Risk factors for lower bone mineral density in older adults with type 1 diabetes: a cross-sectional study

Background

Type 1 diabetes is associated with lower bone mineral density (BMD) and increased
fracture risk, but little is known regarding the effects of diabetes-related factors
on BMD. We assessed whether these factors are associated with lower hip BMD among
older adults with type 1 diabetes.

Methods

This cross-sectional study was embedded in a long-term observational study, the Epidemiology
of Diabetes Interventions and Complications study (EDIC), a cohort of participants
with type 1 diabetes, who were originally enrolled in the Diabetes Control and Complications
Trial (DCCT), and were followed-up for more than 30 years at 27 sites in the USA and
Canada. All active EDIC participants were eligible except if they were pregnant, weighed
above the dual-energy x-ray absorptiometry (DXA) scanner limit, had an implanted neurostimulator,
or were not willing to participate. The primary study outcome was total hip BMD. Hip,
spine, and radius BMD and trabecular bone score (TBS) were measured with DXA at an
annual EDIC visit (2017–19). Time-weighted mean HbA_1c, kidney disease, and peripheral neuropathy were measured annually during EDIC, and
retinopathy was measured every 4 years. Skin intrinsic fluorescence, a measure of
advanced glycation end products (AGEs), and cardiac autonomic neuropathy were assessed
once (2009–10) during EDIC.

Findings

1147 of the 1441 participants who were enrolled in the DCCT trial remained active
EDIC participants at the start of this cross-sectional study. Between Sept 20, 2017,
and Sept 19, 2019, 1094 of 1147 participants were screened for the EDIC Skeletal Health
study. 1058 participants completed at least one of a set of DXA scans and were included
in the analysis. 47·8% were women and 52·2% were men, 96·6% were White and 3·4% were
of other race or ethnicity. The mean age of participants was 59·2 years (SD 6·7).
Higher mean HbA_1c, higher skin intrinsic fluorescence, and kidney disease (but not retinopathy or neuropathy)
were independently associated with a lower total hip BMD. Total hip BMD differed by
–10·7 mg/cm² (95% CI –19·6 to –1·7) for each 1% increase in mean HbA_1c, –20·5 mg/cm² (–29·9 to –11·0) for each 5 unit higher skin intrinsic fluorescence, and –51·7 mg/cm² (–80·6 to –22·7) in the presence of kidney disease. Similar associations were found
for femoral neck and ultra-distal radius BMD, but not for lumbar spine BMD or TBS.

Interpretation

Poorer glycaemic control, AGE accumulation, and kidney disease are independent risk
factors for lower hip BMD in older adults with type 1 diabetes. Maintenance of glycaemic
control and prevention of kidney disease might reduce bone loss and ultimately fractures
in this population. Osteoporosis screening might be particularly important in people
with these risk factors. Further research to identify AGE blockers could benefit skeletal
health.

Funding

National Institute of Diabetes and Digestive and Kidney Disease