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Biomedical subjects

Knut Borch-Johnsen

Publications and source records attributed to Knut Borch-Johnsen.

At least 73 records · Page 4Linked to original sources
PubMed2004

Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites.

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130). The IL6R gene maps to an important candidate locus for type 2 diabetes on chromosome 1q21. An Asp358Ala polymorphism of the IL6R has been reported to associate with obesity in Pima Indians. We investigated the Asp358Ala polymorphism in relation to type 2 diabetes, obesity, and other pre-diabetic quantitative traits among Danish whites. By applying a recessive genetic model in a case-control study of 1,349 type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a significant difference in genotype distribution (P = 0.008) and in allele frequency (Ala-allele 38.3% [95% CI 36.5-40.1] in diabetic subjects vs. 41.2% [40.2-42.2] in control subjects; P = 0.007). The odds ratio for the Asp/Asp carriers versus Ala/Ala carriers was 1.38 (1.09-1.71). Among 4,251 middle-aged glucose-tolerant subjects, the Asp358Ala polymorphism was not associated with estimates of obesity, post-oral glucose tolerance test serum insulin release, or the homeostasis model assessment of insulin resistance index. In conclusion, the Asp358Ala polymorphism of the IL6R associates with type 2 diabetes in Danish whites.

Amino Acid Substitution↗
PubMed2004

A Danish diabetes risk score for targeted screening: the Inter99 study.

OBJECTIVE: To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing. RESEARCH DESIGN AND METHODS: A population-based sample (Inter99 study) of 6,784 individuals aged 30-60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression. RESULTS: The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (P<0.05) associated with the presence of previously undiagnosed diabetes. The area under the receiver operating curve was 0.804 (95% CI 0.765-0.838) for the first half of the Inter99 population, 0.761 (0.720-0.803) for the second half of the Inter99 population, and 0.803 (0.721-0.876) for the ADDITION pilot study. The sensitivity, specificity, and percentage that needed subsequent testing were 76, 72, and 29%, respectively. The false-negative individuals in the risk score had a lower absolute risk of ischemic heart disease compared with the true-positive individuals (11.3 vs. 20.4%; P<0.0001). CONCLUSIONS: We developed a questionnaire to be used in a stepwise screening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.

Adult↗
PubMed2004

A multinational comparison of complications assessment in type 1 diabetes: the DiaMond substudy of complications (DiaComp) level 2.

OBJECTIVE: To describe the global geographic variation of micro- and macrovascular complications in childhood-onset type 1 diabetes assessed by both reported and measured disease and risk factors and relate any such variation to diabetes control and health care activities. RESEARCH DESIGN AND METHODS: The DiaComp study is a multinational (17 countries) cross-sectional study of complications in type 1 diabetes and is comprised of two levels (level 1 includes survey only and level 2 includes survey plus examination). This report concerns level 2, representing 12 countries (n = 892). All participants were diagnosed at <15 years of age and had a diabetes duration of 5-24 years when surveyed. All complications were assessed by self-report and for microalbuminuria by Micral II dipstick, neuropathy by the Michigan Neuropathy Screening Instrument exam, and hypertension using the Hypertension Detection and Follow-up Program (HDFP) protocol. HbA(1c) was determined by using the DCA analyzer. RESULTS: A wide variation in neuropathy, reported renal disease/proteinuria, and hypertension among those of short diabetes duration was noted, with central Europe (Romania and Lithuania) standing out for both self-reported renal disease and measured microalbuminuria and for both self-reported and examined neuropathy. The Caribbean (Puerto Rico) also had high rates of microalbuminuria and examined neuropathy. For those of long duration, variation was more moderate. We found generally good agreement between the reported and clinically determined measures for neuropathy (r = 0.5, P = 0.01) and hypertension (r = 0.61, P = 0.001) as demonstrated by the high overall correlation between examination and self-report for these two complications. However, the agreement between examination and self-report for renal disease/proteinuria was less, with low overall correlation (r = -0.05, P = 0.86) and incongruous centers (Slovakia and Finland). Geographic variation in prevalence was not consistently explained for all complications, even with strong independent prediction by systolic blood pressure, although the variation in microalbuminuria was largely accounted for by self-monitored blood glucose, which was significantly protective. CONCLUSIONS: This report has identified wide variation and geographic patterns in complication prevalence, with a further indication that self-report is generally in agreement with examined prevalence, though less for renal disease/proteinuria. However, this level of DiaComp, with more complete assessment of risk factors and health care practice, was still not able to completely explain the variation in complication prevalence, except for microalbuminuria.

Asia↗
PubMed2003

Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study.

BACKGROUND: Several studies have shown that albuminuria is associated with increased risk for fatal and nonfatal cardiovascular events, independent of conventional risk factors. The partition values for urine albumin-creatinine ratio (UACR) used to identify microalbuminuria have been based on studies that predicted risk in diabetic patients. OBJECTIVE: To determine whether the relation between albuminuria and cardiovascular risk can be used to predict cardiovascular morbidity and mortality in hypertensive patients. DESIGN: Multicenter cohort study derived from a randomized, controlled trial. PATIENTS: 8206 patients with stage II or III hypertension randomly assigned to double-blind therapy with losartan or atenolol. Follow-up was 39 122 patient-years. MEASUREMENTS: Renal glomerular permeability evaluated by UACR. RESULTS: In nondiabetic hypertensive patients with left ventricular hypertrophy, the risk for the composite cardiovascular end point increased continuously as albuminuria increased (P < 0.001 for trend). There was no specific threshold for increased risk. For every 10-fold increase in UACR, hazard ratios in nondiabetic patients increased as follows: composite end point, by 57% (95% CI, 40.6% to 75.0%); cardiovascular mortality, by 97.7% (CI, 66.5% to 235%); all-cause mortality, by 75.2% (CI, 54.0% to 99.4%); stroke, by 51.0% (CI, 28.8% to 76.9%); and myocardial infarction, by 45% (CI, 19.9% to 75.4%) (P < 0.001 for all comparisons). Values were similar in diabetic patients, although for myocardial infarction the trend was weaker and not significant. CONCLUSION: Increased UACR resulted in increasing risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy. We found no thresholds or plateaus. Risk increases at much lower UACR values than has been reported among diabetic patients.

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PubMed2003

Effect of losartan on sudden cardiac death in people with diabetes: data from the LIFE study.

In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, a major reduction of all-cause mortality--especially cardiovascular mortality--in patients with diabetes with left ventricular hypertrophy was reported for treatment with losartan. We postulated post hoc that losartan might have a better effect on sudden cardiac death than atenolol, and we aimed to test this hypothesis. 44 patients with diabetes died of sudden cardiac death; significantly fewer deaths arose in the losartan group (14) than in the atenolol group (30; p=0.027). In the losartan group, five (6%) of 86 patients with diabetes and atrial fibrillation during the trial died of sudden cardiac death compared with nine (2%) of 500 in those without atrial fibrillation. The respective figures for the atenolol group were 14 (13%) of 105 and 16 (3%) of 504. Our results suggest losartan affords better protection against cardiac death from arrhythmias for patients with diabetes mellitus than does atenolol. Importantly, our analyses were exploratory and require confirmation.

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PubMed2003

[Guidelines on diagnosis of type 2 diabetes. Investigation, diagnosis and glucose measurement].

World wide the prevalence of type 2 diabetes is increasing and 30-50% of patients are undiagnosed. Early detection and intervention may decrease the risk of late diabetic complications, and thus clear guidelines for early detection and diagnosis of type 2 diabetes are needed. We recommend those individuals with either previous gestational diabetes; obesity (BMI > 30 kg/m2) and/or two or more relatives with diabetes should be considered eligible for testing for diabetes. In order to make the diagnosis two diabetic glucose values on separate days are required. The diagnosis may be made using plasma glucose or capillary whole blood, but quality control measures are essential for glucose measurements in general practice as well as in departments of clinical biochemistry.

Blood Glucose↗
PubMed2003

Increased transvascular low density lipoprotein transport in insulin dependent diabetes: a mechanistic model for development of atherosclerosis.

BACKGROUND: The increased risk of atherosclerosis associated with diabetes cannot be explained by conventional cardiovascular risk factors alone. We hypothesized that transvascular lipoprotein transport may be increased in patients with diabetes, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis. METHODS: We used an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 24 patients with insulin dependent diabetes mellitus (type 1) and in 30 healthy controls. LDL was individually sampled and autologous 131-iodinated LDL was reinjected intravenously in addition to 125-iodinated albumin, and the 1-h fractional escape rates were taken as indices of transvascular transport. RESULTS: Transvascular LDL transport was 5.7+/-2.2 and 4.0+/-1.8%/h in patients with diabetes and controls (P<0.005); equivalent values for albumin were 6.8+/-2.5 and 5.4+/-2.0%/h (P<0.05). This difference most likely was not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, nephropathy, statin use, or different plasma insulin levels in diabetes patients. CONCLUSION: Transvascular LDL transport may be increased in patients with type 1 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with type 1 diabetes, possibly explaining accelerated development of atherosclerosis.

Adult↗
PubMed2003

Mutational analysis of the UCP2 core promoter and relationships of variants with obesity.

OBJECTIVE: To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain. RESEARCH METHODS AND PROCEDURES: The human UCP2 promoter was characterized by reporter gene analysis in cell lines derived from skeletal muscle, white adipose tissue, and embryonic tissue. We analyzed the core promoter for polymorphisms in 60 obese subjects. A prevalent polymorphism, the -866 G/A variant, was investigated for association with obesity in 749 men obese as young adults and 816 men of the same age representing the background population. Genotype-phenotype interaction studies were performed in two other population-based samples: one group of middle-aged-to-elderly Danish subjects (mean age, 53 years; range, 30 to 88 years) and one group of 60-year-old Danish subjects. RESULTS: The region up to -1202 bp relative to the UCP2 transcription initiation site gave rise to the highest promoter activity. Eight mutations in this region were identified comprising -866 G/A, -850 G/A, -337 G/C, -41 G/T, -28 insertion T, -5 insertion (cactgcgaagccc), +45 C/T, and +53 G/C, but none of these was associated with consistent alterations in BMI, body fat content, weight gain, or fasting levels of plasma glucose and serum insulin. DISCUSSION: Variation of the UCP2 promoter including the single common variant (-866 A/G) is not associated with obesity or obesity-related intermediary phenotypes in Danish subjects.

Adipose Tissue↗
PubMed2003

The prevalence and incidence of visual impairment in people of age 20-59 years in industrialized countries: a review.

BACKGROUND: Reviews on the prevalence of blindness and low vision in persons of age 20 to 59 years are lacking. We have therefore carried out a review based on a Medline search. METHODS: The review was confined to epidemiological studies performed in Western Europe, North America and Australia covering the age group 20 to 59 years where there were comparable definitions of blindness and low vision according to the IAPB and WHO classification of blindness and low vision. RESULTS: Three surveys, four register studies and two studies based on multiple sources matched our selection criteria. Blindness and low vision are described separately. Blindness: Only one study, based on multiple sources, covered the whole age group 20 to 59 years. In this study the overall prevalence of blindness was 0.08%. The prevalence of blindness was 0.04% among those 20-39 years old, whereas in the age group 40-59 years it was 0.1% in two surveys and one study on multiple sources. However, the prevalence was higher, 0.5% among whites and 0.7% among colored, in The Baltimore Eye Study. The definition of blindness was similar in all three studies. Low vision: Three studies provided data on the prevalence of low vision in the age group 20-59 years, although the number of cases was very small. In one study the prevalence of a visual acuity < or = 6/24 to 6/48 was 0.07% and in another the prevalence was 0.17% using < 6/18 to 0.5/60. No person with low vision was found in the third study. CONCLUSIONS: The existing epidemiological data on blindness and low vision among adults aged 20 to 59 years are insufficient. Epidemiological studies based on multiple sources are needed for the study of rare conditions such as blindness and low vision.

Adult↗
PubMed2003

Evidence for an association between the Leu162Val polymorphism of the PPARalpha gene and decreased fasting serum triglyceride levels in glucose tolerant subjects.

The aim of the study was to investigate whether genetic variation in the peroxisome proliferator-activated receptor-alpha (PPARalpha) is associated with type 2 diabetes and altered lipid or carbohydrate metabolism in glucose tolerant subjects. Mutation analyses of PPARalpha were performed in 56 type 2 diabetic patients. Six variants were identified: IVS3 + 76T>C, IVS3-19C>T, IVS4 + 35C>T, Leu162Val, Arg178Gly and Ala268Val. In a case-control study comprising 738 type 2 diabetic patients and 524 glucose tolerant subjects, the three exon variants did not show any significant differences in allele frequencies between type 2 diabetic patients and control subjects. The functional Leu162Val polymorphism was further investigated in genotype-phenotype studies involving 340 young, healthy subjects and 502 middle-aged glucose tolerant subjects. The young, healthy subjects who were heterozygous for the Leu162Val variant had, on average, a 20% decrease in fasting serum triglyceride levels (P=0.014). This finding was replicated in middle-aged subjects (P=0.023). The Leu162Val polymorphism was not related to alterations in insulin sensitivity, insulin release or level of glycaemia. In conclusion, the Leu162Val polymorphism of PPARalpha is associated with a decreased level of fasting serum triglyceride in glucose tolerant white subjects.

Adult↗
PubMed2003

European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts).

Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organisations--European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific task force. The ESC Committee for practice guidelines (CPG) supervises and coordinates the preparation of new guidelines and expert consensus documents produced by task forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements.

Adult↗
PubMed2003

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

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.

Adult↗
PubMed2003

The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes.

The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release. In a study comprising 519 unrelated glucose-tolerant subjects, we addressed the question as to whether the E23K variant was related to reduced serum insulin release during an oral glucose tolerance test (OGTT). Furthermore, the polymorphism was examined in a case-control study comprising 803 type 2 diabetic patients and 862 glucose-tolerant control subjects. The E23K variant was associated with significant reductions in the insulinogenic index (P = 0.022) and serum insulin levels under the response curve during an OGTT (0-120 min) (P = 0.014) as well as with an increase in BMI (P = 0.013). In the present study, the association of the E23K polymorphism with type 2 diabetes was not significant (P = 0.26). However, the K23K genotype significantly associated with type 2 diabetes in a meta-analysis of white case and control subjects (n = 2,824, odds ratio [OR] 1.49, P = 0.00022). In conclusion, the widespread E23K polymorphism may have a diabetogenic effect by impairing glucose-induced insulin release and increasing BMI.

Amino Acid Substitution↗
PubMed2003

Genetic variation of the GLUT10 glucose transporter (SLC2A10) and relationships to type 2 diabetes and intermediary traits.

The SLC2A10 gene encodes the GLUT10 facilitative glucose transporter, which is expressed in high amounts in liver and pancreas. The gene is mapped to chromosome 20q12-q13.1, a region that has been shown to be linked to type 2 diabetes. The gene was examined in 61 Danish type 2 diabetic patients, and a total of six variants (-27C-->T, Ala206Thr, Ala272Ala, IVS2 + 10G-->A, IVS4 + 18T-->G, and IVS4 + 26G-->A) were identified and investigated in an association study, which included 503 type 2 diabetic patients and 510 glucose-tolerant control subjects. None of the variants were associated with type 2 diabetes. Interestingly, carriers of the codon 206 Thr allele had 18% lower fasting serum insulin levels (P = 0.002) and 20% lower insulinogenic index (P = 0.03) than homozygous carriers of the Ala allele. These results suggest that variation in the coding region of SLC2A10 does not contribute substantially to the pathogenesis of type 2 diabetes in the examined study population. However, the codon 206 polymorphism may be related to the interindividual variation in fasting and oral glucose-induced serum insulin levels.

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