Hypoglycemic Drugs Research Articles

Cutaneous Adverse Drug Reactions to Antidiabetic Medications and Medical Devices Used in Management of Diabetes Mellitus

Context: Approximately 537 million adults (20 - 79 years) worldwide suffer from diabetes, a number that is estimated to reach 643 million by 2030. With the rising prevalence of diabetes, pharmacological therapy has become a cornerstone for its management. The advent of newer devices and drug categories has led to a multitude of adverse drug reactions, with a significant portion being cutaneous side effects. Given that the majority of patients are on multiple other medications, such as oral hypoglycemic agents, antihypertensives, and drugs for coronary artery disease and dyslipidemia, establishing the specific cause of adverse reactions can be challenging. Since the major step in management depends on avoiding or regulating the dose of the culprit drug, it is crucial for the treating clinician to be aware of the common adverse drug reactions associated with these medications. Objective: The article aims to review the reported cutaneous adverse events of oral hypoglycemic agents, insulin, and newer devices in the management of diabetes mellitus. Evidence Acquisition: A PubMed search was conducted using the keywords 'diabetes,' 'cutaneous side effects,' 'insulin,' 'OHA,' 'sulfonylureas,' 'metformin,' and 'antidiabetic drugs.' Results: New adverse events for each category of drugs are continually being identified and reported. These adverse events range from mild rash/pruritus to severe, life-threatening allergies. Conclusions: The management of any adverse reaction includes identifying and avoiding the causative agent. However, with limited literature on the cutaneous side effects of antidiabetic therapeutics, and many being case reports, it can be difficult for clinicians to diagnose these reactions. Our article provides a concise review of the vast spectrum of cutaneous side effects that these drugs and devices can cause, along with diagnostic tests and management strategies.

Hypoglycemic Response to Dorzagliatin in a Patient With GCK-MODY.

Metformin, insulin, and insulin secretagogues do not alter HbA1c levels in glucokinase maturity-onset diabetes of the young (GCK-MODY). However, the efficacy of the new hypoglycemic drugs on GCK-MODY remains unclear. We describe a case of GCK-MODY with unchanged blood glucose under different therapies during an 8 years' follow-up. His HbA1c and biochemical indices under different hypoglycemic treatments were recorded. Oral glucose-lowering drugs, including thiazolidinediones, dipeptidyl peptidase 4 inhibitor, α-glucosidase inhibitor, and sodium-glucose cotransporter 2 inhibitor that had not been evaluated previously, did not improve the HbA1c level in this patient. However, the glucokinase activator dorzagliatin effectively and safely lowered his HbA1c level. Dorzagliatin was effective and safe in this patient with GCK-MODY, providing potential application prospects for precise treatment of GCK-MODY with dorzagliatin.

Expert consensus on stroke prevention and blood glucose management in patients with type 2 diabetes

Abnormal glucose metabolism is closely related to stroke and has adverse effects on the occurrence, development, and prognosis of stroke. Ideal glycemic control is of great significance in improving the prognosis of stroke. Some hypoglycemic drugs can reduce the risk of stroke occurrence and recurrence in patients with type 2 diabetes. Furthermore, such patients with stroke should strengthen their blood pressure and blood lipid control and use antiplatelet drugs reasonably. The expert consensus group finally established this consensus after discussions pertaining to evidence-based medicine and clinical practice, with the aim to provide a reference for clinical practice.

Study on the in Vitro Inhibitory Activity of Peony Seed Blended Oil on α-Amylase and α-Glucosidase

In recent years, China has been suffering from an increasing number of patients with chronic diseases such as diabetes, hypertension, and heart disease, which are gradually showing a "younger" trend. As health problems become more prominent, choosing good cooking oil has become crucial. People are beginning to realize the significance of a balanced diet and healthy eating habits in maintaining good health. Peony seed oil is rich in nutrients, and its content of unsaturated fatty acids can reach over 85%, with the highest content of α-linolenic acid, which effectively lowers blood sugar. Suppose soybean oil and rapeseed oil are combined and added. In that case, the original efficacy of peony seed oil can be complemented and enhanced, its mechanism of action network can be sound, and its nutritional composition can be enriched. We can obtain an optimal ratio for mixing the above several oils by studying their effects and roles. This paper explored the inhibitory effects of peony seed oil, soybean oil, and rapeseed oil on α-amylase activity and α-glucosidase activity, and their optimal ratios were determined by a one-way test and response surface method. The results showed that the optimal ratio was peony seed oil: soybean oil: rapeseed oil = 60:27:13. The results provide specific technology and reference for the development and utilization of peony and provide a particular theoretical basis for the development of hypoglycemic drugs or health food.

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors: Antidiabetics Medications for Treating Diabetes

Type 2 diabetes (T2D) is a progressive disease, and most patients need to treat with monotherapy and combinations of oral hypoglycaemic drugs. At present about 500 million people worldwide are suffering from T2D. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a novel antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption that result in glycosuria, modest weight loss and improve glycaemic control with a low risk of hypoglycaemia. These are used by T2D patients together with diet and exercise, either alone or in combination with other diabetes medicines. The main side-effects of SGLT-2 inhibitors are urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Some other probable adverse effects are lower limb amputations, risk of bone fractures, Fournier gangrene, male bladder cancer, female breast cancer, orthostatic hypotension, and acute kidney injury. This mini review explains aspects of SGLT-2 inhibitors with treatment procedures and side-effects.

INFLUENCE OF FACTORS OF THE PROGRESSION OF DIABETIC RETINOPATHY ON THE CONTENT OF BLOOD SERUM CLUSTER OF DIFFERENTIATION CHEMOKINE CD54 IN THE OF PATIENTS WITH TYPE 2 DIABETES

Background. An early critical step in the development of endothelial dysfunction and DR is the adhesion of leukocytes to endothelial cells, which is controlled and mediated by specific adhesion marker molecules CD54 (ICAM-1), CD106 (VCAM-1), P-selectin and E-selectin. However, the influence of DR progression factors on CD54 content in blood serum in patients with type 2 diabetes at different stages of DR is insufficiently covered in the literature. Aim: to assess the influence of factors of progression of diabetic retinopathy (age, gender, state of diabetes compensation) on the content of the CD54 in the blood serum of patients with type 2 diabetes at different stages of diabetic retinopathy. Material and methods. An open, one-center, one-moment selective observational study was conducted involving adult patients with type 2 diabetes and DR. The study was conducted in 82 patients with DR (148 eyes). Ophthalmological examination included visometry, perimetry, refractometry, tonometry, biomicroscopy, gonioscopy, ophthalmoscopy, optical coherence tomography. The concentration of the soluble form of CD54 in blood serum was determined by enzyme immunoassay. Statistical analysis included ANOVA and regression analysis. Differences were considered statistically significant if p<0.05. Results. A probable decrease in serum sICAM-1 concentration with increasing severity of DM in patients with HbA1c>7.5% was revealed, as well as a pronounced tendency to decrease the concentration of soluble CD54 in blood serum at the III stage of DM in patients with type 2 DM with HbA1c> 7,5%. During the progression of DR, a probable increase in the concentration of sICAM-1 at the II stage of DR when using insulin therapy. Conclusions. The concentration of soluble CD54 in blood serum in patients with HbA1c>7.5% as the stage of diabetic retinopathy increases probably decreases (p=0.05), and in patients on insulin therapy, the content of sICAM-1 in the II stage of diabetic retinopathy is probably higher than in patients, taking tableted hypoglycemic drugs (р=0.003).

Skin-Related Adverse Reactions Induced by Oral Antidiabetic Drugs-A Review of Literature and Case Reports.

Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account the individual patient's characteristics, among other comorbidities. Antidiabetic drugs can induce cutaneous adverse reactions (CADRs) ranging in severity from mild erythema to serious disorders such as DRESS or Stevens-Johnson syndrome. CADRs can result from hypersensitivity to the drug but can also be related to the mechanism of action of the drug or cross-reactivity with drugs of similar structure. This paper reviews CADRs induced by oral antidiabetic drugs, considering their dermatological manifestations and possible pathomechanisms. Particular attention was paid to specific dermatological conditions such as dipeptidylpeptidase 4 inhibitor-associated bullous pemphigoid or Fournier's gangrene associated with sodium-glucose cotransporter 2 inhibitor therapy. Knowledge of the dermatological manifestations of CADRs is important in clinical practice. Recognition of a skin lesion resulting from an adverse drug reaction allows for appropriate management, which in this case is primarily related to drug discontinuation. This is particularly important in the treatment of T2DM since this disease has a high prevalence in the elderly, who are at higher risk of adverse drug reactions.

Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study.

Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown anti-tumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and non-metformin groups, while competing risk regression was performed to assess cancer-specific death. Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with mean age 59.6 (10.3) years received metformin and 164 patients (139 male patients and 25 female patients) with mean age 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P<0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P<0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P<0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P=0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.

Preparation of a hydrolyzed yeast β-glucan chromium(III) complex and evaluation of its hypoglycemic activity and sub-acute toxicity

Yeast β-glucan (BYG) possesses extremely low solubility that has limited its applications. In this study, we hydrolyzed BYG using snail enzyme to obtain hydrolyzed yeast β-glucan (HBYG) with desirable water solubility and hypoglycemic activity. On the basis of HBYG, HBYG‑chromium(III) complex (HBYG-Cr) was synthesized. The molecular weight of the complex was 4.41 × 104 Da, and the content of trivalent chromium was 8.95 %. The hydroxyl groups of HBYG participated in the coordination and formed the chromium complex. The space conformations of HBYG exhibited remarkable changes after complex formation. HBYG-Cr existed mainly in an amorphous state and presented good dispersibility, and the surface was uneven. The hypoglycemic activity of HBYG-Cr was studied in db/db and C57 mice. The results showed that HBYG-Cr had good hypoglycemic activity. Histopathological studies demonstrated that the liver, kidney, pancreas, and skeletal muscle in the treatment group were significantly improved compared with those in the diabetic model group. The sub-acute toxicity of HBYG-Cr was studied in KM mice and the results indicated that the complex did not cause adverse reactions or toxic side effects. This study broadened the application of yeast β-glucan and provided an important reference for the development of hypoglycemic functional foods and drugs.

TLR3-mediated Astrocyte Responses in High and Normal Glucose Adaptation Differently Regulated by Metformin.

Toll-like receptors 3 (TLR3) are innate immune receptors expressed on a wide range of cell types, including glial cells. Inflammatory responses altered by hyperglycemia highlight the need to explore the molecular underpinnings of these changes in cellular models. Therefore, here we estimated TLR3-mediated response of astrocytes cultured at normal (NG, 5 mM) and high (HG, 22.5 mM) glucose concentrations for 48 h before stimulation with polyinosinic:polycytidylic acid Poly(I:C) (PIC) for 6 h. Seahorse Extracellular Flux Analyzer (Seahorse XFp) was used to estimate the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Although adaptation to HG affected ECAR and OCR, the stimulation of cells with PIC had no effect on ECAR. PIC reduced maximal OCR, but this effect disappeared upon adaptation to HG. PIC-stimulated release of cytokines IL-1β, IL-10 was reduced, and that of IL-6 and iNOS was increased in the HG model. Adaptation to HG reduced PIC-stimulated synthesis of COX-derived oxylipins measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Adaptation to HG did not alter PIC-stimulated p38 activity, ERK mitogen-activated protein kinase, STAT3 and ROS production. Metformin exhibited anti-inflammatory activity, reducing PIC-stimulated synthesis of cytokines and oxylipins. Cell adaptation to high glucose concentration altered the sensitivity of astrocytes to TLR3 receptor activation, and the hypoglycemic drug metformin may exert anti-inflammatory effects under these conditions.

MODY diabetes as an orphan disease: literature review

BACKGROUND. Maturity-onset diabetes of the young (MODY) is the most common form of monogenic diabetes, usually diagnosed before the age of 30 years in non-obese patients with a family history of diabetes mellitus (DM). MODY is relatively rare compared to type 1 and type 2 DM, with various literature estimates affecting only 1-2 % of people with diabetes, but because it is rare, clinicians may misdiagnose it as type 1 or type 2 DM, which happens in most cases. Unlike type 1 DM patients, patients with MODY have preserved pancreatic β-cell function, so lifestyle modification in combination with glucose-lowering therapy, which in some cases may include insulin, may be sufficient interventions as treatment. OBJECTIVE. With the help of literary sources, familiarize yourself with the classification, clinical manifestations, aspects of treatment and prognosis of the main forms of MODY diabetes. MATERIALS AND METHODS. Object: MODY diabetes as an orphan disease. Research method: a review of literary sources. RESULTS. MODY is most often an autosomal dominant disease and is divided into subtypes (MODY1 to MODY14) based on genetic mutation. Subtypes 1-3 are the most common, accounting for 95 % of cases. Treatment usually includes diet, exercise, and, in some cases, insulin or oral hypoglycemic drugs. In general, the prognosis can be quite favorable, provided that carbohydrate metabolism is compensated. CONCLUSIONS. MODY diabetes is a complex genetically determined pathology, and understanding the features of this disease, diagnosis and treatment are of great importance for patients and their families. The development of modern methods of treatment and monitoring of glucose, such as insulin pumps, 24-hour glycemic monitoring and other technologies, may improve the prognosis for patients with MODY. Each patient with MODY diabetes has individual characteristics, which leaves an imprint on the prognosis of the disease and approaches to treatment. The main goal is to maintain a normal level of glucose in the blood to avoid complications.

Subacute behavior of glucose and blood pressure of type 1 diabetic people after strength exercise session: Study protocol

Background: Type 1 Diabetes Mellitus (DM1) is characterized as a severe insulin deficiency resulting from the destruction of beta cells in the pancreas, associated with autoimmunity. The clinical picture of a patient with DM1 includes symptoms such as abnormal thirst, dry mouth, sudden weight loss, frequent urination, lack of energy, tiredness, constant hunger and blurred vision. Systemic arterial hypertension (SAH) is characterized by high levels of pressure in the arteries, being associated with risk factors for coronary artery disease; cerebrovascular accident (CVA); myocardial infarction; heart failure and kidney failure. Regular physical activity in these patients is associated with a reduced risk of future cardiovascular disease, better long-term glycemic control, better cardiovascular fitness, better quality of life, reduced daily insulin requirements and better weight control. Furthermore, it plays an important role in the primary and secondary prevention of diabetes cardiovascular disease, improving general health and well-being. Objective: The present study aims to evaluate the effects of strength training on glycemic parameters after an exercise session, in adult type 1 diabetic individuals, through a randomized controlled clinical trial. Methodology: The sample will be made up of 30 participants with DM1, made up of men and women based on the inclusion/exclusion criteria. Discussion: Practicing physical activity reduces the need for hypoglycemic drugs, also improves metabolic control and helps obese patients lose weight, reducing the risk of cardiovascular diseases and improving the quality of life of these patients. The practice of strength and aerobic training as a non-drug treatment is systematically found in the literature as a fundamental strategy for reducing systemic arterial hypertension and maintaining the cardiovascular system. Both resistance exercise and Pilates are effective for individuals with type 1 diabetes, improving metabolic and clinical control, especially when combined with adequate nutrition and amino acid supplementation. Physical activities reduce the need for hypoglycemic medications, help with weight loss and reduce the risk of cardiovascular diseases. Regular exercise, especially intermittent, significantly reduces the risk of acute hypoglycemia. Furthermore, it improves HDL and LDL levels, essential for reducing cardiovascular risks. Strength and aerobic training are essential for controlling high blood pressure and improving quality of life, with three weekly sessions being recommended for satisfactory results.

Rhodiosin from Rhodiola crenulata effectively alleviate postprandial hyperglycemia by inhibiting both the activity and production of α‑glucosidase

BackgroundEffective control of postprandial blood glucose (PBG) level is essential for the prevention and treatment of diabetes and its complications. Several flavonoids have attracted much attention due to their significant PBG-lowering effects. However, there is still a certain gap in the in vivo hypoglycemic activity of most flavonoids compared to first-line drugs available on the market, and are still lack of the PBG-lowering effects of 8-hydroxyflavones and their structure–activity relationship. PurposeEvaluate hypoglycemic effects of 8-hydroxyflavones from Rhodiola crenulata in vitro and in vivo, especially comparatively analyze the relationship between hypoglycemic effects and flavonoid configuration and reveal the possible mechanism of 8-hydroxyflavones in lowering hyperglycemia. MethodsStarch, maltose, sucrose, and glucose tolerance tests in both diabetic and normal mice were used to evaluate and compare the hypoglycemic effects of 8-hydroxyflavones rhodiosin (RHS), rhodionin (RHN), and herbacetin (HBT). Molecular docking, enzyme kinetics, and immunofluorescence analysis were used to research the possible hypoglycemic mechanisms of 8-hydroxyflavones. ResultsRHS (5 and 10 mg/kg) could efficiently decrease PBG levels in both normal and diabetes mice. Moreover, RHS, RHN, and HBT all had significant PBG-lowering effects in transgenic diabetes mice, and the effects were equivalent to or stronger than acarbose. Further mechanism research indicated that 8-hydroxyflavones achieved PBG-lowering effects by inhibiting both the activity and production of glycosidase. Notably, we have innovatively discovered that inhibiting the expression of glycosidases rather than just their activities may be a new target for hypoglycemic drugs. ConclusionWe have firstly comprehensively and systematically clarified PBG-lowering effects of 8-hydroxyflavones from Rhodiola crenulata, and revealed their structure-activity relationships and hypoglycemic mechanisms. The study demonstrated that the substitution of 8-hydroxy groups in flavonoids could significantly enhance their hypoglycemic effects, which were equivalent to or stronger than commercially available drug acarbose. 8-Hydroxyflavones could be used as therapeutic or health drugs with significant potential to reduce postprandial hyperglycemia.

Research progress on the effects of sodium-glucose linked transporter 2 inhibitors on multiple metabolic disorders in metabolic syndrome.

Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate, posing a serious threat to human health. Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drug. SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion, but also by improving islet β cell function, reducing inflammatory responses, and inhibiting oxidative stress. In addition, SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism; reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function. They can also improve blood lipids by increasing degradation of triacylglycerol; reduce blood uric acid by promoting uric acid excretion in kidney and intestine, and by reducing uric acid synthesis. This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.

SGLT2 inhibitor Dapagliflozin alleviates cardiac dysfunction and fibrosis after myocardial infarction by activating PXR and promoting angiogenesis

BackgroundMyocardial infarction (MI) has emerged as the primary cause of global mortality. Managing blood sugar levels could play a vital role in the treatment of MI. Dapagliflozin (DPG), a commonly used hypoglycemic drug, has demonstrated efficacy in treating heart failure. However, the impact of DPG on MI remains unclear. We aimed to investigate the effects and mechanisms of DPG in relation to MI. Methods and resultsDPG administration alleviated MI-induced cardiac dysfunction and myocardial fibrosis. We also found that DPG administration mitigated cardiomyocyte apoptosis through TUNEL staining. CD31 and α-Sma staining revealed that DPG promotes post-MI angiogenesis in mice. In vitro, using scratch assays, transwell assays, and tube formation assays, we discovered that DPG enhanced HUVEC proliferation capacity. Mechanistically, DPG promoted the expression of extracellular matrix genes and mitochondrial function-related genes. Additionally, molecular docking identified the interaction between DPG and PXR, which activated PXR and recruited it to the promoters of Pgam2 and Tcap, promoting their expressions, thus facilitating angiogenesis and post-MI heart repair. ConclusionsDPG promotes angiogenesis by activating PXR, thereby alleviating cardiac dysfunction and fibrosis after myocardial infarction. This study provides new strategies and targets for the treatment of ischemic disease.

Temporal trends on the prevalence of renal disease and outcomes among patients with diabetes mellitus hospitalized by heart failure: findings from INCAex

ABSTRACT Background To assess 20-year time trends in the prevalence of diabetes mellitus (DM) among inpatients with heart failure (HF) and the influence of coexisting DM and kidney disease (KD) on outcomes. Research design and methods A retrospective study of patients was admitted due to HF, during the period 2000/2019. The period of follow-up was divided into three intervals according to the European Medical Agency approval of newer hypoglycemic drugs. We analyzed in-hospital mortality and outcomes during the follow-up period. Results A total of 4959 patients were included. Over time, prevalence of DM was significantly raising among women with HF (50 to 53.2%) and descending among men (50% to 46.8%, p = 0.02). Total mortality and readmissions were higher in patients with DM during the and second periods. However, no significant differences were found in the third-one (HR 1.14, 95% CI 0.94–1.39, p = 0.181). A protector role of oral hypoglycemic medications was observed in this last period. According to the presence of KD, the patients with both DM and KD were who presented most of the events. Conclusions Over the time analyzed, the prevalence of DM raised among women and decreased among men. DM influenced the prognosis of HF except in the third period when more protective hypoglycemic drugs started to be used.

The Discovery and Development of Glucagon-Like Peptide-1 Receptor Agonists.

Diabetes mellitus has become a serious life-threatening disease. As one of the new drugs for the treatment of diabetes, GLP-1 receptor agonists have attracted a lot of attention. Compared with traditional hypoglycemic drugs, GLP-1 receptor agonists have good safety and tolerability. To a certain extent, they overcome the problem of the short half-life of natural GLP-1 in vivo and can exist stably in patients for a long time, achieving good results in the treatment of diabetes, as well as improving the symptoms of some complications. The GLP-1 receptor agonists in the market are all peptide drugs. Compared with peptide drugs, small molecule agonists have the advantages of low cost and oral administration. In this article, we review the recent research progress of GLP-1 receptor agonists.

Percutaneous injection of autologous platelet gel accelerate healing in diabetic tibial non union: On going longitudinal study

IntroductionIn this study the tibial shaft fracture non unions in diabetes mellitus are evaluated with percutaneous autologous platelet gel supplementation to accelerate union are compared with individually matched control group with autologous iliac crest bone marrow aspirate injection. Material and methodsThis present study was carried out on tibial non unions in diabetic patients recruited in an ongoing longitudinal study over a period of 2006 to 2017, treated by one surgeon at one institute, are included in this report. Each of 18 established tibial atrophic, aseptic non unions treated by percutaneous autologous platelets and iliac crest bone marrow aspirate were followed up on regular basis up till 9 months. The healing of non union was assessed clinically by painless full weight bearing and the radiological union was judged by bridging callus formation observed on at least 3 of 4 cortices in anteroposterior and lateral views. ResultsUnion was observed in 17 (94.4 %) patients of the autologous platelet group. The average time to union was 9.2 weeks (range 8 to 18 weeks) after percutaneous autologous platelet injection (P < 0.0517) .In the control group, union was observed in 14 (77.8 %) patients (P = 0.672). The average time to union following percutaneous bone marrow injection was 11.6 weeks (range 9 to 28 weeks). The proximal 1/3 shaft non union healed comparatively faster than the distal 1/3 shaft tibia (P ≤ 0.0612). No correlation was observed between the comminuted and non comminuted fracture non union (P = 0.789). A significant correlation was noted as regards the non union healing time duration in patients who were on insulin and oral hypoglycemic drugs (P ≤ 0.001) and also about the total duration of diabetes mellitus in years (P ≤ 0.003). ConclusionThis investigation showed that percutaneous autologous platelet gel delivery is sufficient method to obtain union in diabetic tibial fracture non unions, which is less invasive procedure than bone marrow injection. The efficacy of this autologous platelets is once again well established and this study reinforced categorically the previously published report by the author.

Meta-analysis of the Relationship between Type 2 Diabetes Mellitus and Renal Cancer Risk.

This study aimed to investigate the relationship between type 2 diabetes mellitus and the risk of renal cancer. A search was carried out on PubMed, Embase, Web of Science, China Biology Med-icine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and other data-bases. The search period was from 2000 to 2022. The two authors independently conducted literature screening, extracted literature data, and then conducted a literature quality evaluation. The type of study is a cohort study. Meta-analysis was carried out on the included literature through Stata12.0 software, and the combined value was calculated with RR value and 95% confidence interval. Subgroup analysis was carried out to explore the impact of different factors on the overall results. A total of 10 articles were included. Through cohort study, the meta-analysis on the risk of type 2 diabetes and renal cancer showed that the combined effect value Risk Ratio (RR) = 1.57 with 95% Confidence Intervals (CI) (1.36, 1.82) and P<0.05. The difference had a signif-icant impact, indicating that the risk of renal cancer in type 2 diabetes patients was 1.55 times higher than that in non-type 2 diabetes patients. The subgroup analysis showed that the combined effect value RR and 95% CI for men was 1.49 (1.26, 1.75), and the combined effect value RR and 95% CI for women was 1.60 (1.35, 1.88), which was basically consistent. Type 2 diabetes can significantly increase the risk of renal cell carcinoma, and the former is a risk factor for the latter. It is suggested that multi-center studies with larger sample sizes should be conducted in the future, and adjustments should be made according to the type of diabetes, the source of the study population, the pathological type of renal cell carcinoma, the use of hypoglycemic drugs, and other factors, to provide a reliable basis for the study of the relationship between diabetes and renal cell carcinoma. At present, the specific mechanism of diabetes increasing the risk of renal cell carcinoma and whether diabetes increases mortality due to renal cell carcinoma is still unclear and needs further research.

Empagliflozin alleviates neuroinflammation by inhibiting astrocyte activation in the brain and regulating gut microbiota of high-fat diet mice

A high-fat diet can modify the composition of gut microbiota, resulting in dysbiosis. Changes in gut microbiota composition can lead to increased permeability of the gut barrier, allowing bacterial products like lipopolysaccharides (LPS) to enter circulation. This process can initiate systemic inflammation and contribute to neuroinflammation. Empagliflozin (EF), an SGLT2 inhibitor-type hypoglycemic drug, has been reported to treat neuroinflammation. However, there is a lack of evidence showing that EF regulates the gut microbiota axis to control neuroinflammation in HFD models. In this study, we explored whether EF could improve neuroinflammation caused by an HFD via regulation of the gut microbiota and the mechanism underlying this phenomenon. Our data revealed that EF alleviates pathological brain injury, reduces the reactive proliferation of astrocytes, and increases the expression of synaptophysin. In addition, the levels of inflammatory factors in hippocampal tissue were significantly decreased after EF intervention. Subsequently, the results of 16S rRNA gene sequencing showed that EF could change the microbial community structure of mice, indicating that the abundance of Lactococcus, Ligilactobacillus and other microbial populations decreased dramatically. Therefore, EF alleviates neuroinflammation by inhibiting gut microbiota-mediated astrocyte activation in the brains of high-fat diet-fed mice. Our study focused on the gut-brain axis, and broader research on neuroinflammation can provide a more holistic understanding of the mechanisms driving neurodegenerative diseases and inform the development of effective strategies to mitigate their impact on brain health. The results provide strong evidence supporting the larger clinical application of EF.