M.K. Garg

A study of insulin resistance by HOMA-IR and its cut-off value to identify metabolic syndrome in urban Indian adolescents.

Objective: Insulin resistance (IR) and associated metabolic abnormalities are increasingly being reported in the adolescent population. Cut-off value of homeostasis model of assessment IR (HOMA-IR) as an indicator of metabolic syndrome (MS) in adolescents has not been established. This study aimed to investigate IR by HOMA-IR in urban Indian adolescents and to establish cut-off values of HOMA-IR for defining MS. Methods: A total of 691 apparently healthy adolescents (295 with normal body mass index (BMI), 205 overweight, and 199 obese) were included in this cross-sectional study. MS in adolescents was defined by International Diabetes Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. IR was calculated using the HOMA model. Results: Mean height, waist circumference (WC), waist/hip ratio (WHR), waist/height ratio (WHtR), and blood pressure were significantly higher in boys as compared to girls. The HOMA-IR values increased progressively from normal weight to obese adolescents in both sexes. Mean HOMA-IR values increased progressively according to sexual maturity rating in both sexes. HOMA-IR value of 2.5 had a sensitivity of >70% and specificity of >60% for MS. This cut-off identified larger number of adolescents with MS in different BMI categories (19.7% in normal weight, 51.7% in overweight, and 77.0% in obese subjects) as compared to the use of IDF or ATP III criteria for diagnosing MS. Odds ratio for having IR (HOMA-IR of >2.5) was highest with WHtR (4.9, p <0.0001) and WC (4.8, p <0.0001), compared to WHR (3.3, p <0.0001). Conclusions: In Indian adolescents, HOMA-IR increased with sexual maturity and with progression from normal to obese. A HOMA-IR cut-off of 2.5 provided the maximum sensitivity and specificity in diagnosing MS in both genders as per ATP III and IDF criteria. Conflict of interest:None declared.

The relationship between serum 25-hydroxy vitamin D, parathormone and bone mineral density in Indian population

Vitamin D deficiency (VDD) is a global problem. Not all patients with VDD have clinical manifestations or secondary hyperparathyroidism. We studied the interaction between serum 25‐hydroxy vitamin D (25OHD), parathormone (PTH) and bone mineral density (BMD) in Indian adolescents and adults.

Impact of body mass index on thyroid functions in Indian children

There is controversy about the relation of thyroid functions and body mass index. The present study was aimed to assess the relationship between thyroid function and body mass index in Indian school children.

Efficacy of vitamin D loading doses on serum 25-hydroxy vitamin D levels in school going adolescents: an open label non-randomized prospective trial

Abstract Aim: Vitamin D deficiency (VDD) among adolescents is a major health problem in India. The aim of this study was to assess the efficacy of therapeutic/loading doses of vitamin D supplementation on serum 25-hydroxy vitamin D (25OHD) levels in vitamin D deficient adolescents. Methods: A total of 482 out of the 511 subjects recruited for the study were divided into three groups, each group receiving 60,000 IU of vitamin D3 weekly for 4, 6 and 8 weeks followed by 600 IU daily for 12 weeks, respectively. Clinical evaluation was followed by estimation of biochemical markers and serum 25OHD levels. Results: VDD was observed in 94.8% of adolescents. All three vitamin D loading doses were equally efficacious in achieving vitamin D sufficiency >75 nmol/L (>30 ng/mL) in more than 90% subjects in the three groups. Mean 25OHD levels in groups 2 and 3 following maintenance therapy were 67.5±16.5 nmol/L (27.0±6.6 ng/mL) and 70.0±21.8 nmol/L (28.0±8.7 ng/mL), respectively. Conclusion: Supplementing 60,000 IU of vitamin D3 per week for 4–8 weeks, followed by 600 IU daily through fortified milk, is an effective strategy for achieving vitamin D sufficiency in Indian adolescents.

Relationship of lipid parameters with bone mineral density in Indian population

Introduction: Cardiovascular disease and osteoporosis share common risk factors including dyslipidemia. There are conflicting reports of differential relation of various lipid parameters on bone mineral density (BMD). Hence, we studied the correlation between lipid parameters and BMD in healthy adult. Materials and Methods: A total of 2347 participants (male 39.4%; female 60.6%) included in this cross-sectional study were divided according to sex and age. Fasting blood samples were drawn for biochemical parameters. BMD at lumbar spine, femur, and forearm were measured by dual energy X-ray absorptiometry (DXA). Results: In males, BMD at femur and lumbar spine decreased significantly with increasing quartiles of total cholesterol (TC) (P < 0.0001, and 0.004) and low-density lipoprotein cholesterol (LDL-c) (P = 0.001, and 0.01). In premenopausal women, BMD at femoral neck (P = 0.001) and lumbar spine (P = 0.029) showed declining trend with LDL-c (P = 0.007). In postmenopausal women, only BMD at total femur decreased significantly with TC (P = 0.024) and LDL-c (P = 0.036). All above findings were confirmed in correlation studies. In multiple regression analysis after adjusting for age, body mass index, ionized calcium, alkaline phosphatase, 25 hydroxy vitamin D, and parathyroid hormone levels correlation of BMD with TC and LDL-c persisted. TC, LDL-c was higher in subjects with low bone density compared those with normal bone density in both sexes. Conclusions: TC and LDL-c had weak but significant negative correlation with BMD at femur and lumbar spine.

Normative Data of Body Fat Mass and Its Distribution as Assessed by DXA in Indian Adult Population

Dual-energy X-ray absorptiometry (DXA) assessment of body fat mass is precise and highly correlated with under water weighing. In view of ethnic differences, we undertook this study to prepare normative data for body fat mass in apparently healthy adult Indians and correlate it with body mass index (BMI). This cross-sectional population-based study included 2347 subjects (male: 924; female: 1423) aged >20 yr who participated in a general health examination. They were evaluated for anthropometry and body fat mass by DXA. All subjects were categorized as overweight and obese based on standard BMI criteria. Mean age and BMI were 49.1 ± 18.2yr and 25.0 ± 4.7kg/m(2), respectively. Mean percent total and regional fat (trunk, arm, and leg) reached maximum in the age group of 30-40yr in males and 50-60yr in females. Females had significantly higher total and regional fat mass compared with males. Fat mass was positively correlated with age (r = 0.224; p < 0.00001) and BMI (r = 0.668; p < 0.00001). Prevalence of overweight and obesity was seen in 2119 (46.1%) and 536 (13.8%), respectively, according to World Health Organization definition and 64.0% and 31.1%, respectively, as per Indian guidelines. Percent total body fat mass (PTBFM) of 25% in males and 30% in females corresponds to BMI of 22.0kg/m(2) with sensitivity of >80% and specificity of >70% in receiver operating characteristic curve analysis. Body fat mass in Indians is higher than that in Western populations for a given age and BMI. PTBFM of 25% in males and 30% in females corresponds to BMI of 22kg/m(2) in Indians.

Identification of novel GHRHR and GH1 mutations in patients with isolated growth hormone deficiency

OBJECTIVE Human growth is an elementary process which starts at conception and continues through different stages of development under the influence of growth hormone (GH) secreted by the anterior pituitary gland. Variation affecting the production, release and functional activity of GH leads to growth hormone deficiency (GHD), which is of two types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD may result from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1 and HESX1. The present study reports on the molecular screening of GHRHR and GH1 in IGHD patients. METHODS A total of 116 clinically diagnosed IGHD patients and 100 controls were enrolled for the study after taking informed consent. Family history was noted and 5ml blood sample was drawn. Anatomical and/or morphological pituitary gland alterations were studied using magnetic resonance imaging (MRI). DNA from blood samples was processed for screening the GHRHR and GH1 by Sanger sequencing. RESULTS Mean age at presentation of the 116 patients (67 males and 49 females) was 11.71±3.5years. Mean height standard deviation score (SDS) and weight SDS were -4.5 and -3.5 respectively. Nine (7.8%) were familial and parental consanguinity was present in 21 (19.8%) families. Eighty-three patients underwent MRI and morphological alterations of the pituitary were observed in 39 (46.9%). GH1 and GHRHR screening revealed eleven variations in 24 (21%) patients of which, four were novel deleterious, one novel non-pathogenic and six reported changes. CONCLUSIONS GHRHR contributed more to IGHD in our patients which confirmed that GHRHR should be screened first before GH1 in our population. Identification of GH1 and GHRHR variations helped in defining our mutational spectrum which will play a crucial role in providing predictive and prenatal genetic testing to the patients.

Evaluation of surrogate markers for insulin resistance for defining metabolic syndrome in urban Indian adolescents

ObjectiveTo compare parameters of insulin resistance, with special reference to McAuley index, in urban Indian adolescents, and to establish their cut-off values for defining metabolic syndrome.DesignCross-sectional study.SettingSchools located in four different geographical zones of Delhi, India.Participants695 apparently healthy adolescents grouped as normal weight (298), overweight (205) and obese (192).Outcome measuresCut-off point for indices of insulin resistance was assessed by fasting insulin, insulin glucose ratio, and other methods (HOMA model, QUICKI, McAuley index) to define metabolic syndrome.ResultsThe McAuley index increased progressively from normal weight to obese adolescents in both sexes. McAuley index was significantly lower in adolescents with metabolic syndrome (5.36 ± 1.28 vs. 7.05 ± 1.88; P<0.001). McAuley index had the highest area under curve of receiver operator characteristics [0.82 (0.02)] as compared to other indices of insulin resistance. McAuley index of 6.23 had the highest specificity (88%) with sensitivity of 63.3% for diagnosing metabolic syndrome, whereas insulin glucose ratio had the highest sensitivity (79.7%) but low (55.5%) specificity. McAuley index was negatively correlated with height (r= −0.257, P=<0.001), weight (r= −0.537, P=<0.001), body mass index (r= −0.579, P<0.001), waist circumference (r= −0.542, p<0.001), and waist hip ratio (r= −0.268, P<0.001).ConclusionsAmong various parameters of insulin resistance, McAuley index had the highest specificity, and insulin glucose ratio had the highest sensitivity in diagnosing metabolic syndrome in urban Indian adolescents.