Obesity/overweight and asthma control in LEBANESE adults: a cross-sectional study.

BACKGROUND: Studies exploring the association between weight and asthma are not conclusive. Both obesity and asthma have been increasing in Lebanon, their association is not yet documented. The aim of this study is to explore the effect of weight on asthma control in adults. METHODS: This is a cross-sectional study, involving all consecutive asthma patients presenting to the outpatient allergy clinic at the Hotel-Dieu de France (HDF) University Hospital between January 1, 2014 and December 30, 2016. Patients included were those who consented to fill the Asthma Control Test (ACT) after 3 months of therapy. BMI was reported at the same time of the questionnaire. RESULTS: A total of 183 records of diagnosed asthma cases in adults were included. Sixty-three (34.4%) were males and 120 (65.6%) females, with a mean age of 38.5 (SD = 14.3). Ninety patients (49.2%) were of normal weight, 65 (35.5%) overweight and 28 (15.3%) obese. Seventy-one percent had an ACT score ≤ 19, which corresponds to poor asthma control. Patients who were overweight or obese were more likely to have poor asthma control compared to patients who had a normal weight at the time of evaluation. CONCLUSION: In conclusion, our study showed a significant association between asthma control as assessed by the ACT and high BMI defining overweight or obesity. This is the first national study exploring the association between asthma and overweight/obesity in Lebanon. A larger study with sampling from different specialists' sites is needed to draw more conclusions about this association.

SERUM INSULIN-LIKE GROWTH FACTOR 1 IN LEBANESE SCHOOLCHILDREN AND ITS RELATION TO VITAMIN D AND FERRITIN LEVELS.

OBJECTIVE: The aims of our study were to establish reference values for insulin-like growth factor 1 (IGF-1) in Lebanese schoolchildren and to evaluate the relationship between IGF-1 and age, sex, body mass index (BMI), vitamin D, and ferritin. METHODS: This cross-sectional study included 952 Lebanese schoolchildren (495 boys and 457 girls) aged 8 to 18 years. Blood samples were taken from children attending 10 schools with different socio-economic status (SES). Chemiluminescent immunoassays were used for IGF-1, 25 hydroxyvitamin D (25(OH)D), testosterone, and ferritin measurements. RESULTS: The mean age was 13.46 ± 2.80 with no significant difference according to sex. IGF-1 was correlated with age in both sexes (P<.0001); it was higher in girls compared to boys (P = .007) and peaked at the ages of 14 and 12 for boys and girls, respectively. For each age group, the median IGF-1 value was higher compared to the values provided by the kit. IGF-1 was significantly correlated with BMI in boys (r = 0.16, P<.0001) but not girls. In both sexes, IGF-1 was inversely correlated with 25(OH)D and ferritin values. After adjustment for age, BMI, and height, the correlation between IGF-1 and 25(OH)D disappeared, whereas the relationship with ferritin persisted (P<.001 for boys, P = .002 for girls). For both sexes, multivariate regression analysis revealed independent associations between IGF-1 and height, Tanner stage, and ferritin. An association was also noted in boys for BMI and testosterone. CONCLUSION: Our results showed higher and earlier peak IGF-1 values in the pediatric Lebanese population compared to western populations. In addition, an independent inverse relationship was observed between IGF-1 and ferritin. Further studies are needed to identify the reason(s) underlying these results. ABBREVIATIONS: BMI = body mass index CRP = C-reactive protein CV = coefficient of variation GH = growth hormone IGF-1 = insulin-like growth factor 1 25(OH)D = 25 hydroxyvitamin D SES = socio-economic status TSH = thyroid-stimulating hormone.

[Screening of diabetic retinopathy and maculopathy in Lebanese population using retinography and SD-OCT: The role of telemedicine]. / DÉPISTAGE de la RÉTINOPATHE et de la MACULOPATHIE DIABÉTIQUE au LIBAN par RÉTINOGRAPHIE et par SD-OCT: INTÉRÊT de la TÉLÉMÉDECINE.

PURPOSE: Diabetes and diabetic retinopathy (DR) are nowadays a major public health threat. The aim of this study is the screening of DR and diabetic maculopathy (DM) in a primary medical care center in Lebanon. We study also the interest of retinography and of SD-OCT in a telemedicine screening program. METHODS: This is a transversal study of patients with type 2 diabetes and with a regular follow-up in a primary medical care center in Beirut. For every patient, a retinography and an SD-OCT of the macula were obtained. Photos were sent by Internet to the Ophthalmology Department of Hôtel-Dieu de France to be evaluated by a retina specialist. Visual acuity and DR risk factors were assessed. RESULTS: 119 patients were included in this study. Mean age was 51.7 ± 10.2 years (54 females and 65 males). Mean diabetes duration was 12.15 years (SD 6:2). Mean of last three measurements of glycated hemoglobin was 8.1 ± 1.34%. Diabetic retinopathy was detected in 36 patients by retinography (30.3%). Diabetic maculopathy was confirmed by SD-OCT in 13 patients. Visual acuity was significantly correlated with central macular thickness. Mean diabetes duration, mean of last three measurements of glycated hemoglobin, peripheral neuropathy, positive macroalbuminuria and treatment with insulin were independently associated to diabetic retinopathy. CONCLUSION: Teleophthalmology is an efficient way for screening diabetic retinopathy in the Lebanese population. National screening program should be undertaken to adapt teleophthalmology on a larger scale.

Bilateral ovary adrenal rest tumor in a congenital adrenal hyperplasia following adrenalectomy.

OBJECTIVE: In contrast to the high incidence of testicular adrenal rest tumors in adult male patients with congenital adrenal hyperplasia (CAH), ovarian adrenal rest tumors (OARTs) in female CAH patients are rare. In this case report, we describe a case of bilateral OART in a female patient with CAH due to 21-hydroxylase deficiency. METHODS: We present a detailed case report with the clinical, imaging, and laboratory findings of the patient. The pertinent literature is also reviewed. RESULTS: A 17-year-old patient was known to have CAH due to 21-hydroxylase deficiency. Since the second month of her gestational age, her mother was treated with cortisone-replacement therapy. The patient was treated with hydrocortisone and fludrocortisone since the neonatal period. Her pertinent history included a bilateral adrenalectomy at the age of 13 years in 2006, and for 3 years she led a normal puberty life with no complaint with hormonal replacement therapy. Nevertheless, in 2009, she developed a virilizing syndrome. Subsequently, she underwent surgery in December 2009 for right adnexectomy. However, the regression of the masculinizing mass was not complete and worsened several months after the surgery. A new pelvic magnetic resonance image showed the activation of a contralateral ovarian mass, necessitating a left adnexectomy in August 2010. CONCLUSION: This case demonstrates some interesting features of OART that pose challenges to its management. If an OART is detected early enough and glucocorticoid therapy is received, it is possible that the OART will decrease in size following suppression of adrenocorticotropic hormone levels.

Chronic urticaria and autoimmune thyroiditis.

GOAL: Idiopathic chronic urticaria may be associated to other auto-immune diseases, in particular thyroiditis. The goal of our study is to show that this association is higher than the incidence of auto-immune thyroiditis in the general population. METHODS: It is a retrospective observational study including 90 patients with chronic urticaria. We calculated the proportion of patients having associated auto-immune thyroiditis based on a level of anti-TPO >220 mUI/ml. RESULTS: The mean age of patients was 36.7 years with a sex ratio F/H of 2.9/1. The anti-TPO antibodies were positive in 16 patients (17.7%). Eight were euthyroid, seven had hypothyroidism and one had hyperthyroidism with positive anti-TSH receptor antibodies. The percentage of anti-TPO antibodies in the chronic urticaria patients was higher than the control group (17.7 vs. 8.7; p < 0.01). CONCLUSION: This significant association between chronic urticaria and autoimmune thyroiditis may change the medical practice in Lebanon by including anti-TPO and anti-thyroglobulin antibodies in the workup of patients with chronic urticaria.

Vitamin D3 Dose Requirement That Raises 25-Hydroxyvitamin D to Desirable Level in Overweight and Obese Elderly.

CONTEXT: Guidelines for the dosage of vitamin D supplementation vary widely globally. OBJECTIVE: To investigate the impact of 2 vitamin D doses, bracketed between the IOM recommended dietary allowance (RDA) and the upper tolerable limit, on vitamin D nutritional status in elderly individuals. METHODS: This post hoc analysis of data collected from a 12-month, double-blind, randomized control trial included 221 ambulatory participants (≥ 65 years) with a mean BMI of 30.2 kg/m2 and a mean baseline serum 25-hydroxyvitamin D [25(OH)D] level of 20.4 ±â€…7.4 ng/mL, who were recruited from 3 outpatient centers in Lebanon. All participants received 1000 mg of elemental calcium daily from calcium citrate plus the daily equivalent of either 600 IU or 3750 IU of vitamin D3. RESULTS: Mean 25(OH)D level at 12 months was 26.0 ng/mL with low dose and 36.0 ng/mL with high dose vitamin D3. The proportion of participants reaching a value ≥ 20 ng/mL was 86% in the low dose, and 99% in the high dose arms, with no gender differences. The increment of 25(OH)D per 100 IU/day was 1 ng/mL with the low dose, and 0.41 ng/mL with the high dose. Serum 25(OH)D levels at 1 year were highly variable in both treatment arms. Baseline 25(OH)D level and vitamin D dose-but not age, BMI, gender, or season-were significant predictors of serum 25(OH)D level post-intervention. CONCLUSION: The IOM Recommended Dietary Allowance (RDA) of 600 IU/day does not bring 97.5% of ambulatory elderly individuals above the desirable threshold of 20 ng/mL. Country-specific RDAs are best derived taking into account the observed variability and predictors of achieved 25(OH)D levels.

Total, Bioavailable, and Free 25(OH)D Relationship with Indices of Bone Health in Elderly: A Randomized Controlled Trial.

CONTEXT: Questions regarding the superiority of free and bioavailable 25-hydroxyvitamin D [25(OH)D] in predicting health outcomes remain unresolved. OBJECTIVE: This study investigates the impact of vitamin D variables-total, bioavailable, or free 25(OH)D-on indices of bone and mineral metabolism, at baseline and in response to 2 vitamin D doses. DESIGN: Our objectives are implemented as exploratory analyses on data collected in a 1-year, double-blind, randomized controlled trial completed in July 2014. SETTING: Participants were recruited from 3 major hospitals in an ambulatory setting. PARTICIPANTS: Participants were >65 years of age, overweight, and had a baseline serum 25(OH)D between 10 and 30 ng/mL. A total of 221 participants completed the study. INTERVENTION: Subjects were randomized to receive calcium and oral vitamin D3 (600 IU/day or 3750 IU/day) supplementation. RESULTS: Participants who received the higher vitamin D dose had levels that were 1.3- to 1.4-fold higher than those taking the lower dose, for all variables (P value < 0.001). Serum values of bioavailable and free 25(OH)D were associated with total 25(OH)D, with r values of 0.942 and 0.943, respectively (P value < 0.001). Parathyroid hormone (PTH) was negatively associated with all vitamin D variables, with correlation coefficients ranging from -0.22 to -0.25, while calcium and bone turnover markers (carboxy-terminal collagen crosslinks and osteocalcin) did not. Only total 25(OH)D had a positive relationship with % change bone mineral density (BMD) at the femoral neck at 12 months, while only free and bioavailable 25(OH) had a positive relationship with % change total body BMD at 12 months. CONCLUSION: Calculated free and bioavailable 25(OH)D do not appear to be superior to total 25(OH)D in predicting indices of bone health in an elderly population.

Identification of a Variant in APOB Gene as a Major Cause of Hypobetalipoproteinemia in Lebanese Families.

Familial hypobetalipoproteinemia (FHBL) is a codominant genetic disorder characterized by reduced plasma levels of low-density lipoprotein cholesterol and apolipoprotein B. To our knowledge, no study on FHBL in Lebanon and the Middle East region has been reported. Therefore, we conducted genetic studies in unrelated families and probands of Lebanese origin presenting with FHBL, in order to identify the causes of this disease. We found that 71% of the recruited probands and their affected relatives were heterozygous for the p.(Arg490Trp) variant in the APOB gene. Haplotype analysis showed that these patients presented the same mutant haplotype. Moreover, there was a decrease in plasma levels of PCSK9 in affected individuals compared to the non-affected and a significant positive correlation between circulating PCSK9 and ApoB levels in all studied probands and their family members. Some of the p.(Arg490Trp) carriers suffered from diabetes, hepatic steatosis or neurological problems. In conclusion, the p.(Arg490Trp) pathogenic variant seems a cause of FHBL in patients from Lebanese origin, accounting for approximately 70% of the probands with FHBL presumably as a result of a founder mutation in Lebanon. This study is crucial to guide the early diagnosis, management and prevention of the associated complications of this disease.

Multiple pancreatic insulinomas: multislice CT.

Imaging techniques are in permanent evolution and so are their respective sensitivities. We present a case of a patient who had three abdominal CT scans over 10 years for the detection of pancreatic insulinomas. The first was made on an incremental CT and showed no lesion, the second on a single-slice helical CT which revealed a single centimetric tumor of the head of the pancreas, and the third on 64-slice CT which revealed 5 infracentimetric tumors. We do not know if all were present at the first scan but it is possible that these small tumors could have been missed on thick CT scan slices with overlap. The ideal imaging technique for the detection of endocrine pancreatic tumor is not known yet. The detection rates in the latest publications are 80% for CT scans and 70% for MRI, but there is a slight preference for CT scan because of its larger availability and higher resolution.

[Vitamin D status in Lebanese university students].

Vitamin D inadequacy is highly prevalent in Lebanon in young adults, school children and postmenopausal osteoporotic women. However, this prevalence has not been previously studied in university students. Three hundred and eighty-one students (mean age 23.9 +/- 3.9 years), randomly recruited from Saint-Joseph University, were included in this cross-sectional study (201 males and 180 females). Recruitment was performed across all seasons. The mean 25 hydroxyvitamin D (25(OH)D) was 31 +/- 12A ng/ml. 25(OH)D was inversely correlated with BMI and waist circumference (r = -0.18 and r = -0.19,p < 0.001 for both variables). 25(OH)D was significantly different between the winter season and the other seasons (p = 0.023, p = 0.001 and p < 0.0001 for spring, summer and fall respectively). 25(OH)D was lower in men compared to women (29.01 +/- 11.23 versus 33.2 +/- 13A, p < 0.01). This gender difference disappears after adjustment for both season and BMI. In addition, the inverse relation between 25(OH)D and BMI was non significant in the female population. In a stepwise multilinear regression analysis using 25(OH)D as a dependent variable, season and BMI were the independent predictors of vitamin D levels (p < 0.0001 and p = 0.001 respectively). Our results suggest that, in a population of high educational level, vitamin D status is better compared to other subgroups of the Lebanese population. In addition, we found, after adjustment for BMI and season, no gender difference in 25(OH)D levels while the winter season and a high BMI negatively affect vitamin D status.

The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene.

Autosomal dominant hypercholesterolemia (ADH), a major risk for coronary heart disease, is associated with mutations in the genes encoding the low-density lipoproteins receptor (LDLR), its ligand apolipoprotein B (APOB) or PCSK9 (Proprotein Convertase Subtilin Kexin 9). Familial hypercholesterolemia (FH) caused by mutation in the LDLR gene is the most frequent form of ADH. The incidence of FH is particularly high in the Lebanese population presumably as a result of a founder effect. In this study we characterize the spectrum of the mutations causing FH in Lebanon: we confirm the very high frequency of the LDLR p.Cys681X mutation that accounts for 81.5 % of the FH Lebanese probands recruited and identify other less frequent mutations in the LDLR. Finally, we show that the p.Leu21dup, an in frame insertion of one leucine to the stretch of 9 leucines in exon 1 of PCSK9, known to be associated with lower LDL-cholesterol levels in general populations, is also associated with a reduction of LDL-cholesterol levels in FH patients sharing the p.C681X mutation in the LDLR. Thus, by studying for the first time the impact of PCSK9 polymorphism on LDL-cholesterol levels of FH patients carrying a same LDLR mutation, we show that PCSK9 might constitute a modifier gene in familial hypercholesterolemia.

[Autoimmune thyroid disease. Clinical and biological correlations]. / Maladies thyroïdiennes auto-immunes corrélations cliniques et biologiques.

In this article, we analyze the clinical and biological data concerning the autoimmune thyroid diseases in patients recruited in an endocrinology clinic at the university hospital center of Hôtel-Dieu de France between March 2005 and November 2005. We studied 121 patients (51 with Basedow disease and 70 with Hashimoto thyroiditis), between 13 and 68 years old, with a BMI of 24.68 kg/m2 and with a female predominance (105 women). Symptoms of hyperthyroidism represented the most frequent cause of consultation. The distribution of patients regarding their thyroid disease showed that 42.1% of patients had hyperthyroidism (only one patient had subclinical hyperthyroidism), 21.5% had a subclinical hypothyroidism, 28.1% had clinical hypothyroidism and 8.3% had euthyroid goiter. Half of the patients had at least a member of their family whith a thyroid disease. The autoimmune thyroid diseases are strongly associated to other autoimmune diseases and to repetitive spontaneous abortion. Thus, 39% of the married women had had at least one spontaneous abortion and 26.4% of the patients had one or more autoimmune disease associated to their thyroid disease; diabetes mellitus type 1 representing the most frequent one. Concerning the treatment, we remarked a remission of 30 patients (66.7%) with Basedow disease after 18 months of antithyroid drug treatment of 45 patients. In Hashimoto thyroiditis, we remarked a frequent evolution of patients with subclinical hypothyroidism to overt hypothyroidism when medical treatment was not initiated.

Classification and Regression Tree (CART) model of sonographic signs in predicting thyroid nodules malignancy.

PURPOSE: To develop a Classification and Regression Tree (CART) model in order to recognize the most suspicious sonographic features of thyroid nodules and efficiently guide their management. METHODS: 791 thyroid fine needle aspiration cytology (FNAC) performed under ultrasound guidance between January 2015 and January 2017 were reviewed. Retrieved data consisted in qualitative (patient's gender, composition, echogenicity, shape, margins and echogenic foci of the nodule) and quantitative (patient's age and maximal diameter of the nodule) variables as well as the Bethesda score. RESULTS: Patients were 48.5 ±â€¯13.7 years old with female to male ratio of 8:2. The nodules had median size of 2.3 (1.5-3.5) cm with a majority of solid (62.5 %) and isoechoic (50.8 %) features. 700 nodules (88.5 %) had a wider-than-tall shape, 600 (75.9 %) smooth margins and 113 (14.3 %) ill-defined ones. Echogenic foci were absent in 388 nodules (49.1 %) and, when present, largely dominated by punctate foci (32.5 %). Bethesda classes 3, 4 and 5, which require surgery, represented only 10.6 % of cases. They were significantly correlated with the taller-than-wide shape and with solid or predominantly solid features. There was no significant correlation between echostructure and Bethesda scores but we did find more nodules classified Bethesda 4 and 5 in the categories hypoechoic and severely hypoechoic. In the CART model we developed, the sequence leading to most nodules classified Bethesda 4 and 5 is: taller-than-wide shape, solid composition and hypoechoic or severely hypoechoic feature. CONCLUSIONS: Taller-than-wide, solid or predominantly solid, hypoechoic or severely hypoechoic nodules are likely to require surgery and might benefit from FNAC.

Limitations of platform assays to measure serum 25OHD level impact on guidelines and practice decision making.

CONTEXT: Liquid Chromatography Mass Spectroscopy (LC-MS/MS) is the preferred method to measure 25 hydroxyvitamin D (25OHD) levels, but laboratories are increasingly adopting automated platform assays. OBJECTIVE: We assessed the performance of commonly used automated immunoassays, with that of LC-MS/MS, and the National Institute of Standards and Technology (NIST) reference values, to measure 25OHD levels. METHODS/SETTING: We compared serum 25OHD levels obtained from 219 elderly subjects, enrolled in a vitamin D trial, using the Diasorin Liaison platform assay, and the tandem LC-MS/MS method. We also assessed the performance of the Diasorin and Roche automated assays, expressed as mean % bias from the NIST standards, based on the vitamin D External Quality Assessment Scheme (DEQAS) reports, from 2013 to 2017. RESULTS: Serum 25OHD levels were significantly lower in the Diasorin compared to LC-MS/MS assay at baseline, 18.5 ±â€¯7.8 vs 20.5 ±â€¯7.6 ng/ml (p < 0.001), and all other time points. Diasorin (25OHD) = 0.76 × LC-MS/MS (25OHD) + 4.3, R2 = 0.596. The absolute bias was independent of 25OHD values, and the pattern unfit for any cross-calibration. The proportion of subjects considered for vitamin D treatment based on pre-set cut-offs differed significantly between the 2 assays. There also was wide variability in the performance of both automated assays, compared to NIST reference values. CONCLUSION: The performance of most widely used automated assays is sub-optimal. Our findings underscore the pressing need to re-consider current practices with regard to 25OHD measurements, interpretation of results from research studies, meta-analyses, the development of vitamin D guidelines, and their relevance to optimizing health.

Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial.

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C-terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high-dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high-dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.

Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men.

OBJECTIVE: The relationships between adipocytokines, sex steroids and the GH/IGF-I axis is poorly studied and subject to controversy in healthy elderly male subjects. We investigated the association between both adiponectin and leptin, and the metabolic syndrome (MetS), lipid parameters, insulin sensitivity, sex steroids and IGF-I in healthy non-diabetic Lebanese men. DESIGN AND METHODS: In this cross-sectional study, a total of 153 healthy non-diabetic men aged 50 and above (mean age 59.3 +/- 7 years) had a detailed clinical and biological evaluation. Subjects were classified according to the National Cholesterol Education Program criteria of the MetS. Insulin sensitivity was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: Subjects with the MetS had lower adiponectin and higher leptin levels (P < 0.0001 for both variables) compared with individuals without the MetS. Adiponectin was significantly correlated with waist size, triglycerides, high-density lipoprotein (HDL) cholesterol and QUICKI (r = -0.33, -0.26, 0.45 and 0.36 respectively, P < 0.0001 for all variables). The relation between adiponectin and HDL cholesterol, triglycerides and QUICKI remained significant after adjustment for age and body mass index (BMI). Also, leptin was strongly correlated with waist size and QUICKI (r = 0.63 and -0.63 respectively, P < 0.001 for both variables). However, its relation to the lipid profile was weak (for cholesterol r = 0.16, P < 0.05; for triglycerides r = 0.17, P < 0.05) and disappeared after adjustment for BMI. Adiponectin was positively correlated with sex hormone-binding globulin (SHBG) (r = 0.39, P < 0.001) and inversely correlated with free-androgen index (r = -0.24, P < 0.01), estradiol and dehydroepiandrosterone sulfate (r = -0.165, P < 0.05; r = -0.21, P < 0.01 respectively). This difference remained significant for SHBG after adjustment for age and BMI (r = 0.20, P < 0.005). Finally, leptin was inversely correlated with total testosterone and SHBG (r = -0.44, P < 0.001; r = -0.30, P < 0.001 respectively); the relation with testosterone remained significant after adjustment for BMI. No significant relationship of either adiponectin or leptin with GH or IGF-I values was observed. In a stepwise multiple regression analysis, the independent predictors of adiponectin were HDL cholesterol, QUICKI, age and BMI (P < 0.0001, P = 0.005, P = 0.002 and P = 0.047 respectively) while for leptin, it was QUICKI, waist size and testosterone (P < 0.0001, P < 0.0001 and P = 0.004 respectively). The adjusted R2 values were 0.34 and 0.55. CONCLUSION: Our results show that in a healthy elderly male population, both adiponectin and leptin are related to insulin sensitivity, independent of age and BMI. While adiponectin is independently related to triglycerides and HDL cholesterol, the weak relationship of leptin to the lipid profile is completely mediated by BMI. In addition, and more interestingly, both adipocytokines are strongly associated with sex steroids. We speculate that SHBG is regulated by adiponectin and that there is an inhibitory effect of testosterone on the adiponectin gene. Further studies are needed to fully elucidate these relationships.

Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial.

BACKGROUND: It is unclear whether and at what dose vitamin D supplementation affects insulin resistance (IR). OBJECTIVE: We sought to investigate whether vitamin D at doses higher than currently recommended decreases indexes of IR in an ambulatory population of overweight elderly subjects. DESIGN: This double-blind, randomized, controlled multicenter trial enrolled 257 elderly overweight individuals aged ≥65 y with baseline 25-hydroxyvitamin D [25(OH)D] concentrations between 10 and 30 ng/mL. All subjects received 1000 mg calcium citrate/d, with vitamin D administered weekly at an equivalent dose of 600 or 3750 IU/d. The homeostasis model assessment (HOMA) of IR index at 1 y was the primary outcome. We also assessed the McAuley index. RESULTS: In total, 222 subjects (55% women) with a mean ± SD age and body mass index (BMI; in kg/m(2)) of 71 ± 4 y and 30 ± 4, respectively, completed the study. Subjects' baseline characteristics, including IR indexes, were similar across groups: 69% had prediabetes, 54% had hypertension (47% were taking antihypertensive medications), and 60% had hyperlipidemia, nearly half of whom were receiving lipid-lowering drugs. At 1 y, mean ± SD serum 25(OH)D increased from 20 ± 7 to 26 ± 7 ng/mL in the low-dose arm (P < 0.0001) and from 21 ± 8 to 36 ± 10 ng/mL in the high-dose arm (P < 0.001). Median HOMA-IR indexes did not change compared with baseline concentrations and were similar in the high- [2.2 (IQR: 1.5, 2.9)] and low-dose [2.3 (IQR: 1.6, 3.3] treatment groups. Adjusted analyses showed that HOMA-IR was predicted by the baseline HOMA index and BMI but not by vitamin D dose, baseline serum 25(OH)D, or change in 25(OH)D. CONCLUSION: Vitamin D3 at 3750 IU/d did not improve HOMA-IR compared with the Institute of Medicine Recommended Dietary Allowance of 600 IU/d in elderly overweight individuals. This trial was registered at clinicaltrials.gov as NCT01315366.

Pravastatin does not affect insulin sensitivity and adipocytokines levels in healthy nondiabetic patients.

BACKGROUND: The effect of statins on insulin resistance is controversial and poorly studied in nondiabetic subjects. In addition, the effect of statins on leptin and adiponectin has never been studied. METHODS: Forty healthy nondiabetic volunteers (22 men and 18 women) aged 28 to 72 were randomized either to placebo or pravastatin 40 mg daily for a 12-week period. Insulin resistance, assessed using the Quantitative Insulin Sensitivity Check Index (QUICKI), as well as serum leptin and adiponectin levels, was measured at baseline and at the end of therapy. RESULTS: Pravastatin treatment decreased total cholesterol, low-density lipoprotein cholesterol, and triglycerides levels by 24%, 32%, and 14%, respectively ( P < .05 for all), but did not affect glucose and insulin levels, the (QUICKI) index, and adiponectin and leptin levels. When stratification was performed according to QUICKI index or sex, no significant differences were observed in the prevalues and postvalues of leptin, adiponectin, or QUICKI index in the pravastatin group. Adiponectin, leptin, and QUICKI index were statistically higher in women than in men ( P < .001 for both variables). Adiponectin was negatively correlated with body mass index (BMI; r = -0.39, P < .05) and positively correlated with the QUICKI index ( r = 0.54, P < .001) and with high-density lipoprotein cholesterol ( r = 0.50, P < .01). The relation between adiponectin and QUICKI index remained significant after adjustment for sex and BMI ( P = .005 and P = .007, respectively). Leptin was only related to BMI ( r = 0.57, P < .001) and to sex ( P < .001) with no significant correlations with lipid parameters or QUICKI index. Both sex and BMI are independent predictors of leptin ( P < .001 and P < .001). CONCLUSION: A 12-week treatment with pravastatin 40 mg/d does not change the QUICKI index and leptin and adiponectin levels in healthy volunteers. In addition, our results emphasize the importance of sex and BMI in the determination of both adiponectin and leptin. Adiponectin was also related to QUICKI index, whereas this relation was not found with leptin.

Dietary calcium and vitamin D intake in an adult Middle Eastern population: food sources and relation to lifestyle and PTH.

Little is known about calcium and vitamin D intakes in Middle Eastern countries, where the prevalence of hypovitaminosis D is high. This study identifies major sources of calcium and vitamin D in the Lebanese diet, examines lifestyle factors that may influence intake of these nutrients and investigates the relationship between nutritional or lifestyle factors and parathyroid hormone (PTH). Three hundred sixteen young healthy volunteers aged 30 to 50 (men, non-veiled and veiled women) were recruited from different rural and urban Lebanese community centers. Food frequency questionnaire was used to evaluate the consumption of vitamin D and calcium-rich foods. We also measured serum PTH levels. Mean daily calcium and vitamin D intake were respectively 683.8 +/- 281.2 mg and 100.6 +/- 71.0 IU. Daily vitamin D sources were divided as follows: 30.4 +/- 46.4 IU from milk and dairy products, 28.2 +/- 26.3 IU from meat and poultry, 25.8 +/- 25 IU from fish, 8.5 +/- 8.6 IU from eggs, and 7.8 +/- 14.3 IU from sweets (respectively 30.2%, 28%, 25.6%, 8.4% and 7.7% of the total vitamin D intake). Mean daily calcium from animal and vegetable sources were respectively 376.3 +/- 233.6 mg and 307.9 +/- 118.5 mg. Animal/total calcium intake ratio was 52% and was only statistically significantly higher in urban people compared to rural ones. Multivariate analysis showed that male sex and urban residence were independent predictors of both vitamin D and calcium intakes (p < 0.01 and p < 0.01 respectively). In addition, veiling was an independent predictor of low vitamin D intake (p < 0.05) and a high body mass index (BMI) was an independent predictor of low calcium intake (p < 0.05). Finally, PTH was inversely correlated with vitamin D intake and the animal/total calcium intake ratio (r = -0.18 and r = -0.22, p < 0.01), while no significant results were achieved for the vegetable calcium. In a multivariate model, urban living, female gender, low vitamin D and calcium intakes, low animal/total calcium intake ratio, and high BMI, are independent predictors of hyperparathyroidism. The deficient nutritional status of vitamin D and calcium in Lebanon justify the implementation of dietary public health measures. People at most risk for secondary hyperparathyroidism should be advised to increase their dietary calcium (mostly animal calcium) and vitamin D, to take supplements, or to increase their sun exposure.

No association between the -1031 polymorphism in the TNF-alpha promoter region and type 1 diabetes.

Tumor necrosis factor alpha (TNF-alpha) is an important immunomodulator and is believed to be involved in the development or progression of type 1 diabetes. In the following study, we evaluated TNF-alpha promoter polymorphisms at positions -863 and -1031 and their association with type 1 diabetes in a group of 210 diabetic patients from Lebanon. Our results show that in our population, the C allele is predominant at position -863, whereas the A allele is very rare (2%). At position -1031, however, the C and T allele distribution was similar in both the patient (17.8% vs 82.2%, respectively) and the control (21.4% vs 79.6%) groups. No association of TNF-alpha genotype at position 1031 with type 1 diabetes was found as demonstrated by the family-based association test and the transmission disequilibrium test. However, when patient genotypes were compared, the recessive CC genotype was only found in type 1 diabetic males but not in type 1 diabetic females. This observation, however, requires further investigation in a larger sample before conclusive association to gender is suggested. In conclusion, our results demonstrate that no association between TNF-alpha polymorphism and type 1 diabetes seems to exist in our population.