Transmission of Type 2 diabetes to sons and daughters: the D.E.S.I.R. cohort

Abstract

Aims To document the family transmission of Type 2 diabetes to men and women.Method The French D.E.S.I.R. cohort followed men and women over 9 years, with 3-yearly testing for incident Type 2 diabetes. First-and/or second-degree family histories of diabetes were available for 2187 men and 2282 women. Ageadjusted hazard ratios were estimated for various family members and groupings of family members, as well as for a genetic diabetes risk score, based on 65 diabetes-associated loci.Results Over 9 years, 136 men and 63 women had incident Type 2 diabetes. The hazard ratios for diabetes associated with having a first-degree family member with diabetes (parents, siblings, children) differed between men [1.21 (95% CI 0.80, 1.85)] and women [3.02 (95% CI 1.83, 4.99); P interaction =0.006]. The genetic risk score was predictive of diabetes in both men and women, with similar hazard ratios 1.10 (95% CI 1.06, 1.15) and 1.08 (95% CI 1.02, 1.14) respectively, for each additional at-risk allele. In women, the risk associated with having a family member with diabetes persisted after adjusting for the genetic score.Conclusion Women with a family history of diabetes (paternal or maternal) were at risk of developing Type 2 diabetes and this risk was independent of a genetic score; in contrast, for men, there was no association. Diabetes screening and prevention may need to more specifically target women with diabetes in their family, but further studies are required as the number of people with diabetes in this study was small. Diabet. Med. 34, 1615-1622 (2017 IntroductionThe transmission of Type 2 diabetes within the family is well established. In the Framingham Offspring Study, the odds ratios for offspring to have diabetes were 3.5 or 3.4 if the father or the mother has diabetes, respectively, and 6.1 if both have diabetes [1]; in the European InterAct study, these hazard ratios were 3.17 and 2.88 respectively, and 5.14 if both parents have diabetes [2].As discussed by Meigs et al.[1], some studies, but not all, have shown that diabetes is maternally rather than paternally transmitted; however, few studies have assessed family transmission according to the sex of the index case. In the InterAct study, the hazard ratios associated with a firstdegree family history of diabetes were 2.64 for men and 2.77 for women, essentially identical [2]. By contrast, in two cross-sectional studies of people with Type 2 diabetes, more women than men had a parental transmission of diabetes [3,4].In the present study, we analyzed incident diabetes in men and women according to the presence of diabetes in first-and second-degree family members, and in particular in their father and their mother. The impact of a genetic risk score with 65 diabetes-related loci and maternal transmission of diabetes was also investigated. Methods Study populationThe present cohort study used data from the Epidemiological Study on Insulin Resistance syndrome (D.E.S.I.R.) including 1994-1996 [5]. Participants were recruited from volunteers attending free-of...

Diabetic family history in young Japanese persons with normal glucose tolerance associates with k-means clustering of glucose response to oral glucose load, insulinogenic index and Matsuda index

“…FH+ showed a relationship with abnormal OGTT shape by k-means clustering analysis. From the perspective point view of FH, the proportion of females was high among subjects with FH+, consistent with a previous report [ 26 ], and subjects with FH+ displayed higher PG levels after loading. The reasons for this discrepancy are unclear.…”

“…FH1-positive (FH1+) patients with normal glucose tolerance (NGT) are reported to show decreased insulin secretion and sensitivity with as increases in blood pressure, lipid levels, and degree of obesity [ 24 , 25 ]. Females with FH appear more susceptible to diabetes than males with FH [ 26 ]. The effect of FH differs by sex and whether the individual is obese, and also affects lipid levels Consideration of subject characteristics is thus important when investigating the relationship between FH and PG or insulin levels.…”

Lean legacy, heavy heritage: family history of diabetes and its association with young adult body mass index

“…The health effects of family history vary by age, with higher risks for those age 20 and over (Annis et al, 2005) but with mixed findings for minor children (Gilliam et al, 2007). In particular, maternal or paternal diabetes influences the risks of diabetes for both sons and daughters in one study (InterAct Consortium et al, 2013), but only for daughters in another (Balkau et al, 2017). Maternal transmission is more evident than paternal transmission in other studies.…”