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Metformin can prevent hyperglycaemia-induced osteoporosis and decrease the bone fracture rate, but the mechanism has not been fully elucidated. To reveal the mechanism by which metformin affects hyperglycaemia-induced osteoporosis, we treat a mouse osteoporosis cell model with metformin and find that osteoblast mineralization increases and PPARγ expression decreases. Single-cell mRNA sequencing analysis show that PPARγ is highly expressed in the bone tissue of osteoporosis patients, which highlights the role of PPARγ in osteoporosis. Furthermore, we find that PPARγ is the effector through which metformin prevents osteoporosis. We further examine the mechanism of PPARγ regulation and reveal that metformin regulates PPARγ expression through the AMPK pathway and that PPARγ affects osteoblasts through the endoplasmic reticulum stress (ERS) pathway. Moreover, we verify the association between the effect of metformin on bone metabolism and the expression of PPARγ in high-fat diet-induced diabetic rats. Thus, we identify and functionally validate that metformin prevents hyperglycaemia-induced osteoporosis by regulating the AMPK-PPARγ-ERS axis.

Background: Identifying β‐cells dysregulation in type 2 diabetes mellitus (T2DM) is crucial. Weight fluctuations are frequently observed during diabetes treatment. However, the relationship between body composition changes and islet β‐cell function in individuals with T2DM remains insufficiently investigated. Methods: This retrospective longitudinal study encompassed a cohort of 775 T2DM patients, who underwent body composition measuring using dual‐energy X‐ray absorptiometry (DEXA) and followed up for a median of 2.29 years. Key metrics included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), muscle mass index (MMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F), and the appendicular skeletal muscle mass/trunk fat mass ratio (A/T) were then categorized and grouped. Insulin, C‐peptide, and glucose levels were assessed concurrently following a glucose load. β‐cell function included insulin resistance (HOMA‐IR), insulin sensitivity (Matsuda index (MI)), and insulin secretion evaluated by HOMA‐β and C‐peptidogenic index (CGI). Results: Although no significant changes in BMI were observed, patients with T2DM at readmission exhibited higher FMI, TFMI, and ASMI, as well as elevated levels of HOMA‐IR, MI, and CGI compared to baseline measurements. And lower MI, higher levels of CGI, and HOMA‐IR were observed in BMI increased group. Univariate correlation analysis revealed a negative association between changes in BMI (ΔBMI) and ΔMI, while positive associations were observed in both ΔHOMA‐IR and ΔCGI. Among body composition indexes, ΔFMI exhibited the strongest correlation with ΔHOMA‐IR (r = 0.255, p < 0.001), and ΔASMI was positively associated with ΔMI and ΔCGI (r = 0.131 and 0.194, respectively). Moreover, increased levels of BMI and FMI were associated with a greater risk of progressive insulin resistance compared to the decreased, whereas the trend was converse in ASMI and A/T. Conclusions: Increased FMI may partially contribute to the deterioration of insulin resistance, while increased ASMI is associated with improved insulin sensitivity and secretion. Maintaining an appropriate BMI and muscle/fat ratio is conductive to prevent the progression of insulin resistance in patients with T2DM. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to determine whether patients with type 2 diabetes and sarcopenia had a higher risk of infection. Study designs: A cross‐sectional study and a follow‐up study were performed. Method: A total of 2562 patients were enrolled and assessed for body composition and infection status. They were classified into four groups according to body fat (BF) and muscle mass index (ASMI): obese, sarcopenic, sarcopenic obese, and normal. Among these, 275 patients were followed for a median follow‐up period of 1.84 years to evaluate the relationship of changes in skeletal muscle with infection status. Results: The sarcopenic and sarcopenic obese groups showed a higher risk of infection, an increase by 49.6% (OR = 1.496, 95% CI 1.102–2.031) and 42.4% (OR = 1.424, 95% CI 1.031–1.967) compared with the normal group, and also had a higher risk of respiratory infection, an increase by 56.0% (OR = 1.560, 95% CI 1.084–2.246) and 57.4% (OR = 1.574, 95% CI 1.080–2.293), respectively. Patients with the increased ASMI (OR = 0.079, 95% CI 0.021–0.298) represented a lower risk of infection than those with the decreased ASMI. Even a minor change (OR = 0.125, 95% CI 0.041–0.378) against age was beneficial to lowering the risk of infection. However, no association was found in the changes of body mass index and BF with infection status. Conclusions: Sarcopenia, especially in patients with diabetes who are also obese, increases the risk of infection. Maintaining or improving muscle mass is expected to reduce infections. [ABSTRACT FROM AUTHOR]