The G3057A LEPR polymorphism is associated with obesity in Tunisian women.

OBJECTIVES: The aim of this study was to evaluate the effect of the G3057A (rs62589000) LEPR polymorphism on obesity risk and plasma leptin, insulin, and lipid levels in a sample of the Tunisian population. DESIGN AND METHODS: Three hundred and ninety-three obese patients and 317 controls participated in this study. The G3057A genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: In the entire study sample, no significant differences in genotype frequencies were observed between obese patients and controls. However, stratified analysis by gender revealed a quantitative increase in the variant allele (33.3% vs. 25.8%; χ(2)=4.90, p=0.026) in obese women (but not men) compared to controls. When a dominant model of inheritance was assumed, the GA+AA genotypes were more prevalent in these obese female patients than in controls (58.3% vs. 47.8%; χ(2)=4.08, p=0.044). Unconditional logistic regression showed that in women only, obesity risk was significantly higher for homozygotes for the variant allele (OR=2.73, 95% CI 1.03-7.21) and for carriers of GA+AA genotypes (OR=1.53, 95% CI 1.01-2.31) compared with homozygotes for the normal allele. The association between the G3057A LEPR variant and obesity remained statistically significant even after adjustment for age. No relationship was found between the G3057A LEPR polymorphism and leptin and insulin levels. Additionally, this LEPR gene variant had no effect on plasma lipid concentrations. CONCLUSION: There is evidence in this study that the G3057A LEPR polymorphism is associated with obesity in Tunisian women.

The -2548G/A LEP polymorphism is associated with blood pressure in Tunisian obese patients.

OBJECTIVE: To examine the association of a common -2548G/A (rs7799039) promoter variant of the human leptin gene (LEP) with obesity or body mass index (BMI) and its associated phenotypes such as blood pressure variability and the prevalence of hypertension in a sample of the Tunisian population. DESIGN AND METHODS: Two hundred and twenty-nine obese patients were screened and compared with 251 normal weight subjects. The -2548G/A LEP polymorphism was analysed by PCR-RFLP procedure. RESULTS: No significant association was found between the -2548G/A polymorphism and obesity or BMI. However, in obese patients subjects with AA genotype had significantly higher systolic (p = 0.003) and diastolic (p = 0.002) blood pressure compared with those with GA or GG genotypes. Stratified analysis by gender revealed that male patients but not female homozygous for -2548A allele exhibited significantly increased systolic (p = 0.01) and diastolic (p<0.001) blood pressure than did carriers of -2548G allele. Multiple linear regression analysis revealed that AA genotype significantly affect systolic and diastolic blood pressure in obese men. Additionally, significant association between AA genotype and higher prevalence of hypertension was found in male patients (p = 0.03). CONCLUSION: The present study showed that the -2548G/A LEP polymorphism is associated with blood pressure in obese male patients.

Platelet PMCA- and SERCA-type Ca2+ -ATPase expression in diabetes: a novel signature of abnormal megakaryocytopoiesis.

BACKGROUND: Previous studies have shown platelet Ca(2+) abnormalities in diabetes mellitus and some reports suggest abnormal platelet production. Platelet Ca(2+) homeostasis is controlled by a multi-Ca(2+)-ATPase system that includes two plasma membrane Ca(2+)-ATPase (PMCA) and seven sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) isoforms. In addition, we recently found that the expression of PMCA4b and SERCA3 isoforms may serve as new markers of abnormal megakaryocytopoiesis [Nurden P et al. Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia. Blood 2006; 108: 2587-95]. AIM: To analyze the expression of major platelet Ca(2+)-ATPases in 27 patients with type 1 or type 2 diabetes (T1D or T2D) compared with normal donors. METHODS: Investigation of protein and mRNA expressions of PMCA1b and PMCA4b, and SERCA2b, SERCA3a and SERCA3b, using specific Western blotting and reverse transcriptase-polymerase chain reaction, respectively. RESULTS: Remarkably, all patients with T1D were found to present a higher expression of PMCA4b protein (212% +/- 28%; n = 10) and PMCA4b mRNA (155% +/- 16%; n = 17), coupled with a higher expression of SERCA3b mRNA (165% +/- 9%) in some cases. Patients with T2D (n = 10) were also studied for protein expression and were found to present similar major upregulation of the expression of PMCA4b protein (180% +/- 28%; n = 10). Lastly, five of 10 patients with T1D were studied for PMCA4b expression after insulin treatment, with four of five recovering normal expression (96% +/- 15%; n = 5). CONCLUSIONS: Compared with the expression of PMCA4b upon platelet maturation, platelets from diabetic patients exhibit similarities with immature megakaryocytes. Thus, this study reinforces the idea that abnormal megakaryocytopoiesis can provide additional insights into diabetes and could represent a novel therapeutic target for antithrombotic drugs.

Predictive risk factors for deterioration from normoglycemic state to type 2 diabetes mellitus or impaired glucose tolerance in a Tunisian urban population.

OBJECTIVE: To determine the predictive risk factors for the development of type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) in a normoglycemic population. RESEARCH DESIGN AND METHODS: This is a ten-year prospective study in a randomly selected urban population including 1835 subjects aged >=30 years living in Tunis, 1460 were normoglycemic according to 2 hours blood glucose WHO criteria, and 701 among them attended the follow-up assessment ten years later. Subjects with impaired glucose tolerance (IGT) were excluded. Subjects underwent a physical examination including weight/height, iliac circumference (IC) and blood pressure measurements. Fasting and 2-hour venous blood sampling, after a 75 g oral glucose load, were performed for the measurement of plasma glucose (G(0), G(2h)), insulin (I(0), I(2h)), total cholesterol (TC) and glycated hemoglobin (HbA(1c)) levels. RESULTS: Out of the 701 normoglycemic subjects in 1985, 77 developed diabetes and 130 impaired glucose tolerance after 10 years, giving a mean annual incidence rate of 1.1% for diabetes and 1.85% for IGT. Univariate analysis showed that risk factors for diabetes were age, BMI, IC, SBP, G(0) and total cholesterol in both sexes, I(0) and I(2h) in men only and DBP G(2h) and HbA(1c) in women only. Risk factors for IGT were BMI, IC and G(2h) in both sexes, I(2h) in men only and G(0) in women only. Multivariate analysis revealed that BMI, G(0) and G(2h) were independent risk factors for conversion to diabetes or IGT in both sexes, but HbA(1c) and IC were risk factors only in men. CONCLUSION: Early screening and prevention of diabetes must focus on obese subjects, especially those with central fat distribution, and those with moderate increase in fasting and/or two-hour blood glucose levels within the normal range.

[Study of the effect of converting enzyme inhibitors on microalbuminuria in diabetics]. / Etude de l'effet des inhibiteurs de l'enzyme de conversion (IEC) sur la microalbuminurie chez les diabetiques.

The authors report the results of a randomised trial using a converting enzyme inhibitor in 40 microalbuminuric diabetic subjects during 18 months. In the treated group, we observed a reduction of albuminuria from 57.4 mg/24 hours to 35.4 mg/24 hours at the end of the follow up, in contrast with a non significant progression in the group who didn't receive this medication. No significant modification in the clinical and biological parameters was observed during the follow up.

[McCune-Albright syndrome associated with diabetes mellitus]. / Syndrome de McCune-Albright associé à un diabète sucré

McCune-Albright syndrome (MAS) consists of the triad of polyostotic fibrous dysplasia, cutaneous pigmentation, and multiple endocrine abnormalities. Type 1 diabetes mellitus is not included in MAS. We report the case of an 18-year-old girl who presented with McCune-Albright syndrome. The diagnosis was made by the presence of precocious puberty at the age of 6 years, cutaneous pigmentation, polyostotic fibrous dysplasia, and phosphate diabetes. Type 1 diabetes mellitus developed at the age of 16 years. We discuss this case, the relationship between type 1 diabetes mellitus and MAS, with a literature review.

[Evaluation of blood pressure control by ambulatory blood pressure monitoring and study of factors associated with poor blood pressure control in 300 treated hypertensive type 2 diabetic patients]. / Évaluation de l'équilibre tensionnel par la mesure ambulatoire de la pression artérielle et étude des facteurs associés à un mauvais contrôle tensionnel chez 300 diabétiques de type 2 hypertendus traités.

UNLABELLED: Hypertension is frequently associated with type 2 diabetes and is often difficult to control. AIM: Evaluate the frequency of controlled hypertension in our type 2 diabetic patients with known and treated hypertension and determine the factors associated with poor blood pressure control. SUBJECTS AND METHODS: Prospective study concerning 300 type 2 diabetic patients with a known and treated hypertension, sex-ratio: 0.64, mean age: 61.2±9.1 years (37-86). All subjects underwent physical examination, biological investigations and a 24 hours ambulatory blood pressure monitoring (ABPM). RESULTS: Hypertension was well controlled in 70 patients (23.3%). The concordance rate between clinical measure of blood pressure and ABPM was 70.3%. Subjects with uncontrolled hypertension were older (61.8±8.9 vs 59.1±9.3 years, P<0.05), more frequently of male sex (sex-ratio: 0.77 vs 0.34, P<0.01), smokers (36.4 vs 21.7%, P<0.05) and with abdominal adiposity (P<0.05). Duration of diabetes, body mass index and the frequency of peripheral neuropathy, retinopathy and coronary insufficiency were not different between the two groups. Diabetic nephropathy was more frequent (29.8 vs 16.1%, P<0.05) in the group with uncontrolled hypertension. Loss of circadian blood pressure rhythm was noted in 239 patients (79.6%) and it was more frequently observed in patients with uncontrolled hypertension (84 vs 66%, P<0.001). CONCLUSION: Our type 2 diabetic patients had a poorly controlled hypertension. Close monitoring of blood pressure with adjustment of antihypertensive treatment are necessary to improve cardiovascular prognosis of our patients.