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)

The objective of this trial was to compare the metabolic effects of long-term treatment with doxazosin to those of irbesartan in patients with type 2 diabetes and hypertension. We evaluated 96 hypertensive diabetic patients who were randomized to 12 months of double-blind treatment with doxazosin 4 mg/d or irbesartan 300 mg/d. At the end of the study, systolic and diastolic blood pressure (SBP and DBP) were significantly reduced from 152 to 140 mm Hg and from 97 to 87 mm Hg, respectively, with doxazosin (P < 0.01). SBP and DBP were reduced from 150 to 134 mm Hg and from 94 to 83 mm Hg, respectively, with irbesartan (P < 0.01). Irbesartan had significantly better antihypertensive efficacy than doxazosin (P < 0.05). Doxazosin had the greatest effect on glucose metabolism and lipid parameters, with significant (P </= 0.05) reductions observed at study end compared with baseline in glycosylated hemoglobin, fasting plasma glucose, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and Homeostasis Model Assessment Index. In conclusion, both doxazosin and irbesartan reduced BP during long-term treatment, but not to recommended levels, and doxazosin had the more beneficial effect on glucose metabolism and lipid profile.
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PMID:Effects of doxazosin and irbesartan on blood pressure and metabolic control in patients with type 2 diabetes and hypertension. 1589 88

Angiotensin-converting enzyme (ACE) inhibitors have favourable effects on hypertension and diabetic nephropathy, but persistent use may result in incomplete blockade of the renin-angiotensin system. Long-term effects of dual blockade using the ACE inhibitor lisinopril and the long-acting angiotensin II receptor blocker (ARB) telmisartan on blood pressure and albumin excretion rate (AER) were evaluated. Patients with type 2 diabetes mellitus, hypertension (systolic blood pressure [SBP] >or=140 mmHg or diastolic blood pressure [DBP] >or=90 mmHg) and microalbuminuria (AER 30-300 mg/24h) received 20mg of lisinopril or 80 mg of telmisartan once a day for 24 weeks. Patients were then randomised to continuing treatment with the respective monotherapy or with lisinopril plus telmisartan for a further 28 weeks. Significant (P<0.001) declines in SBP (11.1 mmHg versus 10.0 mmHg), DBP (5.6 mmHg versus 5.3 mmHg) and AER (98 mg/24 h versus 80 mg/24 h) were achieved with lisinopril (n=95) or telmisartan (n=97), respectively, after 24 weeks. Subsequent treatment with lisinopril plus telmisartan for 28 weeks resulted in further significant reductions (P<0.001) in SBP, DBP and AER compared with either monotherapy. All treatments were well tolerated. Lisinopril plus telmisartan thus provides superior blood pressure and AER control than either monotherapy. We conclude that use of dual blockade may provide a new approach to prevention of diabetic nephropathy in patients with type 2 diabetes, hypertension and microalbuminuria.
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PMID:Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension. 1611 44

Factors influencing the severity of the metabolic syndrome among obese subjects or the conversion to cardiovascular disease or type 2 diabetes (T2D) remain largely unknown, but there is strong evidence for genetic susceptibilities. Peroxisome proliferator-activated receptor-gamma co-activator-1 (PPARGC1) is a transcriptional co-activator of many nuclear receptors including PPAR-gamma, involved in the regulation of fatty acid oxidation, skeletal muscle fiber type specificity, and gluconeogenesis. Given the critical role of PPARGC1, it becomes a promising candidate gene for the metabolic syndrome and T2D. This study aimed to investigate whether genetic variations in human PPARGC1 gene are associated with metabolic syndrome-related phenotypes and T2D among obese subjects. Molecular screening of the PPARGC1 gene in 24 morbidly obese French-Canadians revealed 13 variants. Eight genetic variations were in introns: c.55-27T>A, c.234+52C>A, c.553-40A>G, c.553-11T>C, c.757+161T>C, c.1793+19C>G, c.2141+192G>A, and c.2293+146A>G, and five were in coding regions: Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, and Thr612Met with a relative allele frequency of 18.5, 5.2, 37.0, 42.5, and 6.8%, respectively. Thr394Thr, Asp475Asp, and Thr528Thr were in linkage disequilibrium with the Gly482Ser variant, the only non-synonymous variant with a relative allele frequency of more than 10%. Association studies were performed with the Gly482Ser variant. In non-diabetics, we compared between genotype differences in metabolic syndrome-related traits (waist girth, SBP, DBP, triglycerides, HDL-cholesterol (C), and fasting glucose levels). There was a difference in mean plasma HDL-C concentrations, the Gly/Gly group had lower concentrations than the Gly/Ser group (P<0.05). These results suggest that the Gly482Ser polymorphism may explain some of the between-obese variance observed in metabolic syndrome-related traits.
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PMID:Effects of the peroxisome proliferator-activated receptor-gamma co-activator-1 Gly482Ser variant on features of the metabolic syndrome. 1612 61

Olmesartan medoxomil is an angiotensin II receptor antagonist. In pooled analyses of seven randomized, double-blind trials, 8 weeks' treatment with olmesartan medoxomil was significantly more effective than placebo in terms of the response rate, proportion of patients achieving target blood pressure (BP) and mean change from baseline in diastolic (DBP) and systolic blood pressure (SBP). Olmesartan medoxomil had a fast onset of action, with significant between-group differences evident from 2 weeks onwards. The drug was well tolerated with a similar adverse event profile to placebo. In patients with type 2 diabetes, olmesartan medoxomil reduced renal vascular resistance, increased renal perfusion, and reduced oxidative stress. In several large, randomized, double-blind trials, olmesartan medoxomil 20 mg has been shown to be significantly more effective, in terms of primary endpoints, than recommended doses of losartan, valsartan, irbesartan, or candesartan cilexetil, and to provide better 24 h BP protection. Olmesartan medoxomil was at least as effective as amlodipine, felodipine and atenolol, and significantly more effective than captopril. The efficacy of olmesartan medoxomil in reducing cardiovascular risk beyond BP reduction is currently being investigated in trials involving patients at high risk due to atherosclerosis or type 2 diabetes.
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PMID:Olmesartan medoxomil: current status of its use in monotherapy. 1732 86

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.
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PMID:Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha. 1734 84

Knowledge about the current status of diabetes management is indispensable for the improvement of diabetes management. We performed a survey to investigate the current trend of diabetes management in elderly Koreans, at eight hospitals located throughout the country. A total of 539 patients with type 2 diabetes older than 65 years (men=224, women=315) were recruited. Their mean age was 71.5+/-4.9 years and BMI 24.3+/-3.4 (men=23.6+/-2.8, women=24.9+/-3.7)kg/m(2), and 38.2% of the patients were obese (BMI> or =25 kg/m(2), men=29.5%, women=44.4%). The mean duration of the diabetes was 13.1+/-9.2 years. Although 37.3% of the patients had A1C below 7.0%, 33.8% of the patients had A1C more than 8.0%. Three hundred and sixty three patients (67.4%) were treated with oral hypoglycemic agents and 175 patients (32.5%) were treated with insulin or combination with oral agents. The glycemic control was better in patients treated with oral agents (oral agent group=7.7+/-4.6%, insulin group=8.5+/-1.9%). Although mean SBP and DBP were 131.4+/-16.7 and 75.9+/-10.4 mmHg, respectively, 67.4% of the patients had hypertension and 38.2% of the patients with hypertension did not reach the goal (<130/80 mmHg). Of 539 elderly patients, 253 patients (47.4%) had dyslipidemia (LDL-C> or =4.1 mmol/l and/or triglyceride> or =2.5 mmol/l and/or HDL-C<1.1 mmol/l) and 72.7% of the patients with dyslipidemia took the lipid lowering agents. However, 47.4% of them did not achieve the goal (LDL-C<2.6 mmol/l and/or triglyceride<1.7 mmol/l and/or HDL-C>1.1 mmol/l). Twenty-eight patients (5.5%) had been admitted to the hospital because of severe hypoglycemia. Half of the patients (57%) had microvascular complications (retinopathy, neuropathy or overt proteinuria), and 28% of the patients had macro-vascular complications (CVD, stroke or peripheral vascular disease). As elderly diabetic patients are usually polymorbid, diabetes mellitus in old age is needed a more comprehensive approach to not only the treatment of hyperglycemia but also of hypertension, dyslipidemia and other associated diseases.
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PMID:Current status of diabetes management in elderly Koreans with diabetes. 1748 70

Glucagon-like peptide-1 (GLP-1) (7-36) is a type of incretin hormone with unique antidiabetic potential. The introduction of orally active GLP-1 offers substantial benefits in the treatment of type 2 diabetes over conventional injection-based therapies. Because the intestinal absorption of GLP-1 is restricted by its natural characteristics, we developed a series of GLP-1 analogues via the site-specific conjugation of biotin-NHS and/or of biotin-poly(ethylene glycol)-NHS at Lys 26 and Lys 34 of GLP-1 (7-36), respectively, in order to improve oral delivery. The resultant GLP-1 analogues, Lys 26,34-DiBiotin-GLP-1 (DB-GLP-1) and Lys 26-Biotin-Lys 34-(Biotin-PEG)-GLP-1 (DBP-GLP-1), were prepared and studied in terms of their chemical, structural, and biological properties. DBP-GLP-1 demonstrated superior proteolytic stability against trypsin, intestinal fluid, and the major GLP-1 inactivation enzyme (dipeptidyl peptidase-IV (DPP-IV)) to native GLP-1 or DB-GLP-1 ( p < 0.001). The in vitro insulinotropic effects of DB-GLP-1 and DBP-GLP-1 showed potent biological activity in a dose-dependent manner, which resembled that of native GLP-1 in terms of stimulating insulin secretion in isolated rat islets of Langerhans. Intraperitoneal glucose tolerance tests (IPGTT) after the oral administration of GLP-1 analogues in diabetic db/db mice demonstrated that DB-GLP-1 and DBP-GLP-1 significantly reduced the AUC 0-180 min of glucose for 3 h by 14.9% and 24.5% compared to that of native GLP-1, respectively ( p < 0.01). In particular, DBP-GLP-1 concentration in plasma rapidly increased 30 min after oral administration in rats, presumably due to improved intestinal absorption. These findings revealed that site-specific biotinylated and biotin-PEGylated GLP-1 is absorbed by intestine and that it has biological activity in vivo. Therefore, we propose that this orally active bioconjugated GLP-1 might be considered as a potential oral antidiabetic agent for type 2 diabetes mellitus.
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PMID:Preparation, characterization, and application of biotinylated and biotin-PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery. 1807 8

The aim of this study was to compare the effect of valsartan/amlodipine and atenolol/amlodipine combination in preventing the recurrence of atrial fibrillation (AF) in hypertensive diabetic patients with a history of recent paroxysmal atrial fibrillation. Two hundred ninety-six hypertensive patients with well-controlled type 2 diabetes in sinus rhythm but with at least 2 ECG-documented episodes of AF in the previous 6 months were randomized to 160 mg of valsartan plus amlodipine (titrated from 2.5 to 10 mg) or to 100 mg of atenolol plus amlodipine (2.5 to 10 mg) in addition to their previous antiarrhythmic treatment (if any) and were followed up for 1 year. Blood pressure (BP) and a 24-hour ECG were evaluated monthly. The patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. SBP/DBP values were significantly reduced after 12 months with valsartan/amlodipine (from 150.4/93.5 to 126.37/7.4 mm Hg, P < 0.001) and atenolol/amlodipine (from 151.1/94.2 to 127.1/77.9 mm Hg, P < 0.001), with no difference between the 2 regimens. At least 1 ECG-documented episode of AF was reported in 20.3% of the patients treated with valsartan/amlodipine and in 34.1% of those treated with atenolol/amlodipine, with a significant difference between treatments (P < 0.01). The positive effect of valsartan/amlodipine combination on AF recurrence was more evident in patients treated with amiodarone or propafenone than in patients treated with other antiarrhythmic drugs or without antiarrhythmic treatment. Despite similar BP reduction, valsartan/amlodipine combination was more effective in patients treated with amiodarone or propafenone than atenolol/amlodipine in preventing new episodes of AF in hypertensive diabetic patients.
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PMID:Comparative evaluation of effect of valsartan/amlodipine and atenolol/amlodipine combinations on atrial fibrillation recurrence in hypertensive patients with type 2 diabetes mellitus. 1835 84

The purpose of this study was to compare the combination treatments of manidipine/delapril and olmesartan/hydrochlorothiazide (HCTZ) in elderly diabetic hypertensives. After a 4-week placebo period, 158 hypertensive patients with type 2 diabetes (age range: 66 to 74 years) were randomized to receive combination treatment of 10 mg manidipine plus 30 mg delapril or 20 mg olmesartan plus 12.5 mg HCTZ for 48 weeks in a prospective, parallel arm trial. After 12 weeks, manidipine or HCTZ was doubled in nonresponders (systolic blood pressure [SBP] > or =130 mmHg and/or diastolic blood pressure [DBP] > or =80 mmHg). Patients were checked at the end of the placebo period and every 12 weeks thereafter. At each visit, lying, sitting and standing BP as well as fasting glycemia, glycosylated hemoglobin (HbA1c), electrolytes, uric acid, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG) were evaluated. Both combinations reduced sitting SBP (-27.7 and -28.3 mmHg, respectively; both p<0.001) and DBP (-15.1 and -14.8 mmHg, respectively; both p<0.01) with no difference between the two treatments. Standing DBP was more markedly reduced by olmesartan/HCTZ (-19.5 mmHg; p<0.001) than by manidipine/delapril (-14.7 mmHg; p<0.05 vs. olmesartan/HCTZ). No changes in metabolic parameters were observed with manidipine/delapril, whereas an increase in HbA1c (+0.7%; p<0.05), uric acid (+0.4 mg/dL; p<0.05) and TG (+41.3 mg/dL; p<0.05), and a decrease in serum potassium (-0.3 mmol/L; p<0.05) and HDL-C (-3.4 mg/dL; p<0.05) were found in the olmesartan/HCTZ group. In conclusion, both combinations were similarly effective in reducing BP in elderly hypertensive diabetic patients. However, manidipine/delapril offered some advantages in terms of the less-pronounced BP orthostatic changes and absence of metabolic adverse effects.
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PMID:Effects of manidipine/delapril versus olmesartan/hydrochlorothiazide combination therapy in elderly hypertensive patients with type 2 diabetes mellitus. 1836 17

Favorable effects of exercise training on cardiovascular prognosis have been reported repeatedly in patients with diabetes mellitus type 2 (DM2). However, little is known about the cardiovascular rehabilitation effects in diabetic patients with coronary artery disease (CAD). This study has evaluated the benefits of combined aerobic-resistance training in two groups of patients--diabetics and non-diabetics--after percutaneous coronary intervention (PCI). Changes in exercise capacity parameters, resting cardiovascular and anthropometrical parameters were evaluated in 77 patients who completed 12-weeks of combined aerobic-resistance training: 32 patients with DM2 (DM) and 45 patients without DM2 (NDM). Significant improvements in exercise capacity (total peak workload [W(peak)], peak workload per kg of body weight [W(peak)/kg], total peak oxygen uptake [VO(2peak)], peak oxygen uptake per kg of body weight [VO(2peak)/kg]) were found in both DM and NDM (p < 0.01 and p < 0.001, respectively). The decrease in resting heart rate (HR(rest)), resting systolic (SBP(rest)) resting diastolic (DBP(rest)) blood pressures, body weight (BW) and BMI in the DM group was not statistically significant. However, there was a statistically significant decrease in SBP(rest), BW and BMI in the NDM group. In conclusion, this study demonstrated similar beneficial effects of combined cardiovascular training on exercise capacity in patients with or without type 2 diabetes mellitus. Our results suggest that the combined cardiac training is well tolerated and useful in secondary prevention in patients with DM2 and CAD.
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PMID:Benefit of combined cardiac rehabilitation on exercise capacity and cardiovascular parameters in patients with type 2 diabetes. 1850 41


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