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Articles by D. R. Witte
Total Records ( 6 ) for D. R. Witte
  K. Faerch , A. Vaag , D. R. Witte , T. Jorgensen , O. Pedersen and K. Borch-Johnsen
  Aims  Screening and prevention strategies for Type 2 diabetes require insight into the aetiological and potentially different risk factors leading to early impairments of fasting plasma glucose (FPG) and 2-h post-load plasma glucose (2hPG) levels. We studied whether risk factors predicting subtle elevations of FPG levels were different from those predicting elevations of 2hPG levels in men and women.

Methods  We used baseline and 5-year follow-up data from middle-aged men and women with normal glucose tolerance (NGT) at baseline in the Danish population-based Inter99 study (n = 3164). Anthropometric and non-anthropometric baseline predictors of the 5-year FPG and 2hPG levels were estimated in linear regression models stratified by gender.

Results  In men, but not in women, smoking and family history of diabetes predicted increased FPG levels, whereas high physical activity predicted a decline in 2hPG levels. Among the anthropometric variables, large waist circumference was the strongest predictor of increased FPG levels in men, whereas high body mass index (BMI) was the strongest predictor of increased FPG levels in women. In both men and women, BMI and waist circumference were equally strong in predicting 2hPG levels. Furthermore, short height predicted increased 2hPG levels in men, and short height and low hip circumference predicted increased 2hPG levels in women.

Conclusions  Risk factors that predict future FPG levels are different from those predicting future 2hPG levels. Furthermore, different risk factors predict glycaemic levels in men compared with women. These findings indicate that different aetiological pathways may lead to Type 2 diabetes in men and women.

  E. J. Brunner , M. J. Shipley , M. G. Marmot , M. Kivimaki and D. R. Witte
  Aims  British guidelines on vascular disease prevention recommend adding a random (casual) blood glucose measurement to a lipid profile in those aged ≥ 40 years. To assess this recommendation, we compared the predictive value of a risk model based on the Framingham risk score alone to one which additionally included information on fasting blood glucose, with respect to incident coronary heart disease (CHD) over 11 years.

Method  Men and women aged 40-63 years in Whitehall II were followed up for incident CHD: death/non-fatal myocardial infarction; angina confirmed by doctor diagnosis or electrocardiogram (ECG) and all first events. Fasting blood glucose was specified as a continuous variable or categorized by World Health Organization (WHO) 1999 glycaemic status (normal glucose tolerance, impaired fasting glucose or newly diagnosed diabetes).

Results  The hazard ratio for incident CHD was 1.10 (95%CI 1.09; 1.12) in men and 1.13 (1.10; 1.17) in women per percentage point increase in Framingham risk. The excess risk remained unchanged in models which added glycaemic status or continuous fasting glucose. The area under the receiver operating characteristic (ROC) curve for the Framingham score and incident coronary heart disease [0.70 (0.68; 0.73)] did not change when glycaemic status or fasting glucose was added to the prediction model. Reclassification with these modified models improved discrimination based on the Framingham score alone when glycaemic status was added, net reclassification improvement 2.4% (95% CI 0.2%; 4.6%), but not when fasting glucose was added.

Conclusion  Better detection of unrecognized diabetes is a valuable consequence of including a random blood glucose in a vascular risk profile. Our results suggest that this strategy is unlikely to improve risk stratification for CHD.

  R. Borg , D. Vistisen , D. R. Witte and K. Borch-Johnsen
  Aims  Glycated haemoglobin (HbA1c) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods.

Methods  We assessed the prevalence of cardiovascular risk factors in individuals with undiagnosed diabetes according to the World Health Organization classification or by the newly proposed HbA1c level ≥ 6.5% among 6258 participants of the Danish Inter99 study. Receiver operating curve analysis assessed the ability of fasting: 2-h plasma glucose and HbA1c to distinguish between individuals at high and low risk of ischemic heart disease, predicted by the PRECARD program.

Results  Prevalence of undiagnosed diabetes was 4.1% [95% confidence interval (CI) 3.7-4.7%] by the current oral glucose tolerance test definition, whereas 6.6% (95% CI 6.0-7.2%) had diabetes by HbA1c levels. HbA1c-defined individuals were relatively older with higher proportions of men, smokers, lipid abnormalities and macro-albuminuria, but they were leaner and had lower blood pressure. HbA1c was better than fasting- and 2-h plasma glucose at distinguishing between individuals of high and low predicted risk of ischaemic heart disease; however, the difference between HbA1c and fasting- and 2-h plasma glucose was not statistically significant.

Conclusions  Compared with the current oral glucose tolerance test definition, more individuals were classified as having diabetes based on the HbA1c criteria. This group had as unfavourable a risk profile as those identified by the oral glucose tolerance test.

  M. E. Jorgensen , K. Borch-Johnsen , D. R. Witte and P. Bjerregaard
  Background and aim  Most studies show that diabetes increases with migration and urbanization. Previous studies from Greenland have shown inconsistent associations between cardiovascular risk and urbanization. Thus, the aim was to study the association between diabetes and urbanization among Greenland Inuit.

Methods  A total of 3089 adult Inuit aged 18 years and older participated in a geographically representative, population-based study ‘Inuit Health in Transition Study’. The examination included a 75 g oral glucose tolerance test and anthropometric measurements. Information on socio-demographic characteristic and health behaviour was obtained by interview or questionnaire. The participants were categorized according to degree of urbanization into three groups based on current place of residence: (1) participants living in towns (> 2000 inhabitants), (2) participants living in small towns (< 2000 inhabitants) and (3) participants living in villages (< 500 inhabitants).

Results  The total prevalence of diabetes was 9% of which 79% were previously unknown. Nine per cent had impaired glucose tolerance and 19% had impaired fasting glycaemia (IFG). Compared with towns, odds rations (ORs) for diabetes and impaired fasting glycaemia were higher in small towns [ORdiabetes = 1.5 (1.0-2.3), ORIFG = 1.9 (1.2-2.3)] and villages [ORdiabetes = 1.2 (0.8-1.9), ORIFG = 1.3 (0.9-2.0)], whereas no association was seen for impaired glucose tolerance. The inverse association between urbanization and diabetes and impaired fasting glycaemia persisted after adjustment for relevant confounders.

Conclusion  Diabetes and impaired fasting glycaemia decreased with urbanization contrary to the results of most studies. It appears that Greenland Inuit follow the pattern usually observed in industrialized countries with the highest risk of diabetes in the lower socio-economic groups.

  L. N. Handlos , D. R. Witte , T. P. Almdal , L. B. Nielsen , S. E. Badawi , A. R. A. Sheikh , M. Belhadj , D. Nadir , S. Zinai and D. Vistisen


To develop risk scores for diabetes and diabetes or impaired glycaemia for individuals living in the Middle East and North Africa region. In addition, to derive national risk scores for Algeria, Saudi Arabia and the United Arab Emirates and to compare the performance of the regional risk scores with the national risk scores.


An opportunistic sample of 6588 individuals aged 30-75 years was screened. Screening consisted of a questionnaire and a clinical examination including measurement of HbA1c. Two regional risk scores and national risk scores for each of the three countries were derived separately by stepwise backwards multiple logistic regression with diabetes [HbA1c ≥ 48 mmol/mol (≥ 6.5%)] and diabetes or impaired glycaemia [HbA1c ≥ 42 mmol/mol (≥ 6.0%)] as outcome. The performance of the regional and national risk scores was compared in data from each country by receiver operating characteristic analysis.


The eight risk scores all included age and BMI, while additional variables differed between the scores. The areas under the receiver operating characteristic curves were between 0.67 and 0.70, and for sensitivities approximately 75%; specificities varied between 50% and 57%. The regional and the national risk scores performed equally well in the three national samples.


Two regional risk scores for diabetes and diabetes or impaired glycaemia applicable to the Middle East and North Africa region were identified. The regional risk scores performed as well as the national risk scores derived in the same manner.

  B. Guigas , J. E. de Leeuw van Weenen , N. van Leeuwen , A. M. Simonis-Bik , T. W. van Haeften , G. Nijpels , J. J. Houwing-Duistermaat , M. Beekman , J. Deelen , L. M. Havekes , B. W. J. H. Penninx , N. Vogelzangs , E. van t Riet , A. Dehghan , A. Hofman , J. C. Witteman , A. G. Uitterlinden , N. Grarup , T. Jorgensen , D. R. Witte , T. Lauritzen , T. Hansen , O. Pedersen , J. Hottenga , J. A. Romijn , M. Diamant , M. H. H. Kramer , R. J. Heine , G. Willemsen , J. M. Dekker , E. M. Eekhoff , H. Pijl , E. J. de Geus , P. E. Slagboom and L. M. t Hart


Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans.


Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis.


rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); = 4.1*10−4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (= 5.5*10−4) but again not in men (= 0.34).


The present data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene.

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