Home About us Contact
|
Home About us Contact | ||
|
|
||
Insulin Levels (insulin + level)
Kinds of Insulin Levels Selected AbstractsLow-carbohydrate (low & high-fat) versus high-carbohydrate low-fat diets in the treatment of obesity in adolescentsACTA PAEDIATRICA, Issue 2 2009S Demol Abstract Aim: To compare the impact of low-carbohydrate diets of different fat content to high-carbohydrate low-fat diet on weight and metabolic parameters in obese adolescents. Methods: Fifty-five patients aged 12,18 years with a body mass index (BMI) above the 95th percentile were randomly allocated to one of three isoenergetic diet regimens. Anthropometric and metabolic measurements were taken after overnight fast, at baseline, after the 12-week intervention and after nine month of follow-up. Results: No significant differences were found among the groups in changes in BMI, BMI-percentile, fat percentage, or metabolic markers at the end of the intervention and at the end of follow-up. Insulin level and homeostasis model assessment (HOMA) level decreased significantly at both time points only in the two low carbohydrate diet groups. Conclusion: All diet regimens are associated with a significant reduction in BMI and improvement of some metabolic parameters in obese adolescents. Low-carbohydrate diets apparently have no advantage over high-carbohydrate low-fat diets. The significant drop in insulin level and HOMA in the low carbohydrate diet groups is noteworthy given the increasing frequency of type-2 diabetes as part of metabolic syndrome in children and youth. The impact of low carbohydrate diets in obese and insulin-resistant youth warrants further investigation. [source] Effects of Hilsa ilisa fish oil on the atherogenic lipid profile and glycaemic status of streptozotocin-treated type 1 diabetic ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2004Ishtiaq Mahmud Summary 1.,The effects of oral administration of Hilsa (Hilsa ilisa) fish oil (1 g oil/kg bodyweight per day) on the lipid profile, platelet aggregation, anti-oxidative status and glycaemic control of streptozotocin (STZ; 90 mg/kg bodyweight)-treated type 1 diabetic rats were compared with those in fish oil-treated or untreated non-diabetic rats. 2.,After 3 weeks of fish oil feeding, plasma total cholesterol decreased in both the non-diabetic and diabetic rats by 35 and approximately 10%, respectively, and triglyceride fell by 69 and 20%, respectively, compared with control rats. 3.,Fish oil feeding decreased non-esterified fatty acids (NEFA) by 29% in diabetic rats but the NEFA level in non-diabetic rats was unaffected. 4.,In non-diabetic and diabetic rats, platelet aggregation decreased by 49 and 37%, respectively, and total anti-oxidant status increased by 18 and 17%, respectively, after fish oil feeding. 5.,Insulin levels increased by 27% in the fish oil-fed non-diabetic rats, whereas insulin levels were markedly decreased in diabetic rats. Glucose levels were not altered at all and fructosamine levels decreased by 29% only in fish oil-fed diabetic rats. 6.,The results of the present study suggest that Hilsa ilisa fish oil may ameliorate the atherogenic lipid profile, platelet hyperaggregation and the anti-oxidative defence of STZ-diabetic rats and the amelioration is thought to be independent of the effects of Hilsa on glycaemic control. [source] Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS)CLINICAL ENDOCRINOLOGY, Issue 6 2009Orit Pinhas-Hamiel Summary Objective, To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels. Design, Prospective case,control study. Setting, Endocrine clinics in the community. Patients, Forty-four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1·645] with PCOS; 16 were lean (BMI SDS <1·036) with PCOS; and 14 were lean (BMI SDS <1·036) without PCOS. Intervention, Blood samples were collected from all girls between 8 and 11 am, after an overnight fast. Main outcome measures, Serum levels of adiponectin, leptin, insulin, Müllerian-inhibiting substance, luteinizing hormone, follicle-stimulating hormone, testosterone, 17-alpha-hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17,-oestradiol. Results, Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10·5 ± 5·5 ,g/ml) compared with that in lean girls with or without PCOS (16·9 ± 8·64 and 18·0 ± 7·4 ,g/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12·3 ± 12·2 vs. 4·5 ± 2·9, P < 0·05), and compared with that in normal weight PCOS adolescents (7·4 ± 4·9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin. Conclusions, Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group. [source] Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patientsDIABETES OBESITY & METABOLISM, Issue 6 2008A. Brunani Aim:, In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. Methods:, From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18,65 years and body mass index 35,50 kg/m2 and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. Results:, A significant weight loss and reduction of fat mass was demonstrated with metformin (,9.7 ± 1.8 kg and ,6.6 ± 1.1 kg) and also with rosiglitazone (,11.0 ± 1.9 kg and ,7.2 ± 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 ± 0.1 vs. 4.4 ± 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 ± 1.5 vs. 8.0 ± 0.,7 ,U/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 ± 8.8 vs. 109.9 ± 10.3, p < 0.005) with a concomitant decrease in ,-cell function as measured by HOMA of ,-cell function (163.2 ± 16.1 vs. 127.4 ± 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. Conclusion:, Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction. [source] Continuous Subcutaneous Glucose Monitoring System in diabetic mothers during labour and postnatal glucose adaptation of their infantsDIABETIC MEDICINE, Issue 4 2008E. Stenninger Abstract Aims To assess a new technique for continuous monitoring of glucose concentration during labour in diabetic mothers. A second objective was to study maternal glucose levels in relation to postnatal glucose adaptation and the need for intravenous (IV) glucose treatment in the newborn infant. Methods Fifteen pregnant women with insulin-treated diabetes mellitus participated in this prospective pilot study. To measure their glucose control during labour we used the Continuous Subcutaneous Glucose Monitoring System (CGMS; Medtronic, Minneapolis, MN, USA) to calculate the mean glucose concentration and the area under the curve (AUC) in the last 120 min before delivery. All infants of these women were transferred to the neonatal care unit for early oral feeding and blood glucose measurements up to 14 h after delivery. Infants received IV glucose if blood glucose values were repeatedly < 2.2 mmol/l. Results All women coped well with the CGMS monitoring. AUC 0,120 min before delivery, mean glucose concentration 0,120 min before delivery and cord plasma insulin level were all significantly associated with the need for IV glucose in the newborn children. Conclusions In this study we found an association between maternal glucose concentrations during labour and postnatal glucose adaptation and need for IV glucose treatment in the infants. Online monitoring of glucose levels during delivery might help us to achieve maternal normoglycaemia and further reduce the risk of postnatal hypoglycaemia in the offspring. [source] Heterogeneity of non-insulin-dependent diabetes expressed as variability in insulin sensitivity, ,-cell function and cardiovascular risk profileDIABETIC MEDICINE, Issue 1 2003K. I. Birkeland Abstract Aims The present study investigated the variability in insulin sensitivity and ,-cell function and their relationship to anti-glutamic acid decarboxylase (GAD) positivity and the metabolic syndrome in a group of patients with non-insulin-dependent diabetes mellitus (NIDDM). Methods Fifty-four subjects aged 59.5 ± 6.1 (mean ± sd) years with NIDDM for 7.9 ± 3.9 years referred to hospital due to poor glycaemic control, were investigated. Insulin sensitivity was determined by the euglycaemic hyperinsulinaemic glucose clamp technique as the glucose disposal rate relative to the insulin level obtained (GDRI), and also estimated with the homeostasis model assessment (HOMA-S). ,-cell function was measured by assaying the fasting and glucagon-stimulated C-peptide levels and with the HOMA-B. Results The insulin sensitivity varied 18-fold between subjects when estimated with the clamp and six-fold when estimated with HOMA-S, and was lower the more criteria for the metabolic syndrome present (P = 0.0001 by anova). The ,-cell function varied four-fold when measured as stimulated C-peptide, and eight-fold when estimated with the HOMA-B. The levels of fasting C-peptide and HOMA-B values tended to be lower in anti-GAD+ (n = 11) than in anti-GAD,subjects (P = 0.06 and P = 0.08, respectively). From previously published coronary risk charts, we estimated the 10-year risk of a coronary heart disease (CHD) event to be > 20% in 17 of 39 patients free from cardiovascular disease at the time of study, 16 of whom qualified for a diagnosis of the metabolic syndrome. Conclusions The wide variations in insulin sensitivity and ,-cell function found among subjects with NIDDM support the notion that the disorder is highly heterogeneous. Reduced insulin sensitivity was clearly related to the metabolic syndrome and an increased risk for CHD. [source] Is postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2005A. Kriketos Abstract Background, Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content. Materials and methods, Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined. Results, The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44·6 ± 4·9 vs. 60·0 ± 4·8 µmol min,1 kg FFM,1, P = 0·037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180,240 min (,0·77 ± 0·11 mmol L,1), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2·13 ± 0·51 vs. 0·70 ± 0·35 mmol L,1, P = 0·03), only in the REL. Conclusions, These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver. [source] Effect of recombinant human erythropoietin on insulin resistance in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 3 2009Essam KHEDR Abstract Insulin resistance is a characteristic feature of uremia. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Treatment with recombinant human erythropoietin (rHuEPO) was said to be associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin resistance in adult uremic hemodialysis (HD) patients including diabetic patients treated with or without rHuEPO. A total of 59 HD patients were studied, patients were divided into 2 groups of subjects: 30 HD patients on regular rHuEPO treatment (group A), and 29 HD patients not receiving rHuEPO (group B) diabetic patients were not excluded. Full medical history and clinical examination, hematological parameters, lipid profile, serum albumin, parathyroid horomone, Kt/V, fasting glucose, and insulin levels were measured in all subjects. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to compare insulin resistance. The results of this study showed that the mean insulin level of HD patients treated with rHuEPO (group A) (17.5 ± 10.6 ,U/mL) was significantly lower than patients without rHuEPO (group B) (28.8 ± 7.7 ,U/mL), (P<0.001). Homeostasis Model Assessment of Insulin Resistance levels in group A were significantly lower than in group B (3.8 ± 2.97, 7.98 ± 4.9, respectively, P<0.001). Insulin resistance reflected by HOMA-IR levels among diabetic patients in group A was significantly lower than among diabetic patients in group B (3.9 ± 3.2, 9.4 ± 7.2, respectively, P<0.001). Also, HOMA-IR levels among nondiabetic patients in group A were significantly lower than among nondiabetic patients in group B (3.7 ± 2.85, 6.9 ± 1.43, respectively, P<0.01). We found a statistically significant negative correlation between duration of erythropoietin treatment, fasting blood glucose, insulin levels, and insulin resistance (r=,0.62, ,0.71, and ,0.57, P<0.001). Patients treated with rHuEPO showed less insulin resistance compared with patients not treated with rHuEPO in diabetic and nondiabetic patients and, duration of erythropoietin treatment is negatively correlated with insulin levels and insulin resistance in HD patients. [source] Antidiabetic activity of flavone from Ipomoea Batatas leaf in non-insulin dependent diabetic ratsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 1 2007Rui Zhao Summary The effects of flavone extracted from Ipomoea batatas leaf (FIBL) on body weight, blood glucose, serum lipid profiles, serum insulin and free radicals in rats with non-insulin dependent diabetes mellitus (NIDDM) were studied. FIBL treatment (25, 50, 100 mg kg,1) for 2 weeks resulted in a significant decrease in the concentration of plasma triglyceride (TG), plasma cholesterol (TC) and weight in NIDDM rats. Furthermore, FIBL markedly decreased fasting plasma insulin level, blood glucose (FBG) level, low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) levels and significantly increased the Insulin Sensitive Index (ISI) and superoxide dismutase (SOD) level in NIDDM rats. In addition, flavone extracted from I. batatas leaf did not show any physical or behavioural signs of toxicity. More significantly, our data demonstrate the FIBL at the dose of 50 mg kg,1 body weight exhibited the optimal effect. The above results suggest that flavone extracted from I. batatas leaf could control blood glucose and modulate the metabolism of glucose and blood lipid, and decrease outputs of lipid peroxidation and scavenge the free radicals in non-insulin dependent diabetic rats. [source] ORIGINAL ARTICLE: The approach to the mechanism of calcitonin gene-related peptide-inducing inhibition of food intakeJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5 2010J.-Y. Sun Summary The aim of this study was to investigate the anorectic mechanism of calcitonin gene-related peptide (CGRP) in rats. Intraperitoneal injection of CGRP (50 ,g/kg) resulted in decline (p < 0.05) in the food intake of rats at 0.5, 1, 2 and 4 h in comparison with saline control. Compared with saline-treated group, the levels of hypothalamic 3,,5,-cyclic adenosine monophosphate (cAMP) and plasma glucagon were increased (p < 0.05) in CGRP-treated group, but insulin level was decreased (p < 0.05). No significant changes (p > 0.05) in the plasma leptin were observed between two treatment groups. Calcitonin gene-related peptide injection down regulated (p < 0.05) both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) genes at mRNA levels, but up regulated (p < 0.05) the expression of cholecystokinin (CCK) gene. The correlations analysis showed that food intake was negatively correlated (p < 0.05) with CCK mRNA, cAMP and glucagon levels. Moreover, there existed negative correlations (p < 0.05) between MCH mRNA and glucagon levels, and positive correlations (p < 0.05) between insulin and leptin levels. The results showed that cAMP acting as the second messenger may play a vital role in the anorectic effects of CGRP. Calcitonin gene-related peptide could stimulate anorexigenic neuropeptides (i.e. CCK) and/or inhibit orexigenic neuropeptides (i.e. NPY and MCH) expression, and ultimately suppressed food intake that was functionally coupled to cAMP/PKA pathway activation. [source] Development and in-vivo evaluation of insulin-loaded chitosan phthalate microspheres for oral deliveryJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2007Udhumansha Ubaidulla Novel chitosan phthalate microspheres containing insulin were prepared by emulsion cross-linking technique. The feasibility of these microspheres as oral insulin delivery carriers was evaluated. The pH-responsive release behaviour of insulin from microspheres was analysed. The ability of chitosan phthalate-insulin microspheres to enhance intestinal absorption and improve the relative pharmacological availability of insulin was investigated by monitoring the plasma glucose and insulin level of streptozotocin-induced diabetic rats after oral administration of microspheres at insulin dose of 20 IU kg,1. In simulated gastric fluid (pH 2.0), insulin release from the microspheres was very slow. However, as the pH of the medium was changed to simulated intestinal fluid (pH 7.4), a rapid release of insulin occurred. The relative pharmacological efficacy for chitosan phthalate microspheres (18.66 ± 3.84%) was almost four-fold higher than the efficacy of the chitosan phthalate-insulin solution administration (4.08 ± 1.52%). Chitosan phthalate microspheres sustained the plasma glucose at pre-diabetic level for at least 16 h. These findings suggest that the microsphere is a promising carrier as oral insulin delivery system. [source] Total and high molecular weight adiponectin concentrations in plasma of patients with end-stage renal disease before and after peritoneal dialysisNEPHROLOGY, Issue 3 2008JAE-HO PARK SUMMARY: Background: Adiponectin is an antiatherogenic adipocyte-derived proteins. The level of plasma adiponectin is inversely correlated to cardiovascular risk in patients with end-stage renal disease (ESRD). The aim of this study was to elucidate the changes of adiponectin concentrations in newly diagnosed ESRD patients after peritoneal dialysis. Methods: In 16 newly diagnosed ESRD patients, total concentrations of adiponectin and high molecular weight (HMW) adiponectin, the HMW ratio (HMWR; ratio of the plasma level of HMW adiponectin to that of total adiponectin), the body mass index (BMI), insulin concentrations, blood glucose and estimation of the insulin sensitivity index by the homeostasis model assessment (HOMRIR) were compared before and after 1 year of peritoneal dialysis. Results: Plasma total adiponectin was decreased from 15.52 ± 9.35 ,g/mL to 11.80 ± 6.84 ,g/mL (P = 0.046), HMW adiponectin was decreased from 9.05 ± 6.48 ,g/mL to 4.83 ± 4.15 ,g/mL (P = 0.009), and HMWR was decreased from 0.51 ± 0.18 to 0.35 ± 0.20 (P = 0.008). Total and HMW adiponectin/BMI ratio was decreased. The BMI was increased from 25.2 ± 5.7 to 25.8 ± 6.2 (P = 0.036). The HOMRIR, insulin level and lipid profile were not changed. Conclusion: Total adiponectin, HMW adiponectin and HMWR were decreased in newly diagnosed ESRD patients after 1 year of peritoneal dialysis. The factors that influence the decrease of the level of adiponectin should be studied in a larger prospective study. [source] Limitations of first-phase insulin response to evaluate insulin secretion in childrenPEDIATRIC DIABETES, Issue 1 2000WS 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] Threshold values of visceral fat and waist girth in Japanese obese childrenPEDIATRICS INTERNATIONAL, Issue 5 2005Kohtaro Asayama AbstractBackground:,In order to define the diagnostic criteria for visceral adipose tissue (VAT) accumulation and abdominal obesity in Japanese youths, a cross-sectional, multicenter study was conducted. Methods:,Subjects were 194 boys and 96 girls ranging in age from 6 to 15 years. Obese youths were classified according to the occurrence of abnormal values in serum triglyceride, alanine aminotransferase or insulin level. A threshold value of each criterion was calculated, using the analysis of receiver operating characteristic (ROC) curve. The areas of total abdominal adipose tissue (AT), VAT and subcutaneous adipose tissue (SAT) were estimated by single slice computed tomography at the level of umbilicus. Results:,VAT area was greater in boys than it was in girls. The critical values for VAT area and waist circumference in all subjects were 54.8 cm2 and 83.5 cm, respectively. The values for the area under the ROC curves were VAT area > total AT area > waist circumference > SAT area > percentage overweight > percentage body fat. The sensitivity and specificity for VAT area were 90.5 and 79.5%, respectively. Those for waist circumference were high enough (> 70%) for clinical use. In the linear regression analysis assigning VAT area as an independent variable and waist circumference as a dependent variable, the expected value for the waist circumference was 82 cm. Conclusion:,In Japanese obese youths ranging in age from 6 to 15 years, the diagnostic criteria for the waist circumference was 82 cm, and that for VAT area was 55 cm2. [source] Low-carbohydrate (low & high-fat) versus high-carbohydrate low-fat diets in the treatment of obesity in adolescentsACTA PAEDIATRICA, Issue 2 2009S Demol Abstract Aim: To compare the impact of low-carbohydrate diets of different fat content to high-carbohydrate low-fat diet on weight and metabolic parameters in obese adolescents. Methods: Fifty-five patients aged 12,18 years with a body mass index (BMI) above the 95th percentile were randomly allocated to one of three isoenergetic diet regimens. Anthropometric and metabolic measurements were taken after overnight fast, at baseline, after the 12-week intervention and after nine month of follow-up. Results: No significant differences were found among the groups in changes in BMI, BMI-percentile, fat percentage, or metabolic markers at the end of the intervention and at the end of follow-up. Insulin level and homeostasis model assessment (HOMA) level decreased significantly at both time points only in the two low carbohydrate diet groups. Conclusion: All diet regimens are associated with a significant reduction in BMI and improvement of some metabolic parameters in obese adolescents. Low-carbohydrate diets apparently have no advantage over high-carbohydrate low-fat diets. The significant drop in insulin level and HOMA in the low carbohydrate diet groups is noteworthy given the increasing frequency of type-2 diabetes as part of metabolic syndrome in children and youth. The impact of low carbohydrate diets in obese and insulin-resistant youth warrants further investigation. [source] Cord plasma concentrations of adiponectin and leptin in healthy term neonates: positive correlation with birthweight and neonatal adiposityCLINICAL ENDOCRINOLOGY, Issue 1 2004Po-Jung Tsai Summary objective, Adiponectin is negatively associated with leptin, insulin and obesity in children and adults. Whereas increases in fetal insulin and leptin are associated with increased weight and adiposity at birth, the role of adiponectin in fetal growth has not yet been determined. The aims of this study were to examine the relationships between adiponectin and insulin, leptin, weight and adiposity at birth in healthy term infants. design and methods, Anthropometric parameters including weight, length, circumferences and skinfold thickness were measured, and plasma lipid profiles, insulin, leptin and adiponectin concentrations in cord blood samples from 226 singleton infants born at term after uncomplicated pregnancies were assayed. results, Cord plasma adiponectin, leptin and insulin levels correlated significantly and positively with birthweight (P = 0·001, P < 0·001, P < 0·001, respectively) and the sum of skinfold thicknesses (P < 0·001, P < 0·001, P < 0·001, respectively). Mean cord plasma adiponectin and leptin levels, but not insulin level, were significantly higher in large-for-gestational-age (LGA) infants compared with appropriate-for-gestational-age (AGA) infants. Cord plasma leptin concentration, but not adiponectin concentration, was significantly higher in female infants than in male infants (P = 0·003 and P = 0·94, respectively). Cord plasma adiponectin concentration correlated positively with leptin level (P = 0·007) but not with insulin level (P = 0·78). conclusions, High adiponectin levels are present in the cord blood. Cord plasma adiponectin and leptin levels are positively correlated with birthweight and adiposity. This suggests that adiponectin may be involved in regulating fetal growth. [source] Active immunization against (Pro3)GIP improves metabolic status in high-fat-fed miceDIABETES OBESITY & METABOLISM, Issue 9 2010I. A. Montgomery Aim: Ablation of gastric inhibitory polypeptide (GIP) receptor signalling can prevent many of the metabolic abnormalities associated with dietary-induced obesity-diabetes. The present study was designed to assess the ability of active immunization against (Pro3)GIP to counter metabolic dysfunction associated with diet-induced obesity in high-fat-fed mice. Methods: Normal male Swiss NIH mice were injected (s.c.) once every 14 days for 98 days with complexed (Pro3)GIP peptide, with transfer to a high-fat diet on day 21. Results: Active immunization against (Pro3)GIP resulted in circulating GIP antibody production and significantly (p < 0.05 p < 0.01) reduced circulating blood glucose concentrations compared to high-fat control mice from day 84 onwards. Glucose levels were not significantly different from lean controls. The glycaemic response to i.p. glucose was correspondingly improved (p < 0.01) in (Pro3)GIP-immunized mice. Furthermore, circulating and glucose-stimulated plasma insulin levels were significantly (p < 0.01 to p < 0.001) depressed compared to high-fat control mice. Liver triglyceride, pancreatic insulin and circulating LDL-cholesterol levels were also significantly reduced in (Pro3)GIP-immunized mice. These changes were independent of any effects on food intake or body weight. The glucose-lowering effect of native GIP was annulled in (Pro3)GIP-immunized mice consistent with the induction of biologically effective GIP-specific neutralizing antibodies. Conclusion: These results suggest that immunoneutralization of GIP represents an effective means of countering the disruption of metabolic processes induced by high-fat feeding. [source] Reactive hypoglycaemia following GLP-1 infusion in pancreas transplant recipientsDIABETES OBESITY & METABOLISM, Issue 8 2010M. R. Rickels The aim of the study was to determine whether reactive hypoglycaemia in pancreas transplant recipients that followed administration of glucagon-like peptide-1 (GLP-1) was associated with excessive insulin, insufficient glucagon, or both. Methodology involved six portally drained pancreas recipients who received GLP-1 (1.5 pmol/kg/min) or placebo infusion on randomized occasions during glucose-potentiated arginine testing. The second subject developed symptomatic hypoglycaemia [plasma glucose (PG) 42 mg/dl] 1 h after GLP-1 administration; subsequent subjects received intravenous glucose following GLP-1, but not placebo, infusion for PG levels <65 mg/dl. Following GLP-1 vs. placebo infusion, PG was lower (58 ± 4 vs. 76 ± 5 mg/dl; p < 0.05) despite administration of intravenous glucose. During hypoglycaemia, insulin levels and the insulin-to-glucagon ratio were greater after GLP-1 vs. placebo infusion (p < 0.05), while glucagon did not vary. It can be concluded from the study that GLP-1 can induce reactive hypoglycaemia in pancreas transplant recipients through excessive insulin secretion associated with an increased insulin-to-glucagon ratio. [source] Short-term effects of metformin in type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 3 2007A. Eriksson Background:, Although metformin is widely used in the management of type 2 diabetes, its mechanism(s) of action is not fully known, and there have been remarkably few reports on short-term effects of the drug. Here, we examined early effects on glucose and lipid metabolism, and on certain adipose tissue and inflammatory markers during treatment for 28 days. Methods:, Twenty-one patients were randomized to metformin (n = 16) or placebo (n = 5) and studied at baseline, 1, 2 and 4 weeks with blood sampling and oral glucose tolerance tests (OGTT). The active group received 500 mg metformin daily in week 1, 500 mg twice daily in week 2 and 1000 mg twice daily in week 3 and 4. Results:, After 7 days of treatment, a reduced area under curve (AUC) for glucose at OGTT with no change in AUC for insulin levels was observed compared with baseline. Insulin sensitivity, as derived from the OGTT by Gutt's index, was increased. Reductions in fasting plasma glucose, total and LDL-cholesterol appeared after 14 days, and reductions in triglycerides, plasminogen activator inhibitor-1 (PAI-1) and leptin after 28 days of treatment. There were no changes in body weight, adiponectin or C-reactive protein. Compared with placebo, the changes between day 0 and day 28 differed significantly with regard to AUC for glucose at OGTT and Gutt's index, and showed strong trends for PAI-1 and leptin. Conclusions:, The data demonstrate that in type 2 diabetes metformin rapidly affects glucose handling without changing the concentrations of insulin. Reductions in PAI-1 and leptin levels indicate that the early effects of metformin involve also the adipose tissue. [source] Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metforminDIABETES OBESITY & METABOLISM, Issue 4 2006Irina Chazova Aim:, To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. Methods:, A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients ,40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. Results:, With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1,35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Conclusions:, Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease. [source] Islet adaptation to insulin resistance: mechanisms and implications for interventionDIABETES OBESITY & METABOLISM, Issue 1 2005B. Ahrén Abstract:, Insulin sensitivity and insulin secretion are reciprocally related such that insulin resistance is adapted by increased insulin secretion to maintain normal glucose and lipid homeostasis. The relation between insulin sensitivity and secretion is curvilinear and mathematically best described as a hyperbolic relation. Several potential mediators have been suggested to be signals for the beta cells to respond to insulin resistance such as glucose, free fatty acids, autonomic nerves, fat-derived hormones and the gut hormone glucagon-like peptide-1 (GLP-1). Failure of these signals or of the pancreatic beta cells to adequately adapt insulin secretion in relation to insulin sensitivity results in inappropriate insulin levels, impaired glucose intolerance (IGT) and type 2 diabetes. Therefore, treatment of IGT and type 2 diabetes should aim at restoring the normal relation between insulin sensitivity and secretion. Such treatment includes stimulation of insulin secretion (sulphonylureas, repaglinide and nateglinide) and insulin sensitivity (metformin and thiazolidinediones), as well as treatment aimed at supporting the signals mediating the islet adaptation (cholinergic agonists and GLP-1). Both, for correct understanding of diabetes pathophysiology and for development of novel treatment modalities, therefore, the non-linear inverse relation between insulin sensitivity and secretion needs to be acknowledged. [source] Effects of a natural extract of (,)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight lossDIABETES OBESITY & METABOLISM, Issue 3 2004H. G. Preuss Aim:, The efficacy of optimal doses of highly bioavailable (,)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. Methods:, A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21,50, BMI >26 kg/m2). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30,60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. Results:, At the end of 8 weeks, body weight and BMI decreased by 5,6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. Conclusion:, The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels. [source] Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertensionDIABETES OBESITY & METABOLISM, Issue 5 2001M. H. Uehara SUMMARY Background Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. Patients and Methods A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. Results Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54 + 1.72 to 7.54 + 1.33 mmol/l, p <,0.05), although HbA1c had decreased in both groups (PG: 6.7±3.0 to 5.9±2.6%; MG: 5.3±1.5 to 4.6±0.9%; p <,0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7±8.0 to 99.2±9.3 mmHg, p <,0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0±62.4 to 38.0±23.0 pmol/l, p <,0.05) and the insulin resistance index (3.5±2.7 to 1.8±1.0, p <,0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8±7.9 to 21.4±14.6 ,g/l; MG: 18.5±10.3 to 18.4±8.9 ,g/l). Dopamine levels increased significantly only in metformin-treated subjects. Conclusions Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels. [source] Clustering of cardiovascular risk factors with diabetes in Chinese patients: the effects of sex and hyperinsulinaemiaDIABETES OBESITY & METABOLISM, Issue 3 2001Z. -R. SUMMARY Objective This study was designed to investigate factors which affect the clustering of cardiovascular risk factors with diabetes in Chinese patients. Research Design and Methods: Six hundred and fifty-four patients with diabetes were assessed comprehensively for diabetes complications and cardiovascular risk factors in a metropolitan hospital in Beijing, China. Insulin resistance and secretion were also evaluated by measurement of glucose and insulin levels before and after a meal tolerance test. Results were analysed according to patient groups stratified by the number of cardiovascular risk factors coexisting with diabetes. Results Cardiovascular risk factors were common in Chinese diabetic patients. The clustering of three or more of these factors with diabetes occurred more often than by chance alone and was associated with postprandial hyperinsulinaemia. Patients with a high number of risk factors were more prone to macrovascular events but did not have higher albuminuria. Using the commonly adopted lower threshold for diagnosing obesity and central obesity in women, there were more women with multiple risk factors. However, this disappeared if the same criteria were used for men and women. Even in the presence of diabetes, cardiovascular risk factors were inadequately controlled in most patients. Conclusions The concurrence of diabetes and other cardiovascular risk factors which constitute the metabolic syndrome is a common phenomenon in urban Chinese diabetic patients. It is associated with hyperinsulinaemia and possibly the female sex. This study emphasises the importance of public health measures to control cardiovascular risk factors in patients with diabetes. [source] Differential effects of short and long duration insulinotropic agents on meal-related glucose excursionsDIABETES OBESITY & METABOLISM, Issue 2 2001C. J. De Souza SUMMARY Aim Abnormal ,-cell function, characterized as the inability of the ,-cell to mount a rapid secretory response to glucose, is a well-established pathology of type 2 diabetes mellitus. These studies were designed to demonstrate the importance of early insulin release on the control of meal-induced glucose excursions by capitalizing on the significant pharmacodynamic differences between several oral insulin secreting agents. Methods Male Sprague Dawley fitted with indwelling jugular cannulas were used to compare the pharmacodynamic profiles of nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent blood samples following the administration of these compounds via oral gavage. In similar animals which were pretrained to consume their daily food intake in two discrete 45-min meals, the effects of compound induced changes in pre-meal, meal and post-meal insulin profiles on glycaemic control were assessed through frequent blood sampling following the administration of these compounds 10 min prior to a 30-min meal. Results There were significant pharmacodynamics differences between the three oral agents tested and the time to elicit peak insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre-meal insulin levels and glucose excursions paralleled those in the control. Conversely, the other three agents, at doses that produced hypoglycaemic responses of similar magnitude, all increased early insulin release (,AUC(-15 to 3 min) = 0.5 ± 0.01, 1.6 ± 0.4, 3.6 ± 0.0, 1.2 ± 0.1 and 1.73 ± 0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively) and curbed glucose excursions during the meal at varying rates and degrees (,AUC(0,30 min) = 39 ± 6, 8 ± 7, 5 ± 7, ,,1 ± 8 and ,,3 ± 8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively). However, unlike Nateg, the longer duration of action of Repag and Glip elicited sustained post-meal relative hypoglycaemia. Conclusion These data support the impact of early and rapid insulin release in the control of prandial and post-meal glycaemia and demonstrate that a short anticipatory burst of insulin, restricted to the beginning of a meal, provides a clear metabolic advantage and prevents post-meal hypoglycaemic episodes when compared to a greater but reactive insulin exposure that follows a meal-induced increase in glucose excursion. [source] Free fatty acids as mediators of adaptive compensatory responses to insulin resistance in dexamethasone-treated ratsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008Michela Novelli Abstract Background Chronic low-dose dexamethasone (DEX) treatment in rats is associated to insulin resistance with compensatory hyperinsulinaemia and reduction in food intake. We tested the hypothesis that the elevation in circulating free fatty acids (FFAs) induced by DEX is the common mediator of both insulin resistance and insulin hyperproduction. Methods For this purpose, an anti-lipolytic agent was administered during DEX treatment to lower lipacidaemia for several hours prior to glucose and insulin tolerance tests. Leptin expression in adipose tissue (by Northern blot) and plasma leptin levels (by radioimmunoassay) were also investigated to verify whether a rise in circulating leptin could be responsible for the anorectic effect of DEX. Results Our data show that a transient pharmacological reduction of elevated plasma FFA levels abates the post-loading hyperinsulinaemia and counteracts the insulin resistance induced by DEX, supporting the hypothesis that the chronic elevation in FFAs is the common mediator of DEX-induced changes. Despite enhanced leptin expression in white adipose tissue, DEX-treated rats show no significant increase in plasma leptin levels. This suggests that the anorectic effect of DEX should be mediated, at least partially, by other factors, possibly related to the influence of concomitantly elevated plasma FFA and insulin levels on the hypothalamic centers regulating feeding. Conclusions Our results sustain the idea that a prolonged increase in plasma FFA levels plays an important role in the adaptive regulation of glucose and energy homeostasis, not only by potentiating insulin secretion but also by providing a signal of ,nutrient abundance' capable of restraining food intake. Copyright © 2007 John Wiley & Sons, Ltd. [source] Evidence for a vicious cycle of exercise and hypoglycemia in type 1 diabetes mellitusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2004A. C. Ertl Abstract Exercise is a cornerstone of diabetes management as it aids in glycemic control, weight management, reducing blood pressure, and improving the quality of life of patients. Unfortunately, owing to the complexity and difficulties of regulating exogenous insulin in a physiologic manner during exercise, physical activity often results in hypoglycemia in patients with type 1 diabetes mellitus (type 1 DM). When glucose levels fall below threshold glycemic levels, neuroendocrine, autonomic nervous system (ANS), and metabolic glucose counterregulatory mechanisms are activated. These hypoglycemic counterregulatory mechanisms in type 1 DM can be blunted irreversibly by disease duration or by acute episodes of prior stress. These reduced (or absent) counterregulatory responses result in a threefold increase in severe hypoglycemia when intensive glycemic control is implemented in type 1 DM 1. Much recent work has been focused on determining the in vivo mechanisms responsible for causing the increased incidence of severe hypoglycemia in type 1 DM. Studies from several laboratories have demonstrated the role played by episodes of antecedent hypoglycemia in producing blunted glucose counterregulatory responses during subsequent exposures of hypoglycemia. Until recently, the mechanisms responsible for exercise related hypoglycemia in type 1 DM have been attributed to relative or absolute increases of insulin levels or incomplete glycogen repletion after physical activity. Owing to the qualitative similarity of neuroendocrine, ANS, and metabolic responses to hypoglycemia and exercise, we have hypothesized that neuroendocrine and ANS counterregulatory dysfunction may also play an important role in the pathogenesis of exercise-related hypoglycemia in type 1 DM. Vicious cycles can be created in type 1 DM, where an episode of hypoglycemia or exercise can feed forward to downregulate neuroendocrine and ANS responses to a subsequent episode of either stress, thereby creating further hypoglycemia (Figure 1). This article will review the recent work that has studied the contribution of counterregulatory dysfunction to exercise-induced hypoglycemia in type 1 DM. Copyright © 2004 John Wiley & Sons, Ltd. 1. Reciprocal vicious cycles may be created in type 1 diabetes mellitus (type 1 DM), whereby an episode of hypoglycemia or exercise can feed forward to downregulate neuroendocrine and autonomic nervous system responses to a subsequent episode of either stress, thereby creating further hypoglycemia [source] Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes1DIABETIC MEDICINE, Issue 5 2008T. Parkner Abstract Aims To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid-acting insulin analogue and once daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. Methods Twenty-one patients with Type 2 diabetes treated with oral glucose-lowering agents were randomized in this two-period crossover study to an equivalent 24-h dose of continuous subcutaneous infusion of insulin aspart and subsequently once-daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded. Results On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre-injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra-subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra-subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic-only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period. Conclusions Basal continuous subcutaneous infusion of a rapid-acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once-daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. [source] Insulin treatment and cardiovascular disease; friend or foe?DIABETIC MEDICINE, Issue 2 2005A point of view Abstract Background Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. Summary of comment Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. Conclusion Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area. [source] Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1, gene and the relationship to ,-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitusDIABETIC MEDICINE, Issue 12 2004J. Lauenborg Abstract Aims In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to ,-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1, (HNF-1,) gene has been associated with decreased serum insulin and C-peptide responses during an oral glucose tolerance test (OGTT) in glucose-tolerant subjects. The aims of the present study were to evaluate the influence of the polymorphism on the serum insulin and C-peptide responses to an OGTT in glucose-tolerant women with and without previous GDM and to investigate if this polymorphism is associated with GDM. Methods The Ala/Val98 polymorphism was measured in 376 women of Danish origin with previous GDM, and in 724 age-matched and 310 middle-aged glucose tolerant women using polymerase chain reaction-restriction fragment length polymorphism. Results The allelic frequency of the Ala/Val98 polymorphism was 0.043 [95% confidence interval (CI) 0.028, 0.057] in women with previous GDM vs. 0.037 (95% CI 0.028, 0.047) in age-matched and 0.039 (95% CI 0.024, 0.054) in middle-age women. Among 117 glucose-tolerant women with previous GDM, 10 carriers of the Ala/Val98 polymorphism had a non-significant 27% and 22% reduction in serum C-peptide and insulin levels, respectively, at 30 min during an OGTT. Seventy-eight control subjects carrying the Ala/Val98 polymorphism had a 10% (P = 0.001) and 16% (P = 0.004) reduction in serum C-peptide and insulin levels, respectively, compared with 956 Ala/Ala control subjects. Conclusions The Ala/Val polymorphism at codon98 of HNF-1, is not associated with GDM in Danish women. However, the codon 98 variant is associated with a significant impairment of serum insulin and C-peptide responses during an OGTT in glucose-tolerant women without previous GDM. [source] | |||||||||||||||||||||||||||||||||||||