We studied more than 1400 adults who had grown up in the city of Delhi, India, at a time of rapid nutritional transition. Even at the age of 30 years, 15.2 percent had impaired glucose tolerance or diabetes, and 4.4 percent had diabetes. Mean 120-minute plasma glucose concentrations after a standard glucose challenge rose by 17 mg per deciliter (0.96 mmol per liter) between the ages of 26 and 32 years, indicating a sharp deterioration in glucose homeostasis at a relatively young age in adult life. The growth of children in whom impaired glucose tolerance or diabetes later developed was characterized by a low body-mass index between birth and two years of age, a young age at adiposity rebound (as defined by the age after infancy at which the body-mass index starts to rise), and a sustained accelerated gain in body-mass index until adulthood.
The study subjects came from a population of neonates representing all live births within a defined area. Since only 18.7 percent of the original cohort participated in the present study, the subjects may well be unrepresentative of the cohort as a whole. However, the differences in their mean size at birth and in childhood, though statistically significant, were trivial. Our analysis was based on internal comparisons within the study sample and would be biased only if the association between early growth and current glucose or insulin status differed between those who were included in the current study and those who were not. Some of these young adults with diabetes may not have had type 2 diabetes; however, since only one required insulin, the number with type 1 diabetes is likely to be small.
Our study had several strengths. It was population-based; gestational age was assessed prospectively; trained personnel collected anthropometric data at frequent intervals; and the relatively young age of subjects ensured minimal modification as a result of complications of disease or medications. The cohort is unique, in that it represents an urban population of people who grew up during a period of rapid nutritional transition in a developing country and who are now having a rapid loss of glucose homeostasis relatively young in adult life.
The mean insulin concentrations in our cohort would be considered high in whites with similar values for body-mass index in Western countries, but such values have been well described in South Asians.18,19
As in earlier reports,4,8,20
we also found that a small size at birth, defined by a low birth weight or ponderal index, was associated with increased plasma glucose and insulin concentrations and insulin resistance during adulthood. It was not, however, associated with the occurrence of impaired glucose tolerance or diabetes in our study. Given the association between birth weight and both fasting and 120-minute glucose concentrations, the lack of a significant association with disease may be due to a loss of sensitivity resulting in the change from a continuous to a dichotomous variable. Consistent with studies in Hertfordshire, United Kingdom,4
and Helsinki, Finland,21
we found that low weight and thinness at one to two years of age were associated with impaired glucose tolerance and diabetes in adulthood. Children who are thin at two years of age tend to have been thin at birth, though postnatal influences such as infection and feeding practices also contribute.
The children in whom impaired glucose tolerance or diabetes later developed were not over-weight or obese in childhood. They remained below the cohort average for body-mass index until the age of 10 years. At the age of 12 years, only 3.3 percent were overweight according to the current definitions, and none were obese. Instead, they were characterized by their high rate of gain in body mass after the age of two years. We propose that an upward trajectory of body-mass index, starting in early childhood, underlies the current epidemic of diabetes in India.
Our findings are remarkably similar to those in the only Western population with comparable data.21
Among 8760 boys and girls who grew up in Helsinki, Finland, during the Second World War, childhood obesity was uncommon, affecting only 0.4 percent at the age of 12 years, according to International Obesity Task Force definitions.17
The 290 children in that study in whom type 2 diabetes developed in adult life had below-average body size at birth and low weight at one year of age. Thereafter, they had an early adiposity rebound and an accelerated gain in weight and body-mass index, but not height. Their mean body-mass index did not exceed the average for the cohort until around five years of age. Early adiposity rebound was associated with low weight and body-mass index at one year of age. The prevalence of type 2 diabetes fell progressively from 8.6 percent in people whose adiposity rebound occurred before the age of five years to 1.8 percent in those in whom it occurred after seven years.
In conclusion, the young adults in our study who had impaired glucose tolerance or diabetes were, as a group, overweight. They were not, however, overweight as young children but, rather, became overweight as a result of an accelerated gain in body mass starting in early childhood, having been thin in infancy. The ability of children to have an accelerated increase in body mass may be a recent phenomenon in India, a consequence of nutritional transition. Our data do not allow us to distinguish between the events that lead to increasing body-mass index and the expression of the diabetic phenotype. However, assuming that the change in body-mass index is causal rather than the result of a simple association, we speculate that the primary prevention of the epidemic of diabetes in India may require measures to prevent children from crossing into higher categories of body-mass index after the age of two years. Individual children will need to have serial measurements of body-mass index for such a growth trajectory to be identified.