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

Abstract

T he role of the liver in the pathogenesis of type 2 diabetes is attracting increasing interest. In a recent study (1), directly determined liver fat content was shown to correlate with several features of insulin resistance in normal weight and moderately overweight subjects independent of BMI and intraabdominal or overall obesity. However, direct measurements of liver fat require ultrasound, computed tomography scan, or proton spectroscopy, and such techniques are unlikely to be recommended for this purpose in routine clinical practice. Fortunately, circulating concentrations of a number of variables appear to give insight into the extent of liver fat accumulation. Among these are ␥-glutamyltransferase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Of these three, ALT is the most specific marker of liver pathology and appears to be the best marker for liver fat accumulation (2). In addition, circulating concentrations of plasminogen activator inhibitor-1 may give insight into the extent of liver fat content (3) but, unlike ALT, its measurement is perhaps not as simple, standardized, or routinely available in laboratories.In light of the above observations, it is of interest that ALT has been shown to predict incident type 2 diabetes in two prospective studies (4,5). Ohlson et al. (4) determined risk factors for diabetes in 766 men, 47 of whom developed diabetes over 13.5 years of follow-up. They reported that elevated ALT predicted diabetes independently of classical predictors inclusive of BMI, blood pressure, triglycerides, and family history. However, diabetes ascertainment was not uniform in their study, and the potential utility of ALT to predict diabetes was not examined in any detail. Vozarovoa et al. (5) examined the ALT levels in a cohort of 370 Pima Indians with normal glucose tolerance, 63 of whom developed diabetes over an average follow-up of 6.9 years. In their analyses, individuals in the top decile for ALT (Ն70 units/l) had a relative risk of 2.5 (95% CI 1.7-3.7) for diabetes compared with those in the bottom decile (ALT Յ12 units/l), with adjustment for age, sex, percentage body fat, clamp-derived insulin resistance, and acute insulin response. The only minor weaknesses in that study were the absence of data on alcohol consumption and routine clinical measures known to predict diabetes, namely fasting lipids and blood pressure. Moreover, they

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

“…The independent association of hepatic enzymes and incident diabetes has now been well described [10][11][12][13]. We found a strong positive correlation between ferritin and the hepatic enzymes, ALT and GGT (r ranging between 0.29 and 0.37, p<0.0001).…”

“…There is now growing evidence for the association of incident diabetes with both the adipocytokine adiponectin [8,9] and hepatic function as measured by the hepatic enzymes alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) [10][11][12][13]. However, their association with ferritin has not been widely studied, nor are there any studies that have adjusted for these markers to test the independence of the ferritin-diabetes association.…”

Predictors of new-onset diabetes mellitus in hypertensive patients: the VALUE trial

“…3,25 The CAPPP study included low-risk patients from Sweden and Finland indicating a less general population. Other known risk factors for diabetes mellitus development evaluated in, for example, West of Scotland Coronary Prevention Study such as high-sensitivity CRP, 26 triglycerides 27 and ALAT, 28 have not been evaluated in our population. There are also developed risk tests or risk scores, for example, the American and the Finnish Diabetes Associations, 29,30 that emphasize on age, BMI, waist, glucose level, diet, physical activity and family history, to calculate a patients risk for diabetes mellitus development.…”

Associations of adiponectin with metabolic and vascular risk parameters in the British Regional Heart Study reveal stronger links to insulin resistance-related than to coronory heart disease risk-related parameters

“…We observed no consistent association between physical activity and adiponectin, although paradoxically levels were significantly reduced in the vigorously active group. Although it has been suggested that exercise may increase adiponectin levels, clinical studies on the effects of exercise training have been conflicting 41,42 and findings in population-based studies are inconsistent. 19,21 Insulin resistance and the metabolic syndrome Strong associations were seen between adiponectin and HOMA-IR after adjustment for waist circumference and the magnitude of correlation was similar to that seen for BMI.…”