Sanctuary International Visitor Support Scheme, Sheffield, UK.
Division of Clinical Medicine, School of Medicine and Population Health, Mellanby Centre for Musculoskeletal Research, University of Sheffield, Sheffield, UK.
Osteoporos Int. 2024 Nov;35(11):1909-1917. doi: 10.1007/s00198-024-07227-w. Epub 2024 Sep 12.
Insulin resistance, defined as an impaired biological response to insulin stimulation in target tissues, arises most frequently in the presence of central obesity. Although obesity is generally associated with increased bone mass, recent data challenge this view and, if complicated by T2DM, obese patients are at high risk for fragility fractures. IR may play a key role in this increased fracture risk through effects on bone quality rather than bone quantity. Further understanding of the mechanisms and approaches to prevent osteoporotic fractures in IR-related diseases is needed.
The dramatic increase in obesity and metabolic syndrome (MetS) over the last half-century has led to a worldwide epidemic of type 2 diabetes mellitus (T2DM) as well as in the incidence of insulin resistance (IR). IR is defined as an impaired biological response to insulin stimulation in target tissues and is primarily related to the liver, muscle, and adipose tissue. The most frequent underlying cause is central obesity, and it is known that excess abdominal adipose tissue secretes increased amounts of free fatty acids, which directly affects insulin signalling, reduces glucose uptake in muscle, and triggers excessive triglyceride synthesis and gluconeogenesis in the liver. When pancreatic β cells are unable to secrete the higher levels of insulin needed, T2DM, the main complication of IR, occurs.
Although obesity is generally associated with increased bone mass, recent data challenge this view and highlight the multifaceted nature of the obesity-bone relationship. Patients with T2DM are at significant risk for well-known complications of diabetes, including retinopathy, nephropathy, macrovascular disease, and neuropathy, but it is clear that they are also at high risk for fragility fractures. Moreover, recent data provide strong evidence that IR may key role in the increased fracture risk observed in both obesity and T2DM.
In this concise review article, the role of IR in increased risk of osteoporotic fractures in MetS, obesity, and T2DM is discussed and summarised, including consideration of the need for fracture risk assessment as a 'preventive measure', especially in patients with T2DM and chronic MetS with abdominal obesity. Personalised and targeted diagnostic and therapeutic approaches to prevent osteoporotic fractures in IR-related diseases are needed and could make significant contributions to health outcomes.
胰岛素抵抗是指在靶组织中对胰岛素刺激的生物学反应受损，它最常发生在中心性肥胖的情况下。尽管肥胖通常与骨量增加有关，但最近的数据对这一观点提出了挑战，如果肥胖伴有 2 型糖尿病（T2DM），肥胖患者发生脆性骨折的风险很高。IR 可能通过对骨质量而不是骨量的影响在增加骨折风险方面发挥关键作用。需要进一步了解与 IR 相关疾病中预防骨质疏松性骨折的机制和方法。
在过去半个世纪中，肥胖症和代谢综合征（MetS）的急剧增加导致了 2 型糖尿病（T2DM）以及胰岛素抵抗（IR）的发病率在全球范围内呈流行趋势。IR 被定义为在靶组织中对胰岛素刺激的生物学反应受损，主要与肝脏、肌肉和脂肪组织有关。最常见的潜在原因是中心性肥胖，已知腹部过多的脂肪组织会分泌出更多的游离脂肪酸，这直接影响胰岛素信号转导，减少肌肉中的葡萄糖摄取，并触发肝脏中过多的甘油三酯合成和糖异生。当胰腺β细胞无法分泌所需的更高水平的胰岛素时，就会发生 IR 的主要并发症 T2DM。
尽管肥胖通常与骨量增加有关，但最近的数据对这一观点提出了挑战，并强调了肥胖与骨骼关系的多面性。T2DM 患者发生糖尿病的已知并发症的风险很高，包括视网膜病变、肾病、大血管疾病和神经病，但很明显，他们发生脆性骨折的风险也很高。此外，最近的数据提供了强有力的证据表明，IR 可能在肥胖和 T2DM 中观察到的骨折风险增加中发挥关键作用。
在这篇简洁的综述文章中，讨论并总结了 IR 在 MetS、肥胖和 T2DM 中增加骨质疏松性骨折风险的作用，包括考虑将骨折风险评估作为一种“预防措施”的必要性，特别是在 T2DM 和伴有腹部肥胖的慢性 MetS 患者中。需要针对与 IR 相关疾病的个性化和靶向诊断和治疗方法来预防骨质疏松性骨折，这可能对健康结果产生重大贡献。
