Abnormalities in insulin secretion in type 2 diabetes mellitus.

Type 2 diabetes mellitus is a multifactorial disease, due to decreased glucose peripheral uptake, and increased hepatic glucose production, due to reduced both insulin secretion and insulin sensitivity. Multiple insulin secretory defects are present, including absence of pulsatility, loss of early phase of insulin secretion after glucose, decreased basal and stimulated plasma insulin concentrations, excess in prohormone secretion, and progressive decrease in insulin secretory capacity with time. beta-cell dysfunction is genetically determined and appears early in the course of the disease. The interplay between insulin secretory defect and insulin resistance is now better understood. In subjects with normal beta-cell function, increase in insulin is compensated by an increase in insulin secretion and plasma glucose levels remain normal. In subjects genetically predisposed to type 2 diabetes, failure of beta-cell to compensate leads to a progressive elevation in plasma glucose levels, then to overt diabetes. When permanent hyperglycaemia is present, progressive severe insulin secretory failure with time ensues, due to glucotoxicity and lipotoxicity, and oxidative stress. A marked reduction in beta-cell mass at post-mortem examination of pancreas of patients with type 2 diabetes has been reported, with an increase in beta-cell apoptosis non-compensated by neogenesis.

Muscle infarction in a young woman with brittle type 1 diabetes.

We present the first case of muscle infarction in a 30-year-old woman who had a 5-year history of type 1 diabetes mellitus that was not complicated by nephropathy, retinopathy or neuropathy. All common causes of muscle infarction were excluded, particularly microangiopathy and a hypercoagulable state. The differential diagnosis included infection (pyomyositis, necrotic fasciitis), focal inflammatory myositis, vascular events, trauma, tumor and diabetic amyotrophy, all of which were excluded. In spite of good glycaemic control, her diabetes remained brittle; alternating states of transient acute hypoglycaemia and hyperglycaemia may have been responsible for the infarction. Brittleness resumed after treatment with subcutaneous insulin infusion using a portable pump. No recurrence of muscle infarction was observed during a 18-month follow-up.

Occurrence of gestational diabetes mellitus, maternal and fetal outcomes beyond the 28th week of gestation in women at high risk of gestational diabetes. A prospective study.

AIM: Among the numerous guidelines defining the diagnostic strategy of gestational diabetes mellitus (GDM), none of them suggest a follow-up in women with risk factors beyond the 28th week of gestation (WG). The primary objective of this study was to assess the incidence of GDM beyond 28 WG in a group of women at high risk. The secondary objectives were to evaluate maternal and fetal outcomes in early and late GDM (between 24-28 WG, and beyond 28 WG), as well as to compare them to a normal glucose tolerance (NGT) group. METHODS: A prospective study conducted in 191 consecutive women. Between 24-28 WG, the diagnosis of GDM was performed in a two-step approach (50 then 75 g). Beyond the 28 WG, the diagnosis of GDM was based on self-monitoring blood glucose (SMBG). All women were educated about an individualized diabetic diet and to perform SMBG daily glucose profiles. RESULTS: Seventy-two percent of the women at risk had developed GDM. Among these, 54% had developed early GDM, between 24-28 WG, and 18% had developed late GDM, beyond the 28th WG. Gestational age of late GDM was estimated 30 WG. In late GDM, onset of diabetes seems to be predicted by an increase in capillary glucose value determined at 22:00 hours, but this needs to be confirmed. Women who develop GDM2 have a significantly higher rate of macrosomia and more important pre-pregnancy overweight, underlining this impact in the occurrence of macrosomia. Finally maternal outcomes were not different in the 3 groups with intensive intervention.

Zygomycosis: an uncommon cause for peripheral facial palsy in diabetes.

Mucormycosis is an emerging fungal infection with a high rate of mortality. Diabetic and immuno-compromised patients are the most frequent hosts. We report a case of rhino-orbito-cerebral mucormycosis revealed by facial palsy in a diabetic, immuno-compromised patient with difficult life conditions. He received intravenous antifungal treatment (amphotericin B) and early surgical debridement and completely recovered with no recurrence after 3 months of follow-up. Physicians should be aware of such atypical clinical presentations due to the need for early appropriate combined medical and surgical management to improve disease recovery and prognosis.

Acute lower limb ischemia is a frequent complication of severe diabetic hyperosmolarity.

AIM: To describe the outcome of intensive care unit (ICU) patients admitted with a hyperglycaemic hyperosmolar non-ketotic syndrome (HHNS), with a specific analysis of precipitating conditions and complications including lower limb ischemia. METHODS: Retrospective review of patients admitted in a university-hospital ICU for HHNS. RESULTS: Seventeen consecutive patients (9F/8M, age: 75 years [57-81] (median [25-75% percentiles], Glasgow Coma score: 13 [12-14]) were admitted for HHNS over an 8-year period (1998-2005). On admission, the blood glucose level was 40.0 mmol/l [26.3-60.8], the corrected serum sodium concentration 167 mmol/l [158-174], and the calculated plasma osmolarity 384 mosmol/l [365-405]. All the patients presented with renal failure due to severe dehydration. An infection was identified as the precipitating factor in 8/17 cases. Three (18%) patients died in the ICU. Non-survivors were significantly older than survivors (P=0.02). Using univariate analysis, no other parameter measured on admission was related to mortality. Four patients (24%) presented with lower limb ischemia. They had a significantly more elevated blood urea nitrogen (P=0.03), creatinine phosphokinase level (P=0.04), and leukocyte count (P=0.02). The bilateral, symmetrical, and distal extremity involvement suggested diminished blood flow due to hyperviscosity, hypotension, vasoconstrictors, or cholesterol emboli rather than a proximal arterial obstruction as causative mechanisms. No patient was treated surgically. Ischemia reversed with fluid loading and resulted in toe dry digital necrosis. CONCLUSION: HHNS is a rare but life-threatening cause of ICU admission. There is a high incidence of lower limb ischemia in HHNS patients, which may be related to dehydration and blood hyperviscosity.