Beta-cell Function (beta-cell + function)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Beta-cell Function

  • pancreatic beta-cell function


  • Selected Abstracts


    The Effect of Rosuvastatin on Insulin Sensitivity and Pancreatic Beta-Cell Function in Nondiabetic Renal Transplant Recipients

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
    A. Sharif
    Interventions to attenuate abnormal glycemia posttransplantation are required. In addition, surrogate markers of declining glycemic control are valuable. Statins may have pleiotropic properties that attenuate abnormal glucose metabolism. We hypothesized statins would improve glucose metabolism and HbA1c would be advantageous as a surrogate for worsening glycemia. We conducted a prospective, randomized, placebo controlled, crossover study in 20 nondiabetic renal transplant recipients at low risk for NODAT and compared effects of rosuvastatin on insulin secretion/sensitivity. Mathematical model analysis of an intravenous glucose tolerance test determined first-phase insulin secretion, insulin sensitivity and disposition index. Second-phase insulin secretion was determined with a meal tolerance test. Biochemical/clinical parameters were also assessed. Rosuvastatin significantly improved total cholesterol (,30%, p < 0.001), LDL cholesterol (,44%, p < 0.001) and triglycerides (,19%, p = 0.013). C-reactive protein decreased but failed to achieve statistical significance (,31%, p = 0.097). Rosuvastatin failed to influence any glycemic physiological parameter, although an inadequate timeframe to allow pleiotropic mechanisms to clinically manifest raises the possibility of a type II statistical error. On multivariate analysis, glycated hemoglobin (HbA1c) correlated with disposition index (R2= 0.201, p = 0.006), first-phase insulin secretion (R2= 0.106, p = 0.049) and insulin sensitivity (R2= 0.136, p = 0.029). Rosuvastatin fails to modify glucose metabolism in low-risk patients posttransplantation but HbA1c is a useful surrogate for declining glycemic control. [source]


    Beta-cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetes

    DIABETIC MEDICINE, Issue 7 2001
    M. J Taverna
    Abstract Background and aims Secondary failure to oral hypoglycaemic agents, a common evolution of long-standing Type 2 diabetes, is usually assessed by non-standardized indices requiring fine clinical assessment, including hyperglycaemia resistant to maximum doses of sulphonylureas despite appropriate diet and follow-up. The goal of this study was to evaluate if HOMA, a modelized plasma insulin/glucose ratio allowing simple evaluation of residual insulin secretion and sensitivity, is a better predictor of the insulin requiring stage than clinical indices. Materials and methods HOMA was measured in 84 Type 2 diabetic patients aged 58 sd 6 years, with diabetes duration 11 4 years, hospitalized because of hyperglycaemia resistant to maximal doses of sulphonylureas (e.g. glibenclamide ,,15 mg/day), with no apparent external reason for hyperglycaemia. Despite reinforced appropriate diet recommendations, 62 of these patients remained hyperglycaemic (insulin-requiring group). Results Age, duration of diabetes, body mass index (BMI) and HOMA value for insulin sensitivity (71 6% vs. 76 7%, normal values 59,161%) were comparable in the two groups. HbA1c was higher (10.0 0.2% vs. 8.3 0.3%, P < 0.001) and HOMA insulin secretion values lower (25 2% vs. 43 6%, normal values 70,150%, P < 0.01) in the insulin-requiring group. Of the following potential predictors: HbA1c >,8%, duration of diabetes ,,10 years, HbA1c combined with diabetes duration, insulin sensitivity ,,40%, insulin secretion ,,20%, the latter showed the best positive predictivity (86% patients with low insulin secretion were insulin-requiring). Conclusions (i) HOMA is a simple and good predictor of the insulin-requiring stage in Type 2 diabetes mellitus; (ii) this stage of diabetes is characterized by a further decline of insulin secretion rather than of insulin sensitivity. Diabet. Med. 18, 584,588 (2001) [source]


    Beta-cell function and insulin sensitivity contribute to the shape of plasma glucose curve during an oral glucose tolerance test in non-diabetic individuals

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2005
    M. Kanauchi
    Summary To clarify whether beta-cell function and/or insulin resistance contributes to the shape of plasma glucose curve during an oral glucose tolerance test (OGTT), we investigated 583 Japanese subjects with normal glucose tolerance (NGT, n = 306) or impaired glucose tolerance (IGT, n = 277). Each subject was subdivided into three shapes of plasma glucose curve as follows: monophasic pattern (M type), biphasic pattern (B type) and two peaks (T type). Homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and insulinogenic index were assessed by plasma glucose and insulin concentrations obtained at fasting or during an OGTT. There was a greater proportion of M type in the IGT group (M = 80.9%, B = 15.5% and T = 3.6%), whereas the prevalence of B and T types was much higher in the NGT group (M = 66.6%, B = 26.5% and T = 6.9%). There were significant differences in the proportions of shape types between the NGT and IGT groups (p = 0.0006). Among the NGT category, insulin sensitivity was significantly higher in the B type than in the M type, and beta-cell function adjusted for insulin resistance was significantly higher in the B and T types than in the M type. Among the IGT category, no significant differences were seen among the three shape types with respect to insulin sensitivity, but the beta-cell function adjusted for insulin resistance was significantly lower in the M type than in the B and T types. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of the shape of plasma glucose curve in Japanese subjects. [source]


    Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

    PEDIATRIC DIABETES, Issue 1 2010
    Claudia Brufani
    Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. Methods: The study group included 510 overweight/obese subjects (3,18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta-cell function was estimated by insulinogenic index. Fat mass was measured by dual-energy x-ray absorptiometry. Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA-IR and glucose-stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA-IR = 4.4 2.5 vs. 3.4 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents. [source]


    Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptin

    DIABETES OBESITY & METABOLISM, Issue 10 2010
    R. Retnakaran
    Aim: Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned that short-term IIT could enable evaluation of the beta-cell protective capacity of OADs, free from confounding hyperglycaemia. We applied this strategy to assess the effect of sitagliptin on beta-cell function. Methods: In this pilot study, 37 patients with T2DM of 6.0 + 6.4 years duration and A1c 7.0 + 0.8% on 0,2 OADs were switched to 4,8 weeks of IIT consisting of basal detemir and premeal insulin aspart. Subjects achieving fasting glucose <7.0 mmol/l 1 day after completing IIT (n = 21) were then randomized to metformin with either sitagliptin (n = 10) or placebo (n = 11). Subjects were followed for 48 weeks, with serial assessment of beta-cell function [ratio of AUCCpep to AUCgluc over Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (AUCCpep/gluc/HOMA-IR)] on 4-h meal tests. Results: During the study, fasting glucagon-like-peptide-1 was higher (p = 0.003) and A1c lower in the sitagliptin arm (p = 0.016). Nevertheless, although beta-cell function improved during the IIT phase, it declined similarly in both arms over time (p = 0.61). By study end, AUCCpep/gluc/HOMA-IR was not significantly different between the placebo and sitagliptin arms (median 71.2 vs 80.4; p = 0.36). Conclusions: Pretreatment IIT can provide a useful strategy for evaluating the beta-cell protective capacity of diabetes interventions. In this pilot study, improved A1c with sitagliptin could not be attributed to a significant effect on preservation of beta-cell function. [source]


    Effects of exendin-4 on islets from type 2 diabetes patients

    DIABETES OBESITY & METABOLISM, Issue 6 2008
    R. Lupi
    Exendin-4 is a dipeptidyl peptidase IV (DPP-IV)-resistant glucagon-like peptide1 (GLP-1) mimetic and its synthetic counterpart, exenatide, is being used in the therapy of type 2 diabetes (T2DM). No information, however, is currently available as for the direct action of exendin-4 on human T2DM islets. In the present study, we exposed pancreatic islets prepared from non-diabetic and T2DM subjects to exendin-4 for 48 h and found that the compound had several, direct beneficial actions on insulin secretion and the expression of genes involved in beta-cell function and differentiation. [source]


    Immuno-intervention and preservation of beta-cell function in type 1 diabetes

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2007
    Paolo Pozzilli
    No abstract is available for this article. [source]


    Higher fasting insulin but lower fasting C-peptide levels in African Americans in the US population,

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2002
    Maureen I. Harris
    Abstract Background Fasting serum insulin and fasting serum C-peptide are risk factors for developing type 2 diabetes. Because of the higher incidence of type 2 diabetes in African Americans and Hispanic Americans, it is likely that these groups may differ from non-Hispanic whites in their levels of insulin and C-peptide. Methods We analyzed data from a nationally representative sample of adults in the US population for whom sociodemographic, clinical, and laboratory information were obtained. The data were used to describe distributions of fasting insulin and fasting C-peptide in non-Hispanic white, non-Hispanic black, and Mexican American men and women aged ,20 years without a medical history of diabetes. Results Among men, Mexican Americans had higher insulin values than non-Hispanic whites and blacks. Among women, both Mexican Americans and blacks had higher insulin values than whites. For C-peptide, differences by sex and race-ethnicity paralleled those seen for fasting insulin with the exception that black men had significantly lower C-peptide values than whites and Mexican Americans. After adjustment for age, fasting plasma glucose (FPG), body mass index (BMI), and waist-to-hip ratio (WHR), the higher levels for insulin in blacks and Mexican Americans remained; both black men and women had significantly lower C-peptide values than whites and Mexican Americans. The molar ratio of fasting C-peptide to fasting insulin was similar for men and women in each race-ethnic group. However, blacks had substantially lower ratios than whites and Mexican Americans. Conclusions We found wide variations in fasting insulin and fasting C-peptide levels by race and ethnicity in US adults that were not explained by confounding factors, primarily measures of obesity. Most notably, the higher fasting insulin and lower fasting C-peptide levels in blacks implies that there is a derangement in insulin clearance and an impairment in beta-cell function in blacks compared with whites and Mexican Americans. Published in 2002 by John Wiley & Sons, Ltd. [source]


    An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized study

    DIABETIC MEDICINE, Issue 6 2004
    T. M. Wallace
    Abstract Aims To investigate the effect of treatment with pioglitazone on beta-cell function and insulin sensitivity in Type 2 diabetes. Methods Thirty subjects with diet-controlled Type 2 diabetes were randomized to 3 months treatment with pioglitazone (n = 19) or placebo (n = 11). All subjects underwent basal sampling for homeostatic model assessment (HOMA), followed by an intravenous glucose tolerance test and hyperglycaemic clamp, followed by an euglycaemic hyperinsulinaemic clamp; at baseline and after treatment. Results All results are expressed as mean (sem). Pioglitazone increased basal insulin sensitivity by 24.7% (7.8) HOMA-%S vs. 2.1% (5.9) in the placebo group (P = 0.02). Stimulated insulin sensitivity, M/I, increased in the pioglitazone group compared with placebo: +15.1 (2.8) l kg,1 min,1 vs. +3.2 (2.9) l kg,1 min,1, respectively (P = 0.009). Pioglitazone increased adiponectin by 39.3 (6.3), ng/ml compared with a decrease of 0.8 (1.3) ng/ml with placebo (P = 0.00004). HOMA-%B increased with pioglitazone, +11.5% (4.8) vs. ,2.0% (4.8) with placebo (P = 0.049), but there was no change in stimulated beta-cell function as determined by hyperglycaemic clamps. There was a significant reduction in the proinsulin/insulin ratio in the pioglitazone group, ,0.057 (0.02) compared with placebo, +0.004 (0.02) (P = 0.03). There was a significant reduction in HbA1c of 0.6% (0.1) in the pioglitazone group compared with placebo (P = 0.003). There was no significant weight gain associated with pioglitazone therapy: +0.7 (sem 0.6) kg vs. +1.1 (sem 0.5) kg in placebo group (P = NS). Conclusions Basal beta-cell function and insulin sensitivity improved following pioglitazone therapy. The improvement in proinsulin to insulin ratio suggests that beta-cells are under less stress. [source]


    Insulin-like growth factors and pancreas beta cells

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2004
    T. W. Van Haeften
    Abstract Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their signalling pathways for pancreas beta-cell development, and for type 2 diabetes. Insulin-like growth factor-I signalling has a lot in common with insulin signalling, and is involved in diverse cellular effects such as antiapoptosis, protein synthesis, cell growth and mitogenesis. Insulin-like growth factor-II can be bound by the insulin receptor A subtype and the IGF-1 receptor, which may explain its antiapoptotic effect. Various knock-out model studies indicate that absence of IGF-I or the IGF-1 receptor is critical for foetal and postnatal growth. Similarly, knock-out models of post-receptor molecules (such as IRS-2) point to the physiological role of IGFs for pancreas beta-cell development. A beta-cell-specific IGF-1 receptor knock out model indicates the importance of IGF-I for beta-cell function. The Goto-Kakizaki (GK) rat, a model for diabetes, has insufficient beta-cell development, which may be related to its defective IGF-II synthesis. As normal pancreas beta cells adapt to the prevailing insulin resistance with increasing beta-cell function, it is possible that insulin resistance interacts with IGF signalling in pancreas beta cells. [source]


    Liraglutide: can it make a difference in the treatment of type 2 diabetes?

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2010
    J. Unger
    Summary Despite advances in the management of type 2 diabetes, glycaemic control remains suboptimal for many patients because of the complexities of disease progression and the need to balance improved glycaemic control against adverse treatment effects, particularly weight gain and hypoglycaemia. Thus, the development of new antidiabetes therapies continues in earnest. Incretin hormones have been the recent focus of research, as they account for up to 70% of the insulin response following a meal. There is also a high concordance between the physiological actions of one hormone, glucagon-like peptide-1 (GLP-1), and the therapeutic needs of patients. As native human GLP-1 has a half life of only approximately 2 min, researchers have developed molecules that act as GLP-1 receptor agonists or inhibit the enzyme responsible for GLP-1 degradation (dipeptidyl peptidase-4). Liraglutide, a human GLP-1 analogue sharing 97% of its amino acid sequence identity with native GLP-1, has been approved for use as monotherapy (not in Europe) and in combination with selected oral agents. In this supplement, we summarise key liraglutide data, offer practical insight into what we might expect of liraglutide in clinical use and examine selected case studies. For reasons of the safety and efficacy of GLP-1 receptor agonists, many thought leaders believe that these will become background therapy for majority of patients in the coming years. This supplement will serve as a resource from which readers can extract information concerning the potential benefits for patients who are overweight, losing pancreatic beta-cell function and drifting towards the ravaging effects of chronic hyperglycaemia. [source]


    Irbesartan has no short-term effect on insulin resistance in hypertensive patients with additional cardiometabolic risk factors (i-RESPOND)

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010
    K. G. Parhofer
    Summary Aims:, Intervention studies have shown that angiotensin receptor blockers (ARB) may reduce the incidence of type 2 diabetes mellitus. It is currently unclear whether short-term therapy with ARBs affects metabolic parameters. Methods:, i-RESPOND, a randomised, controlled, multicentre, double-blind study evaluated the effect of 16 weeks of irbesartan vs. hydrochlorothiazide (HCTZ) on insulin resistance as well as on lipid and inflammatory parameters in hypertensive subjects with metabolic syndrome. Patients received irbesartan (150 mg/d; n = 211) or HCTZ (12.5 mg/d; n = 215), titrated to 300 mg/day and 25 mg/day respectively. In a second part of the study (weeks 16,28), patients initially randomised to irbesartan received additional HCTZ and vice versa. Results:, At week 16 both irbesartan and HCTZ had no effect on insulin resistance measured by the Matzuda index and beta-cell function. Similarly, in the second part of the study (week 16,28) no differences between irbesartan and HCTZ with respect to glucose metabolism were observed. However, irbesartan induced beneficial changes in high-sensitivity-C-reactive protein (hs-CRP) (irbesartan: ,5.5 5.2%; HCTZ + 19.9 6.5%, p = 0.0024) and in urinary albumin/creatinine ratio (ACR) (irbesartan: ,13%; HCTZ + 9%; p = 0.0041) compared with HCTZ despite a similar decrease in blood pressure in both treatment groups. Irbesartan and HCTZ were well tolerated and adverse events were comparable. Conclusion:, Irbesartan did not show significant favourable effects on insulin resistance compared with HCTZ in this study; however, may have beneficial effects on inflammation and microalbuminuria in hypertensive patients with metabolic syndrome. [source]


    Treatment of type 2 diabetes with glucagon-like peptide-1 receptor agonists

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2009
    K. B. Hansen
    Summary The incretin system is an area of great interest for the development of new therapies for the management of type 2 diabetes. Existing antidiabetic drugs are often insufficient at getting patients to glycaemic goals. Furthermore, current treatment modalities are not able to prevent the continued ongoing decline in pancreatic beta-cell function and, lastly, they have a number of side effects including hypoglycaemia and weight gain. Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of pharmacological agents, which improve glucose homeostasis in a multifaceted way. Their effects include potentiation of glucose-stimulated insulin secretion, glucose-dependent inhibition of glucagon secretion and reduction in gastric emptying, appetite, food intake and body weight. Additionally, preclinical data suggest that they may preserve beta-cell mass and function. The incidence of hypoglycaemia with GLP-1 receptor agonists is low, the compounds have clinically relevant effects on body weight, and data are suggesting beneficial effects on cardiovascular risk factors. Exenatide was released in 2005 for the treatment of type 2 diabetes and liraglutide is expected to be approved by the Food and Drug Administration in US and the European Medical Agency in Europe for use in 2009. In this review, the available data on the two drugs are presented and discussed. [source]


    Beta-cell function and insulin sensitivity contribute to the shape of plasma glucose curve during an oral glucose tolerance test in non-diabetic individuals

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2005
    M. Kanauchi
    Summary To clarify whether beta-cell function and/or insulin resistance contributes to the shape of plasma glucose curve during an oral glucose tolerance test (OGTT), we investigated 583 Japanese subjects with normal glucose tolerance (NGT, n = 306) or impaired glucose tolerance (IGT, n = 277). Each subject was subdivided into three shapes of plasma glucose curve as follows: monophasic pattern (M type), biphasic pattern (B type) and two peaks (T type). Homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and insulinogenic index were assessed by plasma glucose and insulin concentrations obtained at fasting or during an OGTT. There was a greater proportion of M type in the IGT group (M = 80.9%, B = 15.5% and T = 3.6%), whereas the prevalence of B and T types was much higher in the NGT group (M = 66.6%, B = 26.5% and T = 6.9%). There were significant differences in the proportions of shape types between the NGT and IGT groups (p = 0.0006). Among the NGT category, insulin sensitivity was significantly higher in the B type than in the M type, and beta-cell function adjusted for insulin resistance was significantly higher in the B and T types than in the M type. Among the IGT category, no significant differences were seen among the three shape types with respect to insulin sensitivity, but the beta-cell function adjusted for insulin resistance was significantly lower in the M type than in the B and T types. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of the shape of plasma glucose curve in Japanese subjects. [source]


    New developments in incretin-based therapies: The current state of the field

    JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 2009
    CDE Diabetes Nurse Educator, Carolyn Robertson APRN
    Abstract Purpose: To update readers on developments in incretin therapies since the previous JAANP supplement in 2007; specifically, to describe clinical data for currently available incretin-based therapies as well as those under consideration by regulatory agencies. Data source: Medline search for peer-reviewed publications. Conclusions: Incretin-based therapies have pharmacologic properties that avoid some key limitations of previous treatments, such as hypoglycemia and weight gain. Certain agents also lower blood pressure and have the potential to reduce cardiovascular risk. The insulin-secreting action of incretin-based therapies only occurs under hyperglycemic conditions, thus minimizing the risk of hypoglycemia, unless combined with a sulfonylurea. The DPP-4 inhibitors are orally administered and demonstrate modest A1c reductions (0.6%,0.8%); the best results occur when combined with metformin. Glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and exenatide have shown greater A1c reductions (typically , 1.1% and as high as 1.7%), and these agents have beneficial ancillary effects, including weight and systolic blood pressure reduction. Both DPP-4 inhibitors and GLP-1 receptor agonists have shown the ability to improve pancreatic beta-cell function in early studies. Implications for practice: Data are provided on the efficacy and tolerability of approved incretin therapies, and on treatments currently in regulatory review, in order to inform readers and guide their practice. [source]


    First phase insulin release and glucose tolerance in children with Fanconi anemia after hematopoietic cell transplantation

    PEDIATRIC BLOOD & CANCER, Issue 2 2009
    Lynda E. Polgreen MD
    Abstract Background Fanconi anemia (FA) is an autosomal and X-linked recessive disease of chromosomal instability, which results in bone marrow failure. Children with FA have been shown to have an increased risk of diabetes mellitus (DM). Procedure A cross-sectional study of glucose and insulin metabolism was conducted in 17 children with FA who had undergone hematopoietic cell transplantation (HCT) at the University of Minnesota. First phase insulin release (FPIR) was determined by intravenous glucose tolerance test (IVGTT). Oral glucose tolerance test (OGTT), lipid panel, blood pressure, and medical history were reviewed for additional metabolic abnormalities. Results Seventeen FA participants, median age 11.3 (range 5.5,17.6) years, were evaluated. IVGTT identified three separate groups: low FPIR, normal FPIR, and high FPIR. Those with low FPIR were more likely to have low BMI, but had normal glucose levels. Those with high FPIR, had high BMI, elevated lipids, and body fat. One patient with normal FPIR had impaired glucose tolerance and another with normal FPIR had impaired fasting glucose. No participant was diagnosed with DM by fasting glucose, 2 hr glucose during OGTT, or hemoglobin A1C. Conclusions The majority of children with FA had normal glucose tolerance and normal beta-cell function after HCT. Two small subsets of patients had lower than expected and higher than expected FPIR. The clinical significance of these differences is not yet known given the normal glucose tolerance and fasting glucose levels in these two groups. Pediatr Blood Cancer 2009;53:191,196. 2009 Wiley-Liss, Inc. [source]


    Limitations of first-phase insulin response to evaluate insulin secretion in children

    PEDIATRIC DIABETES, Issue 1 2000
    WS Cutfield
    The first-phase insulin response (FPIR) is a widely used method to evaluate beta-cell function during the prediabetic phase of evolving type 1 diabetes mellitus (DM). The aim of the present study was to evaluate the influence of clinical and methodological variables on FPIR in normal children and adolescents. Children and adolescents who were first-degree relatives of those with type 1 DM and healthy young adults were studied. All subjects were islet cell antibody-negative. A FPIR test was performed on all subjects while fasting. Insulin samples were drawn at 0, 1, 2, 3, 4, 5, 6, 8, and 10 min after 0.3 g/kg of dextrose. FPIR(1,10) was calculated as the area under the FPIR curve corrected for baseline. Eighty-five subjects aged 4,22 yr were studied, 43 of whom were pre-pubertal, 24 pubertal, and 18 post-pubertal. FPIR(1,10) values were lower in the pre-pubertal group when compared to either the pubertal and post-pubertal groups (415 [179,965, 2SD], 756 [256,2,223] and 684 [235,1,180] mU/L, respectively; p<0.05). Obese subjects had a higher FPIR than non-obese subjects (856 vs. 520 mU/L; p<0.005). Despite correcting for the influence of puberty and obesity, there remained considerable unaccounted variability in FPIR(1,10) (R=0.46). Further variables found to influence FPIR(1,10) were: fasting insulin level (r2=0.49); weight for length index (r2=0.38); peak blood glucose level (r2=0.38, all p<0.001); and pre-pubertal age (r2=0.20, p<0.05). Conclusion: FPIR exhibited wide inter-subject variability and was influenced by a number of clinical and methodological factors that make interpretation more difficult without more specifically defined standards. [source]


    When and how to start insulin therapy in type 2 diabetes

    PRESCRIBER, Issue 19 2007
    Anne Kilvert MD
    Most patients with type 2 diabetes will eventually require insulin due to the progressive decline in beta-cell function. Dr Kilvert describes when to introduce insulin in type 2 diabetes and how the regimen needs to be tailored to the individual patient. Copyright 2007 Wiley Interface Ltd [source]


    Influence of Sirolimus on Cyclosporine-Induced Pancreas Islet Dysfunction in Rats

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009
    H. K. Song
    This study was performed to investigate the effect of sirolimus (SRL) on cyclosporine (CsA)-induced pancreatic islet dysfunction in rats. Three separate studies were performed. First, diabetogenic effect of SRL was evaluated with three different doses (0.15, 0.3 and 0.6 mg/kg). Second, rats were treated with SRL (0.3 mg/kg) with or without CsA (15 mg/kg) for 4 weeks. Third, rats were treated with CsA for 4 weeks, and then switched to SRL for 4 weeks. The effect of SRL on CsA-induced pancreatic islet dysfunction was evaluated by an intraperitoneal glucose tolerance test, plasma insulin concentration, HbA1c level, HOMA-R index, immunohistochemistry of insulin and pancreatic beta islet cell mass. The SRL treatment increased blood glucose concentration in a dose-dependent manner. The combined treatment with SRL and CsA increased blood glucose concentration, Hemoglobin A1c (HbA1c) level, HOMA-R [fasting insulin (mU/mL) x fasting glucose (mmol/L)]/22.5] index and decreased plasma insulin concentration, immunoreactivity of insulin and pancreatic beta islet cell mass compared with rats treated with CsA. CsA withdrawal for 4 weeks improved pancreatic beta-cell function and structure. However, conversion from CsA to SRL further increased blood glucose levels compared with the rats converted from vehicle to SRL. The results of our study demonstrate that SRL is diabetogenic and aggravates CsA-induced pancreatic islet dysfunction. [source]


    The effect of growth hormone treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, small for gestational age children

    CLINICAL ENDOCRINOLOGY, Issue 1 2009
    Sandra W. K. De Kort
    Summary Context, We previously reported that short, small for gestational age (SGA) children who were born preterm have a lower body fat percentage and a higher blood pressure, insulin secretion and disposition index than short SGA children born at term. Whether preterm birth also influences these parameters during GH treatment is unknown. Objective, To compare blood pressure, insulin sensitivity, beta-cell function and body composition during 4 years of GH treatment, between preterm and term short SGA children. Patients, A total of 404 prepubertal non-GH-deficient short SGA children were divided into 143 preterm (< 36 weeks) and 261 term children. Outcome measures, Height, blood pressure (n = 404), body composition measured by dual energy X-ray absorptiometry (DXA) (n = 138) and insulin sensitivity and beta-cell function calculated from a frequent sampling intravenous glucose tolerance test (FSIGT) with tolbutamide (n = 74) or from the homeostasis model assessment of insulin resistance (HOMA-IR) (n = 204). Results, In preterm and term children, GH treatment resulted in a similar decrease in systolic and diastolic blood pressure, body fat percentage, limb fat/total fat ratio and insulin sensitivity, and a similar increase in insulin secretion and disposition index. Lean body mass (LBM) corrected for gender and height increased in term children and did not change in preterm children. Multiple regression analysis revealed that this difference in GH effect on LBM was not associated with gestational age. Conclusion, The effect of GH treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, SGA children. [source]


    Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes

    CLINICAL ENDOCRINOLOGY, Issue 2 2008
    A. Tura
    Summary Objective, Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. Design and patients, A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements, Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Results, Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 42 03 vs. 54 04 10,4 min,1 (U/ml),1; OGTT: 440 7 vs. 472 9 ml min,1 m,2). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 5 vs. 124 7 pmol min,1 m,2 mm,1, P = 00407) and insulin secretion at 5 mm glucose (168 9 vs. 206 10 pmol min,1 m,2, P = 0003). Conclusions, Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis. [source]