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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

Feature selection (Boruta algorithm) analysis for M3 in men. Important attributes are marked in green: abdominal circumference, insulin, body fat percentage, leptin, BMI, diastolic blood pressure, TG, basal FFA, serum glucose and age (mean Z values: 16.65, 13.08, 12.19, 11.77, 6.12, 6.00, 5.39, 4.92 and 4.11, respectively). Yellow and red columns represent attributes that were rejected or ‘tentative’ as being important for M3. These are (in order of importance): systolic blood pressure, GGT, total cholesterol, alcohol consumption, small-dense LDL %, adiponectin, serum-bilirubin, HbA1c, total-LDL %, AST, genetic predisposition, alkaline phosphatase, HDL %, ALT, white blood cell count, LDL-1 %, creatinin, VLDL %. Blue columns represent ‘shadow attributes’. Mean, median, minimum and maximum Z values are represented on ‘Y’ axis
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Fig4: Feature selection (Boruta algorithm) analysis for M3 in men. Important attributes are marked in green: abdominal circumference, insulin, body fat percentage, leptin, BMI, diastolic blood pressure, TG, basal FFA, serum glucose and age (mean Z values: 16.65, 13.08, 12.19, 11.77, 6.12, 6.00, 5.39, 4.92 and 4.11, respectively). Yellow and red columns represent attributes that were rejected or ‘tentative’ as being important for M3. These are (in order of importance): systolic blood pressure, GGT, total cholesterol, alcohol consumption, small-dense LDL %, adiponectin, serum-bilirubin, HbA1c, total-LDL %, AST, genetic predisposition, alkaline phosphatase, HDL %, ALT, white blood cell count, LDL-1 %, creatinin, VLDL %. Blue columns represent ‘shadow attributes’. Mean, median, minimum and maximum Z values are represented on ‘Y’ axis

Mentions: Feature selection analysis (Boruta algorithm) confirmed the difference between sexes (Fig. 3 and Fig. 4). The analysis was carried out separately in males and females to determine the list of ‘important attributes’ for M3, determined by the “Z” value (axis Y: mean, median, minimum and maximum values). ALT proved to be an ‘important’ attribute for M3 only in females besides BMI, BFP, AC, serum insulin and FFA levels (“Z” values see on Fig. 3). In men, on the other hand, none of the transaminase levels, instead leptin, diastolic blood pressure, TG, serum glucose and age were confirmed as ‘important variables’ besides AC, serum insulin, BFP, BMI and FFA which were common with the female group (Fig. 4).Fig. 3


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)

Feature selection (Boruta algorithm) analysis for M3 in men. Important attributes are marked in green: abdominal circumference, insulin, body fat percentage, leptin, BMI, diastolic blood pressure, TG, basal FFA, serum glucose and age (mean Z values: 16.65, 13.08, 12.19, 11.77, 6.12, 6.00, 5.39, 4.92 and 4.11, respectively). Yellow and red columns represent attributes that were rejected or ‘tentative’ as being important for M3. These are (in order of importance): systolic blood pressure, GGT, total cholesterol, alcohol consumption, small-dense LDL %, adiponectin, serum-bilirubin, HbA1c, total-LDL %, AST, genetic predisposition, alkaline phosphatase, HDL %, ALT, white blood cell count, LDL-1 %, creatinin, VLDL %. Blue columns represent ‘shadow attributes’. Mean, median, minimum and maximum Z values are represented on ‘Y’ axis
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Feature selection (Boruta algorithm) analysis for M3 in men. Important attributes are marked in green: abdominal circumference, insulin, body fat percentage, leptin, BMI, diastolic blood pressure, TG, basal FFA, serum glucose and age (mean Z values: 16.65, 13.08, 12.19, 11.77, 6.12, 6.00, 5.39, 4.92 and 4.11, respectively). Yellow and red columns represent attributes that were rejected or ‘tentative’ as being important for M3. These are (in order of importance): systolic blood pressure, GGT, total cholesterol, alcohol consumption, small-dense LDL %, adiponectin, serum-bilirubin, HbA1c, total-LDL %, AST, genetic predisposition, alkaline phosphatase, HDL %, ALT, white blood cell count, LDL-1 %, creatinin, VLDL %. Blue columns represent ‘shadow attributes’. Mean, median, minimum and maximum Z values are represented on ‘Y’ axis
Mentions: Feature selection analysis (Boruta algorithm) confirmed the difference between sexes (Fig. 3 and Fig. 4). The analysis was carried out separately in males and females to determine the list of ‘important attributes’ for M3, determined by the “Z” value (axis Y: mean, median, minimum and maximum values). ALT proved to be an ‘important’ attribute for M3 only in females besides BMI, BFP, AC, serum insulin and FFA levels (“Z” values see on Fig. 3). In men, on the other hand, none of the transaminase levels, instead leptin, diastolic blood pressure, TG, serum glucose and age were confirmed as ‘important variables’ besides AC, serum insulin, BFP, BMI and FFA which were common with the female group (Fig. 4).Fig. 3

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