Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription factor 7-like 2 (TCF7L2) regulates genes involved in cell proliferation and differentiation. The TCF7L2 gene is located on chromosome 10q25 in a region of replicated linkage to type 2 diabetes. Recently, a microsatellite marker in intron 3 (DG10S478) and five correlated single nucleotide polymorphisms (SNPs) were identified in Icelandic individuals that showed strong association with type 2 diabetes, which was replicated in Danish and European-American cohorts. We genotyped four of the SNPs (rs7901695, rs7903146, rs11196205, and rs12255372) in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT; n = 139), and normal glucose tolerance (NGT; n = 342). We compared genotype frequencies in subjects with type 2 diabetes with those with NGT and found marginal association for rs7901695 (P = 0.05; odds ratio [OR] 1.51); comparison between NGT control subjects and the combined type 2 diabetes/IGT case group showed strong association with rs7901695 and rs7903146 (P = 0.008-0.01; OR 1.53-1.57) and marginal association with rs11196205 and rs12255372 (P = 0.07 and P = 0.04, respectively). In an expanded set of 698 Amish subjects without diabetes, we found no association with insulin and glucose levels during a 3-h oral glucose tolerance test. We also genotyped these SNPs in nondiabetic, non-Amish subjects (n = 48), in whom intravenous glucose tolerance tests were performed, and found an association between rs7901695 and rs7903146 and insulin sensitivity (P = 0.003 and P = 0.005, respectively) and disposition index (P = 0.04 and P = 0.007, respectively). These data provide replicating evidence that variants in TCF7L2 increase the risk for type 2 diabetes and novel evidence that the variants likely influence both insulin secretion and insulin sensitivity.
Diabetes 2006 Sep
PMID:Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance. 1693 18

Taurine is the most abundant amino acid in the human body and seems to play an important role in increasing glucose-mediated insulin secretion, as well as in programming beta-cell maturation during the prenatal life in utero. To test the hypothesis that plasma taurine is related to glucose tolerance, insulin sensitivity and insulin secretion in subjects with history of beta-cell dysfunction such as women with history of gestational diabetes (GDM), we studied 72 non-diabetic women with history of GDM (n=43), impaired glucose tolerance (IGT; n=7), and normal glucose tolerance (NGT; n=22) as previously classified by a 100g-3h-OGTT performed between the 24th and the 28th gestational week. Insulin sensitivity (ISIogtt, calculated through Matsuda-DeFronzo index) and a proxy for insulin secretion (basal plasma C-peptide/fasting plasma glucose; CP/glucose) were measured during and after pregnancy. Plasma taurine was measured after a median period of 6 years (2-11 years) from index pregnancy, when glucose tolerance was retested by a 75 g-2h-OGTT. Plasma taurine was significantly lower in women who had experienced GDM and was unrelated to ISIogtt. Moreover, plasma taurine was inversely related to previous gestational area-under-curve of glucose and directly related to post-gestational CP/glucose, as well to CP/glucose measured during pregnancy (p<0.05 for both). The relative risk of altered glucose metabolism during previous pregnancies (IGT+GDM) was higher as plasma taurine decreased, even after adjusting for age, time-lag from pregnancy, body mass index and family history of diabetes (OR: 0.980; CI 95%: 0.963-0.999, p=0.003). In conclusion plasma taurine seems to be a fair marker of altered glucose metabolism during past pregnancies in women with antecedent GDM and appears to be inversely related to the previous as well as to the actual insulin secretion in these subjects.
Diabetes Res Clin Pract 2007 May
PMID:Taurine in women with a history of gestational diabetes. 1699 64

The relationships between insulin secretion and resistance in subjects with newly diagnosed prediabetes (preDM) and type 2 DM according to the presence of metabolic syndrome (MS) were controversial. We performed OGTT on 322 drug naive subjects with a history of hyperglycemia of < or =3 months, and divided into three groups, NGT, preDM (IFG and/or IGT), and T2DM. We also diagnosed these subjects with respect to MS according to ATP III criteria modified by Asia-Pacific guidelines and compared IGI and HOMA-IR. When compare groups stratified by the presence of MS, preDM and T2DM groups with MS showed significantly higher mean HOMA-IR and IGI than those without. When compare groups with respect to glucose tolerance, NGT, preDM, and T2DM subgroups in MS group showed significant higher HOMA-IR and lower IGI according to glucose tolerance. However, NGT, preDM, and T2DM subgroups in non-MS group showed a significant decrease in IGI but no significant difference in HOMA-IR as glucose tolerance worsened. In conclusion, deterioration in IGI and aggravation of HOMA-IR are both important in the primary pathogenesis of diabetes in those with MS. However, IGI deterioration may be the only important factor in the primary pathogenesis of T2DM in the absence of MS.
Diabetes Res Clin Pract 2007 Jun
PMID:Insulin secretion and insulin resistance in newly diagnosed, drug naive prediabetes and type 2 diabetes patients with/without metabolic syndrome. 1714 51

Previous studies have postulated the association between oxidative stress and Type 2 diabetes. Considering the long pre-diabetic period with IGR (impaired glucose regulation) and its high risk of developing diabetes, to test this hypothesis, we have investigated oxidative stress pathways and DNA damage in patients with IGR and newly diagnosed Type 2 diabetes. The study population consisted of 92 subjects with NGT (normal glucose tolerance), 78 patients with IGR and 113 patients with newly diagnosed diabetes. Plasma MDA (malondialdehyde) and TAC (total antioxidative capacity) status, erythrocyte GSH content and SOD (superoxide dismutase) activity were determined. A comet assay was employed to evaluate DNA damage. Compared with subjects with NGT, patients with IGR had reduced erythrocyte SOD activity. Patients with diabetes had a higher plasma MDA concentration, but a lower plasma TAC level and erythrocyte SOD activity, than the NGT group. Correlation analysis revealed a strong positive association between IR (insulin resistance) and MDA concentration, but negative correlations with TAC status and SOD activity. With respect to beta-cell function, a positive association with TAC status and an inverse correlation with GSH respectively, were observed. The comet assay revealed slight DNA damage in patients with IGR, which was increased in patients with diabetes. Significant correlations were observed between DNA damage and hyperglycaemia, IR and beta-cell dysfunction. In conclusion, the results of the present study suggest that hyperglycaemia in an IGR state caused the predominance of oxidative stress over antioxidative defence systems, leading to oxidative DNA damage, which possibly contributed to pancreatic beta-cell dysfunction, IR and more pronounced hyperglycaemia. This vicious circle finally induced the deterioration to diabetes.
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PMID:Oxidative stress, antioxidant status and DNA damage in patients with impaired glucose regulation and newly diagnosed Type 2 diabetes. 1720 2

The loss of early-phase insulin secretion is a characteristic feature of type 2 diabetes mellitus. The aim of this study is to examine when impairment of early-phase insulin secretion occurs and whether it can be related to increase in insulin resistance caused by obesity. We developed an analytical method to qualify the early-phase insulin secretion; that is, we measured C-peptide immunoreactivity (CPR) response to a selective increase in blood glucose level in portal vein during oral glucose load under a euglycemic hyperinsulinemic clamp (clamp-OGL). Glucose infusion rate, hepatic glucose uptake, and CPR response during clamp-OGL were measured in 30 subjects with diabetes who were divided into 3 groups based on body mass index, 13 obese subjects with normal glucose tolerance (O-NGT), 10 obese subjects with impaired glucose tolerance (O-IGT), and 15 healthy subjects. Significant increase in CPR levels at 10 minutes in clamp-OGL compared with those at steady state was observed in healthy subjects and in O-NGT; however, those were small or absent in diabetic patients and in O-IGT. The incremental ratio of CPR was not correlated to the makers of insulin resistance. The early-phase insulin secretion is well maintained in O-NGT; however, early-phase insulin secretion has already been disturbed in obese subjects with glucose intolerance.
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PMID:Early-phase insulin secretion is disturbed in obese subjects with glucose intolerance. 1751 20

We aimed to investigate whether the reduced incretin effect observed in patients with type 2 diabetes is a primary event in the pathogenesis of type 2 diabetes or a consequence of the diabetic state. Eight patients with chronic pancreatitis and secondary diabetes (A1C mean [range] of 6.9% [6.2-8.0]), eight patients with chronic pancreatitis and normal glucose tolerance (NGT; 5.3 [4.9-5.7]), eight patients with type 2 diabetes (6.9 [6.2-8.0]); and eight healthy subjects (5.5 [5.1-5.8]) were studied. Blood was sampled over 4 h on 2 separate days after a 50-g oral glucose load and an isoglycemic intravenous glucose infusion, respectively. The incretin effect (100% x [beta-cell secretory response to oral glucose tolerance test - intravenous beta-cell secretory response]/beta-cell secretory response to oral glucose tolerance test) was significantly (P < 0.05) reduced (means +/- SE) in patients with chronic pancreatitis and secondary diabetes (31 +/- 4%) compared with patients with chronic pancreatitis and NGT (68 +/- 3) and healthy subjects (60 +/- 4), respectively. In the type 2 diabetes group, the incretin effect amounted to 36 +/- 6%, significantly (P < 0.05) lower than in chronic pancreatitis patients with NGT and in healthy subjects, respectively. These results suggest that the reduced incretin effect is not a primary event in the development of type 2 diabetes, but rather a consequence of the diabetic state.
Diabetes 2007 Aug
PMID:Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? 1816 51

The relationship between post-prandial plasma glucose (PPG) and post-challenge plasma glucose (PCG) within individuals was investigated in Japanese population. The oral glucose tolerance test (OGTT) and measurements of PPG 2h after ingestion of a standardized rice-based meal (PPG2h), were performed in 4471 middle-aged Japanese subjects (2774 men and 1697 women, 50.7+/-8.5 years). There was a loose correlation between PPG2h and PCG2h (r=0.327, p<0.001). The diabetes group (n=170) showed the highest PPG2h, followed by the IGT group (n=786) and the NGT group (n=3414) (p<0.05). At the cutoff point of 140 mg/dl (7.8 mmol/l) for PPG2h, specificities were 94.9% for IGT plus diabetes and 92.9% for diabetes, but sensitivities were as low as 23.2% for IGT plus diabetes and 44.7% for diabetes. The correlation of PPG2h with PCG2h was stronger in the obese group (BMI>or=25 kg/m2) than in the lean group (BMI<20 kg/m2). We conclude that the correlation between PPG2h and PCG2h was significant but not very tight. In evaluating PPG2h, if the cutoff point of 140 mg/dl (7.8 mmol/l) for PCG2h is extrapolated, the majority of subjects with dysglycemia could be overlooked.
Diabetes Res Clin Pract 2007 Nov
PMID:The relationship between post-prandial plasma glucose and post-challenge plasma glucose in Japanese population. 1754 Apr 71

The associations of five SNPs (SNPs1-5: A-5468G, A-3333G, C-1794T, C437T and T9148C) of the class II phosphoinositide 3-kinase gamma-subunit (PIK3C2G) gene with type 2 diabetes were examined using a population of the Takahata Study (n (M/W): 2930 (1328/1602); age: 63.3+/-10.2 years), a Japanese community-based study. Quantitative association study of the SNPs with HbA1c levels showed significant association for SNPs 2 and 4 (p=0.018 and 0.004, respectively). A case-control association study of SNP 4 with diabetes by multiple logistic regression analysis showed a significant association of the genotype TT of the SNP with an odds ratio of 2.21 (p=0.001) independently of age, gender and BMI. In the NGT subjects, serum fasting insulin levels in the at-risk genotype group of SNP 4 were significantly lower than those in the others (TT, TC, and CC, 4.9+/-2.6, 5.4+/-3.0, and 5.6+/-3.4muU/ml, respectively; p=0.029).
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PMID:Association of the PIK3C2G gene polymorphisms with type 2 DM in a Japanese population. 1799 25

Chronic subclinical inflammation may be involved in the pathogenesis of Type 2 diabetes. We examined whether elevated WBC count, a marker of inflammation, was associated with worsening of glucose tolerance among Chinese population aged 40 years and over. Based on the 75g OGTT, 1016 subjects aged from 40 to 88 years were classified into four groups: NFG/NGT (n=299), isolated IFG (n=213), IGT (n=213) and Type 2 diabetes (n=291). We compared the WBC count among the four groups and investigated relevant variables associated significantly with the WBC count. The IGT and Type 2 diabetes groups had a significantly higher WBC count than the NFG/NGT and isolated IFG groups. By stepwise regression analyses, we found that waist circumference, DBP, total cholesterol, HDL cholesterol and 2-h PG showed an independent association with the WBC count. In the analysis stratified by sex and smoking status, WBC count was independently associated with age and triglycerides in males, whereas it was associated with BMI, SBP, triglycerides and 2-h PG in females. BMI, SBP, triglycerides and 2-h PG showed an independent association with WBC count in subjects who never smoked. We concluded that an increase in WBC count was associated with the deterioration of glucose tolerance. WBC count was associated with lipid metabolism in males and with various components of the metabolic syndrome in females and subjects who never smoked.
Diabetes Res Clin Pract 2008 Oct
PMID:Association of WBC count and glucose metabolism among Chinese population aged 40 years and over. 1869 86

This study was designed to evaluate effects of exercise therapy on early phase insulin secretion in overweight subjects with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). The subjects consisted of overweight subjects with normal glucose tolerance (NGT, n=10), IGT (n=10) and DM (n=10) (age: 51.1+/-8.2, 56.3+/-8.8 and 58.5+/-6.2 years, respectively). All of these patients performed exercise therapy at lactate threshold intensity for 12 weeks. Before intervention, area under the glucose curve (AUC(PG)) was higher in DM, IGT and NGT groups, and area under the insulin curve (AUC(IRI)) and the early phase insulin secretion as calculated by insulinogenic index was higher in the NGT group than in either the IGT or DM groups (p<0.05). After exercise therapy, the insulin sensitivity, AUC(PG) and AUC(IRI) improved in three groups (p<0.05, respectively). The insulinogenic index increased in IGT and DM groups (p<0.05, respectively), but the changes in the insulinogenic index showed no significant differences between IGT and DM groups. These results suggest that the ss-cell function in subjects with IGT and DM could therefore improve after exercise therapy. Moreover, AUC(PG), AUC(IRI) and insulin sensitivity were also improved no relation to NGT, IGT and DM.
Diabetes Res Clin Pract 2008 Dec
PMID:Effects of low intensity exercise therapy on early phase insulin secretion in overweight subjects with impaired glucose tolerance and type 2 diabetes mellitus. 1892 94


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