Atrial Natriuretic Peptide in the High Normal Range Is Associated With Lower Prevalence of Insulin Resistance

We have previously shown that high levels of atrial natriuretic peptides (ANPs) are associated with decreased risk of future diabetes development; however, the mechanism behind this relationship is not fully understood. In this study, we prospectively analyzed whether baseline plasma levels of midregional proANP (MR-proANP) are associated with insulin resistance and postchallenge incretin secretion after long-term follow-up. MR-proANP was measured in 2243 nondiabetic individuals at baseline examination of the Malmö Diet and Cancer Cardiovascular cohort. At reexamination 16.5 years later, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1, insulin, glucose, and glucagon were measured during an oral glucose tolerance test. Linear regression analyses showed that each 1 SD increment of baseline MR-proANP levels was inversely associated with insulin resistance calculated as homeostasis model assessment of insulin resistance (per 1 SD change, β = −.066, P = .001) at follow-up. A logistic regression analysis showed that each 1 SD increment of baseline ANP levels resulted in lower risk of belonging to the upper quartile of homeostasis model assessment of insulin resistance at follow-up (odds ratio 0.88, 95% confidence interval 0.78–0.99, P = .043). In linear regression analyses, each 1 SD increment in baseline MR-proANP levels was associated with greater GIP release (per 1 SD change, β = .055; P = .020) 120 minutes after 75 g glucose intake but not with glucagon-like peptide-1 release (per 1 SD change, β = .016, P = .493) 120 minutes after 75 g glucose intake at 16.5 years of follow-up. Midlife exposure to ANP within the high normal range is associated with a lower risk of insulin resistance. Furthermore, midlife exposure to ANP within the high normal range is associated with a greater postchallenge GIP secretion at follow-up, possibly explaining the lower prevalence of insulin resistance.