Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism

Abstract

Type II (non-insulin-dependent) diabetes mellitus is characterised by insulin resistance, pancreatic betacell defect, hypertension, dyslipidaemia and central obesity, and is recognised as part of a cluster of cardiovascular risk factors generally known as the Metabolic Syndrome [1]. The Indian Ocean island of Mauritius recently provided the background for a longitudinal epidemiological study (1987±1998) which is now seen as an indicator of the potential global impact of Type II diabetes [2,3]. Mauritius has a multiethnic population of 1.2 million, including people of Asian Indian (66 %), mixed European-African-Indian (31 %) and Chinese (3 %) descent. In 1987, the agestandardised prevalence of Type II diabetes in adults aged 30 years or more was 14.3 %, increasing to Diabetologia (2001) Abstract Aims/hypothesis. To measure oxidative stress, endothelial dysfunction and insulin resistance in Indian Mauritians at different stages of development of Type II (non-insulin-dependent) diabetes mellitus. Methods. Plasma total 8-epi-PGF 2a , an indicator of oxidative stress, was determined in age-matched subjects with normal glucose metabolism (n = 39), impaired glucose tolerance (n = 14), newly diagnosed diabetes (n = 8) and established diabetes (n = 14). Plasma glucose and insulin were measured at baseline and 2 h following an oral glucose tolerance test. Endothelial function was assessed by non-invasive digital pulse wave photoplethysmography. Results. Plasma 8-epi-PGF 2a increased in subjects with impaired glucose tolerance (p < 0.05) compared with control subjects, and was even higher in newly diagnosed diabetic patients (p < 0.01) and established (p < 0.01) diabetic patients. A tendency towards reduced endothelial function in subjects with impaired glucose tolerance became significant in patients with newly diagnosed and established diabetes (p < 0.01), and was correlated with 8-epi-PGF 2a (r = 0.36, p < 0.01). Insulin resistance (homeostasis model assessment) did not change in subjects with impaired glucose tolerance compared with control subjects, but increased in newly diagnosed (p < 0.01) and established (p < 0.001) diabetic subjects. The 8-epi-PGF 2a was correlated with fasting glucose (r = 0.50, p < 0.001), triglycerides (r = 0.40, p < 0.001) and insulin resistance (r = 0.35, p < 0.001). Conclusion/interpretation. Oxidant stress is an early event in the evolution of Type II diabetes and could precede the development of endothelial dysfunction and insulin resistance. [Diabetologia (2001) 44: 706± 712

Impaired Fasting Glucose & 8-Iso-Prostaglandin F2α in Diabetes Disease Progression

“…Our data demonstrates a significant increase in 8-iso-PGF 2α in the IFG group, which means that lipid peroxidation is definitely present during the IFG stage and supports Gopaul, et al's findings that 8-iso-PGF 2α was increased following an oral glucose tolerance test in individuals with no diabetes but with either IFG or impaired glucose tolerance [40]. These authors suggested that oxidative stress identified by elevated 8-iso-PGF 2α levels precedes…”

Association of Oxidative Stress, Insulin Resistance, and Diabetes Risk Phenotypes

“…In Japanese men, plasma concentrations of 8-epi-PGF 2␣ were significantly correlated with glucose clampassessed insulin resistance (8). Plasma concentrations of 8-epi-PGF 2␣ were higher in Indian Mauritians with impaired glucose tolerance compared with similar subjects with normal glucose tolerance (9). In another Indian population, total antioxidant capacity (measured by levels of red cell superoxide dismutase and catalase or plasma reduced glutathione and ascorbic acid) was lower in impaired glucose tolerant subjects than in similar subjects with normal glucose tolerance (7), and in a study of 81 patients with nonalcoholic fatty liver disease and 30 healthy control subjects, oxidative stress (measured by copper-zinc superoxide dismutase activity) was positively correlated with HOMA-IR (10).…”

“…Markers of systemic oxidative stress are elevated in clinical type 2 diabetes (6), but there are only limited data relating the degree of oxidative stress to insulin resistance in pre-diabetic states (7)(8)(9)(10)(11)(12)(13)(14)(15). Investigations have been impeded by limited availability of reliable biomarkers of oxidative stress for use in epidemiological studies.…”

Prevalence of non-insulin-dependent diabetes mellitus and related vascular diseases in southwestern arseniasis-endemic and nonendemic areas in Taiwan.

“…Oxidative stress has been found to induce the development of insulin resistance and endothelial dysfunction by the observations of normal, impaired glucose-tolerant, and diabetic subjects (Gopaul et al 2001). Hypertension, an important component of insulin resistance syndrome, has also been found to be associated with long-term ingested arsenic exposure (Chen et al 1995).…”