Årets Förtjänstfulla Diabetologiska
Avhandling 1998 - Abstract

Umeå Universitet Medical dissertation.
New Series No 552 - ISSN 0346-6612

   From the Departments of Medicine and Nutritional Research, Umeå University, Umeå, Sweden

LIFESTYLE AND HEALTH
    The role of the insulin resistance syndrome in cardiovascular disease and diabetes. The effects of lifestyle intervention.

Bernt Lindahl, Department of Medicine, University Hospital, S-90185 Umeå, Sweden.
   The association between insulin resistance and a cluster of cardiovascular risk factors is now well documented. The risk factors comprised in the insulin resistance syndrome (IRS) are obesity (especially of the upper body type), dyslipidemia with high triglyceride and low HDL-cholesterol levels, hypertension, and a low fibrinolytic activity. Sometimes the syndrome also includes impaired glucose tolerance (IGT). IGT probably represents an intermediate stage in the development towards type 2 diabetes. The mechanisms by which cardiovascular disease is related to insulin resistance are not fully understood. One leading hypothesis focuses on the role of hemostasis in general and especially the association with disturbed fibrinolytic activity. Much evidence supports that the adverse behaviors of modern society, expressed as poor dietary habits, a sedentary lifestyle and high levels of stress, result in the insulin resistance syndrome.

    By using data from the health surveys of the northern Sweden MONICA project (n=758) and the Västerbotten Intervention Study (n=22060), the prevalence of the insulin resistance syndrome and of impaired glucose tolerance in the population was determined. In a nested case-control study, the association between high proinsulin levels and a first acute myocardial infarction was tested. In two lifestyle intervention trials (one uncontrolled and one randomized) specific behavioral modification techniques were used to achieve long-term lifestyle changes.

    High levels of fasting plasma insulin were associated with the presence of several cardiovascular risk factors (body mass index, waist-hip ratio, blood pressure and triglycerides) to low levels of HDL-cholesterol and disturbed fibrinolysis. The studied risk factors clustered as described in the insulin resistance syndrome in about 20 % of the total population. Increased levels of proinsulin, the propeptide of insulin, was significantly associated with subsequent myocardial infarction. The relative risk of having an acute myocardial infarction was three times higher among individuals with high level of proinsulin compared to those with low levels.

    The effect of lifestyle intervention on insulin resistance and obesity was evaluated in two clinical trials with an average weight reduction of five kilograms and an improved physical fitness measured by an increased oxygen consumption of 10-30 %. In both trials, when comparing pre- and postintervention periods, the cardiovascular risk factor profile was improved with a decrease in fasting insulin. In the randomized study, fibrinolysis improved.

    The conclusion is that the insulin resistance syndrome which affects about 20 % of the population in a modern society,can be treated by a comprehensive behavioral intervention program which decreases long-term cardiovascular risk.

Key words:
    insulin resistance, hyperinsulinemia, insulin resistance syndrome, impaired glucose tolerance, lifestyle, behavior, epidemiology.

Original papers
    This thesis is based on the following papers:
I. Lindahl B, Asplund K and Hallmans G. High serum insulin, insulin resistance and their associations with cardiovascular risk factors. The Northern Sweden MONICA population study. J Intern Med 1993; 234: 263-270.

II. Lindahl B, Asplund K, Eliasson M and Evrin P-E. Insulin resistance syndrome and fibrinolytic activity: The Northern Sweden MONICA study. Int J Epidemiol 1996; 25: 291-299.

III. Lindahl B, Weinehall L, Asplund K and Hallmans G. Screening for impaired glucose tolerance. Results from a population-based study of glucose tolerance in 21,057 individuals (accepted Diabetes Care)

IV. Lindahl B, Dinesen B, Eliasson M, Røder M, Jansson J-H, Huhtasaari F, and Hallmans G. High proinsulin concentration precedes acute myocardial infarction in a non-diabetic population. Metabolism 1999; 48: 1197-1202.

V. Lindahl B, Nilsson TK, Asplund K and Hallmans G. Intense non- pharmacological intervention in subjects with multiple cardiovascular risk factors: Decreased fasting insulin levels but only minor effect on plasma plasminogen activator inhibitor (PAI-1) activity. Metabolism 1998; 47: 384-390.

VI. Lindahl B, Nilsson TK, Jansson J-H, Asplund K and Hallmans G. Improved fibrinolysis by intense lifestyle intervention. A randomized trial in subjects with impaired glucose tolerance. J Intern Med 1999; 246: 105-112.