The prevalence of diabetes is increasing globally and India is no exception. The concern is India will have the highest population of diabetics by 2025. The increased prevalence is attributed to aging population, urbanisation, the obesity epidemic and early life exposures. The “fetal origin of disease” hypothesis proposes that gestational programming may critically influence adult health and disease. Gestational programming (intrauterine programming) is a process whereby stimuli or stresses that occur at critical or sensitive periods of development, permanently change structure, physiology and metabolism, which predispose individuals to disease in adult life.
Postponing the onset
Traditionally and convincingly, lifestyle modifications and drug interventions have proved to delay or postpone the development of overt diabetes in persons who have impaired glucose tolerance (IGT) or impaired fasting glucose (pre diabetes). This is a post primary prevention strategy. The primary prevention of Type 2 Diabetes Mellitus (Type 2 DM) at best would mean to keep genetically or otherwise susceptible individuals, normoglycemic, and not only preventing Type 2 DM from developing. The primary prevention of Type 2 Diabetes Mellitus (Type 2 DM) is more important than post primary prevention, as this effort is likely to reverse or halt the epidemic of the disease. Women with Gestational Diabetes Mellitus (GDM) are an ideal group for primary prevention as they are at increased risk of developing diabetes, predominantly Type 2 DM as are their children. Women with GDM have an increased lifetime risk of developing diabetes, at over 3 times compared to controls at 16 years after index pregnancy. By age 17, one-third of children born to GDM mothers have had evidence of pre diabetes or Type 2 DM.
The familial predisposition to Type 2 DM is mediated by both genetic and intrauterine environmental factors. The contribution of the genetic factor may be due to the major role played by maternal mitochondrial DNA in the transmission of the disease. The ovum is well supplied with mitochondria but the sperm contains a few and even those few do not persist in the offspring. At fertilisation, it is the nucleus of the spermatozoan that enters the ovum and thus all the cytoplasm, mitochondria and mitochondrial DNA are exclusively maternally inherited. Maternal inheritance is attributed to mutation in the gene(s) present in mitochondrial DNA and is transmitted invariably by an affected mother to her progeny. However, exposure to diabetic environment in utero was associated with increased occurrence of impaired glucose tolerance and a defective insulin secretory response in adult offspring, independent of genetic predisposition to Type 2 DM. A study of Pima Indians revealed that children exposed in utero to maternal diabetes are at a higher risk of obesity and diabetes than their unexposed siblings, suggesting that the increased risk to the exposed offspring is not exclusively genetic. These observations clearly indicate the need to focus on the intra uterine environment. Alterations of intrauterine environment, in particular, the development of hyperinsulinemia is strongly associated with the development of obesity and prediabetes during childhood and puberty.
The excess maternal fuels cross the placenta and stress the fetal beta cells. The fetus responds to the mixed nutrients by secreting large quantities of insulin. This results in increasing adiposity and accrual of visceral fat that eventually causes decrease in fetal pancreatic reserve and the infant is at risk for developing subsequent diabetes. On the other hand, intrauterine malnutrition causes intrauterine growth retardation and this under nutrition is associated with decreased pancreatic reserve. Thus both small-for-date infants and large-for-date infants are at risk for subsequent diabetes. In India, both under nutrition and over nutrition exist during pregnancy. Speculation that the rise in Type 2 DM in Indian urban population may have been triggered by mild obesity in mothers, leading to glucose intolerance during pregnancy, macrocosmic changes in the fetus and insulin deficiency in adult life. Type 2 DM may be programmed in fetal life, hence diabetes prevention will have to start in early life (in utero) and continue in later life.
The screening for glucose intolerance is usually performed around 24-28 weeks of gestation. But a statistically significant number of GDM mothers deliver big babies despite good glycemic control in the third trimester. This is due to the undetected glucose intolerance in them in the early weeks of gestation that influence fetal growth. ‘Early maternal metabolic imprint may affect the fetal growth.' This observation implies that screening is to be performed in the first trimester itself as the fetal beta cell recognises and responds to maternal glycemic level as early as the 16th week of gestation.
Among ethnic groups in South Asian countries, Indian women have the highest frequency of GDM necessitating universal screening for glucose intolerance during pregnancy in India. Probably the undiagnosed glucose intolerance that has been occurring in the past has resulted in the increased prevalence of diabetes in India. Moreover, women who have GDM, because of their high diabetes risk and young age, are ideally suited to be targeted for lifestyle or pharmacologic interventions to delay or prevent the onset of overt diabetes. Hence, an important public health priority is prevention of diabetes, starting with maternal health pre and post conception. Preventive measures against Type 2 DM should start during the intra uterine period and continue throughout life.
The timely action taken now in screening all pregnant women for glucose intolerance, achieving euglycemia in them and ensuring adequate nutrition may prevent in all probability the vicious cycle of transmitting glucose intolerance from one generation to another. To contain the epidemic of diabetes we have to “Focus on the Fetus for the Future.”
(Dr. V. Seshiah Diabetes Research Institute & Dr. Balaji Diabetes Care Centre, Chennai)
Published - November 13, 2011 04:51 pm IST
