Diabetologisk disputation

Aspects of Insulin Resistance with Special Reference to the Vasoactive Effects of Insulin

Dissertation for the Degree of Docotor of Medical Science in Geriatrics presented at Uppsala University in 1998 April 3

Per-Erik Andersson

Abstract

Insulin resistance, the relative tissue insensitivity to the insulin-mediated promotion of glucose uptake, is considered to be the link between a cluster of cardiovascular risk factors and disorders such as abdominal obesity, dyslipidemia, non-insulin dependent diabetes mellitus, essential hypertension and its complication left ventricular hypertrophy. Results are conflicting whether the mechanism behind insulin resistance involves impairment of insulin-mediated skeletal muscle blood flow.

In a cross-sectional investigation of a study sample (n=320) involving subjects of both sexes, including normotensive and hypertensive subjects of a wide age range, insulin-mediated vasodilation was found to be positively and independently associted with insulin sensitivity, although this effect decreased with ageing. Furthermore, insulin-mediated glucose disposal was positively associated with female sex and negatively associated with age, body mass index, waist/hip ratio, resting heart rate, fasting non-esterified fatty acid levels, hypertensive state and arterial stiffness.

In three intervention studies, two antihypertensive drugs with vasodilating properties had beneficial effects on components of the insulin resistance syndrome. The selective alpha1-blocker doxazosin increased insulin sensitivity and reduced dyslipidemia and plasma fibrinogen. The ACE-inhibitor fosinopril reduced left ventricular wall thickness and this was associated with an increased leg blood flow during hyperinsulinemia.

To conclude, these findings support the hypothesis that insulin-mediated vasodilation contributes to glucose disposal, and that this effect is age- and sex-dependent. Antihypertensive drugs with vasodilating properties may beneficially affect components of the insulin resistance syndrome in essential hypertension.

Key words; insulin resistance, vasodilation, dyslipidemia, left ventricular hypertrophy, arterial stiffnes, alpha blockers, ACE-inhibitors, ultrasonography.

Per-Erik Andersson, Dpt of Public Health and Caring Sciencies/Geriatrics, Uppsala University, Box 609, S-751 25 Uppsala, Sweden Per-Erik.Andersson@geriatrik.uu.se

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