Background. Diabetes mellitus is a complex metabolic disorder characterized by clustering of multiple cardiovascular risk factors. Diabetic albuminuria is associated with increased prevalence of both micro-vascular and macro-vascular complications. This thesis examined vascular function (Flow-mediated dilatation, FMD) in type 2 diabetic patients with particular emphasis on its relationships with nephropathy. Independent predictors for FMD in Chinese population using data from both diabetic and non-diabetic subjects as well as the predictive value of FMD on clinical endpoints and death in type 2 diabetic patients with nephropathy were examined. / Conclusions. In Chinese subjects with or without type 2 diabetes, hyperglycaemia, hypertriglyceridemia, smoking and albuminuria were independent predictors for FMD. Type 2 diabetic subjects with overt nephropathy had impaired endothelium-dependent and endothelium-independent dilatation, suggesting vascular dysfunction beyond the endothelium. In agreement with studies from Caucasians, smoking was the most important determinant for vascular dysfunction in Chinese type 2 diabetic patients with overt nephropathy. Furthermore, FMD was predictive of new onset of cardiovascular events and related death in Chinese type 2 diabetic patients with overt nephropathy. / In diabetic patients with overt nephropathy, smoking (current and ex-smokers), waist hip ratio (WHR) and serum creatinine were independent predictors for impaired FMD. The latter was predictive of advancement of IMT and was an independent predictor for new onset of combined cardiovascular diseases and related death after a follow up period of 42 months (log rank test=6.04, p=0.014 using Cox regression analysis) after controlling for all confounding factors. In addition, fasting total cholesterol and plasma glucose were predictive for all-cause mortality while serum creatinine predicted new onset of renal endpoint. In a subgroup analysis in diabetic patients with overt nephropathy, smokers who developed CVD or ESRD had greater diminution of FMD than those who did not develop clinical endpoints. / Methods and results. FMD was assessed using high-resolution ultrasound scan. In the cross-sectional study, the sample population was divided into four groups according to the presence or absence of type 2 diabetes and level of albuminuria. They included the non-diabetic group (N=52), diabetic group with normoalbuminuria (N=18), diabetic group with microalbuminuria (N=18) and diabetic group with overt nephropathy defined as macroalbuminuria and renal insufficiency (N=22). Compared to non-diabetic subjects, type 2 diabetic subjects with nephropathy had impaired FMD (4.54% +/- 2.25 vs. 2.50% +/- 2.31, p<0.05) and impaired GTN-dependent dilatation (GTND) (14.30% +/- 3.77 vs. 12.70% +/- 4.70, p<0.05). They also had reduced endothelium-dependent dilatation to endothelium-independent dilatation ratio when compared to non-diabetic subjects (0.19 +/- 0.17 vs. 0.32 +/- 0.15, p<0.05). These findings suggest that the impaired vascular dilatation was due to dysfunction of both endothelium and vascular smooth muscle cells. In the entire cohort, fasting plasma glucose, fasting triglyceride, smoking and albuminuria were independent predictors for FMD. / Lai Wai Keung Christopher. / "February 2006." / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6298. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 202-252). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343754 |
| Date | January 2006 |
| Contributors | Lai, Wai Keung Christopher., Chinese University of Hong Kong Graduate School. Division of Medical Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (252 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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