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Hypopituitarism is a known cause of bone mineral loss. This study aimed to evaluate the frequency of osteopenia and osteoporosis in patients with Sheehan's syndrome (SS) and to determine the risk factors. This is a retrospective study of 60 cases of SS that have had a bone mineral density (BMD) measurement. Clinical, biological, and therapeutic data were collected. The parameters of osteodensitometry at the femoral neck and the lumbar spine of 60 patients with SS were compared with those of 60 age-, height-, and weight-matched control women. The mean age at BMD measurement was 49.4 ± 9.9 yr (range: 25-76 yr). The mean duration of SS was 19.3 ± 8.5 yr (range: 3-41 yr). All patients had corticotropin deficiency and were treated with hydrocortisone at a mean daily dose of 26.3 ± 4.1 mg. Fifty-seven patients (95%) had thyrotropin deficiency and were treated with thyroxine at a mean daily dose of 124.3 ± 47.4 µg. Thirty-five of the 49 patients, aged less than 50 yr at diagnosis and having gonadotropin deficiency (71.4%), had estrogen-progesterone substitution. Osteopenia was present in 25 patients (41.7%) and osteoporosis in 21 (35.0%). The BMD was significantly lower in the group with SS than in the control group (p < 0.001). The odds ratio of osteopenia-osteoporosis was 3.1 (95% confidence interval: 1.4-6.8) at the femoral neck and 3.7 (95% confidence interval: 1.7-7.8) at the lumbar spine. The lumbar spine was more frequently affected by low bone mineral mass (p < 0.05). The duration of the disease and the daily dose of hydrocortisone were independently and inversely associated with BMD at the femoral neck. The daily dose of thyroxine was independently and inversely associated with BMD at the lumbar spine. Estrogen-progesterone replacement therapy was not associated with BMD. Low bone mineral mass was very common in patients with SS. The lumbar spine was more frequently affected. The duration of the disease and the doses of hydrocortisone and thyroxine were involved in bone mineral loss., (Copyright © 2016 International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Aims: This study investigates the relationships between matrix metalloproteinases, inflammations mediators and type 2 diabetes mellitus in Tunisians metabolic syndrome (Mets) patients., Methods: The study has included 239 MetS patients and 247 controls. Mets was defined according to the NCEP-ATPIII report. Mets patients were also divided into two categories: 29 MetS non-diabetics and 210 MetS diabetics. Dysglycemia markers, matrix metalloproteinase-9 (MMP-9), Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), tumor necrosis factor α (TNF-α), C-reactive protein (CRP) levels and White Blood Cells (WBC) counts were determined in patients and controls., Results: In our study, the level of inflammatory markers WBC, TNF-α and matrix metalloproteinases (MMP-8 and MMP-9) were significantly higher in diabetic patients with MetS, as compared with non-diabetic MetS patients. Inflammation mediators and MMP-9 were significantly associated with many clinical characteristics of MetS. The use of ROC "Receiver Operating Characteristic" analysis revealed the impact of TNF alpha on diabetes patients with MetS. In fact TNF alpha was found as a sensitive parameter in these patients with a sensitivity of 85%., Conclusion: Inflammation, matrix metalloproteinases and dysglycemia markers are not expressed in isolation but rather concurrently and are continuously interacting with each other, in MetS and diabetics patients. These markers fit with an early stage of cardiovascular disease (CVD); and measuring them could improve the risk evaluation, an early diagnosis, and the prognosis of CVD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background & Objectives: The impact of several environmental and genetic factors on diabetes is well documented. Though the association between the vitamin D receptor (VDR) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been analyzed in different ethnic groups, the results have been inconsistent. The aim of this study was to evaluate the possible association between VDR FokI polymorphism and genetic susceptibility to T2DM in Tunisian population., Methods: A total of 439 unrelated patients with T2DM and 302 healthy controls were included in the study. Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNP) of FokI (T/C: (rs2228570) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis., Results: The genotype distribution and the relative allelic frequencies for the FokI polymorphism were not significantly different between T2DM and controls: in T2DM patients the frequencies of the CC, CT, and TT genotypes were 52.6, 41.0, and 6.1 per cent, respectively, and in controls the genotype frequencies were 55.6, 38.7, and 5.6 per cent, respectively. In our study, the TT genotype of the FokI polymorphism was not associated with T2DM (OR =1.19, 95% CI 0.63 - 2.25, P=0.577)., Interpretation & Conclusions: Our study showed no significant association of the FokI polymorphism in the vitamin D receptor gene with type 2 diabetes mellitus in Tunisian population., Competing Interests: None.

Background and Aims: Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a transcriptional co-activator involved in adaptive thermogenesis, skeletal muscle metabolism, fatty acid oxidation, and gluconeogenesis. Several studies have suggested that the common PGC-1α polymorphism Gly482Ser (rs8192678) may be associated with risk of type 2 diabetes (T2D), with conflicting results. The aim of this study was to analyze whether the Gly482Ser variant is a risk factor for development of T2D in Tunisian population., Methods: In a case-control study 487 unrelated patients with type 2 diabetes and 402 apparently healthy controls were recruited from January 2008 to August 2010. The Gly482Ser polymorphism was determined by PCR-RFLP analysis., Results: A significant difference in genotypes distribution was observed between patients (Gly/Gly: 34.1%; Gly/Ser: 47.1%; Ser/Ser: 18.5%) and controls (Gly/Gly: 43.8%; Gly/Ser: 42.3%; Ser/Ser: 13.9%) (χ(2)=9.44, p=0.009). The T2D patient group showed a significant higher frequency of the Ser allele compared to the controls (43% vs. 34%; OR: 1.35, 95% [CI]: 1.11-1.65, p=0.002). The association between the Gly482Ser polymorphism and T2D remained significant after adjustment for other well-established cardiovascular risk factors., Conclusions: In the current study, a significant and independent association between the Gly482Ser polymorphism (rs8192678) of the PGC-1α gene and T2D in the Tunisian population was found., (Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Aims: Tumor necrosis factor α (TNFα) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF α has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The aim of the present study was to investigate the association between the -863C/A polymorphism in the promoter of the TNFα gene and type 2 diabetes in the Tunisian population., Methods: The polymorphism -863C/A in the TNFα gene was determined in 211 type 2 diabetes patients and 345 healthy controls using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis., Results: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with type 2 diabetes had significantly higher frequency of the CA+AA genotypes compared to controls [35.5% vs. 22.3%; OR (95%CI), 1.91 (1.31-2.8); p=0.001]. The type 2 diabetes patient group showed a significant higher frequency of the A allele compared to the controls (0.19 vs. 0.11; p=0.001). After adjustment by a stepwise logistic regression method, hypertension, dyslipidemia, and CA+AA genotype were found to be significantly associated with T2D., Conclusion: The present study showed a significant and independent association between the -863C/A polymorphism of the TNFα gene and type 2 diabetes in the Tunisian population., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2012. Published by Elsevier SAS.)

Background: The aim of this study was to determine plasma levels of matrix metalloproteinases (MMPs) 2, 3, and 9 and their tissue inhibitors (TIMPs) 1 and 2 in type 2 diabetic patients (T2DM) compared to healthy subjects., Methods: The study involved 54 patients with T2DM and 57 age and gender matched healthy adults as controls. MMPs 2 and 9 were analyzed by gelatin zymography and MMP-3 and TIMPs 1 and 2 by ELISA., Results: For technical feasibility, MMPs 2 and 9 were expressed in pro forms. Pro-MMP-9 was significantly higher (p < 0.05), whereas TIMP-1 and TIMP-2 levels were significantly decreased (p < 0.01) in patients with T2DM compared to controls. The MMP-3/TIMP-1 and the MMP-3/TMP-2 ratios were significantly higher in T2DM patients than controls (p < 0.05). Fasting plasma glucose was inversely correlated with TIMP-1 (r = -0.412, p < 0.01) and TIMP-2 (r = -0.315, p < 0.001), but was not associated with MMPs., Conclusions: The present study identified abnormalities in plasma markers for extracellular matrix metabolism in T2DM. The new parameters would constitute an effective approach to explore the complications of uncontrolled diabetes.

To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3±7.6 years) and 180 postmenopausal women (mean age 53.4±6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDL-cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre- to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objectives: This study was undertaken to investigate the impact of the Pro12Ala (rs1801282) polymorphism of the peroxisome proliferator-activated receptor gamma-2 (PPARgamma-2) gene on obesity or body mass index (BMI) and plasma leptin, insulin, adiponectin and lipid levels in a sample of the Tunisian population., Design and Methods: The study included 387 obese patients and 288 control subjects. The Pro12Ala genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease BstUI., Results: In the whole population, there is no significant difference in genotype frequencies of the Pro12Ala polymorphism between obese patients and controls. However, separate analysis by gender revealed that obese men (but not women) had significantly higher frequency of Pro/Ala genotypes compared to controls (12.2% vs. 4.1%; chi(2)=6.76, p=0.009). In comparison to Pro/Pro homozygotes, Ala-allele bearers had a significantly higher risk of obesity [OR (95% CI)=3.26 (1.28-8.33)]. When obese subjects were stratified according to type 2 diabetes status, the association with obesity was only significant in obese non-diabetic patients [OR (95% CI)=3.74 (1.43-9.74), p=0.007]. Additionally, obese male patients carrying the Ala-allele had significantly higher body mass index (p=0.007) and plasma leptin levels (p=0.023) compared to those homozygous for Pro-allele. The significant effect of Pro12Ala polymorphism on plasma leptin levels disappeared after adjustment for age and BMI., Conclusion: The present study provides evidence that the Pro12Ala polymorphism of the PPARgamma-2 gene is associated with obesity in non-diabetic men from Tunisian origin.

Objectives: The aim of this study was to examine the association of the G-2548A polymorphism of the human leptin gene (LEP) with body mass index (BMI), plasma leptin, insulin, and lipid parameters in a sample of Tunisian population., Design and Methods: Two hundred and twenty nine obese patients (BMI>or=30 kg/m(2)) were screened and compared to 251 normal weight subjects (BMI<25 kg/m(2)). The human leptin gene promoter G-2548A genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease CfoI., Results: In the entire study sample, carriers of -2548A allele had significantly lower leptin levels than homozygous for -2548G allele (14.28+/-9.10 ng/mL vs. 18.27+/-12 ng/mL, p<0.001 respectively) adjusted for BMI and gender. In obese patients but not control, subjects carrying the -2548A allele exhibited lower leptin levels than those with GG genotype (16.96+/-8.27 ng/mL vs. 21.37+/-11.72 ng/mL, p=0.001 respectively) adjusted for BMI and gender. In this group, carriership of the -2548A allele was identified, by multiple linear regression models, as significant independent predictor for leptin levels variability. Separate analyses by gender revealed that only in obese women, the -2548A allele was found to be associated with lower leptin levels independently of BMI (p=0.004)., Conclusions: The present study showed that G-2548A LEP polymorphism is associated with lower leptin levels in Tunisian obese women.

Background and Aims: The leptin receptor (LEPR) plays a crucial role in the regulation of body weight. Several common polymorphisms have been described in the human LEPR gene including the p.Q223R polymorphism (rs1137101). The association of this polymorphism with obesity or related metabolic phenotypes has been controversial. The aim of this study was to investigate the impact of the LEPR p.Q223R polymorphism on body mass index (BMI), plasma leptin and lipid parameters in a sample of the Tunisian population., Methods: The study included 391 obese patients and 302 normal weight subjects. LEPR p.Q223R genotypes were identified by the PCR-RFLP analysis., Results: Obese patients homozygous for RR genotype showed lower leptin levels than those with other genotypes (p = 0.005) adjusted for age, BMI and gender. Stratified analysis by gender revealed that obese male patients carrying the R allele showed significantly lower BMI (p = 0.007) and leptin levels (p = 0.037) than subjects homozygous for the Q allele. In obese women, the LEPR p.Q223R polymorphism was found associated with lower leptin concentrations (p = 0.05). After adjustment for age and BMI, the association between the LEPR variant and plasma leptin remained significant only within female patients (p = 0.027). A general linear model including leptin as dependant variable and age, BMI, menopausal status and genotype as covariates revealed that the LEPR p.Q223R polymorphism is independently associated with leptin levels in obese women (p = 0.026)., Conclusions: Our findings suggest that the LEPR p.Q223R polymorphism influences plasma leptin levels and BMI in obese patients.

Platelet Ca(2+) homeostasis is controlled by a multi-Ca(2+)ATPase system including two PMCA (plasma membrane Ca(2+)ATPase) and seven SERCA (sarco/endoplasmic reticulum Ca(2+)ATPase) isoforms. Previous studies have shown similar platelet Ca(2+) abnormalities in diabetic and hypertensive patients, including an increase in intracellular [Ca(2+)](I), a possible modulation of PMCA activity and increased PMCA tyrosine phosphorylation. Very recently, we found that platelets from diabetic patients also exhibited increased PMCA4b expression. In the present study we looked for further similarities between diabetic and hypertensive patients. We first confirmed a decrease in Ca(2+)ATPase activity (mean 55 + 7%) in mixed platelet membranes isolated from 10 patients with hypertension compared with those from 10 healthy controls. In addition, the decreased Ca(2+)ATPase activity correlated with the DBP of the different patients, as expected for PMCA activity. Second, we performed a pilot study of six hypertensives to examine their expressions of PMCA and SERCA mRNA and proteins. Like the diabetic patients, 100% of hypertensives were found to present a major increase in PMCA4b expression (mean value of 218 +/- 21%). We thus determined that platelets from diabetic and hypertensive patients showed similar increased PMCA4b isoform. Since increased PMCA4b expression was recently found to be associated with a perturbation of megakaryocytopoiesis, these findings may also point to an abnormality in platelet maturation in hypertension.

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.

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.

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.