Elevated Alanine Aminotransferase Predicts New-Onset Type 2 Diabetes Independently of Classical Risk Factors, Metabolic Syndrome, and C-Reactive Protein in the West of Scotland Coronary Prevention Study

Naveed Sattar; Olga Scherbakova; Ian Ford; Denis St. J. O'Reilly; Adrian Stanley; Ewan Forrest; Peter W. MacFarlane; Chris J. Packard; Stuart M. Cobbe; James Shepherd

Disclosures

Diabetes. 2004;53(11) 

In This Article

Results

A total of 139 men (2.33%) developed diabetes over an average follow-up of 4.9 years. Their baseline characteristics are given in Table 1 . Notably, mean ALT was 18% higher in those who subsequently developed diabetes (P < 0.001).

In the correlation analysis ( Table 2 ), elevated ALT was most strongly associated with BMI, triglycerides, fasting glucose, and diastolic blood pressure (all r > 0.10, P < 0.001). AST was less strongly associated with these variables. Both elevated ALT and AST were weakly associated with excessive alcohol intake, but neither was related substantially to CRP. Consistent with the above observations, ALT increased progressively with increasing number of metabolic syndrome abnormalities ranging from 20.9 ± 7.6 units/l in those with no abnormalities to 28.1 ± 10.1 units/l in those with four or more (P < 0.0001 for trend) (Fig. 1), whereas AST did not change significantly (P = 0.27).

Figure 1.

The serum concentrations of ALT and AST in men fulfilling increasing numbers of metabolic syndrome criteria.

ALT Versus Classical Predictors

In a univariate analysis, ALT as a continuous variable was associated with risk of diabetes. A 5-units/l increment had a hazard ratio (HR) of 1.25 (95% CI 1.15-1.34, P < 0.0001). Men in the fourth quartile for ALT, but not those in the second or third quartiles, had a significantly increased risk for diabetes relative to men in the first quartile ( Table 3 ). The relationship was clearly evident in the Kaplan-Meier curve (Fig. 2). In a multivariate analysis, after adjusting for other measured baseline parameters (including BMI, triglycerides, HDL cholesterol, blood pressure, glucose, and alcohol intake), men in the fourth quartile for ALT continued to have a significantly elevated risk for diabetes (HR 2.04 [1.1633-0.508]) ( Table 3 ). Moreover, the predictive ability of ALT persisted when the fourth quartile was compared with the risk in men in the other three quartiles combined (HR 1.72 [1.20-2.48]) (Fig. 3). Similarly, an ALT cutoff of ≥29 units/l improved prediction of diabetes when combined with a fasting glucose cutoff of 6.1 mmol/l (data not shown). By contrast, AST did not predict incident diabetes in univariate or multivariate analyses (data not shown).

Figure 2.

Onset of new diabetes by quartiles of plasma ALT concentration.

Figure 3.

Association of ALT quartiles with incident diabetes with and without adjustment for other risk factors as stated. Risk factors include all parameters considered in the multivariate analysis in Table 3.

ALT Versus Metabolic Syndrome Classification

Elevated ALT continued to predict incident diabetes (HR 2.08 [95% CI 1.48-2.93] for ALT ≥29 versus ALT <29 units/l) even when subjects were categorized as having or not having the metabolic syndrome (Fig. 3). Similarly, further addition of a CRP cutoff 3 mg/l into the latter analysis did not alter the ability of ALT to predict incident diabetes. Finally, we performed a stepwise multivariate analysis of diabetes predictors, with all individual metabolic syndrome criteria cutoffs, a CRP cutoff of 3 mg/l and an ALT cutoff of 29 units/l, entered into the model. In this case, both ALT and CRP continued to independently predict diabetes but low HDL cholesterol and blood pressure did not enter the final model ( Table 4 ).

Pravastatin Effect

All measurements in this analysis, except for repeated fasting glucose concentrations, were made before randomization to active therapy or placebo and are thus unaffected by treatment allocation. Since we have previously shown that pravastatin use did influence progression to diabetes,[13] we included treatment allocation in the multivariate analysis and, in addition, noted that the ALT incident diabetes association was not dissimilar (P = 0.89) in men allocated to pravastatin or placebo.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....