Long-Term Predictors of Insulin Resistance: Role of Lifestyle and Metabolic Factors in Middle-Aged Men

Ulf Risérus, MMED, PHD; Johan Ärnlöv, MD, PHD; Lars Berglund, BSC


Diabetes Care. 2007;30(11):2928-2933. 

In This Article

Abstract and Introduction

Objective: Predictors of insulin resistance have hitherto only been examined in cross-sectional studies without information on lifestyle factors. Few researchers have measured insulin sensitivity directly and compared different metabolic and lifestyle predictors in a large population.
Research Design and Methods: Our aim was to investigate independent long-term predictors of insulin sensitivity in a large population-based sample (the Uppsala Longitudinal Study of Adult Men cohort) of 50-year-old men who underwent a euglycemic clamp 20 years later (n = 770). Subjects with diabetes and treatment of cardiovascular disease at baseline were excluded. In linear regression models, metabolic (BMI, triglycerides, HDL cholesterol, glucose, and blood pressure) and lifestyle factors (physical activity, smoking, saturated fat biomarkers, and socioeconomic status) were independent variables at baseline (age 50 years) and insulin sensitivity-dependent variables at follow-up (age 70 years). A subsample of only normal-weight men from the initial population was also examined (n = 440).
Results: BMI was the strongest predictor of insulin sensitivity even after addition of metabolic factors. One SD (±2.8) increase in BMI corresponded to a mean 19% decrease in insulin sensitivity. After addition of lifestyle factors, all factors except triglycerides and smoking were significant predictors. BMI remained the strongest predictor (ß = -0.67 [95% CI -0.83 to -0.51], P < 0.0001) followed by physical activity, HDL cholesterol, saturated fat, and socioeconomic status (all P < 0.05). BMI remained the strongest predictor in normal-weight subjects also (P < 0.001). In addition, after adjustment for baseline insulin concentrations, BMI remained the strongest predictor (P < 0.001).
Conclusions: Multiple factors, including novel factors such as saturated fat and socioeconomic status, independently predict insulin sensitivity after 20 years. BMI is, however, the single strongest predictor, even in normal-weight subjects.

Insulin resistance, i.e., low insulin sensitivity, precedes type 2 diabetes and is an emerging risk factor for cardiovascular disease.[1] Approximately 25% of the U.S. population has clinically significant insulin resistance.[2] It is therefore important to identify predictors of insulin sensitivity to help optimize prevention. The etiology of insulin resistance is complex as both metabolic/genetic and lifestyle factors contribute. Cross-sectional studies suggest that insulin resistance is more prevalent in obese subjects[3] with hypertriglyceridemia, low HDL cholesterol,[2,4,5] hypertension,[6] and other metabolic aberrations.[4] Lyssenko et al.[7] assessed longitudinal (6 year-follow-up) predictors for type 2 diabetes but not for insulin sensitivity per se. No researchers have, however, adjusted for lifestyle factors or other metabolic syndrome components. Examining which factors predict insulin sensitivity independently from the others could be informative. Socioeconomic status is a factor related to diabetes, but its association with insulin sensitivity per se is unknown. In addition, in only one of the above-mentioned cross-sectional studies[3] was insulin sensitivity assessed by a gold standard technique, i.e., the euglycemic clamp.

Despite the importance of insulin resistance in metabolic diseases, there are no longitudinal data on predictors of insulin sensitivity. To study these, a large longitudinal cohort study including direct assessments (e.g., euglycemic clamp) of insulin sensitivity is required. In addition, such direct measurement must be available at the end of the follow-up time rather than at baseline (or preferably at both occasions). Finally, a long follow-up period is required to allow for impairment of insulin sensitivity over time, with available lifestyle factors in addition to metabolic factors. The Uppsala Longitudinal Study of Adult Men (ULSAM) is a cohort study that may be suitable for addressing this issue as it fulfills two of these criteria. Furthermore, most studies have used insulin resistance as a dichotomous variable defined arbitrarily despite the fact that insulin sensitivity is a continuum. Using the ULSAM cohort, we addressed our current aim: to identify and compare long-term predictors of insulin sensitivity after adjusting for lifestyle factors and socioeconomic status. This is the first multivariate analyses of long-term predictors of clamp-derived insulin sensitivity in a large population-based sample of nondiabetic men followed for 20 years. This study could add new knowledge regarding the role of lifestyle factors in insulin resistance.


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