Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies

K Hidayat; Q-L Fang; B-M Shi; L-Q Qin

doi:10.1007/s00198-021-05934-2

Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies

Osteoporos Int. 2021 Sep;32(9):1693-1704. doi: 10.1007/s00198-021-05934-2. Epub 2021 Apr 16.

Authors

K Hidayat^#^{1

2}, Q-L Fang^#³, B-M Shi⁴, L-Q Qin⁵

Affiliations

¹ Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, China. khemzie_khem@yahoo.com.
² Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, No. 199 Ren'ai Road, Suzhou, 215123, China. khemzie_khem@yahoo.com.
³ Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, China.
⁴ Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, China. shibimin@163.com.
⁵ Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, No. 199 Ren'ai Road, Suzhou, 215123, China. qinliqiang@suda.edu.cn.

^# Contributed equally.

PMID: 33860816
DOI: 10.1007/s00198-021-05934-2

Abstract

Individuals with diabetes mellitus (DM) have an increased risk of fracture. Glycemic control is crucial to the management of DM, but there are concerns pertaining to hypoglycemia development in the course of glycemic control target achievement. The extent to which glycemic control may affect the risk of fracture remains less defined. Hypoglycemia-induced falls have been suggested to contribute to an elevated risk of fracture in DM patients. In this meta-analysis of observational studies, we aimed to investigate the relative contribution of glycemic control, as measured by glycated hemoglobin (HbA1c), and hypoglycemia to the risk of fracture in DM. The PubMed and Web of Science databases were searched for relevant studies. A random-effects model was used to generate summary relative risks (RRs) and 95% confidence intervals (CIs). Both increased HbA1c levels (RR _{per 1% increase} 1.08, 95% CI 1.03, 1.14; n_studies = 10) and hypoglycemia (RR 1.52, 95% CI 1.23, 1.88; n_studies = 8) were associated with an increased risk of fracture. The association between HbA1c levels and the risk of fracture was somewhat nonlinear, with a noticeably increased risk observed at an HbA1c level ≥ 8%. The positive associations of HbA1c levels and hypoglycemia with the risk of fracture did not reach statistical significance in the studies that adjusted for insulin use, hypoglycemia, or falls for the former and in those that adjusted for falls for the latter. In summary, both increased HbA1c levels and hypoglycemia may increase the risk of fracture in patients with DM. The positive association between HbA1c levels and the risk of fracture appears to be, in part, explained by hypoglycemia-induced falls, possibly due to insulin use. The avoidance of hypoglycemia in the course of achieving good glycemic control through the careful selection of glucose-lowering medications may contribute to fracture prevention by reducing the risk of falls related to treatment-induced hypoglycemia.

Keywords: Diabetes mellitus; Fracture; Glycemic control; Hyperglycemia; Hypoglycemia.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Diabetes Mellitus, Type 2*
Glycated Hemoglobin / analysis
Glycemic Control
Humans
Hypoglycemia* / chemically induced
Hypoglycemia* / epidemiology
Hypoglycemic Agents / adverse effects
Observational Studies as Topic

Substances

Glycated Hemoglobin A
Hypoglycemic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding