medwireNews: Higher glycated hemoglobin (HbA1c) and the presence of kidney disease are associated with lower bone mineral density (BMD) in people with type 1 diabetes, study results show.
Total hip BMD was a significant 10.7 mg/cm2 less with each 1% increase in HbA1c among 1058 EDIC participants who underwent dual-energy x-ray absorptiometry, after accounting for variables including age, sex, smoking, BMI, and oral glucocorticoid use. And it was 51.7 mg/cm2 lower among those with versus without kidney disease.
In addition, the accumulation of advanced glycation end products (AGEs), as indicated by skin intrinsic fluorescence, was associated with poorer bone health in this study cohort, who were an average age of 59.2 years at the time of BMD measurement and had an average diabetes duration of 37.7 years.
Specifically, each 5-unit increase in skin intrinsic fluorescence was associated with a 20.5 mg/cm2 lower total hip BMD.
The finding makes this “the first study to demonstrate in type 1 diabetes that AGEs are a risk factor for lower BMD, independent of glycaemic control,” say Ann Schwartz (University of California, San Francisco, USA) and co-researchers.
“In bone, AGEs bind to type I collagen, forming non-enzymatic crosslinks that embrittle the bone matrix and decrease the toughness of cortical bone,” they explain in The Lancet Diabetes & Endocrinology.
Although AGE formation is linked to both hyperglycemia and impaired kidney function, the study authors found that the association between skin intrinsic fluorescence and BMD persisted after accounting for time-weighted average HbA1c and kidney disease.
“Thus, identification of agents that can reduce AGE accumulation might benefit skeletal health,” they suggest.
The majority of the associations seen for total hip BMD were also observed for femoral neck and ultra-distal radius BMD, but not for BMD at the lumbar spine or for trabecular bone score. EDIC is the observational follow-up of the DCCT; whether participants received conventional or intensive glycemic control in DCCT was not associated with BMD.
In a linked commentary, Nicola Napoli (Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy) and Caterina Conte (San Raffaele Roma Open University) describe the study results as “an important advancement in the field, with relevant implications for research and clinical practice for people with type 1 diabetes.”
Noting that HbA1c and kidney function “are routinely assessed during the follow-up of people with type 1 diabetes,” they say that “clinicians should consider these parameters, independent of age, when assessing osteoporosis or fracture risk in this population.”
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Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00103-6
Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00137-1