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Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis

Rahman S, Rahman T, Ismail AA, Rashid AR

Diabetes Obes Metab, 2007 Nov;9(6):767-80.
PMID: 17924861 DOI: 10.1111/j.1463-1326.2006.00655.x

The complications associated with diabetic vasculopathy are commonly grouped into two categories: microvascular and macrovascular complications. In diabetes, macrovascular disease is the commonest cause of mortality and morbidity and is responsible for high incidence of vascular diseases such as stroke, myocardial infarction and peripheral vascular diseases. Macrovascular diseases are traditionally thought of as due to underlying obstructive atherosclerotic diseases affecting major arteries. Pathological changes of major blood vessels leading to functional and structural abnormalities in diabetic vessels include endothelial dysfunction, reduced vascular compliance and atherosclerosis. Besides, advanced glycation end product formation interacts with specific receptors that lead to overexpression of a range of cytokines. Haemodynamic pathways are activated in diabetes and are possibly amplified by concomitant systemic hypertension. Apart from these, hyperglycaemia, non-enzymatic glycosylation, lipid modulation, alteration of vasculature and growth factors activation contribute to development of diabetic vasculopathy. This review focuses on pathophysiology and pathogenesis of diabetes-associated macrovasculopathy.

Matched MeSH terms: Diabetic Angiopathies/etiology*
Fulltext Prevalence of peripheral arterial disease in patients with diabetes mellitus in a primary care setting

Khatoon R, Khoo EM

Med J Malaysia, 2007 Jun;62(2):130-3.
PMID: 18705445 MyJurnal

The aims of the study were to determine the prevalence of peripheral arterial disease (PAD) in diabetic patients and in different ethnic groups at a primary care setting, and to evaluate risk factors associated with PAD in these diabetic patients. A cross sectional study of 200 diabetic patients over 18 years old who attended a primary care clinic at a teaching hospital in Kuala Lumpur, Malaysia was carried out. Face-to-face interviews were conducted using structured questionnaires for demographic characteristics and risk factors evaluation. Blood pressure measurements, assessment of peripheral neuropathy and ankle brachial pressures were performed. PAD was diagnosed by an ankle brachial pressure index (ABPI) of <0.9 on either leg. The overall prevalence of PAD was 16% in this diabetic population. The prevalence of PAD was 5.8% in Malays, 19.4% in Chinese and 19.8% in Indians. The prevalence of peripheral neuropathy was 41%, foot ulcer 9.5%, and gangrene 3.0%. The presence of foot ulcer was weakly associated with PAD (P=0.052). No significant relationships were found between age, gender, smoking status, duration of diabetes mellitus, hypertension, dyslipidaemia, and PAD. PAD is common in the diabetic population of this study.
Study site: primary care clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Diabetic Angiopathies/etiology
Blood pressure variability in patients with diabetes mellitus

Mokhtar RH, Ayob A, Mohd Noor N

Asian Cardiovasc Thorac Ann, 2010 Aug;18(4):344-8.
PMID: 20719784 DOI: 10.1177/0218492310375723

Reduced arterial compliance in patients with diabetes mellitus has been shown in several studies, but it has not been significantly associated with either atherosclerosis or vessel wall thickness. Blood pressure variability is still poorly explored in diabetic patients. The aim of this study was to compare blood pressure variability and arterial compliance in patients with type 2 diabetes mellitus and controls matched for sex, age, and weight. Arterial compliance was measured and noninvasive 24-h ambulatory blood pressure monitoring was performed in 18 diabetic patients and 18 controls. There was significantly higher 24-h systolic blood pressure variability (17.7 +/- 6.8 vs. 14.6 +/- 2.6 mm Hg), diastolic blood pressure variability (15.6 +/- 7.1 vs. 11.4 +/- 3.1 mm Hg), and mean arterial blood pressure variability (14.8 +/- 7.0 vs. 11.1 +/- 2.9) in diabetic patients. Systolic, diastolic, and mean arterial blood pressure variability was significantly higher during daytime but not night time in diabetic patients compared to controls. Diabetic patients also had significantly reduced small artery compliance, but no differences in large artery compliance, cardiac output, or systemic vascular resistance. The findings suggest that hyperglycemia may affect the compliance of the vascular system, resulting in high blood pressure fluctuations.

Matched MeSH terms: Diabetic Angiopathies/etiology
Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study

Rahman S, Ismail AA, Ismail SB, Naing NN, Abdul Rahman AR

Eur J Clin Pharmacol, 2007 Aug;63(8):733-41.
PMID: 17565489 DOI: 10.1007/s00228-007-0315-3

OBJECTIVE: To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).

METHODS: In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.

RESULTS: 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 in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.

CONCLUSIONS: Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.

Matched MeSH terms: Diabetic Angiopathies/etiology
Treatment for diabetic ulcer wounds using a fern tannin optimized hydrogel formulation with antibacterial and antioxidative properties

Lai JC, Lai HY, Nalamolu KR, Ng SF

J Ethnopharmacol, 2016 08 02;189:277-89.
PMID: 27208868 DOI: 10.1016/j.jep.2016.05.032

ETHNOPHARMACOLOGICAL RELEVANCE: Blechnum orientale Linn. (B. orientale) is a fern traditionally used by the natives as a poultice to treat wounds, boils, ulcers, blisters, abscesses, and sores on the skin.
AIM OF THE STUDY: To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds.
MATERIALS AND METHODS: The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey's T-test (P<0.05).
RESULTS: One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5-1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis.
CONCLUSION: The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds.

Matched MeSH terms: Diabetic Angiopathies/etiology