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Articles by K. Borch-Johnsen
Total Records ( 10 ) for K. Borch-Johnsen
  T. W. Boesgaard , S. I. Castella , G. Andersen , A. Albrechtsen , T. Sparso , K. Borch-Johnsen , T. Jorgensen , T. Hansen and O. Pedersen
 

Aims The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the γ-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2−243A→G polymorphism and levels of body mass index (BMI) and estimates of glycaemia.

Methods Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2−243A→G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects.

Results The G-allele was associated with modestly lower BMI (P = 0.01). In a case–control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4–20.6) compared with 17.1% (15.5–18.8) in 968 participants having BMI ≥ 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7–1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 ± 0.8; AG (n = 1792) 5.5 ± 0.8; GG (n = 206) 5.5 ± 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 ± 1.9; AG 8.6 ± 1.9; GG 8.6 ± 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 ± 0.4; AG (n = 1383) 5.3 ± 0.4; GG (n = 153) 5.2 ± 0.4 (P = 9.10−5).

Conclusion The present study suggests that the GAD2−243A→G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.

  E-M. Dalsgaard , T. Lauritzen , T. Christiansen , K. S. Mai , K. Borch-Johnsen and A. Sandbaek
 

Aims The prevalence of diabetes is increasing, and screening of high-risk populations is recommended. A low attendance rate has been observed in many Type 2 diabetes screening programmes, so that an analysis of factors related to attendance is therefore relevant. This paper analyses the association between socioeconomic factors and attendance for Type 2 diabetes screening.

Methods Persons aged 40–69 years (n = 4603) were invited to participate in a stepwise diabetes screening programme performed in general practitioners' offices in the county of Aarhus, Denmark in 2001. The study was population-based and cross-sectional with follow-up. The association between screening attendance in the high-risk population and socioeconomic factors was analysed by odds ratio.

Results Forty-four percent of the estimated high-risk population attended the screening programme. In those with known risk for Type 2 diabetes, attenders were more likely to be older, to be unemployed and to live in the countryside than non-attenders. The risk for Type 2 diabetes was unknown for 21% of the study population; this group was younger and less likely to be cohabitant, skilled, or employed and to have middle or high income than the study population with known risk score for diabetes.

Conclusions A low attendance rate was found in this screening programme for Type 2 diabetes. No substantial socioeconomic difference was found between attenders and non-attenders in the high-risk population. Further research is needed to uncover barriers to screening of Type 2 diabetes in socioeconomically deprived persons.

  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.

  K. Akram , U. Pedersen-Bjergaard , B. Carstensen , K. Borch-Johnsen and B. Thorsteinsson
  Not available
  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. van den Donk , A. Sandbaek , K. Borch-Johnsen , T. Lauritzen , R. K. Simmons , N. J. Wareham , S. J. Griffin , M. J. Davies , K. Khunti and G. E. H. M. Rutten
  Aims  To describe and compare attendance rates and the proportions of people identified with Type 2 diabetes mellitus in people with previously unknown diabetes who participated in screening programmes undertaken in general practice in the UK, Denmark and the Netherlands as part of the ADDITION-Europe study.

Methods  In Cambridge, routine computer data searches were conducted to identify individuals aged 40-69 years at high risk of Type 2 diabetes using the Cambridge Diabetes Risk Score. In Denmark, the Danish Diabetes Risk Score was mailed to individuals aged 40-69 years, or completed by patients visiting their general practitice. In the Netherlands, the Hoorn Symptom Risk Questionnaire was mailed to individuals aged 50-69 years. In these three centres, high-risk individuals were invited to attend subsequent steps in the screening programme, including random blood glucose, HbA1c, fasting blood glucose and/or oral glucose tolerance test. In Leicester, eligible people aged 40-69 years were invited directly for an oral glucose tolerance test. In all centres, Type 2 diabetes was defined according to World Health Organization 1999 diagnostic criteria.

Results  Attendance rates ranged from 20.2% (oral glucose tolerance test in Leicester without pre-stratification) to 95.1% (random blood glucose in opportunistic screening in Denmark in high-risk people). The percentage of people with newly detected Type 2 diabetes from the target population ranged from 0.33% (Leicester) to 1.09% (the Netherlands).

Conclusions  Screening for Type 2 diabetes was acceptable and feasible, but relatively few participants were diagnosed in all participating centres. Different strategies may be required to increase initial attendance and ensure completion of screening programmes.

  S. Soulimane , D. Simon , J. E. Shaw , P. Z. Zimmet , S. Vol , D. Vistisen , D. J. Magliano , K. Borch-Johnsen and B. Balkau
  Aim  We examined the ability of fasting plasma glucose and HbA1c to predict 5-year incident diabetes for an Australian cohort and a Danish cohort and 6-year incident diabetes for a French cohort, as defined by the corresponding criteria.

Methods  We studied 6025 men and women from AusDiab (Australian), 4703 from Inter99 (Danish) and 3784 from DESIR (French), not treated for diabetes and with fasting plasma glucose < 7.0 mmol/l and HbA1c < 48 mmol/mol (6.5%) at inclusion. Diabetes was defined as fasting plasma glucose ≥ 7.0 mmol/l and/or treatment for diabetes or as HbA1c ≥ 48 mmol/mol (6.5%) and/or treatment for diabetes.

Results  For AusDiab, incident fasting plasma glucose-defined diabetes was more frequent than HbA1c-defined diabetes (PMcNemar < 0.0001), the reverse applied to Inter99 (PMcNemar < 0.007) and for DESIR there was no difference (PMcNema = 0.17). Less than one third of the incident cases were detected by both criteria. Logistic regression models showed that baseline fasting plasma glucose and baseline HbA1c predicted incident diabetes defined by the corresponding criteria. The standardized odds ratios (95% confidence interval) for HbA1c were a little higher than for fasting plasma glucose, but not significantly so. They were respectively, 5.0 (4.1-6.1) and 4.1 (3.5-4.9) for AusDiab, 5.0 (3.6-6.8) and 4.8 (3.6-6.3) for Inter99, 4.8 (3.6-6.5) and 4.6 (3.6-5.9) for DESIR.

Conclusions  Fasting plasma glucose and HbA1c are good predictors of incident diabetes defined by the corresponding criteria. Despite Diabetes Control and Complications Trial-alignment of the three HbA1c assays, there was a large difference in the HbA1c distributions between these studies, conducted some 10 years ago. Thus, it is difficult to compare absolute values of diabetes prevalence and incidence based on HbA1c measurements from that time.

  S. B. Haugaard , O. Andersen , T. W. Hansen , J. Eugen-Olsen , A. Linneberg , S. Madsbad , M. H. Olsen , T. Jorgensen , K. Borch-Johnsen and J. Jeppesen
  Aim  To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort.

Methods  The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy individuals). The soluble urokinase plasminogen activator receptor was measured by the ELISA method. To fulfil model assumptions, outcome analyses were stratified by age, and further by smoking, owing to the interaction between the soluble urokinase plasminogen activator receptor and smoking on new-onset diabetes (P < 0.0001).

Results  New-onset diabetes (n = 182) was associated with increased soluble urokinase plasminogen activator receptor levels (P = 0.013). Among 699 middle-aged (41 and 51 years) and 564 older (61 and 71 years) non-smokers, participants in the upper soluble urokinase plasminogen activator receptor quartile had a sex- and age-adjusted relative risk of 6.01 (95% CI 2.17-16.6, P < 0.0006) and relative risk of 3.25 (95% CI 1.51-6.98, P = 0.0025), respectively, for new-onset diabetes compared with participants in the lowest quartile. This relationship remained significant after additional adjustments for C-reactive protein and leukocytes or fasting glucose and insulin or BMI (P < 0.05). The soluble urokinase plasminogen activator receptor was not related to incident diabetes among smokers (P ≥ 0.85).

Conclusions  In these explorative analyses, the soluble urokinase plasminogen activator receptor associated independently with incident diabetes in non-smokers, supporting an immune origin of Type 2 diabetes. Competing disease risk may explain lack of association among smokers.

  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.

  J. A. Black , S. J. Sharp , N. J. Wareham , A. Sandbaek , G. E. H. M. Rutten , T. Lauritzen , K. Khunti , M. J. Davies , K. Borch-Johnsen , S. J. Griffin and R. K. Simmons
 

Aims

Little is known about the long-term effects of intensive multifactorial treatment early in the diabetes disease trajectory. In the absence of long-term data on hard outcomes, we described change in 10-year modelled cardiovascular risk in the 5 years following diagnosis, and quantified the impact of intensive treatment on 10-year modelled cardiovascular risk at 5 years.

Methods

In a pragmatic, cluster-randomized, parallel-group trial in Denmark, the Netherlands and the UK, 3057 people with screen-detected Type 2 diabetes were randomized by general practice to receive (1) routine care of diabetes according to national guidelines (1379 patients) or (2) intensive multifactorial target-driven management (1678 patients). Ten-year modelled cardiovascular disease risk was calculated at baseline and 5 years using the UK Prospective Diabetes Study Risk Engine (version 3β).

Results

Among 2101 individuals with complete data at follow up (73.4%), 10-year modelled cardiovascular disease risk was 27.3% (sd 13.9) at baseline and 21.3% (sd 13.8) at 5-year follow-up (intensive treatment group difference -6.9, sd 9.0; routine care group difference -5.0, sd 12.2). Modelled 10-year cardiovascular disease risk was lower in the intensive treatment group compared with the routine care group at 5 years, after adjustment for baseline cardiovascular disease risk and clustering (-2.0; 95% CI -3.1 to -0.9).

Conclusions

Despite increasing age and diabetes duration, there was a decline in modelled cardiovascular disease risk in the 5 years following diagnosis. Compared with routine care, 10-year modelled cardiovascular disease risk was lower in the intensive treatment group at 5 years. Our results suggest that patients benefit from intensive treatment early in the diabetes disease trajectory, where the rate of cardiovascular disease risk progression may be slowed.

 
 
 
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