Association between higher urinary normetanephrine and insulin resistance in a Japanese population

Abstract

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 may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β =-0.031, p = 0.499, and β =-0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p<0.001) remained significant even after these adjustments (β = 0.107, p = 0.007), whereas U-M did not correlate with HOMA-R. Furthermore, use of the optimal cutoff value of U-NM for the prediction of insulin resistance (HOMA-R >1.6) determined by ROC analysis (0.2577 mg/ gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42-4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population.

Brain Dopamine–Clock Interactions Regulate Cardiometabolic Physiology: Mechanisms of the Observed Cardioprotective Effects of Circadian-Timed Bromocriptine-QR Therapy in Type 2 Diabetes Subjects

“…Thirdly, an increase in PVN NPY and CRH activities observed in cardiometabolic syndrome rodents are strong stimuli leading to increases in SNS tone and HPA axis activity and such (often concurrent) neuroendocrine aberrations are often observed in human cardiometabolic syndrome [305][306][307][308][309][310][311][312][313][314][315][316][317][318][319][320][321][322]. Lastly, increases in noradrenergic/serotonergic input activities to the VMH observed in animal models of cardiometabolic syndrome drive increases in SNS tone and leptin resistance that induce postprandial insulin resistance and glucose intolerance, hypertension, and obesity, all common features of human cardiometabolic syndrome [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339][340][341][342]. The very critical point here is that elevations in SNS tone (with or without increased HPA axis activity) to the liver, white adipose, muscle, vasculature, heart, and immune system not only merely associate with but drive multiple aspects of the cardiometabolic syndrome [305][306]…”

“…Lastly, increases in noradrenergic/serotonergic input activities to the VMH observed in animal models of cardiometabolic syndrome drive increases in SNS tone and leptin resistance that induce postprandial insulin resistance and glucose intolerance, hypertension, and obesity, all common features of human cardiometabolic syndrome [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339][340][341][342]. The very critical point here is that elevations in SNS tone (with or without increased HPA axis activity) to the liver, white adipose, muscle, vasculature, heart, and immune system not only merely associate with but drive multiple aspects of the cardiometabolic syndrome [305][306][307][308][309][310][311][312][313][314][315][316][317][318][319][320][321][323][324][325][326][327][328][329]…”

The role of SGLT2i in attenuating residual cardiovascular risk through blood pressure-lowering: mechanistic insights and perspectives

“…In the presence of insulin resistance, the activity of the MAPK/ET-1 pathway dominates over that of the PI3K/Akt/NO pathway, leading to vasoconstriction with elevated blood pressure prevailing (36). Furthermore, insulin resistance has also been associated with hyperactivated sympathetic tone, activation of the renin-angiotensin aldosterone system, and increased saltsensitivity; all of which are implicated in hypertension (12,(37)(38)(39)(40).…”