Risk of development of diabetes mellitus after diagnosis of gestational diabetes

Background

It is generally appreciated that gestational diabetes is a risk factor for type 2 diabetes. However, the precise relation between these 2 conditions remains unknown. We sought to determine the incidence of diabetes mellitus after diagnosis of gestational diabetes.

Methods

We used a population-based database to identify all deliveries in the province of Ontario over the 7-year period from Apr. 1, 1995, to Mar. 31, 2002. We linked these births to mothers who had been given a diagnosis of gestational diabetes through another administrative database that records people with diabetes on the basis of either physician service claims or hospital admission records. We examined database records for these women from the time of delivery until Mar. 31, 2004, a total of 9 years. We determined the presence of diabetes mellitus according to a validated administrative database definition for this condition.

Results

We identified 659 164 pregnant women who had no pre-existing diabetes. Of these, 21 823 women (3.3%) had a diagnosis of gestational diabetes. The incidence of gestational diabetes rose significantly over the 9-year study period, from 3.2% in 1995 to 3.6% in 2001 (p < 0.001). The probability of diabetes developing after gestational diabetes was 3.7% at 9 months after delivery and 18.9% at 9 years after delivery. After adjustment for age, urban or rural residence, neighbourhood income quintile, whether the woman had a previous pregnancy, whether the woman had hypertension after the index delivery, and primary care level before the index delivery, the most significant risk factor for diabetes was having had gestational diabetes during the index pregnancy (hazard ratio 37.28, 95% confidence interval 34.99–40.88; p < 0.001). Age, urban residence and lower income were also important factors. When analyzed by year of delivery, the rate of development of diabetes was higher among the latest subcohort of women with gestational diabetes (delivery during 1999–2001) than among the earliest subcohort (delivery during 1995 or 1996) (16% by 4.7 years after delivery v. 16% by 9.0 years).

Interpretation

In this large population-based study, the rate of development of diabetes after gestational diabetes increased over time and was almost 20% by 9 years. This estimate should be used by clinicians to assist in their counselling of pregnant women and by policy-makers to target these women for screening and preventionRecently, the US Centers for Disease Control and Prevention predicted a 3-fold rise in the prevalence of diabetes mellitus in the United States between 2005 and 2050, from 16.2 million to 48.3 million.¹ Although evidence to support population-based screening as an approach to stem this epidemic is lacking, targeted screening of high-risk populations has been advocated.^2–5 One group at very high risk for diabetes consists of women with a history of gestational diabetes.During pregnancy, women with gestational diabetes display metabolic abnormalities similar to those of people with type 2 diabetes mellitus, such as insulin resistance and reduced β-cell compensation for that resistance.⁶ After delivery, most of these women return to a euglycemic state, but they are at increased risk for overt type 2 diabetes in the future. The rates of development of type 2 diabetes among women with previous gestational diabetes quoted in the literature have been extremely variable, between 3% and 70%.^7–11 Aside from genetic differences among populations, this large variation in the subsequent development of type 2 diabetes may also be due to the use of diverse tests for glucose tolerance in pregnancy, selection bias and, in particular, duration of follow-up.⁹In light of a growing body of evidence that it is possible to delay the development of diabetes among those at high risk,^12–16 it is important to determine the true risk of type 2 diabetes by means of a population-based study; this will allow accurate assessment of the cost-effectiveness and appropriateness of postpartum case management and screening. We sought to determine the incidence of diabetes mellitus in the years following a diagnosis of gestational diabetes.     

Prolactin and lactation as modifiers of diabetes risk in gestational diabetes

Pregnancy and puerperium are periods of intense hormonal changes. Maternal metabolism adapts to spare the mother from harm on behalf of her developing offspring and major alterations maintain normal glucose tolerance. Insulin secretion increases during a normal pregnancy to compensate for pregnancy-induced insulin resistance and maintain euglycemia. Women at risk for gestational diabetes have insulin resistance before conception. Gestational diabetes develops when a woman at risk is unable to meet the insulin secretory demands imposed by the additional insulin resistance characteristic of pregnancy. The lactogens, human placental lactogen and prolactin, are major stimuli for the adaptation of the endocrine pancreas during gestation. This review discusses the role of lactogens on glucose homeostasis during pregnancy and proposes a mechanism by which the hormonal control of lactation, led by prolactin, may regulate adipocyte biology, glucose and lipid metabolism, and guard postpartum women against type 2 diabetes.     

Genetics of diabetes complications

Chronic hyperglycemia and duration of diabetes are the major risk factors associated with development of micro- and macrovascular complications of diabetes. Although it is believed that hyperglycemia induces damage to the particular cell subtypes, e.g., mesangial cells in the renal glomerulus, capillary endothelial cells in the retina, and neurons and Schwann cells in peripheral nerves, the exact mechanisms underlying these damaging defects are not yet well understood. Clustering of micro- and macrovascular complications in families of patients with diabetes suggests a strong genetic susceptibility. However, until now only a handful number of genetic variants were reported to be associated with either nephropathy (ACE, ELMO1, FRMD3, and AKR1B1) or retinopathy (VEGF, AKR1B1, and EPO), and only a few studies were carried out for genetic susceptibility to cardiovascular diseases (ADIPOQ, GLUL) in patients with diabetes. It is, therefore, obvious that the accumulation of more data from larger studies and better phenotypically characterized cohorts is needed to facilitate genetic discoveries and unravel novel insights into the pathogenesis of diabetic complications.