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Sex influenced association of directly measured insulin sensitivity and serum transaminase levels: Why alanine aminotransferase only predicts cardiovascular risk in men?

Buday B, Pach PF, Literati-Nagy B, Vitai M, Kovacs G, Vecsei Z, Koranyi L, Lengyel C - Cardiovasc Diabetol (2015)

Bottom Line: Significant bivariate correlations were found between clamp measured M3 and all three liver enzymes (ALT, aspartate aminotransferase and gamma-glutamyl transferase) in both sexes.When data were adjusted for possible metabolic confounding factors correlations ceased in the male population but stayed significant in the female group.Moreover, ALT may be used as a simple diagnostic tool to identify insulin resistant subjects only in the female population according to our results.

View Article: PubMed Central - PubMed

Affiliation: Drug Research Center, Department of Metabolism, Balatonfüred, Hungary. budaybarb@hotmail.com.

ABSTRACT

Background: Non alcoholic fatty liver disease (NAFLD) is an independent cardiovascular (CV) risk factor which is closely associated with insulin resistance measured by both direct or indirect methods. Gender specific findings in the relationship between alanine aminotransferase (ALT) and CV disease, the prevalence of NAFLD and type 2 diabetes (T2DM) have been published recently. The aim of the present study was to explore the gender aspects of the association between insulin sensitivity, liver markers and other metabolic biomarkers in order to elucidate the background behind the sex influenced difference in both NAFLD, T2DM and their association with CV risk.

Patients and methods: 158 female (47 normal and 111 impaired glucose intolerant) and 148 male (74 normal and 74 impaired glucose tolerant) subjects were included (mean age: 46.5 ± 8.31 vs. 41.6 ± 11.3, average Hba1c < 6.1 %, i.e. prediabetic population, drug naive at the time of the study). Subjects underwent a hyperinsulinemic normoglycemic clamp to determine muscle glucose uptake (M3), besides liver function tests and other fasting metabolic and anthropometric parameters were determined.

Results: Significant bivariate correlations were found between clamp measured M3 and all three liver enzymes (ALT, aspartate aminotransferase and gamma-glutamyl transferase) in both sexes. When data were adjusted for possible metabolic confounding factors correlations ceased in the male population but stayed significant in the female group. Feature selection analysis showed that ALT is an important attribute for M3 in the female but not in male group (mean Z: 3.85 vs. 0.107). Multiple regression analysis confirmed that BMI (p < 0.0001) and ALT (p = 0.00991) significantly and independently predicted clamp measured muscle glucose uptake in women (R(2) = 0.5259), while in men serum fasting insulin (p = 0.0210) and leptin levels (p = 0.0294) but none of the liver enzymes were confirmed as significant independent predictors of M3 (R(2) = 0.4989).

Conclusion: There is a gender specific association between insulin sensitivity, metabolic risk factors and liver transaminase levels. This might explain the sex difference in the predictive role of ALT elevation for CV disease. Moreover, ALT may be used as a simple diagnostic tool to identify insulin resistant subjects only in the female population according to our results.

No MeSH data available.


Related in: MedlinePlus

Scatter plots for bivariate correlations between liver enzymes and component of metabolic syndrome. Scatter plots in men (black spots) and women (red spots) representing bivariate (Spearman) correlations between HIRI, M3, basal glucose, TG, AC and liver enzymes (ALT, AST, GGT). Correlation coefficients are indicated in black (men), and in red (women). Correction done for BMI, age, HBA1c, genetic disposition and alcohol consumption. Significance level of each correlation is further indicated *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001
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Fig2: Scatter plots for bivariate correlations between liver enzymes and component of metabolic syndrome. Scatter plots in men (black spots) and women (red spots) representing bivariate (Spearman) correlations between HIRI, M3, basal glucose, TG, AC and liver enzymes (ALT, AST, GGT). Correlation coefficients are indicated in black (men), and in red (women). Correction done for BMI, age, HBA1c, genetic disposition and alcohol consumption. Significance level of each correlation is further indicated *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001

Mentions: Scatter plots with Spearman correlation coefficients are shown in Fig. 2 between M3, HIRIOGTT, TG, abdominal circumference (i.e. major components of metabolic syndrome) and ALT. Furthermore, simple bivariate and partial correlation coefficients are listed in Table 2 between liver enzymes (AST, ALT and GGT) and metabolic parameters (including M3, HIRI, blood sugar level, insulin secretion, lipids and adipocytokines), after correcting for age, BMI, alcohol consumption, HbA1c, abdominal circumference (and FSH in females). In males triglyceride, HDL-cholesterol, free fatty acid and AIR show significant correlations with ALT (and AST) after adjusting with the above confounding factors, while in females it is the clamp measured glucose uptake per se along with blood sugar values that stay significantly related after correction is done (see Fig. 2 and Table 2). GGT is rather non sex-specific, i.e. corrected associations with GGT show a similar pattern in both genders.Fig. 2


Sex influenced association of directly measured insulin sensitivity and serum transaminase levels: Why alanine aminotransferase only predicts cardiovascular risk in men?

Buday B, Pach PF, Literati-Nagy B, Vitai M, Kovacs G, Vecsei Z, Koranyi L, Lengyel C - Cardiovasc Diabetol (2015)

Scatter plots for bivariate correlations between liver enzymes and component of metabolic syndrome. Scatter plots in men (black spots) and women (red spots) representing bivariate (Spearman) correlations between HIRI, M3, basal glucose, TG, AC and liver enzymes (ALT, AST, GGT). Correlation coefficients are indicated in black (men), and in red (women). Correction done for BMI, age, HBA1c, genetic disposition and alcohol consumption. Significance level of each correlation is further indicated *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4492083&req=5

Fig2: Scatter plots for bivariate correlations between liver enzymes and component of metabolic syndrome. Scatter plots in men (black spots) and women (red spots) representing bivariate (Spearman) correlations between HIRI, M3, basal glucose, TG, AC and liver enzymes (ALT, AST, GGT). Correlation coefficients are indicated in black (men), and in red (women). Correction done for BMI, age, HBA1c, genetic disposition and alcohol consumption. Significance level of each correlation is further indicated *: p < 0.05, **: p < 0.01, ***: p < 0.001, ****: p < 0.0001
Mentions: Scatter plots with Spearman correlation coefficients are shown in Fig. 2 between M3, HIRIOGTT, TG, abdominal circumference (i.e. major components of metabolic syndrome) and ALT. Furthermore, simple bivariate and partial correlation coefficients are listed in Table 2 between liver enzymes (AST, ALT and GGT) and metabolic parameters (including M3, HIRI, blood sugar level, insulin secretion, lipids and adipocytokines), after correcting for age, BMI, alcohol consumption, HbA1c, abdominal circumference (and FSH in females). In males triglyceride, HDL-cholesterol, free fatty acid and AIR show significant correlations with ALT (and AST) after adjusting with the above confounding factors, while in females it is the clamp measured glucose uptake per se along with blood sugar values that stay significantly related after correction is done (see Fig. 2 and Table 2). GGT is rather non sex-specific, i.e. corrected associations with GGT show a similar pattern in both genders.Fig. 2

Bottom Line: Significant bivariate correlations were found between clamp measured M3 and all three liver enzymes (ALT, aspartate aminotransferase and gamma-glutamyl transferase) in both sexes.When data were adjusted for possible metabolic confounding factors correlations ceased in the male population but stayed significant in the female group.Moreover, ALT may be used as a simple diagnostic tool to identify insulin resistant subjects only in the female population according to our results.

View Article: PubMed Central - PubMed

Affiliation: Drug Research Center, Department of Metabolism, Balatonfüred, Hungary. budaybarb@hotmail.com.

ABSTRACT

Background: Non alcoholic fatty liver disease (NAFLD) is an independent cardiovascular (CV) risk factor which is closely associated with insulin resistance measured by both direct or indirect methods. Gender specific findings in the relationship between alanine aminotransferase (ALT) and CV disease, the prevalence of NAFLD and type 2 diabetes (T2DM) have been published recently. The aim of the present study was to explore the gender aspects of the association between insulin sensitivity, liver markers and other metabolic biomarkers in order to elucidate the background behind the sex influenced difference in both NAFLD, T2DM and their association with CV risk.

Patients and methods: 158 female (47 normal and 111 impaired glucose intolerant) and 148 male (74 normal and 74 impaired glucose tolerant) subjects were included (mean age: 46.5 ± 8.31 vs. 41.6 ± 11.3, average Hba1c < 6.1 %, i.e. prediabetic population, drug naive at the time of the study). Subjects underwent a hyperinsulinemic normoglycemic clamp to determine muscle glucose uptake (M3), besides liver function tests and other fasting metabolic and anthropometric parameters were determined.

Results: Significant bivariate correlations were found between clamp measured M3 and all three liver enzymes (ALT, aspartate aminotransferase and gamma-glutamyl transferase) in both sexes. When data were adjusted for possible metabolic confounding factors correlations ceased in the male population but stayed significant in the female group. Feature selection analysis showed that ALT is an important attribute for M3 in the female but not in male group (mean Z: 3.85 vs. 0.107). Multiple regression analysis confirmed that BMI (p < 0.0001) and ALT (p = 0.00991) significantly and independently predicted clamp measured muscle glucose uptake in women (R(2) = 0.5259), while in men serum fasting insulin (p = 0.0210) and leptin levels (p = 0.0294) but none of the liver enzymes were confirmed as significant independent predictors of M3 (R(2) = 0.4989).

Conclusion: There is a gender specific association between insulin sensitivity, metabolic risk factors and liver transaminase levels. This might explain the sex difference in the predictive role of ALT elevation for CV disease. Moreover, ALT may be used as a simple diagnostic tool to identify insulin resistant subjects only in the female population according to our results.

No MeSH data available.


Related in: MedlinePlus