Dataset Information

Lactate and risk of incident diabetes in a case-cohort of the atherosclerosis risk in communities (ARIC) study.

ABSTRACT:

Background

Oxidative capacity is decreased in type 2 diabetes. Whether decreased oxidative capacity is a cause or consequence of diabetes is unknown. Our purpose is to evaluate whether lactate, a marker of oxidative capacity, is associated with incident diabetes.

Methods and findings

We conducted a case-cohort study in the Atherosclerosis Risk in Communities (ARIC) study at year 9 of follow-up. We evaluated lactate's association with diabetes risk factors at baseline and estimated the hazard ratio for incident diabetes by quartiles of plasma lactate in 544 incident diabetic cases and 533 non-cases. Plasma lactate showed a graded positive relationship with fasting glucose and insulin (P<0.001). The relative hazard for incident diabetes increased across lactate quartiles (P-trend ?0.001). Following adjustment for demographic factors, medical history, physical activity, adiposity, and serum lipids, the hazard ratio in the highest quartile was 2.05 times the hazard in the lowest quartile (95% CI: 1.28, 3.28). After including fasting glucose and insulin the association became non-significant.

Conclusions

Lactate, an indicator of oxidative capacity, predicts incident diabetes independent of many other risk factors and is strongly related to markers of insulin resistance. Future studies should evaluate the temporal relationship between elevated lactate and impaired fasting glucose and insulin resistance.

SUBMITTER: Juraschek SP

PROVIDER: S-EPMC3559502 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Lactate and risk of incident diabetes in a case-cohort of the atherosclerosis risk in communities (ARIC) study.

Juraschek Stephen P SP Shantha Ghanshyam Palamaner Subash GP Chu Audrey Y AY Miller Edgar R ER Guallar Eliseo E Hoogeveen Ron C RC Ballantyne Christie M CM Brancati Frederick L FL Schmidt Maria Inês MI Pankow James S JS Young J Hunter JH

PloS one 20130130 1

<h4>Background</h4>Oxidative capacity is decreased in type 2 diabetes. Whether decreased oxidative capacity is a cause or consequence of diabetes is unknown. Our purpose is to evaluate whether lactate, a marker of oxidative capacity, is associated with incident diabetes.<h4>Methods and findings</h4>We conducted a case-cohort study in the Atherosclerosis Risk in Communities (ARIC) study at year 9 of follow-up. We evaluated lactate's association with diabetes risk factors at baseline and estimated ...[more]

PMID: 23383072

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Project description:Carotid intima-media thickness has been reported to predict kidney function decline. However, whether carotid intima-media thickness is associated with a hard kidney end point, ESRD, has not been investigated.We studied 13,197 Atherosclerosis Risk in Communities participants at visit 1 (1987-1989) without history of cardiovascular disease, including coronary heart disease, stroke, and heart failure, at baseline and assessed whether carotid intima-media thickness measured by B-mode ultrasound is associated with ESRD risk using Cox proportional hazards models. Regarding carotid intima-media thickness parameters, we investigated the mean and maximum values of overall and segment-specific (common, bifurcation, and internal carotid arteries) measurements.Mean age was 54.0 (SD=5.7) years old, and there were 3373 (25.6%) blacks and 7370 (55.8%) women. During a median follow-up of 22.7 years, 433 participants developed ESRD (1.4/1000 person-years). After adjusting for shared risk factors for atherosclerosis and kidney disease, including baseline kidney function, carotid intima-media thickness was significantly associated with ESRD risk (hazard ratio [HR] between quartiles 4 and 1, 1.46; 95% confidence interval [95% CI], 1.02 to 2.08 for overall mean intima-media thickness and HR between quartiles 4 and 1, 1.75; 95% CI, 1.24 to 2.48 for overall maximum intima-media thickness). The associations were largely consistent in demographic and clinical subgroups. When we explored segment-specific intima-media thicknesses, the associations with ESRD were most robust for bifurcation carotid (e.g., adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.49; 95% CI, 1.04 to 2.13 for bifurcation; adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.36; 95% CI, 0.94 to 1.97 for common; and adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 0.93; 95% CI, 0.67 to 1.29 for internal).Carotid intima-media thickness was independently associated with incident ESRD in the general population, suggesting the shared etiology of atherosclerosis and ESRD.

Project description:Cardiovascular risk factors such as aging, smoking, and insulin resistance may lead to atherosclerosis through various mechanisms of which their association with mitochondrial dysfunction may be one of them. In order to examine this hypothesis, we assessed the association between elevated blood lactate, a marker of mitochondrial dysfunction, and carotid atherosclerosis.From a total of 2066 participants from the Atherosclerosis Risk In Communities Carotid MRI study, 1496 were included for this analysis. Wall Thickness and Lipid core presence were measured using gadolinium-enhanced MRI. Blood lactate was categorized into quartiles (Q1: <5.9 mg/dl, Q2: 5.9-7.2 mg/dl, Q3: 7.3-9.2 mg/dl, and Q4: >9.2 mg/dl).Of the 1496 study participants, 763 (51%) were females, 296 (19.8%) African American, 539 (36%) obese and 308 (20.6%) had diabetes. There was a strong and graded association between lactate and wall thickness [Q1: 1.08 mm (95% CI: 1.01 mm-1.15 mm), Q2: 1.33 mm (95% CI: 1.19 mm-1.47 mm), Q3: 1.44 (95% CI: 1.34 mm-1.54 mm) and Q4: 1.62 (95% CI: 1.53 mm-1.71 mm); p for trend <0.001] after adjusting for age, gender, ethnicity, stature, body mass index (BMI), waist circumference, LDL, High sensitivity C reactive protein (HsCRP), statin use, thiazolidinedione use, hypertension, and diabetes. This association was attenuated, but still significant, after adjusting for a marker of insulin resistance, the triglyceride/HDL ratio, [Q1: 0.96 mm (95% CI: 0.82 mm-1.10 mm), Q2: 1.17 mm (95% CI: 1.08 mm-1.26 mm), Q3: 1.18 mm (95% CI: 1.07 mm-1.29 mm), Q4: 1.22 mm (95% CI: 1.13 mm-1.31 mm), p for linear trend 0.039]. There was no association of lactate with lipid core presence after adjustment for wall thickness.Blood lactate is associated with carotid atherosclerosis. Attenuation of the association with adjustment for triglyceride/HDL ratio, a marker of insulin resistance, suggests that lactate's association with carotid atherosclerosis may be related to insulin resistance.

Project description:BACKGROUND:Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD). STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:14,946 participants aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through 2012. PREDICTORS:Race- and sex-specific quartiles of percent-predicted forced vital capacity (FVC) and the proportion of forced expiratory volume in 1 second of expiration to FVC (FEV1/FVC) at baseline determined with spirometry. OUTCOMES:Incident ESRD (defined here as renal replacement therapy or death due to CKD) as the primary outcome and incident CKD (defined here as ESRD, ?25% decline in estimated glomerular filtration rate to a level <60mL/min/1.73m2, or CKD-related hospitalizations/deaths) as the secondary outcome. RESULTS:During a median follow-up of 23.6 years, 526 (3.5%) participants developed ESRD. After adjusting for potential confounders, the cause-specific HR of incident ESRD for the lowest (vs highest) quartile was 1.72 (95% CI, 1.31-2.26) for percent-predicted FVC and 1.33 (95% CI, 1.03-1.73) for FEV1/FVC. Compared to a high-normal lung function pattern, a mixed pattern (ie, percent-predicted FVC<80% and FEV1/FVC<70%; 3.4% of participants) demonstrated the highest adjusted cause-specific HR of ESRD at 2.28 (95% CI, 1.50-3.45), followed by the restrictive pattern (ie, percent-predicted FVC<80% and FEV1/FVC?70%; 4.8% of participants) at 2.03 (95% CI, 1.47-2.81), obstructive pattern (ie, percent-predicted FVC?80% and FEV1/FVC<70%; 18.9% of participants) at 1.47 (95% CI, 1.09-1.99), and low-normal pattern (ie, percent-predicted FVC 80%-<100% and FEV1/FVC?70%, or percent-predicted FVC?80% and FEV1/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar associations were seen with incident CKD. LIMITATIONS:Limited number of participants with moderate/severe lung dysfunction and spirometry only at baseline. CONCLUSIONS:Reduced lung function, particularly lower percent-predicted FVC, is independently associated with CKD progression. Our findings suggest a potential pathophysiologic contribution of reduced lung function to the development of CKD and a need for monitoring kidney function in persons with reduced lung function.

Dataset Information

Lactate and risk of incident diabetes in a case-cohort of the atherosclerosis risk in communities (ARIC) study.

Background

Methods and findings

Conclusions

Publications

Lactate and risk of incident diabetes in a case-cohort of the atherosclerosis risk in communities (ARIC) study.

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