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C-peptide
Terms modified by C-peptide Selected AbstractsPrevalence of obesity and metabolic syndrome in Indigenous Australian youthsOBESITY REVIEWS, Issue 3 2009P. C. Valery Summary We conducted a cross-sectional study of Indigenous youths residing in the Torres Strait region of Australia to assess the prevalence of obesity and the metabolic syndrome. Data on body mass index (BMI), waist circumference, blood pressure, presence of acanthosis nigricans and blood glucose were collected. Fasting glucose, insulin, C-Peptide, HbA1c and lipids were measured, and an oral glucose tolerance test was performed in those with a BMI greater than 25 (childhood-equivalent cut-points) or fasting glucometer reading >5.5 mmol/L. Of 158 youths, 31% were overweight and 15% were obese, 38% had enlarged waist circumference consistent with central obesity, 43% had acanthosis nigricans and 27% were hypertensive. More females than males had enlarged waist circumferences (59% vs. 13%, P < 0.001). Among overweight or obese youth, 56% had significantly elevated insulin (P = 0.021); they also had higher HOMA-IR (P = 0.002). The metabolic syndrome was present in 17% of all youths (mostly females) and in 33% of the overweight or obese subgroup. Type 2 diabetes was diagnosed in two youths. These very high proportions of overweight or obese Torres Strait youth with metabolic risk factors have major public health implications. [source] Effects of C-peptide on forearm blood flow and brachial artery dilatation in patients with type 1 diabetes mellitusACTA PHYSIOLOGICA, Issue 3 2001E. Fernqvist-Forbes Recent studies suggest that C-peptide increases blood flow in both exercising and resting forearm in patients with type 1 diabetes. Now we have studied the effect of C-peptide administration on endothelial-mediated and non-endothelial-mediated arterial responses as well as central haemodynamics in 10 patients with type 1 diabetes in a placebo-controlled double-blind study. Euglycaemia was maintained with an i.v. insulin infusion before and during the study. A high-resolution ultrasound technique and Doppler echocardiography were used to assess haemodynamic functions. Brachial artery blood flow and brachial artery diameter were measured in the basal state, 1 and 10 min after reactive hyperaemia and 4 min after sublingual glyceryl trinitrate administration (GTN; endothelial-independent vasodilatation), both before and after the end of 60-min C-peptide (6 pmol kg,1 min,1) or saline infusion periods. Echocardiographic measurements were also performed before and at the end of the infusion periods. Seven healthy age-matched males served as controls for vascular studies. The patients showed a blunted brachial dilatation after reactive hyperaemia in comparison with the healthy controls (2.1 ± 0.5% vs. 9.3 ± 0.3%, P < 0.001), indicating a disturbed endothelial function. C-peptide infusion compared with saline resulted in increased basal blood flow (33 ± 6%, P < 0.001) and brachial arterial dilatation (4 ± 1%, P < 0.05). Left ventricular ejection fraction seemed to be improved (5 ± 2%, P < 0.05) at the end of C-peptide infusion compared with placebo. The vascular response to reactive hyperaemia and GTN was not affected by C-peptide infusion. Our results demonstrate that physiological concentrations of C-peptide increase resting forearm blood flow, brachial artery diameter and left ventricular systolic function in patients with type 1 diabetes. [source] Earlier triple therapy with pioglitazone in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 9 2009G. Charpentier Aims: This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods: This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA1c) ,6.5%] or titrated up to 45 mg (if HbA1c >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA1c (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ,-cell function (HOMA-B) were calculated. Results: Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA1c and ,2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of <8.5% achieved the HbA1c target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA1c level was , 8.5%, 13% achieved the HbA1c target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions: In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA1c, FPG and surrogate measures of ,-cell function. Patients were more likely to reach target HbA1c levels (< 7.0%) with pioglitazone treatment if their baseline HbA1c levels were < 8.5%, highlighting the importance of early triple therapy. [source] Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009R. E. Pratley Aim:, To evaluate the efficacy and safety of alogliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy. Methods:, After a 2-week screening period, adult patients 18,80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide (open label) plus placebo (single blind). After the run-in period, patients were randomly assigned to double-blind treatment with alogliptin 12.5 mg (n = 203), alogliptin 25 mg (n = 198), or placebo (n = 99) for 26 weeks. The primary end-point was change from baseline to week 26 in glycosylated haemoglobin (HbA1c). Secondary end-points included clinical response rates and changes in fasting plasma glucose, ,-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment ,-cell function), body weight, and safety end-points [adverse events (AEs), clinical laboratory tests, vital signs and electrocardiographic readings]. Results:, The study population had a mean age of 57 years and a mean disease duration of 8 years; it was well balanced for gender (52% women) and was mainly white (71%). The mean baseline HbA1c was approximately 8.1% in each group. Significantly greater least squares (LS) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg (,0.38%) and 25 mg (,0.52%) vs. placebo (+0.01%; p < 0.001), and more patients in the alogliptin 25-mg group had HbA1c levels ,7.0% at week 26 (34.8%, p = 0.002) vs. placebo (18.2%). Proportionately more patients in the alogliptin 12.5 mg (47.3%) and 25 mg (50.5%) groups had an HbA1c reduction ,0.5% from baseline compared with patients in the placebo group (26.3%; p < 0.001). Minor improvements in individual markers of ,-cell function were seen with alogliptin, but no significant treatment group differences were noted relative to placebo. Minor LS mean changes in body weight were noted across groups (placebo, ,0.20 kg; alogliptin 12.5 mg, +0.60 kg; alogliptin 25 mg, +0.68 kg). AEs were reported for 63,64% of patients receiving alogliptin and 54% of patients receiving placebo. Few AEs were treatment limiting (2.0,2.5% across groups), and serious AEs (2.0,5.6%) were infrequent, similar across groups, and generally considered not related to treatment. The incidences of hypoglycaemia for placebo, alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1, 15.8 and 9.6% respectively. Conclusions:, In patients with type 2 diabetes inadequately controlled by glyburide monotherapy, the addition of alogliptin resulted in clinically significant reductions in HbA1c without increased incidence of hypoglycaemia. [source] Improvement of insulin sensitivity and ,-cell function by nateglinide and repaglinide in type 2 diabetic patients , a randomized controlled double-blind and double-dummy multicentre clinical trialDIABETES OBESITY & METABOLISM, Issue 4 2007J. Li Aim:, To evaluate the efficacy of nateglinide vs. repaglinide in blood glucose (BG) control and the effect on insulin resistance and ,-Cell function in patients with type 2 diabetes. Methods:, A randomized controlled double-blind and double-dummy multicentre clinical trial was conducted. A total of 230 Chinese patients with type 2 diabetes were enrolled in five clinical centres. The patients were divided randomly into group A [repaglinide 1.0 mg three times daily (t.i.d.), n = 115] or group B (nateglinide 90 mg t.i.d., n = 115). At baseline and end of the 12-week clinical trial, standard mixed meal tolerance tests were performed. Results:, A total of 223 patients (96.9%) completed the trial. There was no significant difference between repaglinide and nateglinide groups in the effects of reducing fasting blood glucose (FBG), 30-, 60- and 120-min BG during 12 weeks (p > 0.05). At week 12, no significant difference was shown between the two groups in BG or haemoglobin A1c (HbA1c) (p > 0.05). However, the effect on HbA1c in repaglinide group was stronger than that in nateglinide group (p < 0.05). After 12-week treatment, area under the curve (AUC) of BG decreased (p < 0.05), and AUC of insulin and C-peptide (CP) increased in both groups (p < 0.05). The effects of nateglinide on AUC of BG, insulin and CP were similar to that of repaglinide (p > 0.05). There was no significant difference between the two groups in AUC of BG, insulin or CP in week 12 (p > 0.05). Furthermore, homeostasis model assessment of insulin resistance (HOMA-IR) and ,-cell function indexes measured by HOMA-,, ,I30/,G30 and (,I30/,G30)/HOMA-IR were improved significantly in both groups during 12 weeks (p < 0.05). The effects of improving HOMA-IR and ,-cell function indexes in nateglinide group were comparable with that of repaglinide group (p > 0.05). Conclusions:, The efficacy of repaglinide and nateglinide in FBG, postprandial glucose excursion and early-phase insulin secretion is similar. But the effect of repaglinide 1.0 mg t.i.d. on HbA1c is stronger than that of nateglinide 90 mg t.i.d.. This trial had shown that nateglinide and repaglinide could comparably improve insulin sensitivity and ,-cell function. [source] C-peptide an adequate endpoint in type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2009Johnny Ludvigsson No abstract is available for this article. [source] C-peptide constricts pancreatic islet arterioles in diabetic, but not normoglycaemic miceDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008Lina Nordquist Abstract Background Pancreatic islet blood flow is regulated separately from that of the exocrine pancreas, and a consistent finding during impaired glucose tolerance is an increased blood perfusion. The aim of the present study was to investigate whether C-peptide affects pancreatic islet arterioles in normal and diabetic mice. Materials and Methods Control and diabetic C57-Bl mice were studied after 2 weeks of alloxan-induced diabetes. Islet arterioles were dissected and microperfused with Dulbecco's modified Eagle medium (DMEM) solution. The effect of luminal application of mouse C-peptide was investigated. Results C-peptide reduced the diameter of islet arterioles from diabetic mice (,10 ± 4%, P < 0.05) compared to base-line values, whilst arterioles from normoglycaemic animals did not respond to C-peptide (P = 0.2). Conclusion These findings suggest a role for C-peptide in the regulation of islet blood flow, especially during conditions with impaired glucose tolerance. Copyright © 2007 John Wiley & Sons, Ltd. [source] Rosiglitazone combined with insulin preserves islet , cell function in adult-onset latent autoimmune diabetes (LADA)DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Zhiguang Zhou Abstract Background LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic , cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment. Methods LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet , cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet , cell function was evaluated by PCP and ,CP(,CP = PCP-FCP). Results All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for ,CP and PCP levels in both groups. (2) PCP and ,CP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and ,CP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and ,CP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and ,CP levels in insulin + RSG group patients still stayed steady, while PCP and ,CP levels decreased more in the insulin alone group. Conclusions This pilot study suggests that rosiglitazone combined with insulin may preserve islet , cell function in LADA patients. Copyright © 2004 John Wiley & Sons, Ltd. [source] C-peptide makes a comebackDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2003John Wahren Proinsulin C-peptide was for long considered to be without biological activity of its own. New findings demonstrate, however, that it is capable of eliciting both molecular and physiological effects, suggesting that C-peptide is in fact a bioactive peptide. When administered in replacement doses to animal models or to patients with type 1 diabetes, C-peptide ameliorates diabetes-induced functional and structural changes in both the kidneys and the peripheral nerves. It augments blood flow in a number of tissues, notably skeletal muscle, myocardium, skin and nerve. These effects are thought to be mediated via a stimulatory influence on Na+,K+ -ATPase and on endothelial nitric oxide synthase. Specific binding of C-peptide to cell membranes of intact cells and to detergent-solubilized cellular components has been demonstrated, indicating the existence of cell-surface binding sites for C-peptide. A number of intracellular responses are elicited by C-peptide, including a rise in Ca2+ concentration and activation of MAP-kinase signaling pathways. Many but not all of C-peptide's intracellular effects can be inhibited by pertussis toxin, supporting the notion that C-peptide may interact via a G-protein-coupled receptor. Additional data suggest that C-peptide may interact synergistically also in the insulin signaling pathway. Combined, the available observations show conclusively that C-peptide is biologically active, even though its molecular mechanism of action is not as yet fully understood. The possibility that replacement of C-peptide in patients with type 1 diabetes may serve to retard or prevent the development of long-term complications should be evaluated. Copyright © 2003 John Wiley & Sons, Ltd. [source] Higher fasting insulin but lower fasting C-peptide levels in African Americans in the US population,DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2002Maureen I. Harris Abstract Background Fasting serum insulin and fasting serum C-peptide are risk factors for developing type 2 diabetes. Because of the higher incidence of type 2 diabetes in African Americans and Hispanic Americans, it is likely that these groups may differ from non-Hispanic whites in their levels of insulin and C-peptide. Methods We analyzed data from a nationally representative sample of adults in the US population for whom sociodemographic, clinical, and laboratory information were obtained. The data were used to describe distributions of fasting insulin and fasting C-peptide in non-Hispanic white, non-Hispanic black, and Mexican American men and women aged ,20 years without a medical history of diabetes. Results Among men, Mexican Americans had higher insulin values than non-Hispanic whites and blacks. Among women, both Mexican Americans and blacks had higher insulin values than whites. For C-peptide, differences by sex and race-ethnicity paralleled those seen for fasting insulin with the exception that black men had significantly lower C-peptide values than whites and Mexican Americans. After adjustment for age, fasting plasma glucose (FPG), body mass index (BMI), and waist-to-hip ratio (WHR), the higher levels for insulin in blacks and Mexican Americans remained; both black men and women had significantly lower C-peptide values than whites and Mexican Americans. The molar ratio of fasting C-peptide to fasting insulin was similar for men and women in each race-ethnic group. However, blacks had substantially lower ratios than whites and Mexican Americans. Conclusions We found wide variations in fasting insulin and fasting C-peptide levels by race and ethnicity in US adults that were not explained by confounding factors, primarily measures of obesity. Most notably, the higher fasting insulin and lower fasting C-peptide levels in blacks implies that there is a derangement in insulin clearance and an impairment in beta-cell function in blacks compared with whites and Mexican Americans. Published in 2002 by John Wiley & Sons, Ltd. [source] Elevated fasting plasma C-peptide occurs in non-diabetic individuals with fatty liver, irrespective of insulin resistanceDIABETIC MEDICINE, Issue 9 2009G. Perseghin Abstract Aims Studies have pointed to insulin resistance as a pathogenic factor in fatty liver. Although pancreatic B-cell function is believed to be involved, its role is unclear. This study was undertaken to test whether fasting C-peptide, an index of fasting B-cell function, was related to intra-hepatic fat (IHF) content in non-diabetic humans. Methods We assessed, retrospectively, fasting plasma C-peptide concentration in 31 patients with fatty liver and 62 individuals without fatty liver. The IHF content was measured by proton magnetic resonance spectroscopy (1H-MRS), while insulin sensitivity was estimated based on fasting plasma glucose and insulin with the homestasis model assessment (HOMA) 2 method. Results Age, sex and body mass index (BMI) were not different between groups. Patients with fatty liver had higher fasting insulin (P < 0.01), C-peptide (P < 0.005) and lower insulin sensitivity (HOMA2-%S). Fasting insulin alone explained 14% of the IHF content variability (P < 0.001); inclusion of fasting C-peptide in multivariate regression explained up to 32% (P < 0.001). A subgroup analysis was performed by matching 1 : 1 for HOMA2-%S. These data were analysed by conditional logistic regression which showed that, when HOMA2-%S was matched between groups, fasting C-peptide remained the only significant predictor of fatty liver. Conclusions Non-diabetic individuals with fatty liver are characterized by increased fasting plasma C-peptide concentration, irrespective of their insulin resistant state. [source] Effect of RBP4 gene variants on circulating RBP4 concentration and Type 2 diabetes in a Chinese populationDIABETIC MEDICINE, Issue 1 2008C. Hu Abstract Aims Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population. Methods We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured. Results Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively). Conclusion Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism. [source] Low-risk HLA genotype in Type 1 diabetes is associated with less destruction of pancreatic B-cells 12 months after diagnosisDIABETIC MEDICINE, Issue 12 2007M. Spoletini Abstract Aims The role of human leukocyte antigen (HLA) genes in the susceptibility to Type 1 diabetes (T1DM) is well known. However, we do not know whether the degree of pancreatic B-cell destruction depends on different HLA genetic risk. The aim of this study was to analyse the influence of DRB1* and DQB1* genes on the rate of pancreatic B-cell loss in a prospective series of 120 consecutive newly diagnosed T1DM subjects in the first 12 months after diagnosis. Methods Patients were typed for HLA-DRB1* and DQB1* loci by a reverse line blot assay using an array of immobilized sequence-specific oligonucleotide probes. C-peptide, insulin requirement and glycated haemoglobin (HbA1c) were determined at diagnosis and every 3 months for 12 months. The variance of C-peptide as evidence of B-cell loss during follow-up was analysed using the general linear model for repeated-measures procedure. Results Fasting C-peptide in T1DM subjects with low HLA genetic risk was significantly higher when compared with subjects with moderate or high HLA genetic risk from time of diagnosis up to 12 months (P = 0.007 and P = 0.0002, respectively). Nonetheless, the changes in C-peptide levels over a 12-month period did not differ significantly between T1DM subjects with different HLA genetic risks. Conclusions Low-risk HLA genotype in T1DM is associated with less destruction of pancreatic B-cells up to 12 months after diagnosis. These results are useful when designing trials for therapies aimed to prevent the progression of B-cell destruction in recent-onset T1DM. [source] Effect of long-term treatment with rosiglitazone on arterial elasticity and metabolic parameters in patients with Type 2 diabetes mellitus: a 2-year follow-up studyDIABETIC MEDICINE, Issue 11 2007M. Shargorodsky Abstract Aims, Thiazolidinediones may influence the atherogenic process by improving cardiovascular risk factors. The present study was designed to determine the long-term effect of rosiglitazone on arterial compliance and metabolic parameters in patients with Type 2 diabetes. Methods, In an open-label, prospective study, 65 diabetic patients received rosiglitazone orally (4,8 mg/day) for 6 months. After 6 months, the patients continued an open follow-up study and were divided into two groups: group 1 included patients continuing rosiglitazone for 2 years, group 2 included patients discontinuing rosiglitazone and receiving other oral glucose-lowering agents. Lipid profile, glycated haemoglobin (HbA1c), insulin, C-peptide, fibrinogen, high-sensitivity-CRP and homeostasis model assessment,insulin resistance were measured. Arterial elasticity was assessed using pulse wave contour analysis. Results, In patients treated with rosiglitazone for 2 years: the large artery elasticity index (LAEI) increased from 10.0 ± 4.6 to 13.9 ± 4.7 ml/mmHg × 100 after 2 years (P = 0.003). The small artery elasticity (SAEI) index increased significantly from 3.2 ± 1.2 to 5.1 ± 1.9 (P < 0.0001). In patients who discontinued rosiglitazone: LAEI did not change after 6 months, but decreased from 12.1 ± 5.4 to 8.9 ± 3.9 ml/mmHg × 10 (P < 0.0001) at the end of 2 years. SAEI increased during the first 6 months of treatment, from 3.9 ± 1.8 to 5.1 ± 1.5 ml/mmHg × 100 (P < 0.0001) and decreased after discontinuation of rosiglitazone (P = 0.042). Conclusions, Prolonged treatment with rosiglitazone improved arterial elasticity. However, significant deterioration in LAEI and SAEI was observed in patients who discontinued rosiglitazone. The beneficial vascular effect of rosiglitazone on arterial elasticity was independent of glycaemic control. [source] Reduced insulin secretion in normoglycaemic patients with ,-thalassaemia majorDIABETIC MEDICINE, Issue 12 2006N. G. Angelopoulos Abstract Aims To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with ,-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload. Methods We measured fasting glucose, insulin and C-peptide levels in 24 patients with ,-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated. Results Fasting glucose levels in patients were increased compared with control subjects (5.5 ± 0.12 vs. 4.7 ± 0.13 mmol/l, mean ± sem, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SCHOMA) was lower in thalassaemic patients (SCHOMA 88.5 ± 11.11 vs. 184.3 ± 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SCHOMA was higher in the patients with NFG compared with those with IFG patients (110.6 ± 17.63 vs. 66.3 ± 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISIHOMA) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SCHOMA (r = 0.45, P = 0.02) and negatively with ISIHOMA (r = ,0.43, P = 0.03). Conclusions These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in ,-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent. [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] 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] Insulin, insulin propeptides and intima-media thickness in the carotid artery in 58-year-old clinically healthy men.DIABETIC MEDICINE, Issue 2 2002Insulin Resistance study (AIR), The Atherosclerosis Abstract Aims To examine the relationship between specific (intact) insulin, insulin propeptides and subclinical atherosclerosis. Methods A cross-sectional study based on a stratified sampling of randomly selected, clinically healthy 58-year-old men (n = 391). Ultrasound examinations of the carotid arteries were performed with measurement of intima-media thickness (IMT) in the common carotid artery and in the carotid artery bulb. Fasting, cross-reacting plasma insulin (RIA), specific (intact) insulin, proinsulin, 32,33 split proinsulin and C-peptide were measured. Results Plasma concentrations of cross-reacting plasma insulin, specific insulin, proinsulin, 32,33 split proinsulin and C-peptide were univariately associated with common carotid artery IMT. Established risk factors such as blood pressure, smoking, apoB, triglycerides, body mass index (BMI), and waist,hip ratio were also related to IMT. After adjustment for smoking, apoB, blood pressure and triglycerides, cross-reacting plasma insulin, proinsulin and C-peptide but not specific insulin and split 32,33 proinsulin remained associated with carotid artery IMT. No associations remained after adjustment for BMI. Conclusions Fasting plasma proinsulin, C-peptide, and insulin by cross-reacting RIA was associated with common carotid artery IMT independent of several conventional risk factors for atherosclerosis. The multicollinearity between the insulin peptides and propeptides makes it difficult to clarify the exact role of each peptide. [source] Glibenclamide improves postprandial hypertriglyceridaemia in Type 2 diabetic patients by reducing chylomicrons but not the very low-density lipoprotein subfraction levelsDIABETIC MEDICINE, Issue 10 2001I. Skrapari Abstract Aim, There are scarce data dealing with the degree of postprandial lipaemia after sulphonylurea administration. The aim of this study was to examine the effect of acute glibenclamide administration on postprandial lipaemia in Type 2 diabetic patients. Methods, Eight randomly selected Type 2 diabetic individuals, aged 43,65 years (mean, 54 years), who had never received any anti-diabetic drug, were included in the study. Each patient was given a 485 kcal mixed meal (45% fat, 40% carbohydrate and 15% protein) twice on separate days after an overnight fast: once with placebo and once with 5 mg glibenclamide, per os, in a random order. The two tests were performed with an interval of 7 days. Venous blood samples were drawn just before and 2 h, 4 h and 6 h after meal consumption. Total triglyceride levels in plasma, in chylomicrons (CM), in CM-deficient plasma, in very low-density lipoprotein (VLDL) subfractions (VLDL-1, VLDL-2) and in intermediate-density lipoprotein (IDL) were determined. Free fatty acid (FFA) and total cholesterol levels in plasma, as well as high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels in CM-deficient plasma, were also measured. Finally, serum glucose, insulin and C-peptide concentrations were measured in each sample. Results, As expected there was a significant decrease in postprandial glycaemia after glibenclamide administration compared to placebo (mean area under the curve values: AUC = 53.3 ± 18.2 and 69.1 ± 21.6 mm/h, P = 0.00009). In addition, the mean AUC values of insulin and C-peptide were significantly greater after drug administration. The AUC values of total plasma triglyceride and of CM triglyceride following glibenclamide administration were significantly lower compared to placebo, while the AUC values of postprandial triglyceride in CM-deficient plasma and of postprandial triglyceride in VLDL-1, VLDL-2 and IDL were not different after drug administration compared to placebo. Finally, no significant differences were noted in the AUC values of total cholesterol, LDL cholesterol, HDL cholesterol and plasma FFA levels after glibenclamide administration. Conclusions, These results demonstrate that glibenclamide administration improves postprandial hypertriglyceridaemia acutely by reducing postprandial triglycerides of intestinal origin. Diabet. Med. 18, 781,785 (2001) [source] Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitusDIABETIC MEDICINE, Issue 3 2000B. -L. Summary Aims Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects when administered to patients with Type 1 diabetes mellitus. This study was undertaken to determine if combined treatment with C-peptide and insulin might reduce the level of microalbuminuria in patients with Type 1 diabetes and incipient nephropathy. Methods Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patients received s.c. injections of either human C-peptide (600 nmol/24 h) or placebo plus their regular insulin regimen for 3 months. Results Glycaemic control improved slightly during the study and to a similar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretion decreased progressively on average from 58 ,g/min (basal) to 34 ,g/min (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment periods was statistically significant (P < 0.01). In the 12 patients with signs of autonomic neuropathy prior to the study, respiratory heart rate variability increased by 21 ± 9% (P < 0.05) during treatment with C-peptide but was unaltered during placebo. Thermal thresholds were significantly improved during C-peptide treatment in comparison to placebo (n = 6, P < 0.05). Conclusion These results indicate that combined treatment with C-peptide and insulin for 3 months may improve renal function by diminishing urinary albumin excretion and ameliorate autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus. [source] Androgen receptor gene polymorphism and the metabolic syndrome in 60,80 years old Norwegian menINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2010Paal André Skjærpe Summary The metabolic syndrome (MS) includes a clustering of metabolic derangements. Low testosterone levels have been shown to be associated with both components of MS and MS per se. As most androgen-related effects are mediated thorough the androgen receptor (AR), we wanted to investigate to which degree the AR CAG and GGN repeat polymorphisms might be related to MS. Sixty-eight men, 60,80 years old, with subnormal total testosterone levels (,11.0 nmol/L) and 104 men with normal levels (>11.0 nmol/L), participating in a nested case,control study were investigated in this study. Body weight, height, waist circumferences and blood pressure were measured. Fasting blood samples were drawn and an oral glucose tolerance test (OGTT) was performed. The CAG and GGN polymorphisms in the AR gene were determined by direct sequencing of leucocyte DNA. Men with MS had lower CAG repeat number than healthy men (p = 0.007). There were, however, no difference in CAG or GGN repeats length between the groups with subnormal or normal testosterone concentrations. In cross-sectional analyses, men with CAG repeat lengths , 21 had significantly higher fasting glucose, C-peptide and glycosylated haemoglobin (HbA1c) levels (all p < 0.05). In multiple regression analyses, CAG repeat length was an inverse and independent predictor of glucose after an OGTT and of HbA1c levels. We also found that men with more than one component of MS had shorter CAG repeat number (p for trend 0.013) than those with only one component. In conclusion, there were no associations with GGN repeat length, while short CAG repeat length seems to be associated with increased risk of MS. [source] Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer,INTERNATIONAL JOURNAL OF CANCER, Issue 2 2004Annekatrin Lukanova Abstract Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91,11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65,11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15,0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22,1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer. © 2003 Wiley-Liss, Inc. [source] Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgeryJOURNAL OF DIABETES, Issue 1 2010Mousumi BOSE Abstract Background:, The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short- and long-term changes in hormonal determinants of blood glucose. Methods:, Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) levels and the incretin effect on insulin secretion. Results:, The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP) levels, early phase insulin secretion, and other parameters of ,-cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year. Conclusions:, The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery. [source] Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2007Ewert Schulte-Frohlinde Abstract Background and Aim:, Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. Methods:, Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. Results:, In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. Conclusions:, The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation. [source] Labeling of human C-peptide by conjugation with N -succinimidyl-4-[18F]fluorobenzoateJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2001Anna Fredriksson Abstract We have labeled proinsulin connecting peptide (C-peptide) with fluorine-18 (t½=109.7 min) in order to perform in vivo biodistribution and pharmacokinetic studies with position emission tomography (PET). This study reports the optimization of the conjugation labeling in the N-terminal with N -succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). In preparative runs N -4-[18F]fluorobenzoyl-C-peptide ([18F]FB-C-peptide) was produced in 8,12% decay-corrected yields, counted from resolubilized [18F]F,, in less than 5 h. The specific radioactivity of [18F]FB-C-peptide, determined using ELISA for one of the preparations, was around 70 GBq/,mol at end of synthesis. Copyright © 2001 John Wiley & Sons, Ltd. [source] Antidiabetogenic action of Morus rubra L. leaf extract in streptozotocin-induced diabetic ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2010Suman Bala Sharma Abstract Objectives Researchers all over the world are exploring herbal supplements to control diabetes and its complications. This study evaluated the antidiabetic action of Morus rubra L. aqueous leaf extract through its effect on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-induced diabetic rats. Methods The extract was orally administered to diabetic rats (100, 200 and 400 mg/kg body weight) daily for 21 days. Fasting blood glucose was measured on days 0, 7, 14 and 21. At the end of the experiment, blood samples were drawn to measure glucose tolerance, glycosylated haemoglobin, insulin, C-peptide and lipid parameters. Antioxidant enzymes (superoxide dismutase and catalase), reduced glutathione and lipid peroxides were determined in blood and liver tissue. Histopathological examination of pancreatic tissue was also performed. Key findings The extract showed a dose-dependent fall in fasting blood glucose. Treatment with 400 mg/kg extract produced a significant reduction in glycosylated haemoglobin with a concomitant elevation in plasma insulin and C-peptide levels. The altered serum lipids in diabetic rats were significantly restored following treatment with the extract. In erythrocytes, as well as liver, the activity of antioxidant enzymes and content of reduced glutathione were found to be significantly enhanced, while levels of serum and hepatic lipid peroxides were suppressed in extract-fed diabetic rats. Histopathological examination of pancreatic tissue revealed an increased number of islets and ,-cells in extract-treated diabetic rats. ConclusionsM. rubra aqueous leaf extract leads to control over hyperglycaemia and dyslipidaemia. The study also demonstrates its antioxidant nature, and hence it may be protective against diabetic complications. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 79JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003U Del Carro Peripheral neuropathy is one of the most common secondary complications of diabetes mellitus, causing severe and prolonged morbidity. However, clinical and experimental studies have reported that careful glucose control may prevent, stabilize, and/or reverse neuropathy and other chronic diabetic complications. Unfortunately, insulin therapy does not prevent the development or progression of chronic lesions in the vessels, kidneys, eyes, or nerves of the diabetic patient. There is great interest in investigating other forms of endocrine replacement therapy, such as transplantation of the pancreas or of the islets of Langerhans (IT). Diabetic polyneuropathy (DP) evolution is characterized by progressive demyelination and axonal loss and is manifested by signs and symptoms on physical examination and abnormalities in nerve conduction studies (NCS). NCS provide reliable, noninvasive, objective measures of peripheral nerve function and constitute the most important technique for the evaluation of the severity of DP in clinical trials. Several research groups have demonstrated that skin biopsy with measurement of intraepidermal nerve fiber density is another method minimally invasive and repeatable that provides direct pathologic evidence of axonal damage in diabetic neuropathy. Fifty-one consecutive IDDM patients with or without end stage renal disease were enrolled at the moment of islet (Is), kidney (KD), kidney-pancreas (KP) or kidney-islet (KI) transplantation. Patients underwent skin biopsy punch, neurologic examination and neurophysiological investigation. Particularly, 20 pts underwent KP tx, 16 KD tx, 10 islet tx and 5 KI. The patients were comparable for duration of diabetes, dialysis (when present), age, lipid profile. In half of the patients a follow-up of 2 years has been reached. After KP tx, and partially with KI, a complete normalization of glycometabolic control has been achieved, with statistically lower HbA1c in comparison with KD group (KP = 6.2; 0.1% vs. KD = 8.4; 0.5%; p < 0.01). In the KI/Is group, a long-term restoration of islet endocrine function has been achieved, with insulin independence. When this has been lost, a persistent secretion of C-peptide was shown for a long period of time. This was correlated with a global improvement quality of life and vascular structure. Preliminary results will be presented. [source] C-Peptide Deficiency: An Important Pathogenetic Factor In Type 1 Diabetic NeuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000Aaf Sima Background: C-peptide has insulin-like effects and ameliorates the acute nerve conduction defect (NCD) in experimental and human type 1 diabetic neuropathy (DN). Methods: In this study, diabetic BB/Wor-rats were treated with rat C-peptide (75 ng/kg) from onset of diabetes for 8 months (prevention-group, PG). In a separate experiment, 5-mo untreated diabetic BB/Wor-rats were started on the same C-peptide treatment continued to 8 mo of diabetes (intervention group, IG). Results: In the PG, the NCD was significantly decreased (p < 0.001) compared to untreated BB/Wor-rats and was similar to that of normo-C-peptidemic and isohyperglycemic type 2 BBZ rats. This effect was associated with significant preventions of nodal changes (p < 0.001) including axo-glial dysjunction (p < 0.001), which was not different from non-diabetic control rats. Axonal atrophy and Wallerian degeneration were significantly prevented (both p < 0.05). In the IG, the NCD decreased significantly (p < 0.01) during the 3 mo treatment period. Associated with the functional improvement, nodal changes improved significantly (p < 0.001) as did axonal degenerative changes (p < 0.01). C-peptide treatment in the IG resulted in a significant increase in the frequency of regenerating fibers (p < 0.001) compared with untreated 5 mo diabetic rats. Conclusion: These studies demonstrate that C-peptide replacement in type 1 diabetes prevents the chronic NCD and structural changes. Furthermore, C-peptide treatment significantly improves the already established functional and structural abnormalities of DN. This is the first demonstration of a therapeutic improvement of established neuropathy in experimental diabetes. We conclude that C-peptide deficiency in type 1 diabetes is an important pathogenetic component of DN and that its replacement may provide a valuable adjunct to intensive insulin treatment. [source] Fasting c-peptide and insulin-like growth factor-binding protein-1 levels help to distinguish childhood type 1 and type 2 diabetes at diagnosisPEDIATRIC DIABETES, Issue 2 2007Lorraine E Levitt Katz Background:, Children with new onset diabetes (n = 175) were evaluated over 12-months. Patients were presumptively diagnosed with type 2 diabetes mellitus (T2DM) (n = 26) based on obesity, a relative with T2DM, the ability to wean from insulin, and absence of glutamic acid decarboxylase-65 (GAD-65) antibodies. We hypothesized that markers of insulinization at diagnosis, including fasting C-peptide and insulin-like growth factor-binding protein (IGFBP)-1, in addition to initial CO2 levels and urine ketones, would help in distinguishing type 1 diabetes mellitus (T1DM) from T2DM. Results:, Children with T1DM (84 male, 65 female) had a mean age of 8.7 ± 4.3 yr and a racial background of 78% white, 19% black, and 3% other. In contrast, children with T2DM (13 female, 13 male) had a mean age of 14.2 ± 3.1 yr with a racial background of 58% black, 27% white, and 15% other. Fasting C-peptide level was 0.38 ± 0.37 ng/mL in T1DM vs. 2.66 ± 2.14 ng/mL in T2DM; a C-peptide of 0.85 ng/mL had 83% sensitivity in distinguishing T1DM from T2DM. Fasting IGFBP-1 level was 38.1 ± 39.1 ng/mL (T1DM) vs. 3.6 ± 4.5 ng/mL (T2DM); a value of 3.6 ng/dL could distinguish the two types of diabetes with 93% sensitivity. Urinary ketones were found in 79% of children with T1DM compared with 56% of those with T2DM, and the magnitude was associated with type of diabetes. Initial CO2 level for T1DM was 17.9 ± 6.9 mmol/L vs. 22.7 ± 5.7 mmol/L for T2DM; a value of 21.5 mmol/L could distinguish the two types of diabetes with 83% sensitivity. Conclusions:, In addition to obesity, family history of T2DM, and absence of GAD-65 antibodies, children with new-onset T2DM may be distinguished from those with T1DM by a combination of biochemical parameters (C-peptide, IGFBP-1, CO2, and urine ketones). [source] Interactions between metabolic and reproductive functions in the resumption of postpartum fecundityAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2009Claudia Valeggia Lactation has long been recognized as a major determinant of interbirth intervals. The temporal pattern of nursing has been proposed as the mechanism behind lactational amenorrhea. We present a new model of the dynamic regulation of lactational amenorrhea that identifies maternal energy availability as the main determinant of ovarian resumption. Variation in the intensity of lactation remains a component of the model as a determinant of the absolute energetic cost of milk production. However, maternal energy supply determines net energy availability; a larger energy supply leaves a greater net energy surplus than a smaller energy supply (lactation costs being equal). We characterize the hormonal postpartum profile of 70 lactating Toba women of Argentina. We use C-peptide, which reflects maternal insulin production, as a measure of energy availability. Initially low, insulin production rises as the postpartum period progresses, reflecting the declining metabolic load of lactation. A short period of supernormal insulin production precedes menstrual resumption. The high levels of insulin may play a role in stimulating the resumption of ovarian activity, which in turn may help to resolve the transient period of insulin resistance. The dynamics of insulin sensitivity during lactation would aid in synchronizing the resumption of ovarian function with a reduction in the energy demands of milk production. This hypothesis is supported by the sustained weight gain experienced by lactating women during the months preceding the first postpartum menses. The link between fecundity and energy balance could serve as a mechanism for adjusting the duration of lactational amenorrhea to the relative metabolic load of lactation. Am. J. Hum. Biol., 2009. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||