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Bone density risk factors identified for older adults with type 1 diabetes

NEW YORK 27/05 - In older adults with type 1 diabetes, poor glycemic control, advanced glycation end product (AGE) accumulation and kidney disease were independent risk factors for lower hip bone mineral density (BMD) in an observational study.

"People with type 1 diabetes have a five-times higher rate of hip fracture and lower (BMD) than people without diabetes," write Dr. Anne Schwartz of the University of California, San Francisco and colleagues in The Lancet Diabetes and Endocrinology. "However, it is not clear what aspects of diabetes or its management are responsible."

Dr. Schwartz told Reuters Health by email, "An important finding in this study is that kidney disease is associated with lower BMD independent of long-term glycemic control. We had the data on glycemic control (for the previous 30+ years) to be confident that our analyses controlled for this factor. A clinical implication is that measures to specifically prevent kidney disease, beyond maintaining good glycemic control, are likely to have a positive impact on bone density."

"The surprising finding was that AGE accumulation is associated with lower BMD," she said. "We did not compare our results with non-diabetic controls but we can hypothesize from our results that AGE accumulation could be one of the pathways that causes those with T1D to have lower BMD than non-(diabetics)."

"I am not aware of proven clinical approaches to reduce AGE accumulation, other than good glycemic control," she noted. "Our results provide another reason that research in this area is needed."

This cross-sectional study was embedded in a long-term observational study, Epidemiology of Diabetes Interventions and Complications (EDIC), a cohort of participants with type 1 diabetes who were originally enrolled in the Diabetes Control and Complications Trial and were followed for more than 30 years at 27 sites in the U.S. and Canada.

The primary outcome was total hip BMD.

During EDIC, hip, spine, and radius BMD, as well as trabecular bone score (TBS), were measured with DXA at an annual visit (2017-19). Time-weighted mean HbA1c, kidney disease, and peripheral neuropathy were measured annually throughout the study, and retinopathy was measured every four years.

Skin intrinsic fluorescence (a measure of AGE) and cardiac autonomic neuropathy were assessed once (2009-10).

A total of 1,058 patients in the EDIC study who completed at least one of a set of DXA scans were included in the current analysis. Participants' mean age was 59; 48% were women; and 97% were white.

Higher mean HbA1c, 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 for each 1% increase in mean HbA1c; -20.5 mg/cm2 for each 5-unit higher skin intrinsic fluorescence; and -51∙7 mg/cm2 in those with kidney disease.

Similar associations were found for femoral neck and ultra-distal radius BMD, but not for lumbar spine BMD or TBS.

The authors conclude, "Maintenance of glycemic 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."

In a related editorial, Dr. Nicola Napoli of Fondazione Policlinico Universitario Campus Bio-Medico and Dr. Caterina Conte of e, San Raffaele Roma Open University, both in Rome, Italy, commented, "Diabetes guidelines recognize the need to assess bone health in diabetes care, but it is unknown to what extent these recommendations are followed by diabetologists. Efforts are needed to increase the awareness of clinicians on the association between diabetes and bone fragility and to deepen the knowledge on underlying mechanisms, which will also help improve risk stratification and develop targeted therapies."

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