The association between IGF-I and insulin resistance: a general population study in Danish adults

Abstract

Objective: IGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate the association between IGF-I level and insulin resistance in a Danish general population.

Research design and methods: Included were 3,354 adults, aged 19-72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin resistance. Serum IGF-I levels were determined by an immunoassay and grouped into quintiles (Q1-Q5). Linear or multinomial logistic regression analyses were performed.

Results: In the study population, 520 subjects (15.5%) had increased HOMA-IR values above 2.5. After adjustment for age, sex, physical activity, and waist-to-height ratio, a U-shaped association between IGF-I and HOMA-IR was found. Low IGF-I (Q1: odds ratio [OR] 1.65 [95% CI 1.16-2.34], P < 0.01) as well as high IGF-I (Q5: 1.96 [1.38-2.79], P < 0.01) levels were related to a higher odds of increased HOMA-IR values compared with subjects with intermediate (Q3) IGF-I levels. These associations remained statistically significant after the exclusion of subjects with type 2 diabetes and by using the updated computer HOMA2-IR model.

Conclusions: Low- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism of this complex phenomenon has to be elucidated in more detail for future risk stratification.

Figure 1

Association between IGF-I serum concentration and level of HOMA1-IR (upper) and updated computer HOMA2-IR (lower) for the whole study population and after exclusion of subjects with diabetes. Left side: Crude linear regression with restricted cubic splines. Right side: Estimated mean level of HOMA-IR with 95% CI by levels of IGF-I. ANOVA was adjusted for age, sex, physical activity, and waist-to-height ratio. Tests for differences between the middle IGF-I quintile (40–60th) and the remaining groups were performed.*P < 0.05. P values were adjusted for multiple comparison.