Diabete & metabolisme最新文献

Partial recovery of beta-cell function in type 1 diabetes is common after diagnosis by intensive insulin therapy. Residual beta-cell function can be improved by other therapies. Cyclosporin (CyA) and nicotinamide (NA), alone or in combination, can preserve this function, as indicated by the parameters of metabolic control (insulin dose, HbA1C). After suspension of CyA, insulin requirement returns to control values, suggesting loss of residual beta-cell function. The effects induced by withdrawal of NA after 1 year are not known. For the first time, we studied 27 type 1 diabetes patients treated with NA for 12 months and then followed up for 1 year after discontinuance of NA. Another 25 patients treated with NA + CyA and 28 control patients were followed up similarly. Insulin requirement doubled 12 months after discontinuance of NA or NA + CyA, becoming identical to that of controls. As patients showed HbA1C values similar to control subjects, it is likely that beta-cell function deteriorated after discontinuance of therapy. As NA is safer than other agents and its effects are beneficial, longer studies are warranted to investigate NA in prolonged treatments since this compound is also being considered for prevention of type 1 diabetes.

The increase in cardio-vascular morbidity of people with Type 2 diabetes is due to the frequent association of Type 2 diabetes with classical risk factors but also to diabetes per se, whatever the mechanisms involved. From a clinical point of view, it is important to stop smoking, with a great benefit, to treat hypertension with other drugs than diuretics or beta-blockers and to treat dyslipidaemia. The lipid abnormalities often improve with the only glycaemic control. In all cases, the normalisation of HbA1c is a very important therapeutic goal, by diet, exercise, oral hypoglycaemic drugs or insulin if necessary. The treatment will be especially useful in high risk patients, i.e. patients with coronary heart disease, patients with albuminuria, patients with more than 3 risk factors associated with diabetes and/or with high glycaemic levels.

Many studies of Type 2 (non-insulin-dependent) diabetes mellitus assume that the condition is homogeneous and clearly defined. There are, however, several problems with these assumptions. Thus, definition of Type 2 diabetes is one of exclusion of other types (insulin-dependent, malnutrition-related, gestational and other rarer types) and inevitably contains a heterogeneous group of disorders the aetiology of which is largely unclear, and separation from the insulin-dependent type can be problematic. Diagnosis is also imprecise in asymptomatic subjects due to the lack of accurate diagnostic tools and lack of clear distinction of impaired glucose tolerance. An alternative to the oral glucose tolerance test is urgently needed. Epidemiological studies of Type 2 diabetes and its complications are also fraught with difficulties due to variability of the oral glucose tolerance test, potential problems in glucose measurement, heterogeneity, population selection and problems in international comparisons due to differing age ranges and life expectancy. Great care is needed in all studies of Type 2 diabetes to ensure that the groups under study are properly selected, well-defined and fully described.

Type 2, non-insulin-dependent, diabetes is a disease of glucose homeostasis involving up to 5% of the adult population. The percentage of the population with glucose intolerance is even greater, 10%. These later patients are not diagnosed as "diabetics", but 50% of them have non-insulin-dependent diabetes. Globally, 10% of the adult population has or will have Type 2 diabetes, a major health care problem. Characteristically, in patients with Type 2 diabetes, pancreatic insulin secretion is deficient, liver glucose production is increased during the post-absorption period and peripheral glucose consumption, particularly in striated muscles, is decreased due to insulin resistance. There has been much progress in our understanding of the pathogenic mechanisms involved. When clinical manifestations have become apparent, the relative roles of defective insulin secretion and insulin resistance are difficult to distinguish. However, in persons with oral glucose intolerance or in persons with a high risk of developing Type 2 diabetes, these two mechanisms are more easily differentiated. High risk patients can be identified on the basis of our knowledge of genetic factors in Type 2 diabetes. The incidence of Type 2 diabetes is considerably increased in subjects with two diabetic parents. In addition to genetic factors, environmental factors also influence the development of non-insulin-dependent diabetes, contributing to the multifactorial nature of Type 2 diabetes. In order to establish the relative importance of these different factors, it is useful to define the different stages with characteristic degrees of metabolic disorder, insulin secretion abnormalities and insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aims: To study serum Lp(a) levels and other metabolic cardiovascular risk factors in children with Type 1 diabetes mellitus (DM) compared to sex and age matched nondiabetic children. The correlation of Lp(a) serum levels and other lipid parameters with HbA1c concentrations in diabetic children was investigated.

Design: Transversal observational study.

Target population: 36 C-peptide negative Type 1 DM children without microalbuminuria and no macromicrovascular or neurological complications, aged 8 to 15 years; 17 boys, 19 girls. Mean duration of Type 1 DM was 4.99 +/- 3.04 years, daily insulin need were 32.79 +/- 12.64 Units. 41 healthy children with no family history of DM, aged from 8 to 15 years, 26 boys, 15 girls, were studied in parallel as the control group.

Methods: Serum total cholesterol (TC) and triglycerides (TG) were assayed by enzymatic methods, high-density lipoprotein (HDL) cholesterol by enzymatic method after precipitation of very-low-density (VLDL) and low-density lipoprotein (LDL) fractions. The LDL fractions was estimated after serum precipitation as the difference between total cholesterol and supernatant cholesterol concentrations. Apo-AI, apo-AII and apo-B were measured by radial immunodiffusion assays. Serum Lp(a) was measured by monoclonal anti-Lp(a) antibody (ELISA) method and whole blood glycosylated hemoglobin A1c (HbA1c) by high resolution liquid chromatography.

Results: HbA1c concentration in diabetic children was 7.51 +/- 54% vs 4.16 +/- 0.35% in non diabetic children. Lp(a) serum levels did not significantly differ among both groups (25 +/- 22 mg/dl in diabetics subjects, 22 +/- 22 mg/dl in controls). Significant correlation was found between HbA1c levels and each of TC, LDL and TG serum concentrations in the diabetic group. Lp(a) levels were correlated with glycated hemoglobin in the whole diabetic group. But, in the 2 patients with the poorest metabolic control (HbA1c 10.5%) were excluded, the correlation disappeared.

Conclusions: In 36 children aged 5-15 years with uncomplicated Type 1 DM lasting less than 15 years, Lp(a) serum levels did not differ from age-matched controls but highest Lp(a) values were associated with poorest metabolic control.

In an attempt to clarify the question of an involvement of the inhibition of intestinal glucose absorption in the mechanism of action of Metformin, we used several experimental approaches: 1 glucose/lactate measurement in rat portal blood in vivo and 2 in the venous effluent of an isolated perfused rat intestinal segment; 3 metabolism of freshly isolated enterocytes in vitro and tissue distribution of 3H-labeled Metformin was investigated both in vivo and in vitro. Metformin applied intraluminally had no significant effect on portal glycaemia after a glucose load, but lactate increased, whereas in vivo only a high Metformin dosage reduced portal glucose appearance significantly. Although high Metformin concentrations were found in gut biopsies, precise histological analysis in the isolated intestine revealed that it was absent from enterocytes; however the drug accumulated in villous lacteals. Intrarterially applied Metformin decreased glucose absorption in the isolated perfused ileo-jejunal segment. These data suggested that vascular Metformin boosted intestinal anaerobic glucose metabolism. Biochemical measurements performed on freshly isolated enterocytes showed that even high Metformin levels did not interfere with cell respiration or with Na+/K+ ATPase activity. Thus, our data agree with other recent reports, suggesting that even at nontherapeutic concentrations Metformin has no relevant inhibitory effect on intestinal glucose absorption. The data are discussed in the frame of previous divergent observations. The results suggest however that Metformin of vascular origin stimulates glucose consumption by the intestine, which then increases lactate output from the gut.

Sixty Type 1 (insulin dependent) and sixty Type 2 (non insulin dependent) diabetic patients attending a diabetology unit were examined in search of limited joint mobility, Dupuytren's disease, flexor tenosynovitis and carpal tunnel syndrome, in comparison with two populations of 60 non diabetic controls matched for sex and age with the Type 1 and the Type 2 diabetic patients. Microangiopathic and neuropathic complications, glycaemic control, blood pressure and tobacco consumption were simultaneously assessed in 39 of the 60 type 1 and in all the type 2 diabetic patients. The prevalence of the various soft tissue hand lesions was higher in both diabetic populations (respectively Type 1 and Type 2) than in their control populations: Limited joint mobility: 33.3 and 26.7% vs 5.0 and 8.3% (both p < 0.01); Dupuytren's disease: 35.0 and 30.0% vs 6.7 and 10.0% (both p < 0.01); flexor tenosynovitis: 23.3 and 16.7% vs 0.0 and 3.3% (p < 0.01 and p < 0.05); carpal tunnel syndrome: 26.7 and 15.0% vs 3.3 and 5% (p < 0.01 and NS). The prevalence of limited joint mobility in Type 1 diabetes was independently associated with increasing age (p < 0.05) and to lower extent with increasing duration of diabetes (p = 0.05), whereas the prevalence of Dupuytren's disease only correlated with increasing age in both types of diabetes (p < 0.05). In Type 2 diabetes, the prevalence of flexor tenosynovitis also increased independently with age (p < 0.05), and the prevalence of limited joint mobility increased in the opposite way to the body mass index after adjustment on age, duration of diabetes and sex (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)