In the Journals

Liver enzymes predict type 2 diabetes

The development of type 2 diabetes among middle-aged Japanese men is associated with parallel increases in levels of the liver enzymes alanine aminotransferase and gamma-glutamyl transferase, according to findings published in the Journal of Diabetes Investigation.

“When you are becoming obese, your adipocytes store surplus [triglyceride] in the cells until its limits. Afterward, surplus energy will be stored ectopically, especially in the liver. The process would involve hepatocyte injuries,” Hiroshi Yatsuya, MD, professor of Fujita Health University, Japan, and visiting professor of Nagoya University, Japan, told Endocrine Today. “Since liver physiologically maintains fasting glucose levels, its injury could lead to high fasting insulin and eventually to [type 2 diabetes] development.”

Yatsuya and colleagues analyzed data from 2,775 Japanese men enrolled in the Aichi Workers’ Cohort Study from 2002 to 2014. Participants were aged 35 to 66 years (mean age, 48.1 years) at baseline, did not have diabetes and were followed up annually through yearly medical checkups. In 2002, participants underwent fasting blood tests to determine alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels. Three separate groups were created from initial readings: those with lower levels of both ALT and GGT (n = 1,417), those with higher levels of either (n = 803) and those with elevated levels of both (n = 555). The researchers also collected self-reported data on alcohol consumption, smoking status and physical activity.

During the 12-year examination period, 276 participants were diagnosed with type 2 diabetes. Those with higher levels of ALT and GGT were more susceptible to the development of type 2 diabetes vs. those with lower levels of both. On fully adjusted models, HR for diabetes per each 1-standard deviation increase in GGT was 1.1 (95% CI, 0.9-1.3), and HR per each 1-standard deviation increase in ALT was 1.2 (95% CI, 1.1-1.4).

The researchers noted that the participants with higher levels of GGT were also more likely to have higher levels of alcohol consumption, BMI, serum triglycerides, and fasting insulin and blood glucose levels. However, participants with low levels of alcohol consumption and “normal weight” also had higher rates of type 2 diabetes development when GGT and ALT levels were increased, indicating that such confounding factors did not play a significant role in this specific study.

Researchers found that the presence of higher triglyceride levels generally led to more incident type 2 diabetes among those with elevated GGT and ALT readings.

“This finding may indicate that the simultaneous presence of hepatic fat accumulation (high [triglyceride]) and liver injury (high ALT) as well as oxidative stress (high GGT), is etiologically involved in the development of [type 2 diabetes],” the researchers wrote.

Clinicians may be better able to anticipate type 2 diabetes in patients through the addition of liver enzymes, they wrote. With such predictive improvements possible, Yatsuya said clinicians should “intensify lifestyle counseling to individuals with elevated blood GGT and ALT,” while further research could enhance additional clinical applications.

“Liver injury expressed by elevation of both GGT and ALT should be avoided to prevent [type 2 diabetes]. ... Investigations are warranted in those with elevated GGT and ALT for the cause of their elevation so as to plan [type 2 diabetes] preventive measures,” the researchers wrote. “Finally, the molecular pathway leading from the concomitant elevation of triglycerides, ALT, and GGT to [type 2 diabetes] development should be elucidated.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.

The development of type 2 diabetes among middle-aged Japanese men is associated with parallel increases in levels of the liver enzymes alanine aminotransferase and gamma-glutamyl transferase, according to findings published in the Journal of Diabetes Investigation.

“When you are becoming obese, your adipocytes store surplus [triglyceride] in the cells until its limits. Afterward, surplus energy will be stored ectopically, especially in the liver. The process would involve hepatocyte injuries,” Hiroshi Yatsuya, MD, professor of Fujita Health University, Japan, and visiting professor of Nagoya University, Japan, told Endocrine Today. “Since liver physiologically maintains fasting glucose levels, its injury could lead to high fasting insulin and eventually to [type 2 diabetes] development.”

Yatsuya and colleagues analyzed data from 2,775 Japanese men enrolled in the Aichi Workers’ Cohort Study from 2002 to 2014. Participants were aged 35 to 66 years (mean age, 48.1 years) at baseline, did not have diabetes and were followed up annually through yearly medical checkups. In 2002, participants underwent fasting blood tests to determine alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels. Three separate groups were created from initial readings: those with lower levels of both ALT and GGT (n = 1,417), those with higher levels of either (n = 803) and those with elevated levels of both (n = 555). The researchers also collected self-reported data on alcohol consumption, smoking status and physical activity.

During the 12-year examination period, 276 participants were diagnosed with type 2 diabetes. Those with higher levels of ALT and GGT were more susceptible to the development of type 2 diabetes vs. those with lower levels of both. On fully adjusted models, HR for diabetes per each 1-standard deviation increase in GGT was 1.1 (95% CI, 0.9-1.3), and HR per each 1-standard deviation increase in ALT was 1.2 (95% CI, 1.1-1.4).

The researchers noted that the participants with higher levels of GGT were also more likely to have higher levels of alcohol consumption, BMI, serum triglycerides, and fasting insulin and blood glucose levels. However, participants with low levels of alcohol consumption and “normal weight” also had higher rates of type 2 diabetes development when GGT and ALT levels were increased, indicating that such confounding factors did not play a significant role in this specific study.

Researchers found that the presence of higher triglyceride levels generally led to more incident type 2 diabetes among those with elevated GGT and ALT readings.

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“This finding may indicate that the simultaneous presence of hepatic fat accumulation (high [triglyceride]) and liver injury (high ALT) as well as oxidative stress (high GGT), is etiologically involved in the development of [type 2 diabetes],” the researchers wrote.

Clinicians may be better able to anticipate type 2 diabetes in patients through the addition of liver enzymes, they wrote. With such predictive improvements possible, Yatsuya said clinicians should “intensify lifestyle counseling to individuals with elevated blood GGT and ALT,” while further research could enhance additional clinical applications.

“Liver injury expressed by elevation of both GGT and ALT should be avoided to prevent [type 2 diabetes]. ... Investigations are warranted in those with elevated GGT and ALT for the cause of their elevation so as to plan [type 2 diabetes] preventive measures,” the researchers wrote. “Finally, the molecular pathway leading from the concomitant elevation of triglycerides, ALT, and GGT to [type 2 diabetes] development should be elucidated.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.