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Abstract. Abbasi A, Corpeleijn E, van der Schouw YT, Stolk RP, Spijkerman AMW, van der A DL, Navis G, Bakker SJL, Beulens JWJ (University Medical Center Groningen, Groningen; University Medical Centre Utrecht, Utrecht; and National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands) Maternal and paternal transmission of type 2 diabetes: influence of diet, lifestyle and adiposity. J Intern Med 2011; 270: 388–396.
Objective. Transmission of family history of type 2 diabetes to the next generation is stronger for maternal than paternal diabetes in some populations. The aim of the present study was to investigate whether this difference is explained by diet, lifestyle factors and/or adiposity.
Methods. We analysed 35 174 participants from the Dutch contribution to the European Prospective Investigation into Cancer and Nutrition, a prospective population-based cohort (aged 20–70 years) with a median follow-up of 10.2 years. Parental history of diabetes was self-reported. Occurrence of diabetes was mainly identified by self-report and verified by medical records.
Results. Amongst 35 174 participants, 799 incident cases of diabetes were observed. In age- and sex-adjusted analyses, hazard ratio (HR) and 95% confidence intervals (CIs) for diabetes by maternal and paternal diabetes were 2.66 (2.26–3.14) and 2.40 (1.91–3.02), respectively. Maternal transmission of risk of diabetes was explained by diet (9.4%), lifestyle factors including smoking, alcohol consumption, physical activity and educational level (7.8%) and by adiposity, i.e. body mass index and waist and hip circumference (23.5%). For paternal transmission, the corresponding values were 2.9%, 0.0% and 9.6%. After adjustment for diet, lifestyle factors and adiposity, the HRs for maternal (2.20; 95% CI, 1.87–2.60) and paternal (2.23; 95% CI, 1.77–2.80) transmission of diabetes were comparable.
Conclusions. Both maternal and paternal diabetes are associated with increased risk of type 2 diabetes, independently of diet, lifestyle and adiposity. The slightly higher risk conferred by maternal compared to paternal diabetes was explained by a larger contribution of diet, lifestyle factors and adiposity.
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The prevalence of type 2 diabetes, a leading cause of cardiovascular morbidity and mortality, is increasing worldwide . Parental – paternal and/or maternal – history of diabetes is a major determinant of increased risk of diabetes [2–5]. Family history may reflect complex relationships between genetic factors and environmental conditions that are important for developing diabetes . Thus, parental history of diabetes includes environmental risks (e.g. nongenetic familial behaviours, lifestyle and obesity) beyond the genetic risk factors for diabetes .
A greater risk from maternal type 2 diabetes compared to paternal diabetes has been reported in some [7–9] but not all studies [2, 4, 5]. A variety of explanations for this greater importance of maternal diabetes have included the following: genomic imprinting (i.e. the differential expression of inherited susceptibility genes in paternal or maternal generation ); mutations in mitochondrial DNA, which are maternally inherited ; and metabolic programming during intrauterine exposure . It is still not clear to what extent modifiable factors such as diet, lifestyle and obesity can explain the association between maternal or paternal diabetes and risk of diabetes. To our knowledge, only one prospective study amongst female nurses has investigated the contribution of excess adiposity and certain dietary habits . No such longitudinal data are available in men.
The aim of this study was to prospectively investigate the association between parental history of diabetes – maternal and/or paternal – and risk of incident type 2 diabetes in a population-based cohort of male and female adults, i.e. the Dutch contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC-NL). The EPIC-NL study was suitable for this purpose because detailed data on diabetes risk factors such as diet and lifestyle factors were collected in this cohort .
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Baseline characteristics of the study population are summarized in Table 1 by parental diabetes status. When compared with participants without parental history of diabetes, those who reported paternal and/or maternal diabetes were older and more likely to be woman, had a higher BMI, waist and hip circumference and blood pressure, a lower alcohol consumption and education level, were less physically active and were more likely to experience cardiovascular morbidity. Parental diabetes was associated with a lower intake of total energy and carbohydrates, whereas the intake of protein, fat, fibre, vitamin C and vitamin E was higher in participants with parental diabetes.
Table 1. Baseline characteristics by parental history of diabetes in the EPIC-NL study (n = 35 174) a
| ||None||Any parent(s)||Only father||Only mother||Both parents|
|No. (%) of participants||28 696 (81.6)||6478 (18.4)||2187 (6.2)||3941 (11.2)||350 (1.0)|
|Age (years)||48.4 (12.3)1,*||51.6 (10.0)||49.7 (10.8)2,*||52.6 (9.4)||52.0 (9.7)|
|Woman||21 026 (73.3)1,*||5148 (79.5)||1682 (76.9)||3178 (80.6)||288 (82.3)|
|Body mass index (kg m−2)||25.4 (3.9)1,*||26.4 (4.1)||26.0 (3.9)2,*||26.6 (4.2)||27.2 (4.6)|
|Waist circumference (cm)||84.5 (11.2)1,*||86.8 (11.5)||85.8 (11.3)2,*||87.3 (11.6)||88.4 (12.0)|
|Hip circumference (cm)||103.0 (7.9)1,*||104.7 (8.5)||103.9 (7.9)2,*||105.1 (8.7)||105.9 (9.7)|
|Systolic blood pressure (mmHg)||125 (19)1,*||128 (19)||126 (19)2,*||130 (20)||128 (19)|
|Diastolic blood pressure (mmHg)||77.4 (10.6)1,*||78.8 (10.4)||77.9 (10.6)2,*||79.4 (10.4)||78.2 (10.4)|
|Alcohol consumption (g week−1)||11.4 (15.6)1,*||9.9 (14.4)||10.6 (14.4)||9.7 (14.5)||7.9 (12.0)|
|Current smoker||8560 (29.8)1,*||1873 (28.9)||614 (28.1)||1171 (29.7)||88 (25.1)|
|Low educational levelb||15 606 (54.4)1,*||4229 (65.3)||1250 (57.2)2,*||2734 (69.4)||245 (70.0)|
| Inactive||2450 (8.5)1,*||626 (9.7)||185 (8.5)||402 (10.2)||39 (11.1)|
| Moderately inactive||8298 (28.9)||1837 (28.3)||649 (29.7)||1094 (27.8)||94 (26.9)|
| Moderately active||8045 (28.0)||1763 (27.2)||604 (27.6)||1049 (26.6)||110 (31.4)|
| Active||9903 (34.5)||2252 (34.8)||749 (34.2)||1396 (35.4)||107 (30.6)|
| Total energy intake (kcal day−1)||2076.6 (636.7)1,*||1992.3 (601.0)||2004.4 (604.8)||1991.4 (602.4)||1926.6 (556.9)|
|Nutrient intake (g day−1)d|
| Protein||75.5 (10.9)1,*||76.7 (10.9)||76.0 (10.7)2,**||76.9 (11.0)||78.5 (11.7)|
| Fat||77.3 (11.3)1,*||78.4 (11.5)||78.0 (10.8)||78.5 (11.9)||79.1 (11.2)|
| Saturated fat||32.4 (5.8)1,*||33.0 (5.9)||32.6 (5.6)2,**||33.1 (6.0)||33.1 (5.6)|
| Monounsaturated fat||29.4 (5.1)1,**||29.6 (5.2)||29.6 (5.0)||29.6 (5.4)||29.9 (5.2)|
| Polyunsaturated fat||14.9 (3.8)1,*||15.1 (4.0)||15.1 (3.9)||15.1 (4.0)||15.5 (4.1)|
| Cholesterol (mg day−1)||215.9 (58.3)1,*||221.7 (62.6)||218.1 (59.3)2,***||221.9 (64.1)||230.7 (63.9)|
| Carbohydrates||222.3 (30.7)||220.8 (30.7)||221.2 (30.0)||220.6 (31.1)||220.7 (31.3)|
| Mono- and disaccharide||112.5 (29.3)1,***||111.7 (29.5)||111.2 (28.5)||112.1 (29.9)||110.5 (30.9)|
| Fibre||23.3 (4.8)1,*||23.7 (4.8)||23.4 (4.7)2,***||23.8 (4.8)||23.7 (4.6)|
| Vitamin C (mg day−1)||109.2 (45.1)1,*||111.6 (46.1)||110.1 (44.1)||112.4 (47.0)||112.7 (47.8)|
| Vitamin E (mg day−1)||12.2 (3.2)1,*||12.4 (3.3)||12.3 (3.3)||12.4 (3.3)||12.7 (3.5)|
|Hyperlipidaemiae||2268 (7.9)1,*||617 (9.5)||165 (7.5)||414 (10.5)||38 (10.9)|
|Hypertensionf||5889 (20.5)1,*||1621 (25.0)||489 (22.4)||1023 (26.0)||109 (31.1)|
|Myocardial infarction||434 (1.5)1,**||121 (1.9)||28 (1.3)||82 (2.1)||11 (3.1)|
|Stroke||309 (1.1)1,*||101 (1.6)||26 (1.2)||65 (1.6)||10 (2.9)|
|Cancer||1187 (4.1)||264 (4.1)||80 (3.7)||171 (4.3)||13 (3.7)|
Table 2 shows the association between parental history of diabetes and parameters of obesity in participants. We calculated adjusted means of parameters of obesity in each category of parental diabetes accounting for cohort, age, sex, diet and lifestyle factors. Subjects with maternal and/or paternal diabetes had higher BMI (β coefficient, 0.65; 95% CI, 0.55–0.75), waist circumference (β coefficient, 1.88; 95% CI, 1.62–2.15) and hip circumference (β coefficient, 0.93; 95% CI, 0.72–1.13) compared with participants without parental diabetes. This association was stronger for those with both maternal and paternal history of diabetes.
Table 2. Cross-sectional association between parental history of diabetes and body mass index (BMI) and waist and hip circumference (n = 35 174)
|Characteristics||None||Any parent(s)||Only father||Only mother||Both parents|
|BMI (kg m−2)|
| Estimated means (95% CI)a,b||25.8 (25.7–25.8)||26.4 (26.3–26.5)||26.2 (26.0–26.3)||26.5 (26.4–26.7)||27.0 (26.6–27.3)|
| β coefficient (95% CI)||0||0.65 (0.55–0.75)||0.39 (0.23–0.55)||0.75 (0.63–0.88)||1.20 (0.81–1.56)|
|Waist circumference (cm)|
| Estimated means (95% CI)a,b||87.8 (87.7–87.9)||89.7 (89.4–89.9)||89.1 (89.7–89.5)||89.9 (89.6–90.2)||90.9 (89.9–91.9)|
| β coefficient (95% CI)||0||1.88 (1.62–2.15)||1.28 (0.86–1.70)||2.12 (1.79–2.44)||3.12 (2.10–4.13)|
|Hip circumference (cm)|
| Estimated means (95% CI)a,b||102.9 (102.8–103.1)||103.9 (103.7–104.1)||103.4 (103.1–103.8)||104.1 (103.8–104.3)||104.5 (103.7–105.3)|
| β coefficient (95% CI)||0||0.93 (0.72–1.13)||0.50 (0.17–0.83)||1.11 (0.86–1.37)||1.55 (0.75–2.35)|
During a median follow-up of 10.2 years, we observed 799 incident cases of type 2 diabetes (rate of 2.2 per 1000 person-years). In the unadjusted analysis, participants with parental history of diabetes had an approximately 3-fold higher incidence rate of diabetes compared with those who had no parents with diabetes (Table 3; 1.7 vs. 5.0 per 1000 person-years, P < 0.001). Despite the sex differences in each category of parental diabetes, there was no significant interaction of sex with parental diabetes (HR of interaction term, 0.86; 95% CI, 0.60–1.22). In sex-stratified analyses, multivariable-adjusted HRs of diabetes for maternal and paternal history of diabetes were 2.50 (95% CI, 1.72–3.62) and 2.14 (95% CI, 1.72–3.62), respectively, in male participants. In women, these values were 2.15 (95% CI, 1.79–2.6) and 2.32 (95% CI, 1.8–3.0), respectively.
Table 3. Parental history of diabetes, contributing factors and risk of incident type 2 diabetes over 10 years (n = 35 174)
|Model adjustment||Risk of type 2 diabetes, hazard ratio (95% CI)|
|None||Any parent(s)||Only father||Only mother||Both parents|
|Incidence rate, per 1000 person-year||1.7||5.0||3.9||5.1||10.9|
|Crude modela||1 (ref.)||2.90 (2.51–3.34)||2.36 (1.88–2.97)||2.91 (2.46–3.43)||6.21 (4.42–8.71)|
|Model 1||1 (ref.)||2.75 (2.39–3.17)||2.40 (1.91–3.02)||2.66 (2.26–3.14)||5.89 (4.20–8.27)|
|Model 2||1 (ref.)||2.64 (2.29–3.05)||2.40 (1.90–3.01)||2.53 (2.14–2.98)||5.49 (3.91–7.71)|
|Model 3||1 (ref.)||2.58 (2.24–2.97)||2.37 (1.88–2.98)||2.46 (2.09–2.91)||5.02 (3.57–7.06)|
|Model 4||1 (ref.)||2.32 (2.01–2.68)||2.23 (1.77–2.80)||2.20 (1.87–2.60)||3.92 (2.78–5.50)|
In total, crude HRs of incident diabetes for maternal and paternal history of diabetes were 2.91 (95% CI, 2.46–3.43) and 2.36 (95% CI, 1.88–2.97), respectively, when compared with those who reported no parental diabetes. Model 1 in Table 3 shows that adjustment for age and sex modestly attenuated (13.1% reduction) the risk of diabetes by maternal diabetes (HR, 2.66; 95% CI, 2.26–3.14]), whereas this did not contribute to the risk conferred by paternal diabetes (HR, 2.40; 95% CI, 1.91–3.02). After multivariable adjustment (Model 4) for age, sex, diet, lifestyle factors and parameters of obesity, risk of diabetes was comparable for maternal (HR, 2.20; 95% CI, 1.87–2.60) and paternal history of diabetes (HR, 2.23; 95% CI, 1.77–2.80).
It is interesting that age, sex, diet, lifestyle factors and parameters of obesity contributed more to the association between maternal diabetes and risk of diabetes (overall attenuation of 37.1%) than paternal diabetes (overall attenuation of 9.6%). Therefore, we separately added each factor to Model 1 to assess its contribution to the association between category of parental diabetes and risk of diabetes. Parameters of obesity explained 23.5% and 9.6%, respectively, of the risk estimation of diabetes by maternal and paternal diabetes. Risk estimation of maternal diabetes was partly explained (9.4%) by energy intake and dietary determinants, whereas this accounted for only 2.9% of the association between paternal diabetes and risk of diabetes. After adjustment for lifestyle factors, an attenuation of 7.8% was observed in the association between maternal diabetes and risk of diabetes, whereas risk estimation of paternal diabetes was not affected by lifestyle factors.
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In this prospective cohort with over 10 years of follow-up, we found that both maternal and paternal history of diabetes were associated with baseline diabetes risk factors and with an increased risk of incident type 2 diabetes in participants, independent of diet, lifestyle and adiposity. However, the association between maternal diabetes history and risk of diabetes was slightly stronger in the age- and sex-adjusted model compared with paternal history. More than one-third of the maternal transmission of diabetes was explained by age, sex, diet, lifestyle factors (smoking status, alcohol consumption, physical activity and educational level) and parameters of obesity. The association between paternal diabetes and incident diabetes, however, was explained only modestly (approximately 10%) by diet and parameters of obesity.
The main strengths of our study are its large sample size, prospective design, verification of incident diabetes and extensive information about participants’ diet and lifestyle factors. Nevertheless, our study has some limitations. The EPIC-NL cohort almost exclusively comprised Caucasians from the Netherlands, and it is unclear whether our findings could be extended to other ethnic groups. Another limitation is that parental history of diabetes was obtained by self-report which is the usual method in single-generation cohorts. Furthermore, we excluded individuals with missing data or unknown parental history of diabetes. Having unknown family history has been shown to be more common for paternal than for maternal diabetes . However, the baseline characteristics of excluded individuals were similar to those who were included in our analysis. Therefore, it is unlikely that this would have led to recall bias or misclassification by category of parental diabetes of participants who did or did not develop diabetes. We relied on self-reported information about lifestyle and diet, which may be subject to misclassification. However, both the physical activity questionnaire and the FFQ have been validated previously [14, 16, 17]. These studies showed that both questionnaires could be used to rank individuals according to their physical activity or diet. We therefore believe that this did not greatly influence our results. Finally, individuals with type 2 diabetes may remain undiagnosed for several months to years and diagnosis of diabetes is always challenging in observational studies. Some cases of type 2 diabetes may have been undetected, resulting in underestimation of the association between parental diabetes and risk of diabetes in participants.
We first investigated the association between parental history of diabetes and baseline parameters of obesity in cross-sectional analyses. In multivariable-adjusted models, maternal or paternal diabetes was associated with higher BMI and waist and hip circumference. Having both maternal and paternal diabetes was associated with higher parameters of obesity. These findings are in agreement with those of other studies demonstrating that the presence of a maternal or paternal history of diabetes is associated with greater adiposity [21, 22] and weight gain , thus suggesting that diabetes and obesity share some common heritable determinants [5, 24].
A slightly more important role of maternal, compared with paternal, transmission of diabetes was shown in the present study in the age- and sex-adjusted model. This difference (approximately 25%) was explained by diet and adiposity as well as age, sex and lifestyle factors for maternal diabetes. Of note, multivariable models have not been used to assess these factors in previous studies investigating the increased importance of maternal transmission [8, 9, 21]. Amongst these studies, adiposity substantially explained the risk of diabetes transmitted by maternal diabetes, whereas other factors contributed to a lesser extent.
In the present study, both maternal and paternal transmission of diabetes were explained to some extent by obesity parameters, with a 2-fold higher contribution for maternal than for paternal diabetes. The contribution of dietary determinants was also larger in the association between maternal diabetes and risk of diabetes when compared with paternal diabetes. In addition, the influence of age, sex and lifestyle factors was confined to the association between maternal diabetes and risk of diabetes. This finding was not observed in a recent analysis from the Nurses’ Health Study (NHS). In the NHS, BMI rather than waist and hip circumference largely explained the association between both maternal and paternal history of diabetes and risk of type 2 diabetes. In addition to BMI, it was suggested that a higher intake of red meat and sugar-sweetened beverages and lack of alcohol consumption may explain part of the association between family history of diabetes and risk of diabetes . Of interest, in our study, parental history of diabetes was related to a lower intake of total energy and carbohydrates but a higher energy-adjusted intake of fat, protein, fibre, vitamin C and vitamin E. These differences modestly explained the association between maternal diabetes and risk of diabetes, whereas the effect was minimal for paternal transmission. The NHS included a sample of female nurses with limited variation in socio-economic status and with relatively healthy lifestyle behaviours. This selected sample may have led to an underestimation of the extent to which lifestyle factors explain parental transmission of diabetes .
The strong risk conferred by maternal or paternal diabetes was comparable after accounting for diet, lifestyle factors and adiposity. Of note, these factors differently explained maternal and paternal transmission of risk of diabetes. Our findings are consistent with previous evidence indicating a stronger magnitude of maternal transmission of obesity and its association with many lifestyle factors, compared with paternal transmission . A possible explanation for this is that the mother might have more influence on eating habits and other lifestyle behaviours whilst raising her children. Indeed, there may be more contact hours between mothers and children during childhood and in later life, and therefore, the mother’s lifestyle may be more of an example for her children than the father’s. It has been shown that if the mother has a history of diabetes during pregnancy, her child is less likely to follow certain healthy dietary recommendations . Similarly, those with a maternal history of diabetes may be more prone to have an unhealthy diet and lifestyle throughout their lifetime. Finally, there is evidence to suggest an effect of maternal nutrition and weight maintenance during pregnancy on infant birth weight [27, 28]. Birth weight could in turn influence future risk of chronic diseases such as type 2 diabetes [29, 30].
Diabetes is a polygenic disease in which multiple genetic and environmental components play roles throughout all stages of the disease [6, 31]. Beyond the genetic heritability, parental history of diabetes also carries environmental risk factors. In other words, it seems that parents and children share common lifestyle behaviours which will be continued throughout the children’s lifetime. These components, transmitted by maternal or paternal exposures, may explain the heterogeneity of diabetes transmission in different populations.
We conclude that both maternal and paternal history of diabetes are associated with an increased risk of developing type 2 diabetes, independent of diet, lifestyle and adiposity. The slight excess risk conferred by maternal compared to paternal diabetes is explained by a larger contribution to this association of age, sex, diet, lifestyle factors and adiposity.