OBJECTIVE
To gain insight into higher fracture risk in individuals with type 2 diabetes, we determined the association of type 2 diabetes glycemic status and severity with longitudinal changes in peripheral bone density and microarchitecture.
RESEARCH DESIGN AND METHODS
We conducted a longitudinal study of 769 participants from the Framingham Study who underwent high-resolution, peripheral, quantitative computed tomography (HR-pQCT) at the tibia and radius, in 2012-2016 and 2021-2023 (mean 8-year follow-up). Linear regression models estimated mean 8-year percent changes in bone measures, across indicators of diabetes severity, adjusting for age, sex, weight, and height.
RESULTS
The mean age was 67 ± 7 years, and 59% of participants were women. More than half (57%) were normoglycemic (fasting plasma glucose [FPG] <100 mg/dL, not on any treatment), 31% had prediabetes (100 ≤ FPG ≤125 mg/dL), and 12% had type 2 diabetes (FPG >125 mg/dL or on treatment). Adjusted mean percent changes in HR-pQCT bone measures were similar across diabetes severity, including glycemic status, use of diabetes medications, duration of diabetes, and HbA1c. For example, cortical volumetric bone mineral density at the radius changed by -1.50% (95% CI -2.43, -0.56) in type 2 diabetes and -1.96% (-2.53, -1.39), in prediabetes, compared with -2.42% (-2.86, -1.97) in normoglycemia (reference group; all P > 0.05).
CONCLUSIONS
The magnitude of peripheral bone loss over 8 years did not differ between individuals with type 2 diabetes and those with normoglycemia, suggesting that bone deterioration alone does not explain the higher fracture risk in older adults with type 2 diabetes. Future studies should address other contributors to skeletal fragility.
A. Dufour, M. Bouxsein, Mu-Song Gao et al.· Diabetes Care· 0 citations
Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood (n = 6454) and lung (n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank-derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.
Peter Orchard, T. Blackwell, L. Kachuri et al.· Science· 0 citations
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