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bone mineral density in type 1 diabetes mellitus

bone mineral density in type 1 diabetes mellitus

The Study

Bone mineral density of patients suffering from type 1 diabetes mellitus is often reduced due to impaired insulin secretion. However, it is unclear whether the rate of bone mineral density reduction is affected by the type 1 diabetes mellitus subtype. The objective of this study is to understand the difference in bone mineral density across type 1 diabetes mellitus subtypes: slowly progressive (SP), acute-onset (AO), and fulminant (F).

Bone Mineral Density of Type 1 Diabetes Mellitus Patients

Type 1 diabetes mellitus patients have decreased bone mineral density in both the lumbar spine and the femoral neck. Therefore, a higher fracture risk has been implicated in type 1 diabetes mellitus, particularly in older adult populations and postmenopausal women compared with the general population. Bone mineral density screening is critical for these patients at the onset or suspected onset of disease.

Type 1 diabetes mellitus is a disease often caused by the destruction of pancreatic beta cells, which leads to insulin deficiency, and requires lifelong exogenous insulin replacement therapy. According to the diagnostic criteria of the Japan Diabetes Society, three pathogenic definitions of type 1 diabetes mellitus have been demonstrated: slowly progressive (SP), acute-onset (AO), and fulminant (F). 

In patients with acute-onset and fulminant type 1 diabetes mellitus, lifelong insulin treatment initiation is required soon after the diagnosis because of the marked acute progression of insulin deficiency. As the decline in endogenous insulin secretion occurs differently in each subtype, the differences in bone mineral density between the subtypes could be a suitable model to represent the effect of the duration of low insulin exposure on bone mineral density. 


The study is a retrospective, single-center, cross-sectional study conducted at Kobe University Hospital. A total of 170 Japanese adult patients with type 1 diabetes mellitus admitted to the unit for evaluation of diabetic complications between January 2008 and April 2019 and who underwent bone mineral density measurements were enrolled in this study. 

A total of 18 patients were excluded based on the following criteria: estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2; disease duration of <1 year; and medical history of osteoporosis, including treatment with bisphosphonates, selective estrogen receptor modulators, denosumab, and recombinant human parathyroid hormone. 

The scientific study was conducted retrospectively, and all procedures were part of routine medical care. The patients had the option of an opt-out process, where patients were provided with information explaining the data to be collected and the purpose of the study and were given the opportunity to withdraw. 

Biochemical measurements, Other Covariates, and Bone Mineral Density

Anthropometric parameters such as body mass index (BMI) were collected for each patient along with biochemical data, including platelets, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholinesterase, thyroid-stimulating hormone (TSH), free thyroxine (FT4), Ca (correction value), phosphate (P), insulin-like growth factor I (IGF-I), and hemoglobin A1c (HbA1c). 

The onset of type 1 diabetes mellitus, disease duration, and a previous history of cardiovascular diseases was determined by medical review. Evaluation of diabetic neuropathy was based on symptoms, quantitative sensory testing (vibration and monofilament test), and quantitative motor testing (patellar and ankle reflexes)18. 

The bone mineral density of the lumbar spine (L2–L4) and the femoral neck was measured using dual-energy x-ray absorptiometry (DXA; Horizon A DXA System) simultaneously with blood sampling. 


The lumbar spine BMD-Z was lower in the acute-onset than in the slowly progressive subtype (P = 0.03). No differences were observed when compared with the fulminant subtype. The femoral neck BMD-Z tended to be higher in the slowly progressive than in the acute-onset and fulminant subtypes. Multiple regression analyses showed that the lumbar spine BMD-Z was associated with subtypes (AO vs SP) (P = 0.01), but not subtypes (F vs SP), adjusted for sex, duration, retinopathy, and C-peptide immunoreactivity (CPR).

When the patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the acute-onset or fulminant than in the slowly progressive subtype. In contrast, the lumbar spine and femoral neck BMD-Z differed between the acute-onset and slowly progressive only in the second tertiles (both P < 0.01), with a similar tendency between the fulminant and slowly progressive subtypes.

The lower bone mineral density levels in the present type 1 diabetes mellitus participants were consistent with those reported in a previous meta-analysis among other races, indicating that race-based differences in bone metabolism are not significant. This finding also suggests that these participants were suitable for further investigations as a model of bone research in type 1 diabetes mellitus. 

The bone mineral density lowering rates were strongly associated with type 1 diabetes mellitus subtypes, indicating that the rate of endogenous insulin decline may be an important determinant of bone mineral density reduction in this disease. This is also the largest study involving adult Japanese patients with type 1 diabetes mellitus, showing that bone mineral density in those with type 1 diabetes mellitus is lower than that in a similarly aged healthy population. 

A low bone mineral density in type 1 diabetes mellitus is associated with endogenous insulin deficiency, as well as low BMI and diabetic complications. In this study, the disease duration, BMI, and microvascular disease did not differ across the three subtypes, except for diabetic retinopathy. Regarding macrovascular disease, the previous history of cardiovascular disease did not differ across the subtypes, suggesting that these subtypes were suitable for analyzing the relationship between endogenous insulin secretion and bone mineral density in type 1 diabetes mellitus. 

Among the type 1 diabetes mellitus subtypes, bone mineral density undergoes time-dependent changes, which reveals that the bone mineral density decline follows the impaired insulin secretion. These results provide novel insights into the association between the low insulin exposure duration and bone mineral density.


To conclude, this is the first study to observe the variation in the lowering of bone mineral density between the type 1 diabetes mellitus subtypes, acute-onset, slowly progressive, and fulminant, and demonstrates that bone mineral density in the acute-onset group was lower than that in the slowly progressive group.

Since these subtypes have different time courses for insulin dependence, the analysis of bone mineral density across the groups appears to be an excellent model for demonstrating the pathophysiological association between impaired endogenous insulin secretion and reduced bone mineral density in this beta-cell dysfunction disorder.

Further longitudinal prospective studies are needed to clarify these important clinical pathologies.

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