Studies on diabetic and prediabetic vascular disease and the effect of selected therapeutic modalities on associated vasculopathy
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Date
2007
Authors
Sayeeda, Rahman
Journal Title
Journal ISSN
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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.
Description
Ph.D
Keywords
Pharmaceutical science , Diabetes