Treatment Of Type 2 Diabetes Mellitus Research Articles

Metabolic dysfunction-associated steatotic liver disease and the heart.

The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing. Physicians who treat patients with MASLD may acknowledge the strong coincidence with cardiometabolic disease, including atherosclerotic cardiovascular disease (asCVD). This raises questions on co-occurrence, causality, and the need for screening and multidisciplinary care for MASLD in patients with asCVD, and vice versa. Here, we review the interrelations of MASLD and heart disease and formulate answers to these matters. Epidemiological studies scoring proxies for atherosclerosis and actual cardiovascular events indicate increased atherosclerosis in patients with MASLD, yet no increased risk of asCVD mortality. MASLD and asCVD share common drivers: obesity, insulin resistance and type 2 diabetes mellitus (T2DM), smoking, hypertension, and sleep apnea syndrome. In addition, Mendelian randomization studies support that MASLD may cause atherosclerosis through mixed hyperlipidemia, while such evidence is lacking for liver-derived procoagulant factors. In the more advanced fibrotic stages, MASLD may contribute to heart failure with preserved ejection fraction by reduced filling of the right ventricle, which may induce fatigue upon exertion, often mentioned by patients with MASLD. Some evidence points to an association between MASLD and cardiac arrhythmias. Regarding treatment and given the strong co-occurrence of MASLD and asCVD, pharmacotherapy in development for advanced stages of MASLD would ideally also reduce cardiovascular events, as has been demonstrated for T2DM treatments. Given the common drivers, potential causal factors and especially given the increased rate of cardiovascular events, comprehensive cardiometabolic risk management is warranted in patients with MASLD, preferably in a multidisciplinary approach.

PuRenDan alleviates type 2 diabetes mellitus symptoms by modulating the gut microbiota and its metabolites

Ethnopharmacological relevancePuRenDan (PRD) is a traditional Chinese medicine formula comprising five herbs that have been traditionally used to treat type 2 diabetes mellitus (T2DM). While PRD has been shown to be effective in treating T2DM in clinical and animal studies, the mechanisms by which it works on the gut microbiome and metabolites related to T2DM are not well understood. Aim of the studyThe objective of this study was to partially elucidate the mechanism of PRD in treating T2DM through analyses of the gut microbiota metagenome and metabolome. Materials and methodsSprague-Dawley rats were fed high-fat diets (HFDs) and injected with low-dose streptozotocin (STZ) to replicate T2DM models. Then the therapeutic effects of PRD were evaluated by measuring clinical markers such as blood glucose, insulin resistance (IR), lipid metabolism biomarkers (total cholesterol, low-density lipoprotein, non-esterified fatty acids, and triglycerides), and inflammatory factors (tumor necrosis factor alpha, interleukin-6 [IL-6], interferon gamma, and IL-1β). Colon contents were collected, and metagenomics, combined with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry metabolic profiling, was performed to evaluate the effects of T2DM and PRD on gut microbiota and its metabolites in rats. Spearman analysis was used to calculate the correlation coefficient among different microbiota, clinical indices, and metabolites. ResultsPRD exhibited significant improvement in blood glucose and IR, and reduced serum levels of lipid metabolism biomarkers and inflammatory factors. Moreover, the diversity and abundance of gut microbiota undergo significant changes in rats with T2DM that PRD was able to reverse. The gut microbiota associated with T2DM including Rickettsiaceae bacterium 4572_127, Psychrobacter pasteurii, Parabacteroides sp. CAG409, and Paludibacter propionicigenes were identified. The gut microbiota most closely related to PRD were Prevotella sp. 10(H), Parabacteroides sp. SN4, Flavobacteriales bacterium, Bacteroides massiliensis, Alistipes indistinctus, and Ruminococcus flavefaciens. Additionally, PRD regulated the levels of gut microbiota metabolites including pantothenic acid, 1-Methylhistamine, and 1-Methylhistidine; these affected metabolites were involved in pantothenate and coenzyme A biosynthesis, histidine metabolism, and secondary bile acid biosynthesis. Correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. ConclusionOur study provides insights into the gut microbiota and its metabolites of PRD therapy for T2DM. It clarifies the role of gut microbiota and the metabolites in the pathogenesis of T2DM, highlighting the potential of PRD for the treatment of this disease.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: diagnostic and therapeutic aspects. Review

The increase in the prevalence of non‑alcoholic fatty liver disease (NAFLD) occurs in parallel with the global epidemic of obesity and type 2 diabetes mellitus (T2DM) in the world. T2DM is an independent risk factor for the development of NAFLD. At the same time, researchers found that patients diagnosed with NAFLD have a two‑fold increased risk of developing T2DM. NAFLD is encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. NASH is an aggressive form of NAFLD, associated with an increased risk of liver and non‑liver‑related mortality. Liver‑biopsy remains the gold standard for diagnosis, but the majority of patients liver damage can be diagnosed accurately by noninvasive methods.
 The presence of NAFLD in a patient with T2DM makes it difficult to achieve adequate glycemic control, deepens the manifestations of insulin resistance and atherogenic dyslipidemia, increases the risk of serious cardiovascular events and chronic kidney disease. Lifestyle modification and treatment of concomitant T2DM should be undertaken in all patients with NAFLD. To reduce the severity of liver steatosis, weight reduction by 3—5% is necessary, to reduce the inflammatory‑necrotic process, a more significant reduction may be required — up to 10% within 6—12 months. Physical activity increases the sensitivity of insulin receptors, and in combination with diet leads to a significantly significant improvement in biochemical and histological indicators in patients with NAFLD. Early identification and management of patients with intensive dietary and lifestyle modification are essential to prevent the development of advanced liver disease and its complications. Pharmacological therapy should be administered to patients with NASH purposed on the fibrosis inhibition, especially in case of the established predictors of high risk of disease progression (age >50 years, metabolic syndrome, T2DM, or increase in the activity of alanine aminotransferase), as well as to the patients with active NASH with high inflammatory activity.
 At the congress of the European Association for the Study of the Liver (EASL), which took place in Vienna on June 21—24, 2023, a new classification and nomenclature of NAFLD was adopted. It was proposed to replace the term «non‑alcoholic fatty liver disease» to the term «metabolic dysfunction‑associated steatotic liver disease» (MASLD). This diagnosis is established in patients with confirmed steatosis of the liver and one of five cardiometabolic risk factors: obesity, T2DM, insulin resistance, hyperlipidemia, atherosclerosis. The concept of «non‑alcoholic steatohepatitis» (NASH) has been changed to the concept of «metabolic dysfunction‑ associated steatohepatitis» (MASH). Coordination of the views of international and domestic experts in the field of studying this pathology will be important for clinical practice and scientific research.

The Mechanism Underlying the Hypoglycemic Effect of Epimedin C on Mice with Type 2 Diabetes Mellitus Based on Proteomic Analysis.

Type 2 diabetes mellitus (T2DM) has become a worldwide public health problem. Epimedin C is considered one of the most important flavonoids in Epimedium, a famous edible herb in China and Southeast Asia that is traditionally used in herbal medicine to treat diabetes. In the present study, the therapeutic potential of epimedin C against T2DM was ascertained using a mouse model, and the mechanism underlying the hypoglycemic activity of epimedin C was explored using a label-free proteomic technique for the first time. Levels of fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance, as well as contents of malondialdehyde (MDA) and low-density lipoprotein cholesterol (LDL-C) in the 30 mg·kg-1 epimedin C group (EC30 group), were significantly lower than those in the model control group (MC group) (p < 0.05), while the contents of hepatic glycogen, insulin, and high-density lipoprotein cholesterol (HDL-C), as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the EC30 group were notably higher than those in the MC group (p < 0.05). The structures of liver cells and tissues were greatly destroyed in the MC group, whereas the structures of cells and tissues were basically complete in the EC30 group, which were similar to those in the normal control group (NC group). A total of 92 differentially expressed proteins (DEPs) were enriched in the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In the EC30 vs. MC groups, the expression level of cytosolic phosphoenolpyruvate carboxykinase (Pck1) was down-regulated, while the expression levels of group XIIB secretory phospholipase A2-like protein (Pla2g12b), apolipoprotein B-100 (Apob), and cytochrome P450 4A14 (Cyp4a14) were up-regulated. According to the KEGG pathway assay, Pck1 participated in the gluconeogenesis and insulin signaling pathways, and Pla2g12b, Apob, and Cyp4a14 were the key proteins in the fat digestion and fatty acid degradation pathways. Pck1, Pla2g12b, Apob, and Cyp4a14 seemed to play important roles in the prevention and treatment of T2DM. In summary, epimedin C inhibited Pck1 expression to maintain FBG at a relatively stable level, promoted Pla2g12b, Apob, and Cyp4a14 expressions to alleviate liver lipotoxicity, and protected liver tissues and cells from oxidant stress possibly by its phenolic hydroxyl groups.

The Mediterranean diet in the treatment of type 2 diabetes and its complications

The incidence of type 2 diabetes mellitus (T2DM) has gone upward sharply for the past few years. Therefore, the efficient way to combat it has set off a new wave of research. Compared with traditional medication, dietary interventions can also control the development of T2DM with fewer side effects or prevent the onset. Among these studies with different methods and views, the Mediterranean diet (Med diet) can be crucial to prevent and treat T2DM in lifestyle. On the basis of the summary and analysis of relevant literature, this paper has introduced the risk factors and pathogenesis of T2DM and the ingredients and function of the Med diet, followed by the research status of this dietary pattern for the aspects such as hormone and inflammation regulation in treating T2DM. At the end of this paper, the treatment of T2DM aims to focus on nutritional interventions based on the Mediterranean diet in the future, in order to provide a reasonable dietary pattern for T2DM patients as soon as possible.

Regulated intestinal microbiota and gut immunity to ameliorate type 1 diabetes mellitus: A novel mechanism for stem cell-based therapy

Although stem cell transplantation is an effective strategy in the treatment of type 1 diabetes mellitus (T1DM), the mechanisms underlying its therapeutic effects remain unclear. We hypothesized that stem cells target gut microbiota and intestinal mucosal immunity to promote therapeutic effects against T1DM. We investigated the effects of human amniotic mesenchymal stem cells (hAMSCs) on intestinal microbiota and mucosal immunity in streptozotocin-induced T1DM mice. hAMSCs promoted significant reductions in blood glucose levels and increased the number of insulin-secreting cells in the T1DM model. Compared with T1DM model mice, 16S rRNA sequencing revealed significant differences in the composition, diversity, and abundance of microbiota in the ileum of hAMSC-treated mice. Bifidobacterium, Prevotella, and Alcaligenes species were among the 15 most abundant differential bacterial species. LC-MS revealed significant changes in ileal metabolites, and among the top 100 differential metabolites identified, we found that a significant increase in taurine was closely associated with hAMSC therapy. Additionally, we detected significant differences between the two groups with respect to the frequency and phenotype of CD4+ T cell subsets in mesenteric lymph nodes, and hAMSCs promoted significant increases in Th2 and Treg cell frequencies and reduced the frequencies of Th1 and Th17 cells. Moreover, correlation analysis revealed pairwise correlations between differential microflora and differential metabolites and immune signatures. hAMSCs thus have positive effects on the microbiota and their metabolites in the ileum and intestinal mucosal immunity in T1DM. Our findings indicate that gut microbiota and intestinal mucosal immunity may play vital roles in the hAMSC-based treatment of T1DM.

CHARACTERISTICS OF SOME ENZYMES IN BLOOD PLASMA OF DIABETIC HUMANS

Тhe enzymes adenosine deaminase (ADA), dipeptidyl peptidase 4 (DPP4) and glutaminase (GL) are involved in the development of both the type 1 (T1DM) and type 2 diabetes mellitus (T2DM). They can be considered as targets in the prevention and/or treatment of these diseases. The autoimmune response of the body is caused by the post-translational protein modifications, one of which is protein citrullination, when arginine residue transforms to citrulline. This work compares the ADA, DPP4, GL enzymes and protein citrullination in blood plasma from T1DM, T2DM patients and relatively healthy individuals. The enzymes were isolated and purified from the blood samples. We found that DPP4 activity was significantly higher in the plasma of patients compared to controls, particularly in T1DM. Currently the medicines based on DPP4 inhibitors are used in the treatment of T2DM. Our results indicate that this treatment strategy can be recommended in the T1DM treatment as well.

Ginkgolic Acid Derivatives from Ginkgo biloba Show Inhibitory Activity against Protein Tyrosine Phosphatases Associated with Insulin Resistance

Ginkgo biloba L. (Ginkgoacea) contains an abundance of beneficial compounds and has demonstrated positive clinical effects in the management of metabolic syndrome. Recent studies have emphasized its efficacy against type 2 diabetes mellitus (T2DM), including improvements in diabetic nephropathy and retinopathy. Particularly noteworthy are ginkgolic acid analogs, which have shown potential in combating T2DM by inhibiting protein tyrosine phosphatases (PTPs), facilitating glucose uptake, and influencing signaling pathways. In this study, we isolated six derivatives of ginkgolic acid from the MeOH extract of G. biloba leaves with the guidance of liquid chromatography–mass spectrometry (LC/MS). We determined the chemical structures of these isolated compounds as 2-hydroxy-6-(10′-hydroxypentadec-11′(E)-en-1-yl) benzoic acid (1), 2-hydroxy-6-(11′-hydroxypentadec-9′(E)-en-1-yl) benzoic acid (2), 2-hydroxy-6-tridecylbenzoic acid (3), 2-hydroxy-6-pentadecylbenzoic acid (4), 2-hydroxy-6-(12′-hydroxyheptadec-13′(E)-en-1-yl) benzoic acid (5), and 2-hydroxy-6-(11-hydroxyundecyl) benzoic acid (6) using NMR spectroscopic data and LC/MS analysis. To assess their potential for addressing T2DM, we subjected the isolated compounds (1–6) to tests measuring their inhibitory activity against six PTPs: PTPN11, PTPN2, PTP1B, DUSP9, PTPRS, and PTPN9. Among these compounds, compounds 3–5 displayed enzyme inhibition exceeding 90% against all six PTPs. In conclusion, ginkgolic acid derivatives, acting as PTP inhibitors relevant to insulin resistance, hold promise as potential therapeutic candidates for the prevention and treatment of T2DM.

Self-Management Interventions for Adults Living with Type II Diabetes to Improve Patient-Important Outcomes: An Evidence Map.

Self-management interventions (SMIs) may be promising in the treatment of Diabetes Mellitus Type 2 (T2DM). However, accurate comparisons of their relative effectiveness are challenging, partly due to a lack of clarity and detail regarding the intervention content being evaluated. This study summarizes intervention components and characteristics in randomized controlled trials (RCTs) related to T2DM using a taxonomy for SMIs as a framework and identifies components that are insufficiently incorporated into the design of the intervention or insufficiently reported. Following evidence mapping methodology, we searched MEDLINE, CINAHL, Embase, Cochrane, and PsycINFO from 2010 to 2018 for randomized controlled trials (RCTs) on SMIs for T2DM. We used the terms 'self-management', 'adult' and 'T2DM' for content. For data extraction, we used an online platform based on the taxonomy for SMIs. Two independent reviewers assessed eligible references; one reviewer extracted data, and a second checked accuracy. We identified 665 RCTs for SMIs (34% US, 21% Europe) including 164,437 (median 123, range 10-14,559) adults with T2DM. SMIs highly differed in design and content, and characteristics such as mode of delivery, intensity, location and providers involved were poorly described. The majority of interventions aimed to improve clinical outcomes like HbA1c (83%), weight (53%), lipid profile (45%) or blood pressure (42%); 27% (also) targeted quality of life. Improved knowledge, health literacy, patient activation or satisfaction with care were hardly used as outcomes (<16%). SMIs most often used education (98%), self-monitoring (56%), goal-setting (48%) and skills training (42%) to improve outcomes. Management of emotions (17%) and shared decision-making (5%) were almost never mentioned. Although diabetes is highly prevalent in some minority groups, in only 13% of the SMIs, these groups were included. Our findings highlight the large heterogeneity that exists in the design of SMIs for T2DM and the way studies are reported, making accurate comparisons of their relative effectiveness challenging. In addition, SMIs pay limited attention to outcomes other than clinical, despite the importance attached to these outcomes by patients. More standardized and streamlined research is needed to better understand the effectiveness and cost-effectiveness of SMIs of T2DM and benefit patient care.

Trichosanthin alleviates streptozotocin-induced type 1 diabetes mellitus in mice by regulating the balance between bone marrow-derived IL6+ and IL10+ MDSCs

Myeloid-derived suppressor cells (MDSCs) occupy a pivotal role in the intricate pathogenesis of the autoimmune disorder, Type 1 diabetes mellitus (T1DM). Since our previous work demonstrated that trichosanthin (TCS), an active compound of Chinese herb medicine Tian Hua Fen, regulated immune response, we aimed to clarify the efficacy and molecular mechanism of TCS in the treatment of T1DM. To this end, T1DM mouse model was established by streptozotocin (STZ) induction. The mice were randomly divided into normal control group (Ctl), T1DM group (STZ), TCS treated diabetic group (STZ + TCS) and insulin-treated diabetic group (STZ + insulin). Our comprehensive evaluation encompassed variables such as blood glucose, glycosylated hemoglobin, body weight, pertinent biochemical markers, pancreatic histopathology, and the distribution of immune cell populations. Furthermore, we meticulously isolated MDSCs from the bone marrow of T1DM mice, probing into the expressions of genes pertaining to the advanced glycation end product receptor (RAGE)/NF-κB signaling pathway through RT-qPCR. Evidently, TCS exhibited a substantial capacity to effectively counteract the T1DM-induced elevation in random blood glucose, glycosylated hemoglobin, and IL-6 levels in plasma. Pathological scrutiny underscored the ability of TCS to mitigate the damage incurred by islets. Intriguingly, TCS interventions engendered a reduction in the proportion of MDSCs within the bone marrow, particularly within the IL-6+ MDSC subset. In contrast, IL-10+ MDSCs exhibited an elevation following TCS treatment. Moreover, we observed a significant down-regulation of relative mRNA of pro-inflammatory genes, including arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), RAGE and NF-κB, within MDSCs due to the influence of TCS. It decreases total MDSCs and regulates the balance between IL-6+ and IL-10+ MDSCs thus alleviating the symptoms of T1DM. TCS also down-regulates the RAGE/NF-κB signaling pathway, making it a promising alternative therapeutic treatment for T1DM. Collectively, our study offered novel insights into the underlying mechanism by which TCS serves as a promising therapeutic intervention for T1DM.

Lipidomics Profiling of Metformin-Induced Changes in Obesity and Type 2 Diabetes Mellitus: Insights and Biomarker Potential.

Metformin is the first-line oral medication for treating type 2 diabetes mellitus (T2DM). In the current study, an untargeted lipidomic analytical approach was used to investigate the alterations in the serum lipidome of a cohort of 89 participants, including healthy lean controls and obese diabetic patients, and to examine the alterations associated with metformin administration. A total of 115 lipid molecules were significantly dysregulated (64 up-regulated and 51 down-regulated) in the obese compared to lean controls. However, the levels of 224 lipid molecules were significantly dysregulated (125 up-regulated and 99 down-regulated) in obese diabetic patients compared to the obese group. Metformin administration in obese diabetic patients was associated with significant dysregulation of 54 lipid molecule levels (20 up-regulated and 34 down-regulated). Levels of six molecules belonging to five lipid subclasses were simultaneously dysregulated by the effects of obesity, T2DM, and metformin. These include two putatively annotated triacylglycerols (TGs), one plasmenyl phosphatidylcholine (PC), one phosphatidylglycerol (PGs), one sterol lipid (ST), and one Mannosyl-phosphoinositol ceramide (MIPC). This study provides new insights into our understanding of the lipidomics alterations associated with obesity, T2DM, and metformin and offers a new platform for potential biomarkers for the progression of diabetes and treatment response in obese patients.

The short-term cost-effectiveness of once-weekly semaglutide versus once-weekly dulaglutide for the treatment of type 2 diabetes mellitus in Colombian adults.

Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease worldwide and in Colombia, representing one of the main causes of death and placing a considerable burden on healthcare systems. 13 classes of drugs are approved for the treatment of T2DM, with Glucagon-like Peptide-1 (GLP-1) receptor agonists being a first-line treatment option for patients with or at high risk of certain cardiovascular diseases and chronic kidney disease. The objective of this study is to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective. Numbers needed to treat were calculated for different single and composite endpoints of the SUSTAIN 7 trial, annual costs for once weekly semaglutide 1.0 mg and dulaglutide 1.5 mg were extracted from the public SISMED database. With these inputs a cost of control model was developed, to obtain the annual cost of bringing one T2DM patient to relevant clinical outcomes by using semaglutide or dulaglutide. Semaglutide was considered cost-effective compared to dulaglutide across all pre-specified endpoints, even in the different scenarios evaluated in the sensitivity analyses, and in a particularly pronounced manner for weight loss outcomes. Semaglutide at a dose of 1.0 mg once-weekly was cost-effective compared to dulaglutide 1.5 mg across all outcomes in the short-term, making it an appropriate first-line choice in the treatment of T2DM when deciding between these two GLP-1 receptor agonists. This is the first short-term cost-effectiveness study of semaglutide and dulaglutide in T2DM Colombian patients. Our modeled results suggest that once-weekly semaglutide represents a cost-effective option for treating individuals with T2DM in Colombia who are not achieving glycaemia control with metformin, and it would be expected to improve HbA1C, promote greater weight loss and reduce costs from a third-payer perspective compared with treatment with dulaglutide.

Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification.

Astragali Radix (AR) is a common Chinese medicine and food. This article aims to reveal the active role of AR in treating Type 2 diabetes mellitus (T2DM) and its renal protective mechanism. The hypoglycemic active fraction was screened by α-glucosidase and identified by UPLC-QE-Orbitrap-MS spectrometry. The targets and KEGG pathway were determined through the application of network pharmacology methodology. Molecular docking and molecular dynamics simulation technology were used for virtual verification. Subsequently, a mouse model of T2DM was established, and the blood glucose and renal function indexes of the mice after administration were analyzed to further prove the pharmacodynamic effect and mechanism of AR in the treatment of T2DM. HA was determined as the best hypoglycemic active fraction by the α-glucosidase method, with a total of 23 compounds identified. The main active components, such as calycoside-7-O-β-D-glucoside, methylnisoline, and formononetin, were revealed by network pharmacology. In addition, the core targets and the pathway have also been determined. Molecular docking and molecular dynamics simulation techniques have verified that components and targets can be well combined. In vivo studies have shown that AR can reduce blood sugar levels in model mice, enhance the anti-inflammatory and antioxidant activities of kidney tissue, and alleviate kidney damage in mice. And it also has regulatory effects on proteins such as RAGE, PI3K, and AKT. AR has a good therapeutic effect on T2DM and can repair disease-induced renal injury by regulating the RAGE/PI3K/Akt signaling pathway. This study provides ideas for the development of new drugs or dietary interventions for the treatment of T2DM.

Phase 3 efficacy and safety trial of proposed liraglutide biosimilar for reduction of glycosylated hemoglobin (HbA1c) in patients with Type 2 diabetes mellitus

Liraglutide is indicated for glycaemic control in adults with Type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. A proposed biosimilar of liraglutide (Levim Liraglutide) was investigated for efficacy & safety in a phase 3 study against the originator reference liraglutide (Victoza®) manufactured by Novo Nordisk A/S, Denmark. Patients aged 18–65 years of age with glycosylated hemoglobin (HbA1c) between 7 and 10 %, among other criteria, were included in the study. Patients were randomized 1:1 to receive daily doses of either Levim liraglutide or reference liraglutide for 24 weeks. The least square mean (standard error, SE) for the primary efficacy endpoint of reduction in HbA1c% at Week 24 was −1.09 (0.15)% for Levim liraglutide group and −1.04 (0.14)% for reference liraglutide. The upper bound of the confidence interval for treatment difference was less than the non-inferiority margin of 0.4 % at one-sided alpha of 0.025 (P-value = 0.0003). The secondary endpoints for proportion of patients achieving reduction in HbA1c, glycaemic level and weight, changes in cardiovascular parameters and the overall safety profiles of the study drugs were comparable. Levim liraglutide demonstrated non-inferior efficacy and similar safety to reference liraglutide and may be an option in treatment of T2DM (CTRI.nic.in, no. CTRI/2022/02/040261).

Application of Metabolomics and Traditional Chinese Medicine for Type 2 Diabetes Mellitus Treatment.

Diabetes is a major global public health problem with high incidence and case fatality rates. Traditional Chinese medicine (TCM) is used to help manage Type 2 Diabetes Mellitus (T2DM) and has steadily gained international acceptance. Despite being generally accepted in daily practice, the TCM methods and hypotheses for understanding diseases lack applicability in the current scientific characterization systems. To date, there is no systematic evaluation system for TCM in preventing and treating T2DM. Metabonomics is a powerful tool to predict the level of metabolites in vivo, reveal the potential mechanism, and diagnose the physiological state of patients in time to guide the follow-up intervention of T2DM. Notably, metabolomics is also effective in promoting TCM modernization and advancement in personalized medicine. This review provides updated knowledge on applying metabolomics to TCM syndrome differentiation, diagnosis, biomarker discovery, and treatment of T2DM by TCM. Its application in diabetic complications is discussed. The combination of multi-omics and microbiome to fully elucidate the use of TCM to treat T2DM is further envisioned.

Meta-Analysis on the Association Between DPP-4 Inhibitors and Bone Mineral Density and Osteoporosis

Background Type 2 Diabetes Mellitus (T2DM) frequently coexists with osteoporosis and reduced bone mineral density (BMD). Dipeptidyl peptidase-4 inhibitors (DPP-4i), a class of antihyperglycemic agents, are commonly employed in T2DM treatment. However, the influence of DPP-4i on bone health remains unclear and debated. This meta-analysis is conducted to explore the relationship between the use of DPP-4i and changes in BMD, as well as the prevalence of osteoporosis among T2DM patients.Methods We conducted a comprehensive search in PubMed, Embase, and Cochrane Library and Web of Science databases for relevant studies published up until June 2023. Studies included in the meta-analysis were those investigating T2DM patients under DPP-4i treatment, and examining the effects on BMD and osteoporosis. Random-effects models and fixed-effect models were utilized to compute the pooled effects. Heterogeneity among the included studies was evaluated using I² statistics.Results This meta-analysis incorporated a total of 10 studies, encompassing a combined population of 214,541 individuals. The results from this meta-analysis indicated an increase in BMD following DPP-4i usage (SMD 0.15, 95 % confidence interval 0.03-0.26). Additionally, the risk of osteoporosis was significantly reduced (OR 0.90, 95 % confidence interval 0.86-0.94) with very low heterogeneity, recorded at 0 % and 53.0 % respectively. No publication bias was detected in the funnel plot, and sensitivity analyses affirmed the stability of the study's conclusions.Conclusion Our results offer valuable insights into the positive impact of DPP-4i on bone health in T2DM patients, contributing to informed clinical decision-making. These findings may inform the development of more comprehensive T2DM management strategies that account for bone health.

Risk of Anemia and Vitamin B12 Deficiency in Patients with Type 2 Diabetes Mellitus on Metformin Therapy: A Systematic Review and Meta-Analysis

Introduction Metformin is a commonly used medication for the treatment of Type 2 Diabetes Mellitus (T2DM). It has also been hypothesized to reduce the absorption of vitamin B12 in the GI tract. Development of B12 deficiency due to metformin-associated reduced absorption would take years to develop, because vitamin B12 has sufficient stores for 3-10 years. As such, the present systematic review and meta-analysis aims to evaluate the effect of metformin on anemia and vitamin B12 deficiency, with outcomes stratified by duration and dosage of metformin exposure. Methods Electronic searches were conducted on MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to June 2023, supplemented with manual citation search. Two reviewers independently and in duplicate assessed titles, abstracts, and full-text articles, with discrepancies resolved by a third member. Studies considered for inclusion were randomized controlled trials (RCTs) and non-randomized studies (NRS) in any language, evaluating anemia risk in T2DM patients using metformin compared to standard-of-care non-metformin treatments for T2DM . The primary outcome was frequency of anemia. Secondary outcomes included frequency of vitamin B12 deficiency, changes in serum hemoglobin and vitamin B12 levels, folate deficiency, changes in serum folic acid, and homocysteine levels. Results were stratified based on the Metformin Use Index (MUI), which categorizes daily metformin dose in mg x duration in years/1000 into three subgroups: MUI ≤ 5, MUI &amp;gt; 5, and MUI Unspecified (when the primary study did not report or stratify based on metformin dosage and duration). Mantel-Haenszel random effects model was used to synthesize binary and continuous endpoints, providing odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). Results 7443 studies were retrieved from electronic databases and 26 studies comprising 6 RCTs, and 20 NRS were included. In total, 17343 patients were included in this systematic review. Overall, the risk of anemia did not significantly differ between the metformin and control group (OR 1.10 [95%CI 0.64, 1.91]). Subgroup analysis also revealed no significant differences between metformin and control in the MUI ≤ 5 group (OR 1.58 [95%CI 0.54, 4.58]) and the MUI &amp;gt; 5 group (OR 1.12 [95%CI 0.48, 2.65]). Metformin was associated with an increased risk of vitamin B12 deficiency compared to control (OR 2.32 [95%CI 1.51, 3.57]). Subgroup analysis demonstrated that the difference was only significant in the MUI &amp;gt; 5 (OR 3.57 [95%CI 2.98, 4.27]) and the MUI Unspecified groups (OR 2.24 [95%CI 1.48, 3.38]), but not in the MUI ≤ 5 group (OR 1.01 [95%CI 0.83, 1.23]). The subgroup differences were significant (p&amp;lt;0.01). Metformin was associated with a decrease in serum vitamin B12 level (MD -71.55 pmol/L [95%CI -89.27, -53.82]), and change in serum hemoglobin could not be pooled given only one primary study. Serum homocysteine was higher in the metformin group (MD 2.45 µmol/L [95%CI 1.48, 3.41]), and there were no significant differences between metformin and control in both incidence of folate deficiency and change in serum folic acid. Conclusion Metformin use does not appear to increase the risk of anemia compared to placebo or other standard-of-care treatments in T2DM. Vitamin B12 deficiency is associated with metformin use, however likely only in those with longer/greater-dose (metformin use index &amp;gt; 5). Monitoring and supplementation of vitamin B12 level are likely beneficial in this population. Our study is limited by heterogenous criteria for anemia and vitamin B12 deficiency across jurisdictions. Further studies on the safety profile of metformin are recommended to include anemia as an outcome and result-stratification based on metformin dose and duration.

An Observational Study on Type 2 Diabetes Mellitus Related Risk Factors and Complications in In-patient Department at a Tertiary Care Centre in Telangana, India

Aims: To identify the risk factors and complications of type 2 diabetes mellitus (T2DM).&#x0D; Study Design: It is a single-centre, prospective, observational study.&#x0D; Place and Duration of Study: This study site includes in-patient departments of Gandhi Hospital, Secunderabad done for a period of six months between December’2022 to May’2023.&#x0D; Methodology: In-patient cases diagnosed with T1DM, T2DM and pre-diabetes were included in study. A data collection form was drafted that included patient demographics (age, sex, height, weight, history in family, risk factors, past medication history, past medical illnesses- HTN (hypertension), dyslipidemia. Lifestyle of patients if physically active/ sedentary and social history as smoker/ alcoholic noted. Fasting Blood Sugar (FBS) was recorded for T2DM along with BMI in kg/m2. Any micro or macro-vascular complications noted during study period. Medications prescribed were assessed for appropriateness in treating Diabetes Mellitus. Case sheets with complete information regarding patient details were only analyzed.&#x0D; Results: 70 cases were collected and analyzed for diabetes out of which 58 cases comprised of T2DM. The majority study population was males 63.79% and with age group 53-69 years (25 cases, 43.10%) being higher. As per WHO-Diabetes Criteria, Pre-Diabetes was highly prevalent of 58.57% at this study site. Higher cases of T2DM (82.85%) was noted which shows the importance of implementing lifestyle changes to prevent macro and micro vascular complications. Symptoms of T2DM were abdominal pain (15, 25.86%) followed by excessive thirst (20.68%), and tiredness (10%). Major risk factors for T2DM were hypertension (15, 25.86%), smoking habit (22.41%), alcohol and obesity (17.24% each) which may have lead to complications associated with T2DM as Nephropathy in 2 cases followed by retinopathy, ischemic stroke, and diabetic foot each 1 case. Metformin as monotherapy (82.75% cases) was preferred treatment for T2DM at this site followed by Glimepiride (12, 20.68%).&#x0D; Conclusion: Study observations conclude that various risk factors can lead to T2DM, hence it is essential to create awareness among the general population on this. Strategies for preventing DM should also be highlighted such as lifestyle changes and following proper dietary guidelines that would avert any life-threatening conditions.

Systematic Review: Teknologi Needle Free Jet Injection Insulin (NFJI) Efektif Mengontrol Konsentrasi Glukosa Pada Penderita Diabetes Melitus Tipe 2

Needle-free jet injection (NFJI) is a needleless method for insulin delivery in type 2 diabetes mellitus (T2DM) patients. This study evaluates NFJI's effectiveness in controlling blood glucose. In this study, we conducted a systematic review following the PRISMA guidelines, searching six databases (EBSCO Host, ProQuest, PubMed, ScienceDirect, Scopus, and Web of Science). The search yielded a total of 379 articles. We used the following keywords: "Jet injection," "Injection Ject," "Needle-Free Injection," "Insulin," "Diabetes Mellitus Type 2," "Diabetes Type 2," "Type 2 Diabetes," and "Blood Glucose" to identify relevant studies. The aim was to investigate the effectiveness of insulin jet NFJI in controlling blood glucose levels in T2DM patients. We assessed the risk of bias using the Joanna Briggs Institute (JBI) critical appraisal tools checklist. Out of the 379 articles identified, only seven met the inclusion criteria. Among these, six articles employed the Randomized Controlled Trial (RCT) method, while one article used a quasi-experimental design. Respondents in the study consisted of T2DM patients who were divided into two research groups: the intervention group and the control group. The results indicated a significant difference in blood glucose control values between the two groups. NFJI insulin method significantly improves glucose control. It offers advantages like painless, scar-free, low drug preparation, reusability, ease of use, and minimal disease transmission. Recommended for long-term T2DM treatment.

The Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Individuals with Diabetes Mellitus Type two and Heart Failure

Background: SGLT2 Inhibitors are a new family proven by FDA to treat diabetes mellitus type two and because of their cardioprotective effect now used widely in diabetic patients suffering from heart failure. Objective: This study’s goal is to determine the effect of cardioprotective SGLT2 Inhibitors on patients with diabetes mellites and heart failure. Methods: We collected and analyzed fourteen articles, which were published from the period 2015 to 2023, all looking for an influence of SGLT2 inhibitors on diabetics with heart failure. Results: all SGLT2 inhibitors caused a significant decrease in symptoms and hospitalization, morbidity, and mortality and expand the life pattern in patients with heart failure due to the cardiac inflammation reduction, hypertrophy reduction and fibrosis reduction by which they reduce cardiac remodeling. Conclusion: All SGLT2 inhibitors are equally effective in mortality and morbidity reduction in diabetic patients suffering from HF.