The Risk of Type 2 Diabetes in Men Is Synergistically Affected by Parental History of Diabetes and Overweight

PLOS ONE, Dec 2019

Interactions between genetic- and lifestyle factors may be of specific importance for the development of type 2 diabetes. Only a few earlier studies have evaluated interaction effects for the combination of family history of diabetes and presence of risk factors related to lifestyle. We explored whether 60-year-old men and women from Stockholm with a parental history of diabetes are more susceptible than their counterparts without a parental history of diabetes to the negative influence from physical inactivity, overweight or smoking regarding risk of developing type 2 diabetes. The study comprised 4232 participants of which 205 men and 113 women had diabetes (the vast majority type 2 diabetes considering the age of study participants) and 224 men and 115 women had prediabetes (fasting glucose 6.1–6.9 mmol/l). Prevalence odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using logistic regression. Biologic interaction was analyzed using a Synergy index (S) score. The crude OR for type 2 diabetes associated with a parental history of diabetes was 2.4 (95% CI 1.7–3.5) in men and 1.4 (95% CI 0.9–2.3) in women. Adjustments for overweight, physical inactivity and current smoking had minimal effects on the association observed in men whereas in women it attenuated results. In men, but not in women, a significant interaction effect that synergistically increases the risk of developing type 2 diabetes was observed for the combination of BMI>30 and a parental history of diabetes, S 2.4 (95% CI 1.1–5.1). No signs of interactions were noted for a parental history of diabetes combined with physical inactivity and smoking, respectively. In conclusion, obesity in combination with presence of a parental history of diabetes may be particularly hazardous in men as these two factors were observed to synergistically increase the risk of developing type 2 diabetes in men.

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The Risk of Type 2 Diabetes in Men Is Synergistically Affected by Parental History of Diabetes and Overweight

Leander K (2013) The Risk of Type 2 Diabetes in Men Is Synergistically Affected by Parental History of Diabetes and Overweight. PLoS ONE 8(4): e61763. doi:10.1371/journal.pone.0061763 The Risk of Type 2 Diabetes in Men Is Synergistically Affected by Parental History of Diabetes and Overweight Cecilia Wikner 0 Bruna Gigante 0 Mai-Lis Helle nius 0 Ulf de Faire 0 Karin Leander 0 Christian Herder, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, Germany 0 1 Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 2 Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden, 3 Institute of Medicine, Karolinska Institutet , Stockholm , Sweden Interactions between genetic- and lifestyle factors may be of specific importance for the development of type 2 diabetes. Only a few earlier studies have evaluated interaction effects for the combination of family history of diabetes and presence of risk factors related to lifestyle. We explored whether 60-year-old men and women from Stockholm with a parental history of diabetes are more susceptible than their counterparts without a parental history of diabetes to the negative influence from physical inactivity, overweight or smoking regarding risk of developing type 2 diabetes. The study comprised 4232 participants of which 205 men and 113 women had diabetes (the vast majority type 2 diabetes considering the age of study participants) and 224 men and 115 women had prediabetes (fasting glucose 6.1-6.9 mmol/l). Prevalence odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using logistic regression. Biologic interaction was analyzed using a Synergy index (S) score. The crude OR for type 2 diabetes associated with a parental history of diabetes was 2.4 (95% CI 1.73.5) in men and 1.4 (95% CI 0.9-2.3) in women. Adjustments for overweight, physical inactivity and current smoking had minimal effects on the association observed in men whereas in women it attenuated results. In men, but not in women, a significant interaction effect that synergistically increases the risk of developing type 2 diabetes was observed for the combination of BMI.30 and a parental history of diabetes, S 2.4 (95% CI 1.1-5.1). No signs of interactions were noted for a parental history of diabetes combined with physical inactivity and smoking, respectively. In conclusion, obesity in combination with presence of a parental history of diabetes may be particularly hazardous in men as these two factors were observed to synergistically increase the risk of developing type 2 diabetes in men. - Funding: The Swedish Heart and Lung Foundation supported the work, grant number 20100313. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Type 2 diabetes is a major public health problem in both developing- and industrialized countries [1]. The disease is chronic and may cause suffering due to severe complications related to micro- and macrovascular pathology affecting several organs. Furthermore, its status as a strong risk factor for cardiovascular disease is well known [2]. Prediabetes is an intermediate stage in between normal glucose regulation and diabetes and can be characterized by either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) [1]. The current knowledge about the etiology of diabetes and prediabetes is insufficient. Previous studies suggest that genetic factors as well as an array of different lifestyle factors are associated with the onset of type 2 diabetes [3,4,5]. The exact significance of individual genes for disease onset is still only partly resolved although previous twin studies applying quantitative genetic models suggested a substantial genetic component behind this disease [6]. Recent genome-wide association studies have identified 12 new independent loci associated with type 2 diabetes [7] and at present a total of about 50 loci associated with type 2 diabetes have been identified [8,9]. Combined, these loci however only account for about 10% of the observed familial clustering in Europeans [8]. A hereditary component is also suggested from a number of studies that assessed the influence of a family history of diabetes on risk of type 2 diabetes; most studies report a two- to six fold increased relative risk of type 2 diabetes and the associations appear to be independent of lifestyle factors [10,11]. Results from earlier studies are however not consistent regarding the magnitude of sex specific associations [12,13,14]. Overweight and lifestyle related risk factors such as physical inactivity, active smoking and dietary habits have established effects on type 2 diabetes [3,4,5]. Further, metabolic factors such as lipid levels or hypertension are often considere (...truncated)


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Cecilia Wikner, Bruna Gigante, Mai-Lis Hellénius, Ulf de Faire, Karin Leander. The Risk of Type 2 Diabetes in Men Is Synergistically Affected by Parental History of Diabetes and Overweight, PLOS ONE, 2013, Volume 8, Issue 4, DOI: 10.1371/journal.pone.0061763