Associations between new obesity indices and abnormal bone density in type 2 diabetes mellitus patients.

The clinical data analysis found that, compared with the traditional obesity index, the waist-weight ratio (WWR) has more advantages in predicting abnormal bone mineral density in subjects with type 2 diabetes. WWR may serve as a new predictive indicator for osteoporosis in T2DM patients. PURPOSE: This study was designed to explore the correlation between obesity-related indices and bone mineral density (BMD) and its influencing factors in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 528 patients with type 2 diabetes were recruited. Glucose tolerance, insulin stimulation, and blood biochemical tests were conducted on all participants. All subjects underwent dual-energy X-ray bone density testing and were grouped based on the bone density results. RESULTS: Compared with those in the normal BMD group, the waist-to-body weight ratio (WWR) and weight-adjusted-waist index (WWI) in the osteopenia and osteoporosis groups were significantly greater, while body mass index (BMI) was significantly lower (P < 0.05). The logistic regression results showed that the WWR, WWI, and BMI were independently correlated with abnormal BMD in T2DM patients (P < 0.05). WWR and the WWI were negatively correlated with the T-value of bone density in various parts of the body, while BMI was positively correlated with the T-value of bone density (P < 0.05). The area under the working characteristic curve (AUC) for T2DM patients with abnormal bone mass predicted by the WWR [0.806, 95% CI = (0.770-0.843), P < 0.001] was greater than that for patients with other obesity indicators, such as the WWI and BMI. CONCLUSION: We found a positive correlation between the WWR and bone density in T2DM patients. Compared with other obesity indicators, such as BMI and WWI, the WWR has a stronger discriminative ability for T2DM patients with abnormal bone density. Therefore, more attention should be given to the WWR in T2DM patients.

New insights into the roles of olfactory receptors in cardiovascular disease.

Olfactory receptors (ORs) are G protein coupled receptors (GPCRs) with seven transmembrane domains that bind to specific exogenous chemical ligands and transduce intracellular signals. They constitute the largest gene family in the human genome. They are expressed in the epithelial cells of the olfactory organs and in the non-olfactory tissues such as the liver, kidney, heart, lung, pancreas, intestines, muscle, testis, placenta, cerebral cortex, and skin. They play important roles in the normal physiological and pathophysiological mechanisms. Recent evidence has highlighted a close association between ORs and several metabolic diseases. Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally. Furthermore, ORs play an essential role in the development and functional regulation of the cardiovascular system and are implicated in the pathophysiological mechanisms of CVDs, including atherosclerosis (AS), heart failure (HF), aneurysms, and hypertension (HTN). This review describes the specific mechanistic roles of ORs in the CVDs, and highlights the future clinical application prospects of ORs in the diagnosis, treatment, and prevention of the CVDs.

Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism.

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

Liraglutide induced browning of visceral white adipose through regulation of miRNAs in high-fat-diet-induced obese mice.

OBJECTIVE: Obesity is characterized by excessive accumulation of white adipose tissue (WAT). Conversely, brown adipose tissue is protective against obesity. We recently reported liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), could inhibit high-fat-diet-induced obesity by browning of WAT. However, the molecular mechanism involved is not well defined. Hence, we aimed to explore whether GLP-1RA could promote brown remodeling in WAT by regulating miRNAs. METHODS: After the obesity model was successfully constructed, C57BL/6J mice were treated with liraglutide (200 µg/kg/d) or equivoluminal saline subcutaneously for 12 weeks. Then, the deposition of abdominal fat was measured by CT scanning. At the end of the treatments, glucose and insulin tolerance in mice were assessed. Serum lipid levels were monitored and epididymal WAT (eWAT) were collected for analysis. Quantitative real-time PCR and western blot analyses were conducted to evaluate the expression of genes and miRNAs associated with white fat browning. RESULTS: Liraglutide significantly reduced body weight and visceral fat mass. Levels of lipid profile were also improved. Liraglutide upregulated the expression of browning-related genes in eWAT. Meanwhile, the expression level of miRNAs (miR-196a and miR-378a) positively associated with the browning of WAT were increased, while the expression of miR-155, miR-199a, and miR-382 negatively related with browning of WAT were decreased. CONCLUSION: Our findings suggest that liraglutide could promote brown remodeling of visceral WAT by bi-regulating miRNAs; this might be one of the mechanisms underlying its effect on weight loss.

Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis.

Type 2 diabetes mellitus (T2DM) has become one of the most serious public healthcare challenges, contributing to increased mortality and disability. In the past decades, significant progress has been made in understanding the pathogenesis of T2DM. Mounting evidence suggested that gut microbiota (GM) plays a significant role in the development of T2DM. Communication between the GM and the brain is a complex bidirectional connection, known as the "gut-brain axis," via the nervous, neuroendocrine, and immune systems. Gut-brain axis has an essential impact on various physiological processes, including glucose metabolism, food intake, gut motility, etc. In this review, we provide an outline of the gut-brain axis. We also highlight how the dysbiosis of the gut-brain axis affects glucose homeostasis and even results in T2DM.

Update on N6-methyladenosine methylation in obesity-related diseases.

Obesity is a chronic metabolic disease that is closely related to type 2 diabetes mellitus, cardiovascular diseases, nonalcoholic fatty liver disease, obstructive sleep apnea, and osteoarthritis. The prevalence of obesity is increasing rapidly every year and is recognized as a global public health problem. In recent years, the role of epigenetics in the development of obesity and related diseases has been recognized and is currently a research hotspot. N6-methyladenosine (m6A) methylation is the most abundant epigenetic modification in the eukaryotic RNA, including mRNA and noncoding RNA. Several studies have shown that the m6A modifications in the target mRNA and the corresponding m6A regulators play a significant role in lipid metabolism and are strongly associated with the pathogenesis of obesity-related diseases. In this review, the latest research findings regarding the role of m6A methylation in obesity and related metabolic diseases are summarized. The authors' aim is to highlight evidence that suggests the clinical utility of m6A modifications and the m6A regulators as novel early prediction biomarkers and precision therapeutics for obesity and obesity-related diseases.

Exploring the role of gut microbiota in obesity and PCOS: Current updates and future prospects.

Polycystic ovary syndrome (PCOS) is a common endocrine gynecological disorder, and the specific pathogenesis of PCOS has not been elucidated. Obesity is a current major public health problem, which is also vital to PCOS. It can exacerbate PCOS symptoms via insulin resistance and hyperandrogenemia. The treatment of PCOS patients depends on the prevailing symptoms. Lifestyle interventions and weight loss remain first-line treatments for women with PCOS. The gut microbiota, which is a current research hot spot, has a substantial influence on PCOS and is closely related to obesity. The present study aimed to elucidate the function of the gut microbiota in obesity and PCOS to provide new ideas for the treatment of PCOS.

Identification of Basement Membrane Genes and Related Molecular Subtypes in Nonalcoholic Fatty Liver Disease.

Basement membranes (BMs) are widely distributed and highly specialized extracellular matrix (ECM). The goal of this study was to explore novel genes associated with nonalcoholic fatty liver disease (NAFLD) from the perspective of BMs. Sequencing results of 304 liver biopsy samples about NAFLD were systematically obtained from the Gene Expression Omnibus (GEO) database. Biological changes during NAFLD progression and hub BM-associated genes were investigated by differential gene analysis and weighted gene co-expression network analysis (WGCNA), respectively. The nonalcoholic steatohepatitis (NASH) subgroups were identified based on hub BM-associated genes expression, as well as the differences in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and immune microenvironment between different subgroups were compared. Extracellular matrix (ECM) seems to play an important role in the development of NAFLD. Three representative BM-associated genes (ADAMTS2, COL5A1, and LAMC3) were finally identified. Subgroup analysis results suggested that there were significant changes in KEGG signaling pathways related to metabolism, extracellular matrix, cell proliferation, differentiation, and death. There were also changes in macrophage polarization, neutrophils, and dendritic cells abundance, and so on. In conclusion, the present study identified novel potential BM-associated biomarkers and further explored the heterogeneity of NASH that might provide new insights into the diagnosis, assessment, management, and personalized treatment of NAFLD.

Association between Circulating Ectodysplasin A and Diabetic Kidney Disease.

Background: Ectodysplasin A (EDA), a member of the TNF family, plays important roles in ectodermal development, while recent studies expanded its regulatory effects on insulin resistance and lipid metabolism. This study was the first time to investigate the correlation between circulating EDA and albuminuria in patients with T2DM. Methods: A total of 189 T2DM and 59 healthy subjects were enrolled in the study. We analyzed the concentrations of EDA by ELISA. Plasma glucose, insulin, HbA1c, lipids, creatinine, BUN, and UACR were also measured. Insulin resistance and pancreatic cell function were assessed by HOMA. Results: Circulating EDA concentration was significantly increased in T2DM patients and increased with the degree of albuminuria. EDA was positively correlated with age, FIns, HOMA-IR, HOMA-ß, Scr, and UACR, and negatively correlated with eGFR. Linear stepwise regression showed that FIns, HOMA-ß, and UACR were independent influencing factors of EDA. Logistic regression analysis showed that EDA was independently associated with the occurrence of albuminuria in T2DM. ROC curve showed that EDA had an area under the receiver operating curve of 0.701 [95%CI = (0.625 - 0.777), P < 0.001]. Conclusion: EDA is positively correlated with the degree of albuminuria in patients with T2DM and may be involved in the occurrence and progression of diabetic kidney disease (DKD).

Association of serum Tsukushi level with metabolic syndrome and its components.

PURPOSE: Tsukushi (TSK), a novel hepatokine, has recently been pointed out to play an important role in energy homeostasis and glycolipid metabolism. However, there are no clinical studies on the association of TSK with metabolic syndrome (MetS), the typical constellation of metabolic disorders. This study was conducted to explore the relationship between TSK and MetS as well as each of its metabolic component clinically. METHODS: We analyzed in this cross-sectional study serum TSK levels by ELISA in 392 participants, including 90 non-MetS and 302 MetS, to compare TSK in two groups and in different numbers of metabolic components. The odds ratios (OR) of TSK quartile in MetS and each metabolic component were computed by multivariate logistic regression analysis. RESULTS: TSK was substantially higher in MetS than in non-MetS subjects (P < 0.001). TSK increased with the concomitant increase of the number of metabolic components (P for <0.001). Logistic regression analyses demonstrated that the OR of MetS was 2.74 for the highest versus the lowest quartile of TSK (P < 0.001) after adjusting for age, gender, smoking status, alcohol consumption and medication use. Additionally, TSK was associated with the OR of poor HDL-C and elevated fasting glucose (P < 0.05). CONCLUSION: Circulating TSK was higher in MetS patients and linked with MetS risk, suggesting that TSK may play a role in the genesis of MetS and be a potential therapeutic target for MetS. Future study should investigate the connection between TSK levels and MetS pathogenesis.

Potential therapeutic value of melatonin in diabetic nephropathy: improvement beyond anti-oxidative stress.

Diabetic nephropathy (DN) is a common complication of diabetes, and it is also the main cause of chronic renal failure. Physiological/pathological changes mediated by high glucose are the main factors causing injury of DN, including the enhancement of polyol pathway, the accumulation of advanced glycation products (AGEs), and the activation of protein kinase C (PKC) and transforming growth factor-ß (TGF-ß) signals. In addition, the abnormal activation of renin-angiotensin system (RAS) and oxidative stress are also involved. Melatonin is a physiological hormone mainly secreted by the pineal gland which has been proved to be related to diabetes. Studies have shown that exogenous melatonin intervention can reduce blood glucose and alleviate high glucose mediated pathological damage. At the same time, melatonin also has a strong antioxidant effect, and can inhibit the activation of RAS. Therefore, it is of great significance to explore the therapeutic effect and value of melatonin on DN.

Weighted Gene Co-Expression Network Analysis of Immune Infiltration in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Immune cell infiltration is an important component of nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to explore novel genes associated with immune infiltration in the progression of NAFLD. METHODS: CIBERSORT was used to evaluate the abundance of immune infiltration in the human NAFLD via a high-throughput sequencing dataset. Further weighted gene co-expression network analysis (WGCNA) was performed to search for the susceptibility gene module and hub genes associated with differential immune cells. The expression of hub genes in different liver non-parenchymal cell clusters and NAFLD-associated hepatocellular carcinoma (HCC) was also explored. RESULTS: Four hub genes (ITGBL1, SPINT1, COL1A2, and THBS2) were ultimately identified, which may be associated with immune infiltration, fibrosis progression, and activity score. The receiver operating characteristic curve (ROC) analysis suggested that these genes had good predictive value for NASH and advanced fibrosis. A single-cell analysis showed that COL1A2 was highly expressed in hepatic stellate cells (HSCs), especially in the later stage, while SPINT1 was highly expressed in cholangiocytes (Cho). In addition, ITGBL1, COL1A2, and THBS2 might be associated with transforming from nonalcoholic steatohepatitis (NASH) to HCC. Our findings identified several novel genes that might be related to immune infiltration in NAFLD. CONCLUSION: These genes may serve as potential markers for the assessment of immune infiltration as well as therapeutic targets for NAFLD. More studies are needed to elucidate the biological mechanism of these genes in the occurrence and development of NAFLD.

Protein Targeting to Glycogen (PTG): A Promising Player in Glucose and Lipid Metabolism.

Protein phosphorylation and dephosphorylation are widely considered to be the key regulatory factors of cell function, and are often referred to as "molecular switches" in the regulation of cell metabolic processes. A large number of studies have shown that the phosphorylation/dephosphorylation of related signal molecules plays a key role in the regulation of liver glucose and lipid metabolism. As a new therapeutic strategy for metabolic diseases, the potential of using inhibitor-based therapies to fight diabetes has gained scientific momentum. PTG, a protein phosphatase, also known as glycogen targeting protein, is a member of the protein phosphatase 1 (PP1) family. It can play a role by catalyzing the dephosphorylation of phosphorylated protein molecules, especially regulating many aspects of glucose and lipid metabolism. In this review, we briefly summarize the role of PTG in glucose and lipid metabolism, and update its role in metabolic regulation, with special attention to glucose homeostasis and lipid metabolism.

Association between circulating asprosin levels and carotid atherosclerotic plaque in patients with type 2 diabetes.

BACKGROUND: Carotid plaque is one of the typical manifestations and precursors of diabetic cardiovascular complications. As a new adipokine, asprosin participates in the development of diabetes and cardiovascular diseases, and is considered to be closely related to insulin resistance and glucolipid metabolism. This study aimed to analyze the relationship between serum asprosin level and carotid plaque in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 180 patients with T2DM were selected. The basic parameters and biochemical indexes of the subjects were measured, and the serum asprosin concentration of the subjects was detected by ELISA. The carotid plaque was evaluated by color Doppler ultrasound. RESULTS: The level of serum asprosin in the T2DM with carotid plaque group was significantly higher than that in T2DM without carotid plaque group [2.53(1.73-3.21) vs 1.72(1.23-2.34) ng/mL, P < 0.05]. The incidence of carotid plaque in the low, middle and high quartiles was 31.7 %, 48.3 % and 70 % respectively. Correlation analysis showed that serum asprosin was positively correlated with BMI, WHR, SBP, DBP, FIns, LDL-C, HOMA-IR, and HOMA-ß (P < 0.05). Linear regression analysis showed that WHR, DBP, FIns, and LDL-C were independent influencing factors of asprosin. Logistic regression analysis showed that serum asprosin was still significantly correlated with carotid plaque in T2DM patients after adjusting for multiple confounding factors. The area under receiver-operating curve (ROC) of asprosin predicting carotid plaque was 0.701 (0.625-0.777) in T2DM. CONCLUSION: The level of serum asprosin in T2DM patients with carotid plaques is significantly higher, suggesting that asprosin may play a role in the occurrence and development of carotid plaques in T2DM. Detection of this index can provide new clinical evidence for the prevention and treatment of diabetic cardiovascular disease.

Transcriptome analysis of peripheral blood mononuclear cells in patients with type 1 diabetes mellitus.

PURPOSE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic ß cells. The goal of this study was to explore potential biological biomarkers for T1DM. METHODS: Two microarray datasets (GSE55098 and GSE156035) about human peripheral blood mononuclear cells (PBMCs) were systematically extracted from the Gene Expression Omnibus (GEO) database. Common genes were identified from the perspective of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) respectively, and hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis. We also observed the expression of these hub genes in some common autoimmune diseases and predicted transcription factors (TFs) that might be associated with these genes. RESULTS: Seven hub genes (DDIT4, ESCO2, SH3BP4, PRICKLE1, EPM2AIP1, KCNJ15 and GRM8) were finally identified. Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of T1DM. Gene set enrichment analysis (GSEA) suggested that most of these hub genes may be mainly involved in the changes of biological functions such as inflammation, infection, immunity, cancer, and apoptosis. Further, compared with the control group, the expression levels of these hub genes also changed in some other autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary biliary cholangitis (PBC), etc., indicating that they might be the common targets of these autoimmune diseases. CONCLUSIONS: The present study identified novel genes associated with T1DM from the PBMCs perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of T1DM.

DUAL I China: Improved glycemic control with IDegLira versus its individual components in a randomized trial with Chinese participants with type 2 diabetes uncontrolled on oral antidiabetic drugs.

BACKGROUND: DUAL I China, one of the DUAL trials, assessed efficacy/safety of insulin degludec/liraglutide (IDegLira) in Chinese adults with type 2 diabetes (T2D) not controlled by oral antidiabetic drugs (OADs). METHODS: This phase 3a, treat-to-target multicenter trial randomized participants (glycated hemoglobin [HbA1c] 53.0-85.8 mmol/mol; previous metformin ± another OAD) 2:1:1 to IDegLira (n = 361), degludec (n = 179), or liraglutide (n = 180). Primary endpoint was change in HbA1c after 26 weeks. Secondary endpoints included: HbA1c < 53.0 mmol/mol attainment, weight change, treatment-emergent hypoglycemia, end-of-treatment insulin dose, and safety. RESULTS: At 26 weeks, HbA1c had decreased by a mean 18.12 mmoL/moL (IDegLira), 12.37 mmoL/moL (degludec) (estimated treatment difference [ETD] -6.50 mmoL/moL; 95% confidence interval [CI] -7.96, -5.04; P < .0001), and 11.33 mmoL/moL (liraglutide) (ETD -6.87 mmoL/moL; 95% CI -8.33, -5.41; P < 0.0001), indicating noninferiority for IDegLira vs degludec and superiority vs liraglutide. HbA1c < 53.0 mmoL/moL attainment was 77.0% (IDegLira), 46.4% (degludec), and 48.3% (liraglutide). Mean weight change with IDegLira (0.1 kg) was superior to degludec (1.2 kg) (ETD -1.08 kg; 96% CI -1.55, -0.62; P < 0.0001). Severe or confirmed hypoglycemic event rates were 0.24 (IDegLira) and 0.17 (degludec) episodes/participant-year (estimated rate ratio 1.46; 95% CI 0.71, 3.02; P = .3008, not significant). At the end of treatment, the IDegLira insulin dose was lower (24.5 U/d) vs degludec (30.3 U/d) (ETD -5.49 U; 95% CI -7.77, -3.21; P < 0.0001). No unexpected safety issues occurred. CONCLUSIONS: IDegLira is efficacious and well tolerated in Chinese adults with T2D not controlled by OADs.

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ).

Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.

The Role of Fibroblast Growth Factor 19 Subfamily in Different Populations Suffering From Osteoporosis.

Fibroblast growth factor (FGF) 19 subfamily, also known as endocrine fibroblast growth factors (FGFs), is a newly discovered metabolic regulator, including FGF19, FGF21 and FGF23. They play significant roles in maintaining systemic homeostasis, regulating the balance of bile acid and glucolipid metabolism in humans. Osteoporosis is a chronic disease, especially in the current status of aging population, osteoporosis is the most prominent chronic bone disease, leading to multiple complications and a significant economic burden that requires long-term or even lifelong management. Members of the FGF family have been shown to be associated with bone mineral density (BMD), fracture repair and cartilage regeneration. Studies of the FGF19 subfamily in different populations with osteoporosis have been increasing in recent years. This review summarizes the role of the FGF19 subfamily in bone metabolism, and provides new options for the treatment of bone diseases such as osteoporosis.

Efficacy and safety benefits of iGlarLixi versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with suboptimally controlled type 2 diabetes on oral agents: The LixiLan-O-AP randomized controlled trial.

AIMS: To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD). MATERIALS AND METHODS: LixiLan-O-AP (NCT03798054) was a 24-week multicentre study in adults (n = 878, mean age 56.0 years, mean body mass index 26.0 kg/m2 ) with glycated haemoglobin (HbA1c) levels ≥53 mmol/mol (7%) and ≤97 mmol/mol (11%) on OAD(s), randomized (2:2:1) to open-label once-daily iGlarLixi, iGlar or Lixi while on continued metformin ± sodium-glucose cotransporter-2 inhibitors. The primary efficacy endpoint was change in HbA1c. RESULTS: After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (-21 mmol/mol; -1.9%) compared with iGlar (-16 mmol/mol; -1.4%; P < 0.0001) and Lixi (-10 mmol/mol; -0.9%; P < 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2-hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference -1.1 kg; P < 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant-year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%). CONCLUSIONS: iGlarLixi achieved significant HbA1c reductions, to near-normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well-tolerated treatment option for Asian Pacific people with T2D.