Adjusted percent differences in plasma lactate in the ARIC Carotid MRI Study.

<p>Adjusted differences in plasma lactate (vs non-users of diabetes medications) in users of thiazolidinediones, Insulin, Sulfonylureas, and Metformin in those with type 2 diabetes in the ARIC Carotid MRI Study: Percent differences and 95% confidence intervals. Adjusted for age, sex, race, and education, sport and leisure activity, and body mass index.</p

Effect of medication combinations on percent differences and 95% confidence intervals in serum lactate level.

<p>Effect of medication combinations on percent differences and 95% confidence intervals in serum lactate level (mg/dl) among persons with type 2 diabetes in the ARIC Carotid MRI Study. All comparisons based on a model containing age, sex, race, education, sport and leisure activity, and body mass index. Diabetes medication use was constructed as a factor variable with mutually exclusive groups representing each medication separately and in combination. All groups are compared to no diabetes medication use. Not all combinations are shown.</p

Characteristics of 493 Adults Aged 61–84 With Type 2 Diabetes in the ARIC Carotid MRI Study by Diabetes Medication Use.

<p>Bolded values indicate p-values<0.05 for the t-test of the difference for Yes – No.</p><p>All estimates are survey weighted mean (SE) except where indicated as % (SE). SE = linearized standard error.</p>a<p>. Geometric mean and 95% confidence interval for blood lactate (mg/dl).</p

Lactate and Risk of Incident Diabetes in a Case-Cohort of the Atherosclerosis Risk in Communities (ARIC) Study

<div><h3>Background</h3><p>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.</p> <h3>Methods and Findings</h3><p>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 (<em>P</em><0.001). The relative hazard for incident diabetes increased across lactate quartiles (<em>P</em>-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.</p> <h3>Conclusions</h3><p>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.</p> </div

Mean homeostatic model assessment (HOMA-IR) with 95% confidence intervals by baseline plasma lactate quartile.

<p>Mean homeostatic model assessment (HOMA-IR) with 95% confidence intervals by baseline plasma lactate quartile.</p

Baseline (visit 1) characteristics of ARIC participants according to quartiles of plasma lactate.

*<p>The ranges of the plasma lactate quartiles were determined using specimens from the weighted random cohort sample.</p>†<p>Represents the maximum number of participants in each category. Actual number may vary due to missing data.</p>‡<p>Plasma lactate mg/dL may be converted to mmol/L by multiplying by 0.111.</p>§<p>P-trend evaluated with linear or logistic regression using the median lactate value for each quartile as an ordinal variable.</p>∧<p>There were no participants with coronary heart disease in quartile 1. SE not calculated due to small sample size.</p>**<p>Represents geometric mean and interquartile range.</p><p>Note: LDL represents low density lipoprotein. HDL represents high density lipoprotein.</p

Percent change in plasma lactate per 1 unit increase in physiologic correlates of insulin resistance and Pearson correlation coefficient between baseline characteristics and log-base 10 transformed lactate.

*<p>Adjusted for age, gender, race, and center.</p><p>Note: HDL represents high density lipoprotein.</p

Hazard ratios (95% confidence intervals) for developing type 2 diabetes by weighted quartile of lactate concentrations.

<p>Model 1: Age, gender, race, ARIC center, education.</p><p>Model 2: Model 1+ diagnosis of hypertension, prevalent coronary heart disease, smoking status, leisure index, parental history of diabetes.</p><p>Model 3: Model 2+ body mass index, waist circumference.</p><p>Model 4: Model 3+ log₁₀ triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol.</p><p>Model 5a: Model 4+ fasting glucose.</p><p>Model 5b: Model 4+ log₁₀ fasting insulin.</p><p>Model 5c: Model 4+ fasting glucose and log₁₀ fasting insulin.</p>*<p>P-value for trend evaluated using an ordinal variable based on the median lactate in each quartile.</p

Kaplan-Meier cumulative incidence plot with follow-up years as the time axis and incident diabetes as the outcome stratified by baseline plasma lactate value.

<p>A Wald test was performed to assess for a trend across quartiles of lactate.</p

Genetic African ancestry by participant characteristics and study.

<p>ARIC, the Atherosclerosis Risk in Communities Study; JHS, the Jackson Heart Study; MEC, the Multiethnic Cohort; IQR, interquartile range; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).</p>a<p><i>P</i> value was generated from the Wilcoxon rank-sum test or the Kruskal-Wallis test.</p