Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review).

Metformin has been the go­to medical treatment for addressing type 2 diabetes mellitus (T2DM) as a frontline oral antidiabetic. Obesity, cancer and bone deterioration are linked to T2DM, which is considered a metabolic illness. Numerous diseases associated with T2DM, such as tumours, cardiovascular disease and bone deterioration, may be treated with metformin. Intervertebral disc degeneration (IVDD) is distinguished by degeneration of the spinal disc, accompanied by the gradual depletion of proteoglycans and water in the nucleus pulposus (NP) of the IVD, resulting in lower back pain. The therapeutic effect of metformin on IVDD has also attracted much attention. By stimulating AMP­activated kinase, metformin could enhance autophagy and suppress cell senescence, apoptosis and inflammation, thus effectively delaying IVDD. The present review aimed to systematically explain the development of IVDD and mechanism of metformin in the treatment and prevention of IVDD to provide a reference for the clinical application of metformin as adjuvant therapy in the treatment of IVDD.

Global patterns of asthma burden related to environmental risk factors during 1990-2019: an age-period-cohort analysis for global burden of disease study 2019.

BACKGROUND: Change in asthma burden attributed to specific environmental risk factor has not been evaluated. OBJECTIVE: We aimed to explore the age, period, and cohort effects on asthma burden attributable to smoking and occupational asthmagens in different socio-demographic index (SDI) regions and the region and sex disparities. METHODS: Risk factor-specific asthma deaths and disability-adjusted life years (DALYs) rates were extracted from Global Burden of Disease study 2019, estimated by standard Combined Cause of Death Model and DisMod-MR 2.1 modeling tool. Age-period-cohort analysis was conducted to decompose age, period, and cohort effects on asthma burden. RESULTS: Smoking- and occupational asthmagens-related asthma deaths and DALYs rates dropped by > 45% during 1990-2019. In 2019, Africa, South and Southeast Asia had higher asthma burden than other regions. Male had higher asthma burden than female. Among nearly all age groups, low-middle SDI region had the highest smoking-related asthma burden, and low SDI region had the highest occupational asthmagens-related asthma burden. Inverse "V" shaped trend was observed in the above regions with increasing age. For smoking-related asthma deaths and DALYs rates, the most significant improvement of period rate ratio (RR) occurred in high SDI region, decreased from 1.67 (1.61, 1.74) to 0.34 (0.33, 0.36) and 1.61 (1.57, 1.66) to 0.59 (0.57, 0.61), respectively, as well as the cohort effect on smoking-related asthma burden. For occupational asthmagens-related asthma deaths and DALYs rates, the most sharply decrease of period and cohort RR appeared in the high and high-middle SDI regions. Low SDI region showed least progress in period and cohort RR of smoking- and occupational asthmagens-linked asthma burden. CONCLUSION: Smoking- and occupational asthmagens-related asthma burden sharply decreases, but region and sex disparities exist. Policy makers from low SDI region should reinforce tobacco control and prioritize workplace protection.

Will metformin use lead to a decreased risk of thyroid cancer? A systematic review and meta-analyses.

BACKGROUND: It has been reported that metformin use may reduce the risk of thyroid cancer, but existing studies have generated inconsistent results. The purpose of this study was to investigate such association between metformin use and the risk of thyroid cancer. METHODS: Studies of metformin use for the risk of thyroid cancer were searched in Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Database, Wanfang Data, and Chinese Scientific Journals Database (VIP) from the establishment date to December 2022. Newcastle-Ottawa scale is adopted for assessing the methodological quality of included studies, and the inter-study heterogeneity was assessed by using the I-squared statistic. Combined odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated through either fixed-effects or random-effects model according to the heterogeneity. Besides, subgroup analyses, sensitivity analyses and test for publication bias were conducted. RESULTS: Five studies involving 1,713,528 participants were enrolled in the qualitative and quantitative synthesis. The result of the meta-analyses showed that metformin use was associated with a statistically significant lower risk of thyroid cancer (pooled OR = 0.68, 95% CI = 0.50-0.91, P = 0.011). Moreover, in the subgroup analysis, we found that the use of metformin may also aid in the prevention of thyroid cancer in Eastern population (pooled OR = 0.55, 95% CI = 0.35-0.88, P = 0.012) rather than Western population (pooled OR = 0.89, 95% CI = 0.52-1.54, P = 0.685). Sensitivity analysis suggested the results of this meta-analyses were relatively stable. No publication bias was detected. CONCLUSION: Metformin use is beneficial for reducing the risk of thyroid cancer. For further investigation, more well-designed studies are still needed to elucidate the association between metformin use and the risk of thyroid cancer.