HbA1c AND BLOOD PRESSURE MEASUREMENTS: RELATION WITH GENDER, BODY MASS INDEX, STUDY FIELD, AND LIFESTYLE IN LEBANESE STUDENTS.

Objective: The purpose of this study is to determine the prevalence of prediabetes/diabetes in Lebanese university students and to examine the relationship between both hemoglobin A1c (HbA1c) and blood pressure (BP) and gender, body mass index (BMI), study field, and lifestyle factors. Methods: This cross-sectional study was carried out at the Saint-Joseph University of Beirut. A total of 603 students aged 18 to 25 years were recruited from both the medical science campus (MSC) and the social science campus (SSC) between January, 2016, and May, 2018. Waist circumference (WC), BMI, and BP were determined for each student and HbA1c was measured using the Siemens vintage DCA device. Participants completed a self-administered questionnaire about their eating habits and level of physical activity. Results: The mean age of the population was 20.31 ± 1.76 years. The percentage of participants recruited from the MSC was 59.2%. The prevalence of prediabetes was 2.5%. Lower BMI, WC, and HbA1c values, and higher diastolic BP (DBP) were found in MSC students compared to SSC ones. HbA1c, systolic BP (SBP), and DBP were correlated with BMI (P = .02, P<.0001, and P = .017, respectively). HbA1c was not associated with eating habits or physical activity. DBP was inversely associated with physical activity (P = .002), while SBP was positively associated with fast food consumption (P = .003). Conclusion: The present study shows a low prevalence of prediabetes in Lebanese students. BMI and the study field are the main factors predicting HbA1c and BP. Further studies are needed to extrapolate our results to the overall young Lebanese population. Abbreviations: ADA = American Diabetes Association; BMI = body mass index; BP = blood pressure; DBP = diastolic blood pressure; HbA1c = hemoglobin A1c; HTN = hypertension; MSC = medical science campus; SBP = systolic blood pressure; SSC = social science campus; T2D = type 2 diabetes; US = United States; USJ = Saint-Joseph University; WC = waist circumference.

Longitudinal changes of lipid profile in the Lebanese pediatric population.

BACKGROUND: Few studies looked at the prevalence of dyslipidemia in pediatric Middle-Eastern countries. In addition, worldwide longitudinal changes of lipid profile is not well documented. The purpose of this study is to look at the longitudinal changes of lipid parameters in Lebanese school-age children. MATERIALS AND METHODS: A total of 97 subjects (41 girls and 56 boys) aged between 11 and 21 years were included in this study. The subjects were selected among 339 school-age children with a previous abnormal lipid profile who were recruited from 10 schools of varying socio-economic levels (SEL). A fasting lipid profile [total cholesterol (TC), triglycerides (TG) and HDL-cholesterol (HDL-C)] was performed. Non-HDL-cholesterol (Non-HDL-C) was calculated. Weight and height were measured under the same conditions, and BMI percentiles were calculated. A multivariate covariance analysis model (MANCOVA) was used with TG, HDL-C and non-HDL-C as dependent variables with additional post-MANCOVA F tests. RESULTS: The age of the current cohort is 16.5 ± 2.9 years with no significant difference according to gender. The current lipid profile was obtained 3.1 ± 0.7 years following the initial one, with 53.6% of the subjects having it normalized. TC, TG, and non-HDL-C decreased significantly over time in girls, while only TG decreased significantly in boys. No significant changes were observed for HDL-C. Using MANCOVA, a significant time by age interaction was observed (p < 0.0001), while gender, BMI and SEL were found not to be significant. Post-hoc F tests showed that the time by age interaction was driven by TG (p = 0.03) and non-HDL-C (p < 0.001), the larger effect being observed in younger children. CONCLUSION: A high proportion of school-age children normalize their abnormal lipid profile with time. Screening for lipid disorders could be postponed until post puberty age.

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.

Prevalence and predictors of vitamin D deficiency in Lebanon: 2016-2022, before and during the COVID-19 outbreak.

BACKGROUND: Vitamin D deficiency is very common worldwide, particularly in Middle-Eastern countries. Recent Lebanese studies demonstrated an improvement in vitamin D status over time. However, the comparison between the years before and during the COVID-19 outbreak has never been analyzed in the Middle-East area. This study aimed to determine the prevalence and the predictors of 25-hydroxyvitamin D (25(OH)D) levels during the last 7 years. METHODS: Serum 25(OH)D levels from a large laboratory database were retrospectively collected from Hôtel-Dieu de France Hospital between January 2016 and June 2022 (N = 66,127). Data related to age, gender, season and year of sampling were also retrieved. RESULTS: Mean age of the population was 50.6 ± 19 years, 62.7% were women, 5.3% were children and adolescents, 67.6% adults and 27% elderly. Mean serum 25(OH)D level was 25.7 ± 11.9 ng/mL. The overall population with vitamin D sufficiency (>30 ng/mL) was 31.9%. The increase in mean serum 25(OH)D observed between 2016 and 2022 was 6.36 ng/mL (p < 0.0001). The prevalence of 25(OH)D deficiency (<30 ng/mL) decreased from 76.2% in 2016 to 56.5% in 2022 (p < 0.0001) with a significant difference between the period before and during the COVID-19 outbreak (72.3% vs.42.5%, p < 0.0001). In a multivariate logistic regression, older age, female sex, summer season, years of the COVID-19 outbreak and outpatient samples were protective factors against the risk of hypovitaminosis D (p < 0.0001 for all variables). CONCLUSION: Our study showed a continuous positive change in vitamin D status time, most notably after the COVID-19 outbreak. Further studies are needed to assess the clinical impact of the pandemic on vitamin D status in our population.

Reference intervals for thyroid-stimulating hormone, free thyroxine, free triiodothyronine, and total triiodothyronine in the Lebanese adult population.

BACKGROUND: For a better assessment of thyroid function, each laboratory should establish its own reference intervals (RI). In Lebanon, no previous study has been conducted to establish the reference values for thyroid function tests. METHODS: This cross-sectional study included 301 volunteers aged between 18 and 65 years (65.8% women, 34.2% men), free from any thyroid pathology and any condition that could affect thyroid function tests. The reference intervals of thyroid-stimulating hormone (TSH), free T4 (FT4), free T3 (FT3), and total T3 (TT3) were measured on the Roche Cobas e411 machine. 39 subjects tested positive for thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TGAb), were excluded from the study. RESULTS: There was an increase in the 2.5th percentile for the TSH compared to the value provided by the manufacturer (from 0.27 to 0.53 mlU/L) as well as a decrease in the 97.5th percentile for the FT4, TT3, and FT3 (respectively, from 22 to 19.78 pmol/L for FT4, from 3.1 to 2.71 nmol/L for TT3, and from 6.80 to 6.10 pmol/L for FT3). Higher TT3 and FT3 values were noted in men compared to women (respectively, p = 0.068 and p < 0.0001). An age decrease in FT4 and FT3 was also observed (respectively, p = 0.045 and p < 0.0001). CONCLUSION: The established RI of thyroid function tests for the Lebanese population were significantly different from the values recommended by the manufacturer (Roche Diagnostics). Changing our RI values will allow a more accurate diagnosis of thyroid dysfunction.

Lipid Parameters and Proprotein Convertase Subtilisin/Kexin Type 9 in Healthy Lebanese Adults.

Background: High levels of non-HDL cholesterol (non-HDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), and Proprotein convertase subtilisin/kexin type 9 (PCSK9) as well as low levels of HDL-C are strongly associated with cardiovascular disease (CVD). Our study aims to estimate the prevalence of dyslipidemia and high Lp(a) in the Lebanese population and to study the relationship of these variables with gender, age, body mass index (BMI), and PCSK9. Methods: This cross-sectional study was carried out on a sample of healthy volunteers aged 18 to 65. Blood samples were drawn from volunteers for total cholesterol (TC), HDL-C, TG, PCSK9, and Lp(a) measurements. Non-HDL-C was calculated by subtracting HDL-C from TC. Results: In total, 303 volunteer subjects with an average age of 38.9 years were included in the study. Respectively, 44%, 29.8%, and 44% of men had high non-HDL-C and TG with low HDL-C versus 23.5%, 8%, and 37% in women. Non-HDL-C and TG were significantly higher in men than in women, while the reverse was observed for HDL-C (p < 0.0001 for the three comparisons). Non-HDL-C and TG were significantly correlated with age and BMI (p< 0.0001 for all correlations), while HDL-C was inversely correlated with BMI (p < 0.0001) but not with age. Abnormal Lp(a) levels (≥75 nmol/L) were found in 19.1% of the population, predominantly in women (24.1% versus 13.4% in men, p = 0.004). The median PCSK9 and its interquartile was 300 (254−382) ng/L with no gender difference (p = 0.18). None of the following factors: gender, age, BMI, non-HDL-C, HDL-C, or TG, were independently associated with Lp(a), while PCSK9 was significantly correlated with age, non-HDL-C, and TG in both men and women and inversely correlated with HDL-C in men. Dyslipidemia is very common in the Lebanese population and is associated with age, high BMI, and male sex. Lp(a) is higher in women without any correlation with the lipid profile, whereas PCSK9 is associated with non-HDL-C and TG. Further studies are needed to evaluate the potential role of Lp(a) and PCSK9 in predicting CVD in healthy populations.

Circulating PCSK9 Linked to Dyslipidemia in Lebanese Schoolchildren.

In adults, elevated levels of circulating Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) have been associated with increased Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and worse cardiovascular outcomes. However, few studies analyzed the relation between PCSK9 and lipid parameters in pediatric populations. The aim of our study is to evaluate the distribution and the correlation of serum PCSK9 levels with lipid parameters in a sample of Lebanese school children. Using an immunofluorescence assay, we measured serum PCSK9 levels in 681 school children recruited from ten public and private Lebanese schools. We analyzed the association between PCSK9 and age, sex, Body Mass Index (BMI), and lipid parameters (total cholesterol (TC), LDL-C, TG, High-density lipoprotein cholesterol (HDL-C), non-HDL-C, and lipoprotein (a) (Lp(a)). Serum PCSK9 levels were significantly correlated with TC, LDL-C, and non-HDL-C (p value < 0.0001) but not with TG, HDL-C, and Lp(a). PCSK9 levels were also significantly higher in children with high TC, LDL-C, and non-HDL-C (p values = 0.0012, 0.0002, 0.001, respectively). No significant gender differences in PCSK9 were found. In addition, no significant associations between PCSK9 and both age and BMI percentiles were observed. In girls, no difference in PCSK9 values was observed according to menarche while in boys, testosterone levels were not significantly associated with PCSK9. Serum PCSK9 levels were significantly correlated with TC, LDL-C, and non-HDL-C levels. Further studies are needed to find if PCSK9 measurements have an additional value to predict future cardiovascular outcomes in pediatric populations.

Relation between androgens and cardiovascular risk factors in a young population.

OBJECTIVE: The relationship between androgens and blood pressure, insulin resistance, lipid profile, adiponectin and hs-CRP in a young Middle-Eastern population has not been examined previously. We studied this relationship in a randomly selected population of Lebanese students. METHODS: Three hundred and sixty-eight subjects (201 men and 167 women) aged 18-30 years were included in the study. Anthropometric and biological parameters [waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP), triglycerides, total cholesterol, HDL cholesterol, homeostasis model assessment of insulin resistance (HOMA-IR), total testosterone (TT), dehydroepiandrostenedione sulphate (DHEAS), sex hormone-binding globulin (SHBG), adiponectin (ADP) and hs-CRP] were measured. RESULTS: In men, there were inverse associations of both TT and SHBG with body mass index (BMI), WC, HOMA-IR, triglycerides and hs-CRP. After adjustment for major confounders (BMI, WC, age and smoking), associations disappeared except for those between TT and hs-CRP, and for SHBG HOMA-IR, hs-CRP and triglycerides. In women, only SHBG was inversely associated with BMI, WC, HOMA-IR and hs-CRP and positively correlated with adiponectin. Except for the association between SHBG and adiponectin, these correlations disappeared after adjustment for confounders. Although DHEAS appeared to correlate negatively with blood pressure in men, this relationship disappeared after adjustment for confounders, while a relationship between DHEAS and triglycerides in women persisted after such adjustment. In multivariate regression analysis, SHBG was an independent predictor of hs-CRP, triglycerides and HOMA-IR in men and of adiponectin in women. CONCLUSION: Our results suggest that SHBG is independently associated with HOMA-IR, adiponectin, hs-CRP and triglycerides. A gender difference in these associations is observed. Further studies are needed to elucidate these findings.

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.

[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.

Prevalence of Iron deficiency in Lebanese schoolchildren.

BACKGROUND: The prevalence of iron deficiency in the Lebanese pediatric population is unknown. The aim of this study is to estimate this prevalence in Lebanese schoolchildren and to assess the relation between iron status and related factors. SUBJECTS/METHODS: A total of 903 children aged 8-18 years (466 boys and 437 girls) were included in the study. Recruitment was done from ten schools with different SES levels and located in the Great Beirut and Mount Lebanon areas. Serum ferritin was measured in all participants and testosterone was measured only in boys using Immulite chemiluminescent assays. RESULTS: For the entire sample, the median serum ferritin concentration was 30.0 [19.8-44.8] ng/mL and the prevalence of iron deficiency (ferritin < 15 ng/mL) was 14.2%. Iron deficiency was higher in girls compared with boys (respectively, 20.8% and 7.9%). This prevalence varied with the SES (respectively, 11.6%, 11.9%, and 16.8% in high, middle, and low SES, p = 0.09). Iron deficiency increased with age (9.5%, 15.7%, and 17.5%, respectively, for the age groups 8-11, 12-14, and 15-18, p = 0.014) and did not differ between normal, overweight, and obese groups (p = 0.07). In boys, a significant positive correlation was observed between ferritin and total testosterone (rho = 0.150, p = 0.001). CONCLUSION: The prevalence of iron deficiency is relatively low in Lebanon. Younger boys, menstruating girls, and children from low SES are more prone to iron deficiency, while BMI has no impact.

Parathormone Levels in a Middle-Eastern Healthy Population Using 2nd and 3rd Generation PTH Assays.

BACKGROUND: The purpose of the current study is to determine PTH reference values in vitamin-D-replete Lebanese adults using 2nd and 3rd generation PTH assays and to look at the factors that affect PTH variations. METHODS: Fasting PTH was measured using 2nd and 3rd generation Diasorin PTH assays in 339 vitamin-D-replete healthy subjects aged 18 to 63 years (230 men and 109 women) who have normal calcium levels and an eGFR ≥60 ml/mn. 25-OH vitamin D (25(OH)D) was measured using the Diasorin assay. RESULTS: For the 2nd PTH generation, median (IQR) levels were 48.9 (34.9-66.0) pg/ml, and its 2.5th-97.5th percentile values were 19.7-110.5 pg/ml for 25(OH)D values between 20 and 30 ng/ml, and 19.7-110.7 pg/ml for 25(OH)D values ≥30 ng/ml. For the 3rd PTH generation, the median (IQR) values were 23.9 (17.7-30.5) pg/ml, and its 2.5th-97.5th percentile values were, respectively, 9.2 and 50.2 pg/ml for 25(OH)D values between 20 and 30 ng/ml, and 8.4 and 45.4 pg/ml for 25(OH)D values ≥30 ng/ml. The median (IQR) serum 25(OH)D levels were 27.5 (23.8-32.7) ng/ml. 2nd and 3rd generation PTH values are strongly correlated (r = 0.96, p < 0.0001), but poorly concordant (Lin's concordance coefficient 0.365, 95% CI: 0.328-0.401) with observations beyond the 95% Bland-Altman limits of agreement. 2nd and 3rd generation PTH levels did not differ according to gender and were significantly correlated with age but not with 25(OH)D and serum calcium levels. CONCLUSION: Lebanese adult healthy subjects have higher 2nd and 3rd generation PTH levels compared with the reference range provided by the manufacturer. The reference range was not influenced by changing the 25(OH)D cutoff. The clinical significance of the higher PTH levels in our population should be investigated.

Prevalence and status of Lipoprotein (a) among Lebanese school children.

Lipoprotein a (Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease. The prevalence of high Lipoprotein (a) (Lp(a)) in the Lebanese pediatric population is unknown. Our study aims to assess this prevalence and to study the relationship of Lp(a) with the lipid profile, age, body mass index (BMI) and socio-economic status (SES) in Lebanese schoolchildren. A total of 961 children aged 8-18 years (497 boys and 464 girls) were recruited from ten private and public schools in 2013-2014 using a stratified random sample. Schools were selected from the Greater Beirut and Mount Lebanon areas, and were categorized into three subgroups according to the schools' SES status (high, medium, low). Lp(a) was assayed in 2018 on samples previously frozen at - 80 °C. Abnormal Lp(a) levels (≥ 75 nmol/L) were observed in 14.4% of the overall sample (13.5% for boys,15.3% of girls p = 0.56). The median of Lp(a) was 20(10-50) in the whole sample with no significant gender difference. No significant relationship was found between Lp(a) and age. However, Lp(a) was significantly correlated with BMI in whole sample, as well as in boys and girls (p = 0.02, p = 0.03, p = 0.03, respectively). A significant correlation was found between Lp(a) and non-HDL-C in the whole sample as well as in boys and girls (respectively p < 0.001,p = 0.024 and p = 0.03), but not with triglycerides and HDL-C. In a multivariate linear regression analysis, Lp(a) was only independently associated with BMI and non-HDL-C in boys and girls. Lp(a) was independently associated with BMI and non-HDL-C while no significant relationship was observed with age and sex confirming the strong genetic determination of Lp(a).

Comparison between Second- and Third-Generation PTH Assays during Minimally Invasive Parathyroidectomy (MIP).

METHODS: 112 patients (of which 72.3% females) underwent MIP by the same surgeon. Age, sex, body mass index (BMI), pre- and postoperative serum calcium, creatinine, 25(OH)D levels, PTH at baseline (PTH T0), and PTH at 10 minutes after adenoma resection (PTH T10) were recorded. Both PTH 2G and PTH 3G assays were assessed using the Diasorin assays. RESULTS: The mean age was 56.1 ± 14.7 years. Mean value of BMI, preoperative calcium, 25(OH)D, and CKD-EPI-eGFR were, respectively, 26.8 ± 4.8 kg/m2, 110.9 ± 7.9 mg/L, 19.3 ± 9.2 ng/mL, and 88.6 ± 25.6 mL/min/1.73 m2. PTH 2G and PTH 3G assays were well correlated at PTH T0 and PTH T10 (respectively, correlation coefficient 0.74 and 0.72 for intraclass correlation type 3). The median PTH fall was, respectively, of 79.9% and 82.5% for PTH 2G and PTH 3G. Multivariate analysis using the combined PTH 2G and PTH 3G as a dependent variable with 2 repeated measurements (at PTH 0 and PTH 10) showed a significant effect of preoperative calcium on IOPTH fall (p=0.001, effect size 0.13), while no significant effects were observed for sex, age, BMI, and 25(OH)D. CONCLUSION: PTH 2G and PTH 3G assays resulted in a similar drop in IOPTH values. Elevated preoperative calcium levels are the only independent predictor of IOPTH decline. Further studies are needed to determine other factors that can influence PTH kinetics.

A Comprehensive Cohort Analysis Comparing Growth and GH Therapy Response in IGF1R Mutation Carriers and SGA Children.

CONTEXT: IGF1 receptor mutations (IGF1RM) are rare; however, patients exhibit pronounced growth retardation without catch-up. Although several case reports exist, a comprehensive statistical analysis investigating growth profile and benefit of recombinant human growth hormone (rhGH) treatment is still missing. OBJECTIVE AND METHODS: Here, we compared IGF1RM carriers (n = 23) retrospectively regarding birth parameters, growth response to rhGH therapy, near final height, and glucose/insulin homeostasis to treated children born small for gestational age (SGA) (n = 34). Additionally, health profiles of adult IGF1RM carriers were surveyed by a questionnaire. RESULTS: IGF1RM carriers were significantly smaller at rhGH initiation and had a diminished first-year response compared to SGA children (Δ height standard deviation score: 0.29 vs. 0.65), resulting in a lower growth response under therapy. Interestingly, the number of poor therapy responders was three times higher for IGF1RM carriers than for SGA patients (53 % vs. 17 %). However, most IGF1RM good responders showed catch-up growth to the levels of SGA patients. Moreover, we observed no differences in homeostasis model assessment of insulin resistance before treatment, but during treatment insulin resistance was significantly increased in IGF1RM carriers compared to SGA children. Analyses in adult mutation carriers indicated no increased occurrence of comorbidities later in life compared to SGA controls. CONCLUSION: In summary, IGF1RM carriers showed a more pronounced growth retardation and lower response to rhGH therapy compared to non-mutation carriers, with high individual variability. Therefore, a critical reevaluation of success should be performed periodically. In adulthood, we could not observe a significant influence of IGF1RM on metabolism and health of carriers.

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.

Prevalence and predictors of vitamin D inadequacy amongst Lebanese osteoporotic women.

In Middle-Eastern countries, more particularly in Lebanon, the incidence of vitamin D deficiency has been found to be surprisingly high in schoolchildren and young individuals. However, the prevalence and risk factors for vitamin D inadequacy amongst Lebanese osteoporotic women seeking medical health care has never been studied. We analysed vitamin D-inadequacy risk factors among the 251 Lebanese postmenopausal osteoporotic women (from both Muslim and Christian communities) who participated in a vitamin D international epidemiological study. Vitamin D inadequacy prevalence (25-hydroxyvitamin D (25(OH)D) , 30 ng/ml) was 84.9%. 25(OH)D was negatively correlated with BMI (r 20.41; P<0.001) and positively correlated with educational level (r 0.37; P<0.001) and self-reported general health (r 0.17; P<0.01). No significant correlation was found with age and no seasonal variation was observed. There was no significant correlation between 25(OH)D and sun exposure index or vitamin D-rich food consumption. However, 25(OH)D strongly correlated with vitamin D supplement intake (r 0.48; P<0.0001). Muslim community participants had lower 25(OH)D levels compared with their Christian counterparts (P<0.001). They also had higher BMI, lower educational level and vitamin D supplement consumption and followed more frequently a dress code covering the arms (P<0.0001 for all variables). In a multivariate model, in Muslims, inadequate vitamin D supplements and a dress code covering the arms are the independent predictors of 25(OH)D inadequacy (P<0.001 for both variables). However, in Christians, the predictors are inadequate vitamin D supplements, high BMI and low educational level (P<0.001; P=002 and P=0.02 respectively). There is an urgent need to increase vitamin D supplement use in Middle-Eastern osteoporotic women, more particularly in those from the Muslim community.

An epidemiological evaluation of fractures and its determinants among Lebanese schoolchildren: a cross-sectional study.

The purpose of this study is to establish the prevalence and determinants of fractures among 974 Lebanese schoolchildren aged 8-18. Fractures might be less common in the Lebanese pediatric population compared to western populations. Male gender and high SES are independent risk factors for fractures, while 25(OH)D and BMI have no impact. PURPOSE: To establish the prevalence of fractures among Lebanese schoolchildren and its relationship with age, gender, BMI, 25 hydroxyvitamin D (25(OH)D) levels, and socioeconomic status (SES). METHODS: In this cross-sectional study, 974 Lebanese schoolchildren aged 8-18 years old, mean age 13.37 ± 2.92 (508 boys and 466 girls), were recruited from 10 schools with different SES. For each participant, a questionnaire was used to collect data regarding history of fractures. Serum 25(OH)D was also measured. RESULTS: The prevalence of Lebanese children sustaining ≥ 1 fracture was 16.9% and was higher in boys compared to girls (22.2% vs 11.1%, p < 0.0001). A 71.3% of fractures were localized in the upper limbs and 20% of participants had at least one displaced fracture. Children who sustained a fracture had a non-significant higher BMI compared to those without (p = 0.096). The percentage of children with fractures was higher in children from high SES compared to those from middle and low SES (respectively 23.3% vs. 16.3% and 13.8%, p < 0.0001). Fractures occurred at a younger age in girls compared to boys, but this difference was non-significant (p = 0.13). 25(OH)D levels were significantly higher in children with fractures compared to those without (p = 0.017). Finally, female gender was protective against upper limb fractures (p = 0.009). In a logistic regression analysis, male gender and high SES were independently associated with fractures, while BMI and 25(OH)D were not. CONCLUSION: Our study demonstrates that the prevalence of fractures in the Lebanese pediatric population might be lower than western populations. It also confirms that male gender and high SES are independent risk factors for fractures, while 25(OH)D and BMI were not independently associated with fracture risk.

Phalangeal osteosonogrammetry age-related changes and assessment of a Lebanese reference population.

This study was aimed to assess age changes in quantitative ultrasonometry (QUS) of the phalanx in a sample of Lebanese women to determine a reference data for the Lebanese population. Velocity of ultrasound (amplitude-dependent speed of sound; AD-SOS) and the interpretation of the ultra sound signal (ultrasound bone profile index; UBPI) were measured in 211 women with a mean age of 50 years (range 20-79 years) using a DBM sonic Bone profiler device. Women were randomly selected and asked to participate in a nation-wide screening program. Age is an important factor affecting the two parameters: the AD-SOS declines from 2200 m/s at 20 years to 1700 at 80 years. The climacteric condition is another important factor, with significant decrease of the two parameters after the menopause (P<0.0001). This effect is highly influenced by the duration of the postmenopausal period. No influence of weight or height was observed in UBPI variability. The AD-SOS values are similar to those of European population before the age of 50 years. After this age, a significant difference is noted between the two populations. Phalangeal QUS curve of AD-SOS and UBPI are age-dependent. The Lebanese reference curve for AD-SOS is significantly lower from the European curve after the menopause; a 2% decrease in AD-SOS after the age of 50 years can be observed. This decrease in AD-SOS reference values is relevant in the classification of osteoporotic subjects; in fact, if we had used the European reference data set, we had generated 10.9% more Lebanese patients being osteoporotic. Therefore, the use of our standardized reference data reduces the risk of overestimating osteoporosis in the Lebanese population.