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GGT: Diabetes, Metabolic Syndrome, Oxidative Stress and Mortality

As in our IRON Science Library, we will not present a lengthy narrative on each affected body system, but rather we will briefly summarize or quote the relevant take-home points and/or research conclusions from each study. Article titles are linked to abstracts archived at the U.S. National Library of Science. Many articles also have Full free text PDF links. Our Iron Science Library pages include:


Serum gamma-glutamyltransferase and risk of type 2 diabetes mellitus in men and women from the general population (1) Free full text

The object of this 2005 study was to "to examine gender-specific associations between gamma-glutamyltransferase (GGT) and incident type 2 diabetes mellitus in a representative population-based sample in Germany." The study recruited 1,851 men and 1,836 women during its baseline years of 1984 -1985. "A total of 172 cases of incident type 2 diabetes amongst men and 109 amongst women were registered during a mean follow-up period of 14.7 years. In both sexes the risk of type 2 diabetes increased with increasing levels of serum GGT. After multivariable adjustment HRs for incident type 2 diabetes across GGT categories (<25th, <50th, <75th, <87.5th and > or =87.5th percentiles) were 1.0, 1.81, 2.37, 3.41 and 4.24 (P-value for trend <0.0001) in men and 1.0, 1.42, 1.48, 1.95 and 2.41 (P-value for trend 0.0179) in women." The researchers concluded,"The GGT is an important predictor for incident type 2 diabetes in men and women from the general population." [Health-e-Iron note: Tables 2 and 3 from this study and an associated, data-derived Risk Analysis Tables appear directly below]

Table 2

Risk Analysis Table 1

Table 3

 

Health-e-Iron note: [76% of the newly diagnosed diabetes cases occurred among individuals with above median GGT at study entry, while only 40% of the cases were obese at study entry.]


Gamma-glutamyltransferase, obesity, and the risk of type 2 diabetes: observational cohort study among 20,158 middle-aged men and women (2) Free full text

In this 2005 study from Finland, researchers "studied serum GGT as a predictor of type 2 diabetes incidence and a possible interaction between obesity and GGT on the development of type 2 diabetes in men and women." In this study of 20,158 men and women age 25-64 who were followed over more than 12 years, "GGT cut points were set at the 25th, 50th, 75th, and 90th percentiles." "After adjustment for known risk factors of type 2 diabetes, relative risks for incident diabetes across GGT categories were 1.0, 1.2, 2.3, 3.1, and 3.9 among men and 1.0, 0.8, 1.7, 3.5, and 6.4 among women (P for trend < 0.01, respectively). The  research team concluded,"...in women as well as men, serum GGT level within its normal range predicted type 2 diabetes and may modify the well-known association between body mass index and type 2 diabetes." [Health-e-Iron note: Figure 1 and Table 2 from this article appear directly below. Of special note here is that GGT in the upper half of the population range increased the risk of diabetes by 100% in normal BMI ranges, by 150% in the overweight BMI range and by 268% in the obese BMI ranges (after adjusting for several relevant factors).  However, among all subjects, GGT in the upper half of the population range (21 U/L and above for men, or 12 U/L or above for women) increased the risk of incident diabetes by 450%]

 
Risk Analysis Table - The table below was derived from data in above Table 2  from the full text.


Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study (3) Free full text

In another 2005 study of liver enzymes in a population 1,441 men in Mexico City, "Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT (impaired fasting glucose) or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-hour post glucose plasma glucose concentrations. The researchers concluded, with respect to other liver enzymes, "only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress." [Health-e-Iron note; Figure 1 from this article appears below]

Note: NGT = Normal glucose tolerance; and IGT = Impaired glucose tolerance.


Association of serum gamma-glutamyltransferase and alanine aminotransferase activities with risk of type 2 diabetes mellitus independent of fatty liver
 (4)

In this 2009 study of GGT and another liver enzyme in 3,556 non-diabetic men and women, "compared to the first GGT quartile, the odds ratios for developing type 2 diabetes for the second, third, and fourth GGT quartiles were 0.64 (95% CI, 0.25-1.65), 1.12 (0.45-2.78), and 3.07 (1.21-7.76), respectively. The researchers concluded, "Increased serum GGT and ALT levels are independent, additive risk factors for the development of type 2 diabetes mellitus in subjects without fatty liver or hepatic dysfunction."


Associations between gamma-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: a possible implication for oxidative stress (5) Free full text

This 2005 report was preformed by researchers in Italy. "Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1,339 subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy)." "...after adjustments for multiple confounders..., median NT levels (an oxidative stress marker) are significantly associated with the increasing GGT tertile..., but not with the AST and ALT tertiles" The researchers concluded, "GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals." The researchers additionally stated, "in adult healthy subjects without any measurable metabolic abnormality, those with the highest GGT levels present with either higher fasting glucose values (even within the range of normality) and evidence of some oxidative stress or inflammation." [Health-e-Iron note; Figure 1 from this article appears below]


Serum gamma-glutamyl transferase level and diabetes mellitus among US adults (6) Free full text

This 2009 study involved 7,976 National Health and Nutrition Examination Survey 1999-2002 participants in the U.S. The authors reported,"Diabetes mellitus was defined as a fasting glucose > or = 126 mg/dl, nonfasting glucose > or = 200 mg/dl, or use of oral hypoglycemic medication or insulin (n = 805). Higher serum GGT levels were positively associated with diabetes mellitus, independent of, alcohol consumption, body mass index, hypertension and other confounders. Multivariable odds ratio (95% confidence interval) comparing quartile 4 of GGT (>33 U/L) to quartile 1 (<15 U/L) was 2.33 (1.59-3.41), P-trend < 0.0001. This association persisted in separate analysis among men and women." The authors concluded, "In nonparametric models, the positive association between serum GGT and diabetes appeared to be present across the full range of GGT, without any threshold effect. Higher serum GGT levels are positively associated with diabetes mellitus." [Health-e-Iron note: Table #2 from this papers appears below]




Relationship between gamma-glutamyl transferase and glucose intolerance in first degree relatives of type 2 diabetics patients
 (7) Free full text

The aim of this 2011 study conducted in Iran "was to assess the association between serum GGT concentrations and glucose intolerance, in the first-degree relatives (FDR) of type 2 diabetic patients. Among 551 non-diabetic relatives of type 2 diabetes patients, "(The) mean of GGT was 25.3 ± 12.1 IU/L. According to glucose tolerance test, 153 were normal and 217 and 181 were diabetic and prediabetic respectively. Mean of GGT in normal, prediabetic and diabetic patients was 23.5 ± 15.9 IU/L, 29.1 ± 28.1 IU/L and 30.9 ± 24.8 IU/L respectively (p = 0.000). The researchers concluded, "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." [Health-e-Iron note: Figure #1 from this study is below]

 

Three-year increase of gamma-glutamyltransferase level and development of type 2 diabetes in middle-aged men and women: the D.E.S.I.R, cohort (8) Free full text

In this 2006 study from France, the investigators stated, "Among hepatic markers, gamma-glutamyltransferase (GGT) is the main predictor for development of type 2 diabetes, but there are no data to date on changes in GGT and type 2 diabetes incidence." They research team studied 2,071 men and 2,130 women without baseline diabetes.In a fully adjusted model, "...an association between incident type 2 diabetes and unchanged or increased (as opposed to decreased) GGT levels were 2.54 (1.38-4.68) in men (p=0.003) and 2.78 (1.20-6.42) in women (p=0.02)." The team concluded, "An unchanged or increased GGT level over time, even when GGT is in the normal range, is correlated with increasing insulin resistance and is associated with a risk of incident type 2 diabetes in both sexes, independently of baseline GGTwhich is itself a diabetes risk factor."


Distribution, determinants, and prognostic value of gamma-glutamyltransferase for all-cause mortality in a cohort of construction workers from southern Germany (9)

In this 1997 study, "GGT levels were assessed among 8,043 construction workers ages 25-64 who underwent occupational health examinations in six centers in Southern Germany from 1986 to 1988. Study participants were followed for all-cause mortality until 1994."... "There was a strong dose-response relation between serum GGT levels and all-cause mortality (P value for trend < 0.001). Compared with men with GGT levels below 15 U/liter (measured at 25 degrees C), relative risks (95% CI) were 1.46 (0.86-2.49), 1.78 (1.08-2.94), 2.09 (1.26-3.45), and 3.44 (2.20-5.38) for men with GGT levels of 15-19, 20-29, 30-49, and > or = 50 U/liter, respectively. This relation was reduced but not eliminated by control for body mass index, diabetes, hypertension, alcohol consumption, and other covariates in multivariable analysis. The researchers concluded, "Serum GGT is a strong risk indicator of all-cause mortality." [Health-e-iron note: a table demonstrating these results appears below]


Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population (10) Free full text

In this 2009 U.S. study, "death certificate-based 12-year mortality was analyzed among 14,950 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994." "...abnormal GGT (was defined) as >51 U/L in men or >33 U/L in women...."All-cause mortality increased with elevated GGT (HR, 1.5; 95% CI, 1.2-1.8), as did mortality from liver disease (HR, 13.0; 95% CI, 2.4-71.5), neoplasms (HR, 1.5; 95% CI, 1.01-2.2), and diabetes (HR, 3.3; 95% CI, 1.4-7.6), but not from cardiovascular disease (HR, 1.3; 95% CI, 0.80-2.0). The researchers concluded, "In the US population, elevated GGT was associated with mortality from all causes, liver disease, cancer, and diabetes, ...." [Health-e-Iron note: although cardiovascular deaths in this study did not reach statistical significance, the all-cause mortality finding did. You can view many GGT cardiovascular and heart disease papers by linking to our GGT - Heart page] 

 

The value of gamma-glutamyltransferase in cardiovascular risk prediction in men without diagnosed cardiovascular disease or diabetes (11)

In this 2008 prospective study from the U.K. included, "6,997 men aged 40-59 with no history of CVD [cardiovascular disease], (CHD) (coronary heart disease or stroke)] or diabetes drawn from general practices in 24 British towns (who were) followed up for 24 years, "Risk of fatal CHD and CVD mortality was only elevated in the top quarter (22 U/L); risk of stroke tended to increase with increasing GGT. The adjusted relative risks (Q4 vs. Q1) were 1.43 (1.09,1.84) for fatal CHD events, 1.56 (1.20,2.04) for stroke incidence and 1.40 (1.16,1.70) for CVD mortality. When stratified by age groups stronger associations were seen between GGT and CVD mortality in the younger men (<55 years(p=0.01 for interaction)." The researchers concluded, "Elevated GGT is associated with significantly increased risk of stroke, fatal CHD events and CVD mortality independent of established CVD risk factors and may be a useful additional marker for long-term CVD risk."


Relationship of serum gamma-glutamyltransferase to atherogenic dyslipidemia and glycemic control in type 2 diabetes 
(12) Free full text

In 2009, this research team studied an Italian cohort and "evaluated possible interactions between BMI and GGT concentration." ..."in a cohort of 3,633 type 2 diabetic individuals." The investigators observed that "As GGT concentration increased, the association of BMI with atherogenic dyslipidemia and glycemic control strengthened (P = 0.01 and 0.004 for interactions, respectively): in contrast, the association of BMI with hypertension, hypercholesterolemia, and hyperuricemia did not change substantially across GGT quartiles."..."within the lowest GGT quartile, BMI was not associated with atherogenic dyslipidemia or poor glycemic control, whereas in the highest GGT quartile, the prevalence rates ranged from 62.3 to 74.7% for dyslipidemia and from 75.3 to 83% for poor glycemic control. The researchers concluded with this important observation, "These findings suggest that obesity itself may not be a sufficient risk factor for atherogenic dyslipidemia or poor glycemic control in people with type 2 diabetes." [Health-e-Iron note: Figure 1 from this study appears below]



A strong interaction between serum gamma-glutamyltransferase and obesity on the risk of prevalent type 2 diabetes: results from the Third National Health and Nutrition Examination Survey (13) Free full text

In a 2007 study in the U.S., similar the one described immediately above, the investigators "analyzed 4,011 adults > or = 40 years old who participated in the 3rd US National Health and Nutrition Examination Survey."..."BMI was associated with prevalent diabetes only among persons with high normal serum GGT activity (P for interaction = 0.002). In the highest serum GGT quartile, adjusted odds ratios for BMI 25-29.9, 30-34.5, and > or =35 kg/m(2) compared with BMI<25 kg/m(2) were 3.1, 5.1, and 6.2, respectively (P for trend <0.001). In the lowest serum GGT quartile, BMI was not associated with diabetes; corresponding adjusted odds ratios were 1.0, 0.9, 1.8, and 0.8 (P for trend = 0.551). Similar to the conclusion described above, the researchers concluded, "BMI was not associated with prevalent type 2 diabetes when GGT was low normal, suggesting that obesity itself may not be a sufficient risk factor for type 2 diabetes. Practically, this interaction can be useful in clinical settings to identify individuals at high risk for type 2 diabetes." [Health-e-Iron note: Figure 1 from this study appears directly below]


 Fig. 1. Adjusted odds ratios (ORs) and 95% CIs of newly recognized diabetes (205 cases) by category of BMI and quartiles (Q) of serum GGT. Numbers in the table are the numbers of cases and individuals at risk in each category. ORs were adjusted for age, sex, race/ethnicity, poverty income ratio, cigarette smoking, leisure time physical activity, and alcohol consumption; all ORs were calculated with the reference group of subjects with lowest category of both BMI and serum GGT. First and 2nd quartiles of serum GGT were combined because of small numbers of cases of newly recognized diabetes.

 

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes? (14) Free full text

In this 2007 review article the authors hypothesize 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." "...we postulate a two-part hypothesis: that associations of GGT within its normal range with type 2 diabetes may reflect detrimental effects of xenobiotics found in the environment, "we postulate a two-part hypothesis: that the association of serum GGT with type 2 diabetes reflects exposure to POPs, as these substances, which have a very long half-life, may influence diabetes risk by residing in adipose tissue as endocrine disruptors; and that POPs or similar substances may interact with obesity to cause type 2 diabetes. Supporting this hypothesis, cross-sectional investigation of background exposure to POPs in the National Health and Nutrition Examination Survey showed relationships similar to those observed for GGT, including a powerful association with prevalent diabetes and no association between obesity and diabetes for very low POP concentrations. Our hypothesis can be tested in both prospective studies and toxicological studies."

 

Association of gamma-glutamyltransferase with incidence of type 2 diabetes in Japan  (15) Free full text

In 2010 this research group reported the following: "The aim of this research was to examine the association of gamma-glutamyltransferase (GGT) and its interactions with alcohol consumption (alcohol), body mass index (BMI) and/or alanine aminotransferase (ALT) on the incidence of type 2 diabetes (DM) in Japan." "The total number of subjects in this cohort was 39,563." "...the HRs (hazard ratios) of the third and fourth GGT quartiles in women and the fourth GGT quartile in men were significantly higher than those of the first GGT quartile. The association between BMI and the incidence of DM (diabetes mellitus) was enhanced by increased GGT levels in women. When GGT levels were in the second to fourth quartiles, the HRs of obese subjects were significantly higher than those of underweight subjects." "Furthermore, in women, obesity is no longer a risk factor for Diabetes Mellitus when GGT level is low." [Health-e-Iron note: Figure 2 from this study appears  below]



Figure 2 Relation between BMI and the risk of DM among GGT categories. HRs were calculated and adjusted for age, family history of diabetes, smoking habits, baseline glucose type, alcohol consumption and ALT. The first, second, third and fourth quartiles of GGT which were <16, 16 to <24, 24 to <41 and ≥41 U/L for men and <9, 9 to <13, 13 to <19 and ≥19 U/L for women are expressed as gray dotted line, gray solid line, black dotted line and black solid line, respectively. P< 0.05, P< 0.01, P< 0.001; compared with underweight subject by using Cox regression analysis. Interaction between GGT and BMI on the incidence of DM is borderline significant in women (P value for interaction = 0.070), but not in men (P value for interaction = 0.978). BMI, body mass index; DM, type 2 diabetes; GGT, gamma-glutamyltransferase; HR, hazard ratio; ALT, alanine aminotransferase.


Oxidative stress rather than triglyceride accumulation is a determinant of mitochondrial dysfunction in in vitro models of hepatic cellular steatosis (16) Free full text

In this March, 2012 laboratory study of "human hepatoblastoma C3A (liver) cells treated with various combinations of of oleate, octanoate, lactate (L), pyruvate (P) and ammonia (N) acutely or for 72h, before measurements of triglyceride concentration, cell respiration, ROS (reactive oxygen species) production, mitochondrial membrane potential, ketogenesis and gluconeogenesis, TCA cycle metabolite analysis and electron microscopy. The U.K. research team reported: Acutely, LPON treatment (i.e. the above substances) enhanced mitochondrial respiration and ROS formation. After 72h, despite the similarities in triglyceride accumulation, LPON treatment, but not oleate, dramatically affected mitochondrial function as evidenced by decreased respiration, increased mitochondrial membrane potential and ROS formation with concomitant enhanced ketogenesis. The addition of the antioxidant N-acetyl-L-cysteine prevented mitochondrial dysfunction and reversed metabolic changes seen with LPON, strongly suggesting ROS involvement in mediating mitochondrial impairment. The researchers concluded, "Our data indicate that ROS formation, rather than cellular steatosis per se, impairs mitochondrial function. Thus, reduction in cellular steatosis may not always be the desired outcome without concomitant improvement in mitochondrial function and/or reducing of ROS formation."

 

Association between serum gamma-glutamyltransferase and oxidative stress related factors (17)

This 2008 laboratory study was preformed in Japan. The aim was "tTo investigate the main factors correlated with the serum gamma-glutamyltransferase activity." "We measured serum gamma-glutamyltransferase activity in 248 healthy Japanese people and determined its correlations with serum antioxidants, other plasma or serum factors, urinary 8-hydroxydeoxyguanine, and lifestyle factors." "The mean serum gamma-glutamyltransferase activity was 29 IU/L. Gamma-glutamyltransferase activities of males and persons older than 45 years were significantly higher than each counterpart. Gamma-glutamyltransferase levels increased significantly with the number of cigarettes smoked per day and the frequency of alcohol consumption except for the persons who did not take alcohol. Additionally, gamma-glutamyltransferase significantly correlated with urinary 8-hydroxydeoxyguanine, and with more blood factors including serum tocopherols, carotenoids, antioxidative enzymes, lipid peroxide, and free fatty acids than urinary 8-hydroxydeoxyguanine did. In multiple regression analyses, gamma-glutamyltransferase had significant associations with retinol, 8-hydroxydeoxyguanine, docosahexaenoic acid, and cigarette smoking." The researchers concluded, "Our present findings support the hypothesis that gamma-glutamyltransferase can be used as a marker related with oxidative stress."


Serum γ-Glutamyltransferase: Independent Predictor of Risk of Diabetes, Hypertension, Metabolic Syndrome, and Coronary Disease (18) Free full text

This is a 2012 study reported from Turkey. "After appropriate exclusions, a cohort of 1,667 adults of a general population (age 52 ±11 years) was evaluated prospectively at 4 year's follow-up using partly Cox proportional hazard regressions. "Median (interquartile range) GGT activity was 24.9 (17.0; 35.05) U/l in men, 17.0 (12.3; 24.0) U/l in women." "In linear regression analysis, while smoking status was not associated, (male) sex, sex-dependent age, alcohol usage, BMI, fasting triglycerides and C-reactive protein (CRP) were significant independent determinants of circulating GGT." "Strongest independent association existed with diabetes (HR 1.3 (95% CI 1.1; 1.5)) whereas GGT activity tended to marginally predict CHD independent of total bilirubin but not of BMI." The researchers concluded, "... that elevated serum GGT confers, additively to BMI, risk of hypertension, MetS, and type 2 diabetes but only mediates adiposity against CHD risk."


Prospective study of serum gammaglutamyltransferase and risk of NIDDM (19) Free full text

In this 1998 reported study the investigators "carried out a prospective cohort study of incident cases of doctor-diagnosed NIDDM in 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 NIDDM were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records." During the follow-up 194 men developed diabetes. "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 investigators concluded, "These findings suggest that a raised serum GGT level is an independent risk factor for NIDDM. Serum GGT level may be a simple and reliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance." [Health-e-Iron note: the researches of this 1998 study inferred that the relationship of elevated GGT to diabetes might relate to abdominal and liver fat. As noted in other more recent studies on this page, the relationship of GGT to diabetes still exists when appropriate adjustments are made for fat. The more recent studies suggest this relationship is most likely mediated by oxidative stress. Figure 1 from this study appears below. The next article on this page (#18) is a letter to the editor written b by two of the same authors of the editorial (article #2) on our IRON-Diabetes page. This editorial was published was published in 2007 and suggested GGT as a factor in increased oxidative stress could explain an observation very similar to the one found here.]


 

Relationship between γ-Glutamyltransferase, Fasting Plasma Glucose, and Triglycerides in the General Population (20) Free full text

The authors noted "Recent population-based epidemiologic studies have convincingly shown that serum-glutamyltransferase (GGT) activity is associated with many cardiovascular disease risk factors and predicts new-onset type 2 diabetes, hypertension, stroke, and myocardial infarction." "We read with interest the recent article by Lim et al. (see above study #13) on the possible interaction between GGT and obesity and its association with the risk of prevalent type 2 diabetes, findings indicating that obesity itself may not be a sufficient risk factor for diabetes when GGT concentrations approach the lower limit of the reference interval." "The clinical implications of this conclusion are noteworthy because overweight-obese people with GGT concentrations at the lower limit of the reference interval (e.g., 20 U/L) would no longer be considered at high risk of developing diabetes." The researcher preformed a retrospective analysis of results on a cohort of outpatients consecutively referred by general practitioners for routine blood testing in the preceding 9 months. "Cumulative results for GGT, FPG (fasting plasma glucose), and triglycerides were retrieved for 7,267 outpatients >35 years old during a 9-month period. As shown in Table 1 (see below), the concentrations of FPG and triglycerides markedly increased among the GGT categories. Similarly, the frequency of those with FPG ≥7.0 mmol/L, a cutpoint suggestive for diagnosing diabetes according to the American Diabetes Association guidelines, and of those with hypertriglyceridemia (≥1.7 mmol/L by the Third Adult Treatment Panel criteria) increased steadily across the spectrum of GGT thresholds from 16% to 31% for FPG and from 14% to 39% for triglycerides, respectively." "Overall, we agree with the suggestions of Lim et al. (see above study #13) that GGT measurement may be useful in clinical settings for detecting high-risk subpopulations of type 2 diabetes and/or hypertriglyceridemia. Such individuals might benefit from a more intensive therapeutic approach to decrease their global cardiovascular risk, regardless of potential unmeasured effects of lifestyle or obesity. Conceivably, the significant association of serum GGT concentrations with FPG and triglycerides, observed in our investigation, may be biologically explained by some underlying mechanisms such as hepatic steatosis, insulin resistance, and increased oxidative stress. [Health-e-Iron note: Figure 1 from this study appears below]

 

 

Elevated serum gamma-glutamyltransferase activity is associated with increased risk of mortality, incident type 2 diabetes, cardiovascular events, chronic kidney disease and cancer - a narrative review (21)

"This 2010 review examines evidence for an association of high normal serum GGT enzyme activity, mostly within the reference range, with the risk of mortality and major vascular (i.e., cardiovascular morbidity and mortality) and non-vascular outcomes (i.e., incident type 2 diabetes, chronic kidney disease and cancer), independent of alcohol consumption and other prognostic factors."


Relation of Gamma-glutamyltransferase and alcohol drinking with incident diabetes: the HIPOP-OHP study 
(22) Free full text

In this 2010 study, " the relation of GGT or alcohol drinking with DM (diabetes mellitus) incidence considering the body mass index (BMI) in healthy Japanese workers" was investigated. "We followed 3,095 men who did not have DM at baseline for 4 years."Participants with higher GGT (GGT >or=27 U/L) showed an increased risk of diabetes incidence even when their BMI level was low." The researchers concluded, "Higher GGT was associated with a higher incidence of DM irrespective of drinking status or obesity. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers was not low if they were either overweight or had higher GGT." 


Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of gamma-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) (23) Free full text

Researchers in 2010 French study analyzed "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 >or=27 kg/m(2)." "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 >or=27 kg/m(2)." "GGT, either considered as a continuous variable or at levels >or=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 >or=27 kg/m(2)" [Health-e-Iron note: Table 3 from this study appears below]



Gamma-glutamyltransferase activity and development of the metabolic syndrome (International Diabetes Federation Definition) in middle-aged men and women: Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort (24) Free full text

The aim of this 2007 French investigation was to "... study the association of GGT with the development of the metabolic syndrome (MetS). The researchers studied "3-year data from the Data from Epidemiological Study on the Insulin Resistance Syndrome prospective cohort of 1,656 men and 1,889 women without MetS at baseline..." "...the odds ratios for incident MetS increased across baseline GGT quartiles (1, 1.96, 2.25, and 3.81 in men, P < 0.03; and 1, 1.23, 1.80, and 1.58 in women, P < 0.05)." After adjustments for insulin resistance markers, "...men in the highest in comparison to the lowest quartile of GGT retained a significant risk for incident MetS. In women, there was no longer a significant risk. GGT was significantly associated with the 3-year incidence of individual components of the MetS. The researchers concluded, "GGT, a predictor of type 2 diabetes, was associated with a risk of incident MetS. This association was mainly related with insulin resistance but was independent of other confounding factors." [Health-e-Iron note: A Risk Analysis Table derived from the data from this study appears below]


Serum gamma-glutamyl transferase activity predicts future development of metabolic syndrome defined by 2 different criteria (25)

In 2009 this group of Korean investigators "hypothesized that serum concentrations of GGT and ALT are associated with the development of MetS. They studied "15,250 males (mean 38 y) and 6,280 females (mean 41 y)," in 2002 and "analyzed the development of MetS in their follow-up data in 2006." When data gathered in 2002 was divided into quartiles." "In this large prospective study in Koreans, high baseline GGT and ALT concentrations predicted future development of MetS..." [Health-e-Iron note: the investigators in this study prepared an illustrative slide presentation that can be viewed by clicking this LINK]


Cross-sectional and longitudinal association of serum alanine aminotransaminase and γ-glutamyltransferase with metabolic syndrome in middle-aged and elderly Chinese people (26) Free full text

In this 2008 study from China, "A total of 5,404 subjects aged ≥ 40 years were recruited from two urban communities in Shanghai for cross-sectional analyses. A subgroup of 681 participants without MetS at baseline was included in the longitudinal analyses." "Both GGT and ALT were strongly and positively associated with MetS risks in simple and multivariate analyses. Further adjustment for HOMA-IR and ALT did not change the association of GGT and MetS materially, whereas adjustment for HOMA-IR and GGT substantially attenuated the ALT-MetS association." Mean GGT values for each quartile were 14, 20, 28, and 50. In longitudinal analyses, risks of developing MetS were increased across GGT quartiles in a dose-dependent manner after extensive adjustments (odds ratios were 1.00, 1.38, 1.62, and 2.29 for GGT, quartile 1 through quartile 4; P for trend = 0.01)." The researchers concluded, "Our study confirmed significant and independent associations of GGT and ALT with MetS in adult Chinese people. Moreover, GGT might be more effective for indicating the future development of MetS." [Health-e-Iron note: Table 3 from this study appears below]


Serum gamma-glutamyltransferase and development of impaired fasting glucose or type 2 diabetes in middle-aged Japanese men (27) Free full text

This 2003 study investigated "the association between serum GGT and risk for development of diabetes" in Japanese men. The investigators studied the incidence of impaired fasting glucose (IFG) and type 2 diabetes over a seven year period. "With adjustment for potential risk factors for diabetes, the relative risk for IFG compared with serum GGT <16 U L-1 was 1.23 (95% CI, 0.79-1.90), 1.50 (CI, 0.97-2.32) and 1.70 (CI, 1.07-2.71) with serum GGT of 16-24, 25-43 and >/=44 U L-1, respectively (P for trend = 0.014). The respective relative risks for type 2 diabetes compared with serum GGT <16 U L-1 were 2.54 (CI, 1.29-5.01), 2.64 (CI, 1.33-5.23) and 3.44 (CI, 1.69-6.70) (P for trend = 0.002)." The researchers concluded, "The risk for development of IFG or type 2 diabetes increased in a dose-dependent manner as serum GGT increased in middle-aged Japanese men. The increased relative risk for IFG or type 2 diabetes associated with serum GGT was more pronounced in obese men." [Health-e-Iron note: Table 2 from this study appear below]

 

Liver enzymes and incident diabetes: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study (28) Free full text

In this 2008 reported study the investigators "sought to examine the association between plasma concentrations of liver enzymes gamma-glutamyltransferase (GGT) and alanine transaminase (ALT) and incident diabetes, prospectively." "We conducted a case-cohort analysis of data from participants mainly aged 35-65 years in the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. The analytic sample included 787 participants with incident diabetes and 2,224 participants without diabetes." "Concentrations of GGT and ALT were significantly associated with incident diabetes after extensive adjustment. Compared with participants in the lowest quintile of GGT, the adjusted hazard ratios for increasing quintiles were 1.13 (95% CI 0.66-1.93), 1.67 (1.01-2.77), 2.77 (1.71-4.49), and 2.67 (1.63-4.37), respectively (P for linear trend <0.001)." Similar but slightly weaker associations were found for ALT. "The magnitude of the associations were higher among men than women for GGT (P = 0.004) but did not differ significantly between men and women for ALT (P = 0.307)." The investigators concluded, "Concentrations of GGT and ALT were significant predictors of incident diabetes in this study, even at concentrations still considered to be within the normal range." [Health-e-Iron note: Tables 2 and 3 from this study appear below]


 

A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes (29) Free full text

In this 2007 study, investigators in the U.K. studied data from the British Women's Health and Heart Study. "...a random sample of British women aged 60-79 years (N = 3,394; 3,086 without diabetes and 308 with diabetes) was used. "Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin...are stronger in women with diabetes compared to women without diabetes (P for interaction < 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status." "Associations did not differ substantially between obese and non-obese non-diabetic women.The investigators concluded, "elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population." [Health-e-Iron note: Table 1 and Figure 1 from this study appear below]

Figure 1

 

 

Liver enzymes as a predictor for incident diabetes in a Japanese population: the Hisayama study (30) Free full text

In a study 2007 in japan of 1,804 non-diabetic subjects 40 to 79 years of age who were followed prospectively for a mean of 9.0 years, 135 subjects developed diabetes. "In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly with elevating quartiles of serum gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) levels." "after adjusting for comprehensive risk factors and other liver enzymes, the risk of developing diabetes was significantly higher in the highest GGT quartile than in the lowest quartile [odds ratio (OR), 2.54; 95% confidence interval (CI), 1.03 to 6.26 for men; OR, 5.73; 95% CI, 1.62 to 20.19 for women]." The researchers concluded, "Our findings suggest that serum GGT and ALT concentrations are strong predictors of diabetes in the general population, independent of known risk factors." [Health-e-Iron note; Figure 1 from this article appears below]


The relationship of hepatitis antibodies and elevated liver enzymes with impaired fasting glucose and undiagnosed diabetes (31) Free full text

The investigators in this 2008 reported study "analyzed the National Health and Nutrition Examination Survey, 1999 to 2004, a nationally representative sample of the noninstitutionalized US population. Among adults (aged >20 years of age) who were not problem drinkers, we examined hepatitis B and C antibodies and the liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamyl transaminase (GGT) with impaired fasting glucose and undiagnosed diabetes (unweighted, n  5234; weighted, n 172,626,805). "In unadjusted analyses 51% of individuals with undiagnosed diabetes have elevated GGT versus 20% of individuals without diabetes or impaired fasting glucose (P = .01). Similarly, 43% of individuals with undiagnosed diabetes have elevated ALT versus 23% of individuals without diabetes or impaired fasting glucose (P = .01)." "In adjusted analyses, elevated GGT (odds ratio, 2.15; 95% CI, 1.44 –3.20) and ALT (odds ratio, 1.84; 95% CI, 1.06 –3.20) are associated with undiagnosed diabetes. Similarly, in adjusted analyses, elevated GGT (odds ratio, 1.23; 95% CI, 1.00 –1.53) and ALT (odds ratio, 1.44; 95% CI, 1.15–1.79) are associated with impaired fasting glucose." The investigators concluded, "Liver function is associated with undiagnosed diabetes and impaired fasting glucose and may justify further investigation as a risk stratification variable for undiagnosed diabetes or impaired fasting glucose." [Health-e-Iron note: Table #4 from this study appears below]


Serum gamma-glutamyltransferase levels are related to insulin sensitivity and secretion in subjects with abnormal glucose regulation (32)

Reported in 2010, a team of researchers from Italy "performed a cross-sectional analysis of 500 subjects [199 men/301 women, age 47 +/- 11 years, body mass index (BMI) 28.6 +/- 5.5 kg/m(2)] referred to Diabetes Clinics because of potential risk of type 2 diabetes mellitus (T2DM)." "Subjects with normal glucose tolerance showed lower gamma-glutamyltransferase levels compared with those with impaired glucose tolerance (IGT), impaired fasting glucose (IFG)+ IGT and T2DM (ANOVA, p < 0.0001), but not those with IFG." "After further adjustment for BMI, alcohol intake, family history of diabetes, cigarette smoking and physical activity, the top quartile of gamma-glutamyltransferase remained an independent predictor of IFG + IGT (OR 2.62; 95% CI: 1.13-6.07) and T2DM (OR 2.39; 95% CI: 1.20-4.76)." The researchers concluded, "GGT is closely related to insulin resistance, reduced beta-cell function and deterioration of glucose tolerance."

 

Gamma-glutamyltransferase levels and risk of metabolic syndrome: a meta-analysis of prospective cohort studies (33)

In this 2012 reported meta-analysis of nine prospective cohort studies that included 47,499 participants and 5,009 cases of metabolic syndrome, "the association between GGT and MetS was analysed in qualitative and quantitative manners." "When comparing the risk of MetS between the highest versus the lowest category of GGT levels, the pooled RR (Relative Risk) of MetS was 1.63 (95% CI: 1.43-1.82; p < 0.000). The second dose-response analysis of GGT levels per 5 U/l increment with risk of MetS showed that the summary RR of MetS was 1.09 (95% CI: 1.06-1.13; p < 0.000)." "Sensitivity analyses showed that no single study significantly influenced the pooled RRs. "Conclusions:  Our results show that GGT levels are positively associated with risk of MetS independently of alcohol intake. GGT may be a promising marker for predicting MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms in future."

 

Gamma-glutamyltransferase, alanine transaminase and aspartate transaminase levels and the diagnosis of gestational diabetes mellitus (34)

The objective of this 2012 published study undertaken in Malaysia was "To evaluate gamma-glutamyltransferase (GGT), alanine transaminases (ALT) and aspartate transaminases (AST) levels and prevalent gestational diabetes mellitus (GDM)." "Random plasma glucose, GGT, ALT and AST and the 50-g glucose challenge test were done on antenatal women followed by diagnostic 3-point 75-g oral glucose tolerance test within two weeks. GDM was diagnosed by ADA (2011) criteria." "The risk for GDM was higher for women in the highest GGT quartile band compared to the lowest: RR 1.35 95%CI 1.0-1.8; P=0.04. However, after adjustment for confounders, GGT was no longer associated with GDM. There was no correlation between ALT and AST levels and GDM.

 

Gamma-glutamyltransferase level in pregnancy is an independent risk factor for gestational diabetes mellitus (35)

In another gestational diabetes study from Malaysia that was reported in 2008 the reseachers set out "To evaluate the relationship between gamma-glutamyltransferase (GGT) level in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of gestational diabetes (GDM)." "GGT level correlated positively with the 2-hour glucose level (Spearman's rho = 0.112: P < 0.05). GGT values that were stratified into quartiles demonstrated a significant trend with diagnosis of GDM (chi(2) for trend; P = 0.03). Multivariable logistic regression analysis taking into account maternal age, gestational age at OGTT, body mass index and a positive 50-g glucose challenge test (GCT) indicated that high GGT was an independent risk factor for GDM (adjusted odds ratio [AOR] 2.1 95% CI 1.2-3.8: P = 0.01). In the subset of women identified by a positive GCT, on multivariable logistic regression analysis, only high GGT was an independent risk factor for GDM (AOR 2.3 95% CI 1.3-4.2: P = 0.007)." The researchers concluded, "Raised GGT level is an independent risk factor for GDM in high risk pregnant women undergoing OGTT."

 

Can serum gamma-glutamyltransferase levels be useful at diagnosing gestational diabetes mellitus? (36)

 In another 2012 similar gestational diabetes study reported in Turkey, "The aim of this study was to evaluate plasma gamma-glutamyltransferase (GGT) in gestational diabetes mellitus (GDM) in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of GDM and to explore whether this activity is associated with metabolic parameters." "his prospective control study included 37 women with GDM and 42 women with normal glucose tolerance in pregnancy (control group). In the study group (GDM), blood was taken for analyzing 100 g OGTT from women who have abnormal 50 g glucose challenge test (GCT)." "Compared with the controls, the GDM group had significantly higher mean values for serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglyceride and GGT. Within the GDM group, GGT levels were only negatively correlated with high-density lipoprotein (r = -0.41, p = 0.01). GGT was determined to be an independent metabolic parameter for GDM. The researchers concluded, "The increase at GGT level is an independent risk factor for GDM and identified as high-risk women for diagnosis of GDM."

 

The association of higher levels of within-normal-limits liver enzymes and the prevalence of the metabolic syndrome (37) Free full text

The objective of this 2010 study undertaken in Israel was "to evaluate the range of prevalence of MetS in apparently healthy individuals whose liver enzyme concentrations were all within-normal-range." "Analyzed were a cohort of 6,561 men and 3,389 women." "In our study, we found that the prevalence of the MetS doubles if a comparison is made between the first, second and third quintiles of both GGT and ALT. In these quintiles the concentrations of the enzymes are not only regarded as being absolutely normal, but are actually even in the lower range of the "normal" values." In their conclusion the researchers state the following, "Moreover, our findings suggest that even minute changes, still within the so called "normal range" could point towards a potential dysmetabolic state. These observations could therefore lead to avoiding the usage of cut-off values for normalcy for these two biomarkers. In addition, they should encourage the use of both GGT and ALT as continuous biomarkers that could be used for early signaling of dysmetabolism. Finally, our results support the notion that in the era of early detection, prevention and treatment of metabolic disorders, one cannot be confident that relatively low concentrations of liver enzymes exclude the presence of dysmetabolic changes. A practical consequence might therefore be to follow these enzyme concentrations as continuous biomarkers and take into consideration the possibility that even small changes in their concentrations might be of relevance." [Health-e-Iron note: Figure 1 and Table 4 appear below]

 

Role of GGT in diagnosis of metabolic syndrome: A clinic-based cross-sectional survey  (38) Free full text

This study from Turkey was reported in 2010. "The aim of this study is to know if the liver function tests (LFT), especially gamma glutamyl transferase (GGT), have a predictive value in diagnosis of metabolic syndrome (MS)." "A cross-sectional, single-center study was carried out with 908 subjects." "The mean values of alanine amino transferase (ALT), aspartate aminotransferase (AST) and GGT levels were statistically significantly higher in MS group. The mean values of liver enzymes, for female/ male subjects in MS group, AST; ALT and GGT respectively, were; 20.5/19.7 U/l; 25.9/28.5 U/l; 35.9/42.1 U/l. When the sample is divided into quartiles of the GGT levels, increase in GGT is positively correlated with increased MS prevalence. In ROC analysis GGT is as strongly associated with the IDF diagnostic components as is each individual IDF component, except elevated systolic blood pressure. In covariance analysis, there was significant relationship between elevated GGT levels and MS presence after adjustment for age, sex and MS diagnostic criteria; but not AST and ALT levels. In multivariance analysis, in MS group, a high GGT was positively associated with CVD prevalance (odds ratio: 2.011, 95% CI 1.10-4.57) compared to low GGT group independent of age, sex and smoking habits." The researchers concluded, "Elevated liver enzymes, although in normal ranges, especially at upper quartiles, play a central role in early diagnosis of fat overflow to the liver. Regarding the availability and simplicity of these tests in routine clinical practice, they, especially GGT, have potential to be considered in algorithms for metabolic syndrome."

 

Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome (39) Free full text

In this 2008 U.S. study, the research objective was "To establish the relation of oxidized LDL with metabolic syndrome in the general community." "We studied 1,889 participants who were between the ages of 18 and 30 years at the time of recruitment in 1985 and 1986 and living in 1 of 4 US metropolitan areas (41% African American; 56% women) and were seen both at year 15 ... and year 20 examinations (2005-2006)." "The adjusted ORs for incidence of dichotomous components of metabolic syndrome in the highest vs the lowest quintile of oxidized LDL were 2.1 (95% CI, 1.2-3.6) for abdominal obesity, 2.4 (95% CI, 1.5-3.8) for high fasting glucose, and 2.1 (95% CI, 1.1-4.0) for high triglycerides. Low-density lipoprotein cholesterol was not associated with incident metabolic syndrome or with any of its components in the fully adjusted model containing oxidized LDL." The researchers concluded, "Higher concentration of oxidized LDL was associated with increased incidence of metabolic syndrome overall, as well as its components of abdominal obesity, hyperglycemia, and hypertriglyceridemia."

 

Association between serum gamma-glutamyltransferase and dietary factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study (40) Free full text

This study was reported in 2001. The researchers "...examined dietary correlates of serum GGT activity." "Study subjects were 3,146 black and white men and women aged 17-35 y in 1985-1986. A diet history was taken at years 0 and 7. Food items were classified into alcohol; breaded, battered, or canned vegetables; fruit; fruit juice; refined grain; whole grain; dairy; legumes; meat; poultry; fish; fresh or frozen vegetables; nuts; and coffee." "After adjustment for nondietary factors and other food groups, GGT was positively associated with alcohol consumption and meat intake." "Among meat constituents, total dietary heme iron but not saturated fat was positively associated with the serum GGT concentration; saturated fat showed a nonsignificant inverse trend
(Figure 1). Neither monounsaturated nor polyunsaturated fat was significantly associated with serum GGT (Figure 1). Geometric means of year 10 GGT across categories of alcohol consumption (0, 1-9, 10-19, 20-29, and > or = 30 g/d) were 17.7, 18.8, 20.4, 21.8, and 24.8 U/L (P for trend < 0.01); corresponding means across quintiles of meat intake were 19.2, 20.2, 20.5, 21.8, and 21.2 times/wk (P for trend < 0.01). GGT was inversely associated with fruit intake. Among possible meat constituents, dietary heme iron, but not saturated fat, was associated with GGT. Dietary constituents typical of plant foods showed an inverse association. In contrast, vitamin supplements were positively associated with GGT." The researchers concluded, "Serum GGT activity increased in a dose-response manner as alcohol and meat consumption increased and fruit consumption decreased. Heme iron contained in meats and micronutrients contained in fruits may influence GGT metabolism. However, micronutrients taken as supplements had a positive association with GGT." [Health-e-Iron note: Table 1 and Figure 3 from this research appear below] 

FIGURE 3. Geometric x (± SE) of year 10 у-glutamyltransferase (GGT) concentrations according to intake of micronutrients from vitamin and mineral supplements, after adjustment for alcohol consumption, heme iron, vitamin C from food, Beta-carotene from food, folate from food, fiber from food, -tocopherol from food, total energy intake, study center, race, sex, age, BMI, cigarette smoking, and physical activity in CARDIA Study subjects. P for trend is based on logarithmic transformations of the continuous micronutrient variables. Cutoffs of micronutrients from supplements were the recommended dietary allowances (RDA; 46) among men and women aged 19–30 y (vitamin C: 90 mg for men, 75 mg for women; vitamin A: 900 μg for men, 700 μg for women; folate: 400 mg for men, 400 mg for women; and Alpha-tocopherol: 15mg for men, 15mg for women). CARDIA, Coronary Artery Risk Development in Young Adults.

 

Association of serum carotenoids and tocopherols with gamma-glutamyltransferase: the Cardiovascular Risk Development in Young Adults (CARDIA) Study  (41) Free full text

In this 2004 reported study, based on a CARDIA study cohort 3,128 black and white men and women 17-35 years of age in 1985-1986, Serum carotenoids and tocopherols were measured at years 0 and 7, and serum GGT was measured at years 0 and 10." "Circulating concentrations of alpha-carotene, beta-carotene, and beta-cryptoxanthin inversely predicted the serum GGT concentration measured 10 years later in a dose-response manner (P for trend <0.01)." "Adjusted geometric means of serum GGT at year 10 according to quintile of the sum of four carotenoids at year 0 (alpha-carotene, beta-carotene, beta-cryptoxanthin, and zeaxanthin/lutein) were 19.9, 19.4, 18.9, 17.8, and 17.3 U/L (P for trend <0.01). Year 0 alpha-tocopherol was also a significant inverse predictor of year 10 serum GGT concentration (P for trend = 0.03), whereas gamma-tocopherol showed an inconsistent or possibly U-shaped association. However, year 0 serum GGT did not predict serum antioxidants measured 7 years later." The researchers concluded, "Our present findings support the contention that serum GGT concentration is a marker related with oxidative stress." [Health-e-Iron note: Table 3 from this study appears below]

 

 
Serum gamma-glutamyltransferase was differently associated with microalbuminuria by status of hypertension or diabetes: the Coronary Artery Risk Development in Young Adults (CARDIA) Study (42) Free full text

In this 2005 prospective study of 2,478 black and white men and women without microalbuminuria at year 10 of the CARDIA study, "Among individuals who ever had hypertension or diabetes, year 10 serum GGT showed a clear positive dose-response association with incident microalbuminuria (P <0.01 for trend), whereas among individuals with neither hypertension nor diabetes during the study, year 10 GGT showed a U-shaped association with it (P = 0.01 for quadratic term). When the long-term risk was evaluated in 3,895 participants based on serum GGT at year 0 and prevalence of microalbuminuria at year 10 or year 15, the trends were similar but weaker than those of short-term incidence risk. The researchers concluded, "Serum GGT within the physiologic range predicted microalbuminuria among patients with hypertension or diabetes and may act as a predictor of microvascular and/or renal complications in these vulnerable groups. GGT showed a U-shaped association with microalbuminuria among persons who did not develop either hypertension or diabetes." 


The association of gamma-glutamyltransferase and C-reactive protein with IFG/IGT in Chinese adults in Qingdao, China (43)

This study from China was reported in 2011. "A population-based cross-sectional study was conducted in 2006 in Qingdao, China. Data of 1,143 men and 1,689 women aged 35-74 years and free of diabetes at baseline were analyzed. Multivariable logistic regression analysis was performed to estimate the odds ratio (OR) and its 95% confidence interval (CI)." "Compared with the lowest quartile, the ORs (95%CI) for IFG/IGT corresponding to the highest quartile were 0.89 (0.61,1.28) in men and 0.87 (0.64,1.18) in women for CRP and 2.12(1.40,3.38) and 1.87(1.32,2.62) for GGT, when the two were fitted simultaneously in a model adjusting for age, school years, alcohol-drinking, smoking, family history of diabetes, systolic blood pressure, waist circumference, triglycerides and high-density lipoprotein." The researchers concluded, "The elevated GGT, but not CRP, was independently associated with the presence of the IFG/IGT in both genders in this Chinese population."

 

Alanine Aminotransferase, γ-Glutamyltransferase, and Incident Diabetes: The British Women's Heart and Health Study and meta-analysis (44) Free full text

This study was published in the U.K. in 2009. The aim of the researchers was "To estimate and compare associations of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) with incident diabetes." "ALT and GGT were studied as determinants of diabetes in the British Women's Heart and Health Study, a cohort of 4,286 women 60-79 years old (median follow-up 7.3 years)." In addition, "A systematic review and a meta-analysis of 21 prospective, population-based studies of ultrasonography, which diagnosed nonalcoholic fatty liver disease (NAFLD), ALT, and GGT as determinants of diabetes, were conducted, and associations of ALT and GGT with diabetes were compared." The results indicated that, "ALT and GGT both predicted diabetes." "For ALT, the HR was 2.02 (1.59-2.58, I(2) = 27%), and for GGT the HR was 2.94 (1.98-3.88, I(2) = 20%), suggesting that GGT may be a better predictor (P = 0.05)." The researchers concluded, "Findings are consistent with the role of liver fat in diabetes pathogenesis. GGT may be a better diabetes predictor than ALT, but additional studies with directly determined liver fat content, ALT, and GGT are needed to confirm this finding." [Health-e-Iron note: Figure 2 from this article appears directly below]

 

 

Serum gamma glutamyltransferase as a marker of metabolic syndrome and coronary disease likelihood in nondiabetic middle-aged and elderly adults (45) 

In this 2006 study reported by a team of investigators in Turkey the "role of serum gamma glutamyltransferase (GGT) activity as a cardiovascular risk marker was studied basically cross-sectionally." "After appropriate exclusions, 754 men and 802 women were available for analysis who were followed up briefly yielding only 16% of overall cases of coronary heart disease (CHD). By analyzing the sample in tertiles, doubling in GGT activity was found associated with a rise of 74% in metabolic syndrome (MS) likelihood-independent of salient confounders (P < 0.001). This association was mediated by waist circumference. Individuals in the top versus the bottom tertile exhibited an odds ratio for CHD likelihood of 1.81 (95% CI 1.09; 3.02)-independent of age, sex, total cholesterol, systolic blood pressure, impaired fasting glucose, smoking status, alcohol usage and, notably, of waist circumference. This indicated that a doubling in serum GGT activity corresponded to a 45% excess in CHD likelihood, after adjustment for standard risk factors." The researchers concluded, "...waist circumference is a major determinant of serum GGT activity among Turkish adults. Doubling in activity is associated with a (largely waist girth mediated) rise by over one-half in the multiadjusted MS likelihood, and by nearly one-half in the CHD likelihood, independent of waist girth and major risk factors."

 

Effects of Supervised Exercise on Gamma-Glutamyl Transferase Levels in Patients with Isolated Impaired Fasting Glucose and Those with Impaired Fasting Glucose Plus Impaired Glucose Tolerance (46)

The complete abstract from this 2012 study from Austria follows: "To study the effects of a supervised exercise program on serum gamma-glutamyl transferase (GGT), glycemic control and cardiovascular risk factors in pre-diabetic patients with isolated impaired fasting glucose (IFG) and those with IFG plus impaired glucose tolerance (IGT).Out of 60 pre-diabetic patients (30 with isolated IFG and 30 with IFG + IGT) 24 were randomly assigned to the supervised exercise program (1 h twice a week) and 36 only obtained counselling on the risk of diabetes and its prevention. Patients have been followed over a 12-month period. The main findings were that patients with IFG + IGT had increased GGT levels at baseline (49.2±27.4 U/L) compared to subjects with isolated IFG (28.1±21.9 U/L) (p<0.01), and that GGT levels improved only after the supervised exercise intervention within the IFG + IGT subjects ( - 17.7±19.6 U/L). Similarly, baseline triglyceride levels were also higher in IFG + IGT patients (p<0.001) and there was a decrease through exercise intervention in these patients only (p<0.05). GGT is an unspecific marker of oxidative stress and both high plasma glucose and triglycerides levels may produce oxidative stress. Thus, patients with IFG + IGT seem to have higher levels of oxidative stress than those with isolated IFG. Based on the known association between GGT levels and cardiovascular risk factors, IFG + IGT patients may be at higher risk for the development of cardiovascular diseases. The specific effect of regular exercise on GGT in pre-diabetic patients may contribute to the understanding of the preventive effects related to exercise."

 

Biomarkers of oxidative stress and personalized treatment of pulmonary tuberculosis: emerging role of gamma-glutamyltransferase (47) Free full text

This 2012 reported study was undertaken in Africa to "evaluate the impact of acute pulmonary tuberculosis (PTB) and anti-TB therapy on the relationship between AST, ALT, and GGT levels in absence of conditions related to hepatotoxicity; (ii) to evaluate the rate and the time of alterations of AST, ALT, and GGT. The researchers noted, "Tuberculosis is, therefore, characterized by poor antioxidants defense that exposes to oxidative host tissue damage." And "With the current and increasing interest in oxidative stress, emphasis is to develop functional biomarkers of oxidative stress with epidemiological and clinical implications such as gamma-glutamyltransferase (GGT)..." "A prospective followup of 40 adults with active PTB on initial phase and continuation phase anti-TB. Results. Only 3% (n = 1) developed a transient and benign ADR (Adverse Drug Reaction) at day 30 without interruption of anti-TB treatment." "Within normal ranges, GGT decreased significantly from day 0 to day 60, while AST and ALT increased significantly and respectively. During day 0-day 60, there was a significant, negative, and independent association between GGT and AST." The researchers concluded, "The initial two months led to significant improvement of oxidative stress. Values of oxidative markers in normal ranges might predict low rate of ADR." [Health-e-Iron note: The researchers in this study made these observations that are consistent with other reports on this web site: "If serum GGT is a marker of oxidative stress targeted by anti-TB during the initial phase, it might have important implications both clinically and epidemiologically because measurement of serum GGT is easy, reliable, and inexpensive. It is important to evaluate in tuberculosis patients on DOTS intake of fruits and vegetables, which are rich in antioxidants." And "Clinicians should ... be vigilant for conditions related to oxidative stress and deficiency of antioxidant systems."]


Multiple biomarkers and their relative contributions to identifying metabolic syndrome (48)

In this 2009 report the research team undertook to evaluate the biomarkers associated with an increased risk of metabolic syndrome and cardiovascular disease. "We thus compared biomarkers and their association with metabolic syndrome." "We measured the white blood cell count, high-sensitivity C-reactive protein, homeostasis model assessment of insulin resistance (HOMA-IR), homocysteine, cystatin C, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and uric acid levels in 4,624 adults without a medical history of cardiovascular disease." "The HOMA-IR and GGT were most strongly correlated with metabolic syndrome." "The best cut-off value of HOMA-IR and GGT for identifying metabolic syndrome was (1.22, 30 IU/l [men], 1.28, 15 IU/l [women])." The researchers concluded, "HOMA-IR and GGT are most strongly associated with metabolic syndrome, suggesting that theses biomarkers may contribute to identifying metabolic syndrome more than other factors."


The Association between Serum Gamma-Glutamyltransferase within Normal Levels and Metabolic Syndrome in Office Workers: A 4-Year Follow-up Study (49) Free full text

This was a Korean study re[ported in 2012. The research noted, "Serum gamma-glutamyltransferase (GGT) has been suggested as a predictor for development of the metabolic syndrome in non-Korean population, but studies in Korean population are scarce." "The study population consisted of 32,692 office workers who underwent health checkups in both 2005 and 2009. A total of 17,583 with elevated GGT levels, the presence of metabolic syndrome, medication history at baseline, and female office workers were excluded. Finally, 15,109 subjects were included in the final analysis. We measured serum GGT levels and individual metabolic components." "As a quartile of serum GGT increased, 4-year follow-up incidence of the metabolic syndrome increased. After adjustment for age, alcohol drinking status and smoking status in 2005, logistic regression analysis showed that the odds ratios (95% confidence interval) for incident metabolic syndrome in 2009 compared to the lowest quartile and upper quartiles were 1.00 (reference), 1.57 (1.24-2.00), 2.73 (2.17-3.43), 3.78 (3.02-4.74), and statistically significant (P < 0.001), respectively. The research concluded, "These results showed that the higher serum GGT predicted the future development of metabolic syndrome. In Korean male office workers without the metabolic syndrome, the serum GGT levels despite normal levels were associated with an increased risk of incident metabolic syndrome." [Health-e-Iron note: Table #4 from this study appears below]



Liver enzymes concentrations are closely related to prediabetes: findings of the Shanghai Diabetes Study II (SHDS II) (50) Free full text

The objective of this 2012 reported study was "To investigate the relationship of liver enzymes with hyperglycemia in a large population in Shanghai and identify the association between liver enzymes and insulin resistance." "A total of 3,756 participants were enrolled. Each participant underwent an oral glucose tolerance test and completed a questionnaire. Anthropometric indices were recorded and serum samples were collected for measurement." "Liver enzymes concentrations were independently associated with i-IGT, IFG+IGT, and diabetes. With the increase of ALT and GGT concentrations, ORs for i-IGT, IFG+IGT, and diabetes increased gradually. By comparing patients in the highest quartile of GGT concentrations or ALT concentrations with those in the lowest quartile (Q1), ORs for i-IGT, IFG+IGT, or diabetes was significant after adjustment. Both ALT and GGT concentrations were linearly correlated with HOMA-IR and independently associated with HOMA-IR [ALT OR (95% CI): 2.56 (1.51-4.34) P=0.00; GGT OR (95% CI): 2.66 (1.53-4.65) P=0.00]." The researchers concluded, "Serum ALT and GGT concentrations were closely related to pre-diabetes and diabetes in the Shanghai population and positively associated with insulin resistance." [Health-e-Iron note: Figure #1 from this study appears below]

 

The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients (51) Free full text

This study from Korea was reported in 2010. The researcher first noted, "Diabetic peripheral polyneuropathy (DPP) is one of the common complications of diabetes mellitus (DM) and can lead to foot ulcers or amputation. The pathophysiology of DPP includes several factors such as metabolic, vascular, autoimmune, oxidative stress and neurohormonal growth-factor deficiency and recent studies have suggested the use of serum gamma-glutamyl transferase (GGT) as an early marker of oxidative stress. Therefore,we investigated whether serum GGT may be useful in predicting DPP." "We assessed 90 patients with type 2 DM who were evaluated for the presence of DPP using clnical neurologic examinations including nerve conduction velocity studies. We evaluated the association between serum GGT and the presence of DPP." "The prevalence of DPP was 40% (36 cases) according to clinical neurological examinations. The serum GGT concentration was significantly elevated in type 2 diabetic patients with DPP compared to patients without DPP (P < 0.01). There were other factors significantly associated with DPP including smoking (P = 0.019), retinopathy (P = 0.014), blood pressure (P < 0.05), aspartate aminotransferase (P = 0.022), C-reactive protein (P = 0.036) and urine microalbumin/creatinine ratio (P = 0.004). Serum GGT was independently related with DPP according to multiple logistic analysis (P < 0.01)." The researcher concluded, "This study shows that increased levels of serum GGT may have important clinical implications in the presence of DPP in patients with type 2 diabetes."

 

Clustering of Metabolic Risk Factors Is Associated with High-Normal Levels of Liver Enzymes among 6- to 8-Year-Old Children: The PANIC Study (52)

[Health-e-Iron note: we have not included pediatric studies in our Science Libraries because it is our intention to primarily focus on risk factors among adult between the approximate ages of 20 and 75. We've added this 2012 study from Finland, a 2006 study of Pima Indian children in the U.S. and a 2012 study of elementary school children in Korea (studies numbered 53 and 57 below) to emphasize current findings that are consistent with reports from many public health agencies that report dietary habits formed at an early age do not often improve. Several studies on our web site demonstrate that the relative risk of the diseases and early mortality associated with elevated GGT is greatest among individuals under 30 years of age.]

The investigators in this study "studied the associations of clustering of metabolic risk factors with plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in healthy prepubertal children. Methods: The subjects were a representative population sample of 492 children 6-8 years of age." "Children with overweight or obesity, defined by International Obesity Task Force (IOTF) criteria, had a 2.1-times higher risk of having ALT and a 4.5-times higher risk of having GGT in the highest fifth of its distribution than normal weight children. Children in the highest sex-specific third of metabolic syndrome score, body fat percentage, waist circumference, and insulin had a two to three times higher risk of being in the highest fifth of ALT and GGT." The researchers concluded, "Clustering of metabolic risk factors, particularly excess body fat, is associated with high-normal levels of ALT and GGT in prepubertal children. High-normal levels of liver enzymes, especially GGT, and systemic low-grade inflammation could be considered features of metabolic syndrome among children. Subtle changes in liver function may play an important role in the pathogenesis of metabolic syndrome beginning in childhood."

 

GGT and Diabetes among the Pima Indians of Arizona

Serum gamma-glutamyl transpeptidase is a determinant of insulin resistance independently of adiposity in Pima Indian children (53) Free full test

The researchers in this 2006 reported study undertook to "establish whether independent relationships exist between either adiposity or IR (insulin resistance) and hepatic enzymes in a group of Pima Indian children." "In a cross-sectional study, 44 children (22 males and 22 females; 7-11 yr old) were measured for weight (WT), height, percent body fat, and serum activities of ALT, AST, and GGT. Body mass index (kilograms per meter squared) was calculated. IR was calculated from fasting plasma concentrations of glucose and insulin using the homeostasis model assessment (HOMA-IR)." "Hepatic enzymes were positively associated with obesity measures, fasting insulin, and HOMA-IR. GGT was additionally associated with serum lipids and white blood cell count. GGT, but not AST or ALT, was a significant determinant of HOMA-IR independently of age, sex, and WT, body mass index, or percent body fat. The model that accounted for the largest portion of the variance in HOMA-IR included WT (beta = 0.004; P = 0.008) and GGT (beta = 0.20; P = 0.004; total R(2) = 0.62; P < 0.0001)." The researchers concluded, "Significant relationships between adiposity and hepatic enzyme activities exist during childhood in Pima Indians. Whether serum GGT activity predicts the development of T2DM in these children remains to be determined in follow-up studies." [Health-e-Iron note: The Pima Indian population in the U.S. has the highest incidence of type 2 diabetes in the world, approximately five-fold that of their "cousins" in Mexico. We have added Table #1 from this study below to illustrate that GGT levels in these very young children already have reached the high and very high risk categories for diabetes, heart diseases and early mortality among adults. The respective Pima boy and girl mean (average) GGT levels were 24.5 and 22.8 U/L. We've compared these GGT levels with those of comparably aged Korean children (see study #57 below, Table#2). The young Korean boys and girls had mean mean GGT levels of ~ 14.1 and 13.4 U/L respectively, significantly lower than those of the Pima children.

 

We have added several more Pima Indian studies below that further define the extent of this major public health problem. We believe there's a dietary solution to this problem that can be achieved by providing healthier foods to this very high-risk community, inclusive of nutrient dense and antioxidant replete whole foods inclusive of fresh fruits, vegetables, nuts, berries, legumes cocoa beverages and dark chocolate. This is truly a community where the term "overfeed & undernourished" applies. This will likely require a proactive strategy to replace packaged, high calorie, high-fructose, nutrient-poor foods, which likely caused this problem in the first place, with healthier foods. More on the science behind lowering GGT through healthy food choices can be read on our GGT & Healthy Food page and on our More Healthy Foods page.]

 

High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes (54) Free full text

[Health-e-Iron note: This was a study of reported in 2002. Importantly, this study was reported before knowledge regarding the prognostic capability of GGT to forecast developing type 2 diabetes had been widely reported. At that time little was known about the dose-relationship of GGT with incident diabetes. As noted on this page and elsewhere on this web site, that relationship appears at relatively low levels of GGT, even those well-within standard laboratory references ranges.] 

The researchers stated: "The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians." "We measured ALT, AST, and GGT in 451 nondiabetic ... Pima Indians (aged 30 +/- 6 years, body fat 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO] during the low-dose insulin infusion of a hyperinsulinemic clamp) and acute insulin response (AIR) (25-g intravenous glucose challenge)." "Sixty-three subjects developed diabetes over an average follow-up of 6.9 +/- 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGT were related to percent body fat (r = 0.16, 0.17, and 0.11, respectively), M (r = -0.32, - 0.28, and -0.24), and HGO (r = 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT [relative hazard 90th vs.10th centiles (95% CI): 1.9 (1.1-3.3), P = 0.02], but not AST or GGT, predicted diabetes. The researchers concluded, "Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver in the pathogenesis of type 2 diabetes." [Health-e-Iron note: In 2002, when this study was reported, GGT was known mainly as a marker of liver disease or alcohol consumption, but generally only when GGT exceeded the upper interval of standard laboratory reference ranges. Although ~ 21% of the study group had become diabetic during the nearly 7 year follow-up period (somewhat more than half the rate of diabetes in the U.S. Pima community). Table 1 from this study appears below. This study population was relatively young at follow up (~ 30 yrs. of age), consisted of ~ 38% men and ~ 62% women. The researchers used combined gender GGT measures that indicated GGT increased over time, was higher among the individuals that became diabetic during the period and reached a mean level of ~ 50 U/L. Measured in either men or women, GGT of 50 U/L or greater, independent of other risk factors, is predictive of incident diabetes, heart disease and premature mortality as demonstrated in the more recent studies referenced on this web site.]

 

 

Differences in Insulin Resistance in Mexican and U.S. Pima Indians with Normal Glucose Tolerance (55) Free full text

In 2010 another group of investigators reported on the high incidence of insulin resistance as a major risk factor in the development of type 2 diabetes in the U.S. Pima Indian community. This research team noted that the U.S. Pima Indians as "a population with the highest prevalence of type 2 diabetes mellitus in the world. Their Mexican counterpart, living a traditional lifestyle in the mountains of Sonora, have at least 5 times less diabetes than the U.S. Pima Indians." "We evaluated whether Mexican Pima Indians had lower insulin resistance than U.S. Pima Indians." "We compared fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) in 194 Mexican Pima Indians (100 females, 94 males) and 449 U.S. Pima Indians (246 females, 203 males) with normal glucose tolerance from a cross-sectional study." "Unadjusted fasting insulin and HOMA-IR were much lower in the Mexican Pima Indians than in their U.S. counterparts. After adjusting by obesity, age, and sex, mean (95% confidence interval) for fasting insulin was 6.22 (5.34-7.24) vs. 13.56 μU/ml (12.27-14.97) and for HOMA-IR 1.40 (1.20-1.64) vs. 3.07 (2.77-3.40), respectivelyfor Mexican Pima and U.S. Pima Indians. Results were confirmed in subset matched for age, sex, and body fat." Notably, this research team did not report on comparative liver enzymes. The researchers concluded, "...our results indicate that Mexican Pima Indians with normal glucose tolerance have lower insulin resistance in comparison with their genetically related counterparts U.S. Pima Indians, even after controlling for differences in obesity, age, and sex. This finding underscores the importance of lifestyle factors as direct protecting factors against insulin resistance in nondiabetic populations." [Health-e-Iron note: Since this investigations was limited in terms of scope, and did not include biochemical measurements such as GGT, their finding respecting lifestyle factors is consistent with those of other research teams. Certainly lifestyle factors play an important role in the development of insulin resistance and diabetes. In regard to lifestyle factors, this study is consistent with many others in that it does not differentiate nor weight lifestyle factors much beyond the somewhat standard measures of body fat and waistline circumference values and differences in physical activity levels. The authors' referenced literature search as well appears to have been limited in scope. Relative measures of both iron and GGT would likely have added significant prognostic value within the broad scope of "lifestyle factors."  Qualitative and quantitative nutritional differences are most likely the major lifestyle factors that underlay this very significant difference in disease prevalence. This would have been an ideal context in which to measure the unanswered question from the above Pima Indian children's study reported four years earlier, "Whether serum GGT activity predicts the development of T2DM in these children remains to be determined in follow-up studies."]

 

Effects of Traditional and Western Environments on Prevalence of Type 2 Diabetes in Pima Indians in Mexico and the U.S. (56) Free full text

The investigators who published this study in 2006 noted that, "Type 2 diabetes and obesity have genetic and environmental determinants. We studied the effects of different environments on these diseases in Pima Indians in Mexico and the U.S." "Adult Pima-Indian and non-Pima populations in the Sierra Madre mountains of Mexico were examined using oral glucose tolerance tests and assessments for obesity, physical activity, and other risk factors. Results were compared with those from Pima Indians in Arizona. Both Pima populations were typed for DNA polymorphisms to establish their genetic similarity." "The age- and sex-adjusted prevalence of type 2 diabetes in the Mexican Pima Indians (6.9%) was less than one-fifth that in the U.S. Pima Indians (38%) and similar to that of non-Pima Mexicans (2.6%). The prevalence of obesity was similar in the Mexican Pima Indians (7% in men and 20% in women) and non-Pima Mexicans (9% in men and 27% in women) but was much lower than in the U.S. Pima Indians. Levels of physical activity were much higher in both Mexican groups than in the U.S. Pima Indians. The two Pima groups share considerable genetic similarity relative to other Native Americans." The researchers conclude, "The much lower prevalence of type 2 diabetes and obesity in the Pima Indians in Mexico than in the U.S. indicates that even in populations genetically prone to these conditions, their development is determined mostly by environmental circumstances, thereby suggesting that type 2 diabetes is largely preventable. This study provides compelling evidence that changes in lifestyle associated with Westernization play a major role in the global epidemic of type 2 diabetes."

[Health-e-Iron note: we have placed three video links below that describe the historical and cultural framework which led to the serious diabetes problem among the U.S. Pima Indian's. The fourth video suggests the first step toward a healthy solution. These and other similar videos and transcripts can be found at this web page: http://www.unnaturalcauses.org/video_clips.php]

The Problem - How and Why, and What can be done?

CLICK ON TITLE FOR VIDEO LINK 

 

Cultural Loss - Impact on Native American Health

Diabetes among Native Americans – Genes or Environment?

Diabetes Industry and Native American health

Gardening as Cultural Renewal - the Gila Crossing School Program


The Relationship between Serum Gamma-glutamyltransferase Level and Overweight in Korean Urban Children (57) Free full text

This was a study reported in Korea in 2009.  "This study was a cross-sectional study using data on 390 4th grade students of elementary schools in Gunpo, Korea." "Children (mean age = 9.8 yrs.) were divided into 4 groups according to gender-specific quartiles of serum GGT level. Body mass index, waist circumference and body fat percentage were quantified as adiposity indices." "All adiposity indices in children of the highest GGT level quartile were higher than those in children of the lowest quartile. Adjusted odd ratios on overweight of the highest quartile of GGT level compared to the lowest quartile were 14.40 (95% confidence interval [CI], 4.43 to 46.83) in boys and 2.94 (95% CI, 1.06 to 8.16) in girls." The researchers concluded, "This study shows that high serum GGT level is related with overweight in Korean urban children and this relationship is stronger in boys compared to girls." [Health-e-Iron note: Table#2 from this study appears below]




Ultrasonographic Hepatic Steatosis Increases Prediction of Mortality Risk From Elevated Serum Gamma-Glutamyl Transpeptidase Levels (57) Free full text

The aim of this German study reported in 2009 "was to investigate the association of serum gamma-glutamyltransferase (GGT) levels with all-cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association." "We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population-based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis." "Elevated GGT levels were associated with increased risk of mortality in men (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.08-2.05), but not in women (HR 1.30; 95% CI, 0.80-2.12). This association was even stronger in men with hepatic steatosis (HR 1.98; 95% CI, 1.21-3.27). Cause-specific mortality analysis by cardiovascular disease deaths confirmed the sex-specific association. Adjustment for cardiometabolic risk factors did not affect the estimates." The researchers concluded, "In the case of increased GGT levels, liver ultrasound should be performed, not only for diagnosis, but also for further risk stratification." [Health-e-Iron note: Table #3 from this study appears below]


Gamma-glutamyltransferase and diabetes--a 4 year follow-up study  (58) Free full text

The researchers in this 2003 reported study of Korean men noted that, "Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses." "Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes." "A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication." "There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration." The researchers concluded, "This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes." [Health-e-Iron note: Table #2 for this paper appears below]

Did you know?

Donating blood once a year can decrease a male's risk of a heart attack by up to 50%?

VIDEO LINKS

[Health-e-Iron note: Reminder, when GGT is elevated, glutathione and most other antioxidants are insufficient!]

"Understanding Antioxidants" (2:31)

"Antioxidants vs. free radicals" (3:10)


Dr. Mercola on "Is iron helping or slowly killing you?"

Dr. Mercola on iron as "anti-antioxidant?" (8:44)


To learn more about the antioxidant protection afforded by various fruits, you can read more on this site:

 Fruitsinfo.com