SUN-738 - Relationship of Catecholamines to Bone Health in Youth with Obesity and Dysglycemia

The autonomic nervous system (ANS) is implicated in skeletal health (bone quality and strength). Dopamine receptors are found on both osteoblasts and osteoclasts, key regulator cells of bone turnover. The relationship of the ANS sympathetic overdrive in youth with dysglycemia to bone health is not clear. We examined the relationship of urinary catecholamines, including dopamine to creatinine (DA/Cr) and norepinephrine (NE/Cr) ratios, to body composition, whole body and volumetric (v) bone mineral content (BMC), density, and microstructure (quality and strength) in youth across the glycemia spectrum.

56 adolescents (32 females); mean age 15.7 ± 1.7 years, 32% normal weight (NW), 30% overweight-normal glucose tolerance (OW-NGT), 38% OW-impaired glucose regulation (OW-IGR), including prediabetes (n=5) or T2D (n=16); underwent measurement of anthropometrics, body composition and BMC (DXA), bone microarchitecture (HRpQCT) of distal tibia and distal radius, fasting urine for catecholamines and creatinine, and oral glucose tolerance test with glycemic and insulin indices.

Urinary creatinine and catecholamine excretion were not significantly different among the three subject groups. However, the group with OW-IGR tended to have higher urinary DA/Cr (270.4 ± 116.2 mg/g in OW-IGR, 217.2 ± 66.3 mg/g in OW-NGT, and 224.4 ± 69 mg/g in NW; post-hoc p= 0.07 in OW-IGR compared with OW-NGT). In bivariate models, DA/Cr and NE/Cr were inversely related to lean mass (r=-.31, p=0.02, and r=-.26, p=0.049, respectively), and NE/Cr positively related to % body fat (r=.27, p=0.04). Urinary DA and NE were inversely related to insulin sensitivity index (but not after adjusting for creatinine excretion).

DA/Cr was inversely related to whole body BMC (r= -0.32, p= 0.02) and BMD (r= -0.45, p < 0.001), tibia vBMD (r= -0.40, p= 0.004), trabecular (Tb) BMD (r= -0.31, p= 0.024), and whole bone Modulus (r= -0.396, p= 0.004), as well as radial vBMD (r= -0.33, p= 0.016) and TbBMD (r= -0.304, p= 0.028). In a regression model adjusted for age, sex, % body fat, DA/Cr (β= -0.287, p= 0.02) together and independently of %body fat (β= -0.357, p= 0.007) negatively contributed to the variance in whole body BMD (R2= 0.345, p < 0.001). The contribution of DA/Cr to the model was no longer significant after including HOMA-IR in the model.

DA/Cr related to whole body and vBMD as well as to microstructural bone measures at the tibia and radius. Our results suggest a possible contribution of the ANS to the relationship between obesity/dysglycemia and adverse effects on bone health.

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