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Intravenous Glucose Tolerance Test (intravenous + glucose_tolerance_test)
Selected AbstractsA double-blind, placebo-controlled trial of rosiglitazone for clozapine-induced glucose metabolism impairment in patients with SchizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009D. C. Henderson Objective:, The primary purpose of this 8-week double-blind, placebo-controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine-treated subjects with schizophrenia with insulin resistance. Method:, Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. Results:, Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non-significant improvement in SG (0.016 ± 0.006,0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8,7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low-density lipoprotein cholesterol (LDL-C) particle number (987 ± 443,694 ± 415, effect size = 0.30, P = 0.04). Conclusion:, Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine. [source] Exenatide prevents fat-induced insulin resistance and raises adiponectin expression and plasma levelsDIABETES OBESITY & METABOLISM, Issue 10 2008L. Li Background:, Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood. Methods:, In the present study, we examined the effects of exenatide treatment on glucose tolerance (intravenous glucose tolerance test), insulin sensitivity (euglycaemic,hyperinsulinaemic clamps), insulin signalling (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels (visfatin and adiponectin) in high fat,fed rats. Results:, Administration of exenatide (0.5 or 2.0 ,g/kg twice daily × 6 weeks) prevented high-fat diet (HFD),induced increases in body weight, plasma free fatty acids, triglycerides and total cholesterol. Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in exenatide-treated rats, whereas expression and plasma levels of adiponectin increased. Conclusions:, These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat,induced insulin resistance. [source] The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-beingDIABETES OBESITY & METABOLISM, Issue 1 2007R. J. Moon Aim:, As many overweight people with T1DM are insulin resistant, adjuvant therapy with insulin sensitising agents, such as metformin, may be beneficial. This study evaluated the effect of adjuvant metformin in T1DM on insulin sensitivity, diabetic control, body composition, quality of life (QOL) and treatment satisfaction. Materials and Methods:, A 3-month prospective open-labelled pilot study of 16 patients aged 18-40 with T1DM and body mass index (BMI) >25 kg/m2 was performed. The patients received 500-850 mg metformin twice daily. Insulin sensitivity, assessed by a frequently sampled intravenous glucose tolerance test [n=5], body composition, HbA1c and quality of life (QOL) were measured before and after treatment. A retrospective review of 30 patients with T1DM treated with metformin for at least 4 months was also performed. BMI, HbA1c and insulin requirements during metformin treatment was compared to pre-metformin data, and to patients treated with insulin only. Results:, In the pilot study, insulin sensitivity increased significantly from 0.86 ± 0.33 × 10,4/min/(µU/ml) to 1.17 ± 0.48 × 10,4/min/(µU/ml) after 3 months adjuvant therapy (p = 0.043). This was associated with a decreased insulin requirement and mean daily blood glucose. There were no significant changes in HbA1c or body composition. QOL significantly improved (p < 0.002). The retrospective review revealed an initial reduction in HbA1c (0.8 ± 1.4%, p = 0.001). This effect diminished with prolonged treatment. BMI decreased in patients remaining on metformin for a 2-year period (0.5 ± 0.5kg/m2, p = 0.042). Conclusion:, Adjuvant metformin can improve QOL, insulin sensitivity and glycaemic control in overweight adults with T1DM. [source] Minor long-term changes in weight have beneficial effects on insulin sensitivity and ,-cell function in obese subjectsDIABETES OBESITY & METABOLISM, Issue 1 2002A. M. Rosenfalck SUMMARY Aim To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG) and ,-cell function. Design Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet. Subjects Twelve obese patients (11 women, 1 man), age 45.8 ± 10.5 years, body weight (BW) 99.7 ± 13.3 kg, BMI 35.3 ± 2.8 kg/m2. Measurements At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning. Results The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a 19% increase. A significant decrease in both fasting (p =,0.038) and 2 h (p =,0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = , 0.83, p =,0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in SI explaining 67% of the variation. First phase insulin response (AIRg) remained unchanged whereas insulin disposition index increased significantly (p =,0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later. Conclusion In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance. [source] An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized studyDIABETIC MEDICINE, Issue 6 2004T. 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] Prediction of Type 2 diabetes in healthy middle-aged men with special emphasis on glucose homeostasis.DIABETIC MEDICINE, Issue 4 2001Results from 22.5 years' follow-up SUMMARY Aims To study the glucose disappearance rate and fasting blood glucose as predictors of Type 2 diabetes in a 22.5-year prospective follow-up of 1947 healthy non-diabetic men. Subjects and methods Of a cohort of 2014 Caucasian men, the 1947 who had both fasting blood glucose <,110 mg/dl and an intravenous glucose tolerance test were included. A number of other physiological parameters were also determined at baseline. Multivariate Cox regression analyses were used to investigate the possible significance of the glucose disappearance rate and fasting blood glucose as predictors of Type 2 diabetes. Results After 22.5 years' follow-up, 143 cases of Type 2 diabetes had developed. Glucose disappearance rate and fasting blood glucose were moderately correlated (r = ,0.32). Men in the lowest quartile of glucose disappearance rate and highest quartile of fasting blood glucose had markedly higher diabetes rates than all other men (P < 0.0001). After adjusting for each other, age, diabetes heredity, body mass index, physical fitness, triglycerides, cholesterol and blood pressure (Cox model), both glucose disappearance rate and fasting blood glucose remained major predictors of diabetes Conclusions Glucose disappearance rate and fasting blood glucose are, in spite of low intercorrelation, major long-term predictors of Type 2 diabetes in healthy non-diabetic Caucasian men. [source] Age-related analysis of insulin resistance, body weight and arterial pressure in the Zucker fatty ratEXPERIMENTAL PHYSIOLOGY, Issue 1 2009Francesco Di Nardo The evolution with ageing of insulin resistance, body weight (BW) and mean arterial pressure (MAP) was studied in a group of Zucker fatty rats (ZFRs, n= 22), between 7 and 16 weeks of age, compared with an age-matched control group of Zucker lean rats (ZLRs, n= 22). The minimal model of glucose kinetics was applied to estimate glucose effectiveness, SG, and insulin sensitivity, SI, from insulinaemia and glycaemia measured during a 70 min intravenous glucose tolerance test. No correlation was found between SG and age in both ZFR and ZLR groups. No significant changes in mean SG between the two groups indicated no alteration of glucose-mediated glucose disposal. Estimates of SI from individual ZFRs were independent of age and, on average, showed 83% reduction (P < 0.001) compared with the ZLR group. Despite the lack of alteration of SI with age, the ZFR group showed an age-related increase of MAP, which correlated with increasing BW (r = 0.71 and P < 0.001). These results support the hypothesis that in our ZFRs, as a suitable genetic model of obesity and hypertension, insulin resistance is fully established at the age of 7 weeks and remains practically unaltered until at least the sixteenth week. An age-related increase in arterial pressure, observed in this strain, relates more properly to increasing BW, rather than insulin resistance. Development of hypertension with increasing age and BW may result from an enhanced insulin-mediated activity of the sympathetic nervous system, as observed in our previously reported study. [source] Diet-induced central obesity and insulin resistance in rabbitsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1 2008S. Zhao Summary The present study was designed to examine whether rabbits fed a diet containing high fat and sucrose could develop obesity and insulin resistance (IR), the major pathophysiological features of metabolic syndrome. Male Japanese white rabbits were fed either a normal chow diet (control) or high fat and sucrose diet (HFSD) for 36 weeks. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose and insulin were measured. To evaluate glucose metabolism, we performed an intravenous glucose tolerance test. In addition, we compared adipose tissue accumulation in HFSD-fed rabbits with that in normal rabbits. HFSD constantly and significantly led to an increase in body weight of HFSD-fed rabbits, caused by significantly higher visceral adipose tissue accumulation. Although there were no differences in plasma TG, TC, glucose, insulin levels and blood pressure between the two groups, HFSD-fed rabbits showed impaired glucose clearance associated with higher levels of insulin secretion compared to control rabbits. Our results showed that HFSD induced IR and increased adipose accumulation in rabbits, suggesting that HFSD-fed rabbits may become a model for research on human IR and obesity. [source] First phase insulin release and glucose tolerance in children with Fanconi anemia after hematopoietic cell transplantationPEDIATRIC BLOOD & CANCER, Issue 2 2009Lynda 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] Impaired Insulin Sensitivity as an Underlying Mechanism Linking Hepatitis C and Posttransplant Diabetes Mellitus in Kidney RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009S. Baid-Agrawal Aim of this study was to investigate the mechanism/s associating hepatitis C virus (HCV) infection and posttransplant diabetes mellitus in kidney recipients. Twenty HCV-positive and 22 HCV-negative kidney recipients, 14 HCV-positive nontransplant patients and 24 HCV-negative nontransplant (healthy) subjects were analyzed. A 3-h intravenous glucose tolerance test was performed; peripheral insulin sensitivity was assessed by minimal modeling. Pancreatic insulin secretion, hepatic insulin uptake, pancreatic antibodies and proinflammatory cytokines in serum (tumor necrosis factor-,, intereukin-6, high-sensitive C-reactive protein) were also assessed. HCV-positive recipients showed a significantly lower insulin sensitivity as compared to HCV-negative recipients (3.0 ± 2.1 vs. 4.9 ± 3.0 min,1.,U.mL, 1.104, p = 0.02), however, insulin secretion and hepatic insulin uptake were not significantly different. Pancreatic antibodies were negative in all. HCV status was an independent predictor of impaired insulin sensitivity (multivariate analysis, p = 0.008). The decrease of insulin sensitivity due to HCV was comparable for transplant and non-transplant subjects. No significant correlation was found between any of the cytokines and insulin sensitivity. Our results suggest that impaired peripheral insulin sensitivity is associated with HCV infection irrespective of the transplant status, and is the most likely pathogenic mechanism involved in the development of type 2 diabetes mellitus associated with HCV infection. [source] Long-Term Survival of Nonhuman Primate Islets Implanted in an Omental Pouch on a Biodegradable ScaffoldAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009D. M. Berman The aim of this study was to test whether an omental pouch can be used as an alternative site for islet implantation in diabetic monkeys. Here we report the successful engraftment of islets in diabetic cynomolgus monkeys when loaded on a synthetic biodegradable scaffold and placed in an omental pouch. One autologous and five allogeneic diabetic monkey transplants under the cover of steroid-free immune suppression (SFIS) were undertaken. Fasting blood glucose (FBG) and C-peptide (CP), exogenous insulin requirements (EIR), intravenous glucose tolerance test (IVGTT), A1C and histopathology were used to assess islet engraftment and survival. All animals achieved CP levels > 1.0 ng/mL following transplant, a 66,92% posttransplant decrease in EIR and reduced A1C. Following graft removal, CP became negative and histopathological analysis of the explanted grafts demonstrated well-granulated and well-vascularized, insulin-positive islets, surrounded by T-cell subsets and macrophages. Compared to intrahepatic allogeneic islet transplants (n = 20), there was a delayed engraftment for omental pouch recipients but similar levels of CP production were ultimately achieved, with a broad range of IEQ/kg transplanted in both sites. Our results suggest this extrahepatic transplantation site has potential as an alternative site for clinical islet cell transplantation. [source] Noncompartmental pharmacokinetics analysis of glucose-stimulated insulin response in African,American and Caucasian youthsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2009Lanyi Xie Abstract The objective of this study was to examine the differences in glucose and insulin responses between African,American and Caucasian youths and to determine the associations of between-group differences with sex, body mass index (BMI) and pubertal status using a noncompartmental pharmacokinetic approach. Sixteen African,American and 22 Caucasian healthy adolescents were tested using the frequently sampled intravenous glucose tolerance test. Longitudinal t -tests across each observation revealed that (1) African,American youths have higher insulin concentrations between 4 to 19,min; (2) insulin levels remained similar as subjects were grouped according to sex and pubertal status; (3) for glucose, the only difference was found as it approached steady-state basal level (>100,min) between groups with different BMIs. Linear regression showed that insulin concentrations between 4 to 19,min are associated with BMI in Caucasians. African,American youths were found to have higher insulin responses after glucose stimulation and the insulin concentrations were more related to BMI in Caucasians compared with African,Americans. BMI also has a significant effect on the glucose steady state basal level. The acute insulin response to glucose (AIRg) extended to 20,min resulted in a more significant racial difference (p<0.0006) compared with the calculation done over 10,min suggested in the past (p<0.001). Copyright © 2009 John Wiley & Sons, Ltd. [source] Intrabdominal fat is related to metabolic risk factors in Hispanic Americans, African Americans and in girlsACTA PAEDIATRICA, Issue 12 2009K Casazza Abstract Aim:, This study aimed to test the association of individual adipose depots on cardiometabolic outcomes, whether the association varied by depot and if the associations differed by race/ethnicity or gender in early pubertal children. Methods:, Three hundred and twenty children (53% male) aged 7,12 years self-identified as African American (AA; n = 114), European American (EA; n = 120) or Hispanic American (HA; n = 86) participated. Insulin dynamics were assessed by intravenous glucose tolerance test; body composition with DXA; fat distribution with CT. Results:, AA had the least fat in each depot and HA had the most. Fat accumulation negatively impacted cardiometabolic outcomes independent of race/ethnicity or gender. AA and females were reproductively more mature. In AA and HA, each measure of adiposity influenced the insulin sensitivity index (SI), whereas intra-abdominal adipose tissue (IAAT) did not contribute to SI in EA. IAAT was positively associated with blood pressure in AA only. In females, adiposity adversely influenced cardiometabolic outcomes such that total fat mass, IAAT and/or SAAT was inversely associated with SI, and positively associated with blood pressure and fasting insulin. Conclusion:, IAAT is uniquely related to metabolic risk factors in Hispanic Americans, African Americans and girls, suggesting that either the threshold for adverse effects of IAAT is lower, or the IAAT metabolism differs in these groups. [source] Insulin sensitivity, VO2max and body composition in severely obese Swedish children and adolescentsACTA PAEDIATRICA, Issue 1 2009Gunilla Morinder Abstract Aim: The aim of this study was to identify relationships between insulin sensitivity (SI), cardiorespiratory fitness and body composition in severely obese Swedish children and adolescents. Methods: Two hundred and twenty-eight obese children (119 girls, 8,16 years, body mass index (BMI) 23.2,57.0 kg/m2) performed a frequently sampled intravenous glucose tolerance test (FSIVGTT), a submaximal bicycle ergometry test and a dual-energy X-ray absorptiometry (DEXA). Results: Mean SI (SD) was 0.38 (0.32) (×10,5/min/pM). SI correlated positively with relative body mass (BM) VO2max (r = 0.42) (p < 0.001), relative fat-free mass (FFM) VO2max (r = 0.36) (p < 0.001) and negatively with body mass index standard deviation score (BMI SDS) (r =,0.22) (p = 0.001). SI did not correlate with percent body fat (r =,0.01) and absolute VO2max (r = 0.01). In multiple regression analyses with SI as dependent variable, VO2max and body composition, together with gender, age and Tanner stage, explained 20,26% of the variance. Conclusion: Relative (BM) VO2max and relative (FFM) VO2max were stronger predictors of SI than percent body fat in severely obese children and adolescents. The study confirms that cardiorespiratory fitness is of importance for the metabolic syndrome in the studied population. Efforts to improve SI should include physical activity targeting cardiorespiratory fitness also in severely obese children and adolescents. [source] Interactions between TCF7L2 genotype and growth hormone-induced changes in glucose homeostasis in small for gestational age childrenCLINICAL ENDOCRINOLOGY, Issue 1 2010Sandra W. K. De Kort Summary Context, The Transcription factor 7-like 2 (TCF7L2) rs7903146 gene polymorphism has been associated with risk of developing type 2 diabetes mellitus (DM), possibly by decreasing insulin secretion. Small for gestational age (SGA) birth has been associated with type 2 DM in later life. Growth hormone (GH) treatment reduces insulin sensitivity and increases insulin secretion. Therefore, GH-treated SGA children are an ideal group to investigate whether the TCF7L2 rs7903146 genotype is associated with changes in glucose homeostasis. Objective, To determine the impact of the TCF7L2 rs7903146 polymorphism on changes in insulin secretion and insulin sensitivity during 4 years of GH treatment in children born SGA. Subjects, A total of 246 Caucasian short children born SGA, with a median age of 7·8 years. Outcome measures, Insulin sensitivity and insulin secretion were measured by the frequently sampled intravenous glucose tolerance test (FSIGT) (n = 68) and homeostasis model assessment (HOMA) calculations (all). Results, There was no association between rs7903146 genotype and insulin sensitivity or insulin secretion at baseline but after adjustment for possible confounders, insulin secretion was higher in the CT/TT group than in the CC group. During GH treatment, carriers of the rs7903146 T allele had an increase in insulin secretion similar to that of carriers of the CC genotype. The decrease in insulin sensitivity was only significant in the CT/TT group, but the difference in decrease between genotype groups did not reach significance (P = 0·06). The disposition index (insulin secretion × insulin sensitivity), which is an estimate of beta cell function, was not associated with genotype and did not change during GH treatment. Conclusion, The TCF7L2 rs7903146 polymorphism is not associated with the change in insulin secretion during GH treatment in short SGA children. [source] The effect of growth hormone treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, small for gestational age childrenCLINICAL ENDOCRINOLOGY, Issue 1 2009Sandra 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] The impact of acute elevation of non-esterified fatty acids on insulin sensitivity and secretion in women with former gestational diabetesCLINICAL ENDOCRINOLOGY, Issue 1 2005K. A. McLachlan Summary Objectives, Elevations in non-esterified fatty acids (NEFA) have been shown to decrease insulin action and secretion, and are a risk factor for the development of Type 2 diabetes. As women who have had gestational diabetes (GDM) are at increased risk of diabetes, we examined the effect of an acute elevation of NEFA on insulin secretion and action in these women. Patients and design, Nineteen women with recent former GDM and 19 age- and BMI-matched postpartum healthy control subjects underwent a 40-min intravenous glucose tolerance test, with and without a preceding 2-h infusion of 20% Intralipid. Insulin action was assessed by glucose disappearance (Kg) and insulin sensitivity (SI); insulin secretion by first phase insulin release (FPIR) and disposition index (DI). Results, NEFA levels were similarly elevated in both groups by the Intralipid infusion (up to 1·140 ± 0·03 mm). As expected, the lipid infusion significantly reduced Kg (2·15 ± 0·13 vs. 1·69 ± 0·09/min, P < 0·001) and SI (3·14 ± 0·28 vs. 2·13 ± 0·17/min/mUl/min, P < 0·001) in all subjects, and these were significant within the GDM and control subgroups. FPIR was elevated in the Intralipid study in the total group of women (4·50 ± 0·50 vs. 5·02 ± 0·53, P = 0·02), but DI was significantly reduced (12·13 ± 1·1 vs. 8·83 ± 0·7, P < 0·001). There was no significant difference, however, in the absolute or percentage change in Kg, SI or FPIR with lipid infusion between the GDM and control groups. GDM status was not a predictor of the response of Kg, SI or FPIR to lipid infusion, rather, adiposity (% fat), average fasting NEFA levels and basal disposition index were associated. Conclusion, These data suggest that women with former gestational diabetes, in contrast to other prediabetic states, are not more susceptible to the deleterious effects of an acute elevation in nonesterified fatty acids than matched control subjects. [source] Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose toleranceCLINICAL ENDOCRINOLOGY, Issue 1 2005Yi-Jen Hung Summary Objective, This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, ,-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). Methods, Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) , 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. Results, After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4·25 ± 0·22 vs 4·80 ± 0·17 mmol/l, P < 0·001), high-density lipoprotein cholesterol (HDL-C) (1·25 ± 0·07 vs 1·43 ± 0·06 mmol/l, P < 0·05), and low-density lipoprotein cholesterol (LDL-C) (2·70 ± 0·15 vs 3·37 ± 0·17 mmol/l, P < 0·05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic ,-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0·38 ± 0·06 vs 0·54 ± 0·09 × 10,5 min,1/pmol, P < 0·05; 0·017 ± 0·002 vs 0·021 ± 0·001 min,1, P < 0·05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0·05). Conclusion, Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on ,-cell secretory function. [source] Major influence of liver function itself but not of immunosuppression determines glucose tolerance after living-donor liver transplantation,,LIVER TRANSPLANTATION, Issue 4 2006Martin Stockmann Controversial data exists concerning the impact of immunosuppressive therapy on the development of post-transplantation diabetes mellitus (PTDM). Therefore, we investigated glucose metabolism in healthy donors and in recipients of living-donor liver transplants (LD-LTX, n=18) without pre-existing diabetes mellitus before, on day 10, month 6, and month 12 after intervention. The computer-assisted analysis of glucose, insulin, and C-peptide profiles obtained from frequently sampled intravenous glucose tolerance tests allows to achieve an integrated view of factors controlling glucose tolerance, i.e., insulin sensitivity (SI), first and second phase insulin secretion (,1 and ,2). SI of donors declined by day 10 after operation (SI 2.65 ± 0.41 vs. 4.90 ± 0.50 10,4 minute,1 ,U ml,1, P < 0.01) but returned to values as before after 6 months. ,1 did not change. ,2, however, significantly increased by day 10 (8.57 ± 0.82 109 minute,1 to 13.77 ± 1.53 109 minute,1, P < 0.01) but was in the same range as before after 6 months. In parallel to donors SI of recipients progressively increased after LD-LTX. ,1 did not alter in recipients. ,2 continuously decreased and was not different from donors by month 12. The extent of liver injury assessed by liver enzyme concentrations and liver function represented by cholinesterase activity, albumin, and INR were closely related with changes of SI in donors and recipients during the first year after intervention. In conclusion, the extent of liver damage plays a predominant role in regulating glucose tolerance. No impact of immunosuppressive therapy on SI, ,1 and ,2 was detected. Liver Transpl 12:535,543, 2006. © 2006 AASLD. 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