FHS-Onset-Heritability-Diabetes-SM-DC-Revision3.pdf (191.1 kB)

An Early-Onset Subgroup of Type 2 Diabetes: A Multi-Generational, Prospective Analysis in the Framingham Heart Study

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posted on 08.10.2020 by Justin B. Echouffo-Tcheugui, Teemu J. Niiranen, Elizabeth L. McCabe, Mir Henglin, Mohit Jain, Ramachandran S. Vasan, Martin G. Larson, Susan Cheng
Objective: To assess the influence of type 2 diabetes occurring earlier (age <55 years) versus later in life, on the risk of cardiovascular death, and of diabetes in offspring.

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.


This work was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (contracts N01HC25195 and HHSN268201500001I), and the following National Institutes of Health grants: T32 HL125232 (JBET), R01HL093328 (RSV), R01HL107385 (RSV), R01HL126136 (RSV), R00HL107642 (SC), R01HL131532 (SC), and R01HL134168 (SC).