Impact of positive family history and genetic risk variants on the incidence of diabetes: the Finnish Diabetes Prevention Study

Matti I Uusitupa, Alena Stancáková, Markku Peltonen, Johan G Eriksson, Jaana Lindström, Sirkka Aunola, Pirjo Ilanne-Parikka, Sirkka Keinänen-Kiukaanniemi, Jaakko Tuomilehto, Markku Laakso, Matti I Uusitupa, Alena Stancáková, Markku Peltonen, Johan G Eriksson, Jaana Lindström, Sirkka Aunola, Pirjo Ilanne-Parikka, Sirkka Keinänen-Kiukaanniemi, Jaakko Tuomilehto, Markku Laakso

Abstract

Objective: We aimed to investigate the influence of positive family history (FH+) of diabetes and 19 known genetic risk loci on the effectiveness of lifestyle changes and their predictive value on the incidence of type 2 diabetes in the Finnish Diabetes Prevention Study (DPS).

Research design and methods: A total of 522 subjects with impaired glucose tolerance (IGT) were randomized into the control (n = 257) and intervention (n = 265) groups. The mean follow-up was 6.2 years (median 7 years), and the lifestyle intervention, aimed at weight reduction, healthy diet, and increased physical activity, lasted for 4 years (range 1-6 years). An oral glucose tolerance test (OGTT) and assessment of basic clinical variables were performed annually.

Results: The effect of intervention on the incidence of diabetes was almost similar in subjects with FH+ compared with subjects with a negative family history (FH-) of diabetes during the entire follow-up. In the Cox model, including FH, genetic risk SNPs, and randomization group, and adjusted for the effects of age, sex, BMI, and study center, only lifestyle intervention had a significant effect (hazard ratio 0.55, 95% CI 0.41-0.75, P < 0.001) on the incidence of diabetes. Further analyses showed that in addition to the baseline glucose and insulin values, 1-year changes in 2-h glucose and 2-h insulin achieved by lifestyle intervention had a significant effect on the incidence of diabetes.

Conclusions: These results emphasize the effectiveness of lifestyle intervention in reducing the risk of diabetes in high-risk individuals independently of genetic or familial risk of type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT00518167.

Figures

Figure 1
Figure 1
Incidence of type 2 diabetes during the intervention period of 4 years (A) (end indicated by a vertical line) and during the entire follow-up period (B) by FH and randomization group (intervention vs. control) in the DPS. Solid line is for the control group. During the intervention follow-up of 4 years on average, intervention had significant effect on the incidence of type 2 diabetes in the FH+ group (P = 0.0002, *P = 0.0008) but not in the FH- group (P = 0.61, *P = 0.11). During the entire follow-up, intervention had an effect in both FH+ (P = 0.0004, *P = 0.002) and FH− (P = 0.13, *P = 0.006) groups. P is from Kaplan–Meier analysis, *P after adjustment for age, sex, baseline BMI, baseline fasting glucose, and study center in Cox regression model.

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