Diabete & metabolisme最新文献

Insulin-like growth factors (IGF-I and IGF-II) are produced in most tissues, particularly liver. Via endocrine and paracrine or autocrine mechanisms, they play an essential role in cell proliferation and differentiation and complement the metabolic effects of insulin. Similarities between the effects of insulin and IGF in vitro are largely due to cross-reaction, owing to their structural homology as well as that of their receptors. At physiological concentrations, insulin is not mitogenic. Compared with insulin, IGFs have negligible metabolic effects on hepatocytes or adipocytes. However, the presence of the IGF-I receptor in muscle accounts for IGF physiological effects in vivo on glucose uptake and glycogen synthesis. Moreover, recombinant IGF-I administered subcutaneously to healthy subjects or patients with Type 2 diabetes causes a drop in plasma levels of triglycerides and VLDL as well as cholesterol and LDL, but not HDL, and also increases insulin sensitivity. All these responses reflect IGF-I inhibition of insulin and GH secretion. In biological media, IGF-I and IGF-II are reversibly associated with specific high-affinity (10(9)-10(11) M-1) binding proteins (IGFBP-1 to -6) differing in expression according to tissue of origin and playing a variety of roles in IGF transport and half-lives, delivery of IGFs to their target cells and modulation of IGF interactions with their receptors. In the blood, where IGF concentrations are 1,000 times those of insulin, IGFBP-3 (the major form) binds at least 80% of IGFs as 140-kDa complexes which do not cross the capillary endothelium and therefore prevent the insulin-like action of IGFs. Nevertheless, these circulating IGF reserves may be mobilized in response to metabolic needs via limited proteolysis of IGFBP-3 by serine proteases. In the case of IGFBP-1, whose hepatic synthesis is negatively regulated by insulin, plasma concentrations are subject to extensive nycthemeral variation, rising with fasting and dropping after feeding, which may be involved in controlling the access of free IGF-I to its cellular receptors and hence IGF-I-regulated glucose and amino acid uptake. Therapeutic applications of recombinant human IGF-I, currently under trial in the treatment of growth retardation resulting from GH receptor abnormalities, hypercatabolic states and would repair, may also be envisaged for cases of insulin resistance, particularly type 2 diabetes.

Endogenous glucose production (EGP), glucose clearance and insulin sensitivity were measured in 5 subjects with insulinoma before and 3 to 6 months after surgical resection of the tumour. Endogenous glucose production and glucose clearance were evaluated by infusion of [6,6 D2] glucose, and insulin sensitivity was determined by a euglycaemic hyperinsulinaemic glucose clamp. The patients served as their own controls. The postabsorption blood glucose level was low before treatment (0.51 +/- 0.01 g/l) and EGP was 1.86 +/- 0.10 mg kg-1 min-1 (normal value: 2.2 to 2.6 mg kg-1 min-1), whereas the insulin level was relatively high (16.4 +/- 1.6 mU/l). After surgical resection of the insulinoma, the blood glucose level rose to 0.94 +/- 0.02 g/l and EGP to 2.33 +/- 0.04 mg kg-1 min-1, whereas the insulin level fell to 6.4 +/- 0.5 mU/l. Glucose metabolic clearance in the fasting state was 3.68 +2- 0.21 mg kg-1 min-1 before and 2.46 +/- 0.09 (n = 2.44 to 3.46 ml kg-1 min-1) after surgery. Clamp dose-response curves were shifted to the left and insulin sensitivity was improved after surgery. These data suggest that chronic hyperinsulinaemia is associated with inhibition of endogenous glucose production, a rise in basal glucose clearance and a state of insulin insensitivity during the clamp.

To investigate the relationship between microalbuminuria and severity of retinal damage, we studied 86 Albustix-negative insulin-dependent diabetic patients whose disease duration was more than 5 years (age 31.9 +/- 10.9 years; duration 14.7 +/- 7.1 years). Retinopathy was evaluated by fluorescein angiography in four groups of patients: a) 37 (43%) without retinopathy, b) 29 (34%) with background retinopathy, c) 10 (12%) with pre-proliferative retinopathy and d) 10 (12%) with proliferative retinopathy. Microalbuminuria (urinary albumin excretion > 30 mg/24 h) was calculated from timed 24-h urine collection and measured by a radioimmunoassay method. Microalbuminuria was found in 20 patients (23%); 16 of whom showed both retinopathy and microalbuminuria. Diabetic retinopathy was more frequent than microalbuminuria (57% vs 23%). The prevalence of microalbuminuria was significantly higher in the proliferative retinopathy group compared to the group without retinopathy (p < 0.0005) and the background retinopathy group (p < 0.007). The frequency of diabetic retinopathy was significantly higher (p < 0.04) in patients with than without microalbuminuria. These results indicate that microalbuminuria is associated with the presence and severity of diabetic retinopathy in insulin-dependent diabetic patients.

Dietary carbohydrates represent one of the major sources of energy for the human body. However, the main (if not the only) therapy for diabetes since ancient times has been based on reducing dietary carbohydrates drastically because of their effects on blood glucose levels. The introduction of insulin in the 1920s and then of oral hypoglycaemic drugs led to various studies evaluating the biochemical characteristics of carbohydrates and their effects on glucose metabolism in diabetic patients. This review considers the role of dietary carbohydrates in the diet of diabetic patients in the light of the most recent studies and provides a short summary of the biochemistry of carbohydrates and the physiology of carbohydrate digestion.

Des(64,65)-proinsulin (DPRO) is one of several endogenous intermediates arising during the conversion of proinsulin to insulin. In pharmaceutic preparations it is a clear solution containing no other proteins. Animal experiments and preliminary human studies indicated that DPRO should have a protracted time-action profile similar to that of NPH-insulin. Accordingly, we compared the time-action profiles of these two preparations, using the euglycaemic glucose clamp-technique in 9 healthy male volunteers. Different doses of DPRO (0.1, 0.15, 0.2 U/kg) or equipotent doses of NPH ( 0.2, 0.3, 0.4 U/kg) were injected subcutaneously into the abdominal wall. The maximal metabolic effect (GIRmax) of DPRO was greater than that of NPH-insulin (p < 0.05). With increasing doses, GIRmax differed significantly for DPRO but not for NPH-insulin. The time to maximal metabolic effect (tmax) was similar for the three doses of either preparation. However, tmax was reached 30 min earlier with DPRO than with NPH-insulin (p < 0.01). the decline to half-maximal after maximal activity was significantly faster with DPRO than with NPH-insulin (p < 0.0001). Subcutaneous injection of DPRO thus produced a time-action profile between that of regular insulin and NPH-insulin.

The purpose of this study was to evaluate the efficacy of a traditional Chinese treatment (TCT) based on three plants in association with a sulfonylurea, glibenclamide (2.5 mg X 3/d). A 2 X 2 factorial design was adopted for this multicentre randomized double-blind trial involving 4 groups [A = placebo (P) TCT + P glibenclamide; B = P TCT + verum glibenclamide; C = verum TCT + P glibenclamide; D = verum TCT + verum glibenclamide]. Patients included were type 2 diabetic outpatients, 40-70 years of age, treated by diet alone or oral anti-diabetic drugs. Endpoint criteria evaluated were HbA1, blood glucose and plasma insulin (at fasting, and 1 and 2 h after a test meal). At each visit, a clinical examination was performed, and a questionnaire on side effects and associated symptoms was completed. The dose was reduced by half in the case of hypoglycaemia. The 216 patients were recruited in 5 centres [Shanghai (1) = 48, Shanghai (2) = 40, Beijing = 40, Canton = 42, Chengdu = 46 and randomized into treatment groups A, B, C, D (56, 56, 50 and 54 respectively). Eleven patients were withdrawn for administrative reasons. In patients treated with glibenclamide, a significant increase in weight and insulinaemia was observed, together with a significant decrease in blood glucose values; in those receiving TCT, blood glucose values were significantly decreased only 2 h after the test meal. A synergistic effect on blood glucose was observed when both treatments were given. Hypoglycaemia occurred in 19 patients (all in the two verum glibenclamide groups). This first multicentre controlled trial showed that the 3 Chinese plants tested were well-tolerated and effective in Type 2 diabetes as indicated by a significant synergistic effect in association with a sulfonylurea.

The aim of the present study was to investigate the influence of Tolrestat, an aldose-reductase inhibitor, on both oesophageal and cholecystic motility in Type-2 diabetic patients with asymptomatic diabetic neuropathy. Sixty-six patients were randomly assigned to receive Tolrestat 200 mg once daily (33 patients) or were left without specific treatment (33 patients) for 12 months. Efficacy and safety evaluation were done at 4.5 and 12 months by persons blinded to the patient treatment regimen. Scintigraphic evaluation of oesophageal motility showed significant changes in transit time for Tolrestat at 12 months (p < 0.001). There was no significant effect of Tolrestat on cholecystic function in cholecystography, although diabetic patients taking Tolrestat showed a trend toward improvement. The vibration perception threshold at two sites of the dominant leg improved by at least 3 volts in the Tolrestat group and remained unchanged or slightly deteriorated in the control group. Tendon reflexes and blood pressure fall after standing were improved in the Tolrestat group. In conclusion, one-year treatment with Tolrestat significantly improved oesophageal motility and vibration perception in Type-2 diabetic patients with asymptomatic diabetic neuropathy.