Studies on diabetic and prediabetic vascular disease and the effect of selected therapeutic modalities on associated vasculopathy
| dc.contributor.author | Sayeeda, Rahman | |
| dc.date.accessioned | 2014-11-18T02:05:32Z | |
| dc.date.available | 2014-11-18T02:05:32Z | |
| dc.date.issued | 2007 | |
| dc.description | Ph.D | en_US |
| dc.description.abstract | Introduction Type 2 diabetes (T2DM) now accounts for 90% of all diabetes and 80% of deaths in this group are cardiovascular related. The risk of cardiovascular mortality is also substantially higher in individuals with impaired glucose tolerance (IGT) than in those with normal glucose levels and the pathological changes in vascular function begin many years before the diagnosis of overt T2DM. Aim of studies The aims of this thesis are (i) to investigate clinical epidemiology of pre-clinical vasculopathy in newly-diagnosed, untreated T2DM and IGT patients and their normoglycaemic offspring (Study 1), and (ii) to examine whether pharmacological interventions with thiazolidinedione and angiotensin converting enzyme (ACE) inhibitors can reverse pre-clinical vasculopathy in newly diagnosed diabetic and IGT individuals (Study 2). Methodology Initial screening of 1620 subjects was conducted of which, 644 met study criteria. They had oral glucose tolerance test (OGTT) – 70 (10.87%) were T2DM and 66 (10.25%) IGT individuals. For Study 1 (Part 1), the first 30 T2DM and 30 IGT patients were recruited and compared with age- and sex-matched 30 normoglycaemic controls. Haemodynamic variables, pulse wave velocity (PWV) and augmentation index (AI) were measured. Study-1 (Part-2) involved 30 healthy normoglycaemic offspring of T2DM and 30 healthy normoglycaemic offspring of IGT patients, compared with 30 age- and sex-matched healthy offspring of normoglycaemic parents. Haemodynamic variables, PWV and AI were measured. For Study-2, age- and sex-matched 33 T2DM and 33 IGT patients were enrolled, comparing one-year treatment with rosiglitazone, ramipril and placebo. Haemodynamic variables were measured at three treatment phases (1st, 7th and 12th month) and PWV and AI were measured through out the treatment period [1st (week 1, week 2, week 4), 3rd, 5th, 7th, 9th, 11th, and 12th month]. Result In Study-1 (Part-1), PWV was significantly higher in T2DM patients (10.37+2.64vs. 8.70+1.29m/s; p=0.035) and was of borderline significant in IGT subjects (9.54+1.56vs.8.70+1.29m/s, p=0.078) compared to normoglycaemic individuals. Augmentation index was higher of borderline significant in T2DM (134.53+17.32 vs. 129.17+ 11.18 %, p=0.055) and IGT patients (132.02+16.11 vs. 129.17+ 11.18 %, p=0.059) compared to normoglycaemic individuals. In Study 1 (Part-2), offspring of T2DM and IGT patients demonstrated significantly higher AI compared to controls (105.62+14.2 vs. 96.42+7.7, p=0.001; 104.98+11.1 vs. 96.42+7.7%, p=0.004 respectively). Significantly higher PWV was noted in offspring of T2DM compared to offspring of normoglycaemic parents (6.94+0.9 vs.6.33+0.7m/s, p=0.010). It was also found to be significantly higher in the offspring of T2DM compared to that of IGT (6.94+0.9 vs. 6.43+1.1, p=0.021).In Study-2, rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT patients in comparison to placebo on the 12th month of treatment. With rosiglitazone and ramipril, no significant difference was observed in PWV (p=0.962 and p=1.000 respectively) and AI (p=0.897 and p=0.677 respectively) in T2DM patients in comparison to placebo during overall treatment period. Conclusion Newly diagnosed untreated T2DM patients demonstrated early preclinical manifestations of macrovascular diseases as shown by significantly increased PWV. Normoglycaemic healthy offspring of T2DM patients had demonstrable pre-clinical vasculopathy as assessed by significantly increased PWV and AI. Normoglycaemic healthy offspring of IGT individuals had also large artery abnormalities as shown by significantly increased AI. Rosiglitazone significantly reverses pre-clinical vasculopathy in IGT patients as evident by significant decrease in PWV and AI after one-year treatment. After one-year of ramipril treatment, reduction of large artery stiffness was also observed among IGT patients as shown by significant decrease in AI. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/544 | |
| dc.language.iso | en | en_US |
| dc.subject | Pharmaceutical science | en_US |
| dc.subject | Diabetes | en_US |
| dc.title | Studies on diabetic and prediabetic vascular disease and the effect of selected therapeutic modalities on associated vasculopathy | en_US |
| dc.type | Thesis | en_US |
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