OR13-01 Type 1 Diabetes Is Associated With Differential Skeletal Effects At The Onset Of Peak Bone Accrual

Abstract

Abstract Disclosure: A.V. Brossfield: None. K.M. Williams: None. A.B. Sopher: None. D.J. McMahon: None. J. Fernando: None. S. Agarwal: None. M.R. Rubin: None. Objective: Type 1 diabetes (T1D) often develops prior to attainment of peak bone mass, yet few data exist regarding bone accretion in the peri-pubertal period. We hypothesized that T1D have disrupted bone architecture at the onset of peak bone mass accrual in association with hyperglycemia and advanced glycation endproduct (AGE) accumulation. Methods: We enrolled T1D and controls at onset of peak bone accretion (Tanner: girls 2/3, boys 3/4) and assessed aBMD by DXA and volumetric BMD (vBMD), microarchitecture, and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT) with finite element analysis (µFE) at the distal (4%) and proximal (30%) radius and tibia. We assessed time in hyperglycemia (>180 mg/dL) by continuous glucose monitoring and AGE accumulation by skin autofluorescence (SAF). Results: T1D (n=29, age 12.5 ± 0.3 [SE] yr, 79% male, 68% white) vs controls (n=31, 12.2 ± 0.3 yr, 55% male, 68% white) had higher BMI (21.3 ± 1 vs 18.4 ± 0.5 kg/m2; p=0.04), fasting glucose (168.5 ± 9 vs 88.4 ± 2 mg/dL; p<0.0001) and HbA1c (8.4 ± 0.8 vs 5.0 ± 0.2%; p=0.05) with a trend toward higher bone age (13.5 ± 0.3 vs 12.6 ± 0.3 yr, p=0.07) and lower 25OHD (24.0 ± 1 vs 34.8 ± 3 ng/mL, p=0.08). After multivariate adjustment (sex, bone age, height and weight), DXA showed decreased bone area in T1D at the total, sub-total, leg, rib and ultradistal radius, and decreased bone mineral content at the rib, leg and trochanter (ranging from -4.1% to -13.5%, all p <0.05). Multivariate adjusted HRpQCT data showed decreased trabecular area in T1D at the distal radius (169.9 ± 8 vs 201.2 ± 8 mm2; p=0.007) and tibia (578 ± 17 vs 631 ± 17 mm2; p=0.04) and decreased cortical perimeter at the distal radius (56.0 ± 1 vs 60.1 ± 1 mm2; p=0.009). However, T1D had increased cortical vBMD at the distal (698.2 ± 8 vs 663.5 ± 8 mg HA/cm3; p=0.004) and proximal radius (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and tibia (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and increased cortical thickness at the distal radius (0.74 ± 0.03 vs 0.64 ± 0.03 mm; p=0.03). There was no difference in bone strength by µFE. Within T1D, lower trabecular area at the distal radius was associated with higher SAF (β -69.26 ± 30 mm2; p=0.04) while higher cortical vBMD at the distal tibia was associated with higher time in hyperglycemia (β 0.633 ± 0.3 mg HA/cm3; p=0.03). Conclusion: T1D at the onset of peak bone accrual have decreased bone area and mineral content by DXA. They also have decreased trabecular area but increased cortical vBMD by HRpQCT, in association with AGE accumulation and hyperglycemia. We speculate that reduced bone turnover with hyperglycemia might lead to reduced area at more metabolically active trabecular sites but is compensated for by excess mineral accumulation at less active cortical sites, with overall maintenance of bone strength. Follow up will elucidate progression of these alterations during the growth spurt. Presentation: Friday, June 16, 2023