A Strong Interaction between Serum γ-Glutamyltransferase and Obesity on the Risk of Prevalent Type 2 Diabetes: Results from the Third National Health and Nutrition Examination Survey

Lim, Ji Sun; Lee, Dong Hoon; Park, Joo Yun; Jin, Soo Hee; Jacobs, David R.

doi:10.1373/clinchem.2006.079814

Cited by 79 publications

(62 citation statements)

References 21 publications

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“…These findings differ from a previous crosssectional report, which, in a large sample of the US population, showed a stronger association between elevated plasma GGT levels and the risk of prevalent diabetes in persons with obesity than in those with a lower BMI [19]. However, as this study was not prospective and considered only newly recognised diabetes, the potential confounding impact of hyperglycaemia on the level of GGT could not be investigated.…”

Section: Discussioncontrasting

confidence: 91%

Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of γ-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

et al. 2009

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Aims/hypothesis Risk factors for incident type 2 diabetes, in particular, hepatic markers, have rarely been studied in leaner individuals. We aimed to identify the metabolic and hepatic markers associated with incident diabetes in men and women with a BMI of <27 kg/m 2 and to compare them with those in individuals with a BMI of ≥27 kg/m 2 . Methods Risk factors for 9 year incident diabetes were compared in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. Comparisons were made between the 2,947 participants with a BMI of <27 kg/m 2 and the 879 with a BMI of ≥27 kg/m 2 . Results There were 92 incident cases of diabetes in individuals with a BMI of <27 kg/m 2 and 111 in those with a BMI of ≥27 kg/m 2 . Among those who were not markedly overweight, classical biological markers were associated with 9 year incident diabetes, glycaemia being the strongest predictor. γ-Glutamyltransferase (GGT), either considered as a continuous variable or at levels ≥20 U/l, was associated with incident diabetes, with a stronger effect in the BMI <27 kg/m 2 group: OR 1.59 (95% CI 1.29-1.97, p<0.001) in comparison with OR 1.07 (95% CI 0.82-1.38, p=0.63) for those with a BMI of ≥27 kg/m 2 (results after adjustment for alcohol intake, alanine aminotransferase, waist circumference and the HOMA insulin resistance index). Conclusions/interpretation In individuals with a BMI of <27 kg/m 2 , GGT was the strongest predictor of diabetes after fasting hyperglycaemia. This association with incident diabetes remained after adjustment for conventional markers of insulin resistance, suggesting potential interactions between GGT, enhanced hepatic neoglucogenesis and/or early alterations of insulin secretion.

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Section: Discussioncontrasting

confidence: 91%

Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of γ-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

et al. 2009

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“…Furthermore, the association between serum GGT and type 2 diabetes was stronger among the obese, and obesity did not predict the risk of type 2 diabetes among participants with GGT levels at the low end of the normal range [1]. A similar pattern of associations was observed in datasets from the Coronary Artery Risk Development in Young Adults (CARDIA) study [2], the Finland Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (FinMONICA) study [3], the National Health and Nutrition Examination Survey (NHANES) [4], and in German women, but not men [5], leading us to search for new interpretations of serum GGT. Cellular GGT, found on the plasma membrane in most tissues [6], metabolises extracellular glutathione (GSH), the main intracellular antioxidant, allowing precursor amino acids to be reutilised for intracellular GSH re-synthesis [7]a process known as the 'γ-glutamyl cycle' (Fig.…”

mentioning

confidence: 56%

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

2007

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The results of several epidemiological studies of serum γ-glutamyltransferase (GGT) led us to hypothesise that associations of GGT within its normal range with type 2 diabetes may reflect detrimental effects of xenobiotics found in the environment, such as persistent organic pollutants (POPs). Epidemiological observations showed that serum GGT activity within its normal range strongly predicted future type 2 diabetes; the predictability of diabetes from obesity was low with GGT at the low end of the normal range; and GGT showed a positive association with known markers of oxidative stress or inflammation. Experimental findings on cellular GGT suggest that serum GGT levels within the normal range may reflect oxidative stress related to the re-synthesis of intracellular glutathione; however, this interpretation is not completely satisfying because, in its role of regenerating intracellular glutathione, GGT activity should be antioxidative.

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“…Many investigators recommend measurements of plasma enzymes to test for FLHS (Diaz et al, 1999;Walzem et al, 1993) and suggest that enzyme activities are indicative of liver damage in birds, in particular AST, LDH, and GDH. In this study, GGT was measured as it is a more sensitive and specific indicator of liver dysfunction in mammals and birds (Center, 2007;Lim et al, 2007). From studies in humans and animals it has been shown that there is a correlation between GGT and TG in patients with steatohepatitis (Lim et al, 2007;Sakugawa et al, 2004).…”

Section: Discussionmentioning

confidence: 95%

Fatty Liver Haemorrhagic Syndrome in Laying Hens: Field and Experimental Investigations

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Field and experimental investigations were conducted to study the fatty liver haemorrhagic syndrome (FLHS) in caged laying hens. The main goal of the research was to gain a greater understanding of the aetiology and pathogenesis of this non-infectious disease. The disease is characterized by excessive accumulation of fat in the liver and abdominal cavity, subsequent liver rupture, haemorrhage and sudden death of hens. It has been shown that the balance between hepatic synthesis and secretion of lipids is the key point that regulates hepatic and extrahepatic fat deposition in hens. Liver fat accumulation can be increased by many factors, especially nutrition, housing conditions, and inflammatory challenges. A description of normal and abnormal lipid metabolism in the hen, and consequences for hen health and disease (including FLHS) is given in the literature review (Chapter 2).The initial study examined mortality of layer flocks kept in three different housing systems (cage, barn and free range) on the Gatton Campus, University of Queensland (Chapter 4). It was shown that there were no significant differences in mortality rates of hens (6.1%, 6.4% and 5.8%, for cages, barns and free range, respectively) between the housing systems but the causes of death were different. The most common cause of death in hens kept in cages was FLHS with 74% of dead hens dying from the condition. In contrast, FLHS only accounted for 0 to 5% of hen mortality in the other systems. Post-mortem of dead hens and body weight monitoring of flocks throughout the laying cycle were recommended as tools to predict FLHS.An epidemiological survey (Chapter 5) of caged flocks in South-Eastern Queensland was undertaken to explore the prevalence of FLHS in commercial layer flocks. From necropsies of dead birds from 7 flocks of different ages, it was found that approximately 40% of hens died due to FLHS. This result indicated that FLHS continues to be the major cause of mortality in commercial caged laying hens kept in either controlled environment sheds or naturally ventilated sheds. As part of the epidemiological study, a questionnaire was circulated among farms and the responses revealed that there is a general lack of knowledge of FLHS in the industry.The study of the pathogenesis of FLHS is very difficult as it occurs sporadically and over an extended period of time in the field. In the studies in Chapter 6, an oestradiol (E 2 ) hen model was used to study the condition. The administration of exogenous E 2 reproduced the disease in 30 wk old laying hens, and was associated with significant changes in E 2 plasma levels and metabolic iv profiles, increased liver weights, and macroscopic (fat depositions, haemorrhages and haematomas) and microscopic alterations. Hens exposed to E 2 and fed ad libitum diet experienced severe FLHS and had a higher incidence of FLHS than hens that had their feed intake restricted by 10%. One interesting observation from this study (not reported from other investigators) was the alteration of total leukocyte n...

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A Strong Interaction between Serum γ-Glutamyltransferase and Obesity on the Risk of Prevalent Type 2 Diabetes: Results from the Third National Health and Nutrition Examination Survey

Cited by 79 publications

References 21 publications

Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of γ-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of γ-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

Fatty Liver Haemorrhagic Syndrome in Laying Hens: Field and Experimental Investigations

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