A novel variant of the AGPAT2 mutation in generalized congenital lipodystrophy

Inherited lipodystrophies are rare causes of young onset diabetes characterised by abnormal fat distribution with unique set of clinical features. We present a case of 24 year old lady with young onset diabetes mellitus, acromegaloid features, virilisation, hepatomegaly, hypertriglyceridemia with almost complete absence of subcutaneous and visceral adipose tissue as assessed by DXA scan body composition and MRI abdomen. Based on the clinical presentation, a diagnosis of Berardinelli–Seip generalized lipodystrophy was considered. Genetic analysis using next generation sequencing identified a novel homozygous insertion mutation in 1-acylglycerol-3-phosphate O-acyltransferase 2(AGPAT2) gene which was further confirmed with Sanger sequencing

Osteoporosis in Healthy South Indian Males and the Influence of Life Style Factors and Vitamin D Status on Bone Mineral Density

Objective. To study the prevalence of osteoporosis and vitamin D deficiency in healthy men and to explore the influence of various life style factors on bone mineral density (BMD) and also to look at number of subjects warranting treatment. Methods. Ambulatory south Indian men aged above 50 were recruited by cluster random sampling. The physical activity, risk factors in the FRAX tool, BMD, vitamin D, and PTH were assessed. The number of people needing treatment was calculated, which included subjects with osteoporosis and osteopenia with 10-year probability of major osteoporotic fracture >20 percent and hip fracture >3 percent in FRAX India. Results. A total of 252 men with a mean age of 58 years were studied. The prevalence of osteoporosis and osteopenia at any one site was 20% (50/252) and 58%, respectively. Vitamin D deficiency (<20 ng/dL) was seen in 53%. On multiple logistic regression, BMI (OR 0.3; P value = 0.04) and physical activity (OR 0.4; P value < 0.001) had protective effect on BMD. Twenty-five percent warranted treatment. Conclusions. A significantly large proportion of south Indian men had osteoporosis and vitamin D deficiency. Further interventional studies are needed to look at reduction in end points like fractures in these subjects

IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians.

INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results

An uncommon cause for hip pain and limping

Slipped capital femoral epiphysis (SCFE) is characterized by displacement of the capital femoral epiphysis from the femoral neck. An 18-year-old male presented with left hip pain and a limping gait, following a trivial trauma. Radiological examination revealed bilateral SCFE. Clinically and biochemically, he had features of hypopituitarism. His prolactin levels were high and magnetic resonance imaging (MRI) scan showed a pituitary macroadenoma, suggesting a diagnosis of macroprolactinoma causing hypopituitarism and presenting as SCFE. He was started on dopamine agonist cabergoline as well as thyroxine and glucocorticoid replacement treatment. He was also scheduled for an orthopedic surgical procedure for his SCFE

Bone turnover markers: Emerging tool in the management of osteoporosis

Bone is a dynamic tissue which undergoes constant remodeling throughout the life span. Bone turnover is balanced with coupling of bone formation and resorption at various rates leading to continuous remodeling of bone. A study of bone turnover markers (BTMs) provides an insight of the dynamics of bone turnover in many metabolic bone disorders. An increase in bone turnover seen with aging and pathological states such as osteoporosis leads to deterioration of bone microarchitecture and thus contributes to an increase in the risk of fracture independent of low bone mineral density (BMD). These microarchitectural alterations affecting the bone quality can be assessed by BTMs and thus may serve as a complementary tool to BMD in the assessment of fracture risk. A systematic search of literature regarding BTMs was carried out using the PubMed database for the purpose of this review. Various reliable, rapid, and cost-effective automated assays of BTMs with good sensitivity are available for the management of osteoporosis. However, BTMs are subjected to various preanalytical and analytical variations necessitating strict sample collection and assays methods along with utilizing ethnicity-based reference standards for different populations. Estimation of fracture risk and monitoring the adherence and response to therapy, which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are the most important applications of measuring BTMs. This review describes the physiology of bone remodeling, various conventional and novel BTMs, and BTM assays and their role in the assessment of fracture risk and monitoring response to treatment with antiresorptive or anabolic agents