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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 development of drugs in order to block metabolic pathway of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamin E, vitamin C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy.

In patients with insulin-dependent (Type 1) diabetes mellitus abnormal endothelial cell proliferation was considered as one of the possible explanations for the occurrence of retinopathy. Since monocyte-derived factors have been proposed to be involved in endothelial cell growth regulations we have measured the effect of monocyte-conditioned medium (MO-CM) on endothelial cell proliferation and the production of Tumor necrosis factor alpha and interleukin 1-beta, cytokines known to alter endothelial cell functions. The effect of MO-CM in 20 patients with Type 1 diabetes and proliferative retinopathy on endothelial cell proliferation estimated on [3H] thymidine incorporation, was lower to that observed with the MO-CM in 20 normal controls but the difference did not reach the statistical level of significance. The basal tumor necrosis factor alpha secretion expressed by monocytes was significantly lower in the MO-CM from Type 1 diabetes patients (median: 0.49, range 0.13-2.86 ng/10(6) monocytes) than in the MO-CM from the control subjects (median: 1.84, range: 0.13-7 ng-10(6) monocytes) p0.02. The increase in interleukin 1-beta and in tumor necrosis factor alpha production after lipopolysaccharide stimulation were similar in the 2 groups. A low basal tumor necrosis factor production per monocyte may contribute to the development of the diabetic complications as it is involved in several cellular regulation processes.

Among high density lipoprotein particles, LpAI particles which contain apolipoprotein A1 alone, appear to be involved in cholesterol transport from peripheral tissues to the liver. The aim of this cross-sectional study was to examine serum LpAI particle concentrations in Type 1 and Type 2 diabetic patients with renal lesions of differing grades, in comparison with normal controls and with nondiabetic patients presenting with chronic renal failure. LpAI concentrations and LpAI-to-apo A1 ratios were increased in Type 1 diabetic patients with normal albumin excretion. In Type 1 and in Type 2 diabetic patients with increased urinary albumin excretion, LpAI concentrations and LpAI-to-apo A1 ratios were found to be not different from those of normal controls. In diabetic and in nondiabetic patients with chronic renal failure, LpAI concentrations were decreased. These abnormalities may contribute to the development of macrovascular complications.

Hypoglycaemia increases hepatic glucose output; insulin release is suppressed and the secretion of counter regulatory hormones enhanced. Catecholamines and glucagon seem to play a major role. The brain energy content is initially preserved, but the neuronal activity exhibits a 40-60 % decrease. Neither cerebral blood flow, nor oxygen consumption are altered. In addition to glucose, other substrates are metabolized. Cerebral edema may occur. An insulin-storage defect seems to be the main abnormality in insulinoma beta cell function. The most accurate biological tests are the insulin/glucose ratio, stimulation tests and suppression tests such as fasting and insulin-induced hypoglycaemia. Ectopic release of ACTH, HCG, HLP, glucagon or gastrin, is observed in some malignant insulinomas. When inconclusive, classic localising procedures may be effected by selective venous-blood sampling. Hypoglycaemia of extra-pancreatic tumors results from glucose hyperconsumption and decreases in glucose hepatic output, lipolysis and ketogenesis, related to secretion of insulin-like peptides NSILAs or NSILAp. Rare cases of hypoglycaemia related to insulin auto-antibodies of unknown origin have been reported. Alcoholic hypoglycemia results from diminished hepatic glycogen content, alcohol dehydrogenase pathway blockade, reduction of gluconeogenesis defect in the alcohol catabolic catalase pathway and enhancement of peripheral glucose consumption.