Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity.

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity.

Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies.

Genetic determinants of blood pressure traits are associated with carotid arterial thickening and plaque formation in patients with type 2 diabetes.

Objectives: The aim of this study is to explore the contribution of genetically driven cardiometabolic risk factors for development of carotid arterial thickening in patients with type 2 diabetes.

Methods: In total, 12 genetic risk scores for blood pressure, blood lipids and glycaemic traits were constructed. The genetic risk scores were tested for association with carotid intima-media thickness and plaques in patients with type 2 diabetes ( n = 401) and in non-diabetic individuals ( n = 648) and for association with glucose levels in two population-based cohorts ( n = 1328 and n = 6161).

Motor function tests for 0-2-year-old children - a systematic review.

Introduction: There is no evidence on how motor function is best evaluated in children in a low-risk setting. The method used in the Danish Preventive Child Health Examination Programme (DPCHEP) in general practise has not been validated. The objective of this review was to identify existing motor function tests for 0-2-year-old children that were validated for use in the background population and which are suitable for use in the DPCHEP.

Association between the surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis.

Objective: Surfactant protein D (SP-D) is a defense collectin with inflammation-modulating properties. SP-D deficiency inhibits atherosclerosis in vivo, and the circulatory SP-D levels have been previously associated with cardiovascular disease mortality. We hypothesized that plasma SP-D (pSP-D) and SP-D gene (SFTPD) single nucleotide polymorphisms (SNPs) are risk factors for atherosclerosis.

[Organization of treatment and control of type 2 diabetic patients].

The organization of treatment and control of type 2 diabetic patients in Denmark has undergone a major development within the last decade. From being based on local hospital guidelines, treatment and control have moved towards a more organized collaboration between primary and secondary care based on common national guidelines. Quality indicators from primary and secondary care are collected routinely, and gradually an increasingly precise depiction is documented in the National Indicator Project.

Patients newly diagnosed with clinical type 2 diabetes during oral glucocorticoid treatment and observed for 14 years: all-cause mortality and clinical developments.

Chronic exposure to glucocorticoids (GCs) has many side effects including glucose intolerance and diabetes and may accelerate the occurrence of cardiovascular disease and increase mortality. We studied the 14-year clinical development of diabetes in patients diagnosed with diabetes during GC treatment. A population-based sample of 1369 people newly diagnosed with clinical type 2 diabetes underwent a clinical examination at diagnosis, and surviving patients were followed up 6 and 14 years later.

The European EUCCLID pilot study on care and complications in an unselected sample of people with type 2 diabetes in primary care.

Background: European studies on quality of diabetes care in an unselected primary care diabetes population are scarce.

Research Question: To test the feasibility of the set-up and logistics of a cross-sectional EUropean study on Care and Complications in patients with type 2 diabetes (T2DM) in Primary Care (EUCCLID) in 12 European countries.

Method: One rural and one urban practice from each country participated.

Changes in levels of haemoglobin A1c during the first 6 years after diagnosis of clinical type 2 diabetes.

Objective: To assess the variability in levels of glycosylated haemoglobin (HbA(1c)) during the first six years after diagnosis of clinical type 2 diabetes in relation to possible predictors.

Material And Methods: Data were from a population-based sample from general practice of 581 newly diagnosed diabetic patients aged 40 or over. Estimation of HbA(1c) was centralized.

Incidence and remission of specific IgE aeroallergen sensitization from age of 40 to 60 years, and association with alcohol consumption.

Background: Data on incidence and long-term persistence of IgE aeroallergen sensitization in older adults are limited. Alcohol consumption is a strong immune-modulator with a significant impact on the IgE response.

Objectives: We aimed to assess the incidence and remission of aeroallergen sensitization from the age of 40 to 60 years.

The impact of changes in self-rated general health on 28-year mortality among middle-aged Danes.

Objective: Self-rated general health (SRH) predicts future mortality. SRH may change, and these changes may alter the mortality risk. All-cause mortality until the age of 68 and its association with changes in SRH from the age of 40-45, 45-51, and 51-60 years was examined in a cohort of Danes.

Self-rated general health among 40-year-old Danes and its association with all-cause mortality at 10-, 20-, and 29 years' follow-up.

Aims: Self-rated general health (SRH) predicts future mortality. We examined all-cause mortality at 10, 20, and 29 years' follow-up and its association with SRH measured at the age of 40 years in a cohort of 1,198 healthy Danes born in 1936 and who were residents in suburban Copenhagen.

Methods: The association between SRH (dichotomized into good versus poor) and all-cause mortality was estimated in standard time-homogenous Cox regression models adjusting for covariates related to mortality, and in time-heterogeneous Cox regression models without covariate adjustment, where time-heterogeneity features as a separate risk assessment for each of the three follow-up periods defined by the follow-up examinations.

[Validation of methods to identify known diabetes on the basis of health registers].

Introduction: In 2003 the government introduced a national diabetes plan. One of the recommendations was to establish a national diabetes database targeted at monitoring the prevalence of diabetes and quality of diabetes care. The aim of this study is to validate a national algorithm for identification of known diabetes and compare the results with the results from the use of a regional algorithm.

The BIGTT test: a novel test for simultaneous measurement of pancreatic beta-cell function, insulin sensitivity, and glucose tolerance.

Objective: Insulin resistance and impaired beta-cell function are key elements in the pathogenesis of type 2 diabetes. We aimed to develop valid algorithms for estimation of the insulin sensitivity index (S(I)) and acute insulin response (AIR) derived from simple and cheap physiological measurements that could be used in large-scale metabolic, genetic, and epidemiological studies.

Research Design And Methods: For our purpose, data from an oral glucose tolerance test (OGTT) (18 samples during 240 min) and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) (33 samples during 180 min) from 258 individuals with fasting plasma glucose <7 mmol/l and 2-h plasma glucose <7.

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.

[Effects of new treatment criteria and goals in patients with high blood pressure in general practice].

Introduction: This study examined the changes in detection and treatment of hypertension in a rural general practice after the introduction of new guidelines for treatment of hypertension published in 1999 by the Danish Hypertension Society.

Materials And Methods: Data from all patients in practice diagnosed with hypertension on 1 October 1998 were registered (n = 200). By 1 October 2003, 28 patients had left the cohort due to death (n = 26) or moving to other parts of the country (n = 2).

Association of a microsatellite in FASL to type II diabetes and of the FAS-670G>A genotype to insulin resistance.

Type II diabetes is caused by a failure of the pancreatic beta-cells to compensate for insulin resistance leading to hyperglycaemia. There is evidence for an essential role of an increased beta-cell apoptosis in type II diabetes. High glucose concentrations induce IL-1beta production in human beta-cells, Fas expression and concomitant apoptosis owing to a constitutive expression of FasL.

General practitioners may diagnose type 2 diabetes mellitus at an early disease stage in patients they know well.

Background: Continuity of care may not only save time and money for the health care system, but may also be beneficial for the individual patient. How well GPs know their patients may potentially lead to an early diagnosis of a slowly progressive chronic disease like type 2 diabetes mellitus (T2DM). The aim of this paper is to investigate this hypothesis.

Studies of relationships between the GLUT10 Ala206Thr polymorphism and impaired insulin secretion.

Aims: This study aimed to investigate if the previously observed association between the GLUT10 Ala206Thr polymorphism and variation in fasting and oral glucose-induced serum insulin concentrations could be replicated in a large-scale population-based cohort of Danish whites.

Methods: The GLUT10 Ala206Thr polymorphism was genotyped in a case-control study of 880 Type 2 diabetic patients and 4372 glucose-tolerant control subjects. The latter group was also enrolled in an assessment of fasting and post-OGTT circulating levels of plasma glucose and serum insulin in relation to genotype.

Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity.

Background: Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) is a recently identified homologue of the tissue specific coactivator PGC-1alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1alpha is involved in adipogenesis, mitochondrial biogenesis, fatty acid beta oxidation, and hepatic gluconeogenesis.

Methods: We studied variation in the coding region of human PPARGC1B in Danish whites and related these variations to the prevalence of obesity and type 2 diabetes in population based samples.

Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.

The separate and combined effects of the PPARG Pro(12)Ala polymorphism and the KCNJ11 Glu(23)Lys polymorphisms on risk of type 2 diabetes were investigated in relatively large-scale, case-control studies. Separate effects of the variants were examined among 1187/1461 type 2 diabetic patients and 4791/4986 middle-aged, glucose-tolerant subjects. The combined analysis involved 1164 type 2 diabetic patients and 4733 middle-aged, glucose-tolerant subjects.

PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites.

PGC-1alpha is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of PGC-1alpha has previously shown association with arterial hypertension among Austrian men.

Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population.

Aims/hypothesis: The hepatocyte nuclear factor (HNF)-4alpha is an orphan nuclear receptor, which plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion. The gene encoding HNF-4alpha (HNF4A) is located on chromosome 20q12-q13 in a region that in several studies has shown linkage with type 2 diabetes. Recently, two independent studies identified single nucleotide polymorphisms (SNPs) in a 90-kb region spanning HNF4A, which showed strong association with type 2 diabetes in the Finnish and Ashkenazi Jewish populations.

Routine diagnosis of Type 2 diabetes mellitus in general practice and hospitals: how do patients differ?

Objective: To study how Type 2 diabetic patients diagnosed by routine case-finding in primary care differ from patients diagnosed in secondary care with regard to clinical characteristics, symptom-burden and prevalence of complications.

Research Design And Methods: A Danish population-based sample of 1633 newly diagnosed Type 2 diabetic patients, of whom we had detailed information of sociodemographic and clinical characteristics, biochemical measurements, and complications among 1381. Blood and urine analyses were centralized.