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Aspartate aminotransferase - risk marker for type-2 diabetes mellitus or red herring?

Kunutsor SK, Abbasi A, Apekey TA - Front Endocrinol (Lausanne) (2014)

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge , Cambridge , UK.

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Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are common liver enzymes... In a recent review, we synthesized available prospective epidemiological data on the association between AST and incident T2DM... The pooled analyses involving 1,912 incident T2DM cases did not show a significant association between AST and risk of future T2DM... This large study adds to the growing body of evidence that like GGT and ALT, elevated AST level may also be associated with increased risk for T2DM... The prospective evidence on the association between AST and T2DM is inconclusive and this may be attributed to several reasons including: lack of adequate power, unmeasured confounding, or even over-adjustment for potential intermediates by previous studies... Given that levels of serum liver enzymes (GGT, ALT, and AST) (i) are strongly environmentally and genetically correlated with one another, and (ii) have shared genetic variances, the evidence is suggestive of common biological pathways affecting levels of these enzymes... There is therefore a possibility that the association between AST level and risk of T2DM might be mediated through the effects of the other liver enzymes... Details of the review methodology and inclusion/exclusion criteria have been reported previously... Briefly, studies were only included if they had at least 1 year of follow-up, recruited participants from approximately general populations (i.e., did not select participants on the basis of pre-existing diabetes or known liver disease), and excluded participants with marked elevations in AST levels... Data were abstracted on several study characteristics including degree of adjustment for potential confounders (defined as “+” when RRs were adjusted for age and/or sex; “++” further adjustment for established diabetes risk factors; and “+++” additional adjustment for liver enzymes)... Egger’s test was not significant (P = 0.92), consistent with observed funnel plot symmetry... The pattern of findings from the available evidence suggest that elevated AST is associated with increased risk of T2DM after controlling for potential confounding... These results must be interpreted with caution given potential limitations such as effects of residual confounding, variably adjusted data, and the possibility for bias when attempting to assess the impact of putative intermediates such as other liver enzymes (GGT and ALT).

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Related in: MedlinePlus

Prospective studies of aspartate aminotransferase levels and type-2 diabetes mellitus risk, grouped according to covariate adjustment levels. The summary estimates presented were calculated using random-effects models; degree of adjustment: +, adjusted for age and/sex; ++, additionally adjusted for diabetes risk factors; +++, further adjusted for other liver enzymes; AST, aspartate aminotransferase; bars, 95% CI; RR, relative risk.
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Figure 1: Prospective studies of aspartate aminotransferase levels and type-2 diabetes mellitus risk, grouped according to covariate adjustment levels. The summary estimates presented were calculated using random-effects models; degree of adjustment: +, adjusted for age and/sex; ++, additionally adjusted for diabetes risk factors; +++, further adjusted for other liver enzymes; AST, aspartate aminotransferase; bars, 95% CI; RR, relative risk.

Mentions: Data were available on 90,975 participants from 13 unique prospective cohort studies (14–24) (of which, 9 were included in the previous review) (Table S1 in Supplementary Material). The cumulative analysis involved 6,069 incident T2DM cases, collected over average follow-up periods ranging from 3 to 20 years. The pooled random-effects RR (95% CI) for T2DM in a comparison of extreme thirds of AST level was 1.09 (1.03–1.14) in studies that adjusted for potential diabetes risk factors. The corresponding RR was 1.00 (0.96–1.05) in studies that additionally adjusted for other liver enzymes (P for meta-regression = 0.05; Figure 1). There was substantial heterogeneity among the studies that adjusted for diabetes risk factors (I2 = 73%: 54–85%, P < 0.001). The inconsistency was to a large part explained by duration of follow-up (P for meta-regression = 0.004), with combined estimates from studies with follow-up duration ≥5 years (1.28, 95% CI: 1.11–1.49) being stronger than those with shorter follow-up duration (1.02, 95% CI: 0.98–1.05). Egger’s test was not significant (P = 0.92), consistent with observed funnel plot symmetry.


Aspartate aminotransferase - risk marker for type-2 diabetes mellitus or red herring?

Kunutsor SK, Abbasi A, Apekey TA - Front Endocrinol (Lausanne) (2014)

Prospective studies of aspartate aminotransferase levels and type-2 diabetes mellitus risk, grouped according to covariate adjustment levels. The summary estimates presented were calculated using random-effects models; degree of adjustment: +, adjusted for age and/sex; ++, additionally adjusted for diabetes risk factors; +++, further adjusted for other liver enzymes; AST, aspartate aminotransferase; bars, 95% CI; RR, relative risk.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219379&req=5

Figure 1: Prospective studies of aspartate aminotransferase levels and type-2 diabetes mellitus risk, grouped according to covariate adjustment levels. The summary estimates presented were calculated using random-effects models; degree of adjustment: +, adjusted for age and/sex; ++, additionally adjusted for diabetes risk factors; +++, further adjusted for other liver enzymes; AST, aspartate aminotransferase; bars, 95% CI; RR, relative risk.
Mentions: Data were available on 90,975 participants from 13 unique prospective cohort studies (14–24) (of which, 9 were included in the previous review) (Table S1 in Supplementary Material). The cumulative analysis involved 6,069 incident T2DM cases, collected over average follow-up periods ranging from 3 to 20 years. The pooled random-effects RR (95% CI) for T2DM in a comparison of extreme thirds of AST level was 1.09 (1.03–1.14) in studies that adjusted for potential diabetes risk factors. The corresponding RR was 1.00 (0.96–1.05) in studies that additionally adjusted for other liver enzymes (P for meta-regression = 0.05; Figure 1). There was substantial heterogeneity among the studies that adjusted for diabetes risk factors (I2 = 73%: 54–85%, P < 0.001). The inconsistency was to a large part explained by duration of follow-up (P for meta-regression = 0.004), with combined estimates from studies with follow-up duration ≥5 years (1.28, 95% CI: 1.11–1.49) being stronger than those with shorter follow-up duration (1.02, 95% CI: 0.98–1.05). Egger’s test was not significant (P = 0.92), consistent with observed funnel plot symmetry.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge , Cambridge , UK.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are common liver enzymes... In a recent review, we synthesized available prospective epidemiological data on the association between AST and incident T2DM... The pooled analyses involving 1,912 incident T2DM cases did not show a significant association between AST and risk of future T2DM... This large study adds to the growing body of evidence that like GGT and ALT, elevated AST level may also be associated with increased risk for T2DM... The prospective evidence on the association between AST and T2DM is inconclusive and this may be attributed to several reasons including: lack of adequate power, unmeasured confounding, or even over-adjustment for potential intermediates by previous studies... Given that levels of serum liver enzymes (GGT, ALT, and AST) (i) are strongly environmentally and genetically correlated with one another, and (ii) have shared genetic variances, the evidence is suggestive of common biological pathways affecting levels of these enzymes... There is therefore a possibility that the association between AST level and risk of T2DM might be mediated through the effects of the other liver enzymes... Details of the review methodology and inclusion/exclusion criteria have been reported previously... Briefly, studies were only included if they had at least 1 year of follow-up, recruited participants from approximately general populations (i.e., did not select participants on the basis of pre-existing diabetes or known liver disease), and excluded participants with marked elevations in AST levels... Data were abstracted on several study characteristics including degree of adjustment for potential confounders (defined as “+” when RRs were adjusted for age and/or sex; “++” further adjustment for established diabetes risk factors; and “+++” additional adjustment for liver enzymes)... Egger’s test was not significant (P = 0.92), consistent with observed funnel plot symmetry... The pattern of findings from the available evidence suggest that elevated AST is associated with increased risk of T2DM after controlling for potential confounding... These results must be interpreted with caution given potential limitations such as effects of residual confounding, variably adjusted data, and the possibility for bias when attempting to assess the impact of putative intermediates such as other liver enzymes (GGT and ALT).

No MeSH data available.


Related in: MedlinePlus