Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Williams, Kathryn; Sullivan, David; Nicholson, Geoffrey C.; George, Jacob; Jenkins, Alicia J.; Januszewski, Andrzej S.; Gebski, Val; Manning, Patrick J.; Tan, Yong Mong; Donoghoe, Mark; Ehnholm, Christian; Young, Simon; O'Brien, Richard C; Buizen, Luke; Twigg, Stephen M.; Keech, Anthony

doi:10.1016/j.metabol.2015.12.008

Cited by 20 publications

(24 citation statements)

References 57 publications

(94 reference statements)

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“…Meta-analyses also confirmed that low serum ALT levels were associated with increased overall and cardiovascular mortality in older populations [2, 3]. Similar results were reported in patients with heart failure [20], diabetes [21], and previous myocardial infarction or stroke [4]. The exact mechanism involved in the relationship between low serum ALT levels and increased mortality has not yet been elucidated.…”

Section: Discussionsupporting

confidence: 55%

Age-dependent relationship between preoperative serum aminotransferase and mortality after cardiovascular surgery

Nam

Kim

et al. 2019

Aging

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Although serum aminotransferase levels are frequently measured for preoperative evaluation, their prognostic value to postoperative outcomes remain unclear. This study aimed to investigate the relationship between preoperative serum aminotransferase levels and postoperative 90-day mortality in patients undergoing cardiovascular surgery. We included adult patients (n=6264) who underwent cardiovascular surgery between January 2010 and December 2016 at a tertiary academic hospital. Preoperative serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and De Ritis ratio (defined as AST/ALT) were categorized into three groups: low (≤20th percentile), middle (20th–80th percentile), and high (>80th percentile). Of the 6264 patients enrolled (40.4% women; median age, 62 years), 183 (2.9%) died within 90 days postoperatively. Multivariable-adjusted analyses revealed low ALT (hazard ratio 1.58, 95% confidence interval, 1.14–2.18) and high De Ritis ratio (hazard ratio 1.59, 95% confidence interval, 1.15–2.20) were independent predictors of postoperative mortality, but AST did not have a statistically significant association. The association of low ALT and high De Ritis ratio with 90-day mortality was more pronounced in patients older than 60 years (P-values for interaction <0.05). Therefore, preoperative serum aminotransferase levels may be a valuable prognostic marker in patients with cardiovascular surgery, particularly in the elderly.

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Section: Discussionsupporting

confidence: 55%

Age-dependent relationship between preoperative serum aminotransferase and mortality after cardiovascular surgery

Nam

Kim

et al. 2019

Aging

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“…Consequently, patients with such ALT measurements were excluded from analysis whenever incorporating ALT patients' values. There are several comprehensive publications describing the association between decreased level of ALT activity in the peripheral blood, sarcopenia, frailty, and increased risk of all-cause mortality in middle-aged, heterogeneous populations [13,[17][18][19][33][34][35][36].…”

Section: Alt Measurementmentioning

confidence: 99%

Frailty and Sarcopenia Assessment upon Hospital Admission to Internal Medicine Predicts Length of Hospital Stay and Re-Admission: A Prospective Study of 980 Patients

Anani

Goldhaber

Brom

et al. 2020

JCM

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Background: Frailty and sarcopenia are associated with frequent hospitalizations and poor clinical outcomes in geriatric patients. Ascertaining this association for younger patients hospitalized in internal medicine departments could help better prognosticate patients in the realm of internal medicine. Methods: During a 1-year prospective study in an internal medicine department, we evaluated patients upon admission for sarcopenia and frailty. We used the FRAIL questionnaire, blood alanine-amino transferase (ALT) activity, and mid-arm muscle circumference (MAMC) measurements. Results: We recruited 980 consecutive patients upon hospital admission (median age 72 years (IQR 65–79); 56.8% males). According to the FRAIL questionnaire, 106 (10.8%) patients were robust, 368 (37.5%) pre-frail, and 506 (51.7%) were frail. The median ALT value was 19IU/L (IQR 14–28). The median MAMC value was 27.8 (IQR 25.7–30.2). Patients with low ALT activity level (<17IU/L) were frailer according to their FRAIL score (3 (IQR 2–4) vs. 2 (IQR 1–3); p < 0.001). Higher MAMC values were associated with higher ALT activity, both representing robustness. The rate of 30 days readmission in the whole cohort was 17.4%. Frail patients, according to the FRAIL score (FS), had a higher risk for 30 days readmission (for FS > 2, HR = 1.99; 95CI = 1.29–3.08; p = 0.002). Frail patients, according to low ALT activity, also had a significantly higher risk for 30 days readmission (HR = 2.22; 95CI = 1.26–3.91; p = 0.006). After excluding patients whose length of stay (LOS) was ≥10 days, 252 (27.5%) stayed in-hospital for 4 days or longer. Frail patients according to FS had a higher risk for LOS ≥4 days (for FS > 2, HR = 1.87; 95CI = 1.39–2.52; p < 0.001). Frail patients, according to low ALT activity, were also at higher risk for LOS ≥4 days (HR = 1.87; 95CI = 1.39–2.52; p < 0.001). MAMC values were not correlated with patients’ LOS or risk for re-admission. Conclusion: Frailty and sarcopenia upon admission to internal medicine departments are associated with longer hospitalization and increased risk for re-admission.

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“…Our study reported an elevated ALT level increased HCC risk in Chinese type 2 diabetic patients, indicating significant interactions for ALT ≥ 40 IU/L with liver cirrhosis and HBV on HCC risk as well as joint associations of ALT ≥ 40 U/L and chronic liver diseases. In a recent study conducted by Williams et al [ 11 ], they have failed to find an association between ALT levels and cancer mortality in patients with type 2 diabetes. The possible reasons that can explain the different findings are the smaller sample size in Williams’s study (n=9,795 vs. n=46,369) and the shorter follow-up period (5 years vs. 8 years).…”

Section: Discussionmentioning

confidence: 99%

“…However, most studies evaluating the relationship between ALT and HCC have focused on patients with B/C virus infection. A recent study examined the relationship between ALT and cancer-specific mortality in diabetic patients but found no such an association existed [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Interaction and joint effect of ALT and chronic liver disease on liver cancer in type 2 diabetes patients

Liu

Lin

et al. 2017

Oncotarget

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BackgroundThis study examined whether serum alanine transaminase (ALT) and chronic liver diseases were interactively, jointly, or independently associated with hepatocellular carcinoma (HCC) risk in type 2 diabetic patients.Materials and MethodsA retrospective cohort study was conducted in 46,369 Chinese type 2 diabetic patients, aged 30 and older, in National Diabetes Care Management Program in 2002-2004. These data were analyzed by multivariate Cox proportional hazards models.ResultsMean follow-up period was 8.20 years. Multivariate-adjusted hazard ratios of HCC were 2.85 (95% confidence interval, CI: 2.45–3.31), 3.80 (3.04–4.76), and 3.89 (3.08–4.91) for patients with a level of ALT 40–80, 80–120, and >120 U/L, respectively, compared with patients with a level of ALT < 40 U/L after multivariable adjustment. Significant hazard ratios of HCC for patients with a level of ALT ≥ 40 U/L and alcoholic liver damage, nonalcoholic fatty liver disease, liver cirrhosis, hepatitis B virus and hepatitis C virus infection, or any one of these chronic liver diseases compared with patients with ALT level < 40 U/L and no counterpart comorbidity were observed. Significant effect modifications were observed between ALT level with liver cirrhosis and HBV.ConclusionsResults suggest significant effect modification and joint associations of ALT ≥ 40 U/L and chronic liver diseases. Diabetes care should provide lifestyle or treatment interventions to manage ALT level, liver cirrhosis and hepatitis B virus infection for reducing burden of HCC.

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Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Cited by 20 publications

References 57 publications

Age-dependent relationship between preoperative serum aminotransferase and mortality after cardiovascular surgery

Age-dependent relationship between preoperative serum aminotransferase and mortality after cardiovascular surgery

Frailty and Sarcopenia Assessment upon Hospital Admission to Internal Medicine Predicts Length of Hospital Stay and Re-Admission: A Prospective Study of 980 Patients

Interaction and joint effect of ALT and chronic liver disease on liver cancer in type 2 diabetes patients

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