SAT-623 Glucose Intolerance Modifies the Association Between Insulin-Like Growth Factor-1 and All-Cause Mortality

Abstract

Background: Despite an increase in literature on insulin-like growth factor-1 (IGF-1) and its impact on insulin sensitivity, there remains controversy over its association with all-cause mortality. Insulin interacts with IGF-1 and its binding proteins, forming a growth hormone/IGF-1/insulin axis that may be impaired in Type II diabetes and/or prediabetes. We hypothesized that the association between insulin and IGF-1 with all-cause mortality differs in those with glucose intolerance (GI) in a nationally representative U.S. population with long-term follow-up. Methods: A total of 5,283 non-pregnant adults >20 years from the National Health and Nutrition Examination Survey (NHANES)-III (1988-1994) were linked to the National Death Index through 2015. Glucose intolerance was classified as per fasting blood sugar (≥100 mg/dl), hemoglobin A1c (≥5.7%), medication use, or self-reported diagnosis. IGF-1 was categorized into sex-specific quartiles. To analyze the joint impact of insulin and IGF-1, we also categorized participants into four groups: Group I) IGF-1 <230 ng/mL & insulin ≥11 uIU/mL, II) IGF-1 <230 & insulin <11, III) IGF-1 ≥230 & insulin ≥11, and IV) IGF-1 ≥230 & insulin <11. Our primary outcome was all-cause mortality. We used survey design-adjusted Cox regression to estimate the risk of all-cause mortality, adjusting for confounders. Results: Among the 5,283 subjects, 2,214 (42%) had GI. Participants had a mean follow-up of 22.1 years, during which 1,835 (34%) of them died. Those with GI in the highest quartile of IGF-1 had an unadjusted 64% lower risk of all-cause mortality compared to the lowest quartile (GI = unadjusted OR [95% CI]: 0.37 [0.24,0.55]). This association, although protective, was significantly less protective than those with normal glucose tolerance (NGT) (unadjusted OR: 0.16 [0.12,0.23]). After adjusting for confounders, these associations became insignificant (GI = aOR: 1.02 [0.73,1.42], NGT = aOR: 1.04 [0.74,1.46]). When estimating risk of mortality among joint groups of insulin and IGF-1 levels, those in Group I with NGT had 20% increased adjusted odds of mortality (1.30 [1.01,1.71]), while in GI subjects, there was an insignificant increased odds of mortality (1.17 [0.84, 1.62]). Neither subgroup in Group 2 had significant adjusted odds of mortality relative to Group 4. Group 3 subjects with GI had an adjusted, insignificant 24% increased odds of mortality (1.24 [0.91, 1.70]) compared to 70% increased odds in NGT subjects (1.69 [1.18, 2.42]). Conclusion: The differences in odds of all-cause mortality across IGF-1 quartiles in glucose tolerant vs. intolerant individuals suggests that IGF-1 may play less of a protective role in Type II diabetes and prediabetes. Among those with normal glucose, higher insulin levels, regardless of IGF-1 levels, was associated with all-cause mortality. This association did not hold in those with glucose intolerance.