Effects of the Rate of Impaired Insulin Secretion on Bone Mineral Density in Type 1 Diabetes

Background: Type 1 Diabetes mellitus (T1DM) is a well-known condition associated with low bone mineral density (BMD) and bone fracture, in which one of the risk factor is impaired endogenous insulin secretion. However, the association between the rate of impaired insulin secretory capacity in T1DM and BMD remains to be elucidated. Objective: To clarify the effect of the rate of impaired insulin secretion on BMD in T1DM. Patients and Methods: This a retrospective single-center cross-sectional study, in which consecutive one-hundred seventy Japanese patients with T1DM at Kobe University Hospital were registered. According to the diagnostic criteria of The Japan Diabetes Society, patients were stratified into three subtypes; acute-onset (AO) (n =51, male 25%, 39 ± 15 years), slowly-progressive (SP) (n =37, male 37%, 57 ± 14 years), and fulminant (F) (n =12, male 33%, 51 ± 15 years) mainly by insulin secretory capacity at onset of T1DM. Lumbar spine (LS) and femoral neck (FN) BMD Z-score between three groups were evaluated. Results: The LS BMD is lower in AO than SP (p =0.03), while no differences were observed compared to F (SP/AO/F; 0.38 ± 1.08/-0.25 ± 0.96/-0.35 ± 1.01). The FN BMD also tended to be lower in AO than in SP (p =0.08) and in F (p =1.00) (SP/AO/F;0.03 ± 1.01/-0.44 ± 0.96/-0.35 ± 0.70). To identify the factors associated with decreased BMD, the multivariate regression analysis was performed using AO and SP. The LS BMD was associated with the pathogenic group (p =0.01). Since a negative correlation was seen between durations and CPR both in AO and SP group (p <0.01, p <0.01), we divided these subjects into following 5 groups; 1 to 4, 5 to 9, 10 to 14, 15 to 19, and more than 20 years. In these groups, the CPR was lower in AO than in SP in 1 to 4 years (p <0.01). Intriguingly, LS BMD was started to decline in 5 to 9 years (p =0.03) and was still continued in 10 to 14 years (p =0.01). In FN, BMD was started to decline in 10 to 14 years (p =0.01), suggesting the BMD decline followed by impaired insulin secretion. However, the difference of both BMD and CPR between AO and SP groups were not seen in more than 15 years group, indicating this tangent BMD difference is link to the difference of insulin secretion. Conclusions: This study firstly showed that pathogenic subtypes of T1DM differently affected on BMD. A detailed examination of each disease period showed that BMD continued to decrease as impaired insulin secretion.