Background: Gestational glucose intolerance (GGI, abnormal initial gestational diabetes [GDM] screen) conveys an increased risk of future diabetes (DM) , even when GDM criteria is not met. We previously defined subtypes of GGI/GDM according to the underlying mechanism leading to hyperglycemia (insulin resistance vs. deficiency) . We aimed to determine if GGI subtypes are at differential risk for future prediabetes/DM; we hypothesized increased risk with insulin deficient subtypes.
Methods: We defined GGI as glucose loading test 1-hr glucose ≥ 140 mg/dL at > 22 weeks’ gestation. We applied homeostasis model assessment (HOMA) to fasting glucose and insulin at 16-20 weeks’ gestation and classified pregnancies with GGI without GDM into subtypes according to the presence of insulin resistance and/or deficiency. We used Cox proportional-hazards models with time-varying exposures to assess risk of preDM/DM (HbA1c ≥ 5.7% at ≥ 3 months after delivery) in each GGI subtype compared to pregnancies with normal glucose tolerance after adjustment for age, race/ethnicity, health insurance, and first trimester BMI. Women were censored at the time of last HbA1c or GDM diagnosis.
Results: Of 671 women with a median 9.9 years of follow-up, 29% (n=196) developed preDM/DM. Among pregnancies in 113 women with GGI, 54% had the insulin resistant subtype (IR) , 25% had the insulin deficient subtype (ID) , and 16% had the mixed pathophysiology subtype (MP) . Subtypes with insulin deficiency (ID + MP) and insulin resistance (IR) were both associated with increased risk of preDM/DM (ID + MP hazard ratio [HR]=1.8 [1.1-2.9], p=0.02 and IR HR=1.7 [1.1-2.6], p=0.01) . Each insulin deficient subtype also appeared to carry increased risk: ID HR=1.7 (0.9-3.1, p=0.12) and MP HR=2.1 (1.0-4.2, p=0.048) .
Conclusions: GGI confers an increased risk of future prediabetes/DM, regardless of the mechanism leading to glucose intolerance. A combination of insulin resistance and deficiency may convey the highest risk of future prediabetes/DM.
D.J. Selen: None. T. Thaweethai: None. K. James: None. J.L. Ecker: None. J.B. Meigs: Consultant; Quest Diagnostics. C.E. Powe: None.
National Institutes of Health (T32DK007028) , Massachusetts General Hospital (Physician Scientist Development Award and Claflin Distinguished Scholar’s Award)