Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urine albumin (Alb), total protein (TP) and creatinine (Cr) concentrations and the activities of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP) and gamma-glutamyl transpeptidase (GGT) were measured in untimed random urine samples from 157 non-insulin-dependent (NIDDM) diabetic subjects and 54 healthy subjects. In NIDDM subjects the excretions of TP, Alb, NAG, AAP, GGT (expressed in relation to creatinine) were significantly higher and were abnormal in 59.9%, 68.8%, 47.2%, 41.4% and 13.4% of the subjects, respectively. However, 24.5%, 22.4% and 6.1% of NIDDM subjects with normal Alb/Cr ratio had abnormal excretion of NAG, AAP and GGT, respectively. Alb/Cr ratio was greater than 26.8 mg/mmol (considered to be equivalent to albumin excretion of 250 mg/24 h) in 14.6% and between 2.5-26.8 mg/mmol (equivalent to albumin excretion rates of 20-250 mg/24 h) in 54.1% of subjects. In those diabetic subjects with clinical retinopathy only Alb/Cr ratio was higher. Arterial blood pressure was significantly correlated with Alb/Cr (r = 0.365) and NAG/Cr (r = 0.204). We conclude that prevalence of abnormal Alb/Cr is relatively common among Chinese NIDDM subjects.
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PMID:Urinary excretion of albumin and enzymes in non-insulin-dependent Chinese diabetics. 197 40

1. The activity of serum butyrylcholinesterase ('pseudocholinesterase', EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/- 3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.
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PMID:Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus. 814 99

A 45-year-old man had been complaining of thirst and polydypsia for the last 3 months and was diagnosed as having type 2 diabetes mellitus because his fasting blood glucose showed 221 mg/dl with positive urinary ketone. He was hospitalized to a private hospital and Penfil 30R was started. However, serum gamma-GTP and aminotransferases began to elevate after insulin treatment and exceeded 1000 IU/l. Insulin was discontinued and serum gamma-GTP and aminotransferases returned close to the normal range. Since his glycemic control became poor again, Penfil 30R was restarted and serum gamma-GTP and aminotransferases elevated again. Therefore, insulin was discontinued and the patient was referred to the Third Department of Internal Medicine, Yamanashi Medical University Hospital because of liver dysfunction. His plasma glucose decreased by diet therapy, and improved further by the administration of glibenclamide. After obtaining informed consent, Humalin R was challenged. Seven days after insulin injection, serum aminotransferases began to elevate again. Lymphocyte stimulation test was negative against three preparations (Penfil R, Penfil N and Humalin R). The present case suggests that human insulin itself can cause liver dysfunction and we need to pay more attention to liver function tests when we start insulin treatment.
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PMID:A type 2 diabetic patient with liver dysfunction due to human insulin. 1080 59

Interactions between advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the vascular complications in diabetes. We have identified eight novel polymorphisms, of which the -1420 (GGT)n, -1393 G/T, -1390 G/T, and -1202 G/A were in the overlapping PBX2 3' untranslated region (UTR), and the -429 T/C (66.5% TT, 33.5% TC/CC), -407 to -345 deletion (99% I, 1% I/D, 0% D), -374 T/A (66.4% TT, 33.6% TA/AA), and +20 T/A were in the RAGE promoter. To evaluate the effects on transcriptional activity, we measured chloramphenicol acetyl transferase (CAT) reporter gene expression, driven by variants of the -738 to +49 RAGE gene fragment containing the four polymorphisms identified close to the transcriptional start site. The -429 C, -374 A, and 63-bp deletion alleles resulted in a mean increase of CAT expression of twofold (P < 0.0001), threefold (P < 0.001), and fourfold (P < 0.05), respectively, with the -374 T and A alleles yielding highly differential binding of nuclear protein extract from both monocyte- and hepatocyte-derived cell lines. The prevalence of the functional polymorphisms were investigated in subjects with type 2 diabetes (106 with and 109 without retinopathy), with the -429 C allele showing an increase in the retinopathy group (P < 0.05). These data suggest that the polymorphisms involved in differences in RAGE gene regulation may influence the pathogenesis of diabetic vascular complications.
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PMID:Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy. 1137 54

It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. 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 (75-g oral glucose tolerance test) 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. Elevated ALT at baseline was associated prospectively with an increase in HGO (r = 0.21, P = 0.001) but not with changes in M or AIR (both P = 0.1). Higher ALT concentrations were cross-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. 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.
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PMID:High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. 1203 78

Troglitazone maleate (Rezulin) has been associated with severe hepatotoxicity, which led to its withdrawal from the U.S. market in March 2000. Rosiglitazone maleate (Avandia) is being marketed as a safe alternative in the treatment of type 2 diabetes mellitus. We report a case of severe thiazolidinedione-induced cholestatic hepatitis in a 56-year-old female patient at a university hospital who was given rosiglitazone, 8 mg/day, after she developed milder hepatotoxicity while taking troglitazone. Rosiglitazone was discontinued, and the patient was treated with prednisone, azathioprine, and ursodiol. Clinical evaluation and liver biopsy were performed and liver function tests were monitored. After being switched from troglitazone to rosiglitazone the patient developed a severe cholestatic hepatitis with marked jaundice and moderate increases in serum alkaline phosphatase and gamma-glutamyltranspeptidase but only mild increases in serum aminotransferases. Discontinuation of rosiglitazone and treatment with prednisone, azathioprine, and ursodiol led to improvement, albeit with residual injury, dropout of intrahepatic bile ducts, and persisting elevations of serum alkaline phosphatase. Rosiglitazone is not always a safe alternative in patients who have had hepatotoxicity to troglitazone. It is important to monitor the serum alkaline phosphatase in addition to the serum aminotransferases in patients taking thiazolidinediones.
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PMID:Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone. 1214 28

We have compared the concentrations of intracellular glutathione (GSH), glutathione-dependent antioxidative enzymes, the cell death rate and immunophenotype profile of peripheral blood mononuclear cells (PBMC) from healthy donors and from patients with insulin-dependent type II (NIDDM) diabetes mellitus. The IDDM and NIDDM patients had above-normal absolute lymphocyte counts, whereas the percentages of CD3, CD4 adn CD8 T lymphocytes were significantly reduced. In contrast, the absolute number and percentage of B lymphocytes was higher in diabetic patients than in healthy donors. The low intracellular reduced glutathione(GSH) and the unbalanced profile of key enzymes involved in GSH metabolism, gamma-glutamyltransferase (gamma-GT) and glutathione-S-transferase (GST), account for the increased oxidative status of PBMC from diabetic patients. The plasma membranes of PBMC for diabetic patients were less permeable to propidium iodide than those of PBMC from healthy donors, indicating that the apoptotic cell death rate was lower in the cells from diabetic patients. These differences are potentially useful markers of pathogenic metabolic changes which occur during clinical diabetes and if they are confirmed could be use dot identify the onset of diabetes.
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PMID:Apoptosis and oxidative status in peripheral blood mononuclear cells of diabetic patients. 1469 96

ACE gene insertion/deletion (I/D) polymorphism is a well-known risk factor of hypertension, cardiovascular diseases and progression of diabetic nephropathy. In carriers of allele D, serum level of angiotensin-II is higher, which can be associated with increased oxidative stress and subsequent endothelial damage. Albuminuria is a sensitive marker of endothelial damage, while serum activity of the enzyme gamma-glutamyl transferase--that plays important role in the antioxidant defense--may refer to the level of oxidative stress. The present paper reports on a cross-sectional clinical study, where authors have examined on the relation between ACE gene insertion/deletion polymorphism and carbohydrate metabolism, hypertension as well as albuminuria in type 2 diabetics (n = 145). In patients carrying allele D, fructosamine levels were significantly higher (p = 0.007) than in carriers of allele I. Patients with II + ID genotypes and those who were treated with insulin took more antihypertensive drugs than the ones with II genotype or orally treated (p = 0.015). They found a significant association between genotype and fructosamine level (p = 0.023). Association between genotype or modality of treatment of diabetes (oral vs, insulin) and combined treatment of hypertension (number of antihypertensive drugs) was of borderline significance. They found that fructosamin level of patients receiving ACE inhibitor was lower than that of patients not receiving ACE inhibitors. In patients with allele D, they have also found higher activity of gamma-GT and higher albuminuria. From this results and data of the literature the authors conclude that because of insulin resistance (in connection with the presence of allele D), these patients tend to have a worse metabolic state, more advanced glycation products, due to which oxidative stress and endothelial cell damage may develop. As albuminuria and activity of gamma-GT were both found higher in patients with allele D, and our patients did not suffer of any hepatic disease, authors take the consequence that gamma-GT is a marker of the oxidative stress caused by allele D. Endothelial damage may explain that these patients take a higher number of antihypertensive combination. Based on this, D allele may contribute--via increased glycation and oxidative stress--to the target organ damage in type 2 diabetes.
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PMID:[Effect of ACE gene polymorphism on carbohydrate metabolism, on oxidative stress and on end-organ damage in type-2 diabetes mellitus]. 1515 90

When compared with values recorded in 14 control subjects, the 15 overweight patients with type 2 diabetes displayed significantly increased activities of serum alanineaminotransferase (172% of mean values in controls), gamma-glutamyltransferase (253%) and cholinesterase (139%). A much wider dispersion of individual values for the two firstly mentioned enzymes was however noted so that their correlation with serum triglycerides levels were weaker (r = 0.373; p < 0.05 and r = 0.451; p < 0.05 respectively) than the same correlation obtained for serum cholinesterase (r = 0.760; p < 0.001). In two other studies including 28 controls and 30 diabetic patients serum cholinesterase was found to be significantly correlated with serum levels of insulin (r = 0.622; p < 0.001), C-peptide (r = 0.652; p < 0.001) and free fatty acid (r = 0.821; p < 0.001). Circumstantial evidence is provided that insulin resistance and an increased flux of free fatty acids from adipose tissue to the liver would stimulate the hepatic synthesis of serum cholinesterase.
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PMID:Serum cholinesterase activity correlates with serum insulin, C-peptide and free fatty acids levels in patients with type 2 diabetes. 1552 39

Serum gamma-glutamyltransferase (GGT) concentration within its normal range has emerged as an important predictor in the pathogenesis of diabetes. We 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. A prospective cohort study of 20,158 Finnish men and women aged 25-64 yr who participated in cardiovascular risk-factor surveys carried out in four areas during 10 yr. The average follow-up time was 12.7 yr, and there were 388 incident diabetes cases. Serum GGT cut points were at the 25th, 50th, 75th, and 90th percentiles. Initiation of new diabetes medication defined incidence cases. 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). Body mass index appeared to be more strongly associated with type 2 diabetes in both men and women over age 50 yr with GGT median or greater, compared with subjects with GGT less than median. In conclusion, 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.
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PMID:gamma-Glutamyltransferase, obesity, and the risk of type 2 diabetes: observational cohort study among 20,158 middle-aged men and women. 1553 90


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