Antidiabetic Treatment Research Articles

Obesity and type2diabetes (Update 2023)

The body mass index (BMI) is avery crude measure of body fatness in individuals. Even normal weight persons can have too much body fat in cases of alack of muscle mass (sarcopenia), which is why additional measurements of waist circumference and body fatness, e.g. bioimpedance analysis (BIA), are recommended. Lifestyle management including nutrition modification and increase in physical activity are important measures for the prevention and treatment of diabetes. Regarding the treatment of type2diabetes, body weight is increasingly used as asecondary target parameter. The choice of anti-diabetic treatment and additional concomitant therapies is increasingly influenced by body weight. The importance of modern GLP‑1 agonists and dual GLP‑1 GIP agonists increases since these drugs target obesity and type2diabetes. Bariatric surgery is at present indicated with aBMI > 35 kg/m2 with concomitant risk factors, such as diabetes and can lead at least to partial diabetes remission but has to be incorporated into an appropriate lifelong care concept.

DPP IV Inhibitors Activities Prediction as An Anti-Diabetic Agent using Particle Swarm Optimization-Support Vector Machine Method

Diabetes mellitus is a chronic illness that can affect anyone, while the medicine that can entirely cure diabetes has not been discovered yet. Dipeptidyl Peptidase IV (DPP IV) inhibitor is one of the agents with potency as an anti-diabetic treatment. In this work, we utilized the machine learning method to predict the activity of DPP IV as an anti-diabetic agent. We combined Particle Swarm Optimization (PSO) method for features selection and the Support Vector Machine (SVM) for the prediction model. Three SVM kernels, i.e., radial basis function (RBF), polynomial, and linear, were utilized, and their performance was compared. A Hyperparameter tuning procedure was conducted to improve the performance of models. According to the results, we found that the best model obtained from SVM with RBF kernel with the value R2 of train and test set are 0.79 and 0.85, respectively.

Age-dependent prevalence of type 2 diabetes, cardiovascular risk profiles and use of diabetes drugs in Germany using health claims data.

This study evaluates type 2 diabetes mellitus (T2DM) prevalence in Germany, focusing on patients at risk for, or with already established, cardiovascular disease (CVD), as well as their antidiabetic and cardiovascular treatments. Using anonymized claims data from the WIG2 database, we calculated 2018 T2DM prevalence, extrapolating rates to the German statutory health insurance population. In the study period, 3 376 228 patients were eligible in the database. Forming antidiabetic medication groups, we evaluated treatment regimens of patients at risk for, or with already established CVD, based on the REWIND study criteria. We also evaluated their CVD medication prescriptions. Statutory health insurance extrapolated T2DM prevalence was estimated at 11.9%, with higher prevalence rates in older patients. When only patients with prescriptions of antidiabetic drugs were included, prevalence was 7.6%. At least 94% of patients with T2DM medication had at least one risk factor (without considering age) according to REWIND criteria, while 67%-80% had at least two risk factors depending on treatment received. Patients taking insulin combined with oral therapy comprised the largest proportion of patients with at least two REWIND risk factors. Approximately 85% of all patients with T2DM in the population were treated with antihypertensive medication. T2DM is widespread and affects older patients particularly. Most patients with T2DM had at least one CV risk factor, and about half already had established CVD. Early prevention of CVD, which disproportionately affects patients with T2DM, is necessary. Furthermore, the treatment of older patients with T2DM with insulin is still common and needs further evaluation.

Type 2 Diabetes and Parkinson's Disease: A Focused Review of Current Concepts.

Highly reproducible epidemiological evidence shows that type 2 diabetes (T2D) increases the risk and rate of progression of Parkinson's disease (PD), and crucially, the repurposing of certain antidiabetic medications for the treatment of PD has shown early promise in clinical trials, suggesting that the effects of T2D on PD pathogenesis may be modifiable. The high prevalence of T2D means that a significant proportion of patients with PD may benefit from personalized antidiabetic treatment approaches that also confer neuroprotective benefits. Therefore, there is an immediate need to better understand the mechanistic relation between these conditions and the specific molecular pathways affected by T2D in the brain. Although there is considerable evidence that processes such as insulin signaling, mitochondrial function, autophagy, and inflammation are involved in the pathogenesis of both PD and T2D, the primary aim of this review is to highlight the evidence showing that T2D-associated dysregulation of these pathways occurs not only in the periphery but also in the brain and how this may facilitate neurodegeneration in PD. We also discuss the challenges involved in disentangling the complex relationship between T2D, insulin resistance, and PD, as well as important questions for further research. © 2022 International Parkinson and Movement Disorder Society.

Acute Pancreatitis; New Methods for Understanding an Old Problem

Acute pancreatitis is responsible of considerable amount of hospital admissions, and therefore, significant morbidity and mortality in the modern world. The disease poses a significant burden to healthcare systems since its incidence have been rose to as high as 45 subjects in every 100000 population since early 1990s. Excessive alcohol consumption and biliary tract disorders are two most common causes of acute pancreatitis. Other etiological factors include dyslipidemia, surgery or traumatic injury of abdomen, hypercalcemia, infections, inflammation related to vasculitis, tumors of pancreas or ampulla and various drugs. Drugs that cause acute pancreatitis are anti-neoplastic agents (i.e., asparaginase, azathioprine, mercaptopurine), antibiotics (i.e., tetracycline, isoniazid, sulfonamides, metronidazole), anti-inflammatory drugs (i.e., celecoxib, meselamine, leflunomide), thiazide diuretics, anti-diabetic treatments (i.e., exenatide, sitagliptin), and anti-hypertensive and anti-hyperlipidemia therapies (methyl dopa, enalapril, fenofibrate, simvastatin). Medical interventions such as enteroscopy, peritoneal dialysis, endoscopic retrograde colangio-pancreatography, may also induce acute pancreatitis. Cystic fibrosis and pancreas divisum are also contributing conditions to acute pancreatitis.

Attrition and social vulnerability during 2-year-long structured care in type 2 diabetes, the ERMIES randomized controlled trial

BackgroundDiabetes self-management education is exposed to attrition from services and structured ambulatory care. However, knowledge about factors related to attrition in educational programs remains limited. The context of social vulnerability due to low income may interfere. The aim of this study was to identify the sociodemographic, clinical, psychometric, and lifestyle factors associated with attrition from the ERMIES multicentre randomized parallel controlled trial (RCT) that was interrupted due to the combination of both slow inclusion and high attrition.MethodsThe ERMIES trial was performed from 2011 to 2016 on Reunion Island, which is characterized by a multicultural population and high social vulnerability. The original objective of the RCT was to test the efficacy of a2-year structured group self-management education in improving blood glucose in adult patients with nonrecent, insufficiently controlled type 2 diabetes. One hundred participants were randomized to intensive educational intervention maintained over two years (n = 51) versus only initial education (n = 49). Randomization was stratified on two factors: centres (five strata) and antidiabetic treatment (two strata: insulin-treated or not). Sociodemographic, clinical, health-care access and pathway, psychometric and lifestyle characteristics data were collected at baseline and used to assess determinants of attrition in a particular social context and vulnerability. Attrition and retention rates were measured at each visit during the study. Multiple correspondence analysis and Cox regression were performed to identify variables associated with attrition.ResultsThe global attrition rate was 26% during the study, with no significant difference between the two arms of randomization (9 dropouts out of 51 patients in the intervention group and 17 out of 49 in the control group). Male gender, multiperson household, low household incomes (< 800 euros), probable depression and history of hospitalization or medical leave at inclusion were associated with a higher risk of attrition from the study in multivariate regression.ConclusionsSocial context, vulnerability, and health care history were related to attrition in this 2-year longitudinal comparative study of structured care. Considering these potential determinants and biases is of importance in scaling up interventions aimed at the optimization of long-term care in type 2 diabetes mellitus.Trial registrationID_RCB number: 2011-A00046-35, Clinicaltrials.gov number: NCT01425866 (Registration date: 30/08/2011).Source of funding: Ministry of Health, France.

Effect of Anti-Diabetic Medications on Dental Implants: A Scoping Review of Animal Studies and Their Relevance to Humans.

Animal studies have ascertained that hyperglycemia adversely affects bone metabolism and dental implant osseointegration. However, diabetic patients show low occurrence of unfavorable hard or soft peri-implant tissue changes, differences that are possibly due to treatment with anti-diabetic medications. This scoping review aimed to systematically examine the effects of these drugs on implant outcomes and explore the predictive modality of animal studies for clinical practice according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Three electronic databases (MEDLINE, EBSCOHost, and Cochrane) were searched according to the PRISMA-ScR standards for studies on diabetic animals that received titanium implants and anti-diabetic treatments. Risk assessment was performed using the SYRCLE Risk-of-Bias (RoB) tool. Twenty-one papers were included, encompassing six types of medications. Fifteen studies were on T1DM animals, and only six involved T2DM models. T1DM animals were treated with non-insulin drugs in four investigations, while insulin was utilized in 11 other studies. In T2DM experiments, five administered non-insulin drugs, and only one applied locally delivered insulin. Only insulin in T1DM studies produced a positive influence on bone-implant contact (BIC), bone mineral content, and removal torque values. Inappropriate drug selection, inadequate glycemic control, and high RoB depict a mismatch between the research focus and the translational rationale to clinical practice. There remains a knowledge gap regarding T2DM investigations due to the lack of studies. More data are needed concerning intraoral implants and the performance of osseointegrated implants in patients with a later onset of diabetes. Future research should reflect the pathophysiology and treatment of each type of diabetes to ensure clinical applicability.

Impairment in insulin secretion without changes in insulin resistance explains hyperglycemia in patients with acromegaly treated with pasireotide LAR.

Pasireotide is a second-generation somatostatin receptor ligand (SRL) used for treating acromegaly. Its clinical use is limited by adverse effects on glucose homeostasis. The aim of this study was to evaluate longitudinal changes in beta-cell function and insulin sensitivity associated with pasireotide in patients not controlled by first-generation SRLs. We performed a retrospective study. The efficacy (growth hormone (GH)/insulin-like growth factor (IGF-1) concentrations; tumor size) and effect on glucose homeostasis were analyzed in 33 patients. Longitudinal data on oral glucose tolerance tests were available before, shortly (mean ± s.d., 6.1 ± 3.8 months) and long term (24.4 ± 11.1 months) after initiation of pasireotide in 14 patients. Insulin secretion (insulinogenic index; disposition index) and insulin sensitivity were calculated by validated indices. Pasireotide-induced diabetes occurred in 12 patients (36%). It was mediated by impaired insulin secretion, which occurred shortly after initiation of treatment and then remained stable on long term (insulinogenic index, median (min; max), 80 (12; 542) vs 16 (6.4; 101) vs 25 (3.7; 396) pmol/mmol, respectively; P = 0.028; disposition index, 1.45 (0.42; 4.88) vs 0.53 (0.17; 2.63) vs 0.60 (0.22; 1.71), respectively; P = 0.024). No significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia and the need for antidiabetic treatment. Worsening of glycemic control during pasireotide therapy is caused by an impaired insulin secretion, whereas insulin sensitivity is not affected. These findings might be important for the choice of antidiabetic treatment for pasireotide-induced hyperglycemia. Pasireotide, a second-generation SRL used for treating acromegaly, may be associated with glucose metabolism impairment. In a retrospective study of 33 patients, we observed that treatment with pasireotide was associated with normalization of serum IGF-1 in almost 60% of patients, but one-third of patients developed diabetes. In the patients who stopped pasireotide because of hyperglycemia, HbA1c promptly decreased. Longitudinal data in 14 patients show that diabetes is mediated by impaired insulin secretion, which occurred shortly and then remained stable on long term, while no significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-1 concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia.

Metformin in pregnancy and risk of abnormal growth outcomes at birth: a register-based cohort study

IntroductionWe previously reported an increased risk of being small for gestational age (SGA) and a decreased risk of being large for gestational age (LGA) after in utero exposure to metformin...

Sleep disordered breathing and haemoglobin A1c levels within or over normal range and ageing or sex differences: the Nagahama study.

Recently an association between blood glucose dysregulation and sleep disruption was suggested. The association between sleep disordered breathing, most of which is due to obstructive sleep apnea (OSA) in the general population, and diabetic severity, as well as the impact of antidiabetic treatment, remains unclear. This study aimed to investigate these associations as well as age and sex differences. This cross-sectional study evaluated 7,680 community participants as the main cohort (population-based cohort). OSA was assessed by the 3% oxygen desaturation index from pulse oximetry, which was corrected for sleep duration obtained by wrist actigraphy. For arguing the limitations for using pulse oximetry, 597 hospitalised patients, who were assessed by the apnea-hypopnea index from attended polysomnography, were also evaluated as the validation cohort (hospital-based cohort). Moderate-to-severe OSA was more prevalent as haemoglobin A1c (HbA1c) levels increased (<5.6%/5.6%-<6.5%/6.5%-<7.5%/≥7.5%, respectively) in both cohorts (p < 0.001), but only in those without antidiabetic treatment. The HbA1c level was an independent factor for moderate-to-severe OSA (population-based cohort, odds ratio [OR] 1.26, 95% confidence interval [CI] 1.10-1.45; hospital-based cohort, OR 1.69, 95% CI 1.22-2.33, per 1% increase). These associations were more prominent in the middle-aged (aged <60 years) than in the elderly (aged ≥60 years) and in women than in men in both cohorts. The prevalence of moderate-to-severe OSA in patients with antidiabetic treatment in the hospital-based cohort was ≥75% regardless of HbA1c levels. In conclusion, an association between the prevalence of OSA and HbA1c level even within or over the normal range was found only in patients without antidiabetic treatment and was more prominent in the middle-aged and in women.

Onset and mortality of Parkinson’s disease in relation to type II diabetes

ObjectivesThere is growing evidence that Parkinson’s disease and diabetes are partially related diseases; however, the association between the two, and the impact of specific treatments, are still unclear. We evaluated the effect of T2D and antidiabetic treatment on age at PD onset and on all-cause mortality.Research design and methodsThe standardized rate of T2D was calculated for PD patients using the direct method and compared with subjects with essential tremor (ET) and the general Italian population. Age at onset and survival were also compared between patients without T2D (PD-noT2D), patients who developed T2D before PD onset (PD-preT2D) and patients who developed T2D after PD onset (PD-postT2D).ResultsWe designed a retrospective and prospective study. The T2D standardized ratio of PD (N = 8380) and ET (N = 1032) patients was 3.8% and 6.1%, respectively, while in the Italian general population, the overall prevalence was 5.3%. In PD-preT2D patients, on antidiabetic treatment, the onset of PD was associated with a + 6.2 year delay (p < 0.001) while no difference was observed in PD-postT2D. Occurrence of T2D before PD onset negatively affected prognosis (adjusted hazard ratio = 1.64 [95% CI 1.33–2.02]; p < 0.001), while no effect on survival was found in PD-postT2D subjects (hazard ratio = 0.86, [95% CI 0.53–1.39]; p = 0.54).ConclusionsT2D, treated with any antidiabetic therapy before PD, is associated with a delay in its onset. Duration of diabetes increases mortality in PD-preT2D, but not in PD-postT2D. These findings prompt further studies on antidiabetic drugs as a potential disease-modifying therapy for PD.

Improved metabolic efficacy of a dual amylin and calcitonin receptor agonist when combined with semaglutide or empagliflozin

Pharmacotherapies for obesity and type 2 diabetes (T2D) are thought to bridge the gap between lifestyle modification and the weight loss obtained with bariatric surgery. Although the effect of monotherapies, namely amylin and glucagon-like peptide-1 receptor (GLP-1R) agonists, has shown great potential, combination therapy is now becoming a strategy to optimize efficacy for weight management while minimizing adverse effects. This study investigated a dual amylin and calcitonin receptor agonist (DACRA); KBP-066A in combination with the GLP-1R agonist semaglutide or the sodium-glucose co transporter-2 inhibitor (SGLT2i) empagliflozin for anti-obesity and anti-diabetic treatment. The effect of KBP-066A, semaglutide, and empagliflozin alone and in combination was studied with respect to their impact on body weight, food intake, and glucose metabolism in high-fat diet (HFD) and Zucker diabetic fatty (fa/fa) (ZDF) rats. Treatment with KBP-066A and semaglutide lowered body weight by 13% and 9.7%.In contrast, a combination of both KBP-066A + semaglutide reduced body weight by 21% in HFD rats demonstrating superiority compared to monotherapies alone. A combination of KBP-066A with semaglutide or empagliflozin significantly lowered fasting blood glucose, and HbA1C (%) levels in ZDF rats. The complementary action by KBP-066A to GLP-1R agonist and SGLT2i on BW, food intake and glucose control endorsed the potential of DACRAs as an add-on therapy to therapeutic options for T2D and obesity.

In Vivo study of Antidiabetic Activity from Ethanol Extract of Clitoria ternatea L. Flower

Background: Clitoria ternatea L. or telang flower is a plant whose all parts have benefits for the human body. The benefits of telang flower include antioxidant, antidiabetic, antiobesity, anticancer, anti-inflammatory, antibiotic and hepatoprotective agent. Clitoria ternatea L. flower as an antidiabetic treatment works by increasing insulin secretion, inhibiting the formation of advanced glucose end products, as well as inhibiting the work of enzymes involved in the production of glucose in the blood. In this study using an experimental method, using 25 mice which were divided into 5 groups. The negative control group (aquadest), the positive control group (glibenclamide 5 mg), and the three groups with variations in the dose of 96% ethanol extract of telang flower 200, 400, 600 mg/kg BW. The results: The results showed that the negative control group did not experience a decrease in blood sugar levels; the positive control group by giving glibenclamide 5 mg experienced a decrease in blood sugar levels of up to 48.6 mg/dl. In 200 mg dose extract; 400; 600 mg of tested animals showed a decrease in blood sugar up to 48.2 mg/dl, 31.2 mg/dl, 43 mg/dl respectively. The conclusion: Based on the data obtained, it was then analyzed statistically using the One Way ANOVA test, resulting in a significant value &lt;0.05, then the Kruskal-Wallis Test was carried out. It could be concluded that there was a significant difference in decreasing blood sugar levels. Different dose of Clitoria ternatea L. extract gives a significant effect on reducing blood sugar levels.&#x0D; Keywords: Antidiabetic, Extract, Clitoria ternatea L., Flower

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

NAFLD as the metabolic hallmark of obesity.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, associated with a high risk of progression to NASH, liver cirrhosis and hepatocarcinoma. Its prevalence is closely related to obesity (understood as adipose-based disease and insulin resistance), which makes that at present NAFLD can be considered a metabolic dysfunction hallmark, regardless of the body mass index. Despite being such a prevalent condition, with such severe consequences, at present there are no reliable biomarkers for its diagnosis or specific treatment. Significant and sustained weight loss, as well as some antidiabetic treatments, has shown promising results for NAFLD but data needs confirmation in larger clinical trials and longer follow-up. Efforts should be made for a better and more accurate baseline diagnosis (including large-scale genetics), identification of patients at higher risk for progression to NASH as well as adequate treatment, to allow us to offer a personalized approach in NAFLD in the context of precision medicine.

Ethnic and socioeconomic disparities in initiation of second-line antidiabetic treatment for people with type 2 diabetes in England: A cross-sectional study.

To assess any disparities in the initiation of second-line antidiabetic treatments prescribed among people with type 2 diabetes mellitus (T2DM) in England according to ethnicity and social deprivation level. This cross-sectional study used linked primary (Clinical Practice Research Datalink) and secondary care data (Hospital Episode Statistics), and the Index of Multiple Deprivation (IMD). We included people aged 18 years or older with T2DM who intensified to second-line oral antidiabetic medication between 2014 and 2020 to investigate disparities in second-line antidiabetic treatment prescribing (one of sulphonylureas [SUs], dipeptidyl peptidase-4 [DPP-4] inhibitors, or sodium-glucose cotransporter-2 [SGLT2] inhibitors, in combination with metformin) by ethnicity (White, South Asian, Black, mixed/other) and deprivation level (IMD quintiles). We report prescriptions of the alternative treatments by ethnicity and deprivation level according to predicted percentages derived from multivariable, multinomial logistic regression. Among 36 023 people, 85% were White, 10% South Asian, 4% Black and 1% mixed/other. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by ethnicity were 21% (95% confidence interval [CI] 19-23%), 20% (95% CI 18-22%), 19% (95% CI 16-22%) and 17% (95% CI 14-21%) among people with White, South Asian, Black, and mixed/other ethnicity, respectively. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by deprivation were 22% (95% CI 20-25%) and 19% (95% CI 17-21%) for the least deprived and the most deprived quintile, respectively. When stratifying by prevalent cardiovascular disease (CVD) status, we found lower predicted percentages of people with prevalent CVD prescribed SGLT2 inhibitors compared with people without prevalent CVD across all ethnicity groups and all levels of social deprivation. Among people with T2DM, there were no substantial differences by ethnicity or deprivation level in the percentage prescribed either SGLT2 inhibitors, DPP-4 inhibitors or SUs as second-line antidiabetic treatment.

Adherence to antidiabetic treatment among patients managed in primary care centres in Spain: the INTENSE study

AimsTo determine the degree and factors related to non-insulin antidiabetic drug (NIAD) adherence in people with type 2 diabetes mellitus (DM2) treated in primary carecentres in Spain. Methods: We did a cross-sectional study. During the study visit, variables related todifferent clinical characteristics, Adherence to Refills and Medications Scale Spanishversion (ARMS-e) and usage of NIAD were collected. We estimated the adherence toNIADs using the proportion of days covered (PDC) equation. Results: In total, 515 participants were included in the study. The mean PDC ratio was70.6 ( ± 28.9), and 50.5% (260) were classified as good adherent (PDC ≥80). Good adherence was highest among users of metformin (67.3%) and lowest among the participants using thiazolidinedione (0.8%). The score for ARMS-e was higher in the poor adherence group. In the multivariable analysis, HbA1c and the use of GLP1-RA or SGLT-2i were negatively associated with good adherence (odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.54, 0.82, OR: 0.20, 95%CI: 0.08, 0.46; OR: 0.56, 95%CI: 0.35, 0.89, respectively). Conclusions: Adherence to NIADs observed in our study is far from optimal. HbA1c and ARMS-e items could be used as adherence indicators to encourage treatment changes to improve T2DM control.

RF28 | PSUN183 Intestinal microbiota composition in patients with type 2 diabetes and effects of 12 weeks of oral anti-diabetic treatment

Abstract Introduction The cause-effect relationships of dysbiosis and type 2 diabetes are complex and remain to be elucidated, very likely a two-way interaction. The aim of the study was to evaluate intestinal microbiota composition in patients with type 2 diabetes. Material and Methods This is a case-control study among patients with type 2 diabetes. Individuals were eligible if they were aged ≥18 years, were newly diagnosed with type 2 diabetes, had HbA1c levels ≥6.5 and ≤10.0%, and have been treated for oral antidiabetic agents for 3 months. The primary endpoint was the change from baseline in intestinal microbiota compositon after 12 weeks of treatment and comparison with healthy controls. Secondary endpoints were; change from baseline in intestinal microbiota composition after 12 weeks of oral antidiabetic monotherapy and comparison with healthy controls. A minimum of 5 mL fresh stool sample was collected at Day O of the study and 12 weeks later in a 15 mL Falcon tube and rapidly transferred to −80 °C to be stored in an upright position until DNA extraction. The V3 and V4 regions of the 16S rRNA gene were amplified following the 16S Metagenomic Sequencing Library Preparation. RESULTS: During the study period, 44 eligible patients were planned to enroll the study. Detailed analysis has been performed in 24 patients with type 2 diabetes (receiving oral antidiabetic treatment, metformin or linagliptin) and 10 age-matched healthy controls. The Chao-1 and Shannon Index were lower in the type 2 diabetes group before and after treatment groups (p&amp;lt;0.01 for both). PCoA plots were constructed to demonstrate separation of groups of samples for unweighted UniFrac distance, weighted UniFrac distance, and Bray–Curtis dissimilarity distance and no statistically significant differences between or within the type 2 diabetes and healthy control groups. At the first visit (before treatment), at phylum level, Bacteroidetes abundance have been observed in diabetic group, while Actinobacteria and Firmicutes in healthy controls. At genera level, we observed Gemmiger and Collinsella predominance in diabetes group; however, Faecalibacterium, Bacteroides and Alistipes in healthy controls. After 12 weeks of treatment, at genera level, Lactobacillus, Rothia and Collinsella increased in type 2 diabetes group however, microbiota composition was still different comparing the healthy controls. In patients receiving 12 weeks of metformin, Prevotella and Lactobacillus increased at genera level while Dialister and Ruminocococcus decreased. DISCUSSION: We report that there is a substantial change in the composition of the gut microbiota in patients with type 2 diabetes. We observed the beneficial effects as relative abundance of short chain fatty acid producing bacteria increased (eg, Prevotella, Lactobacillus) in metformin group. The interaction of the anti-diabetic drugs with gut microbiota have been less studied, further studies will highlight the clinical effect of these alteration in intestinal microbiota composition in diabetes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:37 p.m. - 12:42 p.m.

Clinical Utility of a Digital Therapeutic Intervention in Indian Patients With Type 2 Diabetes Mellitus: 12-Week Prospective Single-Arm Intervention Study.

Patients with type 2 diabetes mellitus (T2DM) having elevated levels of blood glucose and glycated hemoglobin (HbA1c) are at higher risk of macro- and microvascular complications. Nonetheless, the goal of achieving glycemic control cannot be met with the use of pharmacotherapy alone. The recent emergence of digital therapeutic tools has shown the possibility of improving the modifiable risk factors and self-management of diabetes. The aim of this study was to examine the clinical utility of a digital therapeutic intervention as an add-on therapy to achieve glycemic control in patients with T2DM. This was a 12-week prospective, single-arm digital intervention study in patients with T2DM receiving regular antidiabetic treatment. The eligibility criteria included male and female patients with HbA1c≥6.5%, functional English literacy, and a mobile phone capable of running the intervention app. Outcome measures of the study were mean changes in HbA1c, fasting blood glucose (FBG), postprandial blood glucose (PPBG), BMI, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index at the end of 12 weeks. A total of 128 participants completed the study period of 12 weeks. There were 54.7% (70/128) men and 45.3% (58/128) women with a mean age of 48.48 years (SD 10.27). At the end of 12 weeks, the mean change in HbA1c, FBG, PPBG, and BMI for the overall study population was -0.84% (P<.001), -8.39 mg/dl (P=.02), -14.97 mg/dl (P<.001), and -0.24 kg/m2 (P=.06), respectively. Among the participants showing improvement in the HbA1c value at the end of 12 weeks (responders), the mean change in HbA1c, FBG, PPBG, and BMI was -1.24% (P<.001), -12.42 mg/dl (P=.003), -21.45 mg/dl (P<.001), and -0.34 kg/m2 (P=.007), respectively. There was an increase in HOMA-IR values for the overall study population (0.54, P=.29). HbA1c response showed a significant association with a baseline HbA1c level ≥7.5%, no prior history of smoking, and no prior COVID-19 infection, as well as with higher levels of program engagement. A digital therapeutic intervention when used alongside standard medications significantly reduces HbA1c, FBG, and PPBG levels in patients with T2DM.

Metformin therapy as a strategy to compensate anti-VEGF resistance in patients with diabetic macular edema.

Diabetic macular edema (DME) is the complication of diabetic retinopathy, the leading cause of vision loss among diabetic patients. Metformin is the main antidiabetic treatment. It is preferable for its great anti-angiogenic and anti-inflammatory effects. Anti-vascular endothelial growth factor (VEGF) therapy is the preferable treatment for DME despite its lack of convincing results in some patients. To assess whether the combination of metformin and anti-VEGF drugs may decrease the risk of anti-VEGF resistance among DME patients. We included DME patients with a central retinal thickness (CRT) ≥ 250 μm who consecutively underwent at least 3 anti-VEGF therapies from January 1, 2020, to December 30, 2021. Anti-VEGF resistance was defined as persistent macular edema with decreased CRT ≤ 25% after 3 anti-VEGF injections. 109 patients were considered for this research, of whom 65 (59.6%) were resistant to anti-VEGF therapy. The mean CRT of the non-metformin group decreased from 344.88 ± 129.48 to 318.29 ± 123.23 (20.85%) and from 415.64 ± 144.26 to 277.11 ± 99.25 (31.51%) (P = .031) in the metformin group. Moreover, the metformin group had fewer resistant patients than the non-metformin, 24 (45.3%) versus 41 (73.2%). Furthermore, a considerable gain in visual acuity was observed in both groups, with a BCVA gain of 40.41% in the metformin group and 39.9% in the non-metformin group. Metformin may be combined with an anti-VEGF drug to minimize the risk of anti-VEGF resistance among DME patients. Moreover, it can serve to design effective therapeutic deliveries.