Diabetes Development (diabetes + development)

Distribution by Scientific Domains

Selected Abstracts

Pregnancy and lactation have anti-obesity and anti-diabetic effects in Ay/a mice

E. N. Makarova
Abstract Aim:, Dominant ,yellow' mutation at the mouse agouti locus (Ay) results in obesity. Pregnancy and lactation are characterized by large energy demand. The aim of this study was to investigate whether obesity would develop in pregnant and suckling Ay mice. Methods:, Body weight and food intake in pregnancy, lactation, and after weaning, plasma leptin, insulin, corticosterone and blood glucose concentrations on days 7, 13 and 18 of pregnancy, days 1, 10, 21 and 80 postpartum, glucose and insulin tolerance on pregnancy days 7 and 18 were measured in C57Bl/6J mice of a/a (normal metabolism) and Ay/a genotypes. The same parameters were also measured in age-matched virgin females. Results:, Virgin Ay/a females exhibited hyperphagia, enhanced body weight, glucose intolerance and normal blood parameters at the mating age. With age, they developed obesity, hyperleptinaemia, hyperinsulinaemia and hyperglycaemia. Obesity did not develop in mated Ay/a mice; during suckling, they had equal food intake and body weight as a/a mice. During pregnancy, glucose tolerance was enhanced in Ay/a mice and became equal in both genotypes. In both genotypes, concentrations of hormones increased, and glucose decreased from pregnancy day 7 to day 18 and returned to normal values after parturition. Ay/a mice did not differ from a/a in corticosterone, insulin and glucose levels during pregnancy and lactation, in leptin levels during suckling; however, Ay/a mice had two times higher leptin levels than a/a during pregnancy. After weaning, Ay/a mice began to eat and weigh more than a/a exhibiting normal metabolic parameters for 50 days. Conclusion:, Pregnancy and lactation retard obesity and diabetes development in Ay mice. [source]

Impaired glucose regulation and type 2 diabetes in children and adolescents

Kerstin Kempf
Abstract Diabetes mellitus in paediatric patients used to be almost exclusively type 1, but in recent years, case series as well as hospital-based and population-based studies indicated that the number of children and adolescents with type 2 diabetes (T2DM) has been increasing. This development is alarming since T2DM in youth is usually not an isolated condition, but accompanied by other cardiovascular risk factors such as obesity, dyslipidaemia, hypertension and low-grade inflammation. In adults, numerous studies provided detailed data on prevalence, incidence and risk factors for the development of T2DM, but for children and adolescents clinical and experimental data are still rather limited. This review provides an overview about the epidemiology and pathogenesis of T2DM in youth and about impaired glucose regulation as major risk factor for diabetes development with a special focus on the recent literature on clinical and lifestyle-related risk factors. Differences in incidence and prevalence across different populations indicate that ethnic background and genetic pre-disposition may be important risk determinants. In addition, epigenetic factors and foetal programming appear to confer additional risk before birth. Among the environmental and lifestyle-related risk factors there is evidence that obesity, hypercaloric diet, physical inactivity, socio-economic position (SEP), smoking, low-grade inflammation, psychosocial stress and sleeping patterns contribute to the risk for T2DM. However, the assessment of the relevance of risk factors and of incidence or prevalence estimates in youth is complicated by methodological issues that are also discussed. Copyright 2008 John Wiley & Sons, Ltd. [source]

Prevention of diabetes in NOD mice at a late stage by targeting OX40/OX40 ligand interactions

Abstract Autoreactive T,cells play a major role in the development of insulin-dependent diabetes mellitus, suggesting that costimulatory molecules that regulate T,cell responses might be essential for disease progression. In NOD mice, CD28/B7 and CD40/CD40 ligand,(L) interactions control the onset of diabetes from 2 to 4,weeks of age, but blocking these molecules has little effect after this time. Hence, it is possible that other ligand/receptor pairs control a later phase of disease. We now show that OX40 is expressed on CD4 and CD8 T,cells several weeks prior to islet destruction, which is initiated around weeks,12,14, and that OX40L is present on dendritic cells in both secondary lymphoid organs and the pancreas from 11 to 13,weeks of age. Blocking OX40L at 6, 9, or 15,weeks after birth had little effect on disease; however, inhibiting OX40/OX40L interactions at week,12, or continuous treatment from week,12 onwards, significantly reduced the incidence of diabetes. Histological examination showed that islet destruction was prevented and insulitis reduced by targeting OX40L. These studies show that OX40/OX40L interactions form a late checkpoint in diabetes development and suggest that these molecules are realistic targets for therapeutic intervention. [source]

Micronutrients and the Risk of Type 1 Diabetes: Vitamin D, Vitamin E, and Nicotinamide

Elina Hypponen Ph.D., M.P.H., M.Sc.
Evidence from animal experiments and human observational studies suggests that some dietary micronutrients may protect against the development of type 1 diabetes. The most promising data so far have been obtained for a beneficial role of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes development remain hypothetical. Despite plausible theoretical background evidence from animal experiments and supportive data from pilot studies, randomized, controlled trials using nicotinamide have not provided any evidence for a beneficial effect. [source]

Production of a recombinant cholera toxin B subunit-insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetes

Yoshikazu Yuki
Abstract Mucosally induced tolerance is an attractive strategy for preventing or reducing autoimmune diseases. Here, we produced a recombinant CTB fusion protein linked with autoantigen T cell epitope of insulin B chain peptide 9,23 (C19S) at levels up to 200 mg/L culture media in Brevibacillus choshinensis secretion-expression system. Receptor-competitive assay showed that the CTB-insulin peptide binds to GM1 receptor almost equivalent degree as the native form of CTB. Non-obese diabetes (NOD) mice that spontaneously develop an insulin-dependent diabetes were nasally immunized with CTB-insulin peptide (5 g) for three times. The nasal treatment significantly reduced the development of insulin-dependent diabetes and peptide specific DTH responses after systemic immunization with the insulin peptide B 9,23(C19S) in CFA. Nasal administration of as high as 50 g of the peptide alone demonstrated a similar level of the disease inhibition. In contrast, all mice given 5 g of the insulin peptide alone or 5 g of insulin peptide with 25 g of the free form of CTB did not lead to the suppression of diabetes development and DTH responses. Because molecular weight of the insulin peptide is about one tenth of that of the CTB-insulin peptide, the results demonstrate that the recombinant hybrid of autoantigen and CTB increased its tolerogenic potential for nasal administration by up 100-fold on molar base of autoantigen peptide. Taken together, nasally-induced tolerance by administration of the recombinant B.choshinensis -derived hybrid protein of CTB and autoantigen T cell-epitope peptide could be useful mucosal immunetherapy for the control of T cell-mediated autoimmune diseases. 2005 Wiley Periodicals, Inc. [source]

Liver disease as risk factor for cystic fibrosis-related diabetes development

L Minicucci
Abstract Aim: To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. Methods: Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. Results: Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43,93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1= 58.4 27% predicted versus 67.4 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. Conclusion: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance. [source]