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

Abstract

AbstractObjectiveIndia is a double world capital for early life undernutrition and type 2 diabetes. We aimed to characterise lifecourse growth and metabolic trajectories in those developing glucose intolerance as young adults, in the Pune Maternal Nutrition Study (PMNS).Research design and MethodsPMNS 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 beta cell compensation accounting for prevailing insulin sensitivity (disposition index).ResultsAt 18 years (N=619) 37% men and 20% women were glucose intolerant (184 prediabetes, 1 diabetes) despite 48% being underweight (BMI<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 the glucose intolerant had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had a 2.5- and 4.0-fold higher risk respectively of 18-year glucose intolerance; this finding was replicated in two other cohorts.ConclusionInadequate compensatory insulin secretory response to increasing insulin insensitivity from early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia in childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.