Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight

Aims/hypothesis

The fetal insulin hypothesis suggests that variation in the fetal genotype influencing insulin secretion or action may predispose to low birthweight and type 2 diabetes. We examined associations between 25 confirmed type 2 diabetes risk variants and birthweight in individuals from the Danish Inter99 population and in meta-analyses including Inter99 data and reported studies.

Methods

Midwife records from the Danish State Archives provided information on mother’s age and parity, as well as birthweight, length at birth and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. We genotyped 25 risk alleles showing genome-wide associations with type 2 diabetes.

Results

Birthweight was inversely associated with the type 2 diabetes risk alleles of ADCY5 rs11708067 (β?=??33 g [95% CI ?55, ?10], p?=?0.004) and CDKAL1 rs7756992 (β?=??22 g [95% CI ?43, ?1], p?=?0.04). The association for the latter locus was confirmed in a meta-analysis (n?=?24,885) (β?=??20 g [95% CI ?29, ?11], p?=?5?×?10^?6). The HHEX-IDE rs1111875 variant showed no significant association among Danes (p?=?0.09); however, in a meta-analysis (n?=?25,164) this type 2 diabetes risk allele was associated with lower birthweight (β?=??16 g [95% CI ?24, ?8], p?=?8?×?10^?5). On average, individuals with high genetic risk (≥25 type 2 diabetes risk alleles) weighed marginally less at birth than those with low genetic risk (<25 type 2 diabetes risk alleles) (β?=??35 g [95% CI ?69, ?2], p?=?0.037).

Conclusions/interpretation

We report a novel association between the fetal ADCY5 type 2 diabetes risk allele and decreased birthweight, and confirm in meta-analyses associations between decreased birthweight and the type 2 diabetes risk alleles of HHEX-IDE and CDKAL1. No strong general effect on birthweight can be ascribed to the 25 common type 2 diabetes risk alleles.     

The relationship between changes in health behaviour and initiation of lipid-lowering and antihypertensive medications in individuals at high risk of ischaemic heart disease

ABSTRACT: BACKGROUND: It has been hypothesised that health conscious individuals tend to take better care of themselves by greater adherence to preventive medications. We examined, whether long-term changes in dietary habits and physical activity were associated with initiation of lipid-lowering and antihypertensive medications. METHODS: The study population consisted of two subsamples from the population-based cohort Inter99 study (1999-2006) in Copenhagen, Denmark: one with systolic blood pressure>140mmHg (N=557) and one with total cholesterol>7mmol/L (N=314). At a health examination, individuals completed a questionnaire about health behaviour and had their blood pressure and cholesterol measured at baseline and after five years. Data on medications were obtained through linkage to the Registry of Medical Product Statistics. RESULTS: Positive changes in physical activity (odds ratio =3.50; 95% CI 1.23-7.54) and in dietary habits (odds ratio=2.08; 95% CI 1.03-4.21) were associated with an increased initiation of lipid-lowering medications. With respect to antihypertensives, no association was observed in terms of physical activity, but for diet, a positive trend in terms of initiation was observed among those with positive changes in dietary habits (odds ratio=1.58; 95% CI 0.96-2.59). CONCLUSION: Generally, we observed health conscious behaviour in terms of increased initiation of preventive medications among those who reported positive changes in health behaviour. This study therefore suggests that more attention should be given to identifying individuals and groups, who are less health conscious and thereby less likely to engage in either preventive medications or changes in health behaviours.     

It is possible to help smokers in early motivational stages to quit. The Inter99 study

BACKGROUND: In a population-based sample of smokers in early motivational stages, we found a high acceptance of smoking cessation groups. METHODS: Inter99 is a randomized population-based intervention study, in Copenhagen, Denmark. Smokers in all motivational stages were included. All participants underwent a lifestyle consultation and 2,168 smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups. RESULTS: Thirty-five percent were validated to be continuously abstinent at the end of the smoking cessation groups. Eighty-four percent of the smokers achieving sustained abstinence in our study had no serious plans to quit soon before the lifestyle consultation. Motivation to quit before the lifestyle consultation could not predict abstinence. Being a man, and having a job and at least 1 year of vocational training were predictors of abstinence in a multivariate model, whereas high nicotine dependence and living with a smoking spouse were predictors of failure. CONCLUSION: High cessation rates were obtained in a population of heavy smokers with moderate nicotine dependence. It was possible to obtain sustained abstinence in smokers in early motivational stages. These smokers would probably not have been reached by traditional smoking campaigns.     

Diet and exercise intervention in a general population--mediators of participation and adherence: the Inter99 study

BACKGROUND: Drop-out rates are high in many lifestyle programmes. To promote adherence, the aim of this study was to identify mediators of participation in a diet and exercise (DE) intervention in a general population. METHODS: Data were baseline data from a randomized non-pharmacological clinical trial in Copenhagen during 1999-2001. The participation rate was 53.3%. Participants at high risk of ischaemic heart disease (IHD) and who were offered participation in a DE counselling group intervention were included (N = 2022). Clinical characteristics, and demographic, psychosocial and lifestyle factors were measured. RESULTS: Mediators of acceptance of participation were awareness of an unhealthy lifestyle or a bad health, low self-rated care of own health, perceived susceptibility of cardiovascular disease (CVD; overall and associated with lifestyle), high degree of motivation towards dietary changes and low self-efficacy about increasing physical activity. Overweight and impaired glucose tolerance (IGT)/screen-detected diabetes predicted acceptance whereas an absolute risk score for IHD was inverse associated with acceptance. Mediators of high adherence were low self-efficacy about changing dietary habits and perceived susceptibility of CVD and furthermore screen-detected diabetes and overweight predicted high adherence. CONCLUSION: Awareness of unhealthy lifestyle, perceived susceptibility of disease and motivation towards lifestyle changes were important mediators of participation. Screen-detected diabetes/IGT predicted participation and adherence whereas overweight individuals were more likely to accept but also to drop out of the course. The use of an absolute risk score in health promotion should be further evaluated.     

Motives to quit smoking and reasons to relapse differ by socioeconomic status

Objective

To investigate motives, strategies and experiences to quit smoking and reasons to relapse as a function of socioeconomic status.

Methods

A population-based study, Inter99, Denmark. Two thousand six hundred twenty-one daily smokers with a previous quit attempt completed questionnaires at baseline. Cross-sectional baseline-data (1999-2001) were analysed in adjusted regression analyses.

Results.

Consistent findings across the three indicators of socioeconomic status (employment, school education, higher education/vocational training): smokers with low socioeconomic status were significantly more likely than smokers with high socioeconomic status to report that they wanted to quit because smoking was too expensive (OR: 1.85 (1.4-2.4), for school education) or because they had health related problems (OR: 1.75 (1.4-2.2)). When looking at previous quit attempts, smokers with low socioeconomic status were significantly more likely to report that it had been a bad experience (OR: 1.41 (1.1-1.8)) and that they had relapsed because they were more nervous/restless/depressed (OR: 1.43 (1.1-1.8)).

Conclusions.

This study shows that smokers with low socioeconomic status have other motives to quit and other reasons to relapse than smokers with high socioeconomic status. Future tobacco prevention efforts aimed at smokers with low socioeconomic status should maybe focus on current advantages of quitting smoking, using high cost of smoking and health advantages of quitting as motivating factors and by including components of mental health as relapse prevention.