Diabete & metabolisme最新文献

The aim of the present study was to look for possible associations between the blood glucose variability and twenty-four clinical parameters in ninety-eight patients with Type 1 diabetes mellitus treated with multiple injections of insulin or insulin pumps and practising self-monitoring of blood glucose. The blood glucose variability was measured as the standard deviation of glucose values obtained by self-monitoring at five specified time points every two days for four weeks. The blood glucose variability significantly correlated with the mean blood glucose level (r = 0.48, p = 0.0001) and with the number of hypoglycaemic events (r = 0.31, p = 0.002), but not with HbA1c (r = 0.19, p = 0.07). Significant correlations were also found between glucose variability and patients' variations of insulin dosage (r = 0.31, p = 0.004), duration of diabetes (r = 0.22, p = 0.03), and body-mass index (r = 0.20, p = 0.04). Patients with incipient or clinical nephropathy had more variable blood glucose values, compared with patients without signs of nephropathy (p = 0.03). Other parameters studied, such as other late diabetic complications, the C-peptide level, the insulin dose and the level of insulin-binding to antibodies did not relate significantly to the blood glucose variability.

The St Vincent Declaration, signed in 1989 by representatives of diabetes associations and experts in diabetology and public health, as well as representatives of European health ministers, is a programme designed to improve the quality of care provided to diabetics in Europe. In France, one of the tasks of the Conseil Supérieur du Diabète (Diabetes Council) is to ensure that this programme is widely implemented. There are multiple facts to the implementation of this project: specific information for diabetics regarding their care, campaigns aimed at the public and health professionals, the setting up of epidemiological studies, and the organization of management strategies. Diabetologists are in the front line of professionals involved in the implementation of this programme, due to their involvement in diabetic education and in the treatment of diabetes and its complications. Even more than previously, the quality of life of the patients is a key objective.

Gliclazide is a second-generation sulfonylures that is widely used in the treatment of non-insulin-dependent diabetes mellitus (Type 2 diabetes). It has been recommended for use on the basis of both its metabolic and nonmetabolic effects. It has a clear beneficial effect on metabolic control in Type 2 diabetes. Blood glucose and lipid levels are lowered. The glucose-lowering effects are secondary to both enhanced insulin secretion and a decrease in insulin resistance. The former is due to closure of a K+ adenosine triphosphate (ATP) channel in the beta cell. The mechanism whereby insulin action on the liver and muscle are potentiated remains unknown. It does not appear to involve the insulin receptor, and although glycogen synthase activation is enhanced, this is probably not specified. It has proven difficult to separate the metabolic effects of gliclazide form the effects of improved control. The metabolic actions are probably also shared with over sulfonylureas. Gliclazide also has beneficial effects on platelet behavior and function and on the endothelium, in addition to improving free radical status. These effects should be beneficial for the prevention of diabetic microangiopathy. Some evidence has appeared for the prevention of deterioration of diabetic retinopathy, but results are variable and more convincing studies are required. Many of the nonmetabolic effects of gliclazide appear to be unique to this agent. Gliclazide thus appears to be a reasonable choice in the treatment of Type 2 diabetes with diet failure, both from the metabolic and non-metabolic standpoint.

Diabetic macroangiopathy is often viewed as an accelerated and aggravated form of atherosclerosis. Several biological disturbances that are associated with diabetes partially account for a possible aggravation of atherosclerosis. Such are disorders of blood lipids (increased triglyceride concentration, modifications of low density lipoproteins) of haemostatis (increased platelet activity, decreased fibrinolytic activity) or of arterial vasomotility. Yet, many uncertainties and inconsistencies still obfuscate the links between diabetes and atherosclerosis, which remain hypothetical, and debatable. Clinical experience and all clinical epidemiological studies show that the incidence and severity of ischaemic arterial diseases (coronary heart disease, lower limb ischaemia, cerebral ischaemic events) are increased in diabetic individuals. However, intermediates other than worsened atherosclerosis may account for these associations. For instance, several anatomical epidemiological studies, based on routine autopsies, have note consistently found that atherosclerotic lesions (plaques) are larger and more extensive in diabetic than in non-diabetic individuals. The basic mechanisms of diabetic macroangiopathy could therefore be not as closely related to atherosclerosis as is usually thought. Among the non-atherosclerotic lesions that could explain the increased arterial risk in diabetic patients, the best documented and most plausible is arteriosclerosis--a pure sclerosis of the arterial wall (without lipid deposition) which, in its advanced forms, can compromise tissue vascularization. Arteriosclerosis is considered as a normal consequence of arterial ageing which would be accelerated in diabetes. Chronic hyperglycaemia is and independent and influent marker of arterial risk in diabetic patients. It could stimulate arterial sclerosis by enhancing non-enzymatic glycation of various components of the arterial matrix, through formation of advanced glycation end-products (AGEs).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin is frequently considered to be a risk factor for atherosclerosis (or for coronary and vascular disease). Furthermore, hyperinsulinaemia is claimed to be the primary cause underlying the other features which make up the insulin resistance syndrome. However, if proof of these assertions is based only on prospective studies, its value is limited. Only two studies, both carried out, surprisingly, in policemen, have shown convincingly that insulin was a coronary risk factor. In one of the studies, the Paris Prospective Study, the insulin-coronary disease correlation was shown to subside with increasing duration of follow-up. The other prospective studies have failed to evidence a correlation between insulinaemia and cardiovascular events, even with univariate analysis. One study even showed a negative correlation between insulinaemia and coronary complications. In view of the fact that insulinaemia has been shown repeatedly to be associated with classic cardiovascular risk factors--systolic hypertension, decrease in HDL cholesterol, increase in triglycerides, and abdominal obesity--it is highly surprising that univariate analysis has not been able to show the same correlation between insulin and cardiovascular complications. In fact, the combination of elevated insulinaemia and classic risk factors may result in protection against the deleterious effects of these factors. Another possibility would be that insulinaemia is associated with unknown protective factors. Both hypotheses would account for the existence of a correlation between insulin and current cardiovascular disease, as well as the absence of correlation between insulin and later onset of cardiovascular disease.

Beta-cell dysfunction is prominent in Type 2 (non-insulin-dependent) diabetes mellitus. Four types of abnormalities have been described. Oscillatory pattern of insulin-secretion is impaired, with a loss of high frequency pulses and with a reduction in amplitude of slow oscillations. This impairment takes place early in the course of the disease, as does the loss of the first phase of insulin secretion after intravenous glucose. Quantitative (insulin deficiency in relative and absolute terms) and qualitative abnormalities (excess in proinsulin and in 32-33 split proinsulin) have been also observed in Type 2 diabetes. One or several genetic defects seem to be responsible for the development of this beta-cell dysfunction and for Type 2 diabetes mellitus.

The excess risk of cardiovascular disease in Type 1 diabetes mellitus compared to non diabetic subjects is only partially explained by standard risk factors. Several studies suggest that Lp(a) concentrations are increased in Type 1 diabetes mellitus, but data are still controversial. Moreover, a high cardiovascular risk has been reported in diabetic patients with persistent proteinuria. Therefore, the aim of this study was to compare the Lp(a) particle levels in insulin-dependent diabetic patients with or without increased urinary albumin excretion. Cross-sectional study of Lp(a) plasma levels in a population of 140 insulin-dependent diabetic patients: 83 without increased proteinuria, 14 with borderline elevation of urinary albumin excretion, 27 with micro- and 16 with macro-proteinuria. Simultaneous determination of plasma lipids, fasting blood glucose and HbA1c was performed. The mean plasma Lp(a) concentrations and the distribution of the levels were comparable in all of the diabetic patient groups. No relationship existed between Lp(a) and HbA1c, fasting blood glucose or any lipid plasma levels. No influence of albumin excretion rate on Lp(a) levels was observed. These data provide no evidence of a specific contribution of Lp(a) particles to the increased morbidity and mortality from cardiovascular disease observed among patients with nephropathy.

The aim of the present study is based on the comparison of intravenous tolerance testing before and after segmental pancreas autotransplantation in the dog. The results show that such testing must take in account the "glucose diffusion space", using the same glucose load in order to avoid the bias related to the post-operative loss of body weight.

Morbidity and mortality through coronary atherosclerosis are higher in Type 2 diabetic patients than in nondiabetic subjects, roughly by a factor of 2 in males and 3 in females. Methodological problems in attempting to weigh the relative effects of each factor make it difficult to accurately interpret the numerous epidemiological data already available. Three issues are discussed here:--Do diabetics have more "classic" risk factors than nondiabetics? The incidence of hypertension, lipid disorders, and even smoking is practically consistently higher in diabetics, with "diabetic" lipid disorders (decreased HDL cholesterol and hypertriglyceridemia) topping the list.--Do diabetics have specific risk factors which could explain the observed increase in coronary morbidity and mortality? The answer would appear to be yes, as patent microalbuminuria--between 30 and 300 mg/24 hours--is found, as well as retinopathy and an increase in fibrinogen and PAI1 plasminogen activator inhibitor. Recent genetic studies have highlighted the role of Lp (a), and particularly that of angiotensin converting-enzyme gene polymorphism (DD allele).--What are the respective roles of hyperglycalmia and elevated levels of circulating insulin? In contrast to the importance of insulin in nondiabetics as demonstrated in longitudinal studies, insulin appears to play a marginal or even nil role in diabetics once the disease is established. It is probably glycaemia itself which remains the fundamental factor, even though the mechanisms leading from hyperglycemia to macrovascular complications remain unknown.