We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but high fat mass at 8 years. Taller height at 8 years predicted higher fasting plasma insulin concentrations, insulin resistance, and plasma total and LDL cholesterol concentrations. The most insulin-resistant children were those who had short parents but had themselves grown tall. Although the implications of our findings in relation to height are unclear, interventions to improve fetal growth and to control obesity in childhood are likely to be important factors in the prevention of cardiovascular disease and IRS in India.

There is a rapidly increasing epidemic of type 2 diabetes in India and other Asian countries. The thrifty genotype and the thrifty phenotype are two nonexclusive explanations. People in the Indian subcontinent have faced undernutrition for many generations, and Indian babies are among the smallest in the world. However, the diabetes epidemic is of recent origin, and diabetes is more common among urban than rural Indians despite the higher birth weight of urban babies. This suggests that postnatal factors must also contribute. Thus, a life-course model of evolution of insulin resistance and type 2 diabetes, incorporating fetal, postnatal and adult components, seems most appropriate. For a given BMI, Indians have a higher percentage of body fat and more visceral fat than members of other populations. This thin-fat phenotype is present at birth. Neonatal size and body composition are influenced by parental size, maternal food intake, physical activity and circulating concentrations of nutrients and metabolites (folate, glucose, triglycerides, cholesterol etc.). Maternal insulin resistance promotes transfer of nutrients to the fetus. Accelerated childhood growth is another risk factor for adiposity and insulin resistance, especially in children born small. Childhood growth seems to be more influenced by paternal genetic factors, whereas intrauterine growth is more influenced by maternal factors (intrauterine environment). Urban lifestyles, including poor diet and sedentary habits, promote further obesity, insulin resistance and type 2 diabetes. These factors may be amenable to correction. Prevention of type 2 diabetes must begin in utero and continue throughout the life course.

Aims and hypothesis India has the greatest number of diabetic subjects in any one country, but the genetic basis of type 2 diabetes mellitus in India is poorly understood.

Aim-To test the hypothesis that low plasma vitamin B12 concentrations combined with high folate concentrations in pregnancy are associated with higher incidence of gestational diabetes (GDM) and later diabetes.Methods-Women (N=785) attending the antenatal clinics of the Holdsworth Memorial Hospital, Mysore, India had their anthropometry, insulin resistance (Homeostasis Model Assessment) and glucose tolerance assessed at 30 weeks gestation (100g Oral Glucose Tolerance Test/ OGTT; Carpenter-Coustan criteria), and five years after delivery (75g OGTT, WHO 1999). Vitamin B12 and folate concentrations in pregnancy were measured in stored frozen plasma samples.Results-Low vitamin B12 concentrations (<150 pmol/l, B12 deficiency) were observed in 43% of women and low folate concentrations (<7 nmol/l) in 4%. Women with vitamin B12 deficiency had higher body mass index (BMI; P<0.001), sum of skinfolds (P<0.001), insulin resistance (P=0.02) and a higher incidence of GDM (8.7% v 4.6%; OR=2.14, P=0.02; P=0.1 after adjusting for maternal BMI) than non-deficient women. Among vitamin B12-deficient women the incidence of GDM increased with folate concentration (5.6%, 8.8%, 12.8% respectively from lowest to highest third; P for interaction=0.2). B12 deficiency during pregnancy predicted larger skinfolds, increased insulin resistance (P<0.05) and incident diabetes at 5-year follow-up (P=0.02, after adjusting for current BMI).Conclusion-Maternal vitamin B12 deficiency is associated with increased adiposity and, in turn, with increased insulin resistance and GDM, especially in the presence of high folate concentrations. Vitamin B12 deficiency may be an important factor underlying the high risk of diabesity in south Asian Indians.

Aims/hypothesisFTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.MethodsAll studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.ResultsThe FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.Conclusions/interpretationFTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.