GGT in diabetes mellitus

• serum gamma-glutamyltransferase (GGT) levels are raised in obese individuals - a particularly strong association with central obesity has been described. It has been hypothesized that elevated GGT levels are a marker for visceral fat, and specifically for hepatic steatosis (fatty liver), and that hepatic steatosis leads to hepatic insulin resistance. This hypothesis has been studied in a prospective study (1).
  • a group of 7,458 nondiabetic men (aged 40-59 years) followed for a mean of 12.8 years (range 11.5-13.0). The men were randomly selected from general practice lists in 24 British towns
  • cases of non-insulin depedent diabetes mellitus (NIDDM) were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records
  • a total of 194 men developed NIDDM during follow-up
    • mean serum GGT at baseline (geometric mean [95% CI]) was significantly higher in the NIDDM patients than in the rest of the cohort (20.9 [19.3-22.6] vs. 15.3 U/l [15.0-15.6], P < 0.0001)
    • there was a smooth, graded increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a relative risk in the top fifth of the distribution of 6.8 (3.5-12.9) relative to the bottom fifth (trend P < 0.0001)
    • this association was independent of serum glucose and BMI and of other predictors of NIDDM with which GGT is associated, including alcohol intake and physical activity level (adjusted upper to lower fifth relative risk: 4.8 [2.0-11.8], trend P < 0.0001])
  • the authors concluded that these findings suggested that a raised serum GGT level is an independent risk factor for NIDDM. Also serum GGT level may be a simple and reliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance

A study has provided more evidence for the link between GGT level and development of Type 2 Diabetes and impaired fasting glycaemia (IFG) (2). This study however showed that the increased relative risk for IFG or type 2 diabetes associated with serum GGT was more pronounced in obese men.

Significance of raised GGT in first degree relatives of type 2 Diabetics:

• GGT activity could reflect several different processes relevant to diabetes pathogenesis and the increasing rate of type 2 diabetes worldwid e (3)
  • a study was to assess the association between serum GGT concentrations and glucose intolerance, in the first-degree relatives (FDR) of type 2 diabetic patients
  • the study authors concluded that measurement of GGT in FDRs of type 2 diabetic patients may be useful in assessing the risk of diabetes; those with chronically high levels of GGT should be considered as high risk group for diabetes

The NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study is a population based longitudinal study at Murakami Memorial Hospital (Gifu, Japan), which was designed to promote public health by detecting chronic diseases and evaluating their risk factors. Investigators studied the dose-response relationship between GGT and risk of diabetes mellitus in this population (4):

• study results showed an increase of serum GGT levels was independently associated with a higher incidence of diabetes mellitus in this prospective study during 5.4-year follow-up of Japanese participants

Reference:

1. Diabetes Care. 1998 May;21(5):732-7.
2. J Intern Med. 2003 Sep;254(3):287-95.
3. Haghighi S et al. Relationship between gamma-glutamyl transferase and glucose intolerance in first degree relatives of type 2 diabetics patients. J Res Med Sci. 2011 Feb; 16(2): 123–129
4. Zhaoe W et al. The Dose-Response Relationship between Gamma-Glutamyl Transferase and Risk of Diabetes Mellitus Using Publicly Available Data: A Longitudinal Study in Japan. Int J Endocrinol. 2020; 2020: 5356498.