Pierre Jean Guillausseau

Evaluation of a new non‐mydriatic digital camera for detection of diabetic retinopathy

Aims To compare the results of fundus photography using a new non‐mydriatic digital camera with the results of reference standard of Early Treatment Diabetic Retinopathy Study (ETDRS) retinal photographs, for the detection of diabetic retinopathy (DR).

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.

Lipoprotein(a) in Diabetic Patients with and Without Chronic Renal Failure

OBJECTIVE To examine the distribution of Lp(a) plasma levels in patients with IDDM and NIDDM, and in nondiabetic and IDDM patients with chronic renal failure. RESEARCH DESIGN AND METHODS Cross-sectional study of Lp(a) plasma levels in a population of diabetic patients with stable metabolic control, with simultaneous determination of plasma lipids, fasting plasma glucose, and HbA1. Thirty-six patients with IDDM, 90 with NIDDM, and 41 with chronic renal failure (20 IDDM, 21 nondiabetic) were compared with 78 control subjects. RESULTS Lp(a) plasma levels were significantly higher in IDDM and NIDDM patients, as well as in nondiabetic and IDDM patients with chronic renal failure compared with control subjects. No correlation was observed between Lp(a) and lipid plasma levels, fasting plasma glucose, and HbA1. CONCLUSIONS Lp(a) may contribute to the increased prevalence of atherosclerotic disease in diabetic patients and patients with chronic renal failure, especially in IDDM patients whose lipoprotein pattern was not different from that of the control group.

Comparison of HbA1 and Fructosamine in Diagnosis of Glucose-Tolerance Abnormalities

Total glycosylated hemoglobin (HbA1) and fructosamine were evaluated as screening tools for detection of glucose-tolerance abnormalities in 144 asymptomatic subjects undergoing a 75-g oral glucose tolerance test. Subjects were classified according to World Health Organization criteria as having normal (n = 78), impaired (n = 40), or diabetic (n = 26) glucose tolerance. We found good specificity for HbA1 and fructosamine (100 and 97%, respectively) but low sensitivity (15 and 19%, respectively). At the intersection of the curves of sensitivity and specificity drawn from various thresholds of normality, both sensitivity and specificity were 75% for HbA1 and 55% for fructosamine. Thus, neither HbA1 nor fructosamine seems to be suitable for the diagnosis of mild abnormalities in glucose tolerance.

Extra-Pancreatic Manifestations in Diabetes Secondary to Mitochondrial DNA Point Mutation Within the tRNALeu(UUR) Gene

OBJECTIVE A point mutation in the mitochondrial genome has been identified as a cause of diabetes and deafness. We report two pedigrees with and A-to-G transition at nucleotide 3243 of mtDNA within the tRNALeu(UUR) gene and focus our investigations on other localizations of the anomaly, particularly muscle and retina. RESEARCH DESIGN AND METHODS Muscular localization has been studied in probands by invasive and noninvasive methods, including muscle biopsy (evaluation of the proportion of mutated mtDNA in comparison to blood cells, measurement of respiratory chain complex activities and histological and histochemical aspects) and 31P-nuclear magnetic resonance (NMR) spectroscopy. Ophthalmic and angiographic examination of retina, electroretinography, and visual evoked potentials were performed in five subjects. RESULTS This mutation, previously described in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), was expressed more abundantly in muscle than in nucleated blood cells. This low expression in blood cells could hamper the diagnosis for some patients. In addition, despite poor clinical expression, muscle was found to be highly affected. Ragged red fibers and dystrophic mitochondria were observed in muscle biopsy. Histochemical assays showed decreased activity of respiratory chain complexes, and 31P-NMR in vivo data further confirmed the defect of muscle oxidative processes. Exercise-induced lactate production was increased. Finally, in both families, an atypical “salt and pepper” pigmentary retinopathy was observed without consequences on visual acuity. CONCLUSIONS In diabetes secondary to 3243 mtDNA mutation, infraclinical muscular and ocular lesions are frequent. These two locations of the disease, which are easily investigated by simple methods, can help in the diagnosis of this new type of diabetes.

Monitoring of metabolic control in patients with non-insulin-dependent diabetes mellitus on oral hypoglycaemic agents: value of evening blood glucose determination.

Monitoring of metabolic control in patients with non‐insulin‐dependent (Type 2) diabetes (NIDDM) is usually based upon blood glucose assay in the morning (after an overnight fast) and in the postprandial state (breakfast or lunch). However, this schedule does not seek low blood glucose values, especially in the evening. We have conducted a prospective study of laboratory blood glucose profiles (8 am, 9.30 am after a 35 g carbohydrate breakfast and in the evening between 5 and 7 pm). We have included 58 consecutive NIDDM patients regularly followed in our clinic (39 men, age 60 ± 11.5 years, diabetes duration 8.6 ± 6.5 years, BMI 25.5 ± 3 kg m−2 ), treated with the sulphonylurea gliclazide, alone (40–320 mg 24 h−1 , mean 170 ± 110 mg) (group 1, n = 32) or in combination with metformin (1000–3000 mg 24 h−1 , 2400 ± 620 mg) (group 2, n = 26). All patients were stable, with no change in dosage for at least 3 months. Mean glycaemic control was good (group 1 HbA1c : 6.5 ± 1.1 %, group 2: 6.9 ± 0.7 %). Evening blood glucose values were the lowest of the day in 26 patients of group 1 (81.3 %) and in 22 of group 2 (84.6 %). Mean evening blood glucose levels were lower (p = 0.001) than 8 am values (group 1: 5.8 ± 1.4 vs 6.1 ± 1.6 mmol l−1 , group 2: 6.5 ± 1.8 vs 6.9 ± 1.9) and than 9.30 am values (group 1: 7.6 ± 1.5, group 2: 12.3 ± 2.8). No blood glucose values in the hypoglycaemic range were observed. HbA1c was strongly correlated (p = 0.002 to 0.0001) in the whole group with 8 am (r = 0.39), 9.30 am (r = 0.56), and evening blood glucose values (r = 0.42). These results indicate that, in patients treated with the sulphonylurea gliclazide, alone or in combination with metformin, the lowest blood glucose values occur in the evening more frequently (4/5) than in the morning. Therefore, evening blood glucose determination should be performed systematically in the course of the metabolic evaluation of NIDDM patients on oral hypoglycaemic agents. © 1997 John Wiley & Sons, Ltd.

La rétinopathie diabétique du sujet jeune: l'enfant et l'adolescent

Summary Diabetic retinopathy in children and adolescents Diabetic retinopathy rarely occurs before puberty and is never proliferative in prepubescent children. On the opposite, puberty and adolescence are high-risk periods for diabetic retinopathy progression, and call for strict ophthalmologic monitoring. The period between 16 and 18 years of age is particularly critical. Progression towards florid diabetic retinopathy is to be especially feared and should be prevented in the course of adolescence, as this form can be severe and can lead to blindness. Risk factors are probably many, including diabetes duration, difficulties in achieving glycemic control due to increase in insulin requirements, low compliance to treatment, and hormonal changes related to puberty (abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-1) axis). Systematical diabetic retinopathy screening should be performed in adolescents, notably by non-mydriatic fundus photographs. Furthermore, the anticipation of the switch from pediatric to adult structures, together with the careful information and education of parents and children may improve visual prognosis of young diabetic patients, whose life expectancy is high.

Diagnostic clinique et biologique du diabète mitochondrial et particularités de sa prise en charge

Mitochondrial diabetes affects up to 1% of patients with diabetes and is often unrecognised by the physicians. Maternally inherited diabetes and deafness (MIDD) resulting from the mutation 3243A>G of the mitochondrial DNA is the most frequent mutation associated with mitochondrial diabetes. This review summarizes the range of clinical phenotypes associated with MIDD and outlines the advances in genetic diagnosis, pathogenesis and management of these patients.

Switching fibrate to statin in type 2 diabetic patients: Consequences on lipid profile

UNLABELLED Interest of statins in terms of morbid-mortality reduction in primary and secondary prevention in type 2 diabetic patients has broadly been proven in recent studies, while evidence for fibrates preventive effect is considerably weaker. HMGCoA reductase inhibitors are known to decrease low density lipoprotein cholesterol (LDL C) in a greater extension than triglycerides (TG). In type 2 diabetic patients, the dyslipidemic profile is commonly associated with reduced high-density lipoproteins (HDL C), increased TG and normal or mildly elevated LDL C. PATIENTS AND METHODS Type 2 diabetic outpatients (n=45) treated with fibrate with or without history of cardiovascular disease were included. Mean age was 57.7+/-13.2 yr, sex ratio was 16/39 (F/M), and BMI was 29.3+/-4.4 kg/m(2). Non-inclusion criteria were TG>or=3.5 g/L and intolerance to statins or a combined lowering lipid therapy. Serum lipid profile, HbA(1c) and creatin kinase (CK) were assessed under treatment with fibrate, then after a 3-month wash-out period, and after a 6-month treatment with a low dose of atorvastatin (10 mg/day). RESULTS After a 3-month wash-out period, total cholesterol (TC) was 1.98+/-0.31 g/L (m+/-SD), TG 1.63+/-1.09 g/L, HDL C 0.46+/-0.12 g/L, and LDL C 1.22+/-0.31 g/L. Comparing lipid profile with atorvastatin vs fibrate, we observed a significant decrease in TC and LDL C (1.56 vs 1.79 g/L P=0.001, and 0.84 vs 1.09 g/L, P=0.001, respectively). No significant difference between treatments was observed for TG (1.35 vs 1.17 g/L, P=0.06), and HDL C (0.44 vs 0.48 g/L, P=0.15). When treated with atorvastatin, 90% of patients achieved a LDL C<1 g/L, compared to 51% when treated with fibrate (P=0.001). HbA(1c) remained about 7.6+/-1.5%, and CK in the normal range. CONCLUSION In well-controlled type 2 diabetic patients previously treated with fibrate, short-term (6 months) treatment with low-dose atorvastatin (10 mg/day) improves TC and LDL C levels, without any alteration in TG and HDL C levels.

Androgen producing adrenal adenoma. Report on a case associated with hyperparathyroidism

In a 41-year-old hirsute woman, severe hypercalcemia led to the discovery of hyperparathyroidism related to the involvement (hyperplasia/or adenoma) of the 4 parathyroid glands. Plasma and urinary DHA, plasma DHA-sulfate and A 5 steroid precursors were elevated. Steroid hormone hypersecretion was stimulated by hCG and ACTH, and exhibited a paradoxical rise during dexamethasone administration. Computerized tomography scanning as well as arteriography disclosed bilateral adrenal hyperplasia and left adrenal adenoma. Bilateral adrenal vein catheterization indicated a left/right gradient for Δ 5 steroids and Δ 5 steroid sulfates. At surgery a left brown adrenal encapsulated adenoma was removed with a hyperplastic adrenal gland. Results of in vitro studies (adrenal steroid content and incubation) together with postadrenalectomy hormonal results suggest that the left brown adrenal adenoma was the main source of excessive androgen production. The infrequent association of an androgen-producing adrenal adenoma with hyperparathyroidism raises the hypothesis of multiple endocrine neoplasia syndrome. However, evidence for this diagnosis is lacking in the absence of other glandular involvement and of family history.