An investigation into genetic contribution to the relationship between insulin resistance and birth weight

BACKGROUND Insulin resistance has been proposed to be the most likely phenotypic trait that could represent a genetic link between low birth weight and type 2 diabetes, especially in Southeast Asia. Insulin resistance can persist for many years, even decades, before the manifestation of overt diabetes. There have been many studies suggesting a strong genetic basis in the etiology of type 2 diabetes mellitus. There is also ample evidence providing a link with low birth weight and type 2 diabetes in later life. Hence, parental insulin sensitivity could well serve as a representation of the offspring's future insulin resistance state. Association between maternal insulin sensitivity and the incidence of type 2 diabetes mellitus in low birth weight babies is confounded by many factors and hence, has limited value in the determination of any genetic origin of the disease. Therefore, the present study was done to investigate the relationship between paternal insulin sensitivity and the growth parameters of the foetus to determine a genetic link between poor early growth and the increased risk of type 2 diabetes mellitus in later life. MATERIALS AND METHODS The study was performed on 30 healthy fathers and their babies born from nondiabetic mothers. Each father underwent a low-dose short insulin tolerance test (ITT) as a measure of insulin sensitivity. Placental weight was recorded and a blood sample was collected from the placental side of the umbilical cord at birth for measurement of insulin. Measurement of birth weight, length, and head circumference were recorded and ponderal index was calculated from the formula: weight (kg)/ length (cm)(3). Individual parameters of insulin resistance syndrome were measured in the fathers. RESULTS The degree of insulin sensitivity, K(m) (constant for insulin tolerance test) did not correlate with the fetal growth parameters (Ponderal Index r = 0.031, P = 0.870; weight of baby r = 0.010, P = 0.959; length of baby r = 0.087, P = 0.464; head circumference r = 0.280, P = 0.142) or with the fathers' anthropometric measures: body mass index (BMI), blood pressure, fasting glucose, insulin, and lipid profiles. CONCLUSION The data suggest that the mechanism linking insulin resistance with low birth weight is not a genetically determined defect.