Gene/Protein Disease Symptom Drug Enzyme Compound
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The aim of this study was to evaluate the comparative effects of rosiglitazone and metformin on metabolic parameters in recently diagnosed type 2 Greek diabetic patients. A total of 41 drug-naive individuals, with recently diagnosed type 2 diabetes, were randomized in 3 groups: DIET, diet alone; ROSI, diet plus rosiglitazone; and MET, diet plus metformin. Anthropometric indexes, blood pressure, hematological and biochemical parameters were estimated at baseline and after 18 weeks of treatment. We observed a significant decrease of fasting glucose (FBG) (p<0.001), glycated haemoglobin (HbA1c) (ROSI: p=0.001, MET: p<0.001), homeostasis model assessment for insulin resistance (HOMA-IR) (ROSI: p=0.006, MET: p =0.009) and glutamic pyruvic transaminase (SGPT) (ROSI: p=0.004, MET: p=0.003) in both ROSI and MET groups. Metformin significantly reduced fasting insulin (p=0.04), body weight (p=0.026), body mass index (BMI) (p=0.022), waist circumference (p=0.022) and gamma glutamyl transpeptidase (gamma-GT) (p=0.039), while rosiglitazone decreased blood pressure (systolic: p = 0.05, mean: p = 0.03) and alkaline phosphatase (ALP) (p =0.001) compared to baseline values. Combined intervention with rosiglitazone and diet led to a slight, not significant, weight loss. Rosiglitazone and metformin are equaly effective in controling diabetes, decreasing insulin resistance and improving liver function. However, considering the more favorable effects of metformin on body composition and its documented cost-effectiveness, it seems to be preferable in newly diagnosed Greek diabetic patients.
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PMID:Metabolic effects of rosiglitazone and metformin in Greek patients with recently diagnosed type 2 diabetes. 1821 Jul 65

Both elevated liver enzymes and a family history of diabetes mellitus (FHDM) are independent risk factors for type 2 diabetes. This study evaluates the epidemiological association between elevated liver enzymes and FHDM. Subjects included 3512 women workers without diabetes, hepatitis, a smoking habit, or a history of alcohol intake. Blood samples and personal data were collected from all subjects. Subjects with FHDM had a higher mean body mass index (BMI: 23.9kg/m(2) vs. 23.4kg/m(2); p=0.003). Laboratory testing also revealed higher mean fasting plasma glucose (FPG: 5.67mmol/L vs. 5.22mmol/L; p<0.001), asparate aminotransferase (AST: 20.0IU/L vs. 19.2IU/L; p=0.049), alanine aminotransferase (ALT: 18.4IU/L vs. 16.7IU/L; p=0.004), gamma-glutamyltranspeptidase (GGT: 24.1IU/L vs. 20.5IU/L; p<0.001), and triglycerides (TG: 1.09mmol/L vs. 1.00mmol/L; p=0.011) for FHDM subjects, when adjusted for age and BMI. Multiple linear regression analysis revealed that FHDM, age, BMI, FPG, and TG were correlated with GGT (p=0.004 for FHDM; p<0.001 for age, BMI, FPG, and TG). Elevated liver enzymes were associated with FHDM. In particular, elevated GGT was related to FHDM, independent of the other variables. Elevated liver enzymes, probably due to fat deposition in the liver, may play a role in increasing the risk of diabetes in individuals with FHDM.
Diabetes Res Clin Pract 2008 Mar
PMID:Elevated liver enzymes in women with a family history of diabetes. 1824 60

The aim of the study was to assess gamma-glutamyl transpeptidase (gamma-GT), alanine aminotransferase, and aspartate aminotransferase (AST) in the prediction of diabetes and cardiovascular disease (CVD) in subjects free from hepatic diseases other than nonalcoholic fatty liver disease. The present analysis was performed on the cohort of subjects enrolled in the Firenze Bagno a Ripoli (FIBAR) study, a screening program for diabetes performed between 1 March 2001 and 31 December 2003 in the city of Florence on 3124 subjects who underwent an oral glucose tolerance test. Incident cases of diabetes in nondiabetic subjects (n = 2662) were obtained through databases of drug prescriptions, hospital admissions, and lists of subjects eligible for reimbursement. Incident CVD in subjects free of diabetes and CVD at enrollment (n = 2617) was identified through hospital admissions and through the register of causes of death. Mean follow-up was 39.6 +/- 12.0 months and 39.8 +/- 11.4 months for diabetes and CVD, respectively. Yearly incidence of diabetes and CVD was 0.4% and 0.2%, respectively. After adjustment for age and sex, gamma-GT >40 U/L was associated with increased incidence of diabetes and CVD (hazard ratio [95% confidence interval]: 2.54 [1.26-5.11], P < .05 and 2.21 [0.98-5.43], P < .10, respectively). Risk of diabetes, but not of CVD, was increased in patients with gamma-GT in the 25- to 40-U/L range. After adjustment for confounders, AST >40 U/L predicted CVD (hazard ratio, 6.5 [95% confidence interval, 1.5-28.1]), but not diabetes. Elevated gamma-GT or AST is an independent predictor of CVD. An increase of gamma-GT levels above the reference range, or also in the upper reference range, is an independent predictor of incident diabetes.
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PMID:Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study. 1824 12

The aim of study was to investigate the role of serum total (TPL) and high-density lipoprotein phospholipids (HDL-pl) as a risk factor in coronary heart disease (CHD) and metabolic syndrome (MS). In a random sample, total and HDL-pl were measured in 1088 and 642 adults from Turkey, respectively, who have a high prevalence of MS; this was done with an enzymatic method that measures total phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine. Serum TPL and HDL-pl levels were significantly higher in women (TPL, 2.8 mmol/L; HDL-pl, 1.21 mmol/L) than in men. Strong correlations existed between serum TPL levels and non-HDL cholesterol (HDL-C), triglycerides, apolipoprotein (apo) B, complement C3, and gamma-glutamyltransferase. Non-HDL-C, HDL triglyceride, and apo A-I were strongly correlated with HDL-pl. Linear regression analyses revealed HDL-C, apo B, triglycerides, diabetes, and female gender as independent significant determinants of TPL levels in adults. HDL-C and impaired glucose regulation were sole significant variables, together contributing one-quarter of serum HDL-pl. Individuals with MS or diabetes had significantly higher TPL concentrations. The gender- and age-adjusted odds ratio (OR) of TPL for MS was 1.73 (95% confidence interval, 1.35-2.21), whereas the multiadjusted OR of HDL-pl per 1 SD increment corresponded to a significantly reduced independent MS likelihood by 26% in women (and 18% in the entire group). The multiadjusted OR of HDL-pl for CHD in men and women combined was 0.32 (P = .057) corresponding to a reduced CHD likelihood by 32% per 1 SD increment of HDL-pl. Plasma TPL levels point to an adverse relationship to MS, whereas their role in CHD risk needs further investigation. HDL-pls, in contrast, mark substantial protection from MS as well as from CHD.
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PMID:Serum total and high-density lipoprotein phospholipid levels in a population-based study and relationship to risk of metabolic syndrome and coronary disease. 1831 19

To examine whether the response of fasting plasma glucose (FPG) to alcohol consumption differs among individuals, a cross-sectional study was conducted in 6100 men with a body-mass index below 24 who did not take medication for diabetes. Information regarding current medication and lifestyle habits was obtained by a self-reported questionnaire. The subjects were divided into four groups according to their level of alcohol consumption: non-drinkers, light drinkers (1-188ml/week), intermediate drinkers (189-377ml/week), and heavy drinkers (>or=378ml/week). The frequency of subjects with an FPG of 110mg/dl or more rose significantly as alcohol consumption increased, from 6.7% in non-drinkers to 10.1% in intermediate drinkers and 12.1% in heavy drinkers. In contrast, when only the subjects with a gamma-glutamyltransferase level of less than 40IU/L were analyzed, no difference was observed in the frequency of subjects with an FPG level of 110mg/dl or more among the four groups. Multiple logistic regression analysis also revealed similar results. The findings suggested individual variability in the response of FPG to drinking. Appropriate levels of drinking could be different among individuals.
Diabetes Res Clin Pract 2008 Jun
PMID:Relationship between response of gamma-glutamyltransferase to alcohol consumption and levels of fasting plasma glucose. 1834 85

The occurrence of liver disease and raised liver enzymes is common in Type 2 diabetes, and may be multifactorial in origin. Very few studies are available on the exact prevalence of the phenomenon, however. We carried out an observational point-prevalence study of elevated liver enzymes in eight hospital-based Italian diabetes units. Data of 9621 consecutive Type 2 diabetes patients (males, 52.4%; median age, 65 yr) were analyzed, and alanine and aspartate aminotransferase (ALT, AST) and gamma-glutamyltransferase (GGT) levels were related to body mass index (BMI), metabolic control and the presence of the metabolic syndrome. ALT, AST, and GGT levels exceeding the upper limit of normal were present in 16.0%, 8.8%, 23.1%, respectively, the prevalence being higher in males, increasing with obesity class and poor metabolic control, and decreasing with age. Elevated enzymes were systematically associated with most parameters of the metabolic syndrome. After correction for age, gender, BMI, and differences across centers, elevated triglyceride levels/fibrate treatment [odds ratio (OR), 1.57; 95% confidence interval (CI), 1.34- 1.84] and an enlarged waist circumference (OR, 1.47; 95% CI, 1.17-1.85) were the only parameters independently associated with high ALT. In a separate analysis, the presence of metabolic syndrome (Adult Treatment Panel III criteria) was highly predictive of raised liver enzymes. After exclusion of hepatitis B and C positive cases, tested in 2 centers, the prevalence of raised enzymes decreased by approximately 4%, but the association with the metabolic syndrome did not change significantly. In conclusion, the high prevalence of elevated liver enzymes in Type 2 diabetes is in keeping with the well-demonstrated risk of progressive liver disease. A large amount of diabetes patients may require a thorough clinical, laboratory and histological investigation.
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PMID:Prevalence of elevated liver enzymes in Type 2 diabetes mellitus and its association with the metabolic syndrome. 1836 6

Emerging scientific evidence suggests that increases in body iron represent a risk factor for the development of metabolic syndrome and diabetes. The aim of our study was to determine the body iron stores in patients with metabolic syndrome, and to evaluate the potential relationship of iron overload with specific features of the metabolic syndrome, such as fatty liver. A total of 490 individuals were enrolled. The diagnosis of metabolic syndrome was based on National Cholesterol Education Program-Adult Treatment Panel III (ATPIII) criteria. The metabolic syndrome group was consisted of 185 patients having three or more criteria, whereas individuals with less than three criteria constituted the control group. Metabolic syndrome patients displayed higher ferritin concentration as compared to control individuals. Ferritin levels were positively correlated with insulin concentration, as well as with Homeostasis Model Assessment (HOMA) index values. Multiple regression analysis revealed that ferritin was the most important independent determinant of insulin resistance indices. Patients with metabolic syndrome also exhibited increased concentrations of alanine aminotransferase and gamma-glutamyltranspeptidase compared to controls. Multiple regression analysis revealed that ferritin concentration was the most important determinant of gamma-glutamyltranspeptidase levels. Patients with the metabolic syndrome exhibit an increase in body iron stores as well as elevated concentrations of liver enzymes compared to the individuals who do not fulfill the criteria for the diagnosis of this syndrome. Our data support a direct role of increased body iron in the pathogenesis of insulin resistance, whereas iron overload may also contribute to the development of specific features of the metabolic syndrome, such as fatty liver.
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PMID:Increased serum ferritin concentrations and liver enzyme activities in patients with metabolic syndrome. 1837 Jul 38

Leptin receptor (LEPR) plays an important physiological role in energy metabolism. The study addressed the relationship between leptin receptor gene variations and type 2 diabetes mellitus (T2DM). Three single nucleotide polymorphisms (SNPs) of LEPR gene, Arg109Lys (A/G), Asn656Lys (C/G) and Pro1019Pro (C/T) were detected in a northern population in China. Totally, 317 patients with T2DM and 282 healthy controls were recruited randomly from urban communities in Harbin area in the Northeast of China. All polymorphisms were genotyped by Sequenom SNP detection system in both case and control groups. Linkage disequilibria analysis showed moderate linkage disequilibria between the pair-wise SNPs for all three SNPs. Then, we identified the haplotype covering the three SNPs (AGC) with higher risk of T2DM (OR=1.69 (1.09-2.61)), and showed that there existed significant difference between cases and controls (9.8% vs. 6.0%, P=0.02). We also observed significant difference in frequencies of the heterozygous haplotype combination (GGT/AGC), that is 17.0% vs. 8.2% in cases and controls, respectively (P=0.001). It further supported the evidence that the haplotype (AGC) was associated with T2DM. So, AGC haplotype in LEPR gene could be a risk factor associated with T2DM in Northern Chinese.
Diabetes Res Clin Pract 2008 Jul
PMID:The haplotype identified in LEPR gene is associated with type 2 diabetes mellitus in Northern Chinese. 1843 1

We evaluated possible interactions between BMI and serum gamma-glutamyltransferase (GGT) concentration and their effects on the prevalence of poor glycemic control and common comorbidities of diabetes. We assessed whether the association of BMI with poor glycemic control, hypertension, atherogenic dyslipidemia (i.e., high triglycerides and/or low high-density lipoprotein (HDL) cholesterol), hypercholesterolemia, and hyperuricemia differed according to serum GGT concentration in a cohort of 3,633 type 2 diabetic individuals. The associations of BMI with different outcome measures were significant, but the associations varied remarkably by GGT concentration. 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. For example, 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 results remained unchanged after adjustment for sex, age, alcohol consumption, diabetes duration, and diabetes treatment. In conclusion, our findings show that BMI was associated with atherogenic dyslipidemia and poor glycemic control only when serum GGT activity was in its high-normal range. 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.
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PMID:Relationship of serum gamma-glutamyltransferase to atherogenic dyslipidemia and glycemic control in type 2 diabetes. 1905 28

The aim of this study is to examine the association between obesity, metabolic syndrome, physical activity, and elevated gamma-glutamyltransferase (GGT) among Indigenous Australian adults who did not drink alcohol. A cross-sectional study of 791 Indigenous adults in rural North Queensland communities was conducted between 1999 and 2001. Measures included serum GGT, fasting glucose, cholesterol, and triglycerides; resting blood pressure, BMI, and waist circumference; and self-reported physical activity, alcohol intake, and tobacco smoking. Central obesity measured by waist circumference in this population was significantly associated with elevated GGT independently of lifestyle behaviors (Adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 1.2-6.0). Metabolic syndrome (International Diabetes Federation definition) was also strongly associated with increased GGT (OR = 2.6, 95% CI: 1.5-4.6). Habitual physical activity may be slightly protective (OR = 0.9, 95% CI: 0.5-1.6) in this group, but this was not clearly demonstrated in this study. Prevention of type 2 diabetes and cardiovascular disease in this population should emphasize "waist loss" and metabolic health through dietary and other interventions.
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PMID:gamma-Glutamyltransferase, obesity, physical activity, and the metabolic syndrome in indigenous Australian adults. 1914 21


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