Treatment Of Type 2 Diabetes Research Articles

A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice.

Exogenous insulin therapy is the mainstay treatment for Type-1 diabetes (T1D) caused by insulin deficiency. A fine-tuned insulin supply system is important to maintain the glucose homeostasis. In this study, we present a designed cell system that produces insulin under an AND gate control, which is triggered only in the presence of both high glucose and blue light illumination. The glucose-sensitive GIP promoter induces the expression of GI-Gal4 protein, which forms a complex with LOV-VP16 in the presence of blue light. The GI-Gal4:LOV-VP16 complex then promotes the expression of UAS-promoter-driven insulin. We transfected these components into HEK293T cells, and demonstrated the insulin was secreted under the AND gate control. Furthermore, we showed the capacity of the engineered cells to improve the blood glucose homeostasis through implantation subcutaneously into Type-1 diabetes mice.

Comparing Effectiveness and Safety of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2 Diabetes and Varying Baseline HbA1c Levels

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy has been associated with cardiovascular benefits and a few adverse events; however, whether the comparative effectiveness and safety profiles vary with differences in baseline hemoglobin A1c (HbA1c) levels is unknown. To compare cardiovascular effectiveness and safety of treatment with SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP-4i) in adults with type 2 diabetes (T2D) (1) overall and (2) at varying baseline HbA1c levels. A new-user comparative effectiveness and safety research study was conducted among 144 614 commercially insured adults, initiating treatment with SGLT2i or DPP-4i and with a recorded T2D diagnosis at baseline and at least 1 HbA1c laboratory result recorded within 3 months before treatment initiation. The intervention consisted of the initiation of treatment with SGLT2i or DPP-4i. Primary outcomes were a composite of myocardial infarction, stroke, or all-cause death (modified major adverse cardiovascular events [MACE]) and hospitalization for heart failure (HHF). Safety outcomes were hypovolemia, fractures, falls, genital infections, diabetic ketoacidosis (DKA), acute kidney injury (AKI), and lower-limb amputation. Incidence rate (IR) per 1000 person-years, hazard ratios (HR) and rate differences (RD) with their 95% CIs were estimated controlling for 128 covariates. A total of 144 614 eligible adults (mean [SD] age, 62 [12.4] years; 54% male participants) with T2D initiating treatment with a SGLT2i (n = 60 523) or a DPP-4i (n = 84 091) were identified; 44 099 had an HbA1c baseline value of less than 7.5%, 52 986 between 7.5% and 9%, and 47 529 greater than 9%. Overall, 87 274 eligible patients were 1:1 propensity score-matched: 24 052 with HbA1c less than 7.5%; 32 290 with HbA1c between 7.5% and 9%; and 30 932 with HbA1c greater than 9% (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01). The initiation of SGLT2i vs DPP-4i was associated with a reduction in the risk of modified MACE (IR per 1000 person-years 17.13 vs 20.18, respectively; HR, 0.85; 95% CI, 0.75-0.95; RD, -3.02; 95% CI, -5.23 to -0.80) and HHF (IR per 1000 person-years 3.68 vs 8.08, respectively; HR, 0.46; 95% CI, 0.35 to 0.57; RD -4.37; 95% CI, -5.62 to -3.12) over a mean follow-up of 8 months, with no evidence of treatment effect heterogeneity across the HbA1c levels. Treatment with SGLT2i showed an increased risk of genital infections and DKA and a reduced AKI risk compared with DPP-4i. Findings were consistent by HbA1c levels, except for a more pronounced risk of genital infections associated with SGLT2i for HbA1c levels of 7.5% to 9% (IR per 1000 person-years 68.5 vs 22.8, respectively; HR, 3.10; 95% CI, 2.68-3.58; RD, 46.22; 95% CI, 40.54-51.90). In this comparative effectiveness and safety research study among adults with T2D, SGLT2i vs DPP-4i treatment initiators had a reduced risk of modified MACE and HHF, an increased risk of genital infections and DKA, and a lower risk of AKI, regardless of baseline HbA1c.

Cost-Utility of Liraglutide Plus Standard of Care Versus Standard of Care in People with Type2 Diabetes and Cardiovascular Risk in Thailand.

Liraglutide has demonstrated a significant reduction in the primary major composite cardiovascular (CV) outcome (CV death, non-fatal myocardial infarction, non-fatal stroke). This study aimed to determine the cost-utility of adding liraglutide to the standard of care (SoC) for treating type2 diabetes (T2D) in Thailand for three cohorts: people with atherosclerotic cardiovascular disease (ASCVD), with no ASCVD, and all people with T2D. A Markov model was developed to capture the long-term costs and outcomes under the perspective of the healthcare system. Costs were based on local data, the transitional probabilities were derived from the LEADER trial, and utilities were derived from published studies. Future costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed. Compared to SoC, adding liraglutide incurred higher costs and gained more quality-adjusted life-years (QALYs), yielding incremental cost-effectiveness ratios (ICERs) of above 1million Thai baht (THB) for the three cohorts. The most influential parameter was the discount rate. When the annual cost of liraglutide reduced from 87,874 to 30,340THB, 30,116THB, and 31,617THB for all people with T2D, people with ASCVD, and people without ASCVD, respectively, the ICER fell below the local threshold of 160,000THB/QALY. Compared to the SoC treatment, the liraglutide group acquired more clinical benefit in terms of fewer CVD. Sensitivity analyses revealed that with an increase in the level of willingness-to-pay (WTP) threshold, adding liraglutide had an increased chance of being a cost-effective strategy. Compared to the SoC treatment, adding liraglutide at the current cost is not cost-effective at the local WTP. People with T2D with ASCVD would have the most potential gain from adding liraglutide treatment compared to other populations.

Management of Patients with Type1 Diabetes and Autoimmunity in the Emergency Room

As an autoimmune disorder, type 1 diabetes (T1D) is a serious health problem. It's becoming more commonplace as time goes on. The primary goal of this literature review is to examine how early on in the course of T1D treatment emergency departments might be involved in the care of patients who develop autoimmune disorders. Patients with type 1 diabetes are frequently admitted to the hospital, and it is important to screen them for other autoimmune disorders as part of any trial of treatment. Given the significance of the link between T1D and the development of autoimmune diseases, emergency physicians should be prepared to screen for these conditions, and the emergency department policy should be revised to include the provision of screening tools like appropriate questionnaires and a panel of representative autoimmune disease tests.

Identification of Genipin as a Potential Treatment for Type 2 Diabetes.

The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of β-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic β-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca2+. Inhibition of PLC ablated genipin-stimulated Ca2+ increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC/Ca2+ pathway. In vivo, acute administration of genipin stimulated GLP-1 secretion in mice. Chronically, treatment with genipin via oral gavage at 50 mg/kg/day for 6 weeks reversed hyperglycemia and insulin resistance in high-fat-diet (HFD)-induced obese mice. Moreover, genipin alleviated the impaired lipid metabolism and decreased lipid accumulation in the liver of obese mice. These results suggest that naturally occurring genipin might potentially be a novel agent for the treatment of T2D and diet-induced fatty liver disease.

Reduced Expression Level of Protein Phosphatase PPM1E Serves to Maintain Insulin Secretion in Type 2 Diabetes.

Reversible phosphorylation is an important regulatory mechanism. Regulation of protein phosphorylation in β-cells has been extensively investigated, but less is known about protein dephosphorylation. To understand the role of protein dephosphorylation in β-cells and type 2 diabetes (T2D), we first examined mRNA expression of type 2C family (PP2C) of protein phosphatases in islets from T2D donors. Phosphatase expression overall was changed in T2D, and that of PPM1E was most markedly downregulated. PPM1E expression correlated inversely with HbA1c. Silencing of PPM1E increased glucose-stimulated insulin secretion (GSIS) in INS-1 832/13 cells and/or islets from T2D patients while PPM1E overexpression decreased GSIS. Increased GSIS following PPM1E silencing was associated with decreased oxidative stress, elevated cytosolic Ca2+ levels and ATP/ADP ratio, increased hyperpolarization of the inner mitochondrial membrane and phosphorylation of CaMKII, AMPK and acetyl-coA carboxylase. Silencing of PPM1E, however, did not change insulin content. Increased GSIS, cell viability, and activation of AMPK upon metformin treatment in β-cells were observed upon PPM1E silencing. Thus, protein dephosphorylation via PPM1E abrogates GSIS. Consequently, reduced PPM1E expression in T2D may be a compensatory response of β-cells to uphold insulin secretion under metabolic duress. Targeting PPM1E in β-cells may thus represent a novel therapeutic strategy for treatment of T2D.

Nutraceuticals as Supportive Therapeutic Agents in Diabetes and Pancreatic Ductal Adenocarcinoma: A Systematic Review.

The correlation between pancreatic ductal adenocarcinoma (PDAC) and diabetes-related mechanisms support the hypothesis that early therapeutic strategies targeting diabetes can contribute to PDAC risk reduction and treatment improvement. A systematic review was conducted, using PubMed, Embase and Cochrane Library databases, to evaluate the current evidence from clinical studies qualitatively examining the efficacy of four natural products: Curcumin-Curcuma longa L.; Thymoquinone-Nigella sativa L.; Genistein-Glycine max L.; Ginkgo biloba L.; and a low-carbohydrate ketogenic diet in type 2 diabetes (T2D) and PDAC treatment. A total of 28 clinical studies were included, showing strong evidence of inter-study heterogeneity. Used as a monotherapy or in combination with chemo-radiotherapy, the studied substances did not significantly improve the treatment response of PDAC patients. However, pronounced therapeutic efficacy was confirmed in T2D. The natural products and low-carbohydrate ketogenic diet, combined with the standard drugs, have the potential to improve T2D treatment and thus potentially reduce the risk of cancer development and improve multiple biological parameters in PDAC patients.

Novel Muscle-Homing Peptide FGF1 Conjugate Based on AlphaFold for Type 2 Diabetes Mellitus

Drugs for metabolic diseases usually require systemic administration and act on multiple tissues, which may produce some unpredictable side effects. There have been many successful studies on targeted drugs, especially antitumor drugs. However, there is still little research on metabolic disease drugs targeting specific tissues. Fibroblast growth factor 1 (FGF1) is a potential therapy for type 2 diabetes (T2D) without the risk of hypoglycemia. However, the major impediment to the clinical application of FGF1 is its mitogenic potential. We previously engineered an FGF1 variant (named FGF1ΔHBS) to tune down its mitogenic activity via reducing the heparin-binding ability. However, other notable side effects still remained, including severe appetite inhibition, pathogenic loss of body weight, and increase in fatality rate. In this study, we used AlphaFold2 and PyMOL visualization tools to construct a novel FGF1ΔHBS conjugate fused with skeletal muscle-targeted (MT) peptide through a flexible peptide linker termed MT-FGF1ΔHBS. We found that MT-FGF1ΔHBS specifically homed to skeletal muscle tissue after systemic administration and induced a potent glucose-lowering effect in T2D mice without hypoglycemia. Mechanistically, MT-FGF1ΔHBS elicits the glucose-lowering effect via AMPK activation to promote the GLUT4 expression and translocation in skeletal muscle cells. Notably, compared with native FGF1ΔHBS, MT-FGF1ΔHBS had minimal effects on food intake and body weight and did not induce any hyperplasia in major tissues of both T2D and normal mice, indicating that this muscle-homing protein may be a promising candidate for T2D treatment. Our targeted peptide strategy based on computer-aided structure prediction in this study could be effectively applied for delivering agents to functional tissues to treat metabolic or other diseases, offering enhanced efficacy and reducing systemic off-target side effects.

Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes.

Considered a significant risk to health and survival, type 1 diabetes (T1D) is a heterogeneous autoimmune disease characterized by hyperglycemia caused by an absolute deficiency of insulin, which is mainly due to the immune-mediated destruction of pancreatic beta cells. In recent years, the role of immune checkpoints in the treatment of cancer has been increasingly recognized, but unfortunately, little attention has been paid to the significant role they play both in the development of secondary diabetes with immune checkpoint inhibitors and the treatment of T1D, such as cytotoxic T-lymphocyte antigen 4(CTLA-4), programmed cell death protein-1(PD-1), lymphocyte activation gene-3(LAG-3), programmed death ligand-1(PD-L1), and T-cell immunoglobulin mucin protein-3(TIM-3). Here, this review summarizes recent research on the role and mechanisms of diverse immune checkpoint molecules in mediating the development of T1D and their potential and theoretical basis for the prevention and treatment of diabetes. Immune checkpoint inhibitors related diabetes, similar to T1D, are severe endocrine toxicity induced with immune checkpoint inhibitors. Interestingly, numerous treatment measures show excellent efficacy for T1D via regulating diverse immune checkpoint molecules, including co-inhibitory and co-stimulatory molecules. Thus, targeting immune checkpoint molecules may exhibit potential for T1D treatment and improve clinical outcomes.

Type 1 diabetes - What's new in prevention and therapeutic strategies?

Type 1 diabetes (T1D) is an autoimmune disorder, and insulin deficiency is the result of b-cell dysfunction. Treatment of type 1 diabetes requires constant parenteral insulin administration, which can be very burdensome for the patient. Meticulous use of insulin therapy does not protect the patient against complications. Hence, the search for other methods of treatment as well as ways of preventing the onset of diabetes has been ongoing for along time. The main obstacle in the implementation of the prevention task is the need to identify people at risk of developing diabetes before the start of autoimmunity. It seems that primary prevention is still unrealistic at the moment, because we do not know all the factors leading to the activation of autoimmunity processes. Research on the use of late secondary prevention in people who develop glucose tolerance disorders or in the early period after the onset of type1 diabetes are at the most advanced stage. Gene therapy is another attempt at an alternative treatment and prevention of type1 diabetes and still requires further research. Recent years have brought alot of information about the nature of type 1 diabetes and the mechanisms leading to its development. However, it has not yet been established what factors decide about the initiation of autoimmunity and what determines the dynamics of these processes.

Exploring the mechanism of metformin action in Alzheimer's disease and type 2 diabetes based on network pharmacology, molecular docking, and molecular dynamic simulation.

Metformin, which has been shown to be highly effective in treating type 2 diabetes (T2D), is also believed to be valuable for Alzheimer's disease (AD). Computer simulation techniques have emerged as an innovative approach to explore mechanisms. To study the potential mechanism of metformin action in AD and T2D. The chemical structure of metformin was obtained from PubChem. The targets of metformin were obtained from PubChem, Pharm Mapper, Batman, SwissTargetPrediction, DrugBank, and PubMed. The pathogenic genes of AD and T2D were retrieved from the GeneCards, OMIM, TTD, Drugbank, PharmGKB, and DisGeNET. The intersection of metformin with the targets of AD and T2D is represented by a Venn diagram. The protein-protein interaction (PPI) and core targets networks of intersected targets were constructed by Cytoscape 3.7.1. The enrichment information of GO and Kyoto Encyclopedia of Gene and Genomics (KEGG) pathways obtained by the Metascape was made into a bar chart and a bubble diagram. AutoDockTools, Pymol, and Chem3D were used for the molecular docking. Gromacs software was used to perform molecular dynamics (MD) simulation of the best binding target protein. A total of 115 key targets of metformin for AD and T2D were obtained. GO analysis showed that biological process mainly involved response to hormones and the regulation of ion transport. Cellular component was enriched in the cell body and axon. Molecular function mainly involved kinase binding and signal receptor regulator activity. The KEGG pathway was mainly enriched in pathways of cancer, neurodegeneration, and endocrine resistance. Core targets mainly included TP53, TNF, VEGFA, HIF1A, IL1B, IGF1, ESR1, SIRT1, CAT, and CXCL8. The molecular docking results showed best binding of metformin to CAT. MD simulation further indicated that the CAT-metformin complex could bind well and converge relatively stable at 30 ns. Metformin exerts its effects on regulating oxidative stress, gluconeogenesis and inflammation, which may be the mechanism of action of metformin to improve the common pathological features of T2D and AD.

Commentary on Metabolic Health Disparities Affecting the Rio Grande Valley Mexican American Population: Seeking Answers Using Animal Models.

Mexican Americans living in the Rio Grande Valley (RGV) have a high prevalence of type 2 diabetes (T2D). The US-Mexico border frontier has a unique blended culture of American lifestyle and Mexican traditions. Some examples of the cultural traditions are the food and the use of herbal medicine, but these traditions are in danger of disappearing after a very short number of generations living in the United States. This article describes the use of animal models under experimental conditions to solve practical questions (etiology or treatment). We performed studies with murine (ie, mouse and rat) models to elucidate the characteristics of medicinal plants that modulate glucose metabolism and inflammation and protect from bone loss, complications related to T2D. The University of Texas Rio Grande Valley researchers also have collaborated with the University of Texas Health Science Center at San Antonio researchers in performing studies in nonhuman primates (NHP) (ie, baboon) to understand the effect of T2D and diets on organs and tissues. With the new knowledge gained from the use of animal models (murine and NHP), new therapies are discovered for the prevention and treatment of T2D and its related complications, such as bone loss and nonalcoholic fatty liver disease, all of which the Mexican American and other human populations are at high risk of developing.

A review of recent research and development on GLP-1 receptor agonists-sustained-release microspheres.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most commercially available GLP-1 RAs are administered through frequent subcutaneous injections, which may result in poor patient compliance during clinical treatment. To improve patients' compliance, sustained-release GLP-1 RA-loaded microspheres have been explored. This review is an overview of recent progress and research in GLP-1 RA-loaded microspheres. First, the fabrication methods of GLP-1 RA-loaded microspheres including the coacervation method, emulsion-solvent evaporation method based on agitation, premix membrane emulsification technology, spray drying, microfluidic droplet technology, and supercritical fluid technology are summarized. Next, the strategies for maintaining GLP-1 RAs' stability and activity in microspheres by adding additives and PEGylation are reviewed. Finally, the effect of particle size, drug distribution, the internal structure of microspheres, and the hydrogel/microsphere composite strategy on improved release behavior is summarized.

Hepatic targeting of the centrally active cannabinoid 1 receptor (CB1R) blocker rimonabant via PLGA nanoparticles for treating fatty liver disease and diabetes.

Over-activation of the endocannabinoid/CB1R system is a hallmark feature of obesity and its related comorbidities, most notably type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD). Although the use of drugs that widely block the CB1R was found to be highly effective in treating all metabolic abnormalities associated with obesity, they are no longer considered a valid therapeutic option due to their adverse neuropsychiatric side effects. Here, we describe a novel nanotechnology-based drug delivery system for repurposing the abandoned first-in-class global CB1R antagonist, rimonabant, by encapsulating it in polymeric nanoparticles (NPs) for effective hepatic targeting of CB1Rs, enabling effective treatment of NAFLD and T2D. Rimonabant-encapsulated NPs (Rimo-NPs) were mainly distributed in the liver, spleen, and kidney, and only negligible marginal levels of rimonabant were found in the brain of mice treated by iv/ip administration. In contrast to freely administered rimonabant treatment, no CNS-mediated behavioral activities were detected in animals treated with Rimo-NPs. Chronic treatment of diet-induced obese mice with Rimo-NPs resulted in reduced hepatic steatosis and liver injury as well as enhanced insulin sensitivity, which were associated with enhanced cellular uptake of the formulation into hepatocytes. Collectively, we successfully developed a method of encapsulating the centrally acting CB1R blocker in NPs with desired physicochemical properties. This novel drug delivery system allows hepatic targeting of rimonabant to restore the metabolic advantages of blocking CB1R in peripheral tissues, especially in the liver, without the negative CB1R-mediated neuropsychiatric side effects.

Acute Toxicity Assay and Anti-diabetic Activities of Shemmeco Extract in Drosophila melanogaster

In this study the acute toxicity assay and anti- diabetic properties of Shemmeco extract were examined. The LC50 in this study was conducted using the concentrations: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg, 250 mg, 500 mg, 1000 mg, 2500 mg and 5000 mg of extract, each per 10g fly diet. For ten days, Drosophila melanogaster was fed a high diet of sucrose (2.5 g/10 g diet) to elicit insulin resistance type 2 diabetes. The diabetic flies were treated with 5mg, 10mg, 25mg, 50mg and 250 mg per 10 g diet each of Shemmeco extract being safe concentrations from result of acute toxicity and 16mg of metformin/10g diet as standard drug. Glucose content significantly elevated (p<0.05) in diabetes untreated compared to control group. Metformin significantly declined (p<0.05) the glucose content of fruit flies treated with 5 mg (S1) of Shemmeco extract compared to diabetic untreated and metformin treated. The slight decline of glucose content of fruit flies treated with 5mg (S1) of Shemmeco extract therefore indicates that the extract is promising in the treatment of diabetes type 2 if developed further.

The effect of a structured non-pharmacological treatment of type 2 diabetes on glycated hemoglobin and body weight: a randomized controlled trial

BACKGROUND: Non-pharmacological treatments are an integral part of the treatment of all patients with type 2 diabetes (T2D). However, due to many factors, doctors and patients themselves tend to underestimate or completely neglect such effective methods in managing the course of the disease. Despite the high level of evidence of the effectiveness of this type of treatment for T2D, every year scientists around the world continue to actively study the effect of various non-drug methods on the course of the disease.AIM: To study the effect of a 24-week structured non-pharmacological treatment program on glycated hemoglobin reduction and weight loss in middle-aged patients with compensated T2D taking metformin.MATERIALS AND METHODS: A two-group, randomized, parallel-group, blinded trial was designed. Patients with an established diagnosis of T2D in the stage of compensation (HbA1c ≤7%), aged 45–59 years, taking metformin, were randomized to receive either standard non-pharmacological treatment of diabetes according to clinical protocol of T2D treatment in Kazakhstan, or an intensive course of non-pharmacological treatment according to a structured program developed by researchers. The duration of the intervention was 24 weeks. Primary outcomes were glycated hemoglobin, body weight. Secondary outcomes: blood pressure, waist circumference, insulin resistance index (HOMA-IR), lipid profile: total cholesterol, high and low density lipoproteins, triglycerides. The outcomes of the participants in both groups were assessed at baseline, 12 and 24 weeks after randomization. The study is registered with ClinicalTrials.gov NCT04632823.RESULTS: The study included 200 patients, 67 patients completed the study: intervention group n=33, control group n=34. After 24 weeks of observation, patients in the intervention group showed a significant decrease in HbA1c from 6.34% to 6.22%, p<0.001, while for the control group the level of HbA1c remained the same at 6.5% (p=0.703). Patients in both groups significantly reduced body weight, however, the decrease in the intervention group was more significant: by 6.7% of the initial level, while in the control group, only 1.1%. LDL, triglycerides, cholesterol level, HOMA-IR 2, and diastolic blood pressure did not decline significantly in the control group. All biochemical characteristics except triglycerides and LDL decreased significantly in the intervention group.CONCLUSION: The use of a structured program of non-pharmacological treatment of type 2 diabetes mellitus among compensated (HbA1c ≤7%) middle-aged patients who took metformin significantly reduced body weight and glycated hemoglobin in 24 weeks.

Pyuria Is Associated with Dysbiosis of the Urinary Microbiota in Type 2 Diabetes Patients Receiving Sodium–Glucose Cotransporter 2 Inhibitors

Treating type 2 diabetes (T2D) patients with sodium–glucose cotransporter 2 (SGLT2) inhibitors may be associated with an increased risk of urinary tract infections (UTIs), such as diabetes-induced asymptomatic bacteriuria. Pyuria—a condition wherein leukocytes are detected in the urine—is a predictor of UTIs. The aim of this study was to examine the urinary microbiome of Taiwanese T2D patients, with or without pyuria, undergoing SGLT2 treatment. We recruited seven T2D patients, recorded their clinical and biochemical characteristics, and collected their urine samples for 16S metagenomic sequencing. The primary outcomes were the diversity of urinary microbiota and the relative abundance of different species. We found that the microbiome of the pyuria group was significantly less diverse than the non-pyuria group (0.24 ± 0.04 vs. 2.21 ± 0.28, p = 0.002), while the number of operational taxonomic units did not differ significantly (763.5 ± 78.67 and 747 ± 141.3, p = 0.92). Escherichia-Shigella spp. dominated the microbiome of the pyuria group (97.4%–99.4%), and these patients tended to have more comorbidities. In conclusion, pyuria is associated with urinary microbiota dysbiosis in T2D patients being treated with SGLT2 inhibitors.

MiRNA Theranostic Nanoparticles Promote Pancreatic Beta Cell Proliferation in Type 1 Diabetes Model.

Type 1 diabetes (T1D) is a chronic autoimmune disorder which affects the insulin-producing beta cells in the pancreas. A variety of strategies, namely, insulin replacement therapy, engineered vaccines, immunomodulators, etc., have been explored to correct this condition. Recent studies have attributed the development of T1D to the anomalous expression of microRNAs in the pancreatic islets. Here, we describe the protocol for the development of a theranostic approach to modify the expression of aberrant miRNAs. The MRI-based nanodrug consists of superparamagnetic iron oxide nanoparticles conjugated to microRNA-targeting oligonucleotides that can promote proliferation of pancreatic beta cells in a mouse model of T1D. This theranostic approach can successfully serve as a potential therapeutic approach for the targeted treatment of T1D with minimal side effects.

GLP-1 Receptor Agonists and SGLT-2 Inhibitors as Adjuncts to Insulin in Type 1 Diabetes: Benefits and Concerns.

The metabolic control of type 1 diabetes (T1D) is more difficult and complicated than type 2 diabetes (T2D). Although novel basal and prandial insulin analogues and systems for continuous glucose monitoring connected to smart insulin pumps/pens are now available, more than 70% of individuals with T1D do not meet the recommended glucose targets. Intensification of treatment with insulin is associated with an increased risk of hypoglycemia and weight gain. Furthermore, in T1D, there is an increasing prevalence of obesity, dyslipidemia, depression, and other risk factors for cardiovascular disease (CVD). The paracrine regulation of glucagon secretion by insulin in the islet environment is also lost in T1D leading to hyperglucagonemia. Together with these drawbacks, insulin resistance (IR) is present from the early stages of the disease contributing substantially to metabolic dysregulation and β-cell loss (1). The treatment of T1D is therefore staggering, and the way to tackle this is by assigning therapeutic strategies that include targets not only within but also beyond glycemic control.

Coxsackievirus B infection and pathogenesis of type1 diabetes

Epidemiological and experimental studies suggest that enteroviruses (EV) and particularly coxsackievirusesB (CVB) are likely to trigger or accelerate the onset of islet autoimmunity and the development of type1 diabetes (T1D) in genetically susceptible individuals. Several mutually non-exclusive mechanisms have been proposed to explain the involvement of CVB in the pathogenesis of T1D. CVB can infect and persist in the intestine, thymic cells, monocytes/macrophages, ductal cells and pancreatic β-cells, which leads to structural or functional alterations of these cells. A chronic inflammatory response and disruption of tolerance towards β-cells due to CVB infections are able to promote the recruitment and activation of pre-existing autoreactive T-cells and the destruction of β-cells. Vaccine or therapeutic strategies to control EV infections have been developed and open perspectives for the prevention or treatment of T1D.