Glycaemic control and development of retinopathy in type 2 diabetes mellitus: a longitudinal study.

Relationships between glycaemic control, hypertension, and development of microangiopathy have been well documented in Type 1 (insulin-dependent) but not in Type 2 (non-insulin-dependent) diabetes mellitus. Therefore, we have investigated these relationships in a cohort of 64 Type 2 patients free of retinopathy (by angiofluorography), who were regularly followed until development of retinopathy or for at least 7 years as outpatients. Glycaemic control was assessed by 1 to 4 HbA1 determinations per year. Retinal status was monitored by annual angiofluorography. Nonproliferative retinopathy developed in 14 patients (cumulative incidence at 13 years: 29.8%) after a mean diabetes duration of 14.3+/-8.9 years (range 2-27). In multivariate analysis (Cox model), mean HbA1 during follow-up (p < 0.001), and hypertension at first examination (p = 0.09) were associated with the development of retinopathy, but age, sex, BMI, diabetes duration, smoking, and fasting blood glucose were not. The relative risk for developing retinopathy (RR) was 7.2 (IC 95%: 1.61-32.4) in patients with a mean HbA1 during follow-up above the median value of the cohort (8.3%) compared with patients with HbA1 during follow-up below this value. RR was 2.5 (IC 0.8-8) in patients with HbA1 at first examination above compared to below the median value (8.4%). RR was 3.0 (IC 0.9-10) in patients treated for hypertension at baseline compared to those without treatment. A sixfold increase in retinopathy prevalence was observed between patients with mean HbA1 in the highest or lowest quartile of mean HbA1 distribution during follow-up. This longitudinal study indicates a strong association between long-term glycaemic control and the development of diabetic retinopathy in Type 2 diabetes.

Chronic diarrhoea and diabetes mellitus: prevalence of small intestinal bacterial overgrowth.

The mechanisms of chronic diarrhoea, a frequent symptom in diabetes mellitus, are multifactorial and complex, although small intestinal bacterial overgrowth and autonomic neuropathy seem to play a major role. This study evaluated the prevalence of small intestinal bacterial overgrowth and the effects of antibiotic treatment in a population of diabetic patients with chronic diarrhoea (defined as > 3 stools/24 h, weight > 200 g/24 h, duration > 3 weeks). Small intestinal bacterial overgrowth syndrome was diagnosed by glucose-hydrogen breath testing (sensitivity: 78%, specificity: 89%). The characteristics of diarrhoea (duration, number of stools per day, and gastrointestinal symptoms) were noted. Autonomic neuropathy was assessed by cardiac parasympathetic tests. A total of 35 patients were included, 15 with small intestinal bacterial overgrowth syndrome (43%, group 1) and 20 with no bacterial overgrowth (group 2). Age (52.9 +/- 13.5 vs. 53.9 +/- 11.8 years, NS), duration of diabetes (13.8 +/- 9.1 vs. 10.6 +/- 7.8 years, NS), and HbA1c level (10 +/- 2.9 vs. 10.9 +/- 2.4%, NS) were not different between the two groups. In group 1, duration of diarrhoea was longer (18.1 +/- 18.5 vs. 7.75 +/- 4.02 months, P = 0.05), the number of stools higher (7.1 +/- 5.7 vs. 4.6 +/- 2.6/24 h, P < 0.05), and gastrointestinal symptoms more frequent (13 vs. 10, P < 0.05). The prevalence of small intestinal bacterial overgrowth syndrome and gastrointestinal symptoms was not different in patients with and without autonomic neuropathy (9 vs. 8 and 12 vs. 11 respectively, NS). Eight patients with bacterial overgrowth received antibiotics (amoxicillin-clavulanic acid, 1.5 g/24 h for 10 days). Dramatic clinical improvement was observed in 6 out of 8 of these patients. It is concluded that small intestinal bacterial overgrowth should be considered in case of chronic diabetic diarrhoea because of its frequency (43%), facility of diagnosis, and often successful treatment with antibiotics.

Diabetes: from phenotypes to genotypes.

Diabetes mellitus comprises a heterogeneous group of diseases which have chronic hyperglycaemia in common as well as the resulting microvascular, macrovascular and neurological complications of this condition. Familial studies have provided strong evidence for the existence of genetic determinants in the different types of diabetes. In particular, monozygotic twin studies have indicated a higher rate of concordance in non-insulin-dependent (NIDDM) than in insulin-dependent diabetes mellitus (IDDM). In IDDM, 8 susceptibility loci have been identified, notably the HLA complex and insulin promotor gene. Rigorous family studies have identified monogenic subtypes representing 10-15% of all NIDDM: MODY2 related to glucokinase gene mutations, MODY1 and MODY3 secondary to mutation of hepatic nuclear factors, and diabetes resulting from deletion or mutation of mitochondrial DNA. Most NIDDM result from polygenic heredity, and susceptibility genes conducive to increased receptivity to deleterious environmental influences are now under investigation, such as beta 3 adrenergic receptor, FABP2 and OB. Precise analysis of phenotypes in the remaining families or systematic screening of the genome could allow the genes of each subtype to be identified. Finally, susceptibility genes for the increased severity and frequency of vascular complications have been identified, such as angiotensin converting enzyme, aldose reductase and aldehyde dehydrogenase genes. This progress has been facilitated by developments in molecular biology.

[Hypophyseal adenomas: functional and tumor evaluation and therapeutic approaches]. / Adénomes hypophysaires: bilan tumoral et fonctionnel et abords thérapeutiques. therapeutic approaches]

Patients with pituitary adenomas present with hypersecretion syndrome(s), and/or pituitary failure(s), and/or signs of mass effect, or incidentally. Pituitary function evaluation, visual acuity and field check-up, and MRI or at least CAT are compulsory for diagnosis, and for therapeutic approach; surgery for Cushing's disease, dopamine agonists for prolactinomas, somatostatin analogs or surgery for thyrotroph adenomas, surgery and/or somatostatin analogs and/or radiotherapy in acromegaly, surgery with additional irradiation in most adenomas of other types, or even expectation in some instances.

Enhanced susceptibility of low-density lipoprotein to in vitro oxidation in type 1 and type 2 diabetic patients.

Macrovascular disease represents a major cause of morbidity and mortality in patients with diabetes mellitus. Low-density lipoprotein (LDL) is involved in the pathogenesis of atherosclerotic lesions, through modifying processes such as oxidation. We examined the in vitro susceptibility to oxidation and the oxidizability of LDL isolated from the plasma of Type 1 and Type 2 diabetic patients. Two groups of diabetic patients (20 Type 1, 20 Type 2) were compared with sex- and age-matched non-diabetic control groups. In vitro oxidation of the purified LDL preparations was assessed by determination of the kinetics for the formation of conjugated dienes (lag phase duration, maximal rate and maximal dienes concentration) and by measurement of thiobarbituric acid-reacting substances (TBARS) in the presence of copper ions. LDL from both Type 1 and Type 2 diabetic patients exhibited a shorter lag phase duration for conjugated dienes formation (94 +/- 14 vs. 108 +/- 20 and 97 +/- 26 vs. 112 +/- 18 min for Type 1 and Type 2 diabetic groups vs. respective control groups, P < 0.05). We also observed an increase in maximal rate of conjugated dienes formation (2.21 +/- 0.55 vs. 1.52 +/- 0.31 and 2.02 +/- 0.55 vs. 1.52 +/- 0.31 nmol/mg LDL/min, P < 0.01) and of maximal production of TBARS (77.9 +/- 11.8 vs. 65.5 +/- 10.4 and 76.7 +/- 9.9 vs. 65.3 +/- 9.4 nmol/mg LDL protein, P < 0.05) in diabetic groups. Our results demonstrate both a higher susceptibility to oxidation and a higher oxidizability of LDL from diabetic patients, as much for Type 1 as Type 2 diabetic subjects with or without pre-existent vascular complications. This enhanced propensity of LDL oxidation in patients with diabetes mellitus could at least partly be attributable to quantitative and qualitative alterations in the chemical composition of LDL and to the glycoxidation process occurring on these lipoproteins.