PubMed Health⌕ Search

Biomedical subjects

Jacqueline M Dekker

Publications and source records attributed to Jacqueline M Dekker.

At least 19 recordsLinked to original sources
PubMed2006

Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study.

Alanine aminotransferase (ALT) is a marker of non-alcoholic fatty liver disease (NAFLD) and predicts incident type 2 diabetes mellitus (DM2). Recently, ALT was shown to be also associated with endothelial dysfunction and carotid atherosclerosis. We studied the predictive value of ALT for all-cause mortality, incident cardiovascular disease (CVD) and coronary heart disease (CHD) events in a population-based cohort of Caucasian men and women aged 50-75 years, at baseline. The 10-year risk of all-cause mortality, fatal and non-fatal CVD and CHD events in relation to ALT was assessed in 1439 subjects participating in the Hoorn Study, using Cox survival analysis. Subjects with prevalent CVD/CHD and missing data were excluded. As compared with the first tertile, the age- and sex-adjusted hazard ratios (95% confidence intervals) for all-cause mortality, CVD events and CHD events were 1.30 (0.92-1.83), 1.40 (1.09-1.81) and 2.04 (1.35-3.10), respectively, for subjects in the upper tertile of ALT. After adjustment for components of the metabolic syndrome and traditional risk factors, the association of ALT and CHD events remained significant for subjects in the third relative to those in the first tertile, with a hazard ratio of 1.88 (1.21-2.92) and 1.75 (1.12-2.73), respectively. In conclusion, the predictive value of ALT for coronary events, seems independent of traditional risk factors and the features of the metabolic syndrome in a population-based cohort. Further studies should confirm these findings and elucidate the pathophysiological mechanisms.

Aged↗
PubMed2006

Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study.

OBJECTIVE: The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention. METHODS AND RESULTS: In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75]; P interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained approximately 43% of the increase in cardiovascular mortality risk conferred by T2D. CONCLUSIONS: These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients.

Aged↗
PubMed2006

Are retinal microvascular abnormalities associated with large artery endothelial dysfunction and intima-media thickness? The Hoorn Study.

It has been hypothesized that microvascular dysfunction affects endothelial dysfunction of the large arteries, which may explain the relationship of microvascular disease with macrovascular disease. The aim of the present study was to investigate the relationship of retinal microvascular disorders with endothelium-dependent FMD (flow-mediated vasodilatation) and carotid IMT (intima-media thickness). A total of 256 participants, aged 60-85 years, 70 with normal glucose metabolism, 69 with impaired glucose metabolism and 109 with Type II diabetes, were included in this study. All participants were ophthalmologically examined, including funduscopy and two field 45 degrees fundus photography, and were graded for retinal sclerotic vessel abnormalities and retinopathy. Retinal arteriolar and venular diameters were measured with a computer-assisted method. Brachial artery, endothelium-dependent FMD and carotid IMT were assessed ultrasonically as measurements of endothelial function and early atherosclerosis respectively. After adjustment for age, sex and glucose tolerance status, retinal vessel diameters, retinal sclerotic vessel abnormalities and retinopathy were not significantly associated with FMD. In contrast with other retinal microvascular abnormalities, retinal venular dilatation was associated with increased IMT [standardized beta value (95% confidence interval), 0.14 (0.005-0.25)]. This association was attenuated and lost statistical significance after adjustment for cardiovascular risk factors, in particular after correction for fasting insulin. In the present study, retinal microvascular disorders are not independently associated with impaired FMD. In addition, retinal venular dilatation is associated with increased IMT, although non-significantly after multivariable adjustment for cardiovascular risk factors. Therefore our data provide evidence that retinal microvascular disease is of limited value in risk stratification for future cardiovascular events.

Aged↗
PubMed2006

Sagittal abdominal diameter: no advantage compared with other anthropometric measures as a correlate of components of the metabolic syndrome in elderly from the Hoorn Study.

BACKGROUND: The sagittal abdominal diameter has been proposed as a useful measure by which to estimate abdominal obesity and as being more strongly related to components of the metabolic syndrome than are other anthropometric measures. OBJECTIVE: The objective was to study which anthropometric measure (ie, sagittal abdominal diameter, waist circumference, waist-to-hip ratio, waist-to-height ratio, or body mass index) is the strongest correlate of components of the metabolic syndrome (ie, glucose and lipid concentrations and blood pressure) in the elderly. DESIGN: The Hoorn Study is a population-based cohort study in older Dutch men and women. Cross-sectional data were analyzed. Age-adjusted Pearson correlations of anthropometric measures with components of the metabolic syndrome were calculated in 826 subjects (389 men, 437 women) aged 56-83 y. Analyses were performed with adjustment for age and stratification for sex and age (<65 or >/=65 y). RESULTS: No single anthropometric measure was consistently correlated more strongly with components of the metabolic syndrome than were the other measures in either men or women. The associations were generally stronger in younger subjects than in older subjects and in women than in men. For example, the correlation between sagittal abdominal diameter and postload glucose was 0.35 (P < 0.001) in younger and 0.14 (P = 0.051) in older men, and the correlation between waist circumference and postload glucose was 0.33 (P < 0.001) in older women and 0.14 (P = 0.062) in older men. CONCLUSION: The use of sagittal abdominal diameter has no advantages over simpler and more commonly used anthropometric measures such as the waist circumference in older men and women.

Abdominal Fat↗
PubMed2006

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

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

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2006

Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women: the hoorn study.

OBJECTIVE: Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS: The Hoorn Study is a cohort study among Caucasians, aged 50-75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS: Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23-1.18) in men and 0.15 (0.06-0.39) in women for type 2 diabetes and 0.90 (0.51-1.61) and 0.28 (0.16-0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32-1.91] and 0.62 [0.21-1.81]) and with IGM (1.20 [0.61-2.35] and 0.48 [0.26-0.90]), respectively. CONCLUSIONS: A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes.

Adiponectin↗
PubMed2005

Endothelial dysfunction contributes to renal function-associated cardiovascular mortality in a population with mild renal insufficiency: the Hoorn study.

Mildly impaired renal function is associated with cardiovascular morbidity and mortality. There are indications that endothelial dysfunction and/or chronic inflammation, which play an important role in atherothrombosis, are present in early stages of renal insufficiency. This study investigated whether and to which extent endothelial dysfunction and inflammation were related to renal function and contributed to renal function-associated cardiovascular mortality in a population-based cohort (n = 613), aged 50 to 75 yr, that was followed with a median duration of 12.5 yr. During follow-up, 192 individuals died (67 of cardiovascular causes). At baseline, renal function was estimated with serum creatinine, the Cockcroft-Gault formula, and the Modification of Diet in Renal Disease equation of GFR (eGFR). Endothelial function was estimated by plasma von Willebrand factor, soluble vascular cell adhesion molecule-1, and the urinary albumin-creatinine ratio. Inflammatory activity was estimated by plasma C-reactive protein and soluble intercellular adhesion molecule-1. Renal function was mildly impaired (mean eGFR 68 +/- 12 ml/min per 1.73 m(2)) and independently associated with von Willebrand factor (standardized beta -0.09; 95% confidence interval [CI] -0.18 to -0.002; P < 0.05), soluble vascular cell adhesion molecule-1 (standardized beta -0.14; 95% CI -0.22 to -0.05; P < 0.01), and albumin-creatinine ratio (standardized beta -0.15; 95% CI -0.23 to -0.08; P < 0.001) but not with markers of inflammatory activity. Renal function was inversely associated with cardiovascular and all-cause mortality. The relative risk for cardiovascular mortality but not all-cause mortality associated with renal function decreased from 1.22 to 1.12 per 5 ml/min per 1.73 m(2) decrease of eGFR after adjustment for markers of endothelial dysfunction. In conclusion, endothelial dysfunction was related to renal function and contributed to the excess in cardiovascular mortality in this population-based cohort with mild renal insufficiency.

Aged↗
PubMed2005

An exploratory analysis of criteria for the metabolic syndrome and its prediction of long-term cardiovascular outcomes: the Hoorn study.

Studies have shown an increased risk of cardiovascular outcomes with the metabolic syndrome, but information on predictive properties of the National Cholesterol Education Program Adult Treatment Panel 3 (NCEP) criteria is sparse. The authors used data from the Hoorn population-based study in the Netherlands including 2,484 participants aged 50-75 years examined in 1989 and followed for cardiovascular morbidity and mortality through 2000 to assess NCEP criteria, excluding known diabetes or cardiovascular disease. Cluster analyses explored whether NCEP identifies a mixture of heterogeneous groups. For each gender, participants meeting NCEP criteria seemed to be divided into clusters distinguished primarily by triglycerides or high density lipoprotein cholesterol. Cutpoints for components predicting cardiovascular events using classification and survival tree methodology varied by endpoint and gender, but Cox model hazards ratios were relatively comparable regardless of cutpoints (range: 1.3-2.5). Clear gradation in risk of cardiovascular outcomes was evident with increasing number of components, with statistically elevated risk for >or=3 (NCEP) components in men but for >or=2 components in women. Exploratory analyses of alternative metabolic syndrome criteria suggest cardiovascular risk estimates comparable to those derived by using NCEP, but criteria evaluating risk on more of a continuum would potentially allow consideration of alternative definitions by gender or for patients with other risk factors.

Aged↗
PubMed2005

Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study.

BACKGROUND: Different definitions of the metabolic syndrome have been proposed. Their value in a clinical setting to assess cardiovascular disease (CVD) risk is still unclear. We compared the definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP), World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), and American College of Endocrinology (ACE) with respect to the prevalence of the metabolic syndrome and the association with 10-year risk of fatal and nonfatal CVD. METHODS AND RESULTS: The Hoorn Study is a population-based cohort study. The present study population comprised 615 men and 749 women aged 50 to 75 years and without diabetes or a history of CVD at baseline in 1989 to 1990. The prevalence of the metabolic syndrome at baseline ranged from 17% to 32%. The NCEP definition was associated with about a 2-fold increase in age-adjusted risk of fatal CVD in men and nonfatal CVD in women. For the WHO, EGIR, and ACE definitions, these hazard ratios were slightly lower. Risk increased with the number of risk factors. Elevated insulin levels were more prevalent in subjects with multiple risk factors, but metabolic syndrome definitions including elevated insulin level were not more strongly associated with risk. CONCLUSIONS: The metabolic syndrome, however defined, is associated with an approximate 2-fold increased risk of incident cardiovascular morbidity and mortality in a European population. In clinical practice, a more informative assessment can be obtained by taking into account the number of individual risk factors.

Aged↗
PubMed2005

Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women.

OBJECTIVE: In small case-control studies, obesity was associated with worse vitamin D status. Our aim was to assess the association of adiposity (anthropometric measures as well as dual energy x-ray absorptiometry) with serum 25-hydroxyvitamin D (25-OH-D) and serum PTH levels in a large population-based study including older men and women. METHODS: Subjects were participants of the Longitudinal Aging Study Amsterdam and were aged 65 yr and older. In 453 participants, serum 25-OH-D and PTH were determined, and body mass index, waist circumference, waist to hip ratio, sum of skin folds, and total body fat percentage by dual energy x-ray absorptiometry were measured. RESULTS: After adjustment for potential confounders, higher body mass index, waist circumference, and sum of skin folds were statistically significantly associated with lower 25-OH-D (standardized beta values were -0.136, -0.137, and -0.140, respectively; all P < 0.05) and with higher PTH (0.166, 0.113, and 0.114, respectively; all P < 0.05). Total body fat percentage was more strongly associated with 25-OH-D and PTH (-0.261 and 0.287, respectively; both P < 0.001) compared with anthropometric measures. Total body fat percentage remained associated with 25-OH-D after adjustment for PTH, and with PTH after adjustment for 25-OH-D. CONCLUSION: Precisely measured total body fat is inversely associated with 25-OH-D levels and is positively associated with PTH levels. The associations were weaker if anthropometric measures were used, indicating a specific role of adipose tissue. Regardless of the possible underlying mechanisms, it may be relevant to take adiposity into account when assessing vitamin D requirements.

Adipose Tissue↗
PubMed2005

Diabetes-related symptoms and negative mood in participants of a targeted population-screening program for type 2 diabetes: The Hoorn Screening Study.

OBJECTIVE: To determine the level of diabetes-related symptom distress and its association with negative mood in subjects participating in a targeted population-screening program, comparing those identified as having type 2 diabetes vs. those who did not. RESEARCH DESIGN AND METHODS: This study was conducted within the framework of a targeted screening project for type 2 diabetes in a general Dutch population (age 50-75 years). The study sample consisted of 246 subjects, pre-selected on the basis of a high-risk profile; 116 of whom were subsequently identified as having type 2 diabetes, and 130 who were non-diabetic subjects. Diabetes-related symptom distress and negative mood was assessed approximately 2 weeks, 6 months, and 12 months after the diagnosis of type 2 diabetes, with the Type 2 Diabetes Symptom Checklist and the Negative well-being sub scale of the Well-being Questionnaire (W-BQ12), respectively. RESULTS: Screening-detected diabetic patients reported significantly greater burden of hyperglycemic (F = 6.0, df = 1, p = 0.015) and of fatigue (F = 5.3, df = 1, p = 0.023) symptoms in the first year following diagnosis type 2 diabetes compared to non-diabetic subjects. These outcomes did not change over time. The total symptom distress (range 0-4) was relatively low for both screening-detected diabetic patients (median at approximately 2 weeks, 6 months, and 12 months; 0.24, 0.24, 0.29) and non-diabetic subjects (0.15, 0.15, 0.18), and not significantly different. No average difference and change over time in negative well-being was found between screening-detected diabetic patients and non-diabetic subjects. Negative well-being was significantly positive related with the total symptom distress score (regression coefficient beta = 2.86, 95% CI 2.15-3.58). CONCLUSIONS: The screening-detected diabetic patients were bothered more by symptoms of hyperglycemia and fatigue in the first year following diagnosis type 2 diabetes than non-diabetic subjects. More symptom distress is associated with increased negative mood in both screening-detected diabetic patients and non-diabetic subjects.

Affect↗
PubMed2005

Opposite contributions of trunk and leg fat mass with plasma lipase activities: the Hoorn study.

OBJECTIVE: Lipoprotein lipase (LPL) and hepatic lipase (HL) are essential in hydrolysis of triglyceride-rich lipoproteins. LPL activity is negatively, whereas HL activity is positively, associated with total body fat. We determined the associations of trunk and leg fat mass with plasma LPL and HL activities in a cross-sectional study. RESEARCH METHODS AND PROCEDURES: LPL and HL activities were determined in post-heparin plasma in a sample of 197 men and 209 women, 60 to 87 years of age. A total body DXA scan was performed to determine trunk and leg fat mass. RESULTS: In women, but not in men, trunk fat mass was negatively associated with LPL activity, whereas leg fat mass was positively associated, after mutual adjustment and adjustment for age. Standardized betas (95% confidence interval) for trunk and leg fat mass were -0.24 (-0.41; -0.08) and 0.14 (-0.02; 0.31), respectively (interaction by sex, p = 0.03). Larger trunk fat mass was associated with higher HL activity in men [0.48 (0.28; 0.68)] and women [0.40 (0.24; 0.56)]. A negative association of leg fat mass and HL activity was observed in men, although not statistically significant [-0.13 (-0.33; 0.06)], and in women [-0.28 (-0.38; -0.18)]. DISCUSSION: Abdominal fat is associated with unfavorable and femoral fat with favorable LPL and HL activities in plasma.

Abdominal Fat↗
PubMed2005

Interactions of dietary fat intake and the hepatic lipase -480C-->T polymorphism in determining hepatic lipase activity: the Hoorn Study.

BACKGROUND: Gene-nutrient interactions affecting hepatic lipase (HL) activity may contribute to the interindividual variability of the cardiovascular disease risk associated with dietary fat intake. OBJECTIVE: We determined the associations of dietary fat intake with postheparin HL activity and the possible modifying effect of the HL -480C-->T polymorphism on these associations. DESIGN: Subjects were recruited from participants in the 2000-2001 follow-up examination of the Hoorn Study. HL activity was determined in postheparin plasma in a sample of 211 men and 218 women aged 60-87 y. Information about dietary intake of the participants was obtained with a validated food-frequency questionnaire. Linear regression was performed, adjusted for age. RESULTS: Total dietary fat was positively associated with HL activity (standardized beta: 0.11; 95% CI: 0.02, 0.21), and this association was also seen for saturated fat (0.10; 0.01, 0.20) and monounsaturated fatty acid (0.10; 0.01, 0.19). We observed a significant interaction of the HL polymorphism with the relation between total fat intake and HL activity. The association of total fat with HL activity was stronger in subjects with CT (0.27; 0.11, 0.43) and TT (0.39; -0.22, 1.00) genotypes than in subjects with the CC genotype (0.06; -0.06, 0.18; P for interaction < 0.10). The interaction remained statistically significant in models that included age, sex, carbohydrate and protein intakes, and insulin or body mass index. CONCLUSIONS: Higher intakes of total and saturated fat were positively associated with higher HL activity. In addition, the observed association of total fat with HL activity was modified by the HL-480C-->T polymorphism, after adjustment for age, sex, carbohydrate and protein intakes, and insulin or body mass index.

Aged↗
PubMed2005

Mild renal insufficiency is associated with increased left ventricular mass in men, but not in women: an arterial stiffness-related phenomenon--the Hoorn Study.

BACKGROUND: Mild renal insufficiency has recently been recognized as an important risk factor for cardiovascular disease (CVD). The mechanisms underlying this association are incompletely understood. Increased left ventricular mass (LVM) is an independent risk factor for CVD, which is particularly common in end-stage renal disease (ESRD) and which has been shown to be associated with mild renal insufficiency. Increased arterial stiffness has also been shown to be an independent risk factor for CVD in ESRD and has also been associated with mild renal insufficiency. We hypothesized that the association between mild renal insufficiency and increased LVM could be mediated through increased arterial stiffness, and that this may be one of the pathways linking mild renal insufficiency to CVD. We therefore investigated, in a cross-sectional population-based study, the influence of increased arterial stiffness on the association between renal function and LVM. METHODS: The study population consisted of 742 elderly individuals (373 men and 369 women). Renal function was estimated by the serum creatinine level in micromol/L; by the Cockcroft-Gault formula in mL/min and by the Modification of Diet in Renal Disease (MDRD) formula. LVM was obtained by echocardiography. RESULTS: The mean estimates of renal function in men and women were, respectively, 103.7 (SD 17.0) and 86.8 (SD 11.2) micromol/L for the serum creatinine level; 63.4 (SD 12.9) and 61.4 (SD 11.0) mL/min/1.73 m(2) for the Cockcroft-Gault formula; and 59.7 (SD 10.8) and 60.9 (SD 10.5) mL/min per 1.73 m(2) for the MDRD formula. LVM was 93.1 (SD 26.4) g/m(2) in men and 86.7 (SD 22.3) g/m(2) in women. In men, impaired renal function, as estimated by the Cockcroft-Gault and the MDRD formula, was significantly associated with greater LVM after adjustment for age, glucose tolerance, hypertension, and prior CVD [regression coefficient beta (95% CI), 1.28 (0.22 to 2.33) g/m(2) and 1.63 (0.41 to 2.86) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. However, the association between impaired renal function and increased LVM was not statistically significant after adjustment for arterial stiffness estimates [regression coefficient beta (95% CI), 0.02 (-1.60 to 1.64) g/m(2) and 0.54 (-1.25 to 2.33) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. In women, impaired renal function was not significantly associated with greater LVM. CONCLUSION: Our study shows that in a general elderly population, even mild impairment of renal function is associated with adverse changes in left ventricular structure. In men, but not in women, this leads to greater LVM, a process that may be related to increases in arterial stiffness. Importantly, these novel findings suggest that such changes occur early in the process of renal functional deterioration, which may explain, in part, the increase in cardiovascular risk in men with mildly impaired renal function.

Aged↗
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

Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies.

OBJECTIVE: This meta-analysis was undertaken to obtain insight regarding the shape and strength of the relationship between alcohol consumption and the risk of type 2 diabetes, the effects of adjustment for confounders, and the effect of modification by type 2 diabetes definition, sex, and BMI. RESEARCH DESIGN AND METHODS: The 15 original prospective cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average, were followed for 12 years. RESULTS: After pooling the data, a U-shaped relationship was found. Compared with nonconsumers, the relative risk (RR) for type 2 diabetes in those who consumed </=6 g/day alcohol was 0.87 (95% CI 0.79-0.95). For the moderate consumption ranges of 6-12, 12-24, and 24-48 g/day, RRs of 0.70 (0.61-0.79), 0.69 (0.58-0.81), and 0.72 (0.62-0.84) were found, respectively. The risk of type 2 diabetes in heavy drinkers (>/=48 g/day) was equal to that in nonconsumers (1.04 [0.84-1.29]). In general, nonsignificant trends for larger RR reduction associated with moderate alcohol consumption were observed for women compared with men, for crude compared with multivariate-adjusted analyses, and for studies that used self-reports instead of testing for type 2 diabetes definition. No differences in RR reductions were found between individuals with low or high BMI. CONCLUSIONS: The present evidence from observational studies suggests an approximately 30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction is observed in consumers of >/=48 g/day.

Alcohol Drinking↗