Objective India 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 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 beta cell compensation accounting for prevailing insulin sensitivity (disposition index). Results At 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. Conclusion Inadequate 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.

中文翻译：

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子宫内生长不良，β细胞补偿降低和儿童期空腹血糖升高，是年轻印度人对葡萄糖不耐症的预兆

目标印度是早期营养不良和2型糖尿病的双重世界首都。在《浦那孕产妇营养研究》（PMNS）中，我们的目标是在年轻人中出现葡萄糖耐量异常的人群中刻画生命周期的增长和代谢轨迹。研究设计和方法PMNS是一个基于社区的代际出生队列，成立于1993年，提供有关怀孕，童年和青春期的父母和子女的系列信息。我们比较了正常的葡萄糖耐量和葡萄糖耐量参与者的连续生长，胰岛素敏感性和分泌的估计值（HOMA和动态指数）以及占主要胰岛素敏感性的β细胞补偿（处置指数）。结果18岁（N = 619）时，37％的男性和20％的女性不耐葡萄糖（184例糖尿病，1名糖尿病患者），尽管其中48％体重不足（BMI <18.5 kg / m2）。糖耐量不全的参与者从童年起就具有较高的空腹血糖。糖耐量不全的母亲在怀孕时有较高的血糖。葡萄糖耐受不良的参与者出生时较短。所有参与者的胰岛素敏感性都随着年龄的增长而下降，并且葡萄糖耐量低的儿童的代偿性胰岛素分泌一直较低。空腹血糖最高的五分之一的参与者分别在6岁和12岁时发生18岁葡萄糖不耐症的风险分别是2.5倍和4.0倍。这一发现在另外两个队列中得到了重复。结论早期印度人对胰岛素不敏感性增加的代偿性胰岛素分泌反应不足，是印度瘦弱农村印第安人糖耐量低下的主要病理生理学。较小的出生人数，