions over 2 weeks and each session consisted of 8–12 × 60 s intervals at 100% of peak power output. In each experimental condition, tests for glucose, insulin, cortisol, free fatty acids, and insulin sensitivity, measured by oral glucose tolerance test (OGTT), were performed. Results: Sleep deprivation increased glycaemia and insulin levels, as well as the area under the curve. Furthermore, an increase in free fatty acids concentrations and basal metabolism was observed. There were no differences in the concentrations of cortisol. However, HIIT before 24 h of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids. Conclusion: Twenty-four hours of sleep deprivation resulted in acute insulin resistance. However, HIIT is an effective strategy to minimize the deleterious effects promoted by this condition. PMID:29270126

Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat.

OpenAIRE

Walker, A P; Flint, D J

1983-01-01

Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to ...

Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

NARCIS (Netherlands)

Boekel, G.A.J van; Loves, S.; Sorge, A.A. van; Ruinemans-Koerts, J.; Rijnders, T.; Boer, H. de

2008-01-01

OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot

Comparison of the effects of intensive insulin treatment modalities on cardiovascular biomarkers in type 1 diabetes mellitus.

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Cetinkalp, Sevki; Felekoglu, Canan; Karadeniz, Muammer; Boyacıoglu, Hayal; Delen, Yasemin; Yildirim, Eser; Yilmaz, Candeger

2015-01-01

To evaluate effects of intensive insulin treatment modalities on cardiovascular biomarkers in patients with type 1 diabetes mellitus (T1DM). A total of 25 patients with T1DM receiving intensive insulin therapy either in the form of continuous insulin pump (IP group; n=13) or as multiple daily injections (MDI group; n=12) and 13 controls (control group, n=13) were included. Data on demographics, anthropometrics, diabetes history, and laboratory findings including glycemic and lipid parameters, and cardiovascular biomarkers [C-reactive protein (mg/dL), homocysteine (μmol/L), fibrinogen (mg/dL), oxidized LDL (ng/dL), PAI-1 (ng/mL), MCP-1 (pg/mL) and VEGF (pg/mL)] were recorded in each group. Correlation of cardiovascular biomarkers to other parameters was also evaluated in T1DM patients. Apart from significantly higher mean (SD) values for HbA1c [6.1 (0.3) vs. 5.6 (0.5)% (43 (3) vs. 38 (5) mmol/mol), p1.5 (13.6) vs. 58.2 (10.8), p1) in the IP than in the MDI group, no significance difference was noted between insulin treatment modalities as well as between patient and control groups in terms of demographic, anthropometric and laboratory parameters. Negative correlation of MCP-1 to treatment duration (r=-0.615, p=0.025), and HDL-c to CRP (r=-0.685, p=0.010) and VEGF (r=-0.678, p=0.011) was noted in IP group, whereas positive correlation of PAI-1 to diabetes age (r=0.805, p=0.002) and treatment duration was noted in MDI group. Our findings in a cohort of T1DM patients with optimal glycemic control revealed that intensive insulin therapy was not associated with an increase in atherosclerotic markers in T1DM, regardless of whether continuous IP infusion or MDIs was administered. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

International Nuclear Information System (INIS)

Skillman, C.A.; Fletcher, H.P.

1986-01-01

The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

Objectively measured sedentary time may predict insulin resistance independent of moderate- and vigorous-intensity physical activity

NARCIS (Netherlands)

Helmerhorst, Hendrik J. F.; Wijndaele, Katrien; Brage, Søren; Wareham, Nicholas J.; Ekelund, Ulf

2009-01-01

To examine the prospective association between objectively measured time spent sedentary and insulin resistance and whether this association is independent of moderate- and vigorous-intensity physical activity (MVPA) and other relevant confounders. This was a population-based study (Medical Research

Using insulin pen needles up to five times does not affect needle tip shape nor increase pain intensity.

Science.gov (United States)

Puder, Jardena J; Atar, Michael; Muller, Beat; Pavan, Marco; Keller, Ulrich

2005-02-01

Reusing insulin pen needles could help to reduce the increasing economic burden of diabetes. We tested the hypothesis that reusing insulin pen needles leads to needle tip deformity and increased pain. Three blinded reviewers assessed 123 electron microscope pictures analyzing needle tip deformity of insulin pen needles used up to four times by diabetic subjects and up to five times by blinded non-diabetic volunteers. The estimated frequency of needle use was correlated to the actual number of needle use. Pain intensity and unpleasantness of each injection were measured by a visual analogue scale and their differences analyzed by Kruskal-Wallis analysis of variance. Unused needles could be differentiated visually from used needles. However, there was no correlation between the actual and guessed number of times a needle was used (r = 0.07, P = 0.2). Evaluating all 270 injections, neither pain intensity nor unpleasantness increased with repeated injections of the same needles in people with diabetes (P = 0.1 and 0.96) and in the volunteers (P = 0.63 and 0.92). Using pen needles four to five times does not lead to progressive needle tip deformity and does not increase pain intensity or unpleasantness, but could increase convenience and lead to substantial financial savings in Europe of around EUR 100 million/year.

Key elements of successful intensive therapy in patients with type 1 diabetes

Directory of Open Access Journals (Sweden)

Banshi Saboo

2015-01-01

Full Text Available An intensified diabetes management approach (including increased education, monitoring, and contact with diabetes team should be used for adolescents and also for younger children if glycaemic control is not achieved by insulin therapy. Treatment options may include increased frequency of injections (e.g. the patients on 2 bolus may require 3 or 4 bolus injections, change in the type of basal and/or bolus insulin depending on multiple times monitoring for adolescents and for younger children, and change to continuous subcutaneous insulin infusion pump therapy. Results of epidemiology of diabetes interventions and complications (EDIC Research Group, where the Diabetes Control and Complications Trial patients were further followed up almost for a period of 7 years or more showed that intensive therapy significantly reduced and maintained glycated hemoglobin with relative risk reduction of microvascular complications in the intensive therapy group. In addition, intensive treatment reduced the risk of any cardiovascular disease (CVD event by 42% and the risk of nonfatal myocardial infarction, stroke, or death from CVD by 57%. The reduction of microvascular and macrovascular events in the intensively-treated group persisted due to the "legacy effect" or "metabolic memory" of early intensive glycemic control. The main advantage of intensive insulin therapy is that it reduces the rate of diabetes complications, in the long run. Furthermore, it offers flexibility as the doses can be adjusted according to the activity and food consumed. The main disadvantage of intensive insulin therapy is the risk of hypoglycemia especially in type 1 diabetes mellitus and weight gain.

Low-volume high-intensity swim training is superior to high-volume low-intensity training in relation to insulin sensitivity and glucose control in inactive middle-aged women

DEFF Research Database (Denmark)

Connolly, Luke J; Nordsborg, Nikolai Baastrup; Nyberg, Michael Permin

2016-01-01

recovery periods and LIT swam continuously for 1 h at low intensity (average HR = 73 ± 3 % HRmax). Fasting blood samples were taken and an oral glucose tolerance test (OGTT) was conducted pre- and post-intervention. RESULTS: After HIT, resting plasma [insulin] was lowered (17 ± 34 %; P ... adhesion molecule 1 had decreased (P intermittent swimming is an effective and time-efficient training strategy for improving insulin sensitivity, glucose control and biomarkers of vascular function...

Clinical use of the co-formulation of insulin degludec and insulin aspart

DEFF Research Database (Denmark)

Kumar, A; Awata, T; Bain, S C

2016-01-01

(HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...... a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins....

Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

Science.gov (United States)

Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

2016-01-15

Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation.

Science.gov (United States)

Pauly, Marion; Assense, Allan; Rondon, Aurélie; Thomas, Amandine; Dubouchaud, Hervé; Freyssenet, Damien; Benoit, Henri; Castells, Josiane; Flore, Patrice

2017-03-03

Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21-5% FiO 2 , 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy.

Frequency and risk factors of severe hypoglycemia in insulin-treated type 2 diabetes

DEFF Research Database (Denmark)

Akram, Kamran; Pedersen-Bjergaard, Ulrik; Borch-Johnsen, Knut

2006-01-01

Intensive treatment regimens including early initiation of insulin treatment are important to prevent late complications in type 2 diabetes. The assumed risk of severe hypoglycemia (SH) is a major barrier to initiation of insulin treatment. To assess the relevance of this risk we evaluated...... the frequency of SH as reported in the literature. Using Medline and Embase search we identified 11 studies (5 retrospective and 6 prospective) including at least 50 patients with insulin-treated type 2 diabetes followed for at least 6 months in which frequency of SH was reported. The incidence of SH....... Only few studies looked into the impact of risk factors on the rate of SH. Impaired hypoglycemia awareness, high age, long duration of diabetes and insulin therapy increased the risk, while no association was found with HbA1c and insulin dose. The present knowledge of SH in insulin-treated type 2...

Radiation doses to neonates requiring intensive care

International Nuclear Information System (INIS)

Robinson, A.; Dellagrammaticas, H.D.

1983-01-01

Radiological investigations have become accepted as an important part of the range of facilities required to support severely ill newborn babies. Since the infants are so small, many of the examinations are virtually ''whole-body'' irradiations and it was thought that the total doses received might be appreciable. A group of such babies admitted to the Neonatal Intensive Care Unit in Sheffield over a six-month period have been studied. X-ray exposure factors used for each examination have been noted and total skin, gonad and bone marrow doses calculated, supplemented by measurements on phantoms. It is concluded that in most cases doses received are of the same order as those received over the same period from natural background radiation and probably less than those received from prenatal obstetric radiography, so that the additional risks from the diagnostic exposure are small. The highest doses are received in CT scans and barium examinations and it is recommended that the need for these should be carefully considered. (author)

Fixed ratio dosing of pramlintide with regular insulin before a standard meal in patients with type 1 diabetes.

Science.gov (United States)

Riddle, M C; Yuen, K C J; de Bruin, T W; Herrmann, K; Xu, J; Öhman, P; Kolterman, O G

2015-09-01

Amylin is co-secreted with insulin and is therefore lacking in patients with type 1 diabetes. Replacement with fixed ratio co-administration of insulin and the amylin analogue pramlintide may be superior to separate dosing. This concept was evaluated in a ratio-finding study. Patients with type 1 diabetes were enrolled in a randomized, single-masked, standard breakfast crossover study using regular human insulin injected simultaneously with pramlintide 6, 9 or 12 mcg/unit insulin or placebo. Insulin dosage was reduced by 30% from patients' usual estimates. Plasma glucose, glucagon and pramlintide and adverse events were assessed. All ratios reduced 0-3-h glucose and glucagon increments by >50%. No hypoglycaemia occurred. Adverse events were infrequent and generally mild. All pramlintide/insulin ratios markedly and safely reduced glycaemic excursions and suppressed glucagon secretion in the immediate postprandial state. Further study using one of these ratios to explore the efficacy and safety of longer-term meal-time and basal hormone replacement is warranted. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

Science.gov (United States)

Crinó, A; Schiaffini, R; Ciampalini, P; Suraci, M C; Manfrini, S; Visalli, N; Matteoli, M C; Patera, P; Buzzetti, R; Guglielmi, C; Spera, S; Costanza, F; Fioriti, E; Pitocco, D; Pozzilli, P

2005-08-01

A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be

Factors that drive insulin-dosing decisions of diabetes care providers: a vignette-based study in the Netherlands

NARCIS (Netherlands)

Simon, A. C. R.; Schopman, J. E.; Hoekstra, J. B. L.; Abu-Hanna, A.; Gerdes, V. E. A.; Peek, N.; Holleman, F.

2015-01-01

To test how certain patient factors would influence the decision of Dutch care providers regarding insulin dose adjustments. We hypothesize that some of these decisions would diverge from recent evidence and consensus statements. We developed narrative vignettes describing clinical scenarios of

An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial.

Science.gov (United States)

Kim, Gyuri; Bae, Ji Cheol; Yi, Byoung Kee; Hur, Kyu Yeon; Chang, Dong Kyung; Lee, Moon-Kyu; Kim, Jae Hyeon; Jin, Sang-Man

2017-07-18

A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system. This is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits. This clinical trial

Two factors influencing dose reconstruction in low dose range: the variability of BKG intensity on one individual and water content

International Nuclear Information System (INIS)

Zhang, Tengda; Zhang, Wenyi; Zhao, Zhixin; Zhang, Haiying; Ruan, Shuzhou; Jiao, Ling

2016-01-01

A fast and accurate retrospective dosimetry method for the triage is very important in radiation accidents. Electron paramagnetic resonance (EPR) fingernail dosimetry is a promising way to estimate radiation dose. This article presents two factors influencing dose reconstruction in low dose range: the variability of background signal (BKG) intensity on one individual and water content. Comparing the EPR spectrum of dried and humidified fingernail samples, it is necessary to add a procedure of dehydration before EPR measurements, so as to eliminate the deviation caused by water content. Besides, the BKGs of different fingers' nails are not the same as researchers thought previously, and the difference between maximum and minimum BKG intensities of one individual can reach 55.89 %. Meanwhile, the variability of the BKG intensity among individuals is large enough to impact precise dose reconstruction. Water within fingernails and instability of BKG are two reasons that cause the inaccuracy of radiation dose reconstruction in low-dosage level. (authors)

Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin.

Science.gov (United States)

Moser, Othmar; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Obermayer-Pietsch, Barbara; Koehler, Gerd; Hofmann, Peter

2015-01-01

We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567.

Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin.

Directory of Open Access Journals (Sweden)

Othmar Moser

Full Text Available We investigated blood glucose (BG and hormone response to aerobic high-intensity interval exercise (HIIE and moderate continuous exercise (CON matched for mean load and duration in type 1 diabetes mellitus (T1DM.Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A and above (B the first lactate turn point and below the second lactate turn point (C on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark. Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A, 50% (B, and 75% (C dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.BG decrease during HIIE was significantly smaller for B (p = 0.024 and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006 and B (p = 0.004 and respiratory exchange ratio for A (p = 0.003 and B (p = 0.003 were significantly higher compared to CON but not for C.Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567.

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

Science.gov (United States)

Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

1988-11-12

To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy.

Science.gov (United States)

Zuckerwise, Lisa C; Werner, Erika F; Pettker, Christian M; McMahon-Brown, Erin K; Thung, Stephen F; Han, Christina S

2012-08-01

Increased insulin requirements in pregnancy can hinder attainment of glycemic control in diabetic patients. U-500 insulin is a concentrated form of regular insulin that can be a valuable tool in the treatment of patients with severe insulin resistance. A 24-year-old woman with pregestational diabetes mellitus experienced increasing insulin requirements during pregnancy, peaking at 650 units daily. The frequent, large-volume injections of standard-concentration insulin were poorly tolerated by the patient and resulted in nonadherence. She subsequently achieved glycemic control on thrice-daily U-500 insulin. Pregnancy exacerbates insulin resistance in diabetic patients, and these patients may require high doses of insulin. U-500 insulin is an effective alternative for patients with severe insulin resistance and should be considered for pregnant women with difficulty achieving glycemic control.

Extremely short duration high intensity interval training substantially improves insulin action in young healthy males

DEFF Research Database (Denmark)

Babraj, John A; Vollaard, Niels B J; Keast, Cameron

2009-01-01

BACKGROUND: Traditional high volume aerobic exercise training reduces cardiovascular and metabolic disease risk but involves a substantial time commitment. Extremely low volume high-intensity interval training (HIT) has recently been demonstrated to produce improvements to aerobic function...... cycle sprints per session). Aerobic performance (250-kJ self-paced cycling time trial), and glucose, insulin and NEFA responses to a 75-g oral glucose load (oral glucose tolerance test; OGTT) were determined before and after training. RESULTS: Following 2 weeks of HIT, the area under the plasma glucose......, to substantially improve insulin action in young sedentary subjects is remarkable. This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise...

A cross-sectional survey among patients and prescribers on insulin dosing irregularities and impact of mild (self-treated) hypoglycemia episodes in Spanish patients with type 2 diabetes as compared to other European patients.

Science.gov (United States)

Ampudia-Blasco, Francisco J; Galán, Manuel; Brod, Meryl

2014-10-01

In Spain, data suggest that 13.8% of adults have diabetes. Two important aspects in diabetes management are mild hypoglycemic episodes and poor treatment adherence. This study assesses the impact of missed insulin doses and prevalence of mistimed and reduced insulin doses and mild hypoglycemia in patients with type 2 diabetes treated with basal insulin analogues in Spain, and compares the data collected to pooled data from 8 other European countries (OECs). GAPP2 was an international, online, cross-sectional study of diabetic patients aged ≥40 years treated with long-acting insulin analogues and their healthcare professionals. Patients and healthcare professionals were recruited from online research panels. Data reported in Spain are compared to pooled data from 8 OECs. In Spain, 1-3% of patients reported they had reduced, missed, or mistimed at least one insulin does in the previous month. Significantly more OEC patients reported dosing irregularities (15-23%; all P<0.01). In Spain, 77% of patients were worried and 59% felt guilty for missing a dose of basal insulin, while 24% reported that they were very worried about nocturnal hypoglycemia. Significantly fewer OEC patients reported worrying (47%; P<0.01) and feeling guilty (37%; P<0.01) about missing an insulin dose, or worry about nocturnal hypoglycemia (12%; P<0.01). In Spain, patients with type 2 diabetes report fewer dosing irregularities and hypoglycemic episodes as compared to patients from OECs. However, Spanish patients appear to have a reduced quality of life related to hypoglycemia as well as worry and guilt related to insulin dosing irregularities. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

Acute High-intensity Interval Exercise-induced Redox Signaling is Associated with Enhanced Insulin Sensitivity in Obese Middle-aged Men.

Directory of Open Access Journals (Sweden)

Lewan Parker

2016-09-01

Full Text Available Background. Obesity and ageing are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK, and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods. Participants completed a 2 hour hyperinsulinaemic-euglycaemic clamp at rest, and 60 minutes after HIIE (4x4 mins at 95% HRpeak; 2 min recovery periods, separated by 1-3 weeks. Results. Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SAPK phosphorylation (JNK, p38 MAPK and NF-κB and SOD activity (p<0.05. Conclusion. These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 hours after HIIE.

Calcification of human vascular smooth muscle cells: associations with osteoprotegerin expression and acceleration by high-dose insulin

DEFF Research Database (Denmark)

Olesen, Ping; Knudsen, Kirsten Quyen Nguyen; Wogensen, Lise

2007-01-01

Arterial medial calcifications occur often in diabetic individuals as part of the diabetic macroangiopathy. The pathogenesis is unknown, but the presence of calcifications predicts risk of cardiovascular events. We examined the effects of insulin on calcifying smooth muscle cells in vitro...... and measured the expression of the bone-related molecule osteoprotegerin (OPG). Human vascular smooth muscle cells (VSMCs) were grown from aorta from kidney donors. Induction of calcification was performed with beta-glycerophosphate. The influence of insulin (200 microU/ml or 1,000 microU/ml) on calcification...... calcification in human smooth muscle cells from a series of donors after variable time in culture. Decreased OPG amounts were observed from the cells during the accelerated calcification phase. High dose of insulin (1,000 microU/ml) accelerated the calcification, whereas lower concentrations (200 microU/ml) did...

The Mobile Insulin Titration Intervention (MITI) for Insulin Adjustment in an Urban, Low-Income Population: Randomized Controlled Trial.

Science.gov (United States)

Levy, Natalie; Moynihan, Victoria; Nilo, Annielyn; Singer, Karyn; Bernik, Lidia S; Etiebet, Mary-Ann; Fang, Yixin; Cho, James; Natarajan, Sundar

2015-07-17

Diabetes patients are usually started on a low dose of insulin and their dose is adjusted or "titrated" according to their blood glucose levels. Insulin titration administered through face-to-face visits with a clinician can be time consuming and logistically burdensome for patients, especially those of low socioeconomic status (SES). Given the wide use of mobile phones among this population, there is the potential to use short message service (SMS) text messaging and phone calls to perform insulin titration remotely. The goals of this pilot study were to (1) evaluate if our Mobile Insulin Titration Intervention (MITI) intervention using text messaging and phone calls was effective in helping patients reach their optimal insulin glargine dose within 12 weeks, (2) assess the feasibility of the intervention within our clinic setting and patient population, (3) collect data on the cost savings associated with the intervention, and (4) measure patient satisfaction with the intervention. This was a pilot study evaluating an intervention for patients requiring insulin glargine titration in the outpatient medical clinic of Bellevue Hospital Center in New York City. Patients in the intervention arm received weekday SMS text messages from a health management platform requesting their fasting blood glucose values. The clinic's diabetes nurse educator monitored the texted responses on the platform website each weekday for alarm values. Once a week, the nurse reviewed the glucose values, consulted the MITI titration algorithm, and called patients to adjust their insulin dose. Patients in the usual care arm continued to receive their standard clinic care for insulin titration. The primary outcome was whether a patient reached his/her optimal insulin glargine dose within 12 weeks. A total of 61 patients consented and were randomized into the study. A significantly greater proportion of patients in the intervention arm reached their optimal insulin glargine dose than patients in

Mild Caloric Restriction Decreases Insulin Requirements in Patients With Type 2 Diabetes and Severe Insulin Resistance.

Science.gov (United States)

Meehan, Cristina Adelia; Cochran, Elaine; Mattingly, Megan; Gorden, Phillip; Brown, Rebecca J

2015-07-01

Type 2 diabetes (T2D) affects ~10% of the US population, a subset of whom have severe insulin resistance (SIR) (>200 units/d). Treatment of these patients with high-dose insulin presents logistical and compliance challenges. We hypothesized that mild caloric restriction would reduce insulin requirements in patients with T2D and SIR.This was a retrospective study at the National Institutes of Health Clinical Center. Inclusion criteria were as follows: T2D, and insulin dose >200 units/d or >2 units/kg/d. The intervention consisted of mild caloric restriction during a 3 to 6-day hospitalization. The major outcomes were change in insulin dose and blood glucose from admission to discharge.Ten patients met inclusion criteria. Baseline glycated hemoglobin A1c was 10.0 ± 1.6% and body mass index 38.8 ± 9.0 kg/m. Food intake was restricted from 2210 ± 371 kcal/d preadmission to 1810 ± 202 during the hospital stay (16.5% reduction). Insulin dose decreased from 486 ± 291 units/d preadmission to 223 ± 127 at discharge (44% reduction, P = 0.0025). Blood sugars decreased nonsignificantly in the fasting state (from 184 ± 85 to 141 ± 42, P = 0.20), before lunch (239 ± 68 to 180 ± 76, P = 0.057), and at bedtime (212 ± 95 to 176 ± 48, P = 0.19), and significantly decreased before dinner (222 ± 92 to 162 ± 70, P = 0.016).Mild caloric restriction, an accessible and affordable intervention, substantially reduced insulin doses in patients with T2D and SIR. Further studies are needed to determine if the intervention and results are sustainable outside of a hospital setting.

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

Science.gov (United States)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

Insulin resistance in type 1 (insulin-dependent) diabetes: dissimilarities for glucose and intermediary metabolites

NARCIS (Netherlands)

Nijs, H. G.; Radder, J. K.; Poorthuis, B. J.; Krans, H. M.

1990-01-01

To study insulin action on intermediary metabolism in relation to glucose disposal in Type 1 (insulin-dependent) diabetes, 29 patients and 15 control subjects underwent sequential euglycemic clamps (insulin infusion rates 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in 2 hour periods). Dose-response curves

Effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing gastrectomy

Institute of Scientific and Technical Information of China (English)

Han-Cheng Liu; Yan-Bing Zhou; Dong Chen; Zhao-Jian Niu; Yang Yu

2012-01-01

AIM:To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy.METHODS:Within 24 h of intensive care unit management,patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L.Resting energy expenditure (REE),respiratory quotient (RQ),resting energy expenditure per kilogram (REE/kg),and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system.The changes in body composition were analyzed by multi-frequency bioimpedance analysis.Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance.RESULTS:Sixty patients were enrolled.Compared with preoperative baseline,postoperative REE increased by over 22.15％ and 11.07％; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25％ ± 17.74％ and 67.13％ ± 12.76％ supported by parenteral nutrition solutions from 37.56％ ± 11.64％ at the baseline; the level of Ln-HOMA-IR went up dramatically (P ＜ 0.05,respectively) on postoperative days 1 and 3 in the IIT group.Meanwhile the concentration of total protein,albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P ＜ 0.05,respectively).Compared with the CIT group,IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg,P =0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg,P =0.013); and decreased the Ln-HOMA-IR score (P =0.019,0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P

The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes: Implications for Intensive Diabetes Management.

Science.gov (United States)

Paterson, Megan; Bell, Kirstine J; O'Connell, Susan M; Smart, Carmel E; Shafat, Amir; King, Bruce

2015-09-01

A primary focus of the management of type 1 diabetes has been on matching prandial insulin therapy with carbohydrate amount consumed. However, even with the introduction of more flexible intensive insulin regimes, people with type 1 diabetes still struggle to achieve optimal glycaemic control. More recently, dietary fat and protein have been recognised as having a significant impact on postprandial blood glucose levels. Fat and protein independently increase the postprandial glucose excursions and together their effect is additive. This article reviews how the fat and protein in a meal impact the postprandial glycaemic response and discusses practical approaches to managing this in clinical practice. These insights have significant implications for patient education, mealtime insulin dose calculations and dosing strategies.

The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis.

Science.gov (United States)

Jelleyman, C; Yates, T; O'Donovan, G; Gray, L J; King, J A; Khunti, K; Davies, M J

2015-11-01

The aim of this meta-analysis was to quantify the effects of high-intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = -0.49, confidence intervals [CIs] -0.87 to -0.12, P = 0.009; CT: SMD = -0.35, -0.68 to -0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (-0.36 to -0.03, P = 0.021) and body weight decreased by 1.3 kg (-1.9 to -0.7, P HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results. © 2015 World Obesity.

High intensity interval exercise is an effective alternative to moderate intensity exercise for improving glucose tolerance and insulin sensitivity in adolescent boys.

Science.gov (United States)

Cockcroft, Emma J; Williams, Craig A; Tomlinson, Owen W; Vlachopoulos, Dimitris; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2015-11-01

High-intensity interval exercise (HIIE) may offer a time efficient means to improve health outcomes compared to moderate-intensity exercise (MIE). This study examined the acute effect of HIIE compared to a work-matched bout of MIE on glucose tolerance, insulin sensitivity (IS), resting fat oxidation and exercise enjoyment in adolescent boys. Within-measures design with counterbalanced experimental conditions. Nine boys (14.2 ± 0.4 years) completed three conditions on separate days in a counterbalanced order: (1) HIIE; (2) work matched MIE, both on a cycle ergometer; and (3) rest (CON). An oral glucose tolerance test (OGTT) was performed after exercise or rest and the area under curve (AUC) responses for plasma [glucose] and [insulin] were calculated, and IS estimated (Cederholm index). Energy expenditure and fat oxidation were measured following the OGTT using indirect calorimetry. Exercise enjoyment was assessed using the Physical Activity Enjoyment Scale. The incremental AUC (iAUC) for plasma [glucose] was reduced following both MIE (-23.9%, P = 0.013, effect size [ES] = -0.64) and HIIE (-28.9%, P=0.008, ES = -0.84) compared to CON. The iAUC for plasma [insulin] was lower for HIIE (-24.2%, P = 0.021, ES = -0.71) and MIE (-29.1%, P = 0.012, ES = -0.79) compared to CON. IS increased by 11.2% after HIIE (P = 0.03, ES = 0.76) and 8.4% after MIE (P = 0.10, ES = 0.58). There was a trend for an increase in fat oxidation following HIIE (P = 0.097, ES = 0.70). Both HIIE and MIE were rated as equally enjoyable (P > 0.05, ES effective alternative to MIE for improving glucose tolerance and IS in adolescent boys immediately after exercise. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes.

Directory of Open Access Journals (Sweden)

Duk-Hee Lee

2011-01-01

Full Text Available There is emerging evidence that background exposure to persistent organic pollutants (POPs are important in the development of conditions predisposing to diabetes as well as of type 2 diabetes itself. We recently reported that low dose POPs predicted incident type 2 diabetes in a nested case-control study. The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study.The 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2 sera included 8 organochlorine (OC pesticides, 22 polychlorinated biphenyls (PCBs, and 1 polybrominated biphenyl (PBB. Body mass index (BMI, triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA-IR were study outcomes at 2005-06 (year 20. The evolution of study outcomes during 18 years by categories of serum concentrations of POPs at year 2 was evaluated by adjusting for the baseline values of outcomes plus potential confounders. Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Oxychlordane, trans-nonachlor, and hexachlorobenzene also significantly predicted higher triglycerides. Persistent PCBs with ≥7 chlorides predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 with similar dose-response curves.Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases

Personalized State-space Modeling of Glucose Dynamics for Type 1 Diabetes Using Continuously Monitored Glucose, Insulin Dose, and Meal Intake: An Extended Kalman Filter Approach

OpenAIRE

Wang, Qian; Molenaar, Peter; Harsh, Saurabh; Freeman, Kenneth; Xie, Jinyu; Gold, Carol; Rovine, Mike; Ulbrecht, Jan

2014-01-01

An essential component of any artificial pancreas is on the prediction of blood glucose levels as a function of exogenous and endogenous perturbations such as insulin dose, meal intake, and physical activity and emotional tone under natural living conditions. In this article, we present a new data-driven state-space dynamic model with time-varying coefficients that are used to explicitly quantify the time-varying patient-specific effects of insulin dose and meal intake on blood glucose fluctu...

[Comparative analysis of insulin glargine vs. insulin detemir: A cost-minimization study applicable to Colombia].

Science.gov (United States)

Fragozo, Argemiro; Puerta, María Fernanda; Misas, Juan Diego

2015-01-01

More than 90% of subjects diagnosed with diabetes mellitus present with type 2, which is recognized for peripheral insulin resistance. To determine the costs of achieving glycemic target with the use of basal insulin analogs, insulin glargine (IG) once a day vs. insulin detemir (ID) once or twice a day, with a cost minimization model built from a third-party payer perspective in Colombia. A systematic review of comparative clinical trials between IG and ID in patients with insulin-resistant type 2 diabetes was performed to determine data of use, effectiveness and frequency of and adverse events. The goal of glycemic control (effectiveness measure) was defined as HbA1c=7%. The costs of insulin were extracted from the Integrated System of Medication Prices 2012 (Ministerio de Salud y Protección Social de Colombia) and the IMS Consulting Group mobile average cost for the past year as of December, 2012. Sensitivity analyses were performed via Montecarlo simulations for dose and medication costs (insulin). Five publications met inclusion criteria. The range of the difference between insulin doses was 3.2 IU to 33 IU. The percentage of patients requiring two ID doses was 12.6-100%. There were no significant differences in hypoglycemic events. For both retail and institutional channels, there was a higher differential cost between IG vs. ID favoring IG in 4 and 5 studies, respectively. For the retail channel only one study showed the opposite results. As only medication costs are considered, differences in insulin units between IG and ID result in a differential cost in favor of IG that makes it a cost/effective alternative.

Add-on treatment with intermediate-acting insulin versus sliding-scale insulin for patients with type 2 diabetes or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy: a randomized crossover study

NARCIS (Netherlands)

Gerards, M. C.; de Maar, J. S.; Steenbruggen, T. G.; Hoekstra, J. B. L.; Vriesendorp, T. M.; Gerdes, V. E. A.

2016-01-01

The aim of this study was to compare the effectiveness and safety of intermediate-acting insulin (IMI) titrated on body weight and glucocorticoid dose with that of short-acting sliding-scale insulin (SSI) in patients on recurrent high-dose glucocorticoid-containing chemotherapy. We enrolled 26

Prospective analysis of principles and frequency of self-adjustment of insulin dose in people with diabetes type 1 before and after participation in a diabetes treatment and teaching programme.

Science.gov (United States)

Kramer, Guido; Kuniss, Nadine; Jörgens, Viktor; Lehmann, Thomas; Müller, Nicolle; Lorkowski, Stefan; Wolf, Gunter; Müller, Ulrich A; Kloos, Christof

2016-09-01

Insulin dose self-adjustment is an essential part of intensified insulin therapy - nowadays the routine treatment of type 1 diabetes (DM1). The aim of this study was to evaluate principles and frequency of insulin dose self-adjustments in people with DM1 before and one year after participating in a structured diabetes treatment and teaching programme (DTTP) and to determine to which extent the patients followed the way they had been trained. 72 people with DM1 were interviewed before participation in our inpatient (32/72) or outpatient (40/72) DTTP. Sixty-six participants (91.7%) were followed up after one year. The number of adaptations of the insulin dose by the patients was recorded from 28days of the patients' diary. The ability to find the correct dose was tested using five different examples. Metabolic control improved significantly after one year (7.9±1.0 to 7.5±0.8%, p=0.004). The participants performed 86.0±37.1 insulin dosage adaptations per 28days before the DTTP. After one year the frequency increased significantly to 99.1±30.7 per 28days (p=0.011). Before the DTTP, 42 of 72 patients (58.3%) adjusted their insulin dose to correct high blood glucose levels by adjustment rules (factor for correction or correction scheme) and 20 of 72 people (27.8%) by personal experience/feeling. One year after the DTTP, 73% (48/66) used adjustment rules. After participating in an structured education programme, patients adjusted their insulin dosage more frequently. Metabolic control improved despite the fact that many patients did not strictly apply the rules they had been trained for. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Radiation doses received by premature babies in the neonatal intensive care unit

International Nuclear Information System (INIS)

Thierry-Chef, I.; Maccia, C.; Thierry-Chef, I.; Laurier, D.; Tirmarche, M.; Costil, J.

2005-01-01

Purpose. Because of frequent radiological investigations performed in 1 neonatal intensive care unit, a dosimetry study was carried out to assess the level of doses received by premature babies. Materials and methods. In vivo measurements were performed and effective doses were evaluated for single radiographs. Individual cumulative doses received over the period of stay were then estimated, for each premature baby entering the intensive care unit in 2002, taking into account the number of radiographs they underwent. Results. On average, babies stayed for a week and more than one radio-graph was taken per day. Results showed that, even if average doses per radiograph were relatively low (25μSv), cumulative doses strongly depended on the length of stay, and can reach a few mSv. Conclusion. Even if doses per radiograph are in agreement with European recommendations, optimisation of doses is particularly important because premature babies are more sensitive to radiation than adults and because they usually undergo further radiological examinations in other services. On the basis of the results of this dosimetry study, the implementation of a larger study is being discussed. (author)

Variation in 125I-Insulin absorption and blood glucose concentration

International Nuclear Information System (INIS)

Lauritzen, T.; Faber, O.K.; Binder, C.

1979-01-01

The absorption of monocomponent porcine 125 I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily 125 I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the 125 I-insulin dose. A significant correlation (p [de

Posology of insulins: A review of standard textbooks and product inserts.

Science.gov (United States)

Bhutani, Garima; Kalra, Sanjay

2015-01-01

The study is aimed to assess whether the information contained in standard pharmacology, endocrinology, and diabetology textbooks regarding timings of administration, frequency and dose of various insulins is adequate and also to see whether the information contained in these texts is concordant with product inserts. Four standard textbooks of pharmacology, two of diabetology and three of endocrinology were assessed for the published information regarding dose, timing, and frequency of insulin administration. The product inserts of commonly available insulins in India were also studied for the same. Various omissions and disparities could be seen in the coverage of insulins in standard textbooks. Posology information about premixed insulins and basal insulins have been omitted by the majority of the textbooks. Details about dose, frequency and timings of ultra-short acting insulins have also not been covered by all textbooks. Some discrepancies regarding prescribing information was also noted in product inserts, especially in case of newer insulins. Thus, this article stresses upon the need of a uniform source of information for providing adequate and standardized knowledge regarding timing, frequency, and dose of insulins.

High-intensity interval training improves insulin sensitivity in older individuals.

Science.gov (United States)

Søgaard, D; Lund, M T; Scheuer, C M; Dehlbaek, M S; Dideriksen, S G; Abildskov, C V; Christensen, K K; Dohlmann, T L; Larsen, S; Vigelsø, A H; Dela, F; Helge, J W

2018-04-01

Metabolic health may deteriorate with age as a result of altered body composition and decreased physical activity. Endurance exercise is known to counter these changes delaying or even preventing onset of metabolic diseases. High-intensity interval training (HIIT) is a time efficient alternative to regular endurance exercise, and the aim of this study was to investigate the metabolic benefit of HIIT in older subjects. Twenty-two sedentary male (n = 11) and female (n = 11) subjects aged 63 ± 1 years performed HIIT training three times/week for 6 weeks on a bicycle ergometer. Each HIIT session consisted of five 1-minute intervals interspersed with 1½-minute rest. Prior to the first and after the last HIIT session whole-body insulin sensitivity, measured by a hyperinsulinaemic-euglycaemic clamp, plasma lipid levels, HbA1c, glycaemic parameters, body composition and maximal oxygen uptake were assessed. Muscle biopsies were obtained wherefrom content of glycogen and proteins involved in muscle glucose handling were determined. Insulin sensitivity (P = .011) and maximal oxygen uptake increased (P body fat (P < .05) decreased after 6 weeks of HIIT. HbA1c decreased only in males (P = .001). Muscle glycogen content increased in both genders (P = .001) and in line GLUT4 (P < .05), glycogen synthase (P = .001) and hexokinase II (P < .05) content all increased. Six weeks of HIIT significantly improves metabolic health in older males and females by reducing age-related risk factors for cardiometabolic disease. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

High-intensity interval training improves insulin sensitivity in older individuals

DEFF Research Database (Denmark)

Søgaard, D; Lund, M T; Scheuer, C M

2017-01-01

AIM: Metabolic health may deteriorate with age as a result of altered body composition and decreased physical activity. Endurance exercise is known to counter these changes delaying or even preventing onset of metabolic diseases. High-intensity interval training (HIIT) is a time efficient...... alternative to regular endurance exercise, and the aim of this study was to investigate the metabolic benefit of HIIT in older subjects. METHODS: Twenty-two sedentary male (n = 11) and female (n = 11) subjects aged 63 ± 1 years performed HIIT training three times/week for 6 weeks on a bicycle ergometer. Each...... HIIT session consisted of five 1-minute intervals interspersed with 1½-minute rest. Prior to the first and after the last HIIT session whole-body insulin sensitivity, measured by a hyperinsulinaemic-euglycaemic clamp, plasma lipid levels, HbA1c, glycaemic parameters, body composition and maximal oxygen...

Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

Science.gov (United States)

Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

2018-03-14

The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

The brain modulates insulin sensitivity in multiple tissues

NARCIS (Netherlands)

Parlevliet, Edwin T.; Coomans, Claudia P.; Rensen, Patrick C. N.; Romijn, Johannes A.

2014-01-01

Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system. The dose-response effects of insulin differ between the various physiological effects of

Posology of insulins: A review of standard textbooks and product inserts

Directory of Open Access Journals (Sweden)

Garima Bhutani

2015-01-01

Full Text Available Objectives: The study is aimed to assess whether the information contained in standard pharmacology, endocrinology, and diabetology textbooks regarding timings of administration, frequency and dose of various insulins is adequate and also to see whether the information contained in these texts is concordant with product inserts. Materials and Methods: Four standard textbooks of pharmacology, two of diabetology and three of endocrinology were assessed for the published information regarding dose, timing, and frequency of insulin administration. The product inserts of commonly available insulins in India were also studied for the same. Results: Various omissions and disparities could be seen in the coverage of insulins in standard textbooks. Posology information about premixed insulins and basal insulins have been omitted by the majority of the textbooks. Details about dose, frequency and timings of ultra-short acting insulins have also not been covered by all textbooks. Some discrepancies regarding prescribing information was also noted in product inserts, especially in case of newer insulins. Conclusions: Thus, this article stresses upon the need of a uniform source of information for providing adequate and standardized knowledge regarding timing, frequency, and dose of insulins.

Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

Science.gov (United States)

Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

2009-01-01

Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as

Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients.

Science.gov (United States)

Waldhäusl, W K; Bratusch-Marrain, P R; Francesconi, M; Nowotny, P; Kiss, A

1982-01-01

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.

Predicting the effects of organ motion on the dose delivered by dynamic intensity modulation

International Nuclear Information System (INIS)

Yu, C.X.; Jaffray, David; Martinez, A.A.; Wong, J.W.

1997-01-01

Purpose: Computer-optimized treatment plans, aimed to enhance tumor control and reduce normal tissue complication, generally require non-uniform beam intensities. One of the techniques for delivering intensity-modulated beams is the use of dynamic multileaf collimation, where the beam aperture and field shape change during irradiation. When intensity-modulated beams are delivered with dynamic collimation, intra-treatment organ motion may not only cause geometric misses at the field boundaries but also create hot and cold spots in the target. The mechanism for producing such effects has not been well understood. This study analyzes the dosimetric effects of intra-treatment organ motion on dynamic intensity modulation. A numerical method is developed for predicting the intensity distributions in a moving target before dose is delivered with dynamic intensity modulation. Material and Methods: In the numerical algorithm, the change in position and shape of the beam aperture with time were modeled as a three-dimensional 'tunnel', with the shape of the field aperture described in the x-y plane and its temporal position shown in the z-dimension. A point in the target had to be in the tunnel in order to receive irradiation and the dose to the point was proportional to the amount of time that this point stayed in the tunnel. Since each point in the target were analyzed separately, non-rigid body variations could easily be handled. The dependency of the dose variations on all parameters involved, including the speed of collimator motion, the frequency and amplitude of the target motion, and the size of the field segments, was analyzed. The algorithm was verified by irradiating moving phantoms with beams of dynamically modulated intensities. Predictions were also made for a treatment of a thoracic tumor using a dynamic wedge. The changes of target position with time were based on the MRI images of the chest region acquired using fast MRI scans in a cine fashion for a duration

Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

Science.gov (United States)

Anderson, Katie L; Frazier, Hilaree N; Maimaiti, Shaniya; Bakshi, Vikas V; Majeed, Zana R; Brewer, Lawrence D; Porter, Nada M; Lin, Ai-Ling; Thibault, Olivier

2017-02-01

Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Intensive Insulin Therapy: Tight Blood Sugar Control

Science.gov (United States)

... specific situation. McCulloch DK. General principles of insulin therapy in diabetes mellitus. http://www.uptodate.com/home. Accessed Dec. ... Diabetes Association. http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/checking-your-blood- ...

Normal insulin-stimulated endothelial function and impaired insulin-stimulated muscle glucose uptake in young adults with low birth weight

DEFF Research Database (Denmark)

Hermann, T S; Rask-Madsen, C; Ihlemann, N

2003-01-01

of acetylcholine and sodium nitroprusside in the forearm of fourteen 21-yr-old men with low birth weight and 16 controls of normal birth weight. Glucose uptake was measured during intraarterial insulin infusion. Dose-response studies were repeated during insulin infusion. The maximal blood flow during......Low birth weight has been linked to insulin resistance and cardiovascular disease. We hypothesized that insulin sensitivity of both muscle and vascular tissues were impaired in young men with low birth weight. Blood flow was measured by venous occlusion plethysmography during dose-response studies...... acetylcholine infusion was 14.1 +/- 2.7 and 14.4 +/- 2.1 [ml x (100 ml forearm)(-1) x min(-1)] in low and normal birth weight subjects, respectively. Insulin coinfusion increased acetylcholine-stimulated flow in both groups: 18.0 +/- 3.1 vs. 17.9 +/- 3.1 [ml x (100 ml forearm)(-1) x min(-1)], NS. Insulin...

Will the next generation of basal insulins offer clinical advantages?

Science.gov (United States)

Garber, A J

2014-06-01

The 21st century has seen the arrival of several insulin analogue products and the refinement of insulin regimens, with widespread advocacy of continuous titration algorithms and earlier initiation of supplementary insulin therapy (predominantly using basal insulins) in type 2 diabetes. Nevertheless, many insulin-treated diabetes patients remain in poor glycaemic control. This might reflect insufficient titration effort or lax adherence, but these issues could in some cases result from concerns about hypoglycaemia. Certainly there is scope for improving the pharmacokinetic/pharmacodynamic (PK/PD) profile of basal insulin, and three new products offer this prospect. Insulin degludec, now in clinical use, and PEGylated insulin lispro, in development, have greatly extended action profiles that result from two very different, but unique, mechanisms. With once-daily dosing, these insulins produce stable PK/PD profiles at steady state, associated with a low incidence of hypoglycaemia. The feasibility of varied daily dose timing has also been confirmed with insulin degludec. High strength formulations of insulin glargine and insulin degludec offer the prospect of a reduced injection number/volume in high dose users, and in the case of glargine, the PK/PD profile might also be favourably modified. This review considers critically the clinical evidence and expectations we should have for these new basal insulins. © 2013 John Wiley & Sons Ltd.

Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control.

Science.gov (United States)

Soliman, Ashraf T; Omar, Magdi; Assem, Hala M; Nasr, Ibrahim S; Rizk, Mohamed M; El Matary, Wael; El Alaily, Rania K

2002-03-01

Although obesity is a frequent feature of type 2 diabetes mellitus (DM), many patients with type 1 DM are prone to high body mass index (BMI). We measured serum leptin concentrations in a cohort of children (n = 55) with type 1 diabetes mellitus (DM), as well as their anthropometric parameters including BMI, skin fold thickness at multiple sites, and midarm circumference. Glycemic control was assessed by blood glucose (BG) monitoring before meals, and measurement of glycated hemoglobin (HbA1c) and insulin dose/kg/d was recorded. Dietary evaluation and assessment of caloric intake (kg/d) was performed by an expert dietitian. In the newly diagnosed children (n = 10) before initiation of insulin therapy, circulating leptin concentration was significantly lower (1.1 +/- 0.8 ng/dL) versus 5 days after insulin therapy (1.45 +/- 0.7 ng/dL). The decreased leptin level appears to be related to insulinopenia in these patients. In 45 children with type 1 DM on conventional therapy (2 doses of insulin mixture (NPH and regular) subcutaneous (SC) before breakfast and dinner for more than 2 years), serum leptin concentration was significantly higher (2.15 +/- 1 ng/dL) compared with age-matched normal children (1.3 +/- 1 ng/dL). Diabetic children were further divided into 2 groups according to their HbA1c level: group 1 with HbA1C less than 7.5% (less than 2 SD above the mean for normal population) (n = 29) and group 2 with HbA1c greater than 7.5%. (greater than 2 SD above the mean for normal population) (n = 16). Patients with a higher HbA1c level (group 2) had a higher leptin concentration (2.3 +/- 0.8 ng/dL), higher BMI (17.8 +/- 1.7), and were receiving higher insulin dose/kg (0.92 +/- 0.2 U/kg/d) compared with group 1 (lower HbA1c) (1.78 +/- 0.8 ng/dL, 16.7 +/- 1.5, and 0.59 +/- 0.2 U/kg/d, respectively). Group 2 patients had a higher incidence of late morning hypoglycemia (9/29) versus group 1 patients (2/16). Analysis of dietary intake showed that patients with a higher Hb

Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

Science.gov (United States)

Papas, Klearchos K; Bellin, Melena D; Sutherland, David E R; Suszynski, Thomas M; Kitzmann, Jennifer P; Avgoustiniatos, Efstathios S; Gruessner, Angelika C; Mueller, Kathryn R; Beilman, Gregory J; Balamurugan, Appakalai N; Loganathan, Gopalakrishnan; Colton, Clark K; Koulmanda, Maria; Weir, Gordon C; Wilhelm, Josh J; Qian, Dajun; Niland, Joyce C; Hering, Bernhard J

2015-01-01

Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.

Islet Oxygen Consumption Rate (OCR Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

Directory of Open Access Journals (Sweden)

Klearchos K Papas

Full Text Available Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR in predicting clinical islet autotransplant (IAT insulin independence (II. IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity.Membrane integrity staining (FDA/PI, OCR normalized to DNA (OCR/DNA, islet equivalent (IE and OCR (viable IE normalized to recipient body weight (IE dose and OCR dose, and OCR/DNA normalized to islet size index (ISI were used to characterize autoislet preparations (n = 35. Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis.Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001. These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC = 0.94 for IE dose and 0.96 for OCR dose. FDA/PI (AUC = 0.49 and OCR/DNA (AUC = 0.58 did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72.Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.

Application of a Novel Dose-Uncertainty Model for Dose-Uncertainty Analysis in Prostate Intensity-Modulated Radiotherapy

International Nuclear Information System (INIS)

Jin Hosang; Palta, Jatinder R.; Kim, You-Hyun; Kim, Siyong

2010-01-01

Purpose: To analyze dose uncertainty using a previously published dose-uncertainty model, and to assess potential dosimetric risks existing in prostate intensity-modulated radiotherapy (IMRT). Methods and Materials: The dose-uncertainty model provides a three-dimensional (3D) dose-uncertainty distribution in a given confidence level. For 8 retrospectively selected patients, dose-uncertainty maps were constructed using the dose-uncertainty model at the 95% CL. In addition to uncertainties inherent to the radiation treatment planning system, four scenarios of spatial errors were considered: machine only (S1), S1 + intrafraction, S1 + interfraction, and S1 + both intrafraction and interfraction errors. To evaluate the potential risks of the IMRT plans, three dose-uncertainty-based plan evaluation tools were introduced: confidence-weighted dose-volume histogram, confidence-weighted dose distribution, and dose-uncertainty-volume histogram. Results: Dose uncertainty caused by interfraction setup error was more significant than that of intrafraction motion error. The maximum dose uncertainty (95% confidence) of the clinical target volume (CTV) was smaller than 5% of the prescribed dose in all but two cases (13.9% and 10.2%). The dose uncertainty for 95% of the CTV volume ranged from 1.3% to 2.9% of the prescribed dose. Conclusions: The dose uncertainty in prostate IMRT could be evaluated using the dose-uncertainty model. Prostate IMRT plans satisfying the same plan objectives could generate a significantly different dose uncertainty because a complex interplay of many uncertainty sources. The uncertainty-based plan evaluation contributes to generating reliable and error-resistant treatment plans.

Personalized State-space Modeling of Glucose Dynamics for Type 1 Diabetes Using Continuously Monitored Glucose, Insulin Dose, and Meal Intake

Science.gov (United States)

Molenaar, Peter; Harsh, Saurabh; Freeman, Kenneth; Xie, Jinyu; Gold, Carol; Rovine, Mike; Ulbrecht, Jan

2014-01-01

An essential component of any artificial pancreas is on the prediction of blood glucose levels as a function of exogenous and endogenous perturbations such as insulin dose, meal intake, and physical activity and emotional tone under natural living conditions. In this article, we present a new data-driven state-space dynamic model with time-varying coefficients that are used to explicitly quantify the time-varying patient-specific effects of insulin dose and meal intake on blood glucose fluctuations. Using the 3-variate time series of glucose level, insulin dose, and meal intake of an individual type 1 diabetic subject, we apply an extended Kalman filter (EKF) to estimate time-varying coefficients of the patient-specific state-space model. We evaluate our empirical modeling using (1) the FDA-approved UVa/Padova simulator with 30 virtual patients and (2) clinical data of 5 type 1 diabetic patients under natural living conditions. Compared to a forgetting-factor-based recursive ARX model of the same order, the EKF model predictions have higher fit, and significantly better temporal gain and J index and thus are superior in early detection of upward and downward trends in glucose. The EKF based state-space model developed in this article is particularly suitable for model-based state-feedback control designs since the Kalman filter estimates the state variable of the glucose dynamics based on the measured glucose time series. In addition, since the model parameters are estimated in real time, this model is also suitable for adaptive control. PMID:24876585

Potential formula for the calculation of starting and incremental insulin glargine doses: ALOHA subanalysis.

Directory of Open Access Journals (Sweden)

Takashi Kadowaki

Full Text Available BACKGROUND: Pragmatic methods for dose optimization are required for the successful basal management in daily clinical practice. To derive a useful formula for calculating recommended glargine doses, we analyzed data from the Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA study, a 24-week observation of Japanese type 2 diabetes patients. METHODOLOGY/PRINCIPAL FINDINGS: The patients who initiated insulin glargine in basal-supported oral therapy (BOT regimen (n = 3506 were analyzed. The correlations between average changes in glargine dose and HbA1c were calculated, and its regression formula was estimated from grouped data categorized by baseline HbA1c levels. Starting doses of the background-subgroup achieving the HbA1c target with a last-observed dose above the average were compared to an assumed optimal starting dose of 0.15 U/kg/day. The difference in regression lines between background-subgroups was examined. A formula for determining the optimal starting and titration doses was thereby derived. The correlation coefficient between changes in dose and HbA1c was -0.9043. The estimated regression line formula was -0.964 × change in HbA1c+2.000. A starting dose of 0.15 U/kg/day was applicable to all background-subgroups except for patients with retinopathy (0.120 U/kg/day and/or with eGFR<60 mL/min/1.73 m(2 (0.114 U/kg/day. Additionally, women (0.135 U/kg/day and patients with sulfonylureas (0.132 U/kg/day received a slightly decreased starting dose. CONCLUSIONS/SIGNIFICANCE: We suggest a simplified and pragmatic dose calculation formula for type 2 diabetes patients starting glargine BOT optimal daily dose at 24 weeks  =  starting dose (0.15×weight + incremental dose (baseline HbA1c - target HbA1c+2. This formula should be further validated using other samples in a prospective follow-up, especially since several patient groups required lower starting doses.

Studies on the production of insulin radio-immunoassay kit

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Kim, J R; Kim, T H; Kim, Y S [Korea Atomic Energy Research Inst., Seoul (Republic of Korea)

1978-01-01

Insulin was labelled with Iodine-125 in about 35% yield by applying the chloramine-T method. The specific activity of the labelled product was about 100 ..mu..Ci/ug. To use the labelled product for the radioimmunoassay of insulin, the well labelled fractions were selected through a starch gel electrophoresis autoradiography, elution, and subsequent incubations with insulin antibodies. The results of the standardizations using the well labelled insulin fractions for radioimmunoassay indicated that the ratio of the antibody bound (B) to the free (F) insulin-/sup 125/I is 0.2 to 1.6 in the standard insulin dose of up to 50 ..mu..U/ml, the relatively steep dose gradient. Kits were prepared and the stabilities were also checked.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

International Nuclear Information System (INIS)

Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya; Hirose, Takahisa; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

2009-01-01

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

Energy Technology Data Exchange (ETDEWEB)

Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Hirose, Takahisa [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Kawamori, Ryuzo [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Center for Beta Cell Biology and Regeneration, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan); Fujitani, Yoshio, E-mail: fujitani@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Watada, Hirotaka, E-mail: hwatada@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan)

2009-12-18

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

The Effect of Folate Supplementation on Ghrelin of Stomach and Insulin Level of Serum in Male Wistar Rats during 10 Weeks of High Intensity Interval Training

Directory of Open Access Journals (Sweden)

Ali Gorzi

2016-09-01

Full Text Available Abstract Background: High intensity training can lead to lower the appetite. So, the purpose of this study was to investigate the effect of folate supplementation on ghrelin level of stomach and insulin level of serum in male wistar rats during 10 weeks of high intensity interval training (HIIT. Materials and Methods: Twenty seven male Wistar rats (weight= 203.94±27.34 gr, Age: 9 weeks after one week familiarization, were randomly divided into four groups: control (n=6, folate supplementation (n=6, (HIIT (n=7 and HIIT+ folate supplement (n=8. HIIT training protocol started with 30 m/min running on treadmill for 1 min with 10 reps and 2 min active rest at the first week and reached to 75-80 m/min for 1 min with 7 reps and 3 min active rest at last 3 weeks. Acylated ghrelin level of stomach tissue and serum level of insulin were assayed by ELISA kit. Results: The results of Kruskal-vallis analysis showed that the ghrelin level of stomach was increased significantly (p=0.001 in folate+HIIT in compare with HIIT group. Also, insulin level of serum was decreased significantly (p=0.001 in folate +HIIT in compare with control and HIIT groups. Conclusion: Based on our results, folate supplementation during high intensity interval training, increased the ghrelin of stomach and decreased the insulin level of serum. So, it seems that folate supplementation can prevent from losing appetite in athletes who train with high intensity training with interval type.

Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

Science.gov (United States)

Ter Horst, K W; van Galen, K A; Gilijamse, P W; Hartstra, A V; de Groot, P F; van der Valk, F M; Ackermans, M T; Nieuwdorp, M; Romijn, J A; Serlie, M J

2017-08-01

Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3- 2 H 5 ]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m -2 ). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, PInsulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, Pinsulin-glycerol product (r=-0.467, PInsulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, PInsulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, Pinsulin resistance (area under the curve ⩾0.801, Pinsulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.

Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.

Science.gov (United States)

Peyrot, M; Barnett, A H; Meneghini, L F; Schumm-Draeger, P-M

2012-05-01

To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens. Internet survey of 1250 physicians (600 specialists, 650 primary care physicians) who treat patients with diabetes and telephone survey of 1530 insulin-treated patients (180 with Type 1 diabetes, 1350 with Type 2 diabetes) in China, France, Japan, Germany, Spain, Turkey, the UK or the USA. One third (33.2%) of patients reported insulin omission/non-adherence at least 1 day in the last month, with an average of 3.3 days. Three quarters (72.5%) of physicians report that their typical patient does not take their insulin as prescribed, with a mean of 4.3 days per month of basal insulin omission/non-adherence and 5.7 days per month of prandial insulin omission/non-adherence. Patients and providers indicated the same five most common reasons for insulin omission/non-adherence: too busy; travelling; skipped meals; stress/emotional problems; public embarrassment. Physicians reported low patient success at initiating insulin in a timely fashion and adjusting insulin doses. Most physicians report that many insulin-treated patients do not have adequate glucose control (87.6%) and that they would treat more aggressively if not for concern about hypoglycaemia (75.5%). Although a majority of patients (and physicians) regard insulin treatment as restrictive, more patients see insulin treatment as having positive than negative impacts on their lives. Glucose control is inadequate among insulin-treated patients, in part attributable to insulin omission/non-adherence and lack of dose adjustment. There is a need for insulin regimens that are less restrictive and burdensome with lower risk of hypoglycaemia. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

The Mobile Insulin Titration Intervention (MITI) for Insulin Glargine Titration in an Urban, Low-Income Population: Randomized Controlled Trial Protocol.

Science.gov (United States)

Levy, Natalie; Moynihan, Victoria; Nilo, Annielyn; Singer, Karyn; Bernik, Lidia S; Etiebet, Mary-Ann; Fang, Yixin; Cho, James; Natarajan, Sundar

2015-03-13

Patients on insulin glargine typically visit a clinician to obtain advice on how to adjust their insulin dose. These multiple clinic visits can be costly and time-consuming, particularly for low-income patients. It may be feasible to achieve insulin titration through text messages and phone calls with patients instead of face-to-face clinic visits. The objectives of this study are to (1) evaluate if the Mobile Insulin Titration Intervention (MITI) is clinically effective by helping patients reach their optimal dose of insulin glargine, (2) determine if the intervention is feasible within the setting and population, (3) assess patient satisfaction with the intervention, and (4) measure the costs associated with this intervention. This is a pilot study evaluating an approach to insulin titration using text messages and phone calls among patients with insulin-dependent type 2 diabetes in the outpatient medical clinic of Bellevue Hospital Center, a safety-net hospital in New York City. Patients will be randomized in a 1:1 ratio to either the MITI arm (texting/phone call intervention) or the usual-care arm (in-person clinic visits). Using a Web-based platform, weekday text messages will be sent to patients in the MITI arm, asking them to text back their fasting blood glucose values. In addition to daily reviews for alarm values, a clinician will rereview the texted values weekly, consult our physician-approved titration algorithm, and call the patients with advice on how to adjust their insulin dose. The primary outcome will be whether or not a patient reaches his/her optimal dose of insulin glargine within 12 weeks. Recruitment for this study occurred between June 2013 and December 2014. We are continuing to collect intervention and follow-up data from our patients who are currently enrolled. The results of our data analysis are expected to be available in 2015. This study explores the use of widely-available text messaging and voice technologies for insulin titration

Streptozotocin diabetes and insulin resistance impairment of ...

African Journals Online (AJOL)

... insulin resistance impairment of spermatogenesis in adult rat testis: Central Vs local ... Summary: Mammalian reproduction is dynamically regulated by the pituitary ... Group 3 > Streptozotocin-insulin treated group; received a single dose IP ...

Knowledge of carbohydrate counting and insulin dose calculations in paediatric patients with type 1 diabetes mellitus.

Science.gov (United States)

Finner, Natalie; Quinn, Anne; Donovan, Anna; O'Leary, Orla; O'Gorman, Clodagh S

2015-12-01

Patients with type 1 diabetes mellitus (T1DM) who are able to adjust their insulin doses according to the carbohydrate content of a meal, as well as their blood glucose, are likely to have improved glycaemic control (Silverstein et al., 2005). With improved glycaemic control, patients have a lower risk of developing long-term microvascular complications associated with T1DM (Diabetes Control and Complications Trial Research Group, 1993). To assess the carbohydrate and insulin knowledge of patients attending our paediatric diabetes clinic at the University Hospital Limerick (UHL), the validated PedCarbQuiz (PCQ) was applied to our clinic population. This study was completed by applying a questionnaire called the PedCarbQuiz (PCQ) to children exclusively attending our paediatric diabetes clinic at UHL. Of the clinic's 220 patients, 81 participated in the study. The average total PCQ score (%) was higher in the continuous subcutaneous insulin infusion (CSII) group compared with the multiple daily insulin (MDI) injection user group (79.1 ± 12.1 versus 65.9 ± 6.6 p = 0.005). The CSII group also had a higher average carbohydrate score (%) compared with the MDI group (79.4 ± 12.4 versus 66.3 ± 16.2, p = 0.004). This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is better among patients treated with CSII compared with MDI. However, knowledge in both groups is poorer than in the original US sample. This study demonstrates that in a representative Irish regional paediatric T1DM clinic, knowledge of carbohydrates and insulin is poorer than in a US based sample, although this knowledge is better among patients treated with CSII compared with MDI. This highlights the need for improved resources for diabetes and carbohydrate counting education for patients with T1DM.

ICRU reference dose in an era of intensity-modulated radiation therapy clinical trials: Correlation with planning target volume mean dose and suitability for intensity-modulated radiation therapy dose prescription

International Nuclear Information System (INIS)

Yaparpalvi, Ravindra; Hong, Linda; Mah, Dennis; Shen Jin; Mutyala, Subhakar; Spierer, Marnee; Garg, Madhur; Guha, Chandan; Kalnicki, Shalom

2008-01-01

in 3D CRT distributions. Point doses in IMRT are influenced by the degree of intensity modulation as well as calculation grid size utilized. Although the ICRU reference point type prescriptions conceptually may be extended for IMRT dose prescriptions and used as a representative of tumor dose, new universally acceptable dose prescription and specification standards for IMRT based on RTOG IMRT prescription model incorporating dose-volume specification would likely lead to greater consistency among treatment centers

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

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Lee, J [Dept. of Radiation Oncology, Konkuk University Medical Center, Seoul (Korea, Republic of); Chung, J [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designed for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

International Nuclear Information System (INIS)

Lee, J; Chung, J

2015-01-01

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designed for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy

Influence of circulating epinephrine on absorption of subcutaneously injected insulin

International Nuclear Information System (INIS)

Fernqvist, E.; Gunnarsson, R.; Linde, B.

1988-01-01

Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol.kg-1.min-1 i.v., resulting in arterial plasma Epi levels of approximately 6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased approximately 40-50% during the high dose of Epi compared with control (P less than .001). The corresponding decrease from the abdominal depot was approximately 40% (P less than .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

Science.gov (United States)

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

Interfractional Dose Variations in Intensity-Modulated Radiotherapy With Breath-Hold for Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Mitsuhiro [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan); Shibuya, Keiko, E-mail: kei@kuhp.kyoto-u.ac.jp [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan); Nakamura, Akira [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan); Shiinoki, Takehiro [Department of Nuclear Engineering, Kyoto University Graduate School of Engineering, Kyoto (Japan); Matsuo, Yukinori [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan); Nakata, Manabu [Clinical Radiology Service Division, Kyoto University Hospital, Kyoto (Japan); Sawada, Akira; Mizowaki, Takashi; Hiraoka, Masahiro [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan)

2012-04-01

Purpose: To investigate the interfractional dose variations for intensity-modulated radiotherapy (RT) combined with breath-hold (BH) at end-exhalation (EE) for pancreatic cancer. Methods and Materials: A total of 10 consecutive patients with pancreatic cancer were enrolled. Each patient was fixed in the supine position on an individualized vacuum pillow with both arms raised. Computed tomography (CT) scans were performed before RT, and three additional scans were performed during the course of chemoradiotherapy using a conventional RT technique. The CT data were acquired under EE-BH conditions (BH-CT) using a visual feedback technique. The intensity-modulated RT plan, which used five 15-MV coplanar ports, was designed on the initial BH-CT set with a prescription dose of 39 Gy at 2.6 Gy/fraction. After rigid image registration between the initial and subsequent BH-CT scans, the dose distributions were recalculated on the subsequent BH-CT images under the same conditions as in planning. Changes in the dose-volume metrics of the gross tumor volume (GTV), clinical target volume (CTV = GTV + 5 mm), stomach, and duodenum were evaluated. Results: For the GTV and clinical target volume (CTV), the 95th percentile of the interfractional variations in the maximal dose, mean dose, dose covering 95% volume of the region of structure, and percentage of the volume covered by the 90% isodose line were within {+-}3%. Although the volume covered by the 39 Gy isodose line for the stomach and duodenum did not exceed 0.1 mL at planning, the volume covered by the 39 Gy isodose line for these structures was up to 11.4 cm{sup 3} and 1.8 cm{sup 3}, respectively. Conclusions: Despite variations in the gastrointestinal state and abdominal wall position at EE, the GTV and CTV were mostly ensured at the planned dose, with the exception of 1 patient. Compared with the duodenum, large variations in the stomach volume receiving high-dose radiation were observed, which might be beyond the

Increments in insulin sensitivity during intensive treatment are closely correlated with decrements in glucocorticoid receptor mRNA in skeletal muscle from patients with Type II diabetes

DEFF Research Database (Denmark)

Vestergaard, H; Bratholm, P; Christensen, N J

2001-01-01

decreased significantly after intensive insulin treatment. A close correlation was found between increments in glucose uptake during intensive treatment and decrements in skeletal muscle total GCR mRNA (r=0.95, Pmultiple regression analysis), and between glucose uptake and alpha/alpha 2 GCR m RNA...

Economic benefits of improved insulin stability in insulin pumps.

Science.gov (United States)

Weiss, Richard C; van Amerongen, Derek; Bazalo, Gary; Aagren, Mark; Bouchard, Jonathan R

2011-05-01

Insulin pump users discard unused medication and infusion sets according to labeling and manufacturer's instructions. The stability labeling for insulin aspart (rDNA origin] (Novolog) was increased from two days to six. The associated savings was modeled from the perspective of a hypothetical one-million member health plan and the total United States population. The discarded insulin volume and the number of infusion sets used under a two-day stability scenario versus six were modeled. A mix of insulin pumps of various reservoir capacities with a range of daily insulin dosages was used. Average daily insulin dose was 65 units ranging from 10 to 150 units. Costs of discarded insulin aspart [rDNA origin] were calculated using WAC (Average Wholesale Price minus 16.67%). The cost of pump supplies was computed for the two-day scenario assuming a complete infusion set change, including reservoirs, every two days. Under the six-day scenario complete infusion sets were discarded every six days while cannulas at the insertion site were changed midway between complete changes. AWP of least expensive supplies was used to compute their costs. For the hypothetical health plan (1,182 pump users) the annual reduction in discarded insulin volume between scenarios was 19.8 million units. The corresponding cost reduction for the plan due to drug and supply savings was $3.4 million. From the U.S. population perspective, savings of over $1 billion were estimated. Using insulin that is stable for six days in pump reservoirs can yield substantial savings to health plans and other payers, including patients.

Evaluation of the timing and coordination of prandial insulin administration in the hospital.

Science.gov (United States)

Alwan, Dhuha; Chipps, Esther; Yen, Po-Yin; Dungan, Kathleen

2017-09-01

The objective of this study was to examine the relationship between measures of coordinated insulin delivery and capillary blood glucose (CBG) levels among hospitalized patients and to assess nurse perceptions of insulin administration. Hospitalized patients (n=451) receiving rapid acting insulin analog (RAIA) using carbohydrate counting were retrospectively analyzed. Nurses (n=35) were asked to complete an 18-item anonymous survey assessing perception of RAIA dosing. The median time from breakfast CBG to RAIA dose was 93 (IQR 57-138) min. There was no association between timeliness measures and mean CBG at lunch or dinner. Hypoglycemia was rare (N=2). More than half (54%) of nurses were confident all of the time in determining the correct dose of RAIA, though none were confident in administering it on time. The majority of nurses perceived an electronic dosing calculator and a patient reminder to notify the nurse at the end of the meal favorably. The data demonstrate suboptimal coordination of CBG monitoring and insulin doses using a flexible meal insulin dosing strategy, though there was minimal impact on glycemic control. Nurses reported high confidence in the ability to calculate the correct insulin dose but not in the ability to administer it on time. Copyright © 2017 Elsevier B.V. All rights reserved.

Prolactin effect on the insulin content of albino rats in different physiological states

International Nuclear Information System (INIS)

Megahed, Y.M.; Abdel-Wahab, M.F.; El-Mougi, S.M.; El-Sayed, F.B.; Kuwait Univ.)

1980-01-01

The metabolic action of prolactin on insulin levels in plasma and pancreas has been studied. Prolactin was injected in a single dose or single daily doses on 4 successive days into albino rats in six different physiological states. Insulin was determined by radioimmunoassay using 125 I insulin. From the results it is concluded that prolactin injected i.p. influences the output of insulin and stimulates the pancreas to secrete insulin into the plasma. (author)

Insulin and the Brain: A Sweet Relationship With Intensive Care.

Science.gov (United States)

Bilotta, F; Lauretta, M P; Tewari, A; Haque, M; Hara, N; Uchino, H; Rosa, G

2017-01-01

Insulin receptors (IRs) in the brain have unique molecular features and a characteristic pattern of distribution. Their possible functions extend beyond glucose utilization. In this systematic review, we explore the interactions between insulin and the brain and its implications for anesthesiologists, critical care physicians, and other medical disciplines. A literature search of published preclinical and clinical studies between 1978 and 2014 was conducted, yielding 5996 articles. After applying inclusion and exclusion criteria, 92 studies were selected for this systematic review. The IRs have unique molecular features, pattern of distribution, and mechanism of action. It has effects on neuronal function, metabolism, and neurotransmission. The IRs are involved in neuronal apoptosis and neurodegenerative processes. In this systematic review, we present a close relationship between insulin and the brain, with discernible effects on memory, learning abilities, and motor functions. The potential therapeutic effects extend from acute brain insults such as traumatic brain injury, brain ischemia, and hemorrhage, to chronic neurodegenerative diseases such as Alzheimer and Parkinson disease. An understanding of the wider effects of insulin conveyed in this review will prompt anaesthesiologists and critical care physicians to consider its therapeutic potential and guide future studies. © The Author(s) 2015.

[The optimal blood glucose target in critically ill patient: comparison of two intensive insulin therapy protocols].

Science.gov (United States)

Raurell Torredà, Marta; del Llano Serrano, César; Almirall Solsona, Dolors; Catalan Ibars, Rosa María; Nicolás Arfelis, José María

2014-03-04

Recent studies in critically ill patients receiving insulin intravenous therapy (IIT) have shown an increased incidence of severe hypoglycemia, while intermittent subcutaneous insulin «sliding scales» (conventional insulin therapy [CIT]) is associated with hyperglycemia. The objective of this study is to assess whether glycemic control range IIT can affect glucose levels and their variability and to compare it with CIT. Prospective comparative cohort study in intensive care unit, with 2 study periods: Period 1, IIT with glycemic target range 110-140 mg/dL, and Period 2, IIT of 140-180 mg/dL. In both periods CIT glycemic target was 110-180 mg/dL. We assessed severe hypoglycemia ( 216 mg/L) and the variability of blood glucose. We studied 221 patients with 12.825 blood glucose determinations. Twenty-six and 17% of patients required IIT for glycemic control in Period 1 and 2, respectively. Hypoglycemia was associated with a discontinuous nutritional intake, glycemic target 110-140 mg/dL and low body mass index (BMI) (P = .002). Hyperglycemia was exclusively associated with a history of diabetes mellitus (OR 2.6 [95% CI 1.6 to 4.5]). Glycemic variability was associated with a discontinuous nutritional intake, low BMI, CIT insulinization, diabetes mellitus, elderly and high APACHE II (P < .001). The use of IIT is useful to reduce the variability of blood glucose. Although the 140-180 mg/dL range would be more secure as to presenting greater variability and hyperglycemia, the 110-140 mg/dL range is most suitable. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Selection of well labelled insulin fractions for radioimmunoassay use

Energy Technology Data Exchange (ETDEWEB)

Awh, O D; Kim, J R [Korea Atomic Energy Research Inst., Seoul (Republic of Korea)

1980-06-01

Selection methods of well labelled insulin fractions based on two different criteria were compared to establish an efficient low level RIA of insulin and to elucidate the correlation between the immunoreactivity and the charcoal-adsorptivity of the radioiodine labelled insulin. The result indicated that the selection of well labelled insulin fractions by means of a charcoal-adsorption test is inappropriate. Generally, the distribution of radioactivity, antibody-bindability, and charcoal-adsorptivity of the labelled insulin was not consistent with each other. Thus, the selection should be carried out for every labelling batch to get the utmost assay reliability by antibody-bindability but not by charcoal-adsorptivity. By using the well selected labelled insulin fractions based on antibody-binding, a correct assay for a reference serum was possible, and by extending the incubation time up to 96 hrs, a sharp dose response curve could be obtained even in the range of below 5 ..mu..U/ml standard insulin doses.

Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

Science.gov (United States)

Durrer, Cody; Robinson, Emily; Wan, Zhongxiao; Martinez, Nic; Hummel, Michelle L.; Jenkins, Nathan T.; Kilpatrick, Marcus W.; Little, Jonathan P.

2015-01-01

Background An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all Pexercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (Pobese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. PMID:25710559

Insulin receptor substrates 1 and 2 but not Shc can activate the insulin receptor independent of insulin and induce proliferation in CHO-IR cells

International Nuclear Information System (INIS)

Niessen, Markus; Jaschinski, Frank; Item, Flurin; McNamara, Morgan P.; Spinas, Giatgen A.; Trueb, Thomas

2007-01-01

Ligand-activated insulin receptor (IR) attracts and phosphorylates various substrates such as insulin receptor substrates 1-4 (IRS) and Shc. To investigate how binding affinity for substrate affects signalling we generated chimeric receptors with the β-chain of the insulin receptor containing NPXY motives with different affinities for receptor substrates. We found that the extent of receptor tyrosine phosphorylation positively correlates with binding affinity towards IRS1/2 but not towards Shc. Moreover, overexpression of IRS1 or IRS2 but not of Shc increased IR tyrosine phosphorylation in a dose-dependent manner, also independent of insulin. Molecular truncations of IRS1 revealed that neither the isolated PH and PTB domains nor the C-terminus with the tyrosine phosphorylation sites alone are sufficient for substrate-dependent receptor activation. Overexpression of IRS1 and IRS2 impaired insulin-induced internalization of the IR in a dose-dependent manner suggesting that IRS proteins prevent endosome-associated receptor dephosphorylation/inactivation. IRS1 and IRS2 could therefore target the activated IR to different cellular compartments. Overexpression of IRS1 and IRS2 inhibited insulin-stimulated activation of the MAP kinases Erk1/2 while it increased/induced activation of Akt/PKB. Finally, overexpression of IRS1 and IRS2 but not of Shc induced DNA synthesis in starved CHO-IR cells independent of exogenous growth factors. Our results demonstrate that variations in cellular IRS1 and IRS2 concentration affect insulin signalling both upstream and downstream and that IRS proteins could play instructive rather than just permissive roles in signal transmission

The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

DEFF Research Database (Denmark)

Rosenfalck, A M; Maghsoudi, S; Fisker, S

2000-01-01

The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...... (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ... in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite...

Insulin resistance: vascular function and exercise

Directory of Open Access Journals (Sweden)

Moon-Hyon Hwang

2016-09-01

Full Text Available Insulin resistance associated with metabolic syndrome and Type 2 diabetes mellitus is an epidemic metabolic disorder, which increases the risk of cardiovascular complications. Impaired vascular endothelial function is an early marker for atherosclerosis, which causes cardiovascular complications. Both experimental and clinical studies indicate that endothelial dysfunction in vasculatures occurs with insulin resistance. The associated physiological mechanisms are not fully appreciated yet, however, it seems that augmented oxidative stress, a physiological imbalance between oxidants and antioxidants, in vascular cells is a possible mechanism involved in various vascular beds with insulin resistance and hyperglycemia. Regardless of the inclusion of resistance exercise, aerobic exercise seems to be beneficial for vascular endothelial function in both large conduit and small resistance vessels in both clinical and experimental studies with insulin resistance. In clinical cases, aerobic exercise over 8 weeks with higher intensity seems more beneficial than the cases with shorter duration and lower intensity. However, more studies are needed in the future to elucidate the physiological mechanisms by which vascular endothelial function is impaired in insulin resistance and improved with aerobic exercise.

Qualitative analysis of subcutaneous Lispro and regular insulin injections for stress hyperglycemia: a pilot numerical study.

Science.gov (United States)

Strilka, Richard J; Armen, Scott B; Indeck, Matthew C

2014-09-07

Increased glucose variability (GV) is an independent risk factor for mortality in the critically ill; unfortunately, the optimal insulin therapy that minimizes GV is not known. We simulate the glucose-insulin feedback system to study how stress hyperglycemia (SH) states, taken to be a non-uniform group of physiologic disorders with varying insulin resistance (IR) and similar levels of hyperglycemia, respond to the type and dose of subcutaneous (SQ) insulin. Two groups of 100 virtual patients are studied: those receiving and those not receiving continuous enteral feeds. Stress hyperglycemia was facilitated by doubling the gluconeogenesis rate and IR was stepwise varied from a borderline to a high value. Lispro and regular insulin were simulated with dosages that ranged from 0 to 6 units; the resulting GV was analyzed after each insulin injection. The numerical model used consists of a set of non-linear differential equations with two time delays and five adjustable parameters. The results show that regular insulin decreased GV in both patient groups and rarely caused hypoglycemia. With continuous enteral feeds and borderline to mild IR, Lispro showed minimal effect on GV; however, rebound hyperglycemia that increased GV occurred when the IR was moderate to high. Without a nutritional source, Lispro worsened GV through frequent hypoglycemia episodes as the injection dose increased. The inferior performance of Lispro is a result of its rapid absorption profile; half of its duration of action is similar to the glucose ultradian period. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units, and if such dynamics are present, their clinical effects should be evaluated. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

Science.gov (United States)

Morçöl, T; Nagappan, P; Nerenbaum, L; Mitchell, A; Bell, S J D

2004-06-11

An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.

Effects of exogenous human insulin dose adjustment on body mass ...

African Journals Online (AJOL)

glycaemic control by frequent exogenous insulin injections. To maintain fasting ... mass index in adult patients with type 1 diabetes mellitus at Kalafong Hospital ..... The Diabetes Control and Complications Trial cited in the review by Kaufman[2] also .... in obese insulin-resistant children: A randomized clinical trial. Diabetes ...

Light-intensity physical activity and cardiometabolic biomarkers in US adolescents.

Directory of Open Access Journals (Sweden)

Valerie Carson

Full Text Available BACKGROUND: The minimal physical activity intensity that would confer health benefits among adolescents is unknown. The purpose of this study was to examine the associations of accelerometer-derived light-intensity (split into low and high physical activity, and moderate- to vigorous-intensity physical activity with cardiometabolic biomarkers in a large population-based sample. METHODS: The study is based on 1,731 adolescents, aged 12-19 years from the 2003/04 and 2005/06 National Health and Nutrition Examination Survey. Low light-intensity activity (100-799 counts/min, high light-intensity activity (800 counts/min to <4 METs and moderate- to vigorous-intensity activity (≥ 4 METs, Freedson age-specific equation were accelerometer-derived. Cardiometabolic biomarkers, including waist circumference, systolic blood pressure, diastolic blood pressure, HDL-cholesterol, and C-reactive protein were measured. Triglycerides, LDL- cholesterol, insulin, glucose, and homeostatic model assessments of β-cell function (HOMA-%B and insulin sensitivity (HOMA-%S were also measured in a fasting sub-sample (n=807. RESULTS: Adjusted for confounders, each additional hour/day of low light-intensity activity was associated with 0.59 (95% CI: 1.18-0.01 mmHG lower diastolic blood pressure. Each additional hour/day of high light-intensity activity was associated with 1.67 (2.94-0.39 mmHG lower diastolic blood pressure and 0.04 (0.001-0.07 mmol/L higher HDL-cholesterol. Each additional hour/day of moderate- to vigorous-intensity activity was associated with 3.54 (5.73-1.35 mmHG lower systolic blood pressure, 5.49 (1.11-9.77% lower waist circumference, 25.87 (6.08-49.34% lower insulin, and 16.18 (4.92-28.53% higher HOMA-%S. CONCLUSIONS: Time spent in low light-intensity physical activity and high light-intensity physical activity had some favorable associations with biomarkers. Consistent with current physical activity recommendations for adolescents, moderate- to

Effect of single physical exercise at 35% VO2 max. intensity on secretion activity of pancreas β-cells and 125J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus

International Nuclear Information System (INIS)

Szczesniak, L.; Rychlewski, T.; Banaszak, F.; Kasprzak, Z.; Walczak, M.

1994-01-01

In this report we showed research results of effect of single physical exercise on cycloergometer at 35% VO 2 max. intensity on 125 J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus, secreting and non-secreting endogenous insulin. Insulin secretion was evaluated by measurement of C-peptide by Biodet test (Serono) of sensitivity threshold at 0.3 μg/ml. We indicated in children non-secreting endogenous insulin (n=32) there is statistically essential lower 125 J-insulin binding with erythrocyte receptor in comparison to children group with C-peptide. Physical exercise on cycloergometer at 35% VO 2 max. intensity caused different reaction in range of physiological indices, like acid-base parameters, level of glucose and 125 J-insulin binding and degradation. In children devoid of endogenous insulin we indicated statistically nonessential changes in 125 J-insulin degradation by non-impaired erythrocytes and by hemolizate, as well. 125 J-insulin binding after physical exercise increased in both groups, though change amplitude was different. Obtained research results allowed us to conclude, in children with I-type diabetes, that in dependence of impairment degree of pancreas βcells sensitivity of insulin receptor and/or number of receptors on erythrocyte surface is different

Definition of dose intensity (DI), average relative DI and effective DI

International Nuclear Information System (INIS)

Alberto, P.

1995-01-01

The cytotoxic activity of cancer chemotherapy is related to the dose and to the amount of drug delivered per time unit. the significance of time in the effectiveness of a treatment program is frequently overlooked. The term of dose intensity (DI) is used to define the drug dose delivered per time unit and is expressed as mg/m 2 per week. A delay in the sequence of treatment cycles decreases the DI in the DI in the same proportion as a reduction of dose. Average relative DI corresponds to the mean DI of combined agents and is expressed as a fraction of a similar combination selected as a standard. Di is useful to compare the dose actually received with the prescribed dose. The relation of DI with tumor response or survival has not been fully demonstrated. A threshold DI level for therapeutic activity is evident. Above this threshold, a linear relationship of DI and effectiveness is not obvious, particularly regarding high-dose chemotherapy. The term of DI is more useful in its principle than in the significance of its calculated value. (authors). 19 refs., 3 tabs., 3 figs

Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

Science.gov (United States)

Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

2014-08-01

Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

DEFF Research Database (Denmark)

Vestergaard, H; Andersen, P H; Lund, S

1994-01-01

The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle...... glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin...... were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis of muscle biopsies from...

Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

International Nuclear Information System (INIS)

Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

1982-01-01

In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

Insulin Sensitizing and Antioxidant Effects of Hesperidin and Low Dose Gamma Irradiation in Combination with Rosiglitazone in Type 2 Diabetic Rats

International Nuclear Information System (INIS)

Morcos, N.Y.; Abdel-Ghaffar, A.B.; Osman, S.A.; Mohamed, M.Kh.; Arbid, M.S.; El-Eraky, W.I.

2012-01-01

The present study was designed to investigate the possible ameliorative effect of hesperidin and low dose fÁ-irradiation (LDR) in combination with rosiglitazone in an experimental model of insulin resistance. Type 2 diabetes mellitus (T2DM) was induced in rats by single intraperitoneal injection of streptozotocin (STZ) followed by nicotinamide (NIC) (65 and 110 mg/kg b.wt; i.p respectively). After verifying T2DM in rats, they were subjected to LDR (50 cGy) and then treated with rosiglitazone (4 mg/kg b.wt; p.o) and hesperidin (100 mg/kg b.wt; p.o) for 30 days. Results showed that STZ injection significantly elevated blood glucose, glycosylated hemoglobin (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid peroxides (TBARS; MDA) accompanied with a reduction in adiponectin plasma level, reduced glutathione (GSH) and superoxide dismutase (SOD) serum level. Treatment of diabetic rats with rosiglitazone, hesperidin and LDR significantly reduced blood glucose, HbA1c, insulin, HOMA-IR and MDA levels. Whereas, plasma adiponectin, SOD in serum and GSH plasma level were significantly elevated. Therefore, our data suggest that hesperidin and LDR might be useful adjuvants with rosiglitazone and attenuate insulin resistance and oxidative stress in T2DM.

Insulin analogues with improved absorption characteristics.

Science.gov (United States)

Brange, J; Hansen, J F; Langkjaer, L; Markussen, J; Ribel, U; Sørensen, A R

1992-01-01

The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

Dose deviations caused by positional inaccuracy of multileaf collimator in intensity modulated radiotherapy

International Nuclear Information System (INIS)

Wang, H.C.; Chui, C.S.; Tsai, H.Y.; Chen, C.H.; Tsai, L.F.

2008-01-01

Introduction: Multileaf collimator (MLC) is currently a widely used system in the delivery of intensity modulated radiotherapy (IMRT). The accuracy of the multileaf position plays an important role in the final outcome of the radiation treatment. According to ICRU recommendation, a dose inaccuracy over than 5% of prescribed dose affects treatment results. In order to quantify the influence of leaf positional errors on dose distribution, we set different MLC positional inaccuracy from 0 to 6 mm for step-and-shoot IMRT in clinical cases. Two-dimensional dose distributions of radiotherapy plans with different leaf displacements generated with a commercial treatment planning system. And verification films were used to measure two-dimensional dose distributions. Then a computerized dose comparison system will be introduced to analyze the dose deviations. Materials/methods: We assumed MLC positional inaccuracy from 0 to 6 mm for step-and-shoot IMRT in clinical cases by simulating the different leaf displacements with a commercial treatment planning system. Then we transferred the treatment plans with different leaf offset that may be happened in clinical situation to linear accelerator. Verification films (Kodat EDR2) were well positioned within solid water phantoms to be irradiated by the simulated plans. The films were scanned to display two-dimensional dose distributions. Finally, we compared with the dose distributions with MLC positional inaccuracy by a two-dimensional dose comparison software to analyze the deviations in Gamma indexes and normalized agreement test (NAT) values. Results: In general, the data show that larger leaf positional error induces larger dose error. More fields used for treatment generate lesser errors. Besides, leaf position relative to a field influences the degree of dose error. A leaf lying close to the border of a field leads to a more significant dose deviation than a leaf in the center. Algorithms for intensity modulation also affect

Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

International Nuclear Information System (INIS)

Salhanick, A.I.; Amatruda, J.M.

1988-01-01

Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, the authors investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable [ 14 C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus

Dose to Larynx Predicts for Swallowing Complications After Intensity-Modulated Radiotherapy

International Nuclear Information System (INIS)

Caglar, Hale B.; Tishler, Roy B.; Othus, Megan; Burke, Elaine; Li Yi; Goguen, Laura; Wirth, Lori J.; Haddad, Robert I.; Norris, Carl M.; Court, Laurence E.; Aninno, Donald J. D.; Posner, Marshall R.; Allen, Aaron M.

2008-01-01

Purpose: To evaluate early swallowing after intensity-modulated radiotherapy for head and neck squamous cell carcinoma and determine factors correlating with aspiration and/or stricture. Methods and Materials: Consecutive patients treated with intensity-modulated radiotherapy with or without chemotherapy between September 2004 and August 2006 at the Dana Farber Cancer Institute/Brigham and Women's Hospital were evaluated with institutional review board approval. Patients underwent swallowing evaluation after completion of therapy; including video swallow studies. The clinical- and treatment-related variables were examined for correlation with aspiration or strictures, as well as doses to the larynx, pharyngeal constrictor muscles, and cervical esophagus. The correlation was assessed with logistic regression analysis. Results: A total of 96 patients were evaluated. Their median age was 55 years, and 79 (82%) were men. The primary site of cancer was the oropharynx in 43, hypopharynx/larynx in 17, oral cavity in 13, nasopharynx in 11, maxillary sinus in 2, and unknown primary in 10. Of the 96 patients, 85% underwent definitive RT and 15% postoperative RT. Also, 28 patients underwent induction chemotherapy followed by concurrent chemotherapy, 59 received concurrent chemotherapy, and 9 patients underwent RT alone. The median follow-up was 10 months. Of the 96 patients, 31 (32%) had clinically significant aspiration and 36 (37%) developed a stricture. The radiation dose-volume metrics, including the volume of the larynx receiving ≥50 Gy (p = 0.04 and p = 0.03, respectively) and volume of the inferior constrictor receiving ≥50 Gy (p = 0.05 and p = 0.02, respectively) were significantly associated with both aspiration and stricture. The mean larynx dose correlated with aspiration (p = 0.003). Smoking history was the only clinical factor to correlate with stricture (p = 0.05) but not aspiration. Conclusion: Aspiration and stricture are common side effects after

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

Science.gov (United States)

Pierce, Dwayne A; Russell, Greg; Pirkle, James L

2015-12-01

Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia. © The Author(s) 2015.

Insulin-receptors in diabetes and altered thyroidal status

International Nuclear Information System (INIS)

Chaujar, Meena; Subramanian, G.B.V.; Yadav, H.S.; Chauhan, U.P.S.

1991-01-01

Rats were made hypothyroid by treating with a single dose of 800 μCi of 131 I and hyperthyroid condition was created by administering 90 μg of thyroxine daily for 2 weeks. Diabetes was produced by administering single dose of alloxan monohydrate. Hypothyroid rats showed significant increase in 125 I-insulin binding with its liver plasma membrane receptors with respect to normal rats. In the case of hypothyroid diabetic rats such binding was greater as compared to hypothyroid rats without diabetes. Hyperthyroid rats with respect to normal control rats showed a decrease in 125 I-insulin binding to its liver plasma membrane receptors. When hyperthyroid rats were made diabetic, 125 I-insulin binding to its receptors was further decreased. The study infers that hyper-thyrodism further decreases insulin binding to its receptors which has already been decreased in diabetes. Hypothyroidism, on the other hand, improves upon the decreased insulin binding to its receptors in diabetes. (author). 16 refs., 6 figs., 2 tabs

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

Science.gov (United States)

Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

2016-01-27

variability; its linear dose-response curve rendered the preparation better suited for a sliding-scale protocol. The longer duration of action of subcutaneous regular insulin resulted in better glycemic-control metrics for patients who were continuously postprandial. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units; if present, their clinical effects should be evaluated.

Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

NARCIS (Netherlands)

Yuen, Kevin C. J.; Frystyk, Jan; White, Deborah K.; Twickler, Th B.; Koppeschaar, Hans P. F.; Harris, Philip E.; Fryklund, Linda; Murgatroyd, Peter R.; Dunger, David B.

2005-01-01

OBJECTIVE: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore

Effects of switching from NPH insulin to insulin glargine in patients with type 2 diabetes: the retrospective, observational LAUREL study in Italy.

Science.gov (United States)

Bellia, Alfonso; Babini, Anna C; Marchetto, Paolo E; Arsenio, Leone; Lauro, Davide; Lauro, Renato

2014-04-01

The aim was to observe the effects of switching from neutral protamine Hagedorn (NPH) insulin to insulin glargine on glycaemic control in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice in Italy. This multicenter, observational, retrospective study included 1,011 patients with T2DM who switched from NPH insulin to glargine or were maintained on NPH insulin. The primary outcome was change in HbA1c over 4-8 months. Secondary outcomes included fasting blood glucose (FBG), insulin dose, and hypoglycaemia. The intention-to-treat population consisted of 996 patients (glargine 496; NPH 500). Prior to switching, HbA1c was higher in the glargine than the NPH group [mean (±SD) 8.8 ± 1.4 vs. 7.9 ± 1.2%; p < 0.001]. HbA1c decreased after 4-8 months with glargine (8.2 ± 1.4%; p < 0.001) but not with NPH (8.0 ± 1.4%; p = 0.20). Similar results were observed for FBG. The daily dose of glargine increased from 0.22 ± 0.10 U/kg at the switch to 0.26 ± 0.11 U/kg at study end, while the NPH dose remained stable (0.19 ± 0.09-0.20 ± 0.09 U/kg). While not statistically significant, the percentage of patients with hypoglycaemic episodes during the last month of treatment tended to be less with glargine. No significant change in body weight occurred in either group. Switching patients from NPH insulin to insulin glargine in a real-life setting was associated with significant improvement in glycaemic control. The increase in glargine dose was not accompanied by increased hypoglycaemia or weight gain.

Effects of exercise on insulin binding to human muscle

International Nuclear Information System (INIS)

Bonen, A.; Tan, M.H.; Clune, P.; Kirby, R.L.

1985-01-01

A procedure was developed to measure insulin binding to human skeletal muscle obtained via the percutaneous muscle biopsy technique. With this method the effects of exercise on insulin binding were investigated. Subjects (n = 9) exercised for 60 min on a bicycle ergometer at intensities ranging from 20-86% maximum O 2 consumption (VO 2 max). Blood samples were obtained before, during, and after exercise and analyzed for glucose and insulin. Muscle samples (250 mg) for the vastus lateralis were obtained 30 min before exercise, at the end of exercise, and 60 min after exercise. Two subjects rested during the experimental period. There was no linear relationship between exercise intensities and the changes in insulin binding to human muscle. At rest (n = 2) and at exercise intensities below 60% VO 2 max (n = 5) no change in insulin binding occurred (P greater than 0.05). However, when exercise occurred at greater than or equal to 69% VO 2 max (n = 4), a pronounced decrement in insulin binding (30-50%) was observed (P less than 0.05). This persisted for 60 min after exercise. These results indicate that insulin binding in human muscle is not altered by 60 min of exercise at less than or equal to 60% VO 2 max but that a marked decrement occurs when exercise is greater than or equal to 69% VO 2 max

The impact of extended release exenatide as adjuvant therapy on hemoglobin A1C, weight, and total daily dose of insulin in patients with type 2 diabetes mellitus using U-500 insulin.

Science.gov (United States)

Farwig, Phillip A; Zielinski, Angela J; Accursi, Mallory L; Burant, Christopher J

2017-12-01

To evaluate the efficacy and safety of adjuvant exenatide extended release (ER) therapy in patients treated with regular U-500 insulin. In this retrospective chart review at an ambulatory care center in the Midwest, 18 patients with type 2 diabetes being treated with regular U-500 insulin and adjuvant exenatide ER were identified. These patients were evaluated for outcomes following the addition of exenatide ER. The primary outcome was change in HbA 1C from baseline to 3, 6, and 12months. Secondary outcomes included change in weight, total daily dose (TDD) of insulin, and hypoglycemia. Repeated measures ANOVA was performed to assess the differences in mean scores over four time periods. A total of 18 of 50 patients met inclusion criteria with sufficient data to be included in analysis. HbA 1C showed non-significant findings from baseline to 12months (8.08% vs. 8.23%; p=0.75). A non-significant, modest weight loss occurred (146.4kgvs. 144.2kg; -2.2kg; p=0.31). A significant decrease in TDD of insulin was observed (378 units vs. 326 units; p1). There was a trend towards hypoglycemia from baseline to month 3 post addition of exenatide ER (0.33 events vs. 1.33 events; p=0.055). In patients treated with regular U-500 insulin, adjuvant exenatide ER therapy showed no significant improvement in HbA 1C , but did show modest weight loss as well as decreased insulin requirements to achieve a HbA 1C that was comparable to baseline. Published by Elsevier B.V.

Effect of intensive insulin therapy on macular biometrics, plasma VEGF and its soluble receptor in newly diagnosed diabetic patients.

Science.gov (United States)

Hernández, Cristina; Zapata, Miguel A; Losada, Eladio; Villarroel, Marta; García-Ramírez, Marta; García-Arumí, José; Simó, Rafael

2010-07-01

To evaluate whether intensive insulin therapy leads to changes in macular biometrics (volume and thickness) in newly diagnosed diabetic patients with acute hyperglycaemia and its relationship with serum levels of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). Twenty-six newly diagnosed diabetic patients admitted to our hospital to initiate intensive insulin treatment were prospectively recruited. Examinations were performed on admission (day 1) and during follow-up (days 3, 10 and 21) and included a questionnaire regarding the presence of blurred vision, standardized refraction measurements and optical coherence tomography. Plasma VEGF and sFlt-1 were assessed by ELISA at baseline and during follow-up. At study entry seven patients (26.9%) complained of blurred vision and five (19.2%) developed burred vision during follow-up. Macular volume and thickness increased significantly (p = 0.008 and p = 0.04, respectively) in the group with blurred vision at day 3 and returned to the baseline value at 10 days. This pattern was present in 18 out of the 24 eyes from patients with blurred vision. By contrast, macular biometrics remained unchanged in the group without blurred vision. We did not detect any significant changes in VEGF levels during follow-up. By contrast, a significant reduction of sFlt-1 was observed in those patients with blurred vision at day 3 (p = 0.03) with normalization by day 10. Diabetic patients with blurred vision after starting insulin therapy present a significant transient increase in macular biometrics which is associated with a decrease in circulating sFlt-1. Copyright (c) 2010 John Wiley & Sons, Ltd.

Fall in C-Peptide During First 4 Years From Diagnosis of Type 1 Diabetes: Variable Relation to Age, HbA1c, and Insulin Dose.

Science.gov (United States)

Hao, Wei; Gitelman, Steven; DiMeglio, Linda A; Boulware, David; Greenbaum, Carla J

2016-10-01

We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixed-meal tolerance tests (MMTTs). During semiannual visits, C-peptide values from MMTTs, HbA1c, and insulin doses were obtained. The percentage of individuals with stimulated C-peptide of ≥0.2 nmol/L or detectable C-peptide of ≥0.017 nmol/L continued to diminish over 4 years; this was markedly influenced by age. At 4 years, only 5% maintained their baseline C-peptide secretion. The expected inverse relationships between C-peptide and HbA1c or insulin doses varied over time and with age. Combined clinical variables, such as insulin-dose adjusted HbA1c (IDAA1C) and the relationship of IDAA1C to C-peptide, also were influenced by age and time from diagnosis. Models using these clinical measures did not fully predict C-peptide responses. IDAA1C ≤9 underestimated the number of individuals with stimulated C-peptide ≥0.2 nmol/L, especially in children. Current trials of disease-modifying therapy for type 1 diabetes should continue to use C-peptide as a primary end point of β-cell secretory function. Longer duration of follow-up is likely to provide stronger evidence of the effect of disease-modifying therapy on preservation of β-cell function. © 2016 by the American Diabetes Association.

Radiation Dose Measurement for High-Intensity Laser Interactions with Solid Targets at SLAC

Energy Technology Data Exchange (ETDEWEB)

Liang, Taiee [SLAC National Accelerator Lab., Menlo Park, CA (United States)

2015-09-25

A systematic study of photon and neutron radiation doses generated in high-intensity laser-solid interactions is underway at SLAC National Accelerator Laboratory. We found that these laser-solid experiments are being performed using a 25 TW (up to 1 J in 40 fs) femtosecond pulsed Ti:sapphire laser at the Linac Coherent Light Source’s (LCLS) Matter in Extreme Conditions (MEC) facility. Additionally, radiation measurements were performed with passive and active detectors deployed at various locations inside and outside the target chamber. Results from radiation dose measurements for laser-solid experiments at SLAC MEC in 2014 with peak intensity between 10¹⁸ to 7.1x10¹⁹ W/cm² are presented.

Dosimetric analysis of testicular doses in prostate intensity-modulated and volumetric-modulated arc radiation therapy at different energy levels

Energy Technology Data Exchange (ETDEWEB)

Onal, Cem, E-mail: hcemonal@hotmail.com; Arslan, Gungor; Dolek, Yemliha; Efe, Esma

2016-01-01

The aim of this study is to evaluate the incidental testicular doses during prostate radiation therapy with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) at different energies. Dosimetric data of 15 patients with intermediate-risk prostate cancer who were treated with radiotherapy were analyzed. The prescribed dose was 78 Gy in 39 fractions. Dosimetric analysis compared testicular doses generated by 7-field intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy with a single arc at 6, 10, and 15 MV energy levels. Testicular doses calculated from the treatment planning system and doses measured from the detectors were analyzed. Mean testicular doses from the intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy per fraction calculated in the treatment planning system were 16.3 ± 10.3 cGy vs 21.5 ± 11.2 cGy (p = 0.03) at 6 MV, 13.4 ± 10.4 cGy vs 17.8 ± 10.7 cGy (p = 0.04) at 10 MV, and 10.6 ± 8.5 cGy vs 14.5 ± 8.6 cGy (p = 0.03) at 15 MV, respectively. Mean scattered testicular doses in the phantom measurements were 99.5 ± 17.2 cGy, 118.7 ± 16.4 cGy, and 193.9 ± 14.5 cGy at 6, 10, and 15 MV, respectively, in the intensity-modulated radiotherapy plans. In the volumetric-modulated arc radiotherapy plans, corresponding testicular doses per course were 90.4 ± 16.3 cGy, 103.6 ± 16.4 cGy, and 139.3 ± 14.6 cGy at 6, 10, and 15 MV, respectively. In conclusions, this study was the first to measure the incidental testicular doses by intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy plans at different energy levels during prostate-only irradiation. Higher photon energy and volumetric-modulated arc radiotherapy plans resulted in higher incidental testicular doses compared with lower photon energy and intensity-modulated radiotherapy plans.

Effect of ionizing radiation on aqueous solution of insulin. [Gamma radiation

Energy Technology Data Exchange (ETDEWEB)

Kopoldova, J [Ceskoslovenska Akademie Ved, Prague. Isotopova Laborator Biologickych Ustavu; Nobilis, M [Vyzkumny Ustav pro Farmacii a Biochemii, Prague (Czechoslovakia)

1977-02-01

A 3.1x10/sup -4/ M aqueous solution of insulin was irradiated with /sup 60/Co in oxygenated, oxygen-limited, and oxygen-free atmosphere. The irradiated solutions were separated on a Sephadex G-75 column, and the eluates were determined spectrophotometrically at 280 nm. The decrease in the original content of insulin and the formation of radiation aggregates of insulin in dependence on radiation doses were studied. The total amount and molecular weights of radiation aggregates of insulin increased with increasing radiation dose while their biological activity and content of cys/2 residues decreased.

Radiation Dose to Newborns in Neonatal Intensive Care Units

International Nuclear Information System (INIS)

Bahreyni Toossi, M. T.; Malekzadeh, M.

2012-01-01

With the increase of X-ray use for medical diagnostic purposes, knowing the given doses is necessary in patients for comparison with reference levels. The concept of reference doses or diagnostic reference levels has been developed as a practical aid in the optimization of patient protection in diagnostic radiology. To assess the radiation doses to neonates from diagnostic radiography (chest and abdomen). This study has been carried out in the neonatal intensive care unit of a province in Iran. Entrance surface dose was measured directly with thermoluminescent dosimeters. The population included 195 neonates admitted for a diagnostic radiography, in eight NICUs of different hospital types. The mean entrance surface dose for chest and abdomen examinations were 76.3 μGy and 61.5 μGy, respectively. Diagnostic reference levels for neonate in NICUs of the province were 88 μGy for chest and 98 μGy for abdomen examinations that were slightly higher than other studies. Risk of death due to radiation cancer incidence of abdomens examination was equal to 1.88 × 10 -6 for male and 4.43 × 10 -6 for female. For chest X-ray, it was equal to 2.54 × 10 -6 for male and 1.17 × 10 -5 for female patients. Diagnostic reference levels for neonates in our province were slightly higher than values reported by other studies such as European national diagnostic reference levels and the NRPB reference dose. The main reason was related to using a high mAs and a low kVp applied in most departments and also a low focus film distance. Probably lack of collimation also affected some exams in the NICUs.

A spatially encoded dose difference maximal intensity projection map for patient dose evaluation: A new first line patient quality assurance tool

Energy Technology Data Exchange (ETDEWEB)

Hu Weigang; Graff, Pierre; Boettger, Thomas; Pouliot, Jean [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California 94143 (United States); and others

2011-04-15

Purpose: To develop a spatially encoded dose difference maximal intensity projection (DD-MIP) as an online patient dose evaluation tool for visualizing the dose differences between the planning dose and dose on the treatment day. Methods: Megavoltage cone-beam CT (MVCBCT) images acquired on the treatment day are used for generating the dose difference index. Each index is represented by different colors for underdose, acceptable, and overdose regions. A maximal intensity projection (MIP) algorithm is developed to compress all the information of an arbitrary 3D dose difference index into a 2D DD-MIP image. In such an algorithm, a distance transformation is generated based on the planning CT. Then, two new volumes representing the overdose and underdose regions of the dose difference index are encoded with the distance transformation map. The distance-encoded indices of each volume are normalized using the skin distance obtained on the planning CT. After that, two MIPs are generated based on the underdose and overdose volumes with green-to-blue and green-to-red lookup tables, respectively. Finally, the two MIPs are merged with an appropriate transparency level and rendered in planning CT images. Results: The spatially encoded DD-MIP was implemented in a dose-guided radiotherapy prototype and tested on 33 MVCBCT images from six patients. The user can easily establish the threshold for the overdose and underdose. A 3% difference between the treatment and planning dose was used as the threshold in the study; hence, the DD-MIP shows red or blue color for the dose difference >3% or {<=}3%, respectively. With such a method, the overdose and underdose regions can be visualized and distinguished without being overshadowed by superficial dose differences. Conclusions: A DD-MIP algorithm was developed that compresses information from 3D into a single or two orthogonal projections while hinting the user whether the dose difference is on the skin surface or deeper.

A spatially encoded dose difference maximal intensity projection map for patient dose evaluation: a new first line patient quality assurance tool.

Science.gov (United States)

Hu, Weigang; Graff, Pierre; Boettger, Thomas; Pouliot, Jean

2011-04-01

To develop a spatially encoded dose difference maximal intensity projection (DD-MIP) as an online patient dose evaluation tool for visualizing the dose differences between the planning dose and dose on the treatment day. Megavoltage cone-beam CT (MVCBCT) images acquired on the treatment day are used for generating the dose difference index. Each index is represented by different colors for underdose, acceptable, and overdose regions. A maximal intensity projection (MIP) algorithm is developed to compress all the information of an arbitrary 3D dose difference index into a 2D DD-MIP image. In such an algorithm, a distance transformation is generated based on the planning CT. Then, two new volumes representing the overdose and underdose regions of the dose difference index are encoded with the distance transformation map. The distance-encoded indices of each volume are normalized using the skin distance obtained on the planning CT. After that, two MIPs are generated based on the underdose and overdose volumes with green-to-blue and green-to-red lookup tables, respectively. Finally, the two MIPs are merged with an appropriate transparency level and rendered in planning CT images. The spatially encoded DD-MIP was implemented in a dose-guided radiotherapy prototype and tested on 33 MVCBCT images from six patients. The user can easily establish the threshold for the overdose and underdose. A 3% difference between the treatment and planning dose was used as the threshold in the study; hence, the DD-MIP shows red or blue color for the dose difference > 3% or < or = 3%, respectively. With such a method, the overdose and underdose regions can be visualized and distinguished without being overshadowed by superficial dose differences. A DD-MIP algorithm was developed that compresses information from 3D into a single or two orthogonal projections while hinting the user whether the dose difference is on the skin surface or deeper.

Reduction in cardiovascular risk factors and insulin dose, but no beta-cell regeneration 1 year after Roux-en-Y gastric bypass in an obese patient with type 1 diabetes

DEFF Research Database (Denmark)

Dirksen, Carsten; Jacobsen, Siv H; Bojsen-Møller, Kirstine N

2013-01-01

Experience with Roux-en-Y gastric bypass in patients with type 1 diabetes is very limited, despite an increasing prevalence of obesity also in this population. We describe changes in anthropometric measures, insulin dose, HbA1c, blood pressure, lipid status, and metabolic response to a liquid mixed...... meal throughout the first year after RYGB in an obese patient with type 1 diabetes. No change in HbA1c was observed, but a 48% reduction in weight-adjusted insulin dose and improvements in cardiovascular risk factors was seen 1 year after surgery. Exaggerated secretions of anorexigenic gut hormones...

Oat beta-glucan ameliorates insulin resistance in mice fed on high-fat and high-fructose diet

Directory of Open Access Journals (Sweden)

Jie Zheng

2013-12-01

Full Text Available Methods: This study sought to evaluate the impact of oat beta-glucan on insulin resistance in mice fed on high-fat and high-fructose diet with fructose (10%, w/v added in drinking water for 10 weeks. Results: The results showed that supplementation with oat beta-glucan could significantly reduce the insulin resistance both in low-dose (200 mg/kg−1 body weight and high-dose (500 mg/kg−1 body weight groups, but the high-dose group showed a more significant improvement in insulin resistance (P<0.01 compared with model control (MC group along with significant improvement in hepatic glycogen level, oral glucose, and insulin tolerance. Moreover, hepatic glucokinase activity was markedly enhanced both in low-dose and high-dose groups compared with that of MC group (P<0.05. Conclusion: These results suggested that supplementation of oat beta-glucan alleviated insulin resistance and the effect was dose dependent.

Humalog(®) KwikPen™: an insulin-injecting pen designed for ease of use.

Science.gov (United States)

Schwartz, Sherwyn L; Ignaut, Debra A; Bodie, Jennifer N

2010-11-01

Insulin pens offer significant benefits over vial and syringe injections for patients with diabetes who require insulin therapy. Insulin pens are more discreet, easier for patients to hold and inject, and provide better dosing accuracy than vial and syringe injections. The Humalog(®) KwikPen™ (prefilled insulin lispro [Humalog] pen, Eli Lilly and Company, Indianapolis, IN, USA) is a prefilled insulin pen highly rated by patients for ease of use in injections, and has been preferred by patients to both a comparable insulin pen and to vial and syringe injections in comparator studies. Together with an engineering study demonstrating smoother injections and reduced dosing error versus a comparator pen, recent evidence demonstrates the Humalog KwikPen device is an accurate, easy-to-use, patient-preferred insulin pen.

The early use of insulin in type 2 diabetes

Directory of Open Access Journals (Sweden)

PHILIP LEVY

2004-06-01

Full Text Available 60?70% of all patients with Type 2 Diabetes Mellitus will ultimately require insulin therapy for the management of their diabetes. Irisulin may be used alone, or in combination with oral agents. The early use of insulin can be very important in decreasing the incidence of micro-vascular complications and in helping to delay the onset of macro-vascular complications. The United Kingdom Prospective Diabetes Study and the Kumamoto Study have shown the beneficial effects of good glucose control in type 2 diabetes mellitus. The DECODE study has related overall mortality to the level of glucose control and specifically to the postprandial glucose. The American Association of Clinical Endocrinologists has established a goal of 6.5% or less for HgbAlc. The appropriate use of insulin will allow us to achieve this goal without causing the patient any undue harm. There are many barriers to insulin therapy including psychological barriers of both the patient and the doctor, and unrealistic fears of both insulin therapy and therapy with self-administered injections. These barriers will be discussed as well as methods to overcome them. Insulin therapy is beneficial and has no long term adverse effects. The incidence of severe hypoglycemia is extremely low in type 2 diabetes. Weight gain is minimal. Insulin therapy by reducing glucose toxicity may also increase the effectiveness of oral anti-hyperglycemic agents. The physician taking care of patients with diabetes should be aggressive and should have no fears of initiating insulin therapy. Insulin dosage is flexible and good control is possible in most patients. The most common use of insulin in type 2 diabetes is as an add-on to oral agents if control with oral agents alone is unsatisfactory. Frequently this involves the use of a single dose of intermediate or long acting insulin or an insulin mixture in the evening. If control is not attained with a single dose, then the patient can be placed on an insulin

Performance of a glucose meter with a built-in automated bolus calculator versus manual bolus calculation in insulin-using subjects.

Science.gov (United States)

Sussman, Allen; Taylor, Elizabeth J; Patel, Mona; Ward, Jeanne; Alva, Shridhara; Lawrence, Andrew; Ng, Ronald

2012-03-01

Patients consider multiple parameters in adjusting prandial insulin doses for optimal glycemic control. Difficulties in calculations can lead to incorrect doses or induce patients to administer fixed doses, rely on empirical estimates, or skip boluses. A multicenter study was conducted with 205 diabetes subjects who were on multiple daily injections of rapid/ short-acting insulin. Using the formula provided, the subjects manually calculated two prandial insulin doses based on one high and one normal glucose test result, respectively. They also determined the two doses using the FreeStyle InsuLinx Blood Glucose Monitoring System, which has a built-in, automated bolus calculator. After dose determinations, the subjects completed opinion surveys. Of the 409 insulin doses manually calculated by the subjects, 256 (63%) were incorrect. Only 23 (6%) of the same 409 dose determinations were incorrect using the meter, and these errors were due to either confirmed or potential deviations from the study instructions by the subjects when determining dose with meter. In the survey, 83% of the subjects expressed more confidence in the meter-calculated doses than the manually calculated doses. Furthermore, 87% of the subjects preferred to use the meter than manual calculation to determine prandial insulin doses. Insulin-using patients made errors in more than half of the manually calculated insulin doses. Use of the automated bolus calculator in the FreeStyle InsuLinx meter minimized errors in dose determination. The patients also expressed confidence and preference for using the meter. This may increase adherence and help optimize the use of mealtime insulin. © 2012 Diabetes Technology Society.

Anti-inflammatory effects of insulin.

Science.gov (United States)

Dandona, Paresh; Chaudhuri, Ajay; Mohanty, Priya; Ghanim, Husam

2007-07-01

This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit. The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease. The anti-inflammatory action of insulin provides a neutralizing effect to balance macronutrient induced inflammation on the one hand and the possibility of using insulin as an anti-inflammatory drug on the other. The actions of macronutrients and insulin described above explain why insulin resistant states like obesity and type 2 diabetes are associated with oxidative stress, inflammation and atherosclerosis. They also suggest that insulin may be antiatherogenic.

Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

DEFF Research Database (Denmark)

Øzbay, Aygen; Møller, Niels; Juhl, Claus

2012-01-01

and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses...... of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction...... of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development...

Redesigning an intensive insulin service for patients with type 1 diabetes: a patient consultation exercise

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Ozcan S

2013-06-01

Full Text Available Seyda Ozcan,1–3 Helen Rogers,3 Pratik Choudhary,3 Stephanie A Amiel,3 Alison Cox,3 Angus Forbes2,3 1Department of Medical Nursing, Florence Nightingale Nursing Faculty, Istanbul University, Istanbul, Turkey; 2Department of Primary and Intermediate Care, Florence Nightingale School of Nursing and Midwifery, King’s College London, London, United Kingdom; 3Department of Diabetes, King's College Hospital NHS Foundation Trust, London, United Kingdom Context: Providing effective support for patients in using insulin effectively is essential for good diabetes care. For that support to be effective it must reflect and attend to the needs of patients. Purpose: To explore the perspectives of adult type 1 diabetes patients on their current diabetes care in order to generate ideas for creating a new patient centered intensive insulin clinic. Methods: A multi-method approach was used, comprising: an observational exercise of current clinical care; three focus groups (n = 17; and a survey of service users (n = 419 to test the ideas generated from the observational exercise and focus groups (rating 1 to 5 in terms of importance. The ideas generated by the multi-method approach were organized thematically and mapped onto the Chronic Care Model (CCM. Results: The themes and preferences for service redesign in relation to CCM components were: health care organization, there was an interest in having enhanced systems for sharing clinical information; self-management support, patients would like more flexible and easy to access resources and more help with diabetes technology and psychosocial support; delivery system design and clinical information systems, the need for greater integration of care and better use of clinic time; productive relationships, participants would like more continuity; access to health professionals, patient involvement and care planning. The findings from the patient survey indicate high preferences for most of the areas for service

Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature

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Niko Bekjarovski

2013-09-01

How to cite this article: Bekjarovski NG. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature. Asia Pac J Med Toxicol 2013;2:114-6.

Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity

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Bruckbauer A

2013-02-01

Full Text Available Antje Bruckbauer,1 Michael B Zemel1,21NuSirt Sciences Inc, 2Department of Nutrition, University of Tennessee, Knoxville, TN, USABackground: The purpose of this study was to determine whether a mixture of the polyphenol, resveratrol, and the leucine metabolite, hydroxymethylbutyrate (HMB, acts synergistically with low doses of metformin to impact insulin sensitivity and AMP-activated protein kinase-dependent outcomes in cell culture and in diabetic mice.Methods: C2C12 skeletal myotubes and 3T3-L1 adipocytes were treated with resveratrol 0.2 µM, HMB 5 µM, and metformin 0.1 mM alone or in combination. db/db mice were treated for 2 weeks with high (1.5 g/kg diet, low (0.75 g/kg diet, or very low (0.25 g/kg diet doses of metformin alone or in combination with a diet containing resveratrol 12.5 mg and CaHMB 2 g/kg.Results: The combination of metformin-resveratrol-HMB significantly increased fat oxidation, AMP-activated protein kinase, and Sirt1 activity in muscle cells compared with metformin or resveratrol-HMB alone. A similar trend was found in 3T3L1 adipocytes. In mice, the two lower doses of metformin exerted no independent effect but, when combined with resveratrol-HMB, both low-dose and very low-dose metformin improved insulin sensitivity (HOMAIR, plasma insulin levels, and insulin tolerance test response to a level comparable with that found for high-dose metformin. In addition, the metformin-resveratrol-HMB combination decreased visceral fat and liver weight in mice.Conclusion: Resveratrol-HMB combined with metformin may act synergistically on AMP-activated protein kinase-dependent pathways, leading to increased insulin sensitivity, which may reduce the therapeutic doses of metformin necessary in the treatment of diabetes.Keywords: diabetes, AMP-activated protein kinase, Sirt1, fat oxidation

Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

Science.gov (United States)

Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

2014-10-20

Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

Streptozotocin Aggravated Osteopathology and Insulin Induced Osteogenesis Through Co-treatment with Fluoride.

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Yang, Chen; Zhang, Mengmeng; Li, Yagang; Wang, Yan; Mao, Weixian; Gao, Yuan; Xu, Hui

2015-12-01

The role of insulin in the mechanism underlying the excessive fluoride that causes skeletal lesion was studied. The in vitro bone marrow stem cells (BMSC) collected from Kunming mice were exposed to varying concentrations of fluoride with or without insulin. The cell viability and early differentiation of BMSC co-treated with fluoride and insulin were measured by using cell counting kit-8 and Gomori modified calcium-cobalt method, respectively. We further investigated the in vivo effects of varying dose of fluoride on rats co-treated with streptozotocin (STZ). Wistar rats were divided into six groups which included normal control, 10 mg fluoride/kg day group, 20 mg fluoride/kg day group, STZ control, STZ+10 mg fluoride/kg day group, and STZ+20 mg fluoride/kg day group. The rats were administered with sodium fluoride (NaF) by gavage with water at doses 10 and 20 mg fluoride/kg day for 2 months. In a period of one month, half of rats in every group were treated with streptozotocin (STZ) once through intraperitoneal injection at 52 mg/kg body weight. The serum glucose, HbA1c, and insulin were determined. Bone mineral content and insulin release were assessed. The results showed insulin combined with fluoride stimulated BMSC cell viability in vitro. The bone mineral content reduced in rats treated with higher dose of fluoride and decreased immensely in rat co-treated with fluoride and STZ. Similarly, a combination treatment of a high dose of fluoride and STZ decreased insulin sensitivity and activity. To sum up, these data indicated fluoride influenced insulin release, activity, and sensitivity. Furthermore, the insulin state in vivo interfered in the osteogenesis in turn and implied there was a close relation between insulin and bone pathogenesis in the mechanism of fluoride toxicity.

Dose rate laser simulation tests adequacy: Shadowing and high intensity effects analysis

International Nuclear Information System (INIS)

Nikiforov, A.Y.; Skorobogatov, P.K.

1996-01-01

The adequacy of laser based simulation of the flash X-ray effects in microcircuits may be corrupted mainly due to laser radiation shadowing by the metallization and the non-linear absorption in a high intensity range. The numerical joint solution of the optical equations and the fundamental system of equations in a two-dimensional approximation were performed to adjust the application range of laser simulation. As a result the equivalent dose rate to laser intensity correspondence was established taking into account the shadowing as well as the high intensity effects. The simulation adequacy was verified in the range up to 4·10 11 rad(Si)/s with the comparative laser test of a specially designed test structure

An observational study comparing continuous subcutaneous insulin infusion (CSII) and insulin glargine in children with type 1 diabetes.

Science.gov (United States)

Schiaffini, Riccardo; Ciampalini, Paolo; Spera, Sabrina; Cappa, Marco; Crinó, Antonino

2005-01-01

The advantages of continuous subcutaneous insulin infusion (CSII) or insulin glargine have been demonstrated both in adult and paediatric diabetic patients; however, as no data comparing these two approaches during childhood are available, we have examined the efficacy of these two intensive approaches. We retrospectively evaluated data from 36 diabetic children, who had changed their previous insulin regimen [with isophane insulin (NPH) at bedtime] because of HbA1c levels >8.0%. Twenty patients underwent CSII, while the other 16 (significantly younger for age) started insulin glargine at bedtime. At 6 and 12 months, CSII-treated patients showed a significant reduction in HbA1c values from 8.5 +/- 1.8 to 7.4 +/- 1.1% and to 7.6 +/- 1.2%, respectively. The insulin requirement significantly decreased from 0.93 +/- 0.2 IU/kg to 0.73 +/- 0.2 IU/kg of body weight and to 0.74 +/- 0.15 IU/kg of body weight, respectively, while no significant differences were observed for BMI SDS, fructosamine and severe hypoglycaemic events. The patients treated with glargine showed a small decline in HbA1c values from 8.9 +/- 1.7 to 8.3 +/- 0.9% (not significant) in the first 6 months of treatment and to 8.2 +/- 0.9% after 12 months. The basal insulin supplementation can be supplied effectively in children with type 1 diabetes by either CSII or insulin glargine. As previously reported for adults, it is confirmed that CSII is the best current intensive approach aimed to the improvement of glycaemic control.

Measurement of irradiation doses secondary to bedside radiographs in a medical intensive care unit

Energy Technology Data Exchange (ETDEWEB)

Boles, J M; Boussert, F; Manens, J P; Le Cam, B; Bellet, M; Garre, M

1987-01-01

The authors prospectively studied the radiation doses to radio-sensitive organs secondary to bedside radiographs in intensive care patients and in a control phantom. Dosimeters were taped on different organs during each bedside X-ray. The mean radiation doses, expressed in 10(-5) Gy (m-rad), for an ''average patient'' who was hospitalized 9 days and had 6 chest X-rays were respectively: 292 to the sternal bone marrow; 239 to the thyroid gland; 3 to the testes; 1 to the ovaries; 605 to the eye for 2 maxillary sinus X-rays. No diffused irradiation was measured during a 2-month period in the intensive care unit nor on dosimeters worn by four nurses.

Reversal of the toxic effects of cachectin by concurrent insulin administration.

Science.gov (United States)

Fraker, D L; Merino, M J; Norton, J A

1989-06-01

Rats treated with recombinant human tumor necrosis factor-cachectin, 100 micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in body weight gain vs. saline-treated controls. Concurrent neutral protamine hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of these changes to control levels without causing any treatment deaths. The improvement seen with insulin was dose independent. Five days of cachectin treatment caused a severe interstitial pneumonitis, periportal inflammation in the liver, and an increase in wet organ weight in the heart, lungs, kidney, and spleen. Concurrent insulin treatment led to near total reversal of these histopathologic changes. Cachectin treatment did not significantly change blood glucose levels from control values of 130-140 mg/dl, but insulin plus cachectin caused a significant decrease in blood glucose from 1 through 12 h after injection. Administration of high-dose insulin can near totally reverse the nutritional and histopathologic toxicity of sublethal doses of cachectin in rats.

Oral insulin reloaded: a structured approach.

Science.gov (United States)

Zijlstra, Eric; Heinemann, Lutz; Plum-Mörschel, Leona

2014-05-01

Optimal coverage of insulin needs is the paramount aim of insulin replacement therapy in patients with diabetes mellitus. To apply insulin without breaking the skin barrier by a needle and/or to allow a more physiological provision of insulin are the main reasons triggering the continuous search for alternative routes of insulin administration. Despite numerous attempts over the past 9 decades to develop an insulin pill, no insulin for oral dosing is commercially available. By way of a structured approach, we aim to provide a systematic update on the most recent developments toward an orally available insulin formulation with a clear focus on data from clinical-experimental and clinical studies. Thirteen companies that claim to be working on oral insulin formulations were identified. However, only 6 of these companies published new clinical trial results within the past 5 years. Interestingly, these clinical data reports make up a mere 4% of the considerably high total number of publications on the development of oral insulin formulations within this time period. While this picture clearly reflects the rising research interest in orally bioavailable insulin formulations, it also highlights the fact that the lion's share of research efforts is still allocated to the preclinical stages. © 2014 Diabetes Technology Society.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

Science.gov (United States)

Yamazaki, Ricardo K; Brito, Gleisson A P; Coelho, Isabela; Pequitto, Danielle C T; Yamaguchi, Adriana A; Borghetti, Gina; Schiessel, Dalton Luiz; Kryczyk, Marcelo; Machado, Juliano; Rocha, Ricelli E R; Aikawa, Julia; Iagher, Fabiola; Naliwaiko, Katya; Tanhoffer, Ricardo A; Nunes, Everson A; Fernandes, Luiz Claudio

2011-04-28

Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Insulin release by glucagon and secretin

DEFF Research Database (Denmark)

Kofod, Hans; Andreu, D; Thams, P

1988-01-01

Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated...... the release of insulin at 10 mM D-glucose, and their effects were indistinguishable with respect to the dynamics of release, dose-response relationship, and glucose dependency. However, measurements of cAMP accumulation in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-4) M...... potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different....

Detemir as a once-daily basal insulin in type 2 diabetes

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Nelson SE

2011-08-01

Full Text Available Scott E NelsonCleveland Family Medicine, Cleveland, Mississippi, USABackground: Insulin detemir, a long-acting basal insulin analog, is labeled for once-daily or twice-daily dosing in patients with type 1 (T1DM or type 2 (T2DM diabetes mellitus. Protocols for some earlier clinical studies of detemir evaluated twice-daily dosing, which may have generated the misperception that detemir should be prescribed twice daily for most patients. This review examines pharmacokinetic and pharmacodynamic (PK/PD, observational, and controlled studies that have evaluated once-daily and twice-daily detemir in patients with T2DM to determine the efficacy and safety of once-daily dosing.Methods: PubMed was searched using the keywords “detemir,” “once daily,” “twice daily,” and “type 2 diabetes” with the limits of clinical trial, human, and English.Results: Detemir has a relatively flat time–action profile and duration of action of up to 24 hours for patients with T2DM. Once-daily dosing is the most commonly used detemir regimen reported in observational studies, and controlled clinical studies indicate that once-daily dosing controls glycosylated hemoglobin when detemir is administered alone or in combination with a prandial insulin or oral antidiabetes drugs. In comparative clinical trials, detemir had a similar time–action profile and duration of action to another long-acting insulin analog, glargine, with less within-subject variability. Once-daily detemir was associated with no weight gain or less weight gain than comparator regimens. For patients who had not achieved glycemic control with a basal dose of once-daily detemir, adding a prandial insulin provided better glycemic control, less postprandial hypoglycemia, and a lower total daily dose of detemir than twice-daily detemir. Involvement of a multidisciplinary team and the use of a holistic approach for the treatment of T2DM patients are recommended to achieve and maintain the best

Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Science.gov (United States)

Viscarra, Jose A; Rodriguez, Ruben; Vazquez-Medina, Jose Pablo; Lee, Andrew; Tift, Michael S; Tavoni, Stephen K; Crocker, Daniel E; Ortiz, Rudy M

2013-08-01

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation.

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

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Suk Chon

2011-02-01

Full Text Available BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

Science.gov (United States)

Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A psychophysical account of patient non-adherence to medical prescriptions. The case of insulin dose adjustment.

Science.gov (United States)

Reach, G

2013-02-01

Diabetic patients often do not adjust their insulin doses using the algorithms that they have been taught. While this behavior may intuitively have a number of causes, such as the complexity of the decision or the fear of hypoglycaemia, we propose in this article a more general, "psychophysical", explanation based on behavioral economics concepts used to describe decisions made under uncertainty and risk. The concepts discussed herein may not be familiar to clinicians, who will find here an introduction to theories that may be helpful in understanding some aspects of non-adherence to medical prescriptions. 1) The Prospect Theory of Kahneman and Tversky proposes that choices made in the context of risk are subject to loss aversion. 2) Decisions under uncertainty use mental short cuts called "heuristics", which can lead to biases; for instance, overestimating the probability of the risk. 3) To understand the very concept of risk, emotions must be considered with a special focus on anticipated regret. 4) Finally, selection difficulty is an important determinant of the preference for the status quo. These concepts may be relevant for understanding a preference for the status quo in decisions made in a context of uncertainty and risk, such as insulin dose adjustment. We suggest that these mental mechanisms may also be involved in other aspects of patients' non-adherence. As other common human behaviors, non-adherence may actually often be a consequence of biases resulting from our ways of thinking, being both cognitive and emotional, and, according to Kahneman, more often "fast" than "slow". Empirical studies are needed to support this hypothesis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Meal replacement reduces insulin requirement, HbA1c and weight long-term in type 2 diabetes patients with >100 U insulin per day.

Science.gov (United States)

Kempf, K; Schloot, N C; Gärtner, B; Keil, R; Schadewaldt, P; Martin, S

2014-04-01

Despite high insulin doses, good glycaemic control is often lacking in type 2 diabetes patients and new therapeutic options are needed. In a proof of principle study, an energy-restricted, protein-rich meal replacement (PRMR) was examined as a means of reducing insulin requirement, HbA1C and body weight. Obese type 2 diabetes patients (n = 22) with >100 U insulin per day replaced, in week 1, the three main meals with 50 g of PRMR (Almased-Vitalkost) each (= 4903 kJ day(-1) ). In weeks 2-4, breakfast and dinner were replaced, and, in weeks 5-12, only dinner was replaced. Clinical parameters were determined at baseline, and after 4, 8 and 12 weeks, as well as after 1.5 years of follow-up. The Wilcoxon signed-rank test was used for the intention-to-treat analysis and the Mann-Whitney U-test for subgroup analyses. The 12-week-programme was completed by 15 participants (68%). After 1 week, the mean insulin dose was reduced from 147 (75) U to 91 (55) U day(-1) (P = 0.0001), and to 65 (32) U (P fasting blood glucose, triglycerides and high-density lipoprotein cholesterol improved significantly. After 1.5 years, insulin requirement and weight remained significantly lower than baseline. Participants who continued PRMR further reduced their HbA1c, weight and insulin dose. Two patients were able to stop insulin therapy altogether. Energy-restricted PRMR was effective in reducing insulin requirement of type 2 diabetes patients with intensified insulin therapy accompanied by a reduction of HbA1c, weight and other cardiometabolic risk factors. With the continuous use of PRMR, glycaemic control might be improved in the long term. © 2013 The British Dietetic Association Ltd.

Effects of heparin on insulin binding and biological activity

International Nuclear Information System (INIS)

Kriauciunas, K.M.; Grigorescu, F.; Kahn, C.R.

1987-01-01

The effect of heparin, a polyanionic glycosaminoglycan known to alter the function of many proteins, on insulin binding and bioactivity was studied. Cultured human lymphocytes (IM-9) were incubated with varying concentrations of heparin, then extensively washed, and 125 I-labeled insulin binding was measured. Heparin at concentrations used clinically for anticoagulation (1-50 U/ml) inhibited binding in a dose-dependent manner; 50% inhibition of binding occurred with 5-10 U/ml. Scatchard analysis indicated that the decrease in binding was due to a decrease in both the affinity and the apparent number of available insulin receptors. The effect occurred within 10 min at 22 degrees C and persisted even after the cells were extensively washed. Inhibition of insulin binding also occurred when cells were preincubated with heparinized plasma or heparinized serum but not when cells were incubated with normal serum or plasma from blood anticoagulated with EDTA. By contrast, other polyanions and polycations, e.g., poly-L-glutamic acid, poly-L-lysine, succinylated poly-L-lysine, and histone, did not inhibit binding. Heparin also inhibited insulin binding in Epstein-Barr (EB) virus-transformed lymphocytes but had no effect on insulin binding to isolated adipocytes, human erythrocytes, or intact hepatoma cells. When isolated adipocytes were incubated with heparin, there was a dose-dependent inhibition of insulin-stimulated glucose oxidation and, to a lesser extent, of basal glucose oxidation. Although heparin has no effect on insulin binding to intact hepatoma cells, heparin inhibited both insulin binding and insulin-stimulated autophosphorylation in receptors solubilized from these cells

A comparison of radiation treatment techniques for carcinomas of the larynx and hypopharynx using 3-D dose distributions and intensity modulation

International Nuclear Information System (INIS)

Morris, David; Miller, Elizabeth P.; Rosenman, Julian; Sailer, Scott; Tepper, Joel

1997-01-01

Purpose/Objective: Patients with carcinomas of the larynx and hypopharynx often cannot be treated effectively with a lateral/low anterior neck combination because the midline block will cover the tumor bed. Common alternatives to this approach often produce serious dose inhomogeneities. Our study was to determine whether modern 3D treatment planning techniques with intensity modulation could overcome these dose inhomogeneities and also allow us to omit the problematic posterior neck electron boost which often gives poor nodal coverage. Materials and Methods: Dose distribution studies were performed on patients who had received post-operative radiation following laryngectomy for advanced staged cancer. The clinical tumor volume or CTV (surgical bed and at-risk nodal stations) was defined on planning CT images. Four commonly used alternative plans, the MGH 'minimantle', 'kicked-out' laterals, the University of Florida 3-field, and a standard 3 field with a lateral cord block were evaluated using the Plan UNC (PLUNC) treatment planning software. New plans that might also preclude the use of posterior neck electrons were also evaluated. The plans were then intensity modulated to reduce the well known cold spots as described previously in IJROBP August 1991, Vol. 21, No. 3. All dose distributions were evaluated for dose homogeneity, minimum and maximum CTV dose, and dose to normal critical structures. The inhomogeneities were determined using standard dose-volume histogram (DVH) techniques but positional information was gathered by dividing the CTV into sensible anatomic regions and studying the DVH for each separately. Results: For the mini-mantle approach, intensity modulation substantially improved the dose inhomogeneities but did not affect the minimum CTV dose and had no effect on the cord dose. Intensity modulation decreased the maximum CTV dose (110% vs. 130%) but had the undesirable effect of lessening the dose difference between cord and CTV. For the kicked

A randomized controlled clinical trial investigating the effect of calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress and insulin resistance in pregnant women at risk for pre-eclampsia.

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Asemi, Z; Samimi, M; Heidarzadeh, Z; Khorrammian, H; Tabassi, Z

2012-05-15

Increased levels of pro-inflammatory factors, markers of oxidative stress and insulin resistance during pregnancy have been associated with the development of pre-eclampsia. There is some evidence to suggest that calcium supplement and aspirin can reduce the risk of the disorder. To our knowledge, no reports are available indicating the effects of consumed calcium supplement plus aspirin on high sensitivity C-reactive protein (hs-CRP), oxidative stress parameters and insulin resistance in pregnant women at risk for pre-eclampsia. This study was designed to investigate the effects of consumed calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress parameters and insulin resistance among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was carried out among 42 pregnant women at risk for pre-eclampsia, primigravida, aged 18-40 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to received either the placebo (n = 22) or calcium supplement plus low-dose aspirin (n = 20) for 9 weeks. Calcium supplement plus low-dose aspirin were containing 500 mg carbonate calcium plus 80 mg aspirin. Fasting blood samples were taken at baseline and after 9 weeks intervention to measure serum hs-CRP, oxidative stress parameters including plasma Total Antioxidant Capacity (TAC) and Total Glutathione (GSH), Fasting Plasma Glucose (FPG), serum insulin and HOMA-IR score. Consumption of calcium supplement plus low-dose aspirin resulted in a significant difference serum hs-CRP levels as compared to the placebo (102.87 vs. 3227.75 ng mL(-1), p = 0.01). Also, mean changes for plasma TAC (68.96 vs. -74.46 mmol L(-1), p = 0.04) and total GSH levels (304.33 vs. -39.33 micromol L(-1), p = 0.03) were significantly different between the two groups. No significant differences were found comparing calcium supplement plus low-dose aspirin and placebo in terms of their effects on FPG

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

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Iagher Fabiola

2011-04-01

Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Influence of gamma-irradiation upon the chemical and biological properties of insulin

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Salemink, P J.M.; Kolkman-Roodbeen, J C; Gribnau, T C.J.; Janssen, P S.L.; Veen, A.J. van der

1987-06-19

Partially purified insulin preparations of bovine and porcine origin, were subjected to gamma-irradiation with doses ranging from 1.0 up to 25 kGy at 0/sup 0/C or ambient temperature. The susceptibility of insulin to the irradiation was determined by chromatography, electrophoresis and assay of the biological activity. The sterilizing effect of the gamma-irradiation was investigated for Bacillus pumilus as well as for artificial mixtures of lactose and several bacilli. It is concluded that the sterilizing dose for the investigated insulins was greater than or equal to 2.2 kGy. At doses up to 25 kGy at 0/sup 0/C no specific radiolytic products were detectable, whereas the biological activity was fully retained. The content of dimers and the content of related peptides appeared to increase gradually with the irradiation dose absorbed. No effects of long-term storage could be demonstrated on biological and chemical properties of insulin after 2.2, 4.5 and 7.5 kGy. 21 refs.; 4 figs.; 5 tabs.

What Are the Safety Considerations for Insulin Control for Athletes?

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McDaniel, Larry W.; Olson, Sara; Gaudet, Laura; Jackson, Allen

2010-01-01

Athletes diagnosed with diabetes may have difficulty with their blood sugar levels fluctuating during intense exercise. Considerations for athletes with insulin concerns may range anywhere from exercise rehabilitation to the use of an automatic insulin pump. The automatic insulin pump is a small battery-operated device about the size of a pager.…

Treatment Dosing Patterns and Clinical Outcomes for Patients with Type 2 Diabetes Starting or Switching to Treatment with Insulin Glargine (300 Units per Milliliter) in a Real-World Setting: A Retrospective Observational Study.

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Gupta, Shaloo; Wang, Hongwei; Skolnik, Neil; Tong, Liyue; Liebert, Ryan M; Lee, Lulu K; Stella, Peter; Cali, Anna; Preblick, Ronald

2018-01-01

Usage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 to assess whether the benefits observed in clinical trials translate into real-world settings. This was a retrospective observational study using medical record data obtained by physician survey for patients starting treatment with insulin glargine at a strength of 100 units per milliliter (Gla-100) or Gla-300, or switching to treatment with Gla-300 from treatment with another basal insulin (BI). Differences in dosing and clinical outcomes before versus after treatment initiation or switching were examined by generalized linear mixed-effects models. Among insulin-naive patients starting BI treatment, no difference in the final titrated dose was observed in patients starting Gla-300 treatment versus those starting Gla-100 treatment [least-squares (LS) mean 0.43 units per kilogram vs 0.44 units per kilogram; P = 0.77]. Both groups had significant hemoglobin A 1c level reductions (LS mean 1.21 percentage points for Gla-300 and 1.12 percentage points for Gla-100 ; both P per kilogram before switch vs 0.58 units per kilogram after switch; P = 0.02). The mean hemoglobin A 1c level was significantly lower after switching than before switching (adjusted difference - 0.95 percentage points, 95% CI - 1.13 to - 0.78 percentage points ; P per patient-year were significantly lower (relative risk 0.17, 95% CI 0.11-0.26; P < 0.0001). Insulin-naive patients starting Gla-300 treatment had fewer hypoglycemic events, a similar hemoglobin A 1c level reduction, and no difference in insulin dose versus patients starting Gla-100 treatment. Patients switching to Gla-300 treatment from treatment with

Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients.

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Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

2015-05-01

Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

International Nuclear Information System (INIS)

Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.

2012-01-01

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged ≤7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

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Minglong Shao

Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

Some remarks on non-monotonic effects at low radiation intensities, on the problem of extrapolating doses between high and low intensities and on the problem of thresholds

International Nuclear Information System (INIS)

Delattre, P.

1983-01-01

On the basis of a general descriptive framework which takes into account the intensity factor and the time distribution of radiation, a detailed justification for which is to be found in earlier publications, the three fundamental problems mentioned in the title of this paper can be approached in a new way. If the biological effect e for a given dose D delivered at different radiation intensities phi is studied, we find that the curve e=f(phi) can exhibit non-monotonic shapes. This type of phenomenon is known in pharmacology and toxicology and may well exist also for low- or medium-intensity radiation effects. Extrapolation of the effects of a given dose between high and low radiation intensities phi is usually carried out by means of an empirical linear or linear-quadratic formulation. This procedure is insufficiently justified from a theoretical point of view. It is shown here that the effects can be written in the form e=k(phi)D and that the factor of proportionality k(phi) is a generally very complicated function of phi. Hence, the usual extrapolation procedures cannot deal with certain ranges of values of phi within which the effects observed at a given dose may be greater than when the dose is delivered at higher intensity. The problem of thresholds is actually far more difficult than the current literature on the subject would suggest. It is shown here, on the basis of considerations of qualitative dynamics, that several types of threshold must be defined, starting with a threshold for the radiation intensity phi. All these thresholds are interrelated hierarchically in fairly complex ways which must be studied case by case. These results show that it is illusory to attempt to define a universal notion of threshold in terms of dose. The conceptual framework used in the proposed approach proves also to be very illuminating for other studies in progress, particularly in the investigation of phenomena associated with ageing and carcinogenesis. (author)

Radiation dose in the neonatal intensive care unit of Antoine Beclere Hospital

International Nuclear Information System (INIS)

Lebreton, C.; Rehel, J. L.; Aubert, B.; Musset, D.

2006-01-01

As part of a program aiming a better knowledge of the medical exposure of the french population and in the frame of the principle of optimisation, a study of radiation doses to neonates was carried out in neonatal intensive care unit of Antoine Beclere hospital. From March to August 2005, entrance surface dose (ESD) received by 63 neonates classified according the their weight (184 X-ray examinations) was measured with thermoluminescent dosimeters (TLD) during examination. The mean ESD ESD per exposure was found between 20 and 37 μGy according to the weight of neonates. The newborn of less than 1000 g at birth have a mean of 20 X-ray examinations. Above 1000 g the number of X-ray examinations was between 5 and 8.5. During their stay in neonatal intensive care unit, the total ESD of neonates was from 500 μGy for the smallest Neonates (<1000 g) and the other respectively. Results indicate that neonate exposition, is very small compared with french and international data. ESD was significantly lower than the french reference level of 80 μGy. (Author)

Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents.

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Home, Philip D; Dain, Marie-Paule; Freemantle, Nick; Kawamori, Ryuzo; Pfohl, Martin; Brette, Sandrine; Pilorget, Valérie; Scherbaum, Werner A; Vespasiani, Giacomo; Vincent, Maya; Balkau, Beverley

2015-05-01

It is of interest to understand how insulin therapy currently evolves in clinical practice, in the years after starting insulin in people with type 2 diabetes. We aimed to describe this evolution prospectively over 4 years, to assist health care planning. People who had started any insulin were identified from 12 countries on three continents. Baseline, then yearly follow-up, data were extracted from clinical records over 4 years. Of the 2999 eligible people, 2272 were followed over 4 years. When starting insulin, mean (SD) duration of diabetes was 10.6 (7.8) years, HbA1c 9.5 (2.0)% (80 [22]mmol/mol) and BMI 29.3 (6.3)kg/m(2). Initial insulin therapy was basal 52%, premix 23%, mealtime+basal 14%, mealtime 8% and other 3%; at 4 years, 30%, 25%, 33%, 2% and 5%, respectively, with 5% not on insulin. Insulin dose was 20.2U/day at the start and 45.8U/day at year 4. There were 1258 people (55%) on their original regimen at 4 years, and this percentage differed according to baseline insulin regimen. HbA1c change was -2.0 (2.2)% (-22 [24]mmol/mol) and was similar by final insulin regimen. Hypoglycaemia prevalence was <20% in years 1-4. Body weight change was mostly in year 1, and was very variable, mean +2.7 (7.5)kg at year 4. Different insulin regimens were started in people with differing characteristics, and they evolved differently; insulin dose, hypoglycaemia and body weight change were diverse and largely independent of regimen. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

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Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

2017-04-01

Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m 2 ) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR ( P HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR prevalence in other anthropometric, cardiovascular, strength, and endurance performance measurements in insulin-resistant women. These

Personalized State-space Modeling of Glucose Dynamics for Type 1 Diabetes Using Continuously Monitored Glucose, Insulin Dose, and Meal Intake: An Extended Kalman Filter Approach.

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Wang, Qian; Molenaar, Peter; Harsh, Saurabh; Freeman, Kenneth; Xie, Jinyu; Gold, Carol; Rovine, Mike; Ulbrecht, Jan

2014-03-01

An essential component of any artificial pancreas is on the prediction of blood glucose levels as a function of exogenous and endogenous perturbations such as insulin dose, meal intake, and physical activity and emotional tone under natural living conditions. In this article, we present a new data-driven state-space dynamic model with time-varying coefficients that are used to explicitly quantify the time-varying patient-specific effects of insulin dose and meal intake on blood glucose fluctuations. Using the 3-variate time series of glucose level, insulin dose, and meal intake of an individual type 1 diabetic subject, we apply an extended Kalman filter (EKF) to estimate time-varying coefficients of the patient-specific state-space model. We evaluate our empirical modeling using (1) the FDA-approved UVa/Padova simulator with 30 virtual patients and (2) clinical data of 5 type 1 diabetic patients under natural living conditions. Compared to a forgetting-factor-based recursive ARX model of the same order, the EKF model predictions have higher fit, and significantly better temporal gain and J index and thus are superior in early detection of upward and downward trends in glucose. The EKF based state-space model developed in this article is particularly suitable for model-based state-feedback control designs since the Kalman filter estimates the state variable of the glucose dynamics based on the measured glucose time series. In addition, since the model parameters are estimated in real time, this model is also suitable for adaptive control. © 2014 Diabetes Technology Society.

Glucose-lowering effect and glycaemic variability of insulin glargine, insulin detemir and insulin lispro protamine in people with type 1 diabetes.

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Derosa, G; Franzetti, I; Querci, F; Romano, D; D'Angelo, A; Maffioli, P

2015-06-01

To compare, using a continuous glucose monitoring (CGM) system, the effect on glycaemic variability of insulin glargine, detemir and lispro protamine. A total of 49 white people with type 1 diabetes, not well controlled by three times daily insulin lispro, taken for at least 2 months before study and on a stable dose, were enrolled. The study participants were randomized to add insulin glargine, detemir or lispro protamine, once daily, in the evening. We used a CGM system, the iPro Digital Recorder (Medtronic MiniMed, Northridge, CA, USA) for 1 week. Glycaemic control was assessed according to mean blood glucose values, the area under the glucose curve above 3.9 mmol/l (AUC(>3.9)) or above 10.0 mmol/l (AUC(>10.0)), and the percentage of time spent with glucose values >3.9 or >10.0 mmol/l. Intraday glycaemic variability was assessed using standard deviation (s.d.) values, the mean amplitude of glycaemic excursions and continuous overlapping of net glycaemic action. Day-to-day glycaemic variability was assessed using the mean of daily differences. The s.d. was found to be significantly lower with insulin lispro protamine and glargine compared with insulin detemir. AUC(>3.9) was higher and AUC(>10.0) was lower with insulin lispro protamine and glargine compared with detemir. The mean amplitude of glycaemic excursions and continuous overlapping net glycaemic action values were lower with insulin lispro protamine and glargine compared with detemir. In addition, the mean of daily differences was significantly lower with insulin lispro protamine and glargine compared with detemir. Fewer hypoglycaemic events were recorded during the night-time with insulin lispro protamine compared with glargine and detemir. The results suggest that insulin lispro protamine and glargine are more effective than detemir in reducing glycaemic variability and improving glycaemic control in people with type 1 diabetes. Insulin lispro protamine seems to lead to fewer hypoglycaemic

A method to dynamically balance intensity modulated radiotherapy dose between organs-at-risk

International Nuclear Information System (INIS)

Das, Shiva K.

2009-01-01

The IMRT treatment planning process typically follows a path that is based on the manner in which the planner interactively adjusts the target and organ-at-risk (OAR) constraints and priorities. The time-intensive nature of this process restricts the planner from fully understanding the dose trade-off between structures, making it unlikely that the resulting plan fully exploits the extent to which dose can be redistributed between anatomical structures. Multiobjective Pareto optimization has been used in the past to enable the planner to more thoroughly explore alternatives in dose trade-off by combining pre-generated Pareto optimal solutions in real time, thereby potentially tailoring a plan more exactly to requirements. However, generating the Pareto optimal solutions can be nonintuitive and computationally time intensive. The author presents an intuitive and fast non-Pareto approach for generating optimization sequences (prior to planning), which can then be rapidly combined by the planner in real time to yield a satisfactory plan. Each optimization sequence incrementally reduces dose to one OAR at a time, starting from the optimization solution where dose to all OARs are reduced with equal priority, until user-specified target coverage limits are violated. The sequences are computationally efficient to generate, since the optimization at each position along a sequence is initiated from the end result of the previous position in the sequence. The pre-generated optimization sequences require no user interaction. In real time, a planner can more or less instantaneously visualize a treatment plan by combining the dose distributions corresponding to user-selected positions along each of the optimization sequences (target coverage is intrinsically maintained in the combination). Interactively varying the selected positions along each of the sequences enables the planner to rapidly understand the nature of dose trade-off between structures and, thereby, arrive at a

Characterization of the chicken muscle insulin receptor

International Nuclear Information System (INIS)

Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

1987-01-01

Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

Effects of different doses of atorvastatin on NF-κB, inflammatory factors and insulin resistance in elderly patients with early diabetic nephropathy

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Ying Liu

2016-01-01

Full Text Available Objective: To explore the effects of different doses of atorvastatin on NF-κB, inflammatory factors and insulin resistance in elderly patients with early diabetic nephropathy. Methods: A total of 150 cases with elderly early diabetic nephropathy were randomly divided into two groups according to the random number table method. Group A (n=75 was treated with atorvastatin tablets at a dose of 10 mg/d, while group B (n=75 was treated at a dose of 20 mg/d. The NF-κB, inflammatory factors and insulin resistance were detected and compared between the two groups. Results: After treatment, UAER (52.87±7.78 μg/min, SCr (70.43±6.76 μmol/L and BUN (4.04±0.40 mmol/L of group B were significantly decreased compared with before treatment and post-treated group A (P<0.05; phosphorylation level of NF-κB p65 after treatment was (0.80±0.17 μg/min in the peripheral blood of patients from group B, which was significantly reduced compared with before treatment and post-treated group A (P<0.05; inflammatory factors including TNF-α (52.80±7.78 ng/L, IL-6 (70.43±6.76 ng/L and Hs-CRP (4.04±0.40 mg/L of group B after treatment also declined significantly compared with before treatment and post-treated group A (P<0.05; while HbAlc and FBG were not significantly changed after treatment in both groups, and there was no significant difference in each group before and after treatment; FINS (9.88±0.85 mU/L and HOMA-IR (3.36±0.33 of group B after treatment were significantly lowered compared with before treatment and posttreated group A (P<0.05. Conclusions: High dose atorvastatin can inhibit the activity of NF- κB p65 and levels of inflammation, and improve renal function and insulin resistance in elderly patients with early diabetic nephropathy, making it a promising means for clinical application.

Assessment of quality of glycemic control in intensive care patients treated with an insulin infusion at a teaching hospital.

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Gauthier, Lyne; Ferguson, Jessica; Dubé, Anne-Isabelle; Nguyen, Patrick Viet-Quoc; Beauchesne, Marie-France; Boutin, Jean-Marie

2014-04-01

To describe the quality of glycemic control in patients in intensive care units (ICUs) treated with an intravenous (IV) insulin infusion at a teaching hospital. This retrospective study included patients admitted to the ICU and treated with an IV insulin infusion for at least 12 h between August 1 and November 30, 2011. Medical charts were reviewed. The primary quality indicator for glycemic control was the mean percent of blood glucose values per patient in the 6.1 to 8 mmol/L target range. A total of 351 patients were included; 61.5% of subjects had no known diabetes. Admissions were mainly for surgery (61.3%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16.8±7.3. The mean percent of blood glucose values per patient in the 6.1 to 8 mmol/L range was 35% for all subjects and 26.2% for patients with diabetes. If a target of 6.1 to 10 mmol/L was considered, those values became 63% and 54.6%. At least 1 episode of hyperglycemia (>10 mmol/L), hypoglycemia (quality of glycemic control in patients in the ICU at our hospital needs to be improved. A new computerized IV insulin protocol is currently being tested. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Repeated prolonged whole-body low-intensity exercise: effects on insulin sensitivity and limb muscle adaptations

DEFF Research Database (Denmark)

Helge, Jørn Mikael; Overgaard, Kristian; Damsgaard, Rasmus

2006-01-01

arbitrary units) than in the arm (54 ± 9 arbitrary units) and was not changed in the leg, but was increased (P increased glucose transporter expression in arm muscle may compensate for the loss of lean body mass...... or body mass, were not affected by the crossing. Citrate synthase activity was higher (P muscle (16 ± 2 µmol · g-1 · min-1) and was unchanged after the crossing. Muscle GLUT4 protein concentration was higher (P ...This study investigates the effect of prolonged whole-body low-intensity exercise on insulin sensitivity and the limb muscle adaptive response. Seven male subjects (weight, 90.2 ± 3.2 kg; age, 35 ± 3 years) completed a 32-day unsupported crossing of the Greenland icecap on cross-country skies...

Ease of use and patient preference injection simulation study comparing two prefilled insulin pens.

Science.gov (United States)

Clark, Paula E; Valentine, Virginia; Bodie, Jennifer N; Sarwat, Samiha

2010-07-01

To determine patient ease of use and preference for the Humalog KwikPen* (prefilled insulin lispro [Humalog dagger] pen, Eli Lilly and Company, Indianapolis, IN, USA) (insulin lispro pen) versus the Next Generation FlexPen double dagger (prefilled insulin aspart [NovoRapid section sign ] pen, Novo Nordisk A/S, Bagsvaerd, Denmark) (insulin aspart pen). This was a randomized, open-label, 2-period, 8-sequence crossover study in insulin pen-naïve patients with diabetes. Randomized patients (N = 367) received device training, then simulated low- (15 U) and high- (60 U) dose insulin injections with an appliance. Patients rated pens using an ease of use questionnaire and were asked separately for final pen preferences. The Insulin Device 'Ease of Use' Battery is a 10-item questionnaire with a 7-point scale (higher scores reflect greater ease of use). The primary objective was to determine pen preference for 'easy to press to inject my dose' (by comparing composite scores [low- plus high-dose]). Secondary objectives were to determine pen preference on select questionnaire items (from composite scores), final pen preference, and summary responses for all questionnaire items. On the primary endpoint, 'easy to press to inject my dose,' a statistically significant majority of patients with a preference chose the insulin lispro pen over the insulin aspart pen (68.4%, 95% CI = 62.7-73.6%). Statistically significant majorities of patients with a preference also favored the insulin lispro pen on secondary items: 'easy to hold in my hand when I inject' (64.9%, 95% CI = 58.8-70.7%), 'easy to use when I am in a public place' (67.5%, 95% CI = 61.0-73.6%), and 'overall easy to use' (69.9%, 95% CI = 63.9-75.4%). A statistically significant majority of patients had a final preference for the insulin lispro pen (67.3%, 95% CI = 62.2-72.1%). Among pen-naïve patients with diabetes who had a preference, the majority preferred the insulin lispro pen over the insulin aspart pen with regard

Implementation of subcutaneous insulin protocol for non-critically ill hospitalized patients in andalusian tertiary care hospitals.

Science.gov (United States)

Martínez-Brocca, María Asunción; Morales, Cristóbal; Rodríguez-Ortega, Pilar; González-Aguilera, Beatriz; Montes, Cristina; Colomo, Natalia; Piédrola, Gonzalo; Méndez-Muros, Mariola; Serrano, Isabel; Ruiz de Adana, Maria Soledad; Moreno, Alberto; Fernández, Ignacio; Aguilar, Manuel; Acosta, Domingo; Palomares, Rafael

2015-02-01

In 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). To analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. A descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n=306) hospitalized for ≥48 hours in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. 288 patients were included for analysis (62.5% males; 70.3±10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5-61.2%) of patients, 63.1% SM vs. 37.8% SQ (P<.05). Alternatives to insulin regimen based on basal-bolus-correction included sliding scale insulin (43.7%), diet (31.3%), oral antidiabetic drugs (17.2%), premixed insulin (1.6%), and others (6.2%). For patients previously on oral antidiabetic drugs, in-hospital insulin dose was 0.32±0.1 IU/kg/day. In patients previously on insulin, in-hospital insulin dose was increased by 17% [-13-53], and in those on insulin plus oral antidiabetic drugs, in-hospital insulin dose was increased by 26.4% [-6-100]. Supplemental insulin doses used for<40 IU/day and 40-80 IU/day were 72.2% and 56.7% respectively. HbA1c was measured in 23.6% of patients (95CI%: 18.8-28.8); 27.7% SM vs. 13.3% SQ (P<.05). Strategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

The effect of dietary fiber and other factors on insulin response: role in obesity.

Science.gov (United States)

Ullrich, I H; Albrink, M J

1985-07-01

Epidemiologic evidence favors the hypothesis that obesity may result from the fiber-depleted diet of industrialized societies. Since hyperinsulinemia is a universal characteristic and perhaps causal of obesity, the possibility is considered that dietary factors causing excess insulin secretion might lead to obesity. Dietary glucose causes a slightly greater insulin rise than cooked starch containing an equal amount of carbohydrate, and high fiber starchy foods cause a much lesser insulin response than does glucose in solution. Doubling the dose of carbohydrate in a meal causes only a small increase in glucose response but a large increase in insulin response. Dietary fiber could act by displacing some of the carbohydrate that would normally be absorbable in the small intestine, or could translocate the carbohydrate to a point lower in the intestinal tract where less effect on insulin secretion would be observed. Evidence is presented that a higher fiber diet is associated with a higher concentration of fasting circulating free fatty acids, a lesser post-cibal decrease in circulating free fatty acids and triglycerides and less chronic increase in fasting triglycerides than a low fiber diet. These differences are associated with a lesser insulin response to high fiber meals. The extreme fluctuations between the fed and fasted states seen with low fiber diets are thus dampened by high fiber diets. The less complete inhibition of lipolysis during the fed state, and more intense lipolysis during fasting, suggested by the above data, might tend to prevent obesity. The mechanisms of the lesser insulin response to high rather than low fiber meals are not known, but the possibility that dietary fiber decreases the GIP response is considered.

Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome.

Science.gov (United States)

Meyer, Caroline; McGrath, Barry P; Teede, Helena Jane

2007-03-01

We aimed to determine the impact of medical therapy for symptom management on insulin resistance, metabolic profiles, and surrogate markers of cardiovascular disease in polycystic ovary syndrome (PCOS), an insulin-resistant pre-diabetes condition. One hundred overweight women (BMI >27 kg/m2), average age 31 years, who were nonsmokers, were not pregnant, did not have diabetes, and were off relevant medications for 3 months completed this 6-month open-label controlled trial. Randomization was to a control group (higher-dose oral contraceptive [OCP] 35 microg ethinyl estradiol [EE]/2 mg cyproterone acetate, metformin [1 g b.d.] or low-dose OCP [20 microg EE/100 microg levonorgestrel + aldactone 50 mg b.d.]). Primary outcome measures were insulin resistance (area under curve on oral glucose tolerance test) and surrogate markers of cardiovascular disease including arterial stiffness (pulse wave velocity [PWV]) and endothelial function. All treatments similarly and significantly improved symptoms including hirsutism and menstrual cycle length. Insulin resistance was improved by metformin and worsened by the high-dose OCP. Arterial stiffness worsened in the higher-dose OCP group (PWV 7.46 vs. 8.03 m/s, P insulin resistance. In overweight women with PCOS, metformin and low- and high-dose OCP preparations have similar efficacy but differential effects on insulin resistance and arterial function. These findings suggest that a low-dose OCP preparation may be preferable if contraception is needed and that metformin should be considered for symptomatic management, particularly in women with additional metabolic and cardiovascular risk factors.

Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

Science.gov (United States)

2015-01-01

Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

The changes in levels of C-P and insulin in glucose tolerance test in rats with experimental non-insulin dependent diabetes mellitus

International Nuclear Information System (INIS)

Liu Xinqiu; Lei Ming

2001-01-01

The changes in levels of C-P and insulin were investigated in the GT test in rats with non-insulin dependent diabetes mellitus. In order to establish a model of non-insulin dependent diabetes mellitus (NIDDM), the authors injected rats with small dose streptozocoi (i.v.). Two weeks after the injection, the rats developed impaired glucose tolerance (IGT). Then, they were fed with high energy diet for eight weeks to form NIDDM. The results showed that the highest peak time of C-P and insulin in NIDDM was remarkably later than that in normal subjects, the highest peak time was in two hours (P < 0.05). The data suggest that level of C-P could accurately respond to level of insulin, and this experimental non-insulin dependent diabetes mellitus model is ideal

Prediction of the association state of insulin using spectral parameters.

Science.gov (United States)

Uversky, Vladimir N; Garriques, Liza Nielsen; Millett, Ian S; Frokjaer, Sven; Brange, Jens; Doniach, Sebastian; Fink, Anthony L

2003-04-01

Human insulin exists in different association states, from monomer to hexamer, depending on the conditions. In the presence of zinc the "normal" state is a hexamer. The structural properties of 20 variants of human insulin were studied by near-UV circular dichroism, fluorescence spectroscopy, and small-angle X-ray scattering (SAXS). The mutants showed different degrees of association (monomer, dimers, tetramers, and hexamers) at neutral pH. A correlation was shown between the accessibility of tyrosines to acrylamide quenching and the degree of association of the insulin mutants. The near-UV CD spectra of the insulins were affected by protein association and by mutation-induced structural perturbations. However, the shape and intensity of difference CD spectra, obtained by subtraction of the spectra measured in 20% acetic acid (where all insulin species were monomeric) from the corresponding spectra measured at neutral pH, correlate well with the degree of insulin association. In fact, the near-UV CD difference spectra for monomeric, dimeric, tetrameric, and hexameric insulin are very distinctive, both in terms of intensity and shape. The results show that the spectral properties of the insulins reflect their state of association, and can be used to predict their oligomeric state. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:847-858, 2003

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

Science.gov (United States)

Liang, Hanyu; Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J; Musi, Nicolas

2018-01-01

The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

Pitfalls of insulin pump clocks: technical glitches that may potentially affect medical care in patients with diabetes.

Science.gov (United States)

Aldasouqi, Saleh A; Reed, Amy J

2014-11-01

The objective was to raise awareness about the importance of ensuring that insulin pumps internal clocks are set up correctly at all times. This is a very important safety issue because all commercially available insulin pumps are not GPS-enabled (though this is controversial), nor equipped with automatically adjusting internal clocks. Special attention is paid to how basal and bolus dose errors can be introduced by daylight savings time changes, travel across time zones, and am-pm clock errors. Correct setting of insulin pump internal clock is crucial for appropriate insulin delivery. A comprehensive literature review is provided, as are illustrative cases. Incorrect setting can potentially result in incorrect insulin delivery, with potential harmful consequences, if too much or too little insulin is delivered. Daylight saving time changes may not significantly affect basal insulin delivery, given the triviality of the time difference. However, bolus insulin doses can be dramatically affected. Such problems may occur when pump wearers have large variations in their insulin to carb ratio, especially if they forget to change their pump clock in the spring. More worrisome than daylight saving time change is the am-pm clock setting. If this setting is set up incorrectly, both basal rates and bolus doses will be affected. Appropriate insulin delivery through insulin pumps requires correct correlation between dose settings and internal clock time settings. Because insulin pumps are not GPS-enabled or automatically time-adjusting, extra caution should be practiced by patients to ensure correct time settings at all times. Clinicians and diabetes educators should verify the date/time of insulin pumps during patients' visits, and should remind their patients to always verify these settings. © 2014 Diabetes Technology Society.

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

Science.gov (United States)

Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

2017-02-01

To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Hepatic 123I-insulin binding kinetics in non-insulin-dependent (Type 2) diabetic patients after i.v. bolus administration

International Nuclear Information System (INIS)

Oolbekkink, M.; Veen, E.A. van der; Heine, R.J.; Hollander, W. den; Nauta, J.J.P.

1989-01-01

Insulin binding kinetics in the liver were studied in non insulin dependent (Type 2) diabetic patients, by i.v. bolus administration of 123 I-insulin. Eight Type 2 diabetic patients were compared with six male volunteers. Uptake of 123 I-insulin by liver and kidneys was measured by dynamic scintigraphy with a gamma camera during 30 min. Images of liver and kidneys appeared within 2-3 min after administration of 123 I-insulin at a dose of 1 mCi (37 MBq). Peak radioactivity for the liver was found 7.5±0.2 and 6.9±0.3 min after injection for the healthy and the diabetic subjects, respectively (N.S.). The percentage 123 I-insulin hepatic uptake was not significantly different for the diabetic and the healthy subjects. Although a large variation exists for maximal uptake of radioactivity within both groups, the data suggest that binding differences in the liver in Type 2 diabetic patients, as compared to healthy subjects, may not account for hepatic insulin resistance. (orig.)

Polymer gel measurement of dose homogeneity in the breast: comparing MLC intensity modulation with standard wedged delivery

International Nuclear Information System (INIS)

Love, P A; Evans, P M; Leach, M O; Webb, S

2003-01-01

Polymer gel dosimetry has been used to measure the radiotherapy dose homogeneity in a breast phantom for two different treatment methods. The first 'standard' method uses two tangential wedged fields while the second method has three static fields shaped by multileaf collimators (MLCs) in addition to the standard wedged fields to create intensity modulated fields. Gel dose distributions from the multileaf modulation treatment show an improved dose uniformity in comparison to the standard treatment with a decreased volume receiving doses over 105%

Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin

Science.gov (United States)

Begg, Denovan P.; May, Aaron A.; Mul, Joram D.; Liu, Min; D’Alessio, David A.; Seeley, Randy J.

2015-01-01

Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake. PMID:25667307

Decrease of glucose-induced insulin secretion of rat pancreatic islets after irradiation in vitro

Energy Technology Data Exchange (ETDEWEB)

Heinzmann, D; Nadrowitz, R; Besch, W; Schmidt, W; Hahn, H J [Zentralinstitut fuer Diabetes, Karlsburg (German Democratic Republic); Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

1983-01-01

In vitro irradiation of rat pancreatic islets up to a dose of 2.5 Gy did neither alter glucose- nor isobutylmethyl xanthine (IBMX)-induced insulin secretion. Insulin as well as glucagon content of irradiated islets corresponded to that of the control tissue. So it was in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. There was no indication of an enhanced hormone output in the radiation medium and it is to be suggested that higher radiation doses affect the insulin release of pancreatic islets in vitro. This must be taken into consideration for radioimmunosuppression experiments.

Intensity-Modulated Radiotherapy for Craniospinal Irradiation: Target Volume Considerations, Dose Constraints, and Competing Risks

International Nuclear Information System (INIS)

Parker, William; Filion, Edith; Roberge, David; Freeman, Carolyn R.

2007-01-01

Purpose: To report the results of an analysis of dose received to tissues and organs outside the target volume, in the setting of spinal axis irradiation for the treatment of medulloblastoma, using three treatment techniques. Methods and Materials: Treatment plans (total dose, 23.4 Gy) for a standard two-dimensional (2D) technique, a three-dimensional (3D) technique using a 3D imaging-based target volume, and an intensity-modulated radiotherapy (IMRT) technique, were compared for 3 patients in terms of dose-volume statistics for target coverage, as well as organ at risk (OAR) and overall tissue sparing. Results: Planning target volume coverage and dose homogeneity was superior for the IMRT plans for V 95% (IMRT, 100%; 3D, 96%; 2D, 98%) and V 107% (IMRT, 3%; 3D, 38%; 2D, 37%). In terms of OAR sparing, the IMRT plan was better for all organs and whole-body contour when comparing V 10Gy , V 15Gy , and V 20Gy . The 3D plan was superior for V 5Gy and below. For the heart and liver in particular, the IMRT plans provided considerable sparing in terms of V 10Gy and above. In terms of the integral dose, the IMRT plans were superior for liver (IMRT, 21.9 J; 3D, 28.6 J; 2D, 38.6 J) and heart (IMRT, 9 J; 3D, 14.1J; 2D, 19.4 J), the 3D plan for the body contour (IMRT, 349 J; 3D, 337 J; 2D, 555 J). Conclusions: Intensity-modulated radiotherapy is a valid treatment option for spinal axis irradiation. We have shown that IMRT results in sparing of organs at risk without a significant increase in integral dose

High cumulative insulin exposure : a risk factor of atherosclerosis in type 1 diabetes?

NARCIS (Netherlands)

Muis, MJ; Bots, ML; Bilo, HJG; Hoogma, RPLM; Hoekstra, JBL; Grobbee, DE; Stolk, RP

Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a

High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

NARCIS (Netherlands)

Muis, Marian J.; Bots, Michiel L.; Bilo, Henk J. G.; Hoogma, Roel P. L. M.; Hoekstra, Joost B. L.; Grobbee, Diederick E.; Stolk, Ronald P.

2005-01-01

Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a

Insulin in the arcuate nucleus of the hypothalamus reduces fat consumption in rats

NARCIS (Netherlands)

van Dijk, G; de Groote, C; Chavez, M; van der Werf, Y; Steffens, AB; Strubbe, JH

1997-01-01

Data are accumulating that insulin acting in the central nervous system is a physiological regulator of food intake and body weight, presumably via its effect in the hypothalamus. The present study investigated whether infusion of a small dose of insulin into two major hypothalamic insulin-binding

Antibody-Mediated Extreme Insulin Resistance: A Report of Three Cases.

Science.gov (United States)

Kim, Han Na; Fesseha, Betiel; Anzaldi, Laura; Tsao, Allison; Galiatsatos, Panagis; Sidhaye, Aniket

2018-01-01

Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance, such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated. Encouragingly, immunomodulatory regimens have recently been published that induce remission at high rates. We describe 3 cases of extreme insulin resistance mediated by anti-insulin receptor autoantibodies or insulin autoantibodies. All cases were effectively treated with an immunomodulatory regimen. Although cases of extreme insulin resistance are rare, it is important to be aware of autoimmune causes, recognize suggestive signs and symptoms, and pursue appropriate diagnostic evaluation. Prompt treatment with immunomodulators is key to restoring euglycemia in patients with autoimmune etiologies of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Dose determination in radiotherapy for photon beams modified by static intensity modulators

International Nuclear Information System (INIS)

Castellanos Lopez, M.E.

1998-01-01

The static intensity modulators, used in radiotherapy, modify the spectral composition of the beam and lead to specific problems of the dose calculation. The aim of this work was to establish a three dimensional calculation, global and accurate, adapted to the primary-diffused separation algorithm and valid for any static modulator type. A theoretical study, experimentally verified, allowed the evaluation of the primary fluence, resulting from metallic sheets placed between photons beams of 6 to 23 MV nominal energy. It has been showed that the diffused, coming from the modulators, could be neglected for weak thickness and for the relative dose variation. In return it leads to significant variations of many % on the absolute dose and must be take into account for the bigger thicknesses. Corrective methods for the primary fluence have been proposed. From the energy spectra of the beam, the metallic modulator influence has been studied on the primary and diffused components of the dose and improvements of the calculation method have been proposed. These improvements are based on the modulator representation as a transmission matrix and on semi-empirical corrective factors. (A.L.B.)

Dosimetric performance of an enhanced dose range radiographic film for intensity-modulated radiation therapy quality assurance

International Nuclear Information System (INIS)

Olch, Arthur J.

2002-01-01

Film-based quality assurance (QA) is an important element of any intensity modulated radiation therapy (IMRT) program. XV2 film is often used for IMRT QA, however, it has saturation and energy response limitations which hinder accurate film dosimetry. A new commercially released ready-pack film has been introduced that has an extended dose range (EDR2), reportedly allowing measured doses above 600 cGy without saturation. Also, this film may have less energy dependence due to its composition. The purpose of this paper is to study and compare the two types of film with respect to absolute dose accuracy for IMRT plans, percent depth dose accuracy for square fields between 2 and 20 cm, ability to measure composite plan isodoses and single beam fluence maps for IMRT cases, and sensitivity to processor variations over time. In 19 IMRT patient QA tests, the EDR2 film was able to achieve an absolute dose accuracy of better than 2% vs over 4% for XV2 film. The EDR2 film was able to reproduce ionization chamber and diode-measured percent depth doses to 20 cm depth generally to within 1% over the range of field sizes tested compared to about 10% for the XV2 film. When compared to calculations, EDR2 film agreed better than XV2 film for both composite plan isodoses and single beam fluence intensity maps. The EDR2 film was somewhat more resistant to processor changes over time than the XV2 film, with a standard deviation of dose reproducibility of less than 2% compared to 6%, respectively

Evaluation of current trends and recent development in insulin therapy for management of diabetes mellitus.

Science.gov (United States)

Nawaz, Muhammad Sarfraz; Shah, Kifayat Ullah; Khan, Tahir Mehmood; Rehman, Asim Ur; Rashid, Haroon Ur; Mahmood, Sajid; Khan, Shahzeb; Farrukh, Muhammad Junaid

2017-12-01

Diabetes mellitus is a major health problem in developing countries. There are various insulin therapies to manage diabetes mellitus. This systematic review evaluates various insulin therapies for management of diabetes mellitus worldwide. This review also focuses on recent developments being explored for better management of diabetes mellitus. We reviewed a number of published articles from 2002 to 2016 to find out the appropriate management of diabetes mellitus. The paramount parameters of the selected studies include the insulin type & its dose, type of diabetes, duration and comparison of different insulin protocols. In addition, various newly developed approaches for insulin delivery with potential output have also been evaluated. A great variability was observed in managing diabetes mellitus through insulin therapy and the important controlling factors found for this therapy include; dose titration, duration of insulin use, type of insulin used and combination therapy of different insulin. A range of research articles on current trends and recent advances in insulin has been summarized, which led us to the conclusion that multiple daily insulin injections or continuous subcutaneous insulin infusion (insulin pump) is the best method to manage diabetes mellitus. In future perspectives, development of the oral and inhalant insulin would be a tremendous breakthrough in Insulin therapy. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

A method to determine insulin responsiveness in synaptosomes isolated from frozen brain tissue.

Science.gov (United States)

Franklin, Whitney; Taglialatela, Giulio

2016-03-01

Studying the insulin signaling response at the synapse is an important approach to understand molecular mechanisms involved in disease-related neurodegenerative processes. We developed a method for studying the insulin responsiveness at the synaptic level by isolating functional synaptosomes from fresh or frozen tissue and exposing them to insulin in the presence of ATP (a critical step) to detect insulin receptor (IR) activation. We performed an ATP dose-response curve, insulin dose-response curve, and insulin response time course to optimize this method. We also demonstrated that our protocol reflects the degree of insulin responsiveness in vivo by using an animal model of known insulin resistance, AtENPP1-Tg mice. This method is advantageous over other methods detecting IR in total brain homogenates due to the ability to detect IR response without confounding contributions from other cell areas and cell types also expressing IR. Furthermore, ex vivo insulin stimulation can be compared to baseline synaptosomes obtained from the same animal which improves reliability and statistical power while decreasing the number of animals required to perform individual experiments. We have developed a reliable, efficient method to measure insulin-driven ex vivo phosphorylation of the synaptosomal insulin receptor that can reliably reflect the pre-existing insulin responsiveness status in the CNS of the animal. To the best of our knowledge, this is the first evidence of stimulation of isolated synaptosomes with insulin and a promising new technique to study the synaptic CNS insulin responsiveness under physiological or disease conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

[The use of continuous subcutaneous insulin infusion (CSII) with personal insulin pumps in the treatment of children and adolescents with diabetes type 1].

Science.gov (United States)

Jarosz-Chobot, Przemysława

2004-01-01

This paper sums up recently published researches on the continuous subcutaneous insulin infusion (CSII) with the use of insulin pump in children and adolescents with diabetes type 1. Obtaining a balance in the organism metabolism in childhood and adolescence diabetology is nowadays one of the most important rules of the diabetes management in children. One of the modern ways to achieve that goal is the intensive insulin therapy model with use of the insulin pump. In this paper the advantages and disadvantages as well as the indications and contraindications for the CSII in children and adolescents with diabetes are widely discussed.

Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children.

Science.gov (United States)

Ferira, Ashley J; Laing, Emma M; Hausman, Dorothy B; Hall, Daniel B; McCabe, George P; Martin, Berdine R; Hill Gallant, Kathleen M; Warden, Stuart J; Weaver, Connie M; Peacock, Munro; Lewis, Richard D

2016-04-01

Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9–13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.

Decrease of glucose-induced insulin secretion of pancreatic rat islets after irradiation in vitro

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Heinzmann, D; Nadrowitz, R; Besch, W; Schmidt, W; Hahn, H J

1983-01-01

Irradiation of pancreatic rat islets up to a dose of 2.5 Gy did neither alter glucose-nor IBMX-induced insulin secretion studied in vitro. The insulin as well as glucagon content of irradiated islets were similar as in the control tissue. This was also true in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. Since we did not find indications of an enhanced hormone output in the radiation medium, we want to suggest that higher irradiation doses affect insulin release of pancreatic islets in vitro. This observation has to be taken into account for application of radioimmunosuppression for transplantation.

Intensity-modulated radiation therapy for nasopharyngeal carcinoma parotid sparing with euivalent uiform dose optimization

International Nuclear Information System (INIS)

Yue Weiyou; Dai Jianrong; Gao Li

2006-01-01

Objective: The aim of this study was to evaluate the role of an euivalent uiform dose (EUD) based optimization algorithm in sparing the parotids of patients with nasopharyngeal carcinoma (NPC) when they are treated with intensity-modulated radiation therapy (IMRT). Methods: 12 patients were randomly selected from the NPC patients who received IMRT treatments. For these patients, the treatment plans were designed with physical optimization constraints (dose/dose-volume constraints). Based on these plans, new plans were designed through replacing the physical constraints with maximum EUD for parotids, while keeping the physical objectives for targets and other organs at risk(OARs) unchanged. Comparison was then made between the new plan, which had EUD constraints to parotids, and the former for each individual patient. Results: While maintaining the dose to the targets and the other OARs un- changed, optimization with EUD constraints to parotids decreased the mean dose and V 30 of parotids significantly, simultaneously, the dose of target volume and other organs at risk keep stable, the values of probability were less than 0.05 by T-test. Conclusions: The doses to parotids can be reduced through optimization with EUD constraints. This finding is quite helpful to reduce the occurrence rate of parotid complications, and to provide spaces for escalating target dose. (authors)

Insulin signaling pathways in lepidopteran steroidogenesis

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Wendy eSmith

2014-02-01

Full Text Available Molting and metamorphosis are stimulated by the secretion of ecdysteroid hormones from the prothoracic glands. Insulin-like hormones have been found to enhance prothoracic gland activity, providing a mechanism to link molting to nutritional state. In silk moths (Bombyx mori, the prothoracic glands are directly stimulated by insulin and the insulin-like hormone bombyxin. Further, in Bombyx , the neuropeptide prothoracicotropic hormone (PTTH appears to act at least in part through the insulin-signaling pathway. In the prothoracic glands of Manduca sexta, while insulin stimulates the phosphorylation of the insulin receptor and Akt, neither insulin nor bombyxin II stimulate ecdysone secretion. Involvement of the insulin-signaling pathway in Manduca prothoracic glands was explored using two inhibitors of phosphatidylinositol-3-kinase (PI3K, LY294002 and wortmannin. PI3K inhibitors block the phosphorylation of Akt and 4EBP but have no effect on ecdysone secretion, or on the phosphorylation of the MAPkinase, ERK. Inhibitors that block phosphorylation of ERK, including the MEK inhibitor U0126, and high doses of the RSK inhibitor SL0101, effectively inhibit ecdysone secretion. The results highlight differences between the two lepidopteran insects most commonly used to directly study ecdysteroid secretion. In Bombyx, the PTTH and insulin-signaling pathways intersect; both insulin and PTTH enhance the phosphorylation of Akt and stimulate ecdysteroid secretion, and inhibition of PI3K reduces ecdysteroid secretion. By contrast, in Manduca, the action of PTTH is distinct from insulin. The results highlight species differences in the roles of translational regulators such as 4EBP, and members of the MAPkinase pathway such as ERK and RSK, in the effects of nutritionally-sensitive hormones such as insulin on ecdysone secretion and molting.

Effect of single physical exercise at 35% VO{sub 2} max. intensity on secretion activity of pancreas {beta}-cells and {sup 125}J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus; Einfluss der einmaligen Koerperanstrengung von 35% VO{sub 2} max. auf Sekretionsfaehigkeit von B-Zellen der Bauchspeicheldruese und auf Bindungs-und Degradationsfaehigkeit von {sup 125}J-Insulin durch Erythrozytenrezeptoren bei Kindern mit Diabetes mellitus

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Szczesniak, L; Rychlewski, T [Lehrstuhl fuer Physiologie, Biochemie und Hygiene, Akademie fuer Koerpererziehung, Poznan (Poland); Banaszak, F; Kasprzak, Z; Walczak, M [3. Klinik von Kinderkrankheiten, Medizinische Akademie, Poznan (Poland)

1994-12-31

In this report we showed research results of effect of single physical exercise on cycloergometer at 35% VO{sub 2} max. intensity on {sup 125}J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus, secreting and non-secreting endogenous insulin. Insulin secretion was evaluated by measurement of C-peptide by Biodet test (Serono) of sensitivity threshold at 0.3 {mu}g/ml. We indicated in children non-secreting endogenous insulin (n=32) there is statistically essential lower {sup 125}J-insulin binding with erythrocyte receptor in comparison to children group with C-peptide. Physical exercise on cycloergometer at 35% VO{sub 2} max. intensity caused different reaction in range of physiological indices, like acid-base parameters, level of glucose and {sup 125}J-insulin binding and degradation. In children devoid of endogenous insulin we indicated statistically nonessential changes in {sup 125}J-insulin degradation by non-impaired erythrocytes and by hemolizate, as well. {sup 125}J-insulin binding after physical exercise increased in both groups, though change amplitude was different. Obtained research results allowed us to conclude, in children with I-type diabetes, that in dependence of impairment degree of pancreas {beta}cells sensitivity of insulin receptor and/or number of receptors on erythrocyte surface is different.

Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Lau IT

2017-06-01

Full Text Available Ip Tim Lau,1 Ka Fai Lee,2 Wing Yee So,3 Kathryn Tan,4 Vincent Tok Fai Yeung5 1Department of Medicine, Tseung Kwan O Hospital, 2Department of Medicine and Geriatrics, Kwong Wah Hospital, 3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, 4Department of Medicine, Queen Mary Hospital, University of Hong Kong, 5Department of Medicine and Geriatrics, Our Lady of Maryknoll Hospital, Hong Kong, China Objective: To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300, a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DMMaterials and methods: Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies.Results: In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time–action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6–12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%–17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300.Conclusion: Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities. Keywords: diabetes mellitus, long-acting insulin, insulin glargine

An evaluation of prefilled insulin pens: a focus on the Next Generation FlexPen®

Directory of Open Access Journals (Sweden)

Estella M Davis

2010-08-01

Full Text Available Estella M Davis, Emily L Sexson, Mikayla L Spangler, Pamela A ForalDepartment of Pharmacy Practice, Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska, USAAbstract: Insulin pen delivery systems are preferred by patients over the traditional vial and syringe method for insulin delivery because they are simple and easy to use, improve confidence in dosing insulin, and have less interference with activities and improved discretion with use. Insulin manufacturers have made numerous improvements to their first marketed pen devices and are now introducing their next generation of devices. Design modifications to the newest generation of prefilled insulin pen devices are intended to improve the ease of use and safety and continue to positively impact adherence to insulin. This review focuses on the Next Generation FlexPen® with regard to design considerations to reduce injection force, improve accuracy and ease of use, and evaluate the preference of patient and health-care provider compared with other disposable, prefilled insulin pen devices.Keywords: diabetes, dose accuracy, injection force, patient preference, insulin pen device

Refractory hyperglycaemia induced by glucose-insulin-potassium infusion in acute myocardial infarction

NARCIS (Netherlands)

Svilaas, Tone; van der Horst, I.C.C.; Nijsten, M.W.N.; Zijlstra, F.

2006-01-01

Background. Recent randomised clinical trials have not confirmed the beneficial effects of glucose-insulin-potassium (GIK) infusion observed in experimental models of myocardial ischaemia and infarction. Methods. We investigated glucose levels and insulin dose in 107 patients treated with

Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

Directory of Open Access Journals (Sweden)

De Sukanya

2010-09-01

Full Text Available Abstract Background Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (RCT is to determine the efficacy and effectiveness of two different structured lifestyle interventions differing in diet composition on insulin sensitivity, in adolescents with clinical insulin resistance and/or prediabetes treated with metformin. Methods/design This study protocol describes the design of an ongoing RCT. We are recruiting 108 (54 each treatment arm 10 to 17 year olds with clinical features of insulin resistance and/or prediabetes, through physician referral, into a multi-centred RCT. All participants are prescribed metformin and participate in a diet and exercise program. The lifestyle program is the same for all participants except for diet composition. The diets are a high carbohydrate, low fat diet and a moderate carbohydrate, increased protein diet. The program commences with an intensive 3 month dietary intervention, implemented by trained dietitians, followed by a 3 month intensive gym and home based exercise program, supervised by certified physical trainers. To measure the longer term effectiveness, after the intensive intervention trial participants are managed by either their usual physician or study physician and followed up by the study dietitians for an additional 6 months. The primary outcome measure, change in insulin sensitivity, is measured at 3, 6 and 12 months. Discussion Clinical insulin resistance and prediabetes in the paediatric population are rapidly emerging clinical problems with serious health outcomes. With

Dose profile analysis of small fields in intensity modulated radiotherapy

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Medel B, E. [IMSS, Centro Medico Nacional Manuel Avila Camacho, Calle 2 Nte. 2004, Barrio de San Francisco, 72090 Puebla, Pue. (Mexico); Tejeda M, G.; Romero S, K., E-mail: romsakaren@gmail.com [Benemerita Universidad Autonoma de Puebla, Facultad de Ciencias Fisico Matematicas, Av. San Claudio y 18 Sur, Ciudad Universitaria, 72570 Puebla, Pue.(Mexico)

2015-10-15

Full text: Small field dosimetry is getting a very important worldwide task nowadays. The use of fields of few centimeters is more common with the introduction of sophisticated techniques of radiation therapy, as Intensity Modulated Radiotherapy (IMRT). In our country the implementation of such techniques is just getting started and whit it the need of baseline data acquisition. The dosimetry under small field conditions represents a challenge for the physicists community. In this work, a dose profile analysis was done, using various types of dosimeters for further comparisons. This analysis includes the study of quality parameters as flatness, symmetry, penumbra, and other in-axis measurements. (Author)

BPN, a marine-derived PTP1B inhibitor, activates insulin signaling and improves insulin resistance in C2C12 myotubes.

Science.gov (United States)

Xu, Qi; Luo, Jiao; Wu, Ning; Zhang, Renshuai; Shi, Dayong

2018-01-01

Insulin resistance is a key feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling cascade and has attracted intensive investigation in recent T2DM therapy study. BPN, a marine-derived bromophenol compound, was isolated from the red alga Rhodomela confervoides. This study investigated the effects of BPN on the insulin signaling pathway in insulin-resistant C2C12 myotubes by inhibiting PTP1B. Molecular docking study and analysis of small- molecule interaction with PTP1B all showed BPN inhibited PTP1B activity via binding to the catalytic site through hydrogen bonds. We then found that BPN permeated into C2C12 myotubes, on the one hand, activated insulin signaling in an insulin-independent manner in C2C12 cells; on the other hand, ameliorated palmitate-induced insulin resistance through augmenting insulin sensitivity. Moreover, our studies also showed that PTP1B inhibition by BPN increased glucose uptake in normal and insulin-resistant C2C12 myotubes through glucose transporter 4 (GLUT4) translocation. Taken together, BPN activates insulin signaling and alleviates insulin resistance and represents a potential candidate for further development as an antidiabetic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

High intensity interval training improves liver and adipose tissue insulin sensitivity

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Katarina Marcinko

2015-12-01

Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

Energy Technology Data Exchange (ETDEWEB)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

2013-02-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

International Nuclear Information System (INIS)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

2013-01-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [ 3 H]glucose and 2-deoxy[ 14 C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer

NARCIS (Netherlands)

deGraaf, H; Willemse, PHB; Bong, SB; Piersma, H; Tjabbes, T; vanVeelen, H; Coenen, JLLM; deVries, EGE

1996-01-01

The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF

Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin

Science.gov (United States)

Mady, Mohsen M.; Elshemey, Wael M.

2011-06-01

Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660 cm-1) and Amide II band (at about 1546 cm-1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule.

Does a patient-managed insulin intensification strategy with insulin glargine and insulin glulisine provide similar glycemic control as a physician-managed strategy? Results of the START (Self-Titration With Apidra to Reach Target) Study: a randomized noninferiority trial.

Science.gov (United States)

Harris, Stewart B; Yale, Jean-François; Berard, Lori; Stewart, John; Abbaszadeh, Babak; Webster-Bogaert, Susan; Gerstein, Hertzel C

2014-01-01

OBJECTIVE Diabetes self-management is universally regarded as a foundation of diabetes care. We determined whether comparable glycemic control could be achieved by self-titration versus physician titration of a once-daily bolus insulin dose in patients with type 2 diabetes who are unable to achieve optimal glycemia control with a basal insulin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes, an HbA1c level >7% (53 mmol/mol), and either nocturnal hypoglycemia episodes or an insufficient basal insulin glargine level (with or without oral agents) to achieve a fasting plasma glucose level ≤6 mmol/L (108 mg/dL) were studied. Participants all had bolus insulin glulisine added at breakfast and were allocated to either algorithm-guided patient self-titration or physician titration. The primary outcome was an HbA1c level ≤7% (53 mmol/mol) without severe hypoglycemia. RESULTS After a mean (SD) follow-up of 159.4 days (36.2 days), 28.4% of participants in the self-titration arm vs. 21.2% in the physician titration arm achieved an HbA1c level of ≤7% (53 mmol/mol) without severe hypoglycemia (between-group absolute difference 7.2%; 95% CI -3.2 to 17.7). The lower end of this 95% confidence interval was within the predetermined noninferiority boundary of -5% (P noninferiority = 0.011). CONCLUSIONS In stable patients with type 2 diabetes who are receiving doses of basal insulin glargine who require bolus insulin, a simple bolus insulin patient-managed titration algorithm is as effective as a physician-managed algorithm.

Radiation dose reduction in a neonatal intensive care unit in computed radiography

International Nuclear Information System (INIS)

Frayre, A.S.; Torres, P.; Gaona, E.; Rivera, T.; Franco, J.; Molina, N.

2012-01-01

The purpose of this study was to evaluate the dose received by chest x-rays in neonatal care with thermoluminescent dosimetry and to determine the level of exposure where the quantum noise level does not affect the diagnostic image quality in order to reduce the dose to neonates. In pediatric radiology, especially the prematurely born children are highly sensitive to the radiation because of the highly mitotic state of their cells; in general, the sensitivity of a tissue to radiation is directly proportional to its rate of proliferation. The sample consisted of 208 neonatal chest x-rays of 12 neonates admitted and treated in a Neonatal Intensive Care Unit (NICU). All the neonates were preterm in the range of 28–34 weeks, with a mean of 30.8 weeks. Entrance Surface Doses (ESD) values for chest x-rays are higher than the DRL of 50 μGy proposed by the National Radiological Protection Board (NRPB). In order to reduce the dose to neonates, the optimum image quality was achieved by determining the level of ESD where level noise does not affect the diagnostic image quality. The optimum ESD was estimated for additional 20 chest x-rays increasing kVp and reducing mAs until quantum noise affects image quality. - Highlights: ► Entrance surface doses (ESD) in neonates were measured. ► Doses measured in neonates examinations were higher than those reported by literature. ► Reference levels in neonatal studies are required. ► Radiation protection optimization was proposed.

Optimum bolus wizard settings in insulin pumps in children with Type 1 diabetes

DEFF Research Database (Denmark)

Andersen, A J B; Ostenfeld, A; Pipper, C B

2016-01-01

: Optimum insulin pump settings at pump initiation depend on both insulin requirements and use of the pump. Settings need to be individualized because the standardized calculation factors are not constant for children. There is a need to develop specific age- and insulin dose-dependent calculation factors.......AIM: To evaluate current insulin pump settings in an optimally regulated paediatric population using bolus wizard. METHODS: We used a retrospective study design to analyse data from 124 children on insulin pump therapy who had optimum HbA1c levels [

Pharmacokinetics of insulin following intravenous and subcutaneous administration in canines.

Science.gov (United States)

Ravis, W R; Comerci, C; Ganjam, V K

1986-01-01

Studies were conducted to examine the absorption and disposition kinetics of insulin in dogs following intravenous (IV) and subcutaneous (SC) administration of commercial preparations. After IV and SC dosing, the plasma levels were described by models which considered basal insulin level contributions. Intersubject variation in the disposition kinetics was small with half-lives of 0.52 +/- 0.05 h and total body clearances of 16.21 +/- 2.08 ml min-1 kg-1. Calculated insulin plasma secretion rates in the canines were 14.4 +/- 3.3 mUh-1 kg-1. Following SC injection of regular insulin, the rate and extent of absorption were noted to be quite variable. The absorption process appeared first-order with half-life values of 2.3 +/- 1.3 h and extents of absorption of 78 +/- 15 per cent with a range of 55-101 per cent. Insulin absorption from SC NPH preparations was evaluated as being composed of two zero-order release phases, a rapid and a slow release phase. With a dose of 1.65 U kg-1, the rapid release phase had an average duration of 1.5 h and a rate of 580 +/- 269 mUh-1 (4.2 per cent of dose) while the slow phase had a zero-order rate of 237 +/- 92 mU h-1 which continued beyond 12 h. The extent of absorption from the NPH preparation was 23.6 +/- 5.1 per cent and was significantly lower than that for the regular injection.

Insulin internalization in isolated rat hepatocytes

International Nuclear Information System (INIS)

Galan, J.; Trankina, M.; Noel, R.; Ward, W.

1990-01-01

This project was designed to determine whether neomycin, an aminoglycoside antibiotic, has a significant effect upon the pathways of ligand endocytosis in isolated rat hepatocytes. The pathways studied include receptor-mediated endocytosis and fluid-phase endocytosis. Neomycin causes a dose-dependent acceleration of 125 I-insulin internalization. Since fluid-phase endocytosis can also be a significant factor in 125 I-insulin internalization, lucifer yellow (LY), a marker for fluid-phase endocytosis, was incorporated into an assay similar to the 125 I-insulin internalization procedure. In the presence of 5 mM neomycin, a significant increase in LY uptake was evident at 0.2 and 0.4 mg/ml of LY. At 0.8 mg/ml, a decrease in LY uptake was observed. The increased rate of 125 I-insulin internalization in the presence of neomycin was intriguing. Since one action of neomycin is to inhibit phosphoinositidase C, it suggests that the phosphotidylinositol cycle may be involved in ligand internalization by hepatocytes. At low insulin concentrations, receptor-mediated uptake predominates. Fluid-phase uptake can become an important uptake route as insulin concentrations are increased. Since neomycin stimulates fluid-phase endocytosis, it must also be taken into account when measuring ligand internalization

Skin dose for head and neck cancer patients treated with intensity-modulated radiation therapy(IMRT)

Science.gov (United States)

Fu, Hsiao-Ju; Li, Chi-Wei; Tsai, Wei-Ta; Chang, Chih-Chia; Tsang, Yuk-Wah

2017-11-01

The reliability of thermoluminescent dosimeters (ultrathin TLD) and ISP Gafchromic EBT2 film to measure the surface dose in phantom and the skin dose in head-and-neck patients treated with intensity-modulated radiation therapy technique(IMRT) is the research focus. Seven-field treatment plans with prescribed dose of 180 cGy were performed on Eclipse treatment planning system which utilized pencil beam calculation algorithm(PBC). In calibration tests, the variance coefficient of the ultrathin TLDs were within 3%. The points on the calibration curve of the Gafchromic film was within 1% variation. Five measurements were taken on phantom using ultrathin TLD and EBT2 film respectively. The measured mean surface doses between ultrathin TLD or EBT2 film were within 5% deviation. Skin doses of 6 patients were measured for initial 5 fractions and the mean dose per-fraction was calculated. If the extrapolated doses for 30 fractions were below 4000 cGy, the skin reaction grading observed according to Radiation Therapy Oncology Group (RTOG) was either grade 1 or grade 2. If surface dose exceeded 5000 cGy in 32 fractions, then grade 3 skin reactions were observed.

Basal insulin analogues in the treatment of diabetes mellitus: What progress have we made?

OpenAIRE

Kalra, Sanjay

2015-01-01

Over the past few decades, continuous progress has been made in the development of insulin therapy. Basal insulins were developed around 60 years ago. However, existing basal insulins were found to have limitations. An ideal basal insulin should have the following properties viz. longer duration of action, a flat time-action profile, low day-to-day glycaemic variability, and the potential for flexible dosing. Basal insulins have advanced over the years, from lectin and neutral protamine Haged...

Differential regulation of insulin-like growth factor binding protein-1 and -2 by insulin in the baboon (Papio anubis endometrium

Directory of Open Access Journals (Sweden)

Fazleabas Asgerally T

2008-01-01

Full Text Available Abstract Background The purpose of this study was to examine the effect of insulin on expression and synthesis of IGFBP-1 and IGFBP-2 in the baboon endometrium in vitro. Methods Baboon endometrial explants collected from cycling, ovariectomized, steroid-treated, simulated-pregnant and pregnant animals were cultured for 48 h in the presence or absence of insulin, with or without estradiol, progesterone and hCG. Results Insulin clearly inhibited IGFBP-1 production and mRNA expression in a time- and dose-dependent manner, whereas IGFBP-2 synthesis was not significantly affected. The inhibitory effects of insulin on IGFBP-1 were more evident in explants of non-pregnant tissue or tissue away from the implantation site. In the absence of insulin, synthesis of IGFBP-1 was induced in explants with low levels of de novo synthesis whereas IGFBP-2 synthesis was inhibited. This effect was potentiated by steroids and hCG in the explant cultures. Conclusion Insulin differentially regulates endometrial IGFBP-1 and IGFBP-2 secretion in the baboon.

Automatic computation of radioimmunoassay data. Insulin and C-peptide

Energy Technology Data Exchange (ETDEWEB)

Toyota, T; Kudo, M; Abe, K [Hirosaki Univ., Aomori (Japan). School of Medicine; Kawamata, F; Uehata, S

1975-09-01

Radioimmunoassay provided dose response curves which showed linearity by the use of logistic transformation (Rodbard). This transformation which was applicable to radioimmunoassay should be useful for the computer processing of insulin and C-peptide assay. In the present studies, standard curves were analysed by testing the fit of analytic functions to radioimmunoassay of insulin and C-peptides. A program for use in combination with the double antibody technique was made by Dr. Kawamata. This approach was evidenced to be useful in order to allow automatic computation of data derived from the double antibody assays of insulin and C-peptides. Automatic corrected calculations of radioimmunoassay data of insulin was found to be satisfactory.

Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism

OpenAIRE

Shin, Andrew C.; Fasshauer, Martin; Filatova, Nika; Grundell, Linus A.; Zielinski, Elizabeth; Zhou, Jian-Ying; Scherer, Thomas; Lindtner, Claudia; White, Phillip J.; Lapworth, Amanda L.; Ilkayeva, Olga; Knippschild, Uwe; Wolf, Anna M.; Scheja, Ludger; Grove, Kevin L.

2014-01-01

Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α keto-acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors ...

[Phenylephrine dosing error in Intensive Care Unit. Case of the trimester].

Science.gov (United States)

2013-01-01

A real clinical case reported to SENSAR is presented. A patient admitted to the surgical intensive care unit following a lung resection, suffered arterial hypotension. The nurse was asked to give the patient 1 mL of phenylephrine. A few seconds afterwards, the patient experienced a hypertensive crisis, which resolved spontaneously without damage. Thereafter, the nurse was interviewed and a dosing error was identified: she had mistakenly given the patient 1 mg of phenylephrine (1 mL) instead of 100 mcg (1 mL of the standard dilution, 1mg in 10 mL). The incident analysis revealed latent factors (event triggers) due to the lack of protocols and standard operating procedures, communication errors among team members (physician-nurse), suboptimal training, and underdeveloped safety culture. In order to preempt similar incidents in the future, the following actions were implemented in the surgical intensive care unit: a protocol for bolus and short lived infusions (del Dolor. Published by Elsevier España. All rights reserved.

High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization

International Nuclear Information System (INIS)

Hurkmans, Coen W.; Meijer, Gert J.; Vliet-Vroegindeweij, Corine van; Sangen, Maurice J. van der; Cassee, Jorien

2006-01-01

Purpose: Recently a Phase III randomized trial has started comparing a boost of 16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young women. Our main aim was to develop an efficient simultaneously integrated boost (SIB) technique for the high-dose arm of the trial. Methods and Materials: Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A tangential field intensity-modulated radiotherapy technique added to a sequentially planned 3-field boost (SEQ) was compared with a simultaneously planned technique (SIB) using inverse optimization. Normalized total dose (NTD)-corrected dose volume histogram parameters were calculated and compared. Results: The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and 2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost receiving more than 95% of the prescribed dose was 97% or more for both techniques. Also, the mean lung dose and mean heart dose did not differ much between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a significantly more conformal irradiation of the PTV-boost. The volume of the PTV-breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost dose could be reduced considerably using the SIB as compared with the SEQ from 129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). Conclusions: A high-dose simultaneously integrated breast boost technique has been developed. The unwanted excessive dose to the breast was significantly reduced

Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

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Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

2002-01-01

Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Munck af Rosenschöld, Per; Oh, Jung Hun; Hunt, Margie [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kollmeier, Marisa [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Happersett, Laura; Yorke, Ellen; Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jackson, Andrew, E-mail: jacksona@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2014-02-01

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the

Relationship between TCF7L2 Relative Expression in Pancreas Tissue with Changes in Insulin by High Intensity Interval Training (HIIT in Type 2 Diabetes Rats

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Mojtaba Eizadi

2017-03-01

Full Text Available Introduction: Both environmental and genetic factors have been implicated in the development of type 2 diabetes (T2D. The objectives of the present study were: 1 to investigate the effect of high intensity interval training (HIIT on fasting glucose, insulin and TCF7L2 expression in pancreas tissue of T2D rats, 2 to determine the relation between TCF7L2 expression with insulin changes in the HIIT and control groups. Methods: In the present applied-experimental study, T2D male Wistar rats induced by intraperitoneal streptozotocin-nicotinamide were assigned to control (no-training and HIIT (5 times/week/12-week groups. Fasting glucose, serum insulin and TCF7L2 expression in pancreas tissues of both groups were measured after lasted exercise and compared between 2 groups by independent T test. Also, the relation between TCF7L2 expression and insulin of HIIT to the control group was assessed by Pearson correlations. Results: The HIIT training in the training group was associated with improved fasting glucose compared with the control group (P<0.001. A significant increase was observed in serum insulin levels (P< 0.001. Also, there was seen a significant decrease in TCF7L2 expression in pancreas tissues in HIIT group compared with the control group (P= 0.038. Significant negative correlation was found between TCF7L2 expression and insulin changes of the HIIT to control groups (r=0.84, P=0.034. conclusion: HIIT training is associated with improvements in glycemic control and insulin secretion in T2D rats. Based on these data, this improvement can be attributed to decrease in TCF7L2 expression at pancreas tissues by HIIT training.

Improvement in dose escalation using off-line and on-line image feedback in the intensity modulated beam design for prostate cancer treatment

International Nuclear Information System (INIS)

Yan, D.; Birkner, M.; Nuesslin, F.; Wong, J.; Martinez, A.

2001-01-01

Purpose: To test the capability of dose escalation in the IMRT process where the organ/patient temporal geometric variation, measured using either off-line or on-line treatment CT and portal images, are adapted for the optimal design of intensity modulated beam. Materials and Methods: Retrospective study was performed on five prostate cancer patients with multiple CT scans (14∼17/patient) and daily portal images obtained during the treatment course. These images were used to determine the displacements of each subvolume in the organs of interest caused by the daily patient setup and internal organ motion/deformation. The temporal geometric information was processed in order of treatment time and fed into an inverse planning system. The inverse planning engine was specifically implemented to adapt the design of intensity modulated beam to the temporal subvolume displacement and patient internal density changes. Three image feedback strategies were applied to each patient and evaluated with respect to the capability of safe dose escalation. The first one is off-line image feedback, which designs the beam intensity based on the patient images measured within the first week of treatment. The second is an on-line 'the target of the day' strategy, which designs the beam intensity in daily bases by using 'the image of the day' alone. The last one is also the on-line based. However, it designs the instantaneous beam intensity based on also dose distribution in each organ of interest received prior to the current treatment. For each of the treatment strategies, the minimum dose delivered to the CTV was determined by applying the identical normal tissue constraints of partial dose/volumes. This minimum dose was used to represent the treatment dose for each patient. Results: The off-line strategy appears feasible after 5 days of image feedback. The average treatment dose among the patients can be 10% higher than the one in the conventional IMRT treatment where the inverse

Exercise volume and intensity: a dose-response relationship with health benefits.

Science.gov (United States)

Foulds, Heather J A; Bredin, Shannon S D; Charlesworth, Sarah A; Ivey, Adam C; Warburton, Darren E R

2014-08-01

The health benefits of exercise are well established. However, the relationship between exercise volume and intensity and health benefits remains unclear, particularly the benefits of low-volume and intensity exercise. The primary purpose of this investigation was, therefore, to examine the dose-response relationship between exercise volume and intensity with derived health benefits including volumes and intensity of activity well below international recommendations. Generally healthy, active participants (n = 72; age = 44 ± 13 years) were assigned randomly to control (n = 10) or one of five 13-week exercise programs: (1) 10-min brisk walking 1×/week (n = 10), (2) 10-min brisk walking 3×/week (n = 10), (3) 30-min brisk walking 3×/week (n = 18), (4) 60-min brisk walking 3×/week (n = 10), and (5) 30-min running 3×/week (n = 14), in addition to their regular physical activity. Health measures evaluated pre- and post-training including blood pressure, body composition, fasting lipids and glucose, and maximal aerobic power (VO2max). Health improvements were observed among programs at least 30 min in duration, including body composition and VO2max: 30-min walking 28.8-34.5 mL kg(-1) min(-1), 60-min walking 25.1-28.9 mL kg(-1) min(-1), and 30-min running 32.4-36.4 mL kg(-1) min(-1). The greater intensity running program also demonstrated improvements in triglycerides. In healthy active individuals, a physical activity program of at least 30 min in duration for three sessions/per week is associated with consistent improvements in health status.

Insulin Increases Expression of TRPC6 Channels in Podocytes by a Calcineurin-Dependent Pathway

DEFF Research Database (Denmark)

Xia, Shengqiang; Liu, Ying; Li, Xinming

2016-01-01

and protein in podocytes. Insulin increased TRPC6 transcripts in a time and dose-dependent manner. The insulin-induced elevation of TRPC6 transcripts was blocked in the presence of tacrolimus, cyclosporine A, and NFAT-inhibitor (each p ANOVA and Bonferroni's multiple comparison test). Transcripts......, cyclosporine A, and NFAT-inhibitor blocked that insulin effect (p ANOVA). Immunofluorescence showed that insulin increased TRPC6-expression on the cell surface. Fluorescence-spectrophotometry and manganese quench experiments indicated that the increased TRPC6-expression after insulin...

Intensity of the absorbing dose of the gamma rays in the air of Krusevac during and after nuclear accident in Chernobil

International Nuclear Information System (INIS)

Fortuna, D.

1997-01-01

In this paper are compared overage daily values of the intensity of the absorbing doses of the gamma rays in the air of Krusevac, during and after nuclear accident in Cernobil. Average daily values of intensity of the absorbing doses of gamma rays in the air of Krusevac, immediately after nuclear accident in Cernobil were, three to seven time higher than of the average daily values of the natural rays. (author)

Pharmacokinetics of a porcine insulin zinc suspension in diabetic dogs.

Science.gov (United States)

Graham, P A; Nash, A S; McKellar, Q A

1997-10-01

Ten dogs with naturally occurring diabetes mellitus were injected with a highly purified porcine insulin zinc suspension at a dose according to their expected requirement. Plasma insulin and glucose concentrations were measured at two-hourly intervals over 24 hours following injection. There were either one or two peaks in plasma insulin concentration: one at about four hours (mean 4.3 +/- 1.3 [SD]) and another at about 11 hours (mean 11 +/- 1.85) after the injection. The second insulin peak was seen in only eight dogs. Persistence of elevated plasma insulin concentrations ranged from 14 to 24 hours (mean 17.4 +/- 3.65). These results compare favourably with those published for other intermediate-acting insulin preparations used to treat canine diabetes mellitus and suggest that this preparation has useful properties for the successful management of many canine diabetics.

Effects of 12-week high-intensity interval training on plasma visfatin concentration and insulin resistance in overweight men

Directory of Open Access Journals (Sweden)

Hasan Matinhomaee

2014-06-01

Full Text Available The purpose of this study was to determine the effects of 12 weeks of high-intensity interval training (HIIT on visfatin and insulin resistance (IR in overweight adult men during a weight-loss program. Eighteen overweight men (age = 31.8 ± 9.2 years; body mass index = 28.6 ± 1.4 kg/m2 were randomly recruited into one of the two groups, namely, HIIT (3 days/week, 20 minutes/day; 85–95% peak oxygen uptake and diet-induced weight-loss combined (DHIIT; n = 10 and diet-induced weight loss only (DIO; n = 8. The DHIIT and DIO groups undertook a 12-week weight-loss intervention using a moderate isocaloric energy-deficit diet. Both DHIIT and DIO groups demonstrated a significant reduction in body weight (p < 0.01. Total fat mass (p < 0.05 and lean body mass (p < 0.05 were decreased in the DIO group with no significant changes in abdominal fat mass, plasma insulin concentration, homeostasis model assessment-estimated IR (HOMA-IR, blood glucose level, and plasma visfatin. In the DHIIT group, total fat mass (p < 0.01, abdominal fat mass (p < 0.05, plasma insulin concentration (p < 0.05, plasma visfatin (p < 0.01, and HOMA-IR (p < 0.05 were reduced and lean body mass remained unchanged. In conclusion, adding a low-volume 20-minute HIIT (three times/week to an energy-deficit diet not only can improve the efficiency of weight-loss program in the reduction of body fat, plasma visfatin levels, and HOMA-IR, but also has a reservation effect on lean body mass.

Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies

Directory of Open Access Journals (Sweden)

Bhalla NK

2006-08-01

Full Text Available Abstract Background and purpose Intensity modulated radiotherapy (IMRT is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities. The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. Materials and methods During the period January 2002 to March 2004, 12 patients of various sites of malignancies in the thoracic region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms. Results An average dose reduction of the mean values by 73% to the heart, 69% to the right lung and 74% to the left lung, with respect to the GTV could be achieved with IMRT. The 2 year disease free survival was 59% and 2 year overall survival was 59%. The average number of IMRT fields used was 6. Conclusion IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs.

Short-term intensive insulin therapy could be the preferred option for new onset Type 2 diabetes mellitus patients with HbA1c > 9.

Science.gov (United States)

Weng, Jianping

2017-10-01

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease. Currently, the typical clinical therapeutic pathway for the disease consists of the stepwise addition of antihyperglycemic preparations over time, followed lastly by insulin therapy when functional β-cell capacity is severely deteriorated. Recognizing the complexity of disease management, personalized (precision) medicine approaches may enable the physician to tailor diabetes treatment based on HbA1c levels, body mass index (BMI), efficacy, risk of hypoglycemia, risk of weight gain, age, safety, cost, and even genetic characteristics. Although insulin therapy has traditionally been recommended as the last option in the sequential treatment algorithm of T2DM, it is notable that several guidelines and consensus statements suggest consideration of insulin as part of a first-line regimen. In the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive T2DM 2017 management algorithm, insulin is recommended for T2DM patients presenting with symptoms and an HbA1c >9.0%. In addition, the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus statement recommends initial insulin therapy as an option when HbA1c ≥9%, and definite consideration with HbA1c ≥10-12%, and mentions that it may be possible to taper off insulin once initial glucotoxicity is reversed and to consider transfer to other types of non-insulin therapies. Based on accumulating evidence, an expert group has endorsed the concept of short-term intensive insulin (STII) therapy as an option for some patients with T2DM at the time of diagnosis. Notably, the latest Israeli guidelines suggest considering immediate, sometimes short-term, insulin treatment for patients with HbA1c >9% or with symptoms. It has been reported that nearly one-quarter (23%) of newly diagnosed T2DM patients in the US had an HbA1c ≥9.0% prior to initiation of treatment. For such

Clinical evidence and mechanistic basis for vildagliptin’s effect in combination with insulin

Science.gov (United States)

Schweizer, Anja; Foley, James E; Kothny, Wolfgang; Ahrén, Bo

2013-01-01

Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs) in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with vildagliptin, metformin, and basal insulin could be an attractive therapeutic option. PMID:23431062

Use of Insulin and Insulin Analogs and Risk of Cancer — Systematic Review and Meta-Analysis of Observational Studies

Science.gov (United States)

Karlstad, Øystein; Starup-Linde, Jacob; Vestergaard, Peter; Hjellvik, Vidar; T. Bazelier, Marloes; K. Schmidt, Marjanka; Andersen, Morten; Auvinen, Anssi; Haukka, Jari; Furu, Kari; de Vries, Frank; L. de Bruin, Marie

2014-01-01

Background: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies. Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk. PMID:24215311

MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin

International Nuclear Information System (INIS)

Zhang, Zi-wei; Guo, Rui-wei; Lv, Jin-lin; Wang, Xian-mei; Ye, Jin-shan; Lu, Ni-hong; Liang, Xing; Yang, Li-xia

2017-01-01

Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells. However, whether it is involved in insulin-induced changes of VSCMs has not been determined. In this study, we found that insulin induced proliferation, migration, and dedifferentiation of mouse VSMCs in a dose-dependent manner. Furthermore, the stimulating effects of high-dose insulin on proliferation, migration, and dedifferentiation of mouse VSMCs were found to be associated with the attenuation of the inhibitory effects of miR-99a on IGF-1R and mTOR signaling activities. Finally, we found that the inducing effect of high-dose insulin on proliferation, migration, and dedifferentiation of VSMCs was partially inhibited by an active mimic of miR-99a. Taken together, these results suggest that miR-99a plays a key regulatory role in the pathogenesis of insulin-induced proliferation, migration, and phenotype conversion of VSMCs at least partly via inhibition of IGF-1R and mTOR signaling. Our results provide evidence that miR-99a may be a novel target for the treatment of hyperinsulinemia-induced atherosclerosis. - Highlights: • Suggesting a new mechanism of insulin-triggered VSMC functions. • Providing a new therapeutic strategies that target atherosclerosis in T2DM patients. • Providing a new strategies that target in-stent restenosis in T2DM patients.

Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension

DEFF Research Database (Denmark)

de Courten, Maximilian; Ferrari, P; Schneider, M

1993-01-01

Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients......To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model...... [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg...

Potential role of insulin signaling on vascular smooth muscle cell migration, proliferation, and inflammation pathways.

Science.gov (United States)

Cersosimo, Eugenio; Xu, Xiaojing; Musi, Nicolas

2012-02-15

To investigate the role of insulin signaling pathways in migration, proliferation, and inflammation of vascular smooth muscle cells (VSMCs), we examined the expression of active components of the phosphatidyl inositol 3 (PI-3) kinase (p-Akt) and mitogen-activated protein kinase (MAPK) (p-Erk) in primary cultures of VSMCs from human coronary arteries. VSMCs were treated in a dose-response manner with insulin (0, 1, 10, and 100 nM) for 20 min, and Akt and Erk phosphorylation were measured by Western blot analysis. In separate experiments, we evaluated the effect of 200 μM palmitate, in the presence and absence of 8 μM pioglitazone, on insulin-stimulated (100 nM for 20 min) Akt and Erk phosphorylation. The phosphorylation of Akt and Erk in VSMCs exhibited a dose dependency with a three- to fourfold increase, respectively, at the highest dose (100 nM). In the presence of palmitate, insulin-induced Akt phosphorylation was completely abolished, and there was a threefold increase in p-Erk. With addition of pioglitazone, the phosphorylation of Akt by insulin remained unchanged, whereas insulin-stimulated Erk phosphorylation was reduced by pioglitazone. These data in VSMCs indicate that high palmitate decreases insulin-stimulated Akt phosphorylation and stimulates MAPK, whereas preexposure peroxisome proliferator-activated receptor-γ agonist pioglitazone preserves Akt phosphorylation and simultaneously attenuates MAPK signaling. Our results suggest that metabolic and mitogenic insulin signals have different sensitivity, are independently regulated, and may play a role in arterial smooth muscle cells migration, proliferation, and inflammation in conditions of acute hyperinsulinemia.

Acceleration of intensity-modulated radiotherapy dose calculation by importance sampling of the calculation matrices

International Nuclear Information System (INIS)

Thieke, Christian; Nill, Simeon; Oelfke, Uwe; Bortfeld, Thomas

2002-01-01

In inverse planning for intensity-modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look-up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low-dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well-known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan

Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients

DEFF Research Database (Denmark)

Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik

2015-01-01

insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. STUDY DESIGN AND METHODS: Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m2) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU......-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first...

Principles and frequency of self-adjustment of insulin dose in people with diabetes mellitus type 1 and correlation with markers of metabolic control.

Science.gov (United States)

Kramer, Guido; Kuniss, Nadine; Kloos, Christof; Lehmann, Thomas; Müller, Nicolle; Wolf, Gunter; Lorkowski, Stefan; Müller, Ulrich A

2016-06-01

Insulin dose self-adjustment (ISA) to different blood glucose levels, carbohydrate intake, exercise or illness is a core element of structured education programmes for people with diabetes mellitus type 1 (DM1). The aim of this study was to register the patients' current principles and frequency of ISA and to check the ability for correct adjustments. 117 people with DM1 (mean HbA1c 7.1%, diabetes duration 24y) were interviewed in a tertiary care centre. The number of ISA was drawn from the last 28days of the patients' diary. The ability to find the correct insulin dose was assessed using five different calculation examples. All patients had participated in a structured education programme. Mean frequency of ISA was 72.1±29.4 per 28days. ISA by adjustment rules was used in 48% (56/117) and by personal experience or feeling in 44% (52/117). Patients adjusting by feeling were older, did less ISA and had lower social status. There were no differences in HbA1c (feeling 7.2±0.8 vs. rules 7.0±0.9, p=0.403), non severe hypoglycaemia (feeling 1.7±1.8 vs. rules 1.9±1.9, p=0.132) and comprehensibility of ISA between both groups. Overall, the participants answered on average 2.8±2.3 of the five calculation examples correctly. Although all people were trained to use a factor for correction for ISA in case of high premeal blood glucose levels, only half of the patients adjusted their insulin dosage using the complex rules from the treatment and education programme. Patients, who performed their ISA based upon feeling, did not show worse metabolic control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Radiation dose reduction in a neonatal intensive care unit in computed radiography.

Science.gov (United States)

Frayre, A S; Torres, P; Gaona, E; Rivera, T; Franco, J; Molina, N

2012-12-01

The purpose of this study was to evaluate the dose received by chest x-rays in neonatal care with thermoluminescent dosimetry and to determine the level of exposure where the quantum noise level does not affect the diagnostic image quality in order to reduce the dose to neonates. In pediatric radiology, especially the prematurely born children are highly sensitive to the radiation because of the highly mitotic state of their cells; in general, the sensitivity of a tissue to radiation is directly proportional to its rate of proliferation. The sample consisted of 208 neonatal chest x-rays of 12 neonates admitted and treated in a Neonatal Intensive Care Unit (NICU). All the neonates were preterm in the range of 28-34 weeks, with a mean of 30.8 weeks. Entrance Surface Doses (ESD) values for chest x-rays are higher than the DRL of 50 μGy proposed by the National Radiological Protection Board (NRPB). In order to reduce the dose to neonates, the optimum image quality was achieved by determining the level of ESD where level noise does not affect the diagnostic image quality. The optimum ESD was estimated for additional 20 chest x-rays increasing kVp and reducing mAs until quantum noise affects image quality. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Progress in the development of insulin pumps and their advanced automatic functions].

Science.gov (United States)

Prázný, Martin

2015-04-01

Patients with type 1 diabetes are exposed to permanent burden consisting of careful glucose self-monitoring and precise insulin dosage based on measured glucose values, carbohydrates content in the food and both planned and non-planned physical activity. Erroneous insulin dosing causes frequent both hypoglycemia and hyperglycemia. Hypoglycemia is, however, the most clinically significant complication limiting the optimal diabetes control. Automatic features for insulin dosage integrated in insulin pumps are thus very important. Low glucose suspend (LGS) and Predictive Low Glucose Management (PLGM) use glucose sensor values to prevent hypoglycemia, shorten the time spent in hypoglycemic range and present further step forward to fully closed-loop system of insulin treatment.

Rational Design of Glucose-Responsive Insulin Using Pharmacokinetic Modeling.

Science.gov (United States)

Bakh, Naveed A; Bisker, Gili; Lee, Michael A; Gong, Xun; Strano, Michael S

2017-11-01

A glucose responsive insulin (GRI) is a therapeutic that modulates its potency, concentration, or dosing of insulin in relation to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. Current GRI design lacks a theoretical basis on which to base fundamental design parameters such as glucose reactivity, dissociation constant or potency, and in vivo efficacy. In this work, an approach to mathematically model the relevant parameter space for effective GRIs is induced, and design rules for linking GRI performance to therapeutic benefit are developed. Well-developed pharmacokinetic models of human glucose and insulin metabolism coupled to a kinetic model representation of a freely circulating GRI are used to determine the desired kinetic parameters and dosing for optimal glycemic control. The model examines a subcutaneous dose of GRI with kinetic parameters in an optimal range that results in successful glycemic control within prescribed constraints over a 24 h period. Additionally, it is demonstrated that the modeling approach can find GRI parameters that enable stable glucose levels that persist through a skipped meal. The results provide a framework for exploring the parameter space of GRIs, potentially without extensive, iterative in vivo animal testing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lithium formate EPR dosimetry for verifications of planned dose distributions prior to intensity-modulated radiation therapy

Science.gov (United States)

Gustafsson, H.; Lund, E.; Olsson, S.

2008-09-01

The objective of the present investigation was to evaluate lithium formate electron paramagnetic resonance (EPR) dosimetry for measurement of dose distributions in phantoms prior to intensity-modulated radiation therapy (IMRT). Lithium formate monohydrate tablets were carefully prepared, and blind tests were performed in clinically relevant situations in order to determine the precision and accuracy of the method. Further experiments confirmed that within the accuracy of the current method, the dosimeter response was independent of beam energies and dose rates used for IMRT treatments. The method was applied to IMRT treatment plans, and the dose determinations were compared to ionization chamber measurements. The experiments showed that absorbed doses above 3 Gy could be measured with an uncertainty of less than 2.5% of the dose (coverage factor k = 1.96). Measurement time was about 15 min using a well-calibrated dosimeter batch. The conclusion drawn from the investigation was that lithium formate EPR dosimetry is a promising new tool for absorbed dose measurements in external beam radiation therapy, especially for doses above 3 Gy.

Lithium formate EPR dosimetry for verifications of planned dose distributions prior to intensity-modulated radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Gustafsson, H; Lund, E [Department of Medical and Health Sciences, Radiation Physics, Faculty of Health Sciences, Linkoeping University, S-581 85 Linkoeping (Sweden); Olsson, S [Division of Radiation Physics, Linkoeping University Hospital, S-581 85 Linkoeping (Sweden)], E-mail: hakgu@imv.liu.se

2008-09-07

The objective of the present investigation was to evaluate lithium formate electron paramagnetic resonance (EPR) dosimetry for measurement of dose distributions in phantoms prior to intensity-modulated radiation therapy (IMRT). Lithium formate monohydrate tablets were carefully prepared, and blind tests were performed in clinically relevant situations in order to determine the precision and accuracy of the method. Further experiments confirmed that within the accuracy of the current method, the dosimeter response was independent of beam energies and dose rates used for IMRT treatments. The method was applied to IMRT treatment plans, and the dose determinations were compared to ionization chamber measurements. The experiments showed that absorbed doses above 3 Gy could be measured with an uncertainty of less than 2.5% of the dose (coverage factor k = 1.96). Measurement time was about 15 min using a well-calibrated dosimeter batch. The conclusion drawn from the investigation was that lithium formate EPR dosimetry is a promising new tool for absorbed dose measurements in external beam radiation therapy, especially for doses above 3 Gy.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

International Nuclear Information System (INIS)

Ben-Josef, Edgar; Schipper, Mathew; Francis, Isaac R.; Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel; Simeone, Diane M.; Sonnenday, Christopher; Abrams, Ross; Leslie, William; Khan, Gazala; Zalupski, Mark M.

2012-01-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥1500/mm 3 , platelets ≥100,000/mm 3 , creatinine 2 /100 min intravenously) was given on days −22 and −15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥3, neutropenic fever, or deterioration in performance status to ≥3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

Cost calculation for a flash glucose monitoring system for UK adults with type 1 diabetes mellitus receiving intensive insulin treatment.

Science.gov (United States)

Hellmund, Richard; Weitgasser, Raimund; Blissett, Deirdre

2018-04-01

To estimate the costs associated with a flash glucose monitoring system as a replacement for routine self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes mellitus (T1DM) using intensive insulin, from a UK National Health Service (NHS) perspective. The base-case cost calculation was created using the maximum frequency of glucose monitoring recommended by the 2015 National Institute for Health and Care Excellence guidelines (4-10 tests per day). Scenario analyses considered SMBG at the frequency observed in the IMPACT clinical trial (5.6 tests per day) and at the frequency of flash monitoring observed in a real-world analysis (16 tests per day). A further scenario included potential costs associated with severe hypoglycaemia. In the base case, the annual cost per patient using flash monitoring was £234 (19%) lower compared with routine SMBG (10 tests per day). In scenario analyses, the annual cost per patient of flash monitoring compared with 5.6 and 16 SMBG tests per day was £296 higher and £957 lower, respectively. The annual cost of severe hypoglycaemia for flash monitoring users was estimated to be £221 per patient, compared with £428 for routine SMBG users (based on 5.6 tests/day), corresponding to a reduction in costs of £207. The flash monitoring system has a modest impact on glucose monitoring costs for the UK NHS for patients with T1DM using intensive insulin. For people requiring frequent tests, flash monitoring may be cost saving, especially when taking into account potential reductions in the rate of severe hypoglycaemia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Gamma Amino Butyric Acid Attenuates Liver and Kidney Damage Associated with Insulin Alteration in γ-Irradiated and Streptozotocin-Treated Rats

International Nuclear Information System (INIS)

Saada, H.N.; Eltahawy, N.A.; Hammad, A.S.; Morcos, N.Y.S.

2016-01-01

Gamma aminobutyric acid (GABA) is one of the inhibitory neurotransmitters that may have the ability to relive the intensity of stress. The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in modulating insulin disturbance associated with liver and kidney damage in γ-irradiated and streptozotocin-treated rats. Irradiation was performed by whole body exposure to 6 Gy from a Cs-137 source. Streptozotocin (STZ) was administered in a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to γ-irradiated and STZ-treated-rats. The results obtained showed that γ-irradiation induced hyperglycemia, hyperinsulinaemia and insulin resistance (similar to type 2 Diabetes), while STZ-treatment produced hyperglycemia, insulin deficiency with no insulin resistance detected (similar to type 1 Diabetes). In both cases, significant increases of alanine amino transferase (ALT) and aspartate amino transferase (AST) activities, urea and creatinine levels were recorded in the serum. These changes were associated with oxidative damage to the liver and kidney tissues notified by significant decreases of superoxide dismutase (SOD ), catalase and glutathione peroxidase ( GSH-Px) activities in parallel to significant increases of malondialdehyde (MDA) and advanced oxidation protein products ( AOPP) levels. The administration of GABA to irradiated as well as STZ-treated rats regulated insulin and glucose levels, minimized oxidative stress and reduced the severity of liver and kidney damage. It could be concluded that GABA could be a useful adjunct to reduce some metabolic complications associated with insulin deficiency and insulin resistance

The role of insulin pump therapy for type 2 diabetes mellitus.

Science.gov (United States)

Landau, Zohar; Raz, Itamar; Wainstein, Julio; Bar-Dayan, Yosefa; Cahn, Avivit

2017-01-01

Many patients with type 2 diabetes fail to achieve adequate glucose control despite escalation of treatment and combinations of multiple therapies including insulin. Patients with long-standing type 2 diabetes often suffer from the combination of severe insulin deficiency in addition to insulin resistance, thereby requiring high doses of insulin delivered in multiple injections to attain adequate glycemic control. Insulin-pump therapy was first introduced in the 1970s as an approach to mimic physiological insulin delivery and attain normal glucose in patients with type 1 diabetes. The recent years have seen an increase in the use of this technology for patients with type 2 diabetes. This article summarizes the clinical studies evaluating insulin pump use in patients with type 2 diabetes and discusses the benefits and shortcomings of pump therapy in this population. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy and safety of an insulin infusion protocol in a surgical ICU.

Science.gov (United States)

Taylor, Beth E; Schallom, Marilyn E; Sona, Carrie S; Buchman, Timothy G; Boyle, Walter A; Mazuski, John E; Schuerer, Douglas E; Thomas, James M; Kaiser, Christy; Huey, Way Y; Ward, Myrna R; Zack, Jeanne E; Coopersmith, Craig M

2006-01-01

Hyperglycemia is associated with complications in the surgical intensive care unit. The purpose of this study was to determine the efficacy and safety of nurse-driven insulin infusion protocols in lowering blood glucose (BG) in critical illness. All patients in a 24-bed surgical intensive care unit who required i.v. insulin infusions during 3 noncontiguous 6-month periods from 2002 to 2004 were evaluated. In the preintervention phase, 71 patients received a physician-initiated insulin infusion without a developed protocol. They were compared with 95 patients who received a nurse-driven insulin infusion protocol with a target BG of 120 to 150 mg/dL and to 119 patients who received a more stringent protocol with a target BG of 80 to 110 mg/dL. There was a stepwise decrease in average daily BG levels, from 190 to 163 to 132 mg/dL (p < 0.001). The less stringent protocol decreased the time to achieve a BG level < 150 mg/dL from 14.1 to 7.4 hours compared with physician-driven management (p < 0.05) resulting in similar time on an insulin infusion (53 versus 48 hours). The more intensive protocol brought BG levels < 150 mg/dL in 7.2 hours and < 111 mg/dL in 13.6 hours, but increased the length of time a patient was on an insulin infusion to 77 hours. The incidence of severe hypoglycemia (BG < 40 mg/dL) was statistically similar between the groups, ranging between 1.1% and 3.4%. Implementation of a nurse-driven protocol led to more rapid and more effective BG control in critically ill surgical patients compared with physician management. Tighter BG control can be obtained without a significant increase in hypoglycemia, although this is associated with increased time on an insulin infusion.

Clinical evidence and mechanistic basis for vildagliptin's effect in combination with insulin

Directory of Open Access Journals (Sweden)

Schweizer A

2013-02-01

Full Text Available Anja Schweizer,1 James E Foley,2 Wolfgang Kothny,2 Bo Ahrén31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Department of Clinical Sciences, Lund University, Lund, SwedenAbstract: Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4 inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with

Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

Science.gov (United States)

Hemmingsen, Bianca; Christensen, Louise Lundby; Wetterslev, Jørn; Vaag, Allan; Gluud, Christian; Lund, Søren S; Almdal, Thomas

2012-04-19

A(1c), weight gain, and insulin dose, compared with insulin alone; trial sequential analyses showed sufficient evidence for a HbA(1c) reduction of 0.5%, lower weight gain of 1 kg, and lower insulin dose of 5 U/day. There was no evidence or even a trend towards improved all cause mortality or cardiovascular mortality with metformin and insulin, compared with insulin alone in type 2 diabetes. Data were limited by the severe lack of data reported by trials for patient relevant outcomes and by poor bias control.

Insulin Radioimmunoassay for Clinical Research in Psychiatric, Pancreatic, Cirrhotic and Irradiated Patients

Energy Technology Data Exchange (ETDEWEB)

Czerniak, P.; Chlebowski, J.; Kulcar, S.; Boruchowski, Sabina [Department Of Radiotherapy and Isotopes and Department of Psychiatry, Tel-Aviv University Medical School (Israel); Faculty for Continuing Medical Education, Tel-Hashomer Hospital, Tel-Hashomer (Israel)

1970-02-15

A modified Hales-Randle method for insulin radioimmunoassay is described. An insulin response curve was established in normal cases after glucose loading. Pathological changes were then investigated in patients and animals before and after therapeutic, operative and radiological procedures. Four representative groups of this material will be illustrated. (1) Psychotic patients (acute and chronic schizophrenics, neurotics and depressives) were examined with the aim of learning about the variable effects produced by insulin shock-therapy, as well as for biochemical diagnosis purposes in psychotics. Highest insulin response curves were found in chronic schizophrenics with improvement after insulin therapy. Schizophrenics without improvement presented different curves. Lowest insulin values were found in acute schizophrenia. Depressives and anxiety neurotics showed insulin tolerance curves similar to those of non-psychotic patients. (2) Pancreatic patients. Special attention was paid to pancreatic carcinoma (insulinoma excepted). In most cases of pancreatic carcinoma a very low and flat insulin tolerance curve was found. The above findings may be of a diagnostic importance in this condition, which is clinically hardly recognized. (3) Liver cirrhotic patients. A special group of shunt operated patients was investigated. The study was performed on eight liver cirrhotics before and after porto-caval or reno-splenal shunt operation. The plasma insulin level was examined in the vena cava, renal and cubital blood. The influence of tolbutamide was analysed. The normally occurring retention of insulin by normal hepatic tissue was found to be considerably disturbed. Other interesting changes were observed. (4) The plasma insulin level in the radiologically exposed. Experimental and clinical studies were performed, with insulin doses before and after radiation. Whole body X-ray exposure (300 rads) to rats resulted in a rapid lowering of insulin or its disappearance. Recovery was

I-123-insulin: A new marker for hepatoma

International Nuclear Information System (INIS)

Sodoyez, J.C.; Goffaux, F.S.; Fallais, C.; Bourgeois, P.

1984-01-01

Previous studies have demonstrated that carrier-free I-123-Tyr Al4 insulin was taken up by the liver (by a saturable mechanism) and by the kidneys (by a non saturable mechanism). Autoradiographs of rat liver after injection of I-125-insulin showed that binding specifically occurred at the plasma membrane of the hepatocytes. I-123-Insulin binding to the hepatocyte plasma membrane appeared mediated by specific receptors. Indeed it was blocked by antibodies to the insulin receptors and by an excess of native insulin. Futhermore insulin derivatives with low biological potency (proinsulin and desoctapeptide insulin) did not inhibit I-123-insulin binding to the hepatocytes. I-123-Insulin (1.3 mCi) was I.V. injected into a patient in whom the right liver lobe was normal (normal uptake of Tc-99m-colloid sulfur) but the left liver lobe was occupied by a voluminous hepatoma (no uptake of Tc-99m-colloid sulfur). Liver blood supply was also studied by Tc-99m-pyrophosphate-labeled red cells. Computer analysis of the data revealed that compared to the normal liver lobe, binding of I-123-insulin to the hepatoma was more precocious (vascularization through the hepatic artery and not the portal vein), more intense and more prolonged (half-lives were 6 min in the normal liver and 14 min in the hepatoma). These results are consistent with characteristics of hepatoma cells in culture in which high insulin binding capacity contrasts with a markedly decreased insulin degrading activity. It is concluded that I-123-insulin may be used as a specific marker of hepatoma in man

Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat

International Nuclear Information System (INIS)

Manin, M.; Broer, Y.; Balage, M.; Rostene, W.; Grizard, J.

1990-01-01

Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function

Effects of insulin on ketogenesis following fasting in lean and obese men

NARCIS (Netherlands)

Soeters, Maarten R.; Sauerwein, Hans P.; Faas, Linda; Smeenge, Martijn; Duran, Marinus; Wanders, Ronald J.; Ruiter, An F.; Ackermans, Mariëtte T.; Fliers, Eric; Houten, Sander M.; Serlie, Mireille J.

2009-01-01

The ketone bodies (KBs) D-3-hydroxybutyrate (D-3HB) and acetoacetate (AcAc) play a role in starvation and have been associated with insulin resistance. The dose-response relationship between insulin and KBs was demonstrated to be shifted to the right in type 2 diabetes patients. However, KB levels

Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin in liposomes

International Nuclear Information System (INIS)

Stevenson, R.W.; Patel, H.M.; Parsons, J.A.; Ryman, B.E.

1982-01-01

The biologic action of insulin entrapped in liposomes (phospholipid vesicles) has been investigated following subcutaneous injection to dogs made diabetic with a combination of alloxan and streptozotocin. The fate of the liposomally entrapped material was determined by injecting rats subcutaneously with either 125 I-insulin or the labeled polysaccharide 14 C-inulin, incorporated in liposomes labeled with 3 H-cholesterol. Injection of liposome insulin (0.75 U/kg) to five diabetic dogs resulted in a mean (+/- SEM) blood glucose fall from 16.4 +/- 0.8 to 2.9 +/- 0.4 mmol/L. The glucose level had still not returned to baseline after 24 h and, correspondingly, immunoreactive insulin (IRI) could still be detected in frozen and thawed plasma 24 h after injection. In contrast, the hypoglycemic effect of the same dose of free insulin with or without empty liposomes virtually ended within 8 h and IRI levels returned to baseline by 3 h after injection. In experiments on rats with liposomally entrapped 125 I-insulin or 14 C-inulin the proportion of the injected dose of tracer recoverable by excision of the injection site remained constant after about 1 h and 70% of the dose was still fixed in subcutaneous tissue for at least 5 h thereafter. When the plasma collected 3 h after subcutaneous injection of labeled liposomes containing 125 I-insulin was passed through a column of Sepharose 6B, 50-75% of the 125 I-activity was found in the fractions associated with intact liposomes. One possibility for the persistence of the hypoglycemic effect and of measurable IRI following injection of liposome insulin could be the presence of intact liposomes in the circulation for many hours after adsorption had ceased

Analysis of Biochemical Control and Prognostic Factors in Patients Treated With Either Low-Dose Three-Dimensional Conformal Radiation Therapy or High-Dose Intensity-Modulated Radiotherapy for Localized Prostate Cancer

International Nuclear Information System (INIS)

Vora, Sujay A.; Wong, William W.; Schild, Steven E.; Ezzell, Gary A.; Halyard, Michele Y.

2007-01-01

Purpose: To identify prognostic factors and evaluate biochemical control rates for patients with localized prostate cancer treated with either high-dose intensity-modulated radiotherapy (IMRT) or conventional-dose three-dimensional conformal radiotherapy 3D-CRT. Methods: Four hundred sixteen patients with a minimum follow-up of 3 years (median, 5 years) were included. Two hundred seventy-one patients received 3D-CRT with a median dose of 68.4 Gy (range, 66-71 Gy). The next 145 patients received IMRT with a median dose of 75.6 Gy (range, 70.2-77.4 Gy). Biochemical control rates were calculated according to both American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definitions. Prognostic factors were identified using both univariate and multivariate analyses. Results: The 5-year biochemical control rate was 60.4% for 3D-CRT and 74.1% for IMRT (p < 0.0001, first ASTRO Consensus definition). Using the ASTRO Phoenix definition, the 5-year biochemical control rate was 74.4% and 84.6% with 3D-RT and IMRT, respectively (p = 0.0326). Univariate analyses determined that PSA level, T stage, Gleason score, perineural invasion, and radiation dose were predictive of biochemical control. On multivariate analysis, dose, Gleason score, and perineural invasion remained significant. Conclusion: On the basis of both ASTRO definitions, dose, Gleason score, and perineural invasion were predictive of biochemical control. Intensity-modulated radiotherapy allowed delivery of higher doses of radiation with very low toxicity, resulting in improved biochemical control

Biological activity of alligator, avian, and mammalian insulin in juvenile alligators: plasma glucose and amino acids.

Science.gov (United States)

Lance, V A; Elsey, R M; Coulson, R A

1993-02-01

The biological activity of alligator, turkey, and bovine insulin on plasma glucose and plasma amino acids was tested in fasted juvenile alligators. Preliminary experiments showed that the stress associated with taking the initial blood sample resulted in a hyperglycemic response lasting more than 24 hr. Despite repeated bleedings no additional hyperglycemic events occurred, and blood glucose declined slowly over the next 7 days. Under these conditions the smallest dose of insulin eliciting a hypoglycemic response was 40 micrograms/kg body wt. A dose of 400 micrograms/kg body wt of either alligator or bovine insulin caused a pronounced hypoglycemia by 12 hr postinjection. Maximum decline in plasma glucose occurred at 24 to 36 hr with a slow return to control levels by 120 hr. There were no significant differences in the hypoglycemic responses to any of the three insulins tested. The decline in plasma amino acids was much more rapid than the decline in plasma glucose in response to insulin. Even at the 40 micrograms/kg body wt dose a significant difference from saline-injected control was seen at 2 hr postinjection. Maximum decline in plasma amino acids occurred at 8 to 12 hr with a return to baseline by 36 hr. These results show that the relatively conservative changes in the sequence of alligator insulin (three amino acid substitutions in the B-chain compared with that of chicken) have little effect on biological activity and that alligator insulin receptors do not appear to discriminate among the three insulins.

Effect of Insulin Therapy using Hyper-insulinemic Normoglycemic Clamp on Inflammatory Response in Brain Dead Organ Donors.

Science.gov (United States)

Aljiffry, M; Hassanain, M; Schricker, T; Shaheen, M; Nouh, T; Lattermann, R; Salman, A; Wykes, L; Metrakos, P

2016-05-01

Brain death is a major stress that is associated with a massive inflammatory response and systemic hyperglycemia. Severe inflammation leads to increased graft immunogenicity and risk of graft dysfunction; while acute hyperglycemia aggravates the inflammatory response and increases the risk of morbidity and mortality. Insulin therapy not only controls hyperglycemia but also suppresses inflammation. The present study is to investigate the anti-inflammatory properties and the normoglycemia maintenance of high dose insulin on brain dead organ donors. 15 brain dead organ donors were divided into 2 groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The changes of serum cytokines, including IL-6, IL-10, IL-1β, IL-8, TNFα, TGFα and MCP-1, were measured by suspension bead array immunoassay and glucose by a glucose monitor. Compared to controls, insulin treated donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L, pinsulin treated donors compared with those in controls. High dose insulin therapy decreases the concentrations of inflammatory cytokines in brain dead donors and preserves normoglycemia. High dose of insulin may have anti-inflammatory effects in brain dead organ donors and therefore, improve the quality of donor organs and potentially improve outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

Radiation doses and risks to neonates undergoing common radiographic examinations in the neonatal intensive care unit

International Nuclear Information System (INIS)

McParland, B.J.; Lee, R.

1996-01-01

Neonates in the-Neonatal Intensive Care Unit (NICU) can receive large numbers of radiographs owing to the clinical conditions they may present. More neonatal radiation dosimetry data are required for three fundamental reasons: (1.) to aid in the establishment of reference dose levels for interinstitutional comparisons; (2.) to improve childhood cancer risk estimates following neonatal exposure; and (3.) to indicate appropriate directions for dose reduction. This paper describes an investigation of two different NICU radiological techniques with significantly different neonate doses. While patient-matched images taken with both techniques were assessed in a blind review, this component of the study is beyond the scope of this paper and is not discussed here. (author)

Effect of lipoprotein-associated phospholipase A2 inhibitor on insulin resistance in streptozotocin-induced diabetic pregnant rats.

Science.gov (United States)

Wang, Guo-Hua; Jin, Jun; Sun, Li-Zhou

2018-06-21

This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

Multivariate analysis of factors predicting prostate dose in intensity-modulated radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Tomita, Tsuneyuki [Division of Radiology, Osaka Red Cross Hospital, Osaka (Japan); Nakamura, Mitsuhiro, E-mail: m_nkmr@kuhp.kyoto-u.ac.jp [Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Hirose, Yoshinori; Kitsuda, Kenji; Notogawa, Takuya; Miki, Katsuhito [Division of Radiology, Osaka Red Cross Hospital, Osaka (Japan); Nakamura, Kiyonao; Ishigaki, Takashi [Department of Radiation Oncology, Osaka Red Cross Hospital, Osaka (Japan)

2014-01-01

We conducted a multivariate analysis to determine relationships between prostate radiation dose and the state of surrounding organs, including organ volumes and the internal angle of the levator ani muscle (LAM), based on cone-beam computed tomography (CBCT) images after bone matching. We analyzed 270 CBCT data sets from 30 consecutive patients receiving intensity-modulated radiation therapy for prostate cancer. With patients in the supine position on a couch with the HipFix system, data for center of mass (COM) displacement of the prostate and the state of individual organs were acquired and compared between planning CT and CBCT scans. Dose distributions were then recalculated based on CBCT images. The relative effects of factors on the variance in COM, dose covering 95% of the prostate volume (D{sub 95%}), and percentage of prostate volume covered by the 100% isodose line (V{sub 100%}) were evaluated by a backward stepwise multiple regression analysis. COM displacement in the anterior-posterior direction (COM{sub AP}) correlated significantly with the rectum volume (δVr) and the internal LAM angle (δθ; R = 0.63). Weak correlations were seen for COM in the left-right (R = 0.18) and superior-inferior directions (R = 0.31). Strong correlations between COM{sub AP} and prostate D{sub 95%} and V{sub 100%} were observed (R ≥ 0.69). Additionally, the change ratios in δVr and δθ remained as predictors of prostate D{sub 95%} and V{sub 100%}. This study shows statistically that maintaining the same rectum volume and LAM state for both the planning CT simulation and treatment is important to ensure the correct prostate dose in the supine position with bone matching.

Acute pain induces insulin resistance in humans

DEFF Research Database (Denmark)

Greisen, J.; Juhl, C.B.; Grøfte, Thorbjørn

2001-01-01

Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin. Methods: Ten healthy male volunteers underwent two...... randomly sequenced hyperinsulinemic–euglycemic (insulin infusion rate, 0.6 mU · kg-1 · min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0–10, just before...... the clamp procedure (study P). In the other study, no pain was inflicted (study C). Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 ± 1.87 mg · kg-1 · min-1 (mean ± SD) in study C to 4.97 ± 1.38 mg · kg-1 · min-1 in study P (P

Effects of B Vitamins Overload on Plasma Insulin Level and Hydrogen Peroxide Generation in Rats.

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Sun, Wuping; Zhai, Mingzhu; Zhou, Qian; Qian, Chengrui; Jiang, Changyu

2017-08-31

It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H₂O₂ levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H₂O₂ generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.

The additional dose to radiosensitive organs caused by using under-collimated X-ray beams in neonatal intensive care radiography

International Nuclear Information System (INIS)

Datz, H.; Ben-Shlomo, A.; Margaliot, M.; Bader, D.; Sadetzki, S.; Juster-Reicher, A.; Marks, K.; Smolkin, T.; Zangen, S.

2008-01-01

Radiographic technique and exposure parameters were recorded in five Israeli Neonatal Intensive Care Units for chest, abdomen and both chest and abdomen X-ray examinations. Equivalent dose and effective dose values were calculated according to actual examination field size borders and proper technique field size recommendations using PCXMC, a PC-based Monte Carlo program. Exposure of larger than required body areas resulted in an increase of the organ doses by factors of up to 162 (testes), 162 (thyroid) and 8 (thyroid) for chest, abdomen and both chest and abdomen examinations, respectively. These exposures increased the average effective dose by factors of 2.0, 1.9 and 1.3 for the chest, abdomen and both chest and abdomen examinations, respectively. Differences in exposure parameters were found between the different neonatal intensive care units - tube voltage, current-time product and focal to skin distance differences up to 13, 44 and 22%, respectively. Reduction of at least 50% of neonate exposure is feasible and can be implemented using existing methodology without any additional costs. (authors)

[The effect of mineral water on serotonin and insulin production (an experimental study)].

Science.gov (United States)

Polushina, N D

1998-01-01

Radioimmunoassay (DRG kits) and orthotoluidine test were conducted to measure blood serotonin, insulin and glucose in 70 intact Wistar rat males before and after a course of drinking mineral water Essentuki 17 (MW). After the MW drinking course, a single dose of mineral water increases basal levels of serotonin and insulin, sensitivity of endocrine cells to MW. Serotonin and insulin rose maximally on minute 5 after the drink while in contrast to minute 15 and 30 before initiation of the MW drinking course. A direct correlation was found between blood concentrations of serotonin and insulin.

Impact of geometric uncertainties on dose calculations for intensity modulated radiation therapy of prostate cancer

Science.gov (United States)

Jiang, Runqing

Intensity-modulated radiation therapy (IMRT) uses non-uniform beam intensities within a radiation field to provide patient-specific dose shaping, resulting in a dose distribution that conforms tightly to the planning target volume (PTV). Unavoidable geometric uncertainty arising from patient repositioning and internal organ motion can lead to lower conformality index (CI) during treatment delivery, a decrease in tumor control probability (TCP) and an increase in normal tissue complication probability (NTCP). The CI of the IMRT plan depends heavily on steep dose gradients between the PTV and organ at risk (OAR). Geometric uncertainties reduce the planned dose gradients and result in a less steep or "blurred" dose gradient. The blurred dose gradients can be maximized by constraining the dose objective function in the static IMRT plan or by reducing geometric uncertainty during treatment with corrective verification imaging. Internal organ motion and setup error were evaluated simultaneously for 118 individual patients with implanted fiducials and MV electronic portal imaging (EPI). A Gaussian probability density function (PDF) is reasonable for modeling geometric uncertainties as indicated by the 118 patients group. The Gaussian PDF is patient specific and group standard deviation (SD) should not be used for accurate treatment planning for individual patients. In addition, individual SD should not be determined or predicted from small imaging samples because of random nature of the fluctuations. Frequent verification imaging should be employed in situations where geometric uncertainties are expected. Cumulative PDF data can be used for re-planning to assess accuracy of delivered dose. Group data is useful for determining worst case discrepancy between planned and delivered dose. The margins for the PTV should ideally represent true geometric uncertainties. The measured geometric uncertainties were used in this thesis to assess PTV coverage, dose to OAR, equivalent

Insulin Therapy in Diabetic Hyperglycemic Emergencies

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Diana Machado Ramírez

2014-09-01

Full Text Available Background: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state are two of the most serious metabolic emergencies in diabetic patients. Objective: to identify the type of metabolic complications (diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state in order to analyze the patients’ outcome considering the plasma pH levels, as well as the mode of insulin administration. Method: a cross-sectional descriptive study was conducted in 52 patients admitted to the intensive care unit of the Enrique Cabrera Hospital from 2000 to 2007. The variables analyzed included: type of diabetes mellitus, type of acute complication, mode of insulin administration, blood gas analysis and outcome. Results: diabetic ketoacidosis occurred in 57.5 % of the type 1 diabetic patients and in the 42.5 % of the type 2 diabetics. None of the type 1 diabetics developed hyperglycemic hyperosmolar nonketotic state and this complication was observed in 23.0 % of the patients with diabetes type 2. Microdosing was the mode of insulin administration that predominated in both ketoacidosis and hyperglycemic state cases. Mortality was higher in the hyperglycemic state (67 % and using microdoses in the insulin therapy. Conclusions: diabetic ketoacidosis was the major complication. Mortality from diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state was high and the mode of insulin administration was inadequate in some patients.

Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids.

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Gojda, Jan; Straková, Radka; Plíhalová, Andrea; Tůma, Petr; Potočková, Jana; Polák, Jan; Anděl, Michal

2017-01-01

Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p BCAA tests with no change in the placebo group. An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent. © 2017 S. Karger AG, Basel.

Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

Directory of Open Access Journals (Sweden)

Fangming Xiu

2014-01-01

Full Text Available Hyperglycemia (HG and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

Glucorticoids/insulin ratio in irradiated animal blood

International Nuclear Information System (INIS)

Mizina, T.Yu.

1990-01-01

Similar changes in blood levels of immunoreactive insulin (IRI) and glucocorticoids (GC) were observed in rats, mice and dogs after X-irradiation with lethal doses. The use of the blood GC/IRI ratio indices in estimating the functional status of the exposed organism is discussed

Effect of subcutaneous injection of insulin on 18F-FDG myocardial imaging in diabetics

International Nuclear Information System (INIS)

Tian Yueqin; Shi Rongfang; Guo Feng; Wei Hongxing; Wu Qingwen; Liu Xiujie

2001-01-01

Objective: To evaluate the effect of subcutaneous injection of insulin on 18 F-fluorodeoxyglucose (FDG) myocardial imaging in patients with diabetes mellitus. Methods: Fifty-seven patients with coronary artery disease complicated with diabetes mellitus [mean age (60 +- 8) years] underwent 18 F-FDG PET and dual isotope simultaneous acquisition SPECT with 99 Tc m -MIBI/ 18 F-FDG. Thirty minutes before FDG injection, blood glucose was measured with an automatic glucose analyzer and insulin was subcutaneously used, the dose was adjusted according to the level of blood glucose. Results: Regression analysis showed that the insulin was positively associated with blood glucose. The linear regression analysis showed that the correlation between dose of insulin (y) and blood glucose (x) was good, r 0.8172; the linear regression equation was y = -5.4 + 1.2x. 52 of 57 images were of good quality with 91% success rate. Conclusion: Subcutaneous injection of insulin is an effective and simple method for obtaining cardiac FDG images of good quality in patients with diabetes mellitus

[Hypertension and insulin treatment in type 2 diabetes].

Science.gov (United States)

Ben Salem Hachmi, L; Bouguerra, R; Maatki, O; Smadhi, H; Turki, Z; Hraoui, S; Ben Slama, C

2007-08-01

Insulin resistance and endogenous hyperinsulinemia are associated with blood hypertension. The aim of this analysis is to estimate the prevalence of blood hypertension one year after insulin treatment in type 2 diabetic patients. and methods: This is a retrospective clinical study of 178 type 2 diabetic patients (57 men and 121 women) insulin treated since at least one year. Mean age is 62 +/- 10 years and mean duration of diabetes is ten years. All patients had a clinical and biological control before treatment with insulin and at least three controls during the first year of insulin treatment (anthropometric measurements, blood pressure, fasting plasma glucose, HbA1C). WHO definition of hypertension is used (blood pressure >or=140 / 90 mmHg). At baseline, 48% of patients have hypertension. After insulin treatment, the prevalence of hypertension significantly increase to 53% (94 / 178) three months later (p=0.008), to 54.5% (98 / 178) six months later (p=0.001) and to 55.6% (99 / 178) twelve months later. This increase in hypertension frequency is associated with a significant weight gain and a better blood glucose control. Insulin therapy may contribute to the development of blood hypertension. It promotes renal sodium retention and increases sympathetic nervous system activity. In the UKPDS intensive blood glucose control with insulin is not associated with an increase of macro vascular complications. These observational data suggest the need for further study of the relationship between exogenous insulin and hypertension.

Efficacy and safety of teneligliptin in addition to insulin therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by continuous glucose monitoring.

Science.gov (United States)

Yajima, Takahiro; Yajima, Kumiko; Hayashi, Makoto; Takahashi, Hiroshi; Yasuda, Keigo

2016-12-01

Appropriate glycemic control without hypoglycemia is important in patients with type 2 diabetes on hemodialysis. Teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, can be used without dose adjustment for these patients. Using continuous glucose monitoring (CGM), we evaluated the efficacy and safety of adding teneligliptin to insulin therapy. Twenty-one type 2 diabetes mellitus patients on hemodialysis treated with insulin were enrolled. After the adjustment of insulin dose, their blood glucose level was monitored by CGM. Insulin dose was reduced after teneligliptin administration. The median total daily insulin dose significantly reduced from 18 (9-24)U to 6 (0-14)U (p1). Maximum, mean, and standard deviation of blood glucose level on the hemodialysis and non-hemodialysis days did not change after teneligliptin administration. However, minimum blood glucose level was significantly elevated on the hemodialysis day after teneligliptin administration (from 3.9±1.0mmol/L to 4.4±0.9mmol/L, p=0.040). The incidence of asymptomatic hypoglycemia on the hemodialysis day detected by CGM significantly decreased from 38.1% to 19.0% (p=0.049). Teneligliptin may contribute toward reducing the total daily insulin dose and preventing hypoglycemic events on the hemodialysis day in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of basal-supported oral therapy (BOT) using insulin glargine in patients with poorly controlled type 2 diabetes.

Science.gov (United States)

Suzuki, Daisuke; Umezono, Tomoya; Miyauchi, Masaaki; Kimura, Moritsugu; Yamamoto, Naoyuki; Tanaka, Eitaro; Kuriyama, Yusuke; Sato, Hiroki; Miyatake, Han; Kondo, Masumi; Toyoda, Masao; Fukagawa, Masafumi

2012-07-20

To determine the clinical usefulness of basal-supported oral therapy (BOT) using insulin glargine in Japanese patients with type 2 diabetes. We compared HbA1c levels, body weight, and insulin doses before the introduction of BOT and in the final month of the observation period in 122 patients with type 2 diabetes who received BOT with insulin glargine between October 2007 and July 2009. To exclude the possible effects of seasonal changes in glycemic control, 57 of the 122 patients were followed-up for one year and examined for changes in HbA1c levels, body weight, and insulin dose. Examination of all cases (n=122) showed a significant decrease in HbA1c (before BOT: 8.7±1.8, after: 7.1±1.1%), but no significant change in body weight (before: 63.1±16.1, after: 63.8±17.0 kg). The mean observation period was 10.5±6.4 months. Insulin doses were significantly increased during the study. HbA1c levels improved significantly in patients on non-insulin-secreting drugs (biguanide, α-glucosidase inhibitor and thiazolidine derivatives) than those on insulin-secreting drugs (SU agents and glinides). BOT with insulin glargine is a useful strategy that can achieve good glycemic control in clinical practice without causing serious hypoglycemia. The introduction of BOT before exhaustion of pancreatic β cells may increase its effectiveness.

Insulin Degludec/Insulin Aspart Administered Once Daily at Any Meal, With Insulin Aspart at Other Meals Versus a Standard Basal-Bolus Regimen in Patients With Type 1 Diabetes

Science.gov (United States)

Hirsch, Irl B.; Bode, Bruce; Courreges, Jean-Pierre; Dykiel, Patrik; Franek, Edward; Hermansen, Kjeld; King, Allen; Mersebach, Henriette; Davies, Melanie

2012-01-01

OBJECTIVE To evaluate efficacy and tolerability of a co-formulation of insulin degludec and insulin aspart (IDegAsp) with insulin aspart (IAsp) at other meals compared with basal-bolus therapy using insulin detemir (IDet) and IAsp. RESEARCH DESIGN AND METHODS Adults (n = 548) with type 1 diabetes (A1C 7.0–10.0%; BMI ≤35.0 kg/m2) were randomized 2:1 in a 26-week, multinational, parallel-group, treat-to-target trial to IDegAsp or IDet. IDegAsp was given with a meal, and IDet was given in the evening, with a second (breakfast) dose added if needed. RESULTS Non-inferiority for IDegAsp versus IDet was confirmed; A1C improved by 0.75% with IDegAsp and 0.70% with IDet to 7.6% in both groups (estimated treatment difference IDegAsp − IDet: –0.05% [95% CI –0.18 to 0.08]). There was no statistically significant difference between IDegAsp and IDet in the rates of severe hypoglycemia (0.33 and 0.42 episodes/patient-year, respectively) or overall confirmed (plasma glucose <3.1 mmol/L) hypoglycemia (39.17 and 44.34 episodes/patient-year, respectively). Nocturnal confirmed hypoglycemia rate was 37% lower with IDegAsp than IDet (3.71 vs. 5.72 episodes/patient-year, P < 0.05). Weight gain was 2.3 and 1.3 kg with IDegAsp and IDet, respectively (P < 0.05). Total insulin dose was 13% lower in the IDegAsp group (P < 0.0001). No treatment differences were detected in Health-Related Quality of Life, laboratory measurements, physical examination, vital signs, electrocardiograms, fundoscopy, or adverse events. CONCLUSIONS IDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet, with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy. PMID:22933438

Benefits of combination of insulin degludec and liraglutide are independent of baseline glycated haemoglobin level and duration of type 2 diabetes

DEFF Research Database (Denmark)

Rodbard, Helena W; Buse, John B; Woo, Vincent C

2016-01-01

liraglutide, irrespective of baseline HbA1c. In DUAL II, insulin dose and hypoglycaemia rate were similar with IDegLira and IDeg (maximum dose limited to 50 U) independent of baseline HbA1c. The reduction in HbA1c with IDegLira was independent of disease duration and previous insulin dose but varied depending...... of disease progression stage including baseline glycated haemoglobin (HbA1c), disease duration and previous insulin dose. RESULTS: Across four categories of baseline HbA1c (≤7.5-9.0%), HbA1c reductions were significantly greater with IDegLira (1.1-2.5%) compared with IDeg or liraglutide alone in DUAL I...

Monte Carlo simulation on hard X-ray dose produced in interaction between high intensity laser and solid target

International Nuclear Information System (INIS)

Yang Bo; Qiu Rui; Li Junli; Zhang Hui

2014-01-01

The X-ray dose produced in the interaction between high intensity laser and solid target was studied by simulation using Monte Carlo code. Compared with experimental results, the calculation model was verified. The calculation model was used to study the effect on X-ray dose with different electron temperatures, target materials (including Au, Cu and PE) and thicknesses. The results indicate that the X-ray dose is mainly determined by the electron temperature, and will be affected by the target parameters. X-ray dose of Au is about 1.2 times that of Cu, and is about 5 times that of PE (polyethylene). In addition, compared with other target thickness, when target thickness is the mean range of electron in the target, X-ray dose is relatively large. These results will provide references on evaluating the ionizing radiation dose for laser devices. (authors)

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Mathew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Simeone, Diane M.; Sonnenday, Christopher [Department of Surgery, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Khan, Gazala; Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States)

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) was given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local

The function of androgen/androgen receptor and insulin growth factor‑1/insulin growth factor‑1 receptor on the effects of Tribulus terrestris extracts in rats undergoing high intensity exercise.

Science.gov (United States)

Wu, Yin; Yang, Hongfang; Wang, Xiaohui

2017-09-01

Our previous study demonstrated that treatment with Tribulus terrestris (TT) extracts (120 mg/kg) promoted the muscle weight gain and performance of rats undergoing high intensity exercise. The present study was designed to explore the mechanisms underlying the effect of treatment with TT extracts and the involvement of androgens, the androgen receptor (AR), insulin growth factor‑1 (IGF‑1) and the IGF‑1 receptor (IGF‑1R). A total of 32 Sprague‑Dawley rats were randomly divided into groups as follows: Control; TT, treated with TT extracts, E, high intensity exercise; E+TT, high intensity exercise plus TT treatment. The rats of the E and E+TT groups underwent high intensity exercise with a progressively increasing load for 5 weeks, and TT extracts were intragastrically administered in the TT and E+TT rats 30 min prior to training. TT extract composition was analyzed using ultra‑high performance liquid chromatography‑quadrupole‑time of flight mass spectrometry. Testosterone and IGF‑1 plasma levels and AR, IGF‑1R and myosin heavy chain (MHC) protein levels in muscles were determined by ELISA and western blotting, respectively. The saponins tigogenin and diosgenin comprised ~71.35% of the total peak area. Compared with the E group, TT extracts increased the testosterone and IGF‑1 plasma levels, and AR, IGF‑1R and MHC protein levels in the gastrocnemius of rats undergoing high intensity exercise, accompanied with increased body weight and gastrocnemius weight. In conclusion, the effect of TT extracts on the performance of high intensity exercise rats may be attributed to increased levels of circulating testosterone and IGF‑1 and increased AR and IGF‑1R protein expression levels in the gastrocnemius, resulting in increased muscle weight and increased MHC in the gastrocnemius. The present study provided preliminary evidence supporting the use of TT extracts as a dietary supplement for the promotion of skeletal muscle mass increase and the

An audit of the insulin-tolerance test in 255 patients with pituitary disease

DEFF Research Database (Denmark)

Lange, Martin; Svendsen, Ole L; Skakkebaek, Niels E

2002-01-01

The insulin-tolerance test (ITT) is currently considered to be the gold standard for evaluating adults suspected of GH deficiency (GHD). The aim of this study was to determine factors that may influence nadir blood glucose (BG) when using a mean insulin dose of 0.1 IU/kg body weight. Furthermore...

Implantable batteryless device for on-demand and pulsatile insulin administration

Science.gov (United States)

Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

2017-04-01

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Sodium arsenite impairs insulin secretion and transcription in pancreatic β-cells

International Nuclear Information System (INIS)

Diaz-Villasenor, Andrea; Sanchez-Soto, M. Carmen; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia; Hiriart, Marcia

2006-01-01

Human studies have shown that chronic inorganic arsenic (iAs) exposure is associated with a high prevalence and incidence of type 2 diabetes. However, the mechanism(s) underlying this effect are not well understood, and practically, there is no information available on the effects of arsenic on pancreatic β-cells functions. Thus, since insulin secreted by the pancreas plays a crucial role in maintaining glucose homeostasis, our aim was to determine if sodium arsenite impairs insulin secretion and mRNA expression in single adult rat pancreatic β-cells. Cells were treated with 0.5, 1, 2, 5 and 10 μM sodium arsenite and incubated for 72 and 144 h. The highest dose tested (10 μM) decreased β-cell viability, by 33% and 83%, respectively. Insulin secretion and mRNA expression were evaluated in the presence of 1 and 5 μM sodium arsenite. Basal insulin secretion, in 5.6 mM glucose, was not significantly affected by 1 or 5 μM treatment for 72 h, but basal secretion was reduced when cells were exposed to 5 μM sodium arsenite for 144 h. On the other hand, insulin secretion in response to 15.6 mM glucose decreased with sodium arsenite in a dose-dependent manner in such a way that cells were no longer able to distinguish between different glucose concentrations. We also showed a significant decrease in insulin mRNA expression of cells exposed to 5 μM sodium arsenite during 72 h. Our data suggest that arsenic may contribute to the development of diabetes mellitus by impairing pancreatic β-cell functions, particularly insulin synthesis and secretion

Comparison of solubilized and purified plasma membrane and nuclear insulin receptors

International Nuclear Information System (INIS)

Wong, K.Y.; Hawley, D.; Vigneri, R.; Goldfine, I.D.

1988-01-01

Prior studies have detected biochemical and immunological differences between insulin receptors in plasma membranes and isolated nuclei. To further investigate these receptors, they were solubilized in Triton X-100 partially purified by wheat germ agglutinin-agarose chromatography. In these preparations, the nuclear and plasma membrane receptors had very similar pH optima (pH 8.0) and reactivities to a group of polyclonal antireceptor antibodies. Further, both membrane preparations had identical binding activities when labeled insulin was competed for by unlabeled insulin (50% inhibition at 800 pM). Next, nuclear and plasma membranes were solubilized and purified to homogeneity by wheat germ agglutinin-agarose and insulin-agarose chromatography. In both receptors, labeled insulin was covalently cross-linked to a protein of 130 kilodaltons representing the insulin receptor α subunit. When preparations of both receptors were incubated with insulin and then adenosine 5'-[γ- 32 P]triphosphate, a protein of 95 kilodaltons representing the insulin receptor β subunit was phosphorylated in a dose-dependent manner. These studies indicate, therefore, that solubilized plasma membrane and nuclear insulin receptors have similar structures and biochemical properties, and they suggest that they are the same (or very similar) proteins

Inverse association between soya food consumption and insulin resistance in Japanese adults.

Science.gov (United States)

Nakamoto, Mariko; Uemura, Hirokazu; Sakai, Tohru; Katsuura-Kamano, Sakurako; Yamaguchi, Miwa; Hiyoshi, Mineyoshi; Arisawa, Kokichi

2015-08-01

The purpose of the present study was to examine the association between soya food consumption and insulin resistance using baseline data of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan. This cross-sectional study included 1274 subjects, aged 34-70 years at baseline, living in Tokushima Prefecture between 2008 and 2013. Fasting blood samples were collected and information on lifestyle characteristics including soya food intake and medical history were obtained using a structured self-administered questionnaire. The homeostasis model assessment of insulin resistance (HOMA-IR) was measured and those with HOMA-IR ≥ 2.5 were defined as having insulin resistance. Multiple logistic regression models were used to analyse the association between soya product intake and the prevalence of insulin resistance. Rural communities located in Tokushima Prefecture, Japan, between 2008 and 2013. A total of 1148 adults (565 men and 583 women), aged 34-70 years. The frequency of intake of miso soup, total non-fried soya products and total soya products showed significant inverse dose-response relationships with insulin resistance, after adjustments for potential confounders. When soya product intake was calculated as soya protein and isoflavone, the odds ratios of insulin resistance decreased significantly as the estimated intake of soya protein increased. Furthermore, significant inverse dose-response relationships were observed for total non-fried soya products and total soya products, after adjustment for total vegetable or total fibre consumption. The present results indicate that the intake of soya products and non-fried soya products is associated with reduced insulin resistance in the Japanese population.

Basal and insulin-stimulated skeletal muscle sugar transport in endotoxic and bacteremic rats

International Nuclear Information System (INIS)

Westfall, M.V.; Sayeed, M.M.

1988-01-01

Membrane glucose transport with and without insulin was studied in soleus muscle from 5-h endotoxic rats (40 mg/kg Salmonella enteritidis lipopolysaccharide), and in soleus and epitrochlearis muscles from 12-h bacteremic (Escherichia coli, 4 X 10(10) CFU/kg) rats. Glucose transport was measured in muscles by evaluating the fractional efflux of 14 C-labeled 3-O-methylglucose ( 14 C-3-MG) after loading muscles with 14 C-3-MG. Basal 3-MG transport was elevated in soleus muscles from endotoxic as well as in soleus and epitrochlearis muscles from bacteremic rats compared with time-matched controls. Low insulin concentrations stimulated 14 C-3-MG transport more in bacteremic and endotoxic rat muscles than in controls. However, sugar transport in the presence of high insulin dose was attenuated in soleus and epitrochlearis muscles from bacteremic rats and soleus muscles from endotoxic rats compared with controls. Analysis of the dose-response relationship with ALLFIT revealed that the maximal transport response to insulin was significantly decreased in both models of septic shock. Sensitivity to insulin (EC50) was increased in endotoxic rat muscles, and a somewhat similar tendency was observed in bacteremic rat soleus muscles. Neural and humoral influences and/or changes in cellular metabolic energy may contribute to the increase in basal transport. Shifts in insulin-mediated transport may be due to alterations in insulin-receptor-effector coupling and/or the number of available glucose transporters

Enhanced Glucose Tolerance and Pancreatic Beta Cell Function by Low Dose Aspirin in Hyperglycemic Insulin-Resistant Type 2 Diabetic Goto-Kakizaki (GK Rats

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Layla Amiri

2015-07-01

Full Text Available Background/Aim: Type 2 diabetes is the most common metabolic disorder, characterized by insulin resistance and pancreatic islet beta-cell failure. The most common complications associated with type 2 diabetes are hyperinsulinemia, hyperglycemia, hyperlipidemia, increased inflammatory and reduced insulin response. Aspirin (ASA and other non-steroidal anti-inflammatory drugs (NSAIDs have been associated with the prevention of diabetes, obesity and related cardiovascular disorders. Aspirin has been used in many clinical and experimental trials for the prevention of diabetes and associated complications. Methods: In this study, five month old Goto-Kakizaki (GK rats, which showed signs of mild hyperglycemia (fasting blood glucose 80-95 mg/dl vs 55-60 mg/dl Wistar control rats were used. Two subgroups of GK and Wistar control rats were injected intraperitoneally with 100 mg aspirin/kg body weight/ day for 5 weeks. Animals were sacrificed and blood and tissues were collected after performing glucose tolerance (2 h post 2g IP glucose ingestion tests in experimental and control groups. Results: Aspirin caused a moderate decrease in hyperglycemia. However, we observed a significant improvement in glucose tolerance after ASA treatment in GK rats compared to the nondiabetic Wistar rats. Also, the ASA treated GK rats exhibited a significant decrease in insulinemia. ASA treatment also caused a marked reduction in the pro-inflammatory prostaglandin, PGE2, which was significantly higher in GK rats. On the other hand, no significant organ toxicity was observed after ASA treatment at this dose and time period. However, the total cholesterol and lipoprotein levels were significantly increased in GK rats, which decreased after ASA treatment. Immunofluorescence staining for insulin/glucagon secreting pancreatic cells showed improved beta-cell structural and functional integrity in ASA-treated rats which was also confirmed by SDS-PAGE and Western blot analysis

Neonatal doses from X ray examinations by birth weight in a neonatal intensive care unit

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Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T

2003-07-01

The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)

Neonatal doses from X ray examinations by birth weight in a neonatal intensive care unit

International Nuclear Information System (INIS)

Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T.

2003-01-01

The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)

Behaviours, thoughts and perceptions around mealtime insulin usage and wastage among people with type 1 and type 2 diabetes mellitus: A cross-sectional survey study.

Science.gov (United States)

Van Brunt, Kate; Pedersini, Riccardo; Rooney, Jillian; Corrigan, Sheila M

2017-04-01

People with diabetes who use mealtime insulin (MTI) were surveyed about insulin wastage and injection habits when insufficient insulin remains in a disposable prefilled pen/cartridge to administer a full dose in a single injection. Cross-sectional, online, self-reported survey of MTI usage/wastage behaviour in 400 adults with type 1 (n=120) or type 2 (n=280) diabetes mellitus administering >20units/day of MTI via 100units/ml prefilled pens/cartridges for ⩾1month, conducted in France, Germany, Italy and UK. Participants' mean±standard deviation age was 54.5±12.2years, body mass index was 29.9±7.2kg/m 2 and duration of MTI therapy was 8.6±7.8years. They administered 3.7±5.9 injections/day with meals, using 11.3±18.0 prefilled pens/cartridges per month. Overall, 63.5% split the dose across two prefilled pens/cartridges (i.e. administered two injections to obtain a full dose), 15.0% used just what remained in their current pen (i.e. took a lower-than-prescribed dose) and 36.3% discarded prefilled pens/cartridges still containing insulin (i.e. took full dose with new pen). The latter participants discarded a mean 5.5±8.2 prefilled pens/cartridges monthly still containing insulin, each containing 8.6±8.7 units of insulin. Participants who wasted insulin considered it frustrating, time-consuming and painful to inject twice. Patients taking >20units/day MTI can find transitions between insulin pens challenging. This study highlights the need to identify ways of improving transitions between pens to make transitions easier for insulin users, which could potentially improve adherence to prescribed doses and reduce waste. Copyright © 2016 Eli Lilly and Company. Published by Elsevier B.V. All rights reserved.

Metabolic effects of resistance or high-intensity interval training among glycemic control-nonresponsive children with insulin resistance.

Science.gov (United States)

Álvarez, C; Ramírez-Campillo, R; Ramírez-Vélez, R; Martínez, C; Castro-Sepúlveda, M; Alonso-Martínez, A; Izquierdo, M

2018-01-01