The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects.
CONTEXT: Hepatic lipase plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein by involvement in reverse cholesterol transport and the formation of atherogenic small dense low-density lipoprotein. OBJECTIVES: The objective was to investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped in the Inter99 study (n = 6070), the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n = 8662), and in additional type 2 diabetic patients (n = 1,064) and glucose-tolerant control subjects (n = 360). RESULTS: In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039-0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 x 10(-10)) supported by association in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers. CONCLUSIONS: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A allele. This interaction may have potential implications for public health and disease prevention.
BACKGROUND: A high prevalence of impaired glucose tolerance and unknown type 2-diabetes in patients with coronary heart disease and no previous diagnosis of diabetes have been reported. The aims of the present study were to investigate the prevalence of abnormal glucose regulation (AGR) 3 months after an acute ST-elevation myocardial infarction (STEMI) in patients without known glucometabolic disturbance, to evaluate the reliability of a 75-g oral glucose tolerance test (OGTT) performed very early after an acute STEMI to predict the presence of AGR at 3 months, and to study other potential predictors measured in-hospital for AGR at 3 months. METHODS: This was an observational cohort study prospectively enrolling 224 STEMI patients treated with primary PCI. An OGTT was performed very early after an acute STEMI and was repeated in 200 patients after 3 months. We summarised the exact agreement observed, and assessed the observed reproducibility of the OGTTs performed in-hospital and at follow up. The patients were classified into glucometabolic categories defined according to the World Health Organisation criteria. AGR was defined as the sum of impaired fasting glucose, impaired glucose tolerance and type 2-diabetes. RESULTS: The prevalence of AGR at three months was 24.9% (95% CI 19.1, 31.4%), reduced from 46.9% (95% CI 40.2, 53.6) when measured in-hospital. Only, 108 of 201 (54%) patients remained in the same glucometabolic category after a repeated OGTT. High levels of HbA1c and admission plasma glucose in-hospital significantly predicted AGR at 3 months (p
Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data.
Research Centre, Centre hospitalier de l'Université de Montréal-Hôtel-Dieu, Department of Medicine, University of Montreal, 3850 St. Urbain Street, Rm 8-202, Montreal, Quebec H2W 1T7, Canada. email@example.com
The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired glucose tolerance is associated with a significant risk reduction in the development of diabetes, hypertension and cardiovascular complications. Kaiser and Sawicki have accused the investigators of the STOP-NIDDM Trial of major biases in the conduct of the study, of manipulating the data and of conflict of interest. The aim of this paper is to present data and explanations refuting these allegations. In the STOP-NIDDM Trial, 61 subjects were excluded from the efficacy analysis before unblinding for legitimate reasons: failure to satisfy major entry criteria (n=17) and lack of post-randomisation data (n=44). Blinding and randomisation were carried out by an independent biostatistician. Titration of placebo/acarbose is well described in the protocol and in the study design paper. Of the study population, 9.3% had a fasting plasma glucose of > or =7.0 mmol/l at screening and could have been diabetic according to the new diagnostic criteria. However, even if these subjects are excluded, patients having acarbose treatment still saw a significant risk reduction in the development of diabetes (p=0.0027). The changes in weight are consistent in different publications and are related to different times of follow-up and assessment. Weight change does have an effect on the development of diabetes, but acarbose treatment is still effective even after adjusting for this (p=0.0063). The cardiovascular endpoints were a clearly designated assessment in the original protocol, and only those defined in the protocol and ascertained by the independent Cardiovascular Event Adjudication Committee were used in the analysis. Hypertension was defined according to the most recent diagnostic criteria. The STOP-NIDDM Trial results are scientifically sound and credible. The investigators stand strongly behind these results demonstrating that acarbose treatment is associated with a delay in the development of diabetes, hypertension and cardiovascular complications in a high-risk population with IGT.
Glucometabolic disturbances are associated with myocardial dysfunction. Brain natriuretic peptides (BNP) are used for detecting myocardial dysfunction in clinical practice. However, studies on elderly subjects and gender-specific analyses are sparse.
We examined cross-sectional associations between Nt-proBNP and 1) fasting plasma glucose (FPG), and 2) categories of glucometabolic disturbances, in middle-aged and older subjects (1266 men, 526 women), applying multivariate linear regression analysis.
FPG was positively correlated with Nt-proBNP among middle-aged men (p = 0.04) and negatively albeit non-significantly (p = 0.1) among middle-aged women. Weaker non-significant correlations were seen among older subjects. Middle-aged men with new-onset and prevalent diabetes had higher Nt-proBNP than the reference group (FPG =5.0 mmol/L): 9.53 (p = 0.002) and 8.23 (p = 0.02) vs. 5.71 pmol/L. No differences in Nt-proBNP between categories of glucometabolic disturbance were observed among older men or women.
The results indicate an age- and gender difference in the ability of Nt-proBNP to identify myocardial dysfunction in relation to glucometabolic disturbances. Therefore, Nt-proBNP should be used with caution as a general surrogate marker for myocardial dysfunction in this setting.
BACKGROUND: Alimentary lipemia has been associated with coronary heart disease and common carotid artery intima-media thickness (IMT). This study was designed to investigate the relations of subclasses of postprandial triglyceride-rich lipoproteins (TRLs) with IMT. METHODS AND RESULTS: Ninety-six healthy 50-year-old men with an apolipoprotein (apo) E3/E3 genotype underwent an oral fat tolerance test and B-mode carotid ultrasound examination. The apo B-48 and apo B-100 contents of each fraction of TRLs were determined as a measure of chylomicron remnant and VLDL particle concentrations. In the fasting state, LDL cholesterol (P
The definition and treatment of glucose intolerance during pregnancy are matters of intense controversy. Our goal was to examine the value of the 75-g oral glucose tolerance test (OGTT) in terms of its ability to predict birth weight percentile in a group of women with singleton pregnancies who received minimal treatment for their glucose intolerance.
We reviewed the results of OGTTs performed between 24 and 28 weeks' gestation in a group of 300 consecutive high-risk women (mean age 29.5 years [95% confidence interval, CI, 28.9-30.1]; parity 1.5 [95% CI 1.4-1.7]) whose plasma glucose level 1 hour after a randomly administered 50-g glucose load was 8.0 mmol/L or above. These data were compared with results for a randomly selected control group of 300 women whose plasma glucose level 1 hour after a 50-g glucose load was less than 8.0 mmol/L (mean age 28.0 years [95% CI 27.4-28.6]; parity 1.5 [95% CI 1.3-1.6]).
For 76 (25.3%) of the 300 high-risk women, the plasma glucose level 2 hours after a 75-g glucose load (confirmatory OGTT) was 7.8 mmol/L or more, but only 6 of these were treated with insulin, which emphasizes the low level of intervention in this group. Thirty (10.0%) of the neonates in this group were large for gestational age (LGA; adjusted weight at or above the 90th percentile). This proportion did not significantly differ from the proportion for the control group (25 or 8.3%). After exclusion of the 6 insulin-treated women, simple correlations between birth weight percentile and fasting or 2-hour plasma glucose levels were very weak (r = 0.23 and 0.16 respectively; p
Cites: Am J Obstet Gynecol. 1990 Jul;163(1 Pt 1):86-922375375
AIMS: Impaired fasting glucose (IFG) below the diagnostic threshold for diabetes mellitus (DM) is associated with macrovascular pathology and increased mortality after percutaneous coronary interventions. The study goal was to determine whether pre-operative fasting blood glucose (fB-glu) is associated with an increased mortality after coronary artery bypass grafting (CABG). METHODS AND RESULTS: During 2001-03, 1895 patients underwent primary CABG [clinical DM (CDM) in 440/1895; complete data on fB-glu for n=1375/1455]. Using pre-operative fB-glu, non-diabetics were categorized as having normal fB-glu ( or =6.1 mmol/L). fB-glu was normal in 59%. The relative risks of 30 day and 1 year mortality compared with patients with normal fB-glu was 1.7 [95% confidence interval (CI): 0.5-5.5] and 2.9 (CI: 0.8-11.2) with IFG, 2.8 (CI: 1.1-7.2) and 1.9 (CI: 0.5-6.3) with SDM vs. 1.8 (CI: 0.8-4.0) and 1.6 (CI: 0.6-4.3) if CDM, respectively. The receiver operator characteristic area for the continuous variable fB-glu and 1 year mortality was 0.65 (P=0.002). CONCLUSION: The elevated risk of death after CABG surgery known previously to be associated with CDM seems also to be shared by a group of similar size that includes patients with IFG and undiagnosed DM.
Whether glucose and insulin are differently associated with the risk of coronary heart disease (CHD) mortality is unclear. We aimed to estimate the association between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR), fasting serum insulin (FI) and fasting plasma glucose (FPG) with incident CHD mortality in a prospective study including middle-aged nondiabetic Finnish men. During an average follow-up of 20 years, 273 (11 %) CHD deaths occurred. In a multivariable Cox regression analysis adjusted for age, body mass index, systolic blood pressure, serum LDL-cholesterol, cigarette smoking, history of CHD, alcohol consumption, blood leukocytes and plasma fibrinogen, the hazard ratios (HRs) for CHD mortality comparing top versus bottom quartiles were as follows: 1.69 (95 % CI: 1.15-2.48; p = 0.008) for HOMA-IR; 1.59 (1.09-2.32; p = 0.016) for FI; and 1.26 (0.90-1.76; p = 0.173) for FPG. These findings suggest that IR and FI, but not FPG, are independent risk factors for CHD mortality. Further studies could help clarify these results in terms of screening and risk stratification, causality of the associations, and therapeutical implications.
In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM.
In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry - BORIS who were ?18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol?l(-1)) and WHO (6.1 mmol?l(-1)). Elevated HbA1c was defined according to ADA (cut-off 39 mmol?l(-1)). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry.
The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52-46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87-7.45) compared with those who had fasting glucose levels
Cites: BMJ. 2000 May 6;320(7244):1240-310797032
Cites: Int J Obes (Lond). 2014 Jan;38(1):40-523828099
BACKGROUND: More and better data are needed to understand the action of physical activity (PA) on insulin resistance and the concomitant relation with body fat in adolescence. OBJECTIVE: We examined the relation between total PA and intensity levels with insulin resistance under special consideration of waist circumference and skinfold thickness. DESIGN: This was a cross-sectional study of 613 adolescents (352 girls, 261 boys) with a mean (+/-SD) age of 15.5 +/- 0.5 y from Sweden and Estonia. Total, low, moderate, and vigorous PA was measured by accelerometry. Body fat estimators included waist circumference and the sum of 5 skinfold thicknesses. Fasting insulin and glucose were measured, and insulin resistance was calculated according to the homeostasis model assessment (HOMA). Linear regression analysis and analysis of covariance were used to determine the association between PA and insulin resistance while considering body fat. All estimates were adjusted for sex, country, pubertal status, and indicators of body fat when applicable. RESULTS: Total, moderate, and vigorous PA were inversely correlated with HOMA. Body fat estimators were positively correlated with HOMA. Significant contrasts in HOMA concentrations were seen when comparing the lower 2 tertiles with the upper tertile of PA indicators. Repeating the analysis with body fat estimators showed significant contrasts in HOMA concentrations when comparing the lower tertiles with the upper tertile. CONCLUSION: In view of an increase in obesity in young people, the results accentuate the role of PA in sustaining metabolic balance in adolescence and the potential benefit of an increase of time spent at higher PA levels for youth with relatively elevated amounts of body fat.