Biomedical subjects

Knut Borch-Johnsen

Publications and source records attributed to Knut Borch-Johnsen.

At least 19 recordsLinked to original sources

PubMed2007

The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites.

Food intake and weight gain are influenced by endocannabinoids whose actions are regulated by the fatty acid amide hydrolase (FAAH) enzyme. The homozygous Thr/Thr genotype of the functional Pro129Thr variant (rs324420) in the gene encoding FAAH was recently reported to associate with overweight and obesity in white and black populations. We investigated the Pro129Thr variant in relation to overweight and obesity in a relatively large population-based study sample of Danish whites (n=5,801). In case-control studies of obesity, a borderline association with the major Pro allele was identified; however, after correction for multiple testing, no association was found. Furthermore, a possible association between the major Pro allele and obesity was not supported by studies of obesity-related quantitative traits. In conclusion, in a large study sample, we were unable to find robust evidence of an association of the Pro129Thr FAAH variant with overweight, obesity, and any related quantitative traits among the examined whites.

Adult↗

PubMed2007

Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution.

We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.

Asian People↗

PubMed2006

Relationships between the functional PPARalpha Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people.

Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor capable of regulating the expression of genes involved in peroxisomal and mitochondrial beta-oxidation pathways. The common Leu162Val polymorphism in the gene encoding PPARalpha has inconsistently shown association with quantitative traits related to obesity, type 2 diabetes, and dyslipidaemia. We genotyped the Leu162Val polymorphism in 1383 patients with type 2 diabetes and 4401 control subjects with normal glucose tolerance (NGT) without showing any association between diabetes and genotype. In addition, the Leu162Val polymorphism was not associated with WHO-defined obesity or dyslipidaemia in case-control settings involving 961 obese and 2563 lean subjects and 1399 dyslipidaemic and 4399 normolipidaemic subjects, respectively. Quantitative trait studies of metabolic variables were carried out in 5799 middle-aged, treatment-naïve subjects showing a difference in fasting serum triglyceride concentrations among homozygous Val-carriers (Leu/Leu+Leu/Val, n=5782, 1.33+/-1.35 mmol/l vs. Val/Val, n=17, 2.22+/-2.4 mmol/l, p=0.007). Similarly, Val/Val was associated with increased fasting serum total cholesterol concentrations (p=0.01). In conclusion, in a relative large-scale study of middle-aged whites we found no evidence of association between the PPARalpha Leu162Val polymorphism and obesity or type 2 diabetes. If replicated, the Val162Val variant may, however, confer an increase in fasting levels of serum lipids.

Aged↗

PubMed2006

Gender differences in the association between westernization and metabolic risk among Greenland Inuit.

BACKGROUND: The Inuit have gone through an accelerated process of modernization especially since 1950. Primarily because of the dietary transition, westernisation is expected to influence the Inuit's metabolic risk in a negative way with respect to cardiovascular risk. The aim was to analyze metabolic risk factors among Inuit in Greenland and Denmark and their relation to westernization. METHODS: 1173 adult Inuit participated in a health survey in Greenland and Denmark. The examination included a 75 g OGTT. BMI, waist-to-hip ratio, and blood pressure were measured. P-glucose, s-insulin, lipids and urine-albumin/creatinine ratio were analysed. Westernization was estimated by place of residence and language. RESULTS: The prevalence of the metabolic syndrome was 20.3% among men and 19.5% among women (p = 0.73). The association between the metabolic syndrome and westernization was different for men and women. For men there was an increase in prevalence of the metabolic syndrome with westernization within Greenland, but the variation was less pronounced than the difference between the migrants and the Inuit in Greenland. Age, family history of diabetes, and non-smoking were directly associated with the metabolic syndrome, whereas high physical activity was negatively associated with the metabolic syndrome. For women there was a significant negative association between westernization and the metabolic syndrome among the three population groups in Greenland, whereas the prevalence was not significantly lower among female migrants compared with Inuit women in Greenland. Age, family history of diabetes, non-smoking, and low education were associated with the metabolic syndrome. CONCLUSIONS: The effect of westernization on metabolic risk was different for men and women. For men physical inactivity due to a decrease in subsistence hunting and fishing seems to increase the metabolic risk; for women higher education is associated with a more favorable risk profile.

Adult↗

PubMed2006

Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects.

CONTEXT: The type 2 iodothyronine deiodinase (D2) catalyzes the conversion of T(4) to the active form of thyroid hormone, which is a critical regulator of thermogenesis and glucose metabolism. A Thr92Ala polymorphism in the gene encoding D2 (DIO2) has been reported to associate with insulin resistance. OBJECTIVE: The aim of the present study was to assess the impact of the DIO2 Thr92Ala variant on type 2 diabetes (T2D), obesity, and related quantitative metabolic traits including measures of insulin resistance. Because DIO2 is activated through a beta-adrenergic receptor-dependent pathway, we further hypothesized that variation in the ADRB genes interacts with DIO2 Thr92Ala variant to influence metabolic traits. DESIGN AND PATIENTS: The DIO2 polymorphism was genotyped in a total of 7342 white subjects including 1405 T2D patients. RESULTS: We detected no significant association of the DIO2 Thr92Ala polymorphism with T2D or obesity. We observed nominal significant associations of genotype with increased area under the serum insulin curve during an oral glucose tolerance test (P = 0.03) and elevated fasting plasma glucose (P = 0.02) in homozygous Ala92 allele carriers, the latter strengthened by epistasis with the ADRB2 Gly16Arg variant in a double recessive model (P = 0.004). However, after permutation procedure, performed to correct for multiple hypothesis testing, the associations did not reach study-wide significance. CONCLUSIONS: The DIO2 Thr92Ala variant does not confer an increased risk of T2D, obesity, or insulin resistance.

Adult↗

PubMed2006

Association between neuromedin U gene variants and overweight and obesity.

BACKGROUND: Neuromedin U (NMU) is an anorexic neuropeptide expressed in the hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice overexpressing Nmu are hypophagic and lean. OBJECTIVE: Our objective was to investigate whether variants in NMU are associated with human obesity. DESIGN: The coding region of NMU was analyzed for variants in obese Czech children and obese Danish adults. Identified missense variants were investigated for cosegregation with obesity in families or association with obesity in the general population. SETTING: The study was performed at Steno Diabetes Center, Denmark, and Department of Pediatrics, Charles University, Czech Republic. SUBJECTS AND METHODS: A total of 289 Czech children and adolescents with early-onset obesity and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean and unrelated Czech subjects. RESULTS: The rare NMU Arg165Trp variant cosegregated with childhood obesity in a Czech family. Homozygous carriers of the Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2-0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval, 0.7-1.1) among 3265 overweight and obese subjects (body mass index >or= 25 kg/m2) [odds ratio, 2.5 (1.2-5.3); P = 0.01]. CONCLUSION: Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.

Adolescent↗

PubMed2006

[Metabolic syndrome in a global perspective. Significance for public health].

The term "metabolic syndrome" refers to the clustering of a number of cardiovascular risk factors (obesity, hypertension, dyslipidemia and hyperglycemia) believed to be related to insulin resistance. The prevalence of each of these diseases as well as the metabolic syndrome is increasing world wide. Obesity, hypertension, dyslipidemia and diabetes are no longer diseases of the wealthy. By 2025, three out of four people with diabetes will be living in 3rd world countries, and similar trends are likely for the other components of the syndrome. Preventive action is urgently needed, and studies in China and India have proven to be effective.

Global Health↗

PubMed2006

Variation in CAPN10 in relation to type 2 diabetes, obesity and quantitative metabolic traits: studies in 6018 whites.

The first type 2 diabetes (T2D) gene to be identified in a genome wide scan followed by positional cloning was CAPN10 encoding the cysteine protease calpain-10. Subsequently, a large number of studies have investigated variation in CAPN10 in relation to T2D. Two CAPN10 single nucleotide polymorphisms (SNPs), the SNP43 (rs3792267) and the SNP44 (rs2975760), have been associated with T2D in some, but not all studies conducted in a wide range of ethnicities. We investigated the two SNPs for association with T2D in a relatively large, homogenous population of Danish whites (n = 1359 T2D cases, n = 4659 normoglycemic and glucose-tolerant control subjects), however, no significant associations of the SNP43 or the SNP44 variant with T2D were found. Neither were the two variants associated with obesity, and no association of either variant with diabetes-related quantitative traits was found in a study involving a population-based sample of 5698 middle-aged subjects. Meta-analyses, however, of the present and previously published studies involving 15,368 (SNP43) or 13,628 (SNP44) subjects yielded odds ratios of 1.09 (95% CI 1.02-1.16, p = 0.007) and 1.15 (1.07-1.23, p = 0.0002), respectively, for association with T2D. In conclusion, in a relatively large study sample of whites we found no consistent evidence of association of the CAPN10 SNP43 or SNP44 with T2D, obesity, or related quantitative traits, although meta-analyses of these two CAPN10 SNPs demonstrated an association with T2D.

Blood Glucose↗

PubMed2006

Representativeness in population-based studies: a detailed description of non-response in a Danish cohort study.

BACKGROUND: Decreasing rates of participation in population-based studies increasingly challenge the interpretation of study results, in both analytic and descriptive epidemiology. Consequently, estimates of possible differences between participants and non-participants are increasingly important for the interpretation of study results and generalization to the background population. METHODS: An age-specific, population-based cohort of 1,198 individuals was examined at age 40, 45, 51, and 60. Participants were compared with non-participants and when possible also with the background population using a wide range of detailed information on somatic and mental health collected at each examination, including data from a clinical examination, biochemical measurements, questionnaires, interviews, and public registers. RESULTS: Participation rates were higher than 80% at examinations at age 40, 45, and 51, but decreased to 65% at age 60. At the baseline investigation at age 40, analyses indicated that participants were representative of the cohort as well as the background population. However, the mortality rate was higher among non-participants in the succeeding 20 years. Among living cohort members at the 60-year examination, non-participants had lower socioeconomic status, higher hospitalization rate, and a worse overall health profile than participants. CONCLUSIONS: The detailed data presented reinforce the contention that the health profile of non-participants is typically worse than that of participants. The results also indicate that while data from public registers give easily accessible information about non-participants, these crude proxy measures of health may not be enough to document representativeness.

Adult↗

PubMed2006

Lifestyle modifies obesity-associated risk of cardiovascular disease in a genetically homogeneous population.

BACKGROUND: The association between obesity and cardiovascular disease risk differs across populations. Whether such differences in obesity-related risk factors exist within population groups of the same genetic origin but with differences in lifestyle remains to be determined. OBJECTIVE: The aim was to analyze whether obesity was associated with the same degree of metabolic disturbances in 2 groups of genetically homogeneous Inuit who were exposed to considerable differences in lifestyle. DESIGN: We studied obesity and cardiovascular disease risk factors in a cross-sectional population survey of 2311 Inuit living in Denmark (n = 995) or Greenland (n = 1316). The participants received an oral-glucose-tolerance test. Blood tests were supplemented by structured interviews and anthropometric and blood pressure measurements. RESULTS: The trend in the association between obesity and metabolic effects was not significantly different in the Inuit populations, but the values of several risk factors were significantly different. At any given level of obesity, Inuit residents in Greenland had lower blood pressure and lower concentrations of triacylglycerol and postchallenge plasma glucose and insulin than did the Inuit migrants in Denmark. The trend in the association with obesity categories was different only for HDL cholesterol, with higher concentrations observed in women Inuit migrants in Denmark than in women Inuit residents in Greenland. CONCLUSIONS: The health risk associated with obesity clearly varies within groups of Inuit living in Greenland and Inuit migrants living in Denmark. The findings indicate that lifestyle factors modify the cardiovascular disease risk associated with obesity.

Adult↗

PubMed2006

Association between dietary glycemic index, glycemic load, and body mass index in the Inter99 study: is underreporting a problem?

BACKGROUND: The few studies examining the potential associations between glycemic index (GI), glycemic load (GL), and body mass index (BMI) have provided no clear pictures. Underreporting of energy intake may be one explanation for this. OBJECTIVE: We examined the associations between GI, GL, and BMI by focusing on the confounding factor of total energy intake and the effect of exclusion of low energy reporters (LERs). DESIGN: This was a cross-sectional study of 6334 subjects aged 30-60 y. Dietary intake was estimated from a food-frequency questionnaire. GI and GL were estimated by using white bread as the reference food. Underreporting of energy intake was assessed as reported energy intake divided by basal metabolic rate (EI/BMR); LERs were defined as those having an EI/BMR < 1.14. Univariate and multiple linear regression models were used to test for associations between GI, GL, and BMI. The confounders were sex, age, smoking, physical activity, alcohol intake, and energy intake. All analyses were conducted on 1) the entire population and 2) a subsample excluding LERs. RESULTS: In the univariate analyses of the entire population, GL was inversely associated with BMI. No association was observed for GI. After full adjustment (including energy intake), both GI and GL were positively associated with BMI. When LERs were excluded, GL was positively associated with BMI in all analyses, and GI was positively associated with BMI in the multiple analyses. CONCLUSIONS: We showed a positive association between GI, GL, and BMI. Energy adjustment and the exclusion of LERs significantly affected the results of the analysis; thus, we stress the importance of energy adjustment.

Adult↗

PubMed2006

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors.

BACKGROUND: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. METHODS: In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. RESULTS: Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). CONCLUSION: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.

Adult↗

PubMed2006

Screen-detected diabetes, hypertension and hypercholesterolemia as predictors of cardiovascular mortality in five populations of Asian origin: the DECODA study.

BACKGROUND: The World Health Organization (WHO) predicts that the Asia Pacific region will experience an increase in cardiovascular disease (CVD) as a result of demographic changes and an increasing prevalence of diabetes. The aims of this study were to assess the predictive value of glucose tolerance status as a risk factor for CVD and identify a high-risk group for fatal CVD in population-based studies of Asians. DESIGN: A meta-analysis of five prospective cohort studies of Japanese and Asian Indian origin from five countries. METHODS: A total of 6573 subjects without a history of CVD from five prospective studies were followed for 5-10 years. Diabetes at baseline was diagnosed according to 1999 WHO criteria. Hazard ratios for death from CVD were estimated using a Cox proportional hazard model, adjusting for glucose tolerance status together with established risk factors for CVD. RESULTS: The meta-analysis showed that the overall hazard ratios (95% confidence interval) for CVD mortality corresponding to the presence of screen-detected diabetes, hypertension and hypercholesteremia were 3.42 (2.23-5.23), 1.57 (1.10-2.24) and 1.49 (1.05-2.10), respectively. Stratified multivariate analysis of the pooled data showed that subjects with screen-detected diabetes in the presence of hypertension or hypercholesteremia had the highest risk of CVD in individuals without previous CVD or diabetes. Subjects with screen-detected diabetes in the presence of hypertension or hypercholesteremia comprised 78% of CVD deaths that occurred in all subjects with screen-detected diabetes. CONCLUSIONS: The early detection of undiagnosed diabetes in hypertension or hypercholesteremia may have clinical and public health implications for the primary prevention of rapidly increasing diabetes-related atherosclerotic CVD in Asian populations.

Asia↗

PubMed2006

A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes.

Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp of the P2 promoter and the associated exon 1D of HNF4A for variations associated with diabetes in 114 patients with type 2 diabetes, 72 MODYX probands, and 85 women with previous gestational diabetes mellitus. A -192c/g mutation was found in five patients. We screened 1,587 diabetic subjects and 4,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total cholesterol compared with matched control subjects. Furthermore, the mutation disrupted the binding of an unidentified sequence-specific DNA binding complex present in human islet extracts. Also, two novel linked polymorphisms in the P2 promoter at positions -1107g/t and -858c/t were identified. These variants were not significantly associated with type 2 diabetes or any pre-diabetic traits. In conclusion, a rare, novel mutation that disrupts a protein binding site in the pancreatic HNF4A promoter associates with late-onset diabetes.

Adult↗

PubMed2006

The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility: the DAMAGE study.

The short-chain l-3-hydroxyacyl-CoA dehydrogenase (SCHAD) protein is involved in the penultimate step of mitochondrial fatty acid oxidation. Previously, it has been shown that mutations in the corresponding gene (HADHSC) are associated with hyperinsulinism in infancy. The presumed function of the SCHAD enzyme in glucose-stimulated insulin secretion led us to the hypothesis that common variants in HADHSC on chromosome 4q22-26 might be associated with development of type 2 diabetes. In this study, we have performed a large-scale association study in four different cohorts from the Netherlands and Denmark (n = 7,365). Direct sequencing of HADHSC cDNA and databank analysis identified four tagging single nucleotide polymorphisms (SNPs) including one missense variant (P86L). Neither the SNPs nor haplotypes investigated were associated with the disease, enzyme function, or any relevant quantitative measure (all P > 0.1). The present study provides no evidence that the specific HADHSC variants or haplotypes examined do influence susceptibility to develop type 2 diabetes. We conclude that it is unlikely that variation in HADHSC plays a major role in the pathogenesis of type 2 diabetes in the examined cohorts.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2006

Risk scores for type 2 diabetes can be applied in some populations but not all.

OBJECTIVE: Risk scores based on phenotypic characteristics to identify individuals at high risk of having undiagnosed diabetes have been developed in Caucasian populations. The impact of known risk factors on having undiagnosed type 2 diabetes differs between populations from different ethnic origin, and risk scores developed in Caucasians may not be applicable to other ethnic groups. This study evaluated the performance of one risk score in nine populations of diverse ethnic origin. RESEARCH DESIGN AND METHODS: Data provided by centers from around the world to the DETECT-2 project were used. The database includes population-based surveys with information on at least 500 people without known diabetes having a 75-g oral glucose tolerance test. To date, 52 centers have contributed data on 190,000 individuals from 34 countries. In this analysis, nine cross-sectional studies were selected representing diverse ethnic and regional backgrounds. The risk score assessed uses information on age, sex, blood pressure treatment, and BMI. RESULTS: This analysis included 29,758 individuals; 1,805 individuals had undiagnosed diabetes. The performance of the risk score varied widely, with sensitivity, specificity, and percentage needing further testing ranging between 12 and 57%, 72 and 93%, and 2 and 25%, respectively, with the worse performance in non-Caucasian populations. This variation in performance was related to differences in the association between prevalence of undiagnosed diabetes and components of the risk score. CONCLUSIONS: A typical risk score developed in Caucasian populations cannot be applied to other populations of diverse ethnic origins.

Body Mass Index↗

PubMed2006

Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study.

OBJECTIVE: Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events. RESEARCH DESIGN AND METHODS: In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR. RESULTS: Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were approximately 33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR. CONCLUSIONS: Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials.

Aged↗

PubMed2006

A multinational assessment of complications in type 1 diabetes: the DiaMond substudy of complications (DiaComp) level 1.

The objectives of this study were to describe the global geographic variation of microvascular and macrovascular complications in childhood onset type 1 diabetes (T1D) and to relate any such variation to diabetes care activities such as self blood glucose monitoring and intensive insulin therapy. The DiaComp study is a multinational (17 countries) cross-sectional study of complications in T1D (n=2,657). All participants were diagnosed at < 15 years of age and had a diabetes duration of 5-24 years when surveyed. Complications were assessed by self-report of physician diagnosis. Twenty-two centres in 17 countries achieved at least a 67% response rate and are included in the analyses. Central European centres exhibited high rates of retinopathy (Lithuania=31.6%, Romania=24.2%), laser treatment (Lithuania=25.4%) and neuropathy (Lithuania=29.9%, Romania=12.4%) in those with short duration of diabetes (5-15 years), as did Cuba for neuropathy (15.4%). For retinopathy the geographic variation in the short-duration group was also pronounced, ranging from 1.6% in Italy to 41.6% in Lithuania, and from 0% in Brazil, Italy and Australia, to 29.9% in Lithuania for laser treatment. Variation was less dramatic for the prevalence of complications in the long-duration group (15-25 years). Hypertension and duration were strong consistent predictors of all complications, while women had higher prevalence for half the complications (retinopathy, laser treatment and renal disease). Intensive insulin therapy and self-monitoring of blood glucose showed little association with prevalence of complications. In conclusion, this first population-based account of the geographic variation of T1D complications has demonstrated substantial variation. However, the healthcare practice variables that were measured contributed little toward explaining this variation.

Adolescent↗