Dataset Information

Catechol-O-methyltransferase association with hemoglobin A1c.

ABSTRACT: Catecholamines have metabolic effects on blood pressure, insulin sensitivity and blood glucose. Genetic variation in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines, is associated with cardiometabolic risk factors and incident cardiovascular disease (CVD). Here we examined COMT effects on glycemic function and type 2 diabetes.We tested whether COMT polymorphisms were associated with baseline HbA1c in the Women's Genome Health Study (WGHS), and Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), and with susceptibility to type 2 diabetes in WGHS, DIAbetes Genetics Replication And Meta-analysis consortium (DIAGRAM), and the Diabetes Prevention Program (DPP). Given evidence that COMT modifies some drug responses, we examined association with type 2 diabetes and randomized metformin and aspirin treatment.COMT rs4680 high-activity G-allele was associated with lower HbA1c in WGHS (?=-0.032% [0.012], p=0.008) and borderline significant in MAGIC (?=-0.006% [0.003], p=0.07). Combined COMT per val allele effects on type 2 diabetes were significant (OR=0.98 [0.96-0.998], p=0.03) in fixed-effects analyses across WGHS, DIAGRAM, and DPP. Similar results were obtained for 2 other COMT SNPs rs4818 and rs4633. In the DPP, the rs4680 val allele was borderline associated with lower diabetes incidence among participants randomized to metformin (HR=0.81 [0.65-1.00], p=0.05).COMT rs4680 high-activity G-allele was associated with lower HbA1c and modest protection from type 2 diabetes. The directionality of COMT associations was concordant with those previously observed for cardiometabolic risk factors and CVD.

SUBMITTER: Hall KT

PROVIDER: S-EPMC4924514 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Catechol-O-methyltransferase association with hemoglobin A1c.

Hall Kathryn T KT Jablonski Kathleen A KA Chen Ling L Harden Maegan M Tolkin Benjamin R BR Kaptchuk Ted J TJ Bray George A GA Ridker Paul M PM Florez Jose C JC Mukamal Kenneth J KJ Chasman Daniel I DI

Metabolism: clinical and experimental 20160414 7

<h4>Aims</h4>Catecholamines have metabolic effects on blood pressure, insulin sensitivity and blood glucose. Genetic variation in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines, is associated with cardiometabolic risk factors and incident cardiovascular disease (CVD). Here we examined COMT effects on glycemic function and type 2 diabetes.<h4>Methods</h4>We tested whether COMT polymorphisms were associated with baseline HbA1c in the Women's Genome Health Study (WGHS), ...[more]

PMID: 27282867

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Project description:Hemoglobin A1c (HbA1c) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it.To evaluate the association between SCT and HbA1c for given levels of fasting or 2-hour glucose levels among African Americans.Retrospective cohort study using data collected from 7938 participants in 2 community-based cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). From the CARDIA study, 2637 patients contributed a maximum of 2 visits (2005-2011); from the JHS, 5301 participants contributed a maximum of 3 visits (2000-2013). All visits were scheduled at approximately 5-year intervals. Participants without SCT data, those without any concurrent HbA1c and glucose measurements, and those with hemoglobin variants HbSS, HbCC, or HbAC were excluded. Analysis of the primary outcome was conducted using generalized estimating equations (GEE) to examine the association of SCT with HbA1c levels, controlling for fasting or 2-hour glucose measures.Presence of SCT.Hemoglobin A1c stratified by the presence or absence of SCT was the primary outcome measure.The analytic sample included 4620 participants (mean age, 52.3 [SD, 11.8] years; 2835 women [61.3%]; 367 [7.9%] with SCT) with 9062 concurrent measures of fasting glucose and HbA1c levels. In unadjusted GEE analyses, for a given fasting glucose, HbA1c values were statistically significantly lower in those with (5.72%) vs those without (6.01%) SCT (mean HbA1c difference, -0.29%; 95% CI, -0.35% to -0.23%). Findings were similar in models adjusted for key risk factors and in analyses using 2001 concurrent measures of 2-hour glucose and HbA1c concentration for those with SCT (mean, 5.35%) vs those without SCT (mean, 5.65%) for a mean HbA1c difference of -0.30% (95% CI, -0.39% to -0.21%). The HbA1c difference by SCT was greater at higher fasting (P?=?.02 for interaction) and 2-hour (P?=?.03) glucose concentrations. The prevalence of prediabetes and diabetes was statistically significantly lower among participants with SCT when defined using HbA1c values (29.2% vs 48.6% for prediabetes and 3.8% vs 7.3% for diabetes in 572 observations from participants with SCT and 6877 observations from participants without SCT; P<.001 for both comparisons).Among African Americans from 2 large, well-established cohorts, participants with SCT had lower levels of HbA1c at any given concentration of fasting or 2-hour glucose compared with participants without SCT. These findings suggest that HbA1c may systematically underestimate past glycemia in black patients with SCT and may require further evaluation.

Project description:ImportancePreoperative hyperglycemia is associated with adverse postoperative outcomes among patients who undergo surgery. Whether preoperative hemoglobin A1c (HbA1c) or postoperative glucose levels are more useful in predicting adverse events following surgery is uncertain in the current literature.ObjectiveTo examine the use of preoperative HbA1c and early postoperative glucose levels for predicting postoperative complications and readmission.Design, setting, and participantsIn this observational cohort study, inpatient gastrointestinal surgical procedures performed at 117 Veterans Affairs hospitals from 2007 to 2014 were identified, and cases of known infection within 3 days before surgery were excluded. Preoperative HbA1c levels were examined as a continuous and categorical variable (<5.7%, 5.7%-6.5%, and >6.5%). A logistic regression modeled postoperative complications and readmissions with the closest preoperative HbA1c within 90 days and the highest postoperative glucose levels within 48 hours of undergoing surgery.Main outcomes and measuresPostoperative complications and 30-day unplanned readmission following discharge.ResultsOf 21 541 participants, 1193 (5.5%) were women, and the mean (SD) age was 63.7 (10.6) years. The cohort included 23 094 operations with measurements of preoperative HbA1c levels and postoperative glucose levels. The complication and 30-day readmission rates were 27.2% and 14.7%, respectively. In logistic regression models adjusting for HbA1c, postoperative glucose levels, postoperative insulin use, diabetes, body mass index (calculated as weight in kilograms divided by height in meters squared), and other patient and procedural factors, peak postoperative glucose levels of more than 250 mg/dL were associated with increased 30-day readmissions (odds ratio, 1.18; 95% CI, 0.99-1.41; P = .07). By contrast, a preoperative HbA1c of more than 6.5% was associated with decreased 30-day readmissions (odds ratio, 0.85; 95% CI, 0.74-0.96; P = .01). As preoperative HbA1c increased, the frequency of 48-hour postoperative glucose checks increased (4.92, 6.89, and 9.71 for an HbA1c <5.7%, 5.7%-6.4%, and >6.5%, respectively; P < .001). Patients with a preoperative HbA1c of more than 6.5% had lower thresholds for postoperative insulin use.Conclusions and relevanceEarly postoperative hyperglycemia was associated with increased readmission, but elevated preoperative HbA1c was not. A higher preoperative HbA1c was associated with increased postoperative glucose level checks and insulin use, suggesting that heightened postoperative vigilance and a lower threshold to treat hyperglycemia may explain this finding.

Dataset Information

Catechol-O-methyltransferase association with hemoglobin A1c.

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Catechol-O-methyltransferase association with hemoglobin A1c.

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