Poor in-utero growth, reduced beta cell secretion and high plasma glucose in childhood are harbingers of glucose intolerance in young Indians

Background India is the worlds paradoxical double capital for early life undernutrition and type 2 diabetes. The Pune Maternal Nutrition Study (PMNS) birth cohort offered a unique opportunity to investigate childhood growth and glucose-insulin metabolism as precursors to glucose intolerance in young adulthood. Methods PMNS is a community-based pre-conceptional birth cohort established in 1993, with serial information on parents, and on their children through pregnancy, childhood and adolescence. We compared the childrens growth and glucose-insulin indices between those who were and were not glucose intolerant at age 18 years (ADA criteria). We developed a prediction model for 18-year glucose intolerance and replicated it in two other cohorts (Extended PMNS and Pune Childrens Study). Findings At age 18 years (N=619) 37% men and 20% women were glucose intolerant even though 48% were underweight (BMI<18.5 kg/m2). Glucose intolerant participants were shorter at birth, and had lower insulin secretion (both sexes) and insulin insensitivity (men) in childhood than those with normal glucose tolerance. Fasting plasma glucose (FPG) concentrations at 6- and 12-years of age strongly predicted glucose intolerance at 18 years. The risk was 2.5 times higher in the highest compared to the lowest quintile at 6 years, and 4.5 times at 12 years. Comparable findings were seen in the other cohorts. Mothers of glucose intolerant participants had higher glycemia in pregnancy. Interpretation Glucose intolerance in young rural Indians can be traced to linear growth faltering in-utero, reduced beta-cell secretion and higher glycemia since childhood. Our findings mandate a strategy for diabetes prevention starting much earlier than the current practice.