Antihyperglycemic Research Articles

12524 Predictive Factors For Type 2 Diabetes Remission: Insights From A Digital Twin Intervention Program At 18 Months

Abstract Disclosure: P. Shamanna: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. M. Thajudeen: None. A. Balasubramanian: None. S.R. Joshi: None. Background and aims: Digital twin (DT) platform uses Artificial Intelligence (AI) and Internet of Things, to integrate multi-dimensional data for precision nutrition and health recommendations via the mobile app. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Evidence suggests that remission is more likely in individuals with early type 2 diabetes (T2D) who are not using insulin therapy and who can engage in significant weight loss. We evaluated the predictive value of baseline parameters on T2D remission, including duration of diabetes, HbA1c levels, diabetic medications as drug count, and CGM metrics, with the objective to improvise the patient selection strategies for remission Methods We analyzed T2D patients (n=209) who completed 18 months of digital twin intervention. Potential predictors were examined by logistic regression analyses, with model performance evaluated by accuracy, precision, recall, and Area under the Receiver Operating Characteristic Curve (AUC-ROC) metrics. Results The model achieved an accuracy of 78.57%, precision of 79.41%, recall of 93.10%, and AUC-ROC of 0.745. Significant inverse associations with remission were observed for the duration of diabetes (OR: 0.74), baseline HbA1c (OR: 0.76), and the number of anti-diabetic medications as oral drugs (OR: 0.77), indicating decreased odds of remission with increasing values. Conversely, positive associations were found for Time Below Range 2 at baseline (OR: 1.22) and HOMA2IR at baseline (OR: 1.24), suggesting increased odds of remission with higher values in these metrics. We describe the Receiver Operating Characteristic (ROC) curve for the diabetes remission prediction model, with the area under the curve (AUC) indicating the model's discriminatory ability. The duration of diabetes emerged as the most significant negative predictor, followed by baseline HbA1c and the number of diabetic drugs, while counterintuitive findings like the positive association of baseline HOMA2IR with remission suggest areas for further investigation. Conclusion We identified baseline parameters significantly influencing the likelihood of T2D remission in people undergoing digital twin intervention. The odds ratios indicate the effect sizes of these predictors, highlighting the importance of personalized, data-driven treatment approaches that potentially enhance remission outcomes. Further validation of these findings in larger external cohorts would be useful. Presentation: 6/1/2024

8099 Pembrolizumab Induced Autoimmune Diabetes: An Abrupt Virulent Onset

Abstract Disclosure: H.F. Belal: None. N. Shaykh: None. A. Rajesh: None. J.M. Chehade: None. Background: Pembrolizumab is a programmed cell death protein 1 inhibitors (PD-1i) approved for the treatment of many solid cancers. Although thyroid abnormalities are among the most common endocrine adverse effects associated with PD-1i, insulin-dependent diabetes mellitus can also occur in up to 1% of patients treated with PD1-i.[1] Clinical Case: A 70-year-old female with past medical history of non-toxic multi-nodular goiter and surgical hypothyroidism was diagnosed with gastric cancer. She had no pancreatic abnormality on PET scan. Her management included four cycles of neo-adjuvant chemotherapy: fluorouracil, cisplatin, trastuzumab and pembrolizumab. She had no personal history of gestational diabetes. Prior to initiating neo-adjuvant chemotherapy her A1c was 5.9%. She was not prescribed any anti-diabetic medications. Her grandmother had type 2 diabetes mellitus. On exam her BMI was 23.73 kg/m². She had no acanthosis nigrans, skin tags or abdominal striae. Eighteen days after completing her second cycle of neo-adjuvant chemotherapy, she presented to the emergency department with nausea, vomiting, polyuria and confusion and was found to be in DKA. Her A1c during admission was 7.1%. Imaging revealed no pancreatitis. Labs showed suppressed C-peptide <0.1 ng/mL (1.1-4.4) in the setting of blood glucose 283 mg/dL (71-99). Her GAD-65 antibody was elevated at 902 U/mL (0.0-5.0). She was diagnosed with PD-1i induced autoimmune diabetes mellitus (PD-1i DM) and subsequently treated with basal and prandial insulin. Conclusion: The mechanism of PD-1i DM is unclear. A proposed mechanism is aberrant T cell activation towards pancreatic islet cells. One study found that 59% of patients with PD-1i DM presented with DKA.[1] In this study, the median time of PD-1i DM onset was 20 weeks after the first treatment cycle. Additionally, 40% of these patient had at least one positive pancreatic autoantibody. A recent meta-analysis found the relative risk of PD-1i DM to be 1.56 (95% CI = 0.95-2.57, P = 0.08).2 This relative risk increased to 2.06 (95% CI = 0.48-8.86, P = 0.33) when PD-1i were combined with cytotoxic T lymphocyte antigen-4 inhibitors.

6680 GLP-1 Agonists in Type 1 Diabetes - Indications and Use

Abstract Disclosure: P. Panjawatanan: None. N. Radovanovic: None. R.J. Comi: None. Introduction: Insulin therapy is the mainstream treatment in patients with Type 1 diabetes. The use of insulin, though mimicking normal physiology, is associated with weight gain. Glucagon-like peptide 1 (GLP-1) agonists are a class of antidiabetic medication that lowers blood sugar levels and helps promote weight loss. We propose that GLP-1 agonists can reverse the trend of weight gain and help lower hemoglobin A1C (A1C) levels in patients with Type 1 diabetes who were gaining weight. Method: A retrospective chart review was performed at a single institution’s endocrine practice over five years. Patients with Type 1 diabetes with concomitant GLP-1 agonists used for at least one year were included. Observed outcomes were the change in A1C, weight, and basal insulin use compared at baseline, 6 months, and 12 months using mixed models repeated measures. The result was reported as estimated means (95%CI). Statistical significance was determined by a p-value less than 0.05. Results: There were 49 patients included in the study. The mean age was 44.7 years old. There were 32 females (65.3%) and 17 males (34.7%). The mean duration of diabetes was 24.6 years. Thirty-five patients (71.4%) used insulin pumps, and fourteen (28.6%) were on multiple daily injections. Overall, patients had been gaining an average of 2.0 kg per year. After the treatment with GLP-1 agonists, weight was significantly reduced at 12 months (90.0 kg (95%CI 84.9-95.1), p<0.001) compared to baseline (97.6 kg (95%CI 92.7-102.5)). The A1C was significantly improved at 12 months (7.6% (95%CI 7.2-7.9), p<0.001) compared to the baseline (8.2% (95%CI 7.9-8.6)). Total daily basal dose was significantly reduced at 12 months (35.8 units (95%CI 29.8-41.9), p<0.001) compared to the baseline (39.2 units (95%CI 33.3-45.1)). The improvement in the parameters was more pronounced at 6 months after treatment but persisted at 12 months. Conclusion: Weight gain is a consequence of insulin usage in both Type 1 and Type 2 diabetes, which considerably impacts treatment outcomes and the development of comorbidities. We conclude that GLP-1 agonists are helpful to reverse the trend of weight gain and help lower A1C levels in patients with Type 1 diabetes who require life-long insulin treatment. Presentation: 6/3/2024

7672 Ketosis-Prone Diabetes - A Case Series

Abstract Disclosure: T. Ismail: None. A. Farooq: None. G. Acharya: None. J. Snitzer: None. Introduction Ketosis-prone diabetes (KPD) is a syndrome that primarily affects African Americans. It is characterized by ketoacidosis, which is like Type 1 Diabetes Mellitus (T1DM). KPD is unique because it lacks identifiable autoimmunity and has a relative insulin deficiency, resembling Type 2 Diabetes Mellitus (T2DM). Therefore, KPD is informally classified as Type 1.5 Diabetes Mellitus. However, the clinical course and outcomes of KPD are like those of T2DM, and managing blood sugar levels is possible through non-insulin antidiabetic medications and dietary interventions. Case Series: Our study involved six patients who were all of African-American ethnicity. There were an equal number of male and female patients, with ages ranging from 21 to 61 years. One patient had a BMI of 27.2, which is considered overweight, while the rest had a BMI in the obese category ory(BMI>30). Two out of six patients had a pre-existing diagnosis of type 2 diabetes mellitus (T2DM) before the initial diabetic ketoacidosis (DKA) event. One patient had prediabetes. All patients required hospitalization for ketoacidosis and hyperglycemia and were found to have a glycated hemoglobin (HbA1c) level of more than 10% during these DKA events. All patients received intravenous hydration and insulin drip treatment and were discharged with a combination of long and rapid-acting insulin regimens. Following the resolution of the first episode of diabetic ketoacidosis (DKA), all six patients experienced a decrease in their insulin requirements for optimal glycemic control. Currently, four patients have discontinued insulin entirely. Moreover, all six patients tested negative for the presence of GAD-65, insulin, and islet antigen-2 antibodies. Among the patients, only one had a previously established autoimmune disease, i.e., inflammatory bowel disease. None of the patients experienced a repeat episode of diabetic ketoacidosis. Conclusion: It is important to note that not all patients who present with Diabetic ketoacidosis have Type 1 Diabetes Mellitus (T1DM). Hence, checking auto-antibodies for T1DM before making a final diagnosis is crucial. C-peptide levels may not accurately reflect the degree of relative permanent insulin deficiency in this population if measured during or immediately after an episode of diabetic ketoacidosis due to glucose toxicity and other factors. Given its prevalence in obese individuals, weight loss through dietary modifications and GLP-1 receptor analogs may be beneficial. Presentation: 6/3/2024

Methanolic stem-bark extracts of Adansonia digitata modulates haematological and antioxidant parameters in streptozotocin-induced diabetic rats

Background and AimDiabetes mellitus is associated with haematological abnormalities and oxidative stress, contributing to disease progression and complications. Adansonia digitata, is a traditional medicinal plant well known for its potential therapeutic properties. This study investigates the effects of methanolic stem-bark extracts of Adansonia digitata on haematological and antioxidant status in streptozotocin-induced diabetic rats. Experimental ProcedureFourty-two wistar rats were distributed into 6 groups of 7 each. Group 1 served as normal control, group 2 to 6 animals were made diabetic by intraperitoneal administration of single dose of 50 mg kg-1 streptozotocin. Group 2 served as the negative control and did not receive treatment, group 3 served as the positive control and received 150 mg kg-1 metformin (Glucophage) (standard drug), while group 4, 5 and 6 received oral treatment of 100 mg kg-1, 200 mg kg-1 and 300 mg kg-1 of Adansonia digitata stem-bark methanolic extract respectively for 21days, after which the animals were sacrificed, and blood and liver were collected for haematological analysis including White Blood cell (WBC), red blood cell (RBC), haemoglobin (HGB), hematocrit (H CT), platelet (PLT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), total bilirubin (TB), direct bilirubin(DB) and indirect bilirubin (IB) concentration and antioxidant parameters including antioxidant enzymes [catalase (CAT) and superoxide dismutase (SOD) activities] and oxidative stress marker [thiobarbituric acid reactive substance (TBARS)]. ResultsSTZ administration evoked a marked (p < 0.05) decline in the level of WBC, RBC, HGB, PLT, LYM and MCV in the diabetic rats when compared with the normal control. Howbeit, treatment with methanolic extracts of adansonia digitata stem-bark led to a profound (p < 0.05) increase in concentrations of these parameters close to the normal. In addition, STZ caused a non-significant (p > 0.05) decrease in MCH and MCHC. On the contrary, STZ caused an insignificant (p > 0.05) increase in the levels of TB and DB, but a significant (p > 0.05) increase IDB level in the diabetic control group when compared with the normal control group, while treatment with stem-bark extracts resulted in a marked (p > 0.05) fall in IDB level. Furthermore, there was a marked (P < 0.05) reduction in the activity of hepatic CAT and SOD and a considerable (P < 0.05) elevation in Malondialdehyde (MDA) level in the hepatic tissue of the diabetic control. Nonetheless, Adansonia digitata stem-bark extracts profoundly (P < 0.05) raised the activities of the enzymes and concomitantly counteracted MDA level. The extract elicited strong potency at 300 mg kg-1 which is comparable to metformin (Glucophage). ConclusionConsequently, this study advocates for the utility of Adansonia digitata extracts for the development of novel drugs for combating diabetes mellitus, associated hematological and oxidative stress complications and other ailments. Further research is needed to evaluate the clinical relevance of these effects in human subjects and to provide information on the sustained efficacy of the extracts in chronic models. Significant statementOxidative stress and hematological abnormalities are two of the consequences linked to diabetes mellitus. Anaemia and poor blood coagulation are two haematological changes that increase the risk of diabetes-related illness and death. Furthermore, oxidative stress is essential to the pathophysiology of diabetic complications such as nephropathy and cardiovascular disease. In addition, there are reports on hematological and biochemical alterations in diabetic subjects arising from the intake of synthetic antidiabetic medications.. Consequent to the safety, ease of use, efficacy, and lack of cytotoxic side effects of plants’ herbs, the study of Adansonia digitata's methanolic stem-bark extracts on haematological and antioxidant parameters in streptozotocin-induced diabetic rats is of paramount importance as the extracts' capacity to modify these parameters, will lead to the development of novel drugs that cures anemia, other blood abnormalities, and oxidative stress linked to diabetes as well as other ailments.

Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial

Intense intermittent fasting regimens safely reduce weight to a similar extent as caloric restriction. A previous trial reported low-frequency 26-week intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) without significant weight loss. During fasting, human growth hormone (HGH) increases substantially, but whether basal HGH modifies the effect of fasting on outcomes of repeated fasting is unknown. In a post hoc analysis of a randomized controlled trial (registration: clinicaltrials.gov, NCT02770313, May 12, 2016), subjects (N = 68) were adults ages 21–70 years with modest cholesterol elevation, ≥1 metabolic syndrome component, available HGH measurements, no chronic disease, and no statin or anti-diabetes medication. Randomization was 1:1 to intermittent fasting (24-hour, water-only, twice-per-week for 4 weeks, then once-per-week for 22 weeks) or 26-week ad libitum control. General linear modeling evaluated the interaction of trial arm with baseline HGH for HOMA-IR changes. Subjects with lower baseline HGH had 26-week HOMA-IR changes (p = 0.003) of −1.04 ± 0.99 for fasting versus 0.60 ± 1.04 for controls. Subjects with higher baseline HGH had HOMA-IR changes (p = 0.26) of −0.69 ± 0.75 (fasting) and −0.42 ± 0.92 (controls). The interaction of fasting with lower baseline HGH was significant (p-interaction=0.004). Results were similar for insulin and glucose. Weight loss at 26 weeks was not significantly different between fasting and controls (−1.74 ± 4.81 kg vs. 0.21 ± 3.50 kg, p = 0.08) and was not correlated with changes in HOMA-IR, insulin, glucose, and HGH. In conclusion, lower baseline HGH modified the effect of low-frequency water-only 24-hour fasting in profoundly reducing HOMA-IR over 26 weeks compared both to controls and to fasting subjects with higher baseline HGH.

Effectiveness and Side Effect Incidence in a Real-World Digital Weight-Loss Service Using Compounded Semaglutide: A Retrospective Comparative Study

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were originally developed in the late 1980s as a class of antidiabetic medication. However, research over the past decade has found them to be a safe and effective weight-loss agent, which has led to the approval of GLP-1 RAs such as Semaglutide as a supplement to lifestyle obesity interventions in multiple countries. When Semaglutide has become commercially unavailable, digital weight-loss services (DWLSs) have prescribed a compounded form of the medication—a practice in which health professionals formulate a replica of the commercial medication to serve ongoing patient needs. Although compounding has been relatively common over the past century, prominent medical bodies have argued that compounding a relatively novel medication such as Semaglutide represents a major safety risk. This study retrospectively compared the weight and side effect outcomes of patients from a large Australian DWLS whose lifestyle coaching was supplemented with either compounded or pure Semaglutide (both groups following the same titration schedule). All data were extracted from the service’s central data repository. To be included in the weight loss analysis, patients needed to have received a minimum of four monthly medication orders between June 2023 and May 2024 and have submitted weight data between 90 and 150 days after the arrival of their first order. All patients who received at least one medication order within the same period were included in the side effect analysis. The mean four-month weight loss percentage was statistically lower in the compounded Semaglutide group (N = 923, M = 9.11, SD = ±5.76) compared to those in the pure Semaglutide group (n = 1858, M = 9.87, SD = ±6.46), t (2032) = −3.15, p = 0.0017. A statistically lower proportion of patients in the compounded Semaglutide group (71.61%) reported at least one side effect than patients in the pure Semaglutide group (77.40%) during the study period, X2 (1, N = 7683) = 32.32, p &lt; 0.001. When side effects were disaggregated into severity categories, a statistical difference was only observed in mild side effects, X2 (1, N = 7683) = 59.16, p &lt; 0.001. A significantly higher rate of patients from the pure Semaglutide group achieved the ten (50.54% vs. 44.64%), X2 (1, N = 7683) = 10.34, p &lt; 0.001, and fifteen (21.42% vs. 12.78%), X2 (1, N = 7683) = 30.43, p &lt; 0.001, percent weight loss thresholds than patients from the compounded Semaglutide group. The findings indicate that compounded Semaglutide can be used as a component of tightly controlled DWLSs with slightly less effectiveness and but with slightly lower side effect incidence when compared to pure Semaglutide.

From Glucose to Neuroprotection: Exploring Antidiabetic Medications as a Novel Approach to Alzheimer's Disease Treatment

From Glucose to Neuroprotection: Exploring Antidiabetic Medications as a Novel Approach to Alzheimer's Disease Treatment

The effects of metformin on inflammation and apoptosis in rats with preeclampsia.

Defined clinically by elevated blood pressure along with either proteinuria and/or maternal organ dysfunction, representing a major cause of morbidity and mortality pregnant women and newborns. Metformin (MET), an oral antidiabetic medication, has been shown to prevent preeclampsia (PE) through various mechanisms, including reducing inflammation, improving endothelial dysfunction, improving mitochondrial function, and altering cellular homeostasis and energy metabolism. Herein, we explored the role of MET in PE and its underlying molecular mechanisms using in in vivo experiments. RT-qPCR, Western blot (WB), and immunohistochemistry (IHC) were conducted to assess the mRNA or protein expression of genes related to mitochondrial apoptosis. Additionally, ELISA was conducted to quantify the expression of mitochondrial apoptosis and inflammation-related genes, as well as PE biomarkers. Treatment with MET in PE rats ameliorated hypertension and proteinuria, altered the expression of PE biomarkers, and significantly inhibited L-NAME-induced inflammation and cell apoptosis. MET modulated the levels of inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10, mitigating inflammation in PE rats. Furthermore, MET regulated mitochondrial outer membrane permeability (MOMP), thereby reducing cell apoptosis occurring in the mitochondrial pathway of PE rats. This study demonstrates that MET alleviates inflammation and cell apoptosis in PE rats by modulating the expression of inflammatory factors and MOMP. Our results indicate that MET has huge therapeutic potential against PE.

Metformin and vitamin D combination therapy ameliorates type 2 diabetes mellitus-induced renal injury in male Wistar rats.

Diabetic kidney disease is a major microvascular diabetes mellitus (DM) complication clinically associated with a gradual renal function decline. Although metformin is a common drug for managing DM, however, monotherapy treatment with any antidiabetic drug will necessitate dosage increment since type 2 DM (T2DM) deteriorates over time due to the increasing pancreatic β-cell dysfunction and will eventually require a combination therapy approach with another antidiabetic medication. Vitamin D is a food supplement that has been proven to have antidiabetic and reno-protective activities. Hence, we explore the combination of vitamin D and metformin on T2DM-induced renal dysfunction. Thirty male Wistar rats were randomized into five (5) groups: control, diabetes untreated, diabetics treated with metformin, vitamin D, and vitamin D + metformin. Vitamin D and metformin significantly reversed DM-induced hyperglycemia, electrolyte imbalance, and dyslipidemia. Also, vitamin D and metformin reversed T2DM-induced increase in serum creatinine and urea and renal lactate, LDH, and oxido-inflammatory response. These observed alterations were accompanied by an increase in proton pump activities and modulation of Nrf2/Nf-κB and XO/UA signaling. This study revealed that vitamin D and/or metformin ameliorated T2DM-induced renal injury.

Antidiabetic and Antihyperlipidemic Activity of Ethanolic Extract of Mentha viridis in Alloxan Induced Diabetic Rats

This research was designed to examine the phytochemicals of Mentha viridis (M. viridis) ethanolic extract and the antidiabetic and antihyperlipidemic activities in alloxan-induced animal models. Diabetes was induced chemically by administering a unit dose of alloxan at 120 mg/kg BW. After alloxan induction, hyperglycemic rats were dealt with ethanolic extract of leaf and whole plant, metformin, and a mixture of leaf extract with metformin and whole plant extract with metformin for two weeks. Ethanolic extract of leaf and whole plant, metformin, and a combination of both leaf and whole plant extract with metformin therapies reduced glucose levels in the blood compared with the diabetic negative control group after two weeks of treatment. However, among the therapies, the ethanolic leaf extract and the combination of whole plant extracts with metformin were found to be the most effective (p&amp;lt;0.05), with reductions of 62.82% and 72.89%, respectively. After diabetes induction, the serum level of TG (triglycerides), TC (total cholesterol), LDL-C (low-density lipoprotein-cholesterol) escalated notably (p&amp;lt;0.05), and HDL-C (high-density lipoprotein-cholesterol) level decreased remarkably (p&amp;lt;0.05) in hyperglycemic rats as opposed to healthy normal rats. Ethanolic leaf extract and a combination of whole plant extract with metformin significantly minimized the elevated extent of TG and LDL-C. They surged HDL-C, but the TC level was reduced by whole plant extract only after two weeks of treatment. The standard procedures were used to identify the phytochemical compounds of the medicinal plant M. viridis. The phytochemical compounds such as alkaloids, resins, tannins, phenols, flavonoids, steroids, and terpenoids appeared in the ethanolic leaf extract of M. viridis. The findings suggest that M. viridis might provide better glycemic control and hypolipidemic effect in diabetic rats when administered alone or combined with oral antidiabetic agents. Incorporating M. viridis extract with metformin in improving hyperglycemic and hyperlipidemic conditions in diabetic rats proves that M. viridis has a synergistic effect, which could enhance the antidiabetic activity of oral hypoglycemic agents.

Gout risk in adults with pre-diabetes initiating metformin

ObjectiveDespite the strong association between gout and pre-diabetes, the role of metformin in gout among individuals with pre-diabetes remains uncertain. We compared the incidence rates of gout in adults with...

Adherence to the nutritional recommendations according to diabetes status in Korean adults: a cross-sectional study

BackgroundNutritional therapy plays a crucial role in diabetes management. Assessing adherence to nutritional recommendations is critical for evaluating whether the current status of nutrition education is appropriate. This study aimed to evaluate adherence to nutritional recommendations according to diabetes status using data from the Korean National Health and Nutrition Examination Survey from 2016 to 2019.MethodsA total of 2,793 participants (55.4% male) were evaluated regarding their adherence to nutritional recommendations. The “aware” group comprised people who had been clinically diagnosed by a physician. The “treated” group comprised people receiving anti-diabetic medications. The “control” group comprised people who achieved an HbA1c level < 6.5%. The “educated” group comprised people who had received nutrition education or counseling at various locations.ResultsAmong the 1,918 individuals in the “aware” group, only 243 (8.7%) had received nutrition education. Adherence to nutritional recommendations was generally low, with people with diabetes showing slightly higher adherence to total energy intake (59.6% vs. 55.3%) and total sugar intake (88.0% vs. 84.5%) than people without diabetes. However, adherence to total carbohydrate intake was poor in both the treated and educated groups (34.3% and 26.0%, respectively) compared to the untreated and non-educated groups (44.4% and 36.0%, respectively).ConclusionsThese findings indicate inadequate nutritional management for people with diabetes in Korea. Nutrition education should be effectively strengthened to achieve nutritional goals.

Impact of glucagon-like peptide-1 receptor agonists on diabetic retinopathy: A meta-analysis of clinical studies emphasising retinal changes as a primary outcome.

To determine if glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with the development and progression of diabetic retinopathy (DR). A systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP-1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta-analysis was pooled using a random-effects model. Analysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP-1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP-1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01). Our findings indicate no elevated risk of incidence of DR linked to GLP-1RA compared to insulin. In fact, GLP-1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP-1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c - a phenomenon not specific to GLP-1RA and warrants further investigation.

Microbiota-derived PPAR-γ signaling and risk of bacterial enteric infection: insight from thiazolidinedione users in a US population-based study.

The ongoing antimicrobial resistant crisis heralds the need for new therapeutics against enteric infection. In mouse models, colon epithelial peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling limits oxygen and nitrate luminal bioavailability, thereby preventing bacterial pathogen colonization. However, whether this mechanism operates similarly in humans remains uncertain. To investigate, we used the cloud-based TriNetX Analytics Platform which aggregates health records from 117 million patients across 66 US healthcare organizations, to assess the risk of bacterial enteric infection among diabetic patients prescribed thiazolidinediones, a class of PPAR-γ agonists. Among 85,117 thiazolidinedione users, we observed a 22-49% lower risk of bacterial enteric infections compared to users of other anti-diabetes medications. This reduction in risk was consistent across high-risk individuals, regardless of sex or age. Similar results were replicated in high-risk patients when thiazolidinedione users were directly compared to those on DPP-4 inhibitors. These findings support the potential protective role of PPAR-γ signaling against bacterial enteric infection and call for further clinical investigation.

Comparison of Effectiveness of Insulin Glargine in Combination with Oral Hypoglycemic Agents Versus Continued Premixed Insulin in Indian Type II Diabetes Patients: Randomized Controlled Trial

Comparison of Effectiveness of Insulin Glargine in Combination with Oral Hypoglycemic Agents Versus Continued Premixed Insulin in Indian Type II Diabetes Patients: Randomized Controlled Trial

Cardiovascular medication adherence testing in patients living with HIV: A single-centre observational study.

People with HIV (PWH) are at an increased risk of developing cardiovascular disease (CVD) compared to HIV-negative individuals. We sought to evaluate the adherence to medications for CVD in PWH and identify factors associated with non-adherence to these medications. We conducted a cross-sectional study at the University Hospitals of Leicester NHS Trust between 16 April 2019 and 8 November 2022. We recruited consecutive PWH, who were attending a routine follow-up outpatient appointment and were prescribed at least one medication for CVD. In addition, we included urinary adherence results of patients with samples collected as part of routine clinical care. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess if their prescribed medications (antihypertensives, diuretics, beta-blockers, lipid-lowering agents, antiplatelets, anticoagulants, antidiabetic medications) were present in the participant's urine sample. Multivariable models were used to identify demographic or clinical features that were associated with non-adherence. A total of 162 PWH were included in the analysis. Median age was 55 [interquartile range (IQR): 50-61] years, 63% were male, average time living with HIV was 15 years (IQR: 11-19) and the majority (98%) had an undetectable HIV viral load. In approximately one-third of patients (59/162), at least one prescribed medication of interest was not detected in urine. Non-adherence to lipid-lowering agents was common (35/88, 40%). On multivariable logistic regression, the number of prescribed cardiovascular medications, was associated with medication non-adherence [medication non-adherence, per one medication increase: adjusted odds ratio (95% confidence interval) = 1.78 (1.34-2.36); p < 0.001]. We found sub-optimal adherence to medications for CVD in PWH. In order to maximize the clinical benefit of statin therapy in PWH, factors requiring consideration include: improved medication adherence, awareness of polypharmacy, educational interventions and quantitative assessment of sub-optimal adherence through chemical adherence testing.

Correlation of Serum Electrolyte Imbalances With Diabetic Duration and Medication Use: A Cross-Sectional Comparative Study.

Certain anti-diabetic medications may exacerbate electrolyte imbalances, potentially complicating glycemic control in diabetic patients. The present study aimed to correlate the serum electrolyte imbalances such as Na+, K+, Ca+2, Cl-, and Mg+2 with the duration of disease, glycemic control, and medication regimens. In this cross-sectional study, 31 patients with type 2 diabetes mellitus (T2DM) and 30 healthy controls, with mean ages of 52.06 and 48.5 years, respectively, were recruited based on eligibility criteria. Data on demographic information, medication history, and duration of diabetes were collected. Fasting blood sugar (FBS), postprandial blood sugar (PPBS), glycated hemoglobin (HbA1C), and serum electrolytes were measured. The data were statistically analyzed. The mean differences in serum electrolytes between T2DM patients and non-diabetic participants were compared using the Mann-Whitney U test, and correlation analysis was performed. A p-value of <0.05 was considered statistically significant. Around 9.6% of participants had diabetes duration of less than one year, while the majority (45%) fell within the 1-5-year duration range. Most diabetic patients (61.2%) exhibited poor glycemic control. Statistically significant differences were observed between the mean FBS, PPBS, and HbA1C levels of T2DM (150, 249, and 8.82, respectively) and control group (95, 114, and 5.52, respectively). Analysis of serum electrolytes showedstatistically significant differences with regard toNa+, K+, andCl-between the diabetic and control groups. Mean sodium and chloride levels were lower and potassium levels were higher in diabetic patients compared to the control group. Negative correlations were observed between sodium and chloride levels and duration of diabetes and HbA1C levels. The study reveals significant electrolyte imbalances in patients with T2DM, characterized by reduced sodium and chloride levels and elevated potassium levels compared to healthy controls. These alterations are closely associated with poor glycemic control and longer disease duration, emphasizing the importance of regular electrolyte monitoring in T2DM management to mitigate potential complications.

Use of Sodium-glucose cotransporter 2 (SGLT 2) inhibitor is associated with reduced emergency room visits and hospitalizations in patients with Chronic obstructive pulmonary disease (COPD) and type 2 Diabetes Mellitus

BackgroundThe Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) are a class of anti-diabetic medications that confer cardio-renal-metabolic (CRM) benefits. Emerging evidence also suggests that these agents provide better benefits for chronic pulmonary conditions, especially chronic obstructive pulmonary disease (COPD). Research questionWe aimed to assess the association between SGLT2i use and outcomes in patients with COPD and concomitant Type 2 Diabetes Mellitus (T2DM). Study design and methodsWe conducted a retrospective cohort study on adults with T2DM and COPD in a primary care clinic from January 01, 2019 to 01/01//2023. Patients were categorized into two groups based on SGLT2i use. We collected demographic information and outcomes such as emergency room (ER) visits, hospitalizations secondary to COPD exacerbation over the period of four years and time to hospitalization and ER visits. Chi-square analysis was used for categorical variables, whereas an unpaired t-test was used for continuous variables. Cox regression was performed to identify significant prognostic factors of hospitalization and ER visits. A Kaplan-Meir analysis was used to visualize the probability of non-hospitalization and the probability of not visiting the ER. Statistical significance was set at p-value <0.05. ResultsOf the 220 patients screened, 94 met the inclusion criteria, of which 20 patients (21.3 %) had SGLT2i use at admission, and 74 (78.7 %) did not. Baseline demographic information were well-matched between the two groups. SGLT2i use was associated with a significant reduction in ER visits (70 % vs. 97.3 %, p-0.001) and the number of hospitalizations (55 % vs 87.8 %, p-0.001). Further multivariate analysis showed lower hazards of hospitalization (adjusted HR-0.156; CI:0.073 to 0.331) and ER visits (HR)-0.232; CI:0.118 to 0.453) in patients on SGLT2i. InterpretationIn patients with T2DM with COPD, SGLT2i use was associated with reduced ER visits and hospitalizations related to COPD. This protective effect of SGLT2i could be explained by reduced systemic proinflammatory markers and increased anti-inflammatory markers via inhibition of Node like receptor protein 3(NLRP3) inflammasome activation in multiple tissues, including the lungs.

Pharmacological Treatment of Obesity: A Review of Current and Future Methods

Introduction and objective Obesity poses a significant public health challenge due to its association with an elevated risk of various chronic diseases, including cardiovascular conditions, type 2 diabetes, and overall mortality. While lifestyle modifications such as dietary changes and increased physical activity remain cornerstone interventions in obesity management, pharmacological treatments have emerged as an adjunctive approach to address this complex condition. The review aims to compare the effectiveness of current pharmacotherapy and show upcoming methods of treatment of obesity. Review methods The review was conducted by searching scientific publications in PubMed, Google Scholar, Clinicaltrials.gov, Summaries of Product Characteristics, URPL, FDA, and EMA databases. The articles on medications available in Poland for treating obesity and the latest clinical trials of upcoming drugs were analyzed, followed by a concise review of the collected data. Abbreviated description of the state of knowledge Currently, in the Polish market, medications available for obesity treatment include orlistat, the combination of naltrexone and bupropion, liraglutide, tirzepatide, and available as part of the target import - semaglutide. Promising clinical trials are being conducted on further medications for weight reduction, including retatrutide, orforglipron, cagrilintide, and amycretin. Regrettably, new and effective medications due to their high cost and insufficient funding. Summary New pharmacotherapy options for obesity, particularly anti-diabetic medications, are rapidly advancing. Glucagon-like peptide-1 (GLP-1) analogs have shown promising results in weight reduction, surpassing previous medications such as orlistat or naltrexone. Recent drugs offer weight loss ranging up to 25%. More studies are underway on novel and increasingly effective medications.