Charlotte Glümer

A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99 (1):

Background Various strategies have been used to induce lifestyle changes to reduce ischaemic heart disease (IHD) with various successes. The aim of Inter99 is to assess the effect on IHD incidence of individually tailored non-pharmacological intervention on lifestyle using a newly developed computer-based health educational tool. The article describes the study and baseline results. Methods From a population of 61,301 individuals two random samples (high intensity intervention group (A), n = 11,708; low intensity intervention group (B), n = 1308) are screened to assess their absolute risk of IHD. Those at high risk receive individual lifestyle counselling. Individuals in group A are furthermore offered lifestyle counselling in groups on smoking cessation or physical activity/diet over a 6-month period. Individuals in group B are referred to their GP. High-risk persons are re-counselled after 1 and 3 years and the whole group is re-invited after 5 years. The remaining 48,285 (group C) are followed by questionnaire. The total population is followed through central registers. Intermediate end-points are changes in lifestyle, cholesterol, blood pressure and body mass index. Final end-point is reduction in incidence of IHD. Results The randomization leads to comparable groups. Participation rate was 52.5%. A total of 60% fulfilled the predetermined criteria for being at high risk for developing IHD. After an individual lifestyle counselling 41% accepted group-based counselling. Conclusion This large randomized population based trial discloses a noticeable need for and acceptance of lifestyle intervention in the general population. Eur J Cardiovasc Prevention Rehab 10:377-386

Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes.

Aims/hypothesisThe cytokine interleukin 6 (IL-6) is an essential regulator of the acute phase response associated with insulin-resistant states including type 2 diabetes and obesity. Three polymorphisms at positions −597, −572, and −174 of the IL6 promoter have been reported to influence IL6 transcription. The aim of this study was to investigate whether the IL6 promoter polymorphisms were associated with features of the WHO-defined metabolic syndrome and related quantitative traits in 7,553 Caucasian Danes.MethodsUsing analysis of PCR-generated primer extension products by mass spectrometry we examined −597 G/A, −572 G/C, and −174 G/C IL6 variants in the population-based Inter99 study cohort of middle-aged people (n=6,164) and in a group of type 2 diabetic patients (n=1,389).ResultsThe −174 G/C and −597 G/A polymorphisms were in strong linkage disequilibrium (R2=0.95). In the Inter99 cohort the −174 G-allele was associated with insulin resistance (p<0.02) and dyslipidaemia (p<0.007) whereas the C-allele of the −572 polymorphism was associated with increased serum insulin release during an OGTT (p<0.0005). Composite genotype or haplotype analyses of all 3 IL6 promoter variants showed associations with type 2 diabetes (p<0.002), obesity (p<0.02), and the metabolic syndrome (p<0.01).ConclusionsThe present studies suggest that single-nucleotide polymorphisms and composite genotypes or haplotypes of the IL6 promoter may be associated with several features of the metabolic syndrome in Caucasians.

Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial

Objective To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. Design Randomised controlled community based trial. Setting Suburbs of Copenhagen, Denmark Participants 59 616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n=11 629) and a control group (n=47 987). Intervention The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening. Main outcome measures The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality. Results 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58 308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58 940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the primary end point (hazard ratio for ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to 1.09; total mortality 1.00, 0.91 to 1.09). Conclusion A community based, individually tailored intervention programme with screening for risk of ischaemic heart disease and repeated lifestyle intervention over five years had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years. Trial registration Clinical trials NCT00289237.

Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action

Aims/hypothesisThe impact of strategies for prevention of type 2 diabetes in isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose tolerance (i-IGT) may differ depending on the underlying pathophysiology. We examined insulin secretion during OGTTs and IVGTTs, hepatic and peripheral insulin action, and glucagon and incretin hormone secretion in individuals with i-IFG (n = 18), i-IGT (n = 28) and normal glucose tolerance (NGT, n = 20).MethodsGlucose tolerance status was confirmed by a repeated OGTT, during which circulating insulin, glucagon, glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels were measured. A euglycaemic–hyperinsulinaemic clamp with [3–3H]glucose preceded by an IVGTT was performed.ResultsAbsolute first-phase insulin secretion during IVGTT was decreased in i-IFG (p = 0.026), but not in i-IGT (p = 0.892) compared with NGT. Hepatic insulin sensitivity was normal in i-IFG and i-IGT individuals (p ≥ 0.179). Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and consequently the disposition index (DI; insulin secretion×insulin sensitivity) during IVGTT (DIIVGTT)) was reduced in both i-IFG and i-IGT (p < 0.005 vs NGT). In contrast, the DI during OGTT (DIOGTT) was decreased only in i-IGT (p < 0.001), but not in i-IFG (p = 0.143) compared with NGT. Decreased levels of GIP in i-IGT (p = 0.045 vs NGT) vs increased levels of GLP-1 in i-IFG (p = 0.013 vs NGT) during the OGTT may partially explain these discrepancies. Basal and post-load glucagon levels were significantly increased in both i-IFG and i-IGT individuals (p ≤ 0.001 vs NGT).Conclusions/interpretationWe propose that differentiated preventive initiatives in prediabetic individuals should be tested, targeting the specific underlying metabolic defects.

The Danish National Health Survey 2010.: Study design and respondent characteristics.

Aims: In 2010 the five Danish regions and the National Institute of Public Health at the University of Southern Denmark conducted a national representative health survey among the adult population in Denmark. This paper describes the study design and the sample and study population as well as the content of the questionnaire. Methods: The survey was based on five regional stratified random samples and one national random sample. The samples were mutually exclusive. A total of 298,550 individuals (16 years or older) were invited to participate. Information was collected using a mixed mode approach (paper and web questionnaires). A questionnaire with a minimum of 52 core questions was used in all six subsamples. Calibrated weights were computed in order to take account of the complex survey design and reduce non-response bias. Results: In all, 177,639 individuals completed the questionnaire (59.5%). The response rate varied from 52.3% in the Capital Region of Denmark sample to 65.5% in the North Denmark Region sample. The response rate was particularly low among young men, unmarried people and among individuals with a different ethnic background than Danish. Conclusions: The survey was a result of extensive national cooperation across sectors, which makes it unique in its field of application, e.g. health surveillance, planning and prioritizing public health initiatives and research. However, the low response rate in some subgroups of the study population can pose problems in generalizing data, and efforts to increase the response rate will be important in the forthcoming surveys.

Association of obesity and insulin resistance with asthma and aeroallergen sensitization.

Background: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization.

There really is an epidemic of type 2 diabetes

The number of people with diabetes has increased throughout the world, and the rate of increase shows no signs of slowing. The Diabetes Atlas estimates that there were 194 million people with diabetes in 2003 and predicts an increase to 333 million by 2025 [1]. Figures from the World Health Organization (WHO) are similar [2]. These prediction models do not require an increase in the incidence of diabetes, but anticipate that the total number of individuals with diabetes will increase because of improved life expectancy, population growth and progressive urbanisation. Studies from many parts of the world have reported an increasing age-specific prevalence of diabetes. Recent data from the National Health and Nutrition Examination Survey (NHANES) studies in the USA show that the prevalence of diagnosed diabetes is relatively constant within each stratum of BMI, but imply that an increasing prevalence and incidence of diabetes would be expected as a consequence of increasing obesity [3]. In Denmark, three population-based surveys were carried out (in 1974, 1996 and 2000) in 60-year-old men and women living in the same geographical area in greater Copenhagen. These showed that prevalence increased from 7.8 through 12.3 to 14.0% in men, and from 5.6 through 6.8 to 13.6% in women [4, 5]. Although this might suggest an increasing incidence of diabetes, it could also be explained by other factors, including the longer survival of individuals with a diagnosis of diabetes. Thus, the central question is: to what extent can this increasing prevalence be explained by improved life expectancy and demographic factors, as against a simple increase in incidence or an imbalance between incidence and mortality? The last of these explanations was first put forward by Stovring et al. [6], using data from a Danish pharmacoepidemiological database, and has been developed further by Green et al. in this issue of the journal [7]. The term ‘diabetes epidemic’ has been used in recent years to describe the increasing burden of this disease. The term ‘epidemic’ was first coined in relation to infectious diseases and refers to a substantial increase in the number of new cases over a short, defined period of time [8]. More recently, the term has been extended to non-communicable diseases such as diabetes and to risk factors such as obesity; however, no specific, universally agreed definition has been adopted. Although the term has been used to describe an increasing prevalence, a true ‘epidemic’ would require an increasing incidence of diabetes. In consequence, loose terminology is partly responsible for the current dilemma. We will discuss potential explanations for the increasing prevalence of diabetes and will use different data sets to quantify the influence of each of these alternative explanations within a model system.

Comparability of venous and capillary glucose measurements in blood

Aim  Diabetes and glucose intolerance are diagnosed by measurement of glucose in blood. Glucose is usually measured as venous plasma or capillary whole blood and diagnostic criteria frequently provide equivalence estimates for these two methods. This study examined the relationship between glucose measured in capillary and venous samples collected at random, fasting and 2 h after oral glucose.

Obesity and central fat pattern among Greenland Inuit and a general population of Denmark (Inter99): Relationship to metabolic risk factors

OBJECTIVE: To investigate whether the obesity observed among the Inuit of Greenland and in a general Danish population was associated with the same degree of metabolic disturbances.DESIGN: Comparison of data from two population-based cross-sectional surveys conducted in 1999–2001.SUBJECTS: A total of 7892 individuals aged 30–60 y, 1108 Inuit participants from the Greenland Population study, and 6784 Danish participants in the Danish Inter99 study.MEASUREMENTS: Height, weight, waist and hip circumference were measured, and BMI and waist-to-hip ratio were calculated. The participants received a standard 75 g OGTT. s-Triglyceride, s-HDL cholesterol, fasting and 2 h p-glucose and s-insulin were analysed. Blood pressure was measured. Information on lifestyle factors was obtained by a questionnaire and interview.RESULTS: The Inuit had lower levels of 2-h glucose and insulin, blood pressure, triglyceride, and higher levels of HDL cholesterol than the Danish participants at any given level of obesity. Fasting glucose and fasting insulin levels within obesity categories were not different in the two populations. Adjustment for physical activity, smoking, school education, and alcohol consumption did not change these findings.CONCLUSION: The trends in the association between obesity and metabolic effects among the Inuit and a Northern European population were the same, but the levels of the risk factors were significantly different. This may be due to genetic factors and differences in body composition.

Serum 25(OH)D and Type 2 Diabetes Association in a General Population: A prospective study

OBJECTIVE This study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis. RESEARCH DESIGN AND METHODS A random sample of the general population of Copenhagen, Denmark, was taken as part of the Inter99 study. Included were 6,405 men and women aged 30–65 years at baseline (1999–2001), with 4,296 participating in the follow-up examination 5 years later (2004–2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)D]. Diabetes was defined based on an oral glucose tolerance test and a glycosylated hemoglobin (HbA1c) test. Secondary outcomes included continuous markers of glucose homeostasis. RESULTS The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio (OR) 0.91 (95% CI 0.84–0.97) in crude analyses. The association became statistically nonsignificant after adjustment for confounders, with an OR per 10 nmol/L of 0.94 (0.86–1.03). Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders. Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels. CONCLUSIONS Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low vitamin D status could be related to deterioration of glucose homeostasis.