An Early-Onset Subgroup of Type 2 Diabetes: A Multi-Generational, Prospective Analysis in the Framingham Heart Study
Research Design and Methods: In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5571 first- and second-generation participants with mortality data; and 2123 initially non-diabetic second-generation participants with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death) - control (non-cardiovascular death) design, and incident diabetes in offspring in relation to parental early-onset diabetes.
Results: Of the participants in two generations (N=5571), there were 1822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus non-cardiovascular death increased with decreasing age of diabetes onset (P<0.001 trend). Compared with persons who never developed diabetes, early-onset diabetes conferred a 1.81-fold odds (95% confidence interval [CI] 1.10-2.97, P=0.02) of cardiovascular death and 1.75-fold (0.96-3.21, P=0.07) odds of coronary death, whereas later-onset diabetes was not associated with greater risk for either (P=0.09 for cardiovascular death; P=0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73-6.07) whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50-3.19).Conclusions: Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.