Fulminant hepatic failure: etiology, viral markers and outcome

Objective: To investigate the etiology and outcome of fulminant hepatic failure (FHF) in children. Setting: Hospital based descriptive. Methods: 36 children (22 males and 14 females) presenting with FHF over a period of one year were investigated. The ages ranged from 1.5 to 9 years. FHF was defined as occurrence of encephalopathy within eight weeks of onset of jaundice with no evidence of pre-existing liver disease. Detailed history, clinical examination, routine biochemical parameters and relevant diagnostic tests were carried out. Viral markers studied were anti HAV-IgM, HBsAg, anti HBc-IgM, anti-HCV and anti HEV-IgM. Results: A viral etiology could be established in 22 children (61.1%). Hepatitis A (n=12), Hepatitis B (n=3), Hepatitis A and B (n=2), and Hepatitis A and E (n=4). Two children had enteric fever (1 with associated HEV), 2 children had Wilson's disease, 1 child had Indian Childhood Cirrhosis (ICC) and 2 children had drug induced hepatitis. Etiological diagnosis was not possible in 8 children (22%). Fourteen children (39%) died. Poor outcome was associated with spontaneous bleeding, raised prothrombin time, lower transaminases and higher bilirubin on admission. Conclusion: Viral hepatitis is the commonest cause of FHF in children. HAV alone or in combination is responsible for upto 50% of all FHF in children. Chronic liver disease can also present as FHF. Etiological diagnosis is not possible to upto one-fourth of all cases

Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's Study

AIMS/HYPOTHESIS:The Pune Children's Study aimed to test whether glucose and insulin measurements in childhood predict cardiovascular risk factors in young adulthood.METHODS:We followed up 357 participants (75% follow-up) at 21 years of age who had undergone detailed measurements at 8 years of age (glucose, insulin, HOMA-IR and other indices). Oral glucose tolerance, anthropometry, plasma lipids, BP, carotid intima-media thickness (IMT) and arterial pulse wave velocity (PWV) were measured at 21 years.RESULTS:Higher fasting glucose, insulin and HOMA-IR at 8 years predicted higher glucose, insulin, HOMA-IR, BP, lipids and IMT at 21 years. A 1 SD change in 8 year variables was associated with a 0.10-0.27 SD change at 21 years independently of obesity/adiposity at 8 years of age. A greater rise in glucose-insulin variables between 8 and 21 years was associated with higher cardiovascular risk factors, including PWV. Participants whose HOMA-IR measurement remained in the highest quartile (n = 31) had a more adverse cardiovascular risk profile compared with those whose HOMA-IR measurement remained in the lowest quartile (n = 28).CONCLUSIONS/INTERPRETATION:Prepubertal glucose-insulin metabolism is associated with adult cardiovascular risk and markers of atherosclerosis. Our results support interventions to improve glucose-insulin metabolism in childhood to reduce cardiovascular risk in later life

Birth weight, childhood and adolescent growth and diabetes risk factors in 21-year old Asian Indians: The Pune Children’s Study

Our objective was to investigate associations of body size (birth weight and body mass index (BMI)) and growth in height, body fat (adiposity) and lean mass during childhood and adolescence, with risk markers for diabetes in young South Asian adults. We studied 357 men and women aged 21 years from the Pune Children’s Study birth cohort. Exposures were 1) birth weight, 21-year BMI, both of these mutually adjusted, and their interaction, and 2) uncorrelated conditional measures of growth in height and proxies for gain in adiposity and lean mass from birth to 8 years (childhood) and 8 to 21 years (adolescence) constructed from birth weight, and weight, height, and skinfolds at 8 and 21 years. Outcomes were plasma glucose and insulin concentrations during an oral glucose tolerance test and derived indices of insulin resistance and secretion. Higher 21-year BMI was associated with higher glucose and insulin concentrations and insulin resistance, and lower disposition index. After adjusting for 21-year BMI, higher birth weight was associated with lower 120-min glucose and insulin resistance, and higher disposition index. In the growth analysis, greater adiposity gain during childhood and adolescence was associated with higher glucose, insulin and insulin resistance, and lower disposition index, with stronger effects from adolescent gain. Greater childhood lean gain and adolescent height gain were associated with lower 120-min glucose and insulin. Consistent with other studies, lower birth weight and higher childhood weight gain increases diabetes risk. Disaggregation of weight gain showed that greater child/adolescent adiposity gain and lower lean and height gain may increase risk

Do components of adult height predict body composition and cardiometabolic risk in a young adult South Asian Indian population? Findings from a hospital-based cohort study in Pune, India: The PUNE Children's Study

Objectives: we investigated whether the relationship between components of height and CVD risk may be explained by body composition. We also examined relationships between parental heights and offspring CVD risk.Design: a cohort study using cross-sectional data.Setting: a secondary care hospital setting in Pune, IndiaParticipants: we studied 357 young adults and their parents in the Pune Children’s Study. Primary and secondary outcomes: We measured weight, total height, leg length, sitting height, plasma glucose, insulin and lipids, and blood pressure. Total and regional lean and fat mass were measured by dual x-ray absorptiometry.Results: leg length was inversely, and sitting height directly related to BMI. Total height and leg length were directly related to lean mass while sitting height was directly related to both lean and fat mass. Leg length was inversely related to systolic blood pressure and 120-minute glucose, independent of lean and fat mass. Sitting height was directly related to systolic blood pressure and triglycerides; these relationships were attenuated on adjustment for lean and fat mass. When examined simultaneously, greater leg length was protective and greater sitting height was associated with a more detrimental CVD risk profile.Conclusions: shorter adult leg length and greater sitting height are associated with a more adverse CVD risk factor profile. The mechanisms need further study but our findings suggest a role for lean and fat mass. <br/

Poor in utero growth and reduced b-cell compensation and high fasting glucose from childhood are harbingers of glucose intolerance in young Indians

OBJECTIVE India is a double world capital of early-life undernutrition and type 2 diabetes. We aimed to characterize life course growth and metabolic trajectories in those developing glucose intolerance as young adults in the Pune Maternal Nutrition Study (PMNS).RESEARCH DESIGN AND METHODS PMNS is a community-based intergenerational birth cohort established in 1993, with serial information on parents and children through pregnancy, childhood, and adolescence. We compared normal glucose-tolerant and glucose-intolerant participants for serial growth, estimates of insulin sensitivity and secretion (HOMA and dynamic indices), and β-cell compensation accounting for prevailing insulin sensitivity.RESULTS At 18 years (N = 619), 37% of men and 20% of women were glucose intolerant (prediabetes n = 184; diabetes n = 1) despite 48% being underweight (BMI &lt;18.5 kg/m2). Glucose-intolerant participants had higher fasting glucose from childhood. Mothers of glucose-intolerant participants had higher glycemia in pregnancy. Glucose-intolerant participants were shorter at birth. Insulin sensitivity decreased with age in all participants, and those with glucose intolerance had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had 2.5- and 4.0-fold higher risks, respectively, of 18-year glucose intolerance; this finding was replicated in two other cohorts.CONCLUSION Inadequate compensatory insulin secretory response to decreasing insulin sensitivity in early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia from childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally