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Biomedical subjects

Knut Borch-Johnsen

Publications and source records attributed to Knut Borch-Johnsen.

At least 55 records · Page 3Linked to original sources
PubMed2005

Model simulation of the patient flow through a screening centre for diabetic retinopathy.

PURPOSE: To construct a quantitative, flexible and simplified mathematical model of the patient flow through the Eye Clinic at the Steno Diabetes Centre (SDC) in order to enable rational dimensioning and assess the effects of modifications. METHODS: Patient data were drawn from the Eye Care database at the SDC. A simple patient flow model was constructed, allowing simultaneous adjustments of all variables, and the model was tested. Two scenarios were simulated: (1) adjusting the algorithm that assigns the follow-up intervals, and (2) increasing the population size to include all patients with diabetes in Copenhagen County. RESULTS: The model can describe the patient flow under steady state conditions, but is less precise in predicting transient changes with the present set-up. Accordingly all simulations were run for a substantial number of iterations. The two scenarios illustrate the usefulness of the model by calculating the required photographic examination capacity for the specific population, thereby allowing better estimations of future dimensioning of the organization. CONCLUSION: The study presents a patient flow model that can be used to illustrate the effects of proposed changes prior to their implementation, specifically with respect to the capacity of the system.

Algorithms↗
PubMed2005

A -30G>A polymorphism of the beta-cell-specific glucokinase promoter associates with hyperglycemia in the general population of whites.

A graded relationship has been reported between fasting and postprandial plasma glucose levels and the subsequent risk of cardiovascular morbidity and mortality. We hypothesized that the GCK -30G>A promoter polymorphism is associated with elevated glycemia in the middle-aged general population of whites, as well as with features of the World Health Organization (WHO)-defined metabolic syndrome. The GCK -30G>A polymorphism was genotyped in the population-based Inter99 study cohort (5,965 subjects) and in 332 nondiabetic subjects and 1,063 patients with type 2 diabetes. In the Inter99 cohort, the GCK -30A allele was associated with increased fasting (P < 0.001) and post-oral glucose tolerance test (OGTT) plasma glucose levels (P < 0.001), and in the same cohort, the GCK -30A allele was more frequent among 1,325 subjects with the metabolic syndrome than among 1,679 subjects without any components of the metabolic syndrome (P = 0.002). Moreover, the GCK -30A allele frequency was higher among 2,587 subjects with impaired glucose regulation (IGR) than among 4,773 glucose-tolerant subjects (17.3% [95% CI 16.2-18.3] vs. 15.0% [14.3-15.7], P < 0.001, odds ratio GG vs. GA 1.21 [1.08-1.36], GG vs. AA 1.62 [1.17-2.24]). In conclusion, the GCK -30G>A polymorphism associates with elevated fasting and post-OGTT glycemia in the middle-aged general population of whites, as well as with IGR and other features of the WHO-defined metabolic syndrome.

Adult↗
PubMed2005

Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene.

Previously, we have shown that a mutation in the mitochondrial DNA-encoded tRNA(Leu(UUR)) gene is associated with type 2 diabetes. One of the consequences of this mutation is a reduced aminoacylation of tRNA(Leu(UUR)). In this study, we have examined whether variants in the leucyl tRNA synthetase gene (LARS2), involved in aminoacylation of tRNA(Leu(UUR)), associate with type 2 diabetes. Direct sequencing of LARS2 cDNA from 25 type 2 diabetic subjects revealed eight single nucleotide polymorphisms. Two of the variants were examined in 7,836 subjects from four independent populations in the Netherlands and Denmark. A -109 g/a variant was not associated with type 2 diabetes. Allele frequencies for the other variant, H324Q, were 3.5% in type 2 diabetic and 2.7% in control subjects, respectively. The common odds ratio across all four studies was 1.40 (95% CI 1.12-1.76), P = 0.004. There were no significant differences in clinical variables between carriers and noncarriers. In this study, we provide evidence that the LARS2 gene may represent a novel type 2 diabetes susceptibility gene. The mechanism by which the H324Q variant enhances type 2 diabetes risk needs to be further established. This is the first report of association between an aminoacyl tRNA synthetase gene and disease. Our results further highlight the important role of mitochondria in glucose homeostasis.

Aged↗
PubMed2005

Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes.

We tested the hypothesis that variants in the gene encoding the prepropeptide YY (PYY) associate with type 2 diabetes and/or obesity. Mutation analyses of DNA from 84 patients with obesity and familial type 2 diabetes identified two polymorphisms, IVS3 + 68C>T and Arg72Thr, and one rare variant, +151C>A of PYY. The common allele of the Arg72Thr variant associated with type 2 diabetes with an allele frequency of the Arg allele of 0.667 (95% CI 0.658-0.677) among 4,639 glucose-tolerant subjects and 0.692 (0.674-0.710) among 1,326 patients with type 2 diabetes (P = 0.005, odds ratio 1.19 [95% CI 1.05-1.35]). The same polymorphism associated with overweight (25 < or = BMI < 30 kg/m2) (P = 0.018, 1.15 [1.02-1.28]). In quantitative trait analyses of a population-based sample of 6,022 subjects, the Arg allele was associated with an increased plasma glucose level 2 h after an oral glucose tolerance test (OGTT) (P = 0.03), an increased area under the curve for the post-OGTT plasma glucose level (P = 0.03), and a lower insulinogenic index (P = 0.01). In conclusion, the common Arg allele of the PYY Arg72Thr variant modestly associates with type 2 diabetes and with type 2 diabetes-related quantitative traits.

Arginine↗
PubMed2005

Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance: the Inter99 study.

OBJECTIVE: To examine the relationship between daily glycemic index, daily glycemic load, simple sugars, dietary fiber, and the prevalence of a measure of insulin resistance in 30- to 60-year-old nondiabetic Danish men and women. RESEARCH DESIGN AND METHODS: The Inter99 study is a nonpharmacological intervention study. We used baseline data and examined cross-sectional associations between carbohydrate-related dietary factors and an estimate of insulin resistance in 5,675 subjects at 30-60 years. The dietary intake was estimated from a self-administered food frequency questionnaire, and insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Multiple regressions were performed with HOMA-IR as the dependent variable and carbohydrate-related factors as explanatory variables. All models were adjusted for age, sex, smoking, physical activity, total energy intake, BMI, and waist circumference. RESULTS: Intake of lactose was positively associated with HOMA-IR (P < 0.0001), whereas daily glycemic load and intake of glucose, fructose, dietary fiber, total carbohydrate, fruit, and vegetables were inversely associated with HOMA-IR (P < 0.05). Intake of dietary fiber explained the associations with daily glycemic load and total carbohydrate and attenuated the association with fruit and vegetables. No significant associations were observed for daily glycemic index or sucrose. CONCLUSIONS: Habitual intake of diets with a high glycemic index and high glycemic load or diets with a high content of total carbohydrate including simple sugars was not associated with the probability of having insulin resistance. Furthermore, intake of dietary fiber was inversely associated with the probability of having insulin resistance.

Adult↗
PubMed2005

Diabetes among Inuit migrants in Denmark.

OBJECTIVES: The study aimed to estimate the prevalence of diabetes and impaired glucose intolerance (IGT) among Inuit migrants living in Denmark, and to compare with findings from Greenland. Further, we analyzed determinants for diabetes and impaired glucose metabolism. STUDY DESIGN: Cross-sectional, population-based epidemiological study. METHODS: This cross-sectional study included randomly selected Inuit migrants in Denmark aged 34 years and above. Diabetes and IGT were diagnosed using the oral glucose tolerance test. Body mass index (BMI) and waist circumference were measured, and blood samples were taken from each subject. Socio-demographic characteristics were investigated using a questionnaire. For comparison, data from the Greenland Population Study were used (n = 917). RESULTS: Of 506 eligible subjects, 256 (51%) participated. Twenty-six subjects had diabetes (10.2%) and twenty-eight had IGT (10.9%). Of those with diabetes, 64% had not been previously diagnosed. The prevalences of diabetes and IGT were not significantly different from those among Inuit in Greenland. Significant predictors of diabetes and impaired glucose metabolism (IGM) were found to be age, waist circumference and physical inactivity. The association between waist circumference and diabetes was significantly stronger among Inuit migrants in Denmark than among Inuit in Greenland. CONCLUSIONS: The prevalence of diabetes is high among the Inuit migrants in Denmark. However, unlike that reported in most studies, the prevalence was not significantly higher in the migrant population compared with the population of origin.

Adult↗
PubMed2004

Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity.

Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro(39)Pro and Ile(178)Ile) and three nonsynonymous variants (Ala(242)Ser, Arg(517)Cys, and Gly(532)Val). Furthermore, the rare Ala(242)Ser was identified in two families and showed partial cosegregation with obesity. The Pro(39)Pro, Ile(178)Ile, and Arg(517)Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg(517)Cys polymorphism allele prevalence was 11.4% [95% confidence interval (CI), 9.7-13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9-11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P = 0.037). In conclusion, it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity.

Adolescent↗
PubMed2004

Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes.

BACKGROUND: The aim of this study was to assess the level of urinary albumin excretion (microalbuminuria), which is associated with increased risk of coronary heart disease and death, in the population. Microalbuminuria has been suggested as an atherosclerotic risk factor. However, the lower cutoff level of urinary albumin excretion is unknown. It is also unknown whether impaired renal function confounds the association. METHODS AND RESULTS: In the Third Copenhagen City Heart Study in 1992 to 1994, 2762 men and women 30 to 70 years of age underwent a detailed cardiovascular investigation program, including a timed overnight urine sample. The participants were then followed up prospectively by registers until 1999 with respect to coronary heart disease and until 2001 with respect to death. During follow-up, 109 incident cases of coronary heart disease and 276 deaths were traced. A urinary albumin excretion above the upper quartile, ie, 4.8 microg/min, was associated with increased risk of coronary heart disease (RR, 2.0; 95% CI, 1.4 to 3.0; P<0.001) and death (RR, 1.9; 95% CI, 1.5 to 2.4; P<0.001) independently of age, sex, renal creatinine clearance, diabetes mellitus, hypertension, and plasma lipids. Lower levels of urinary albumin excretion were not associated with increased risk. CONCLUSIONS: Microalbuminuria, defined as urinary albumin excretion >4.8 microg/min (corresponding to approximately 6.4 microg/min during daytime), is a strong and independent determinant of coronary heart disease and death. Our suggestion is to redefine microalbuminuria accordingly and perform intervention studies.

Adult↗
PubMed2004

Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women.

BACKGROUND: Few studies have evaluated the associations between the metabolic syndrome (by any definition) and mortality. This study examined the age- and sex-specific prevalence of the metabolic syndrome and its association with all-cause and cardiovascular mortality in nondiabetic European men and women. METHODS: The study was based on 11 prospective European cohort studies comprising 6156 men and 5356 women without diabetes and aged from 30 to 89 years, and had a median follow-up of 8.8 years. A modification of the World Health Organization definition of the metabolic syndrome was used. The subjects were considered to have the metabolic syndrome if they had hyperinsulinemia and 2 or more of the following: obesity, hypertension, dyslipidemia, or impaired glucose regulation; however, other definitions were also studied. Hazard ratios for all-cause and cardiovascular mortality were estimated with Cox models in each cohort. Meta-analyses were performed to assess the overall association of the metabolic syndrome with mortality risk. RESULTS: The age-standardized prevalence of the metabolic syndrome was slightly higher in men (15.7%) than in women (14.2%). Of the 1119 deaths recorded during follow-up, 432 were caused by cardiovascular disease. The overall hazard ratios for all-cause and cardiovascular mortality in persons with the metabolic syndrome compared with persons without it were 1.44 (95% confidence interval [CI], 1.17-1.84) and 2.26 (95% CI, 1.61-3.17) in men and 1.38 (95% CI, 1.02-1.87) and 2.78 (95% CI, 1.57-4.94) in women after adjustment for age, blood cholesterol levels, and smoking. CONCLUSIONS: The overall prevalence of the metabolic syndrome in nondiabetic adult Europeans is 15%. Nondiabetic persons with the metabolic syndrome have an increased risk of death from all causes as well as cardiovascular disease.

Adult↗
PubMed2004

Prevention of type 2 diabetes: issues and strategies for identifying persons for interventions.

Because of the ongoing worldwide diabetes epidemic and new evidence that type 2 diabetes can be prevented or delayed, we are compelled to implement prevention efforts. Health policy makers need to bridge the evidence gap left by prevention trials that did not include all groups at risk for developing diabetes. Intensive interventions may be appropriate for groups with similar risk as those studied in clinical trials, while less intense efforts may be considered for those groups that have not been studied. Factors such as structure of the health care system and individual social and economic situations may influence the implementation of prevention efforts. Currently, no universally validated and well-tested method exists to identify all people at high risk for developing diabetes. However, groups that will be targeted for prevention efforts can be identified through several reasonable strategies.

Clinical Trials as Topic↗
PubMed2004

Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy.

OBJECTIVES: To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria. DESIGN: Double-blind, randomized, controlled trial of 4.8 years. SETTING: Out-patient setting. PATIENTS: A total of 8206 with hypertension and left ventricular hypertrophy. INTERVENTIONS: Losartan or atenolol, supplemented with diuretics and/or calcium antagonists to reach blood pressure < 140/90 mmHg MAIN OUTCOME MEASURES: The urine albumin/creatinine ratio, and the primary composite endpoint (CEP) of CV death, myocardial infarction, and stroke. RESULTS: The blood pressure was reduced similarly on losartan (30.2/16.6 mmHg) versus atenolol (29.1/16.8 mmHg). The risk of a primary CEP increased linearly from the lowest to the highest decile of baseline albuminuria. The benefits of losartan versus atenolol for the primary CEP and for stroke tended to be more pronounced among patients above the median value for baseline albuminuria (urine albumin/creatinine ratio, 1.28 mg/mmol). The decrease in albuminuria was significantly greater with losartan versus atenolol throughout the study (a decrease from baseline to year 2 of 33% losartan versus 25% atenolol). One-fifth of the difference in favor of losartan on the primary CEP was explained by the greater reduction in albuminuria on losartan. CONCLUSIONS: Baseline albuminuria is a powerful risk factor for CV events. Baseline albuminuria did not identify the group of patients with greatest benefit on losartan versus atenolol in LIFE. Reduction in albuminuria explained one-fifth of the benefits of losartan versus atenolol.

Aged↗
PubMed2004

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

Studies have shown that albuminuria is associated with increased risk for cardiovascular events. We tested the relationship between albuminuria (UACR) and cardiovascular risk in 8206 hypertensive patients with left ventricular hypertrophy included in the LIFE Study. Follow-up was 39,122 patient years. The risk for the primary composite cardiovascular end point increases continuously from the lowest to the highest decile of baseline UACR. No specific threshold could be identified. In conclusion, albuminuria predicts the outcome in the LIFE Study. The risk for cardiovascular morbidity and mortality among hypertensive patients with left ventricular hypertrophy increases at much lower UACR than has been reported in diabetic patients.

Albuminuria↗
PubMed2004

Screening for diabetic retinopathy using a digital non-mydriatic camera compared with standard 35-mm stereo colour transparencies.

PURPOSE: To investigate the use of a digital non-mydriatic camera for determining the ETDRS clinical level of diabetic retinopathy, and to evaluate its use in a screening setting to appropriately determine the need for referral to an ophthalmologist (ETDRS level > or = 35). METHODS: A total of 83 patients with diabetes were photographed with and without pharmacological pupil dilation at an ophthalmology department using a digital non-mydriatic camera, obtaining two sets of five non-stereoscopic, 45 degree field images of each eye. ETDRS seven standard field, 35-mm stereoscopic colour fundus photographs were also obtained. A subgroup of 59 patients was photographed at an optician's shop using the digital non-mydriatic camera without pupil dilation. RESULTS: There was substantial agreement between the clinical level of diabetic retinopathy assessed from the 35-mm photographs and the digital images: the ophthalmology department (kappa = 0.76) with pupil dilation and (kappa = 0.66) without pupil dilation, respectively, and at the optician's (kappa = 0.60 without pupil dilation). With respect to the need for referral to an ophthalmologist, there was almost perfect agreement in the ophthalmology department (kappa = 0.88) with pupil dilation and (kappa = 0.84) without pupil dilation, respectively, and those taken at the optician's (kappa = 0.87 without pupil dilation). CONCLUSION: A digital non-mydriatic camera may be used in a screening situation to appropriately determine the need for referral to an ophthalmologist (ETDRS level > or = 35).

Adult↗
PubMed2004

Diabetic retinopathy screening using digital non-mydriatic fundus photography and automated image analysis.

PURPOSE: To investigate the use of automated image analysis for the detection of diabetic retinopathy (DR) in fundus photographs captured with and without pharmacological pupil dilation using a digital non-mydriatic camera. METHODS: A total of 83 patients (165 eyes) with type 1 or type 2 diabetes, representing the full spectrum of DR, were photographed with and without pharmacological pupil dilation using a digital non-mydriatic camera. Two sets of five overlapping, non-stereoscopic, 45-degree field images of each eye were obtained. All images were graded in a masked fashion by two readers according to ETDRS standards and disagreements were settled by an independent adjudicator. Automated detection of red lesions as well as image quality control was made: detection of a single red lesion or insufficient image quality was categorized as possible DR. RESULTS: At patient level, the automated red lesion detection and image quality control combined demonstrated a sensitivity of 89.9% and specificity of 85.7% in detecting DR when used on images captured without pupil dilation, and a sensitivity of 97.0% and specificity of 75.0% when used on images captured with pupil dilation. For moderate non-proliferative or more severe DR the sensitivity was 100% for images captured both with and without pupil dilation. CONCLUSION: Our results demonstrate that the described automated image analysis system, which detects the presence or absence of DR, can be used as a first-step screening tool in DR screening with considerable effectiveness.

Area Under Curve↗
PubMed2004

Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus.

Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.

Animals↗