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. DESIGN: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. RESULTS: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10-9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10-9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. CONCLUSION: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.

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). RESULTS: In patients with type 2 diabetes, the genetic risk scores for pulse pressure were positively associated with plaque formation ( ß = 0.036 ± 0.01 standard deviation/allele, p = 0.003). The genetic risk score for diastolic blood pressure was negatively associated with carotid intima-media thickness ( ß = -0.037 ± 0.01 standard deviation/allele, p = 0.005), although not significant after correction for multiple testing ( p < 0.0042). In a meta-analysis of individuals with and without type 2 diabetes, the high-density lipoprotein genetic risk scores showed a trend towards an inverse association with carotid intima-media thickness and plaques, while the low-density lipoprotein genetic risk scores showed a trend towards a positive association with plaque formation but did reach the statistical threshold. CONCLUSION: Genetic loci for pulse pressure are associated with plaque formation among patients with type 2 diabetes, suggesting an underlying genetic contribution to arterial stiffening and atherosclerosis.

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. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. A systematic literature search was performed in PubMed, Embase, SwedMed, PsycInfo and CINAHL in accordance with the inclusion and exclusion criteria. RESULTS: Five motor function tests were identified. The Alberta Infant Motor Scale (AIMS) exclusively assesses motor function, the Harris Infant Neuromotor Assessment also assesses cognition and the Early Motor Questionnaire (EMQ) additionally assesses perception-action integration skills. The Ages and Stages Questionnaire (ASQ) and The Brigance Infant and Toddler Screen include further aspects of development. All test methods, except for the AIMS, are based on parent involvement. CONCLUSIONS: For implementation in the DPCHEP, five motor function tests were potentially adequate. However, the time consumption and extensive use of tools render three of the five tests unsuitable for implementation in the existing programme. The two remaining tests, the ASQ and the EMQ, are parent questionnaires. We suggest that these should be pilot tested with a view to their subsequent implementation in the DPCHEP. It may be considered to present the test elements in a more manageable and systematic way, possibly with illustrations.

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. METHODS: We evaluated individuals who were all 60 years old and participated in The Glostrup Population Study. Subclinical atherosclerosis was diagnosed based on the ultrasonographic measurement of intima-media thickness (IMT) and protruding plaques in the right carotid artery. Associations between cardiovascular traits and the levels of pSP-D (n = 687) or two coding SFTPD SNPs rs3088308 and rs721917 (n = 396) were investigated using multiple linear regressions and logistic regressions. RESULTS: There was no significant association between pSP-D and the presence of plaques or IMT. The SFTPD SNP rs3088308 was nominally associated with the presence of plaques, and rs721917 was nominally associated with IMT. The directions of effects of associations were markedly dependent on current smoking status. CONCLUSIONS: The results do not support that pSP-D levels influence the development of subclinical atherosclerosis. However, the SFTPD SNP data support previous observations from animal studies that SP-D plays a role in the etiology of atherosclerotic disease development. The nominal significant effects are likely to be mediated by structural variant SP-D modulation of effects of tobacco smoking and are independent of pSP-D levels. The data warrant confirmation in larger cohorts.

[Organization of treatment and control of type 2 diabetic patients]. / Organisation af behandling og opfølgning af patienter med type 2-diabetes.

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. Patients receiving oral GC treatment at diagnosis were compared with the other patients. Of 1369 patients, 35 (2.6%) were treated with oral GCs at diabetes diagnosis. At that point, patients on GC therapy were older (69.9 versus 65.3 years, p = 0.007, sex-adjusted) and tended to have lower BMI (26.1 versus 29.1 kg/m(2) , p = 0.023), also 6 years after diagnosis (24.8 versus 28.4, p = 0.011), than patients not being treated with GCs. In a univariate Cox regression model, GC treatment at diagnosis increased all-cause mortality with a hazard ratio (95% confidence interval) of 2.01 (1.39-2.89, p = 0.0002, n = 1369), while this decreased to 1.41 (0.98-2.04, p = 0.065, n = 1369) when adjusted for age and sex and to 1.39 (0.92-2.11, p = 0.12, n = 1086) when risk factors, complications and cancer were added to the model. Apart from differences in age and overweight, patients in this relatively small sample of those diagnosed with clinical type 2 diabetes during GC treatment were comparable at diagnosis and during 14 years of follow-up with those not treated with GCs, including with regard to the adjusted mortality rate.

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. The central coordinating centre randomly selected five patients from each practice. Patient characteristics were assessed including medical history, anthropometric measures, quality indicators, UKPDS-risk engine, psychological and general well-being. RESULTS: We included 103 participants from 22 GPs in 11 countries. Central data and laboratory samples were successfully collected. Of the participants 54% were female, mean age was 66 years and mean duration of diabetes was 9.6 years. Besides, 18% were using insulin, 31% had a history of cardiovascular disease, mean HbA1c was 7.1% (range 6.6-8.0), mean systolic blood pressure was 133.7 mmHg (range 126.1-144.4) and mean total cholesterol was 4.9 mmol/l (range 4.0-6.2). CONCLUSION: A European study on care and complications in a random selection of people with T2DM is feasible. There are large differences in indicators of metabolic control and wellbeing between countries.

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. The changes in levels of HbA(1c) were described by HbA(1c) at diagnosis and a regression line fitted to the HbA(1c) measurements after 1-year follow-up for each patient. The predictive effect of patient characteristics for changes in HbA(1c) was investigated in a multivariate mixed model. RESULTS: During the first year after diabetes diagnosis, HbA(1c) dropped to near normal average level and then started rising almost linearly. A sharp rise in long-term glycaemic level was observed in approximately a quarter of the patients, especially the relatively young. Of 581 patients, 156 (26.9%) patients, however, experienced a fall in HbA(1c) after 1-year follow-up and another quarter showed constant or only slowly rising HbA(1c). The changes in levels of HbA(1c) were only predicted by diagnostic HbA(1c) and age. CONCLUSIONS: During the first 6 years after the diagnosis of clinical type 2 diabetes, changes in levels of HbA(1c) show considerable inter-individual variability with age as the only long-term predictor. The results indicate that it is important to monitor changes in HbA(1c) more closely and intensify treatment of those often relatively young patients who actually experience the beginning of an apparently relentless deterioration of their glycaemic control.

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. DESIGN: Prospective population study started in 1976 with follow-up in 1981, 1987, and 1996. SETTING: Suburban area of Copenhagen. SUBJECTS: A total of 1198 individuals born in 1936. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Among participants with two consecutive SRH ratings the mortality rate per 1000 observation years was 7.6 (95% CI 6.4; 8.9), 8.5 (95% CI 7.1; 10.2), and 8.9 (95% CI 6.4; 10.3) after the 45-, 51-, and 60-year examination. Decline in SRH between two time-points was in bivariate Cox regression analyses associated with an increased mortality risk, the association increasing as participants grew older. Multivariate analysis of the effect of changes of SRH on mortality gave similar results: hazard ratios for declined SRH were (reference: "unchanged good") 1.55 (95% CI 0.93-2.58), 1.96 (95% CI 1.09-3.53), and 2.22 (95% CI 0.97-5.09) at the 40-45, 45-51, and 51-60-year intervals. However, unchanged poor and improved SRH (at the 40-45-year interval) were also associated with an increase, and additional analyses showed that just rating SRH as poor at one rating was associated with increased risk. CONCLUSION: Changes in SRH are associated with higher mortality risks than unchanged good SRH.

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. RESULTS: At the age of 40 years, 153 (14.6%) of 1,045 participants reported poor and 85.4% good SRH. Dead participants totalled 36 at the 10-year, 96 at the 20-year, and 207 at the 29-year follow-up. For poor SRH, mortality hazard ratios (multivariate analysis) were persistently significant, but slowly declining with follow-up time. The time-heterogeneous models explain this feature: increased mortality risk was significant only in the first decade after assessment: 2.30 (95% CI 1.11-4.78) vs. 0.91 (95% CI 0.36-2.31) and 0.73 (95% CI 0.34-1.55). CONCLUSIONS: The association between poor SRH and mortality emphasizes the importance of health personnel taking account of people's health rating, particularly when a recent assessment has been made. SRH is related to death, even when controlling for known covariates, but it is not a long-term effect.

[Validation of methods to identify known diabetes on the basis of health registers]. / Validering af metoder til identifikation af erkendt diabetes på basis af administrative sundhedsregistre.

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. MATERIALS AND METHODS: Patients with diabetes residing in Aarhus County on 31 December 2003 were identified by data from The National Patient Registry, The National Health Insurance Service Registry, the prescription database and the laboratory database in the county. RESULTS: This study identified a total of 8,802 patients with a diagnosis of diabetes which was confirmed by the patients' general practitioners (GP). This corresponds to a prevalence of 2.32% (95% CI: 2.27%2.37%). The national algorithm found 86% of this diabetes population while the regional algorithm found 96%. The sensitivity was increased to 91% by supplementing with information of dispensed prescriptions for anti-diabetics in the national algorithm. The positive predictive value was 89% for the national algorithm as well as for the regional algorithm. CONCLUSION: The national algorithm may be used as a tool for establishing a national diabetes database. Despite a higher sensitivity, the regional algorithm cannot currently be recommended at a national level as it depends on the collection of person-related data which are not available nationally at the present time.

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 <7.8 mmol/l were used for model development and internal validation. Data from an additional 28 individuals were used for external validation. Bergman's minimal model was used to calculate S(I), and the trapezoidal method was used to calculate AIR(0-8 min). Multiple linear regression was applied to derive predictive equations of log(S(I)) and log(AIR(0-8 min)) using data on sex, BMI, plasma glucose, and serum insulin levels obtained during the OGTT. RESULTS: We demonstrate that it is possible to obtain estimates of S(I) (BIGTT-S(I)) and AIR (BIGTT-AIR) that are highly correlated to IVGTT-derived values of S(I) (R(2) = 0.77) and AIR (R(2) = 0.54). In the two validation datasets we obtained similar results. CONCLUSIONS: Data from OGTTs can provide accurate measures of insulin sensitivity and beta-cell function, which can be used in large scale metabolic, genetic, and epidemiological studies.

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.

[Effects of new treatment criteria and goals in patients with high blood pressure in general practice]. / Effekten af nye behandlingskriterier og -mål hos patienter med forhøjet blodtryk i en almen praksis.

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). For the remaining 172 patients, the blood pressure in 1998 and 2003 was found in the case record. The results of physical examinations, risk factors, morbidity rates and treatment were registered. RESULTS: In 1998, the average blood pressure in the study cohort was 157/89 mmHg. By 2003, it had fallen to 141/84 mmHg. The difference in both systolic and diastolic blood pressure was statistically significant (p < 0.001). In 1998, 27 percent of the hypertensive patients in the cohort had reached the target value (< or = 140/90 mmHg). This percentage rose to 55 percent in 2003. The pattern of examinations concerning tracking down risk factors was markedly altered in the period. Pharmacological treatment had substantially increased during the period, with many more patients being treated with more than one drug. CONCLUSION: This study indicates that the introduction of new guidelines has caused considerable changes in the detection, risk evaluation and treatment of hypertension.

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. METHODS: A cross-sectional, population-based study of 1136 patients newly diagnosed with T2DM by their GP. Our main outcomes were how well the GPs' knew their patients (questionnaire) and centralized analysis of glycosylated haemoglobin A(1c). Multivariate linear regression models were used to allow adjustment for confounding variables. RESULTS: GPs classified how well they knew their patients as being not well for 13.5% (153/1136) of their patients, as fairly well for 38.6% (438/1136) and as very well for 48.0% (545/1136). Patients whom the GPs classified as not knowing well had relatively high glycaemic levels compared with levels among other patients, a finding that was confirmed in multivariate linear regression models. CONCLUSIONS: Our data show that the glycaemic level among patients whom the GP characterize as knowing well or fairly well is relatively low compared with among patients whom the GP characterize as not knowing well. We suggest that this reflects a late diagnosis in these patients, and that GPs should be especially aware of undiagnosed T2DM among patients whom they do not know well.

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. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial hypertension were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of hypertension and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for hypertension compared with Gly/X carriers (P=0.001). In conclusion, the Ser allele of PGC-1alpha Gly482Ser confers a significantly reduced risk of hypertension in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women.

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. In the separate analyses, the K allele of the KCNJ11 Glu(23)Lys associated with type 2 diabetes (odds ratio, 1.19; P = 0.0002), whereas the PPARG Pro(12)Ala showed no significant association with type 2 diabetes. The combined analysis indicated that the two polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and we found no evidence for a synergistic interaction between them. Analysis of a model with equal additive effects of the two variants showed that the odds ratio for type 2 diabetes increased with 1.14/risk allele (P = 0.003). Together, the two polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. In conclusion, our results showed no evidence of a synergistic interaction between the KCNJ11 Glu(23)Lys and PPARG Pro(12)Ala polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes.

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.

Individualised treatment goals in diabetes care.

OBJECTIVES: To examine 1) patients' characteristics according to the treatment goal chosen at diabetes diagnosis, and 2) the association between individualised goals for glycated haemoglobin (HbA1c), blood pressure (BP) and lipids, and the risk factor level subsequently achieved. DESIGN: Follow-up study embedded in a multifaceted intervention study directed at doctors encouraging individualised goal-setting in newly diagnosed diabetic patients aged > or = 40 years. SETTING: General practice. SUBJECTS: In all, 243 general practitioners and 674 patients participated. MAIN OUTCOME MEASURES: Risk factors for diabetic complications. RESULTS: Relatively young age, low diagnostic plasma glucose, low BMI, a moderate or high level of physical activity and normoalbuminuria were associated with a treatment goal of good control at diagnosis. After 5 years, median HbA1c was 8.2%, 8.6% and 8.0% in patients with a goal of good, acceptable and poor control, respectively. Patients with a goal of good control versus those with a goal of acceptable control had a lower HbA1c level in a regression analysis adjusted for age, sex, HbA1c at diagnosis, BMI, total cholesterol, fasting triglycerides, BP, physical activity, smoking status and diabetes duration. We found no association between goals and the level of BP and lipids. CONCLUSION: Doctors tend to pursue normoglycaemia in relatively young patients with low blood glucose, low BMI, high activity level and normoalbuminuria. Patients for whom a goal of normoglycaemia was chosen at diagnosis achieved favourable glycaemic control at 5-year follow-up. Whether doctors choosing the goals were good at predicting future glycaemic control, or whether goal-setting is an important motivational factor in achieving optimal glycaemic control needs to be explored.