Prospective association between fasting NEFA and type 2 diabetes: impact of post-load glucose.
OBJECTIVE
Elevated fasting NEFAs are thought to promote type 2 diabetes. Three prospective studies support this concept, showing increased diabetes risk associated with fasting NEFA. However, these prospective associations may be confounded by strong cross-sectional correlations between fasting NEFA and metabolic predictors of diabetes. To examine this assumption, we used cohort data from the Insulin Resistance Atherosclerosis Study (IRAS).


METHODS
Within the IRAS cohort (n = 902, 145 incident cases), we examined nine metabolic variables for their confounding effect on the fasting NEFA-diabetes association: 2 h glucose; fasting plasma glucose; body mass index; waist circumference; waist-to-hip ratio; weight; insulin sensitivity (S (I)); fasting insulin; and acute insulin response. We compared odds ratios for fasting NEFA (log( e ) transformed and adjusted for age, sex, ethnicity and clinic) before and after inclusion of each metabolic variable into a logistic regression model.


RESULTS
Three variables (2 h glucose, BMI and S (I)) cross-sectionally correlated with fasting NEFA (r > or = 0.1, p < 0.05). Unadjusted for metabolic predictors, fasting NEFA levels were positively associated with diabetes risk: OR 1.37 (95% CI 0.87-2.15) per unit on a log scale. All metabolic variables except AIR showed confounding. Inclusion of 2 h glucose reversed the positive association (OR 0.50 [95% CI 0.30-0.82]), whereas other predictors reduced the association to the null. The final model included the variables correlated with baseline fasting NEFA (2 h glucose, BMI and S (I)) and the demographic variables resulting in OR 0.47 (95% CI 0.27-0.81).


CONCLUSIONS
Our results indicate that 2 h glucose strongly confounds the prospective association between fasting NEFA and diabetes; carefully adjusted fasting NEFA levels are inversely associated with diabetes risk.
Department of Community and Family Medicine, Prevention Research Division, Duke University Medical Center, Box 2949, Durham, NC, 27710, USA, dora.ilyasova@duke.edu.
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D
Il'yasova
F
F
Wang
R B
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D'Agostino
A
A
Hanley
L E
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Wagenknecht
D001786:Blood Glucose; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008954:Models, Biological; D016017:Odds Ratio; D012044:Regression Analysis; D018570:Risk Assessment / Q000379:methods; D055105:Waist Circumference / Q000502:physiology; D049629:Waist-Hip Ratio
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin