Diagnosis of diabetes mellitus and intermediate glucose abnormalities in obese patients based on ADA (1997) and WHO (1985) criteria.

AIM: To assess the accuracy of the 1997 ADA criteria for diagnosing diabetes mellitus and related glucose disturbances in comparison with the reference WHO 1985 criteria in obese subjects. PATIENTS AND METHODS: In 286 men and 881 women, 15-84 years of age, with obesity (body mass index (BMI) > or = 30 kg/m2), an oral glucose tolerance test (OGTT) was carried out according to WHO standard. Patients were classified into three categories of glucose tolerance using WHO 1985 (Normal Glucose Tolerance (NGT), Impaired Glucose Tolerance (IGT) and Diabetes Mellitus (DM)) and ADA (Normal Fasting Glucose (NFG), Impaired Fasting Glucose (IFG) and DM) criteria. Prevalence of each category was compared and agreement between the two classifications was assessed. The relation between fasting plasma glucose value and diabetes, as diagnosed by WHO 1985 criteria, was studied using various regression models, cumulative frequency curves, Finch method and ROC curve. RESULTS: Compared with WHO 1985, ADA criteria strongly underestimated the prevalence rate of diabetes (3.7% vs. 10.6%) and intermediate glucose abnormalities (6.0% vs. 22.4%). Agreement between the two classifications was poor (kappa = 0.23). Moreover, many patients defined as glucose-intolerant by the WHO 1985 criteria were shifted to a more favourable metabolic status by ADA criteria. Thus, ADA criteria failed to detect 69% of WHO diabetic patients and 89% with IGT were considered as normal. According to the method, cut-off value of fasting blood glucose for detecting WHO 1985-diagnosed diabetes varied widely, from 5.3 to 6.3 mmol/l and none was satisfactory because of poor sensitivity and positive predictive value. CONCLUSION: The ADA criteria do not appear to be a good substitute for those of the WHO 1985 at identifying diabetes and intermediate glucose abnormalities in an obese population. Since it appears impossible to determine a reliable cut-off value for fasting blood glucose to identify diabetic obese subjects with sufficient sensitivity, our results justify the retention of the OGTT in clinical practice or for epidemiological studies.

Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot. A pilot, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of topical human recombinant basic fibroblast growth factor (bFGF) on the healing of diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS: Seventeen diabetic patients suffering from chronic neuropathic ulcer of the plantar surface of the foot entered a pilot, randomized, double-blind study comparing local application of bFGF with placebo. Main inclusion criteria were a typical neuropathic ulcer of Wagner grade I-III, more than 0.5 cm in the largest diameter, with an abnormally high vibration perception threshold in the absence of significant peripheral vascular disease or wound infection. bFGF or placebo was applied daily during the 6 weeks as inpatients then twice a week for 12 weeks. Evolution of ulcer size was assessed through weekly clinical examination and computerized photographs. RESULTS: In the bFGF group, three of nine ulcers healed compared with five of eight in the placebo group (NS). The weekly reduction in ulcer perimeter and area was identical in both groups, as was the rate of linear advance from entry to the 6th week of treatment (bFGF: 0.053 +/- 0.048 mm vs. placebo: 0.116 +/- 1.129 mm): the same result was obtained at the 11th week. Moreover, percent healed area at the end of the study did not differ significantly. No side effects were observed during bFGF application. CONCLUSIONS: Topical application of bFGF has no advantage over placebo for healing chronic neuropathic diabetic ulcer of the foot. Because diabetes causes significant wound-healing defects, we hypothesized that using a single growth factor might be insufficient to accelerate wound closure of diabetic ulcers.

Renal changes associated with cyclosporine in recent type I diabetes mellitus.

The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, progressively decreased to 6.3 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n = 6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2 +/- 1.5 mm Hg), a rise in renal vascular resistance (approximately 20%), a decrease in glomerular filtration rate (approximately 25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/glomerular filtration ratio increased from 1.07 +/- 0.05% to 1.33 +/- 0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (approximately 50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight. All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients.

Effect of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor, on glucose, insulin, C-peptide and GIP responses to an oral sucrose load in patients with post-prandial hypoglycaemic symptoms.

Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study.

[Methods of analysis of hormonal pulsatility]. / Méthodes d'analyse de la pulsatilité hormonale.

Methods for detection and characterization of episodic fluctuations in circulating hormone levels are frequently used for endocrine investigations, related to the physiological importance of the pulsatile nature of hormone secretion in modulating target-cells response. Several sophisticated methods of pulse analysis have been recently developed and validated, aiming to minimize the false-positive and false-negative error rates. The present report mainly devoted to the clinician aims to analyze and discuss the main features of the most widely used methods for pulse detection.