Association of Urinary Normetanephrine Levels with Increased Insulin Resistance in a General Population

Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings appears to be important. Urinary levels of catecholamine metabolite, normetanephrine (NM) may be such a marker. Therefore, we here examined association of urinary NM levels with insulin secretion and resistance evaluated by HOMA indices in a general population. From 1,149 participants of the 2016 population-based Iwaki study of Japanese, 1,037 individuals with fasting blood glucose levels, 64-140 to assess HOMA indices precisely were enrolled in the study (gender (M/F): 407/630; age: 53.4±15.5). The Iwaki study is a health promotion study of people over 20 years old to prevent lifestyle-related diseases and prolong their lifespans, and, the participants were those who believe themselves as healthy. Their urinary NM levels were 0.20±0.mg/grCr. Univariate linear regression analyses showed a significant association of urinary NM levels with HOMA-R (β= 0.1508, p <0.0001) and HOMA-β (β= -0.1354, p<0.0001). Adjustment with age, gender, and multiple factors correlated with HOMA indices (Body mass index, Triglyceride, Hypertension, %fat, HbA1c) showed a significant association with HOMA-R (β=0.1167, p= 0.0012) but not with HOMA-β (β=0.011, p =0.782). Further, analysis with subjects stratified into 2 groups (risk and non-risk) using the optimal cut-off value of NM to predict insulin resistance (HOMA-R>1.6) determined by ROC analysis (0.215 mg/grCr) showed those at risk had an OR of 2.36 (CI: 1.49-3.74) after adjustment for the factors listed above. Increased urinary NM levels seem to be a marker for insulin resistance, or namely risk for diabetes in general.