BMJ 1994;308:942-945 (9 April)

Papers

Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype?

D R McCance, Sir George E Clark Metabolic Unit, Royal Victoria Hospital, Belfast BT12 6BA.,a D J Pettitt, R L Hanson, L T H Jacobsson, W C Knowler, P H Bennett 

a Diabetes and Arthritis Epidemiology Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona 85014, United States Correspondence to: Dr

Abstract

Objective : To determine the prevalence of diabetes in relation to birth weight in Pima Indians.
Design : Follow up study of infants born during 1940-72 who had undergone a glucose tolerance test at ages 20-39 years.
Setting : Gila River Indian community, Arizona.
Subjects : 1179 American Indians.
Main outcome measure : Prevalence of non-insulin dependent diabetes mellitus (plasma glucose concentration >=11.1 mmol/l two hours after ingestion of carbohydrate).
Results : The prevalence was greatest in those with the lowest and highest birth weights. The age adjusted prevalences for birth weights <2500 g, 2500-4499 g, and >=4500 g were 30%, 17%, and 32%, respectively. When age, sex, body mass index, maternal diabetes during pregnancy, and birth year were controlled for, subjects with birth weights <2500 g had a higher rate than those with weights 2500-4499 g (odds ratio 3.81; 95% confidence interval 1.70 to 8.52). The risk for subsequent diabetes among higher birthweight infants (>=4500 g) was associated with maternal diabetes during pregnancy. Most diabetes, however, occurred in subjects with intermediate birth weights (2500-4500 g).
Conclusions : The relation of the prevalence of diabetes to birth weight in the Pima Indians is U shaped and is related to parental diabetes. Low birth weight is associated with non-insulin dependent diabetes. Given the high mortality of low birthweight infants selective survival in infancy of those genetically predisposed to insulin resistance and diabetes provides an explanation for the observed relation between low birth weight and diabetes and the high prevalence of diabetes in many populations.

Clinical implications

  • Clinical implications

  • Low birth weight has been shown to predict subsequent diabetes in several British populations and interpreted as a reflection of nutritional deprivation in utero

  • This study showed that in Pima Indians aged 20-39 years the association of birth weight and diabetes was U shaped, with the highest prevalence of diabetes occurring in both high and low birthweight infants

  • The association of diabetes with high birth weight is largely explained by the presence of maternal diabetes during pregnancy

  • Despite the excess of diabetes associated with low birth weight this accounted for only 6% of diabetes in this population

  • An alternative hypothesis is proposed - namely, that the association of diabetes and low birth weight may reflect selective survival of small infants genetically predisposed to diabetes and other insulin resistance syndromes


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