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.

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.

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.

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.

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.

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.

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.

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.

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.

Pediatric TSH Reference Intervals and Prevalence of High Thyroid Antibodies in the Lebanese Population.

The aims of this study are to establish reference values for TSH in Lebanese schoolchildren; to look at the relationship between TSH and age, gender, BMI, socioeconomic status (SES), and thyroid antibodies (TAb); and to investigate the prevalence of abnormal TAb in this population. 974 Lebanese schoolchildren aged 8-18 years were recruited from 10 schools of different SES. Third-generation TSH, TPO-Ab, and Tg-Ab measurements were performed using the IMMULITE chemiluminescent immunoassay. The mean TSH is 2.06 ± 1.05 µUI/ml. TSH values are inversely correlated with age (p < 0.0001), are higher in boys than in girls (resp., 2.14 ± 1.10 and 1.98 ± 0.99 µUI/ml, p = 0.017), and are positively correlated with BMI (p < 0.0001). They are also significantly higher in subjects from low-SES schools (p = 0.03) and in girls with positive TAb (p = 0.026). In boys, TSH is independently associated with age, BMI, and schools' SES (p = 0.01, p = 0.03, and p = 0.026, resp.) while in girls, the association is only significant for age and TAb (p = 0.0001 and p = 0.015, resp.). The prevalence of TAb is 4.3% (3% for TPO-Ab and 2.1% for Tg-Ab). Our results showed higher TSH values in the pediatric Lebanese population compared to western populations. TSH varies according to age, gender, BMI, and SES and is associated in girls with TAb.

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.

Relationship between vitamin D receptor gene polymorphisms, cardiovascular risk factors and adiponectin in a healthy young population.

AIM: To explore the association between VDR polymorphisms and several cardiovascular risk factors and adiponectin. MATERIALS & METHODS: Three-hundred and sixty-nine healthy students were randomly selected. Five VDR polymorphisms were genotyped: BsmI rs1544410; Cdx2 rs11568820; ApaI rs7975232; TaqI rs731236 and FokI rs2228570. BMI, waist circumference (WC), blood pressure, lipid/glycemic profiles and adiponectin were assessed. RESULTS: In men, BsmI, ApaI and TaqI were associated with BMI and WC (p < 0.05). FokI was associated with triglycerides and high-density lipoprotein levels (p = 0.0036; p = 0.005) whereas BsmI and Cdx2 were associated with adiponectin levels (p = 0.026; p = 0.048). Associations disappeared after BMI and WC adjustments. In women, ApaI was associated with systolic blood pressure (p = 0.02). CONCLUSION: Our study demonstrated a gender-specific difference between VDR SNPs and various cardiovascular risk factors and adiponectin.

Distribution and correlates of non-high-density lipoprotein cholesterol and triglycerides in Lebanese school children.

BACKGROUND: The prevalence of dyslipidelmia in pediatric Middle-Eastern populations is unknown. Our study aims to investigate the distribution and correlates of non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides among Lebanese school children. METHODS: A total of 969 subjects aged 8-18 years were included in the study (505 boys and 464 girls). Recruitment was done from 10 schools located in the Great Beirut and Mount-Lebanon areas. Non-fasting total cholesterol, triglycerides, and HDL-cholesterol (HDL-C) were measured. Non-HDL-C was calculated. Schools were categorized into 3 socioeconomic statuses (SESs; low, middle, and high). RESULTS: In the overall population, the prevalence of high non-HDL-C (>3.8 mmol/L), very high non-HDL-C (>4.9 mmol/L), and high triglycerides (>1.5 mmol/l) are respectively 9.2%, 1.24%, and 26.6%. There is no significant gender difference for non-HDL-C or triglycerides. Non-HDL-C and triglycerides are inversely correlated with age in girls (P < .0001 for both variables) but not in boys. They are also positively correlated with body mass index (BMI) in boys and girls (P < .0001 for all variables). There is no relationship between schools' socioeconomic process (SES) and non-HDL-C. However, triglycerides are higher in children from lower SES schools. After adjustment for age and body mass index (BMI), testosterone is inversely associated with triglycerides in boys (P < .0001). In a multivariate regression analysis, non-HDL-C is independently associated with age and BMI in girls (P < .0001 for both variables) but only with BMI in boys (P < .0001), whereas triglycerides are independently associated with BMI and schools' SES in both girls and boys. CONCLUSIONS: This study confirms, in our population, the association between obesity and both high non-HDL-C and triglycerides, and between high triglycerides and low SES.

Exome sequencing reveals a mutation in DMP1 in a family with familial sclerosing bone dysplasia.

INTRODUCTION: Hypophosphatemic rickets (HR) comprises a rare group of inherited diseases. Very recently, mutations in the dentin matrix protein 1 (DMP1) gene were identified in patients with an extremely rare autosomal recessive form of HR (ARHR). To date, very few cases of these mutations were reported. MATERIALS AND METHODS: A Lebanese consanguineous family with 2 affected sisters was studied. Patients aged 45 and 47years old presented with short stature, severe genu varum, cranial hyperostosis and a very high bone density that led to a diagnosis of a familial sclerosing bone dysplasia. Molecular analysis of known genes involved in osteopetrosis showed normal results. A combination of genotyping and exome sequencing was performed in order to elucidate the genetic basis of this pathology. RESULTS: Biochemical analysis was consistent with normal serum calcium and 1-25(OH)2D levels, low to normal serum phosphorus and elevated PTH values. Serum c-terminal FGF-23 was elevated in one of the two patients. A homozygous mutation disrupting the initiation codon of the DMP1 gene (OMIM 600980), NM_001079911.2: c.1A>G, p.Met1Val, was identified by exome sequencing and confirmed by Sanger sequencing. CONCLUSION: We report here a family of ARHR secondary to a DMP1 mutation located in the first coding exon of the gene. Our cases show that some ARHR cases may develop with age an unaccountable increase in bone density and bone overgrowth.

Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies.

BACKGROUND: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. OBJECTIVES: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. DATA SOURCES: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. METHODS: We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. RESULTS: Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. CONCLUSIONS: Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.