Both hypo- and hyperglycaemia are associated with increased fracture risk in Japanese people with type 2 diabetes: the Fukuoka Diabetes Registry

Aim: The impact of glycaemic control on fracture risk is controversial, which may be due to the possible presence of hypoglycaemia. The aim of this study was to separately investigate the impacts of severe hypoglycaemia and poor glycaemic control on fracture risk in people with type 2 diabetes. Methods: Overall, 4706 Japanese participants (2755 men and 1951 postmenopausal women) with type 2 diabetes (mean age 66 years) were followed prospectively (a median of 5.3 years; follow-up rate, 97.6%), and were stratified by severe hypoglycaemia status and glycaemic control. The primary outcome was fractures at any anatomic site. Results: Fractures occurred in 662 participants (249 men and 413 women). The age- and sex-adjusted incidence rates (expressed per 1000 person-years) were: 71.2 (multiple episodes of severe hypoglycaemia), 43.1 (one episode), 25.2 [HbA_1c < 53 mmol/mol (< 7%) without severe hypoglycaemia], 28.7 [HbA_1c 53 to < 64 mmol/mol (7% to < 8%) without severe hypoglycaemia], 27.7 [HbA_1c 64 to < 75 mmol/mol (8% to < 9%) without severe hypoglycaemia] and 40.5 [HbA_1c ≥ 75 mmol/mol (≥ 9%) without severe hypoglycaemia]. Multivariate-adjusted hazard ratios (95% confidence intervals) for fractures were 2.24 (1.56, 3.21) in those with multiple episodes of severe hypoglycaemia, and 1.42 (1.04, 1.95) in those with HbA_1c ≥ 75 mmol/mol (≥ 9%) without severe hypoglycaemia, compared with those with HbA_1c < 53 mmol/mol (< 7%) without severe hypoglycaemia. Conclusions: Both severe hypoglycaemia and poor glycaemic control were significantly related to an increased risk of fracture in people with type 2 diabetes, although severe hypoglycaemia conferred a stronger risk.