A case series of diabetic ketoacidosis associated with SGLT2 inhibitors

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly initiated as treatment for type 2 diabetes due to favourable cardiorenal characteristics. However, studies have identified an increased risk of diabetic ketoacidosis (DKA). We carried out a retrospective, case-based study at East and North Herts NHS Trust between February 2018 and December 2020. Fifteen cases of SGLT2i associated DKA were identified in people with presumed type 2 diabetes;33.3% were classed as euglycaemic DKA with a blood glucose of <11mmol/L. All cases were associated with a significant precipitating factor including diarrhoea, vomiting, reduced oral intake and sepsis. One case was related to COVID-19. Two people were subsequently found to have raised islet autoantibodies suggesting type 1 diabetes or latent autoimmune diabetes in adults. It is important that awareness of SGLT2i associated DKA is raised among users and health care practitioners, including the recognition of euglycaemic DKA. Sick day rules should be emphasised and reiterated at clinical encounters. Non-specialists in primary care, oncology and in perioperative settings should be empowered to advocate for temporary withdrawal and there should be readier access to blood ketone monitoring when required. When SGLT2i associated DKA occurs, due consideration should be given to evaluate the diabetes classification and investigate the circumstances of the event. Copyright © 2023 John Wiley & Sons.Copyright © 2023 John Wiley & Sons, Ltd.

An audit looking at why there is an increase in the number of patients with type 2 diabetes presenting in diabetic ketoacidosis in a tertiary hospital

Objectives: To investigate why a tertiary hospital has a high number of patients with type 2 diabetes presenting with diabetic ketoacidosis. Method(s): An audit was carried out looking at all of the inpatient admissions for diabetic ketoacidosis in patients with type 2 diabetes between 2021 and 2022. Any patient with a coding of diabetic ketoacidosis and type 2 diabetes had their inpatient clinical notes evaluated using the following criteria: 1) Were the criteria for diabetes ketoacidosis met? 2) Patient age. 3) Patient anti-diabetic medications. 4) If relevant, who prescribed a sodium-glucose cotransporter- 2 inhibitor and was sick day rule advice given? 5) Did the patient have a concurrent Covid-19 infection? Results: Almost a quarter of patients (24%) included in this audit did not fulfil the diagnostic criteria for diabetic ketoacidosis. For those that did: -Over a quarter of patients (26%) were on sodium-glucose cotransporter-2 inhibitors with the majority being commenced by GPs (81%). There was no documentation as to whether sick day rule advice had been given. -Only 7% of patients had a concurrent Covid-19 infection. -The majority of patients (68%) were aged less than 75 years. Conclusion(s): Coding on discharge summaries is important and junior doctors may need further guidance with regards to the diagnostic criteria for diabetic ketoacidosis. Sodium-glucose cotransporter-2 inhibitors inhibitors are a significant cause of diabetic ketoacidosis in patients with type 2 diabetes and patient sick day rule advice is needed prior to initiation. Covid-19 infection wasn't found to be a significant causative factor.

Clinical evolution of patients with AF and diabetes mellitus in the COVID-19 pandemic. REFADI Registry

Introduction and objectives: To analyze the evolution of patients with atrial fibrillation (AF) and diabetes in the mid-term follow-up during the COVID-19 pandemic and to describe its impact on this population. Method(s): Multicenter and prospective registry that included patients with AF and diabetes attended in cardiology clinics. A multivariate analysis was performed to determine the variables associated with the occurrence of clinical events and mortality. Recruitment was performed in February-December 2019. Result(s): The evolution of 633 patients, 96,2% of those included in the REFADI registry with a median follow-up of 835 days was analyzed (mean age 73.8 +/- 8.5 years, 54.3% male, CHA2DS2-VASc 4,34 +/- 1,4, HAS-BLED 2,47 +/- 0,96) were analyzed. The proportion of anticoagulated patients remained constant (95.6% vs 94.5%;P = .24). There was a decrease in the prescription of vitamin K antagonists (from 31.4% to 19.7%;P < .01), and an increase in the use of direct anticoagulants (from 62.0% to 70.3%;P < .01). During the follow-up there was an increase in the prescription of SGLT2 inhibitors (from 20.0% to 25.5%;P < .01) and GLP1 agonists (from 4.2% to 9.1%;P < .01). During this period, 17.2% of patients died, the majority from cardiovascular causes, 6.4% from COVID-19, 2.8% from stroke, and 1.8% from hemorrhage. Older age, lower ejection fraction, lower hemoglobin levels, and especially lower direct anticoagulants prescription were associated with mortality. Conclusion(s): Patients with AF and diabetes have a high thromboembolic risk and a high risk of developing complications, especially of cardiovascular origin.Copyright © 2023 Sociedad Espanola de Cardiologia

Association between use of novel glucose-lowering drugs and COVID-19 hospitalization and death in patients with type 2 diabetes: a nationwide registry analysis.

AIMS: Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. METHODS AND RESULTS: Patients with T2DM registered in the Swedish National Patient Registry and alive on 1st February 2020 were included. "Incident severe COVID-19" was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA and DPP-4i to analyze the associations between their use and I) incident severe COVID-19, II) risk of 30-day mortality in patients hospitalized for COVID-19.Among 344,413 patients, 39,172 (11%) were treated with SGLT2i, 34,290 (10%) with GLP-1 RA and 53,044 (15%) with DPP-4i; 9,538 (2.8%) had incident severe COVID-19 by 15th May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i were also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA. CONCLUSION: SGLT2i and DPP-4i use was associated with higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA.

Evaluation of the Effect of Underlying Diseases on Mortality of COVID-19 Patients: A Study of 19,985 Cases

Background: The outbreak of a new coronavirus in China in 2019 (COVID-19) caused a global health crisis. Objective(s): This study was performed to investigate the effect of different underlying diseases on mortality in patients with COVID-19. Method(s): This retrospective cohort study was performed on COVID-19 patients admitted to the Shahid Rahimi and Sohada-ye Ashayer teaching hospitals in Khorramabad, Iran, from 2019 to 2021. Data on disease severity, clinical manifestations, mortality, and underlying disorders were collected and analyzed using the SPSS software version 22 at a 95% confidence interval and 0.05 sig-nificance level. Result(s): The study included 9653 men (48%) and 10332 women (52%). Patients with chronic kidney diseases, cancer, chronic obstruc-tive pulmonary disease, hypertension, cardiovascular disease, and diabetes were at higher mortality risk than those without these underlying diseases, respectively. However, there was no significant relationship between asthma and mortality. Also, age > 50 years, male gender, oxygen saturation < 93 on admission, and symptoms lasting <= 5 days were associated with increased mortality. Conclusion(s): Since patients with underlying diseases are at higher mortality risk, they should precisely follow the advice provided by health authorities and receive a complete COVID-19 vaccination series.Copyright © 2022, Author(s).

ANALYSIS OF RISK FACTORS FOR COVID-19-RELATED FATAL OUTCOME IN 337991 PATIENTS WITH TYPE 1 AND TYPE 2 DIABETES MELLITUS IN 2020-2022 YEARS: RUSSIAN NATIONWIDE RETROSPECTIVE STUDY.

BACKGROUND: The coronavirus pandemic has had an extremely negative impact on the patients with diabetes mellitus (DM both in terms of a more severe course of COVID -19 and an increased risk of death. AIM: Analysis of risk factors for death due to COVID -19 in patients with DM type 1 and type 2 (DM1 and DM2). MATERIALS AND METHODS: Retrospective analysis of the database of the national diabetes register (NDR), which included DM patients with COVID-19 and reported virus infection outcome (recovery/or death) in 15 712 DM1 and 322 279 DM2 patients during a 2-year follow-up period (01/02/2020 to 03/04/2022) (discharge date)). RESULT(S): Case fatality rate in patients with DM, who underwent COVID -19 was 17.1% (DM1-8.8%;DM2-17.5%). As a result of multivariate regression analysis of seven significant factors in DM1 and thirteen in DM2 (evaluated by univariate anlisys), a number of the most important predictors of risk for fatal outcome were identified: in DM1 these were age >=65 years (OR =4.01, 95% CI: 1.42-11.36), presence of arterial hypertension (AH) (OR =2.72, 95% CI: 1.03 -7.16) and diabetic foot syndrome (DFS) (OR = 7.22, 95% CI: 1.98-26.29);for T2DM: age >= 65 years (OR =2.53, 95% CI: 1.96-3.27), male (OR =1.51, 95% CI: 1.23-1.84), duration DM >=10 years (OR =2.01, 95% CI: 1.61-2.51), BMI >= 30 kg/m2 (OR =1.26, 95% CI: 1.02-1.55), ASCVD/CKD (OR =1.49, 95% CI: 1.01-2.04), history of diabetic coma (OR =12.97, 95% CI: 1.89-88.99) and presence of disability (OR =1.40, 95% CI: 1.14-1.73). In T2DM, the type of antidiabetic therapy (ADT) prior to COVID -19 (last visit before the development of infection) had a significant impact: Insulin therapy (OR = 1.64, 95% CI: 1.30-2.07), sulfonylureas (SU) (OR =1.51, 95% CI: 1.23-1.84));dipeptidyl peptidase-4 inhibitor (iDPP-4) therapy (OR =0.57, 95% CI: 0.39-0.83) and sodium-glucose cotransporter-2 inhibitor (iSGLT2) therapy (OR =0.64, 95% CI: 0.46-0.88). Vaccination was the most important protective factor in both types of DM: DM1 OR =0.19, 95% CI: 0.06-0.59;SD2 OR =0.20, 95% CI: 0.16-0.26. CONCLUSION(S): The common risk factor for fatal outcome in both DM1 and DM2 was age >=65 years;in DM1 - history of hypertension and DFS, in DM2 - male sex, diabetes duration >=10 years, BMI >=30 kg/m2, history of ASCVD/CKD and diabetic coma, disability. In T2DM, significant differences in risk were observed depending on the type of ADT: insulin and SU therapy were factors that increased the risk of death, whereas therapy with iDPP-4 and iSGLT2 reduced the risk of death. Vaccination reduced the risk of death in DM1 and DM2 by 5.2 and 5-fold, respectively.Copyright © Endocrinology Research Centre, 2022.

Obesity and COVID-19: insights from two pandemics.

This review article discusses the pathophysiological mechanisms of the development of coronavirus infection in obese patients. It has been shown that obesity is considered as the most important risk factor for the development of many comorbid diseases, including severe forms and deaths as a result of a new coronavirus infection. The higher incidence and severity of a new coronavirus infection in obese patients is based on a complex of factors, the main of which are an increase in cardiovascular risk, including a tendency to thrombosis, a decrease in the efficiency of the respiratory system, impaired immune response, and the presence of chronic inflammatory state. The article discusses non-drug approaches and issues of pharmacological therapy in patients with obesity in the context of a pandemic of a new coronavirus infection. It is shown that the implementation of national quarantine measures has led to an increase in physical inactivity, the level of stress and a change in the eating behavior of the population, closing a vicious circle and contributing to an increase in body weight. For this reason, the efforts of physicians of therapeutic specialties should be directed primarily to increasing resistance to infection among obese patients and combating physical inactivity. The main groups of drugs that can be used to combat lipotoxicity are listed. It was noted that infectious disease doctors and endocrinologists can use those groups of drugs that affect the most vulnerable pathogenetic triggers for the development of obesity and comorbidities: hunger and satiety processes, decreased insulin sensitivity, development of lipotoxicity and chronic inflammation. It has been proven that the range of positive effects of new antihyperglycemic drugs from the groups of type 1 glucagon-like peptide agonists and type 2 sodium-glucose transporter inhibitors, combined with a well-studied efficacy and safety profile, represents a new opportunity for the treatment of obesity in the context of a coronavirus infection pandemic.Copyright © 2022 Authors. All rights reserved.

Top 20 Research Studies of 2021 for Primary Care Physicians

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men;rectal bleeding in women;and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.Copyright © 2022 American Academy of Family Physicians.

Pulse of Asia 2021

The proceedings contain 67 papers. The topics discussed include: cardiovascular system and COVID-19;long term sequale on COVID-19;fighting vascular disease: thoughts about 2022 Taiwan hypertension guidelines;quantification of hemodynamic parameters using 4D flow MRI;nanomedicine for the treatment of atherosclerosis;direct thrombus imaging;clinical outcome in patients with deep vein thrombosis;cardiovascular benefits of SGLT-2 inhibitor;central blood pressure and pressure wave reflection in cardiovascular abnormalities: do not put them in shade;association between excess pressure and cognitive function among elderly population;visceral adipose tissue, coronary artery calcification and heart failure: a moderated mediation analysis;and the cardio-ankle vascular index was associated with CHADS2 score in patients with atrial fibrillation: a coupling registry study.

Post COVID-19 syndrome related to diabetes - A brief review

The COVID-19 pandemic, as named by the World Health Organization, emerged in 2019 in Wuhan, China, secondary to the spread of the novel coro-navirus, SARS-CoV-2, that has a human-to-human manner of transmission, with a high transmissibility rate and a lower fatality rate compared to other respiratory syndromes. Patients with diabetes are more susceptible to the most severe complications of COVID-19 and related mortality. The management and treatment of diabetes have been quite difficult during this long COVID-19 pandemic for many reasons, including the reduced patients` access to health care facilities for their regular scheduled visits, leading to excess mortality that has been early reported. Novel antidiabetic drugs such as GLP-1RAs and SGLT-2i may have some beneficial actions on COVID-19 outcome, potentially even interfering with the viral action;yet, many uncertainties still exist about the so-called post-COVID-19 syndrome, for which the diagnostic and therapeutical approach is still not fully defined. Therefore, we need to use the experience gained from the recent events to guide our current and future clinical work and give our patients with diabetes and cardiometabolic diseases better quality of life during COVID-19 and post-COVID-19 time.Copyright © 2022, Verlag Kirchheim and Co. GmbH. All rights reserved.

Another Cause of DKA in T2DM in COVID-19 Pandemic

Background: 47-year Emirati female, has history of T2DM since age of 39. Her overall diabetes poorly controlled with HbA1C of 8.6% (69 mmol/mol IFCC) on Empagliflozin 10 mg OD over the last 2 years well tolerated. NO micro- or macrovascular complications of her diabetes. No other significant medical history apart from hypertension she is taking Amlodipine 10 mg OD for it with good control. She has presented twice to the hospital 24 hours apart. 1st Visit to ER in our Hospital with fever epigastric pain discharged on Ciprofloxacin suspected gastroenteritis with PPI and sent home. Approximately, 24 hours later she presented again with same symptoms namely fever and epigastric pain but this time associated with diarrhea and nausea for last 20 hours. There was no shortness of Breath or cough. This time she has been admitted to isolating room giving suspicion of COVID-19. Vital signs as following: Temp 38.5 HR 105, BP 135/65 mmHg O2 Sats 96%. on RA. On examination, she was conscious, oriented to time place person. No signs of dehydration. abdomen soft non tender, Chest good air entry no added sound. Hear S1-S2 no murmurs. HRCT has been done at ER. HRCT shows wide spread area of multifocal ground glass opacification are seen in both lungs most of them shows peripheral sub-pleural distribution Around small size consolidation are seen within the ground glass opacification, CT findings are in favour of possibility of COVID-19. Result(s): Blood test as following On admission, FBC was normal, with Hb 13.2, WBC 8.0, Plt 388 cellX 10/ul, U/Es: S.NA 132, s.K 4.2 mmo/l, s. Creatinine normal (58 umol/L -NR 49-90 umol/L) LFTs, Amylase and lipase normal, LDH mild elevation 304 U/L (NR 81-234), Very low Phosphate 03 mmol/L (NR 0.87-1.45), D-Dimer 0.6 mg/L (NR 0.0- 0.5), Corrected Calcium normal, S. Ferritin was 242 ug/L (NR 8.00- 388.00 ug/L), Urinalysis Protein =1 and 4+ ketones, CRP was normal 1 mg/dl ( increased to 214 mg/ l 3rd day) before it goes done 41 mg/L on 7th day of admission. Giving the pandemic of COVID 19 and according to MOHAP Criteria for presenting symptoms. This lady underwent HRCT and COVID19 test by Nasal Swab. Meanwhile, Her Venous Blood gas shows sever metabolic acidosis pH 7.107, PCO2 12.90, PCO2 69.10 On RA, BC 8.9, BE -25.5. Blood sugar 13.2 mmol/L with Urinary Ketones of 4+. Patient has put on DKA Protocol according to our Hospital DKA protocol in addition Stopped her SGLT2 and start on Lantus as a basal. She has put on Scale C (which is the higher scale with infusion about 10 units per hour, for about 96 hours (i.e. 4 days till the blood sugar back to normal for Ketones to disappear, her acidosis didn't improve 1st 24 hours till we give her 1.26% of 500 ml of Sodium Bicarbonate over 6 hours. COVID 19 Test back after 72 hours with positive results. Once out of DKA Diabetes team has stopped her Lantus a stared-on Humalog mix 50% 25 unit TDS. Meanwhile, she has received the following medications waiting for COVID 19 test. Treated with Favipiravir 1600 mg BD for 1 day and 600 mg BD, Start Tazocin 4.5 (stopped after 3 days) Metronidazole, and with prophylactic dose of Clexane. The Hydroxychloroquine hasn't started as Prolong QTC has been notice). Discussion(s): This patient presentation with DKA is another example how COVID- 19 could be a reason for DKA, though SGLT2 could be another cause of her presentation, however the huge insulin requirement and unusual prolong DKA status even with sever acidosis is making COVID-19 more likely causing her presentation It. Conclusion(s): We report this case to highlight the fact DKA - and in fact sever resistant DKA need prolong treatment can happen to Patient with T2DM and COVID 19 positive, and special attention to be paid (with early referral to the diabetes team) if the patient already on SGLT2. And we recommend that to have low threshold to start investigation and treatment as early as possible, regardless the type of Diabetes these patient might have.

COVID-19 Precipitating Euglycaemic Diabetic Ketoacidosis with SGLT2 Inhibitor Use.

OBJECTIVE: To describe a patient who developed euglycaemic diabetic ketoacidosis (DKA) in the setting of SGLT2 inhibitor use precipitated by COVID-19. PATIENT AND METHODS: A 52-year-old male with type II diabetes on empagliflozin and no history of DKA presented with symptoms of COVID-19 as well as laboratory findings consistent with euglycaemic DKA. His hospital course was complicated by recurrent episodes of euglycaemic DKA as well as hyperglycaemic DKA. CONCLUSION: SGLT2 inhibitors should be held as early as possible in COVID-19 cases due to the risk of euglycaemic DKA. These patients should also have more intense glucose monitoring. LEARNING POINTS: COVID-19 can precipitate euglycaemic DKA in diabetic patients taking SGLT2 inhibitors.Clinicians should be cognizant that the effects of SGLT2 inhibitors can persist for more than 72 hours after the last dose.Diabetic patients with COVID-19 require closer strict glucose monitoring to reduce the risk of DKA.

Anti-inflammatory effects of sodium-glucose cotransporter-2 inhibitors in COVID-19.

The ongoing pandemic of COVID-19 is intrinsically a systemic inflammatory disorder; hence, those patients suffering an underlying chronic inflammatory disease such as diabetes mellitus are at high risk of severe complications. Preventing or suppressing the inflammatory responses are of importance in diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a newly introduced anti-diabetic drugs that have hypoglycemic effects through the urinary excretion of glucose. They also have an anti-inflammatory potential in diabetes patients, in addition to improving glycemic control, and while there is no direct data available in diabetic patients with COVID-19 disease, there is evidence that suggests that SGLT2i can reduce systemic inflammation and diminish the cytokine storm effect via several cellular mechanisms. In the current review, our aim was to classify and describe the molecular and cellular pathways by which SGLT2i have anti-inflammatory effects in diabetic patients with COVID-19 disease.

Dipeptidyl Peptidase-4 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, and Sodium-Glucose Cotransporter-2 Inhibitors and COVID-19 Outcomes.

PURPOSE: It has been reported that dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have a role in modulation of inflammation associated with coronavirus disease 2019 (COVID-19). This study assessed the effect of these drug classes on COVID-19-related outcomes. METHODS: Using a COVID-19 linkable administrative database, we selected patients aged ≥40 years with at least 2 prescriptions of DPP-4i, GLP-1 RA, or SGLT-2i or any other antihyperglycemic drug and a diagnosis of COVID-19 from February 15, 2020, to March 15, 2021. Adjusted odds ratios (ORs) with 95% CIs were used to calculate the association between treatments and all-cause and in-hospital mortality and COVID-19-related hospitalization. A sensitivity analysis was performed by using inverse probability treatment weighting. FINDINGS: Overall, 32,853 subjects were included in the analysis. Multivariable models showed a reduction of the risk for COVID-19 outcomes for users of DPP-4i, GLP-1 RA, and SGLT-2i compared with nonusers, although statistical significance was reached only in DPP-4i users for total mortality (OR, 0.89; 95% CI, 0.82-0.97). The sensitivity analysis confirmed the main results reaching a significant reduction for hospital admission in GLP-1 RA users and in-hospital mortality in SGLT-2i users compared with nonusers. IMPLICATIONS: This study found a beneficial effect in the risk reduction of COVID-19 total mortality in DPP-4i users compared with nonusers. A positive trend was also observed in users of GLP-1 RA and SGLT-2i compared with nonusers. Randomized clinical trials are needed to confirm the effect of these drug classes as potential therapy for the treatment of COVID-19.

Safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) during the month of Ramadan in patients with type 2 diabetes mellitus in Pakistani population-an observational study from a tertiary care center in Karachi.

BACKGROUND AND AIMS: Primary aim was to assess the safety of SGLT2-i in patients with Type 2 Diabetes Mellitus (T2D) in a real-life scenario during Ramadan by finding the frequency and severity of hypoglycemic/hyperglycemic events, dehydration, and Diabetic ketoacidosis (DKA). Secondary aim was to assess changes in glycated hemoglobin (HbA1c), weight and creatinine levels. METHODS: This prospective, observational, controlled cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan from March 15 to June 30, 2021. Participants were over 21 years of age, on stable doses of SGLT2-I, which was started at least 2 months before Ramadan. Endpoint assessments were done 1 month before and within 6 weeks after Ramadan. RESULTS: Of 102 participants enrolled, 82 completed the study. Most (52%) were males, with mean age 52.2 ± 9.5 years and average duration of T2D 11.2 ± 6.5 years. 63% were on Empagliflozin (mean dose; 14.8 ± 7.2 mg/day) whereas 37% were on Dapagliflozin (mean dose; 8.2 ± 2.7 mg/day). Six (7.3%) documented symptoms of hypoglycemia. However, no episode of severe hypoglycemia, hyperglycemia, dehydration, DKA, hospitalization or discontinuation of SGLT2i was reported. HbA1c changes were (7.7 ± 1.2% from 7.9 ± 2.3%, p 0.34), weight (78.4 ± 12.9 kgs from 78.9 ± 13.3, p 0.23) and eGFR (87.8 ± 27.9 from 94.3 ± 37.6, p < 0.001). The reasons of study participants drop outs were: six did not keep any fasts; four discontinued study participation for personal reasons; three were out of city and missed post Ramadan follow-up, two protocol violation and five could not be contacted for post-Ramadan follow up during the third wave of COVID-19. CONCLUSION: Results showed the safety of SGLT2i agents during Ramadan in the Pakistani population recommending it as a treatment option in adults with T2D, without any additional adverse events.

ANALYSIS OF RISK FACTORS FOR COVID-19-RELATED FATAL OUTCOME IN 337991 PATIENTS WITH TYPE 1 AND TYPE 2 DIABETES MELLITUS IN 2020-2022 YEARS: RUSSIAN NATIONWIDE RETROSPECTIVE STUDY.

BACKGROUND: The coronavirus pandemic has had an extremely negative impact on the patients with diabetes mellitus (DM both in terms of a more severe course of COVID -19 and an increased risk of death. AIM: Analysis of risk factors for death due to COVID -19 in patients with DM type 1 and type 2 (DM1 and DM2). MATERIALS AND METHODS: Retrospective analysis of the database of the national diabetes register (NDR), which included DM patients with COVID-19 and reported virus infection outcome (recovery/or death) in 15 712 DM1 and 322 279 DM2 patients during a 2-year follow-up period (01/02/2020 to 03/04/2022) (discharge date)). RESULT(S): Case fatality rate in patients with DM, who underwent COVID -19 was 17.1% (DM1-8.8%;DM2-17.5%). As a result of multivariate regression analysis of seven significant factors in DM1 and thirteen in DM2 (evaluated by univariate anlisys), a number of the most important predictors of risk for fatal outcome were identified: in DM1 these were age >=65 years (OR =4.01, 95% CI: 1.42-11.36), presence of arterial hypertension (AH) (OR =2.72, 95% CI: 1.03 -7.16) and diabetic foot syndrome (DFS) (OR = 7.22, 95% CI: 1.98-26.29);for T2DM: age >= 65 years (OR =2.53, 95% CI: 1.96-3.27), male (OR =1.51, 95% CI: 1.23-1.84), duration DM >=10 years (OR =2.01, 95% CI: 1.61-2.51), BMI >= 30 kg/m2 (OR =1.26, 95% CI: 1.02-1.55), ASCVD/CKD (OR =1.49, 95% CI: 1.01-2.04), history of diabetic coma (OR =12.97, 95% CI: 1.89-88.99) and presence of disability (OR =1.40, 95% CI: 1.14-1.73). In T2DM, the type of antidiabetic therapy (ADT) prior to COVID -19 (last visit before the development of infection) had a significant impact: Insulin therapy (OR = 1.64, 95% CI: 1.30-2.07), sulfonylureas (SU) (OR =1.51, 95% CI: 1.23-1.84));dipeptidyl peptidase-4 inhibitor (iDPP-4) therapy (OR =0.57, 95% CI: 0.39-0.83) and sodium-glucose cotransporter-2 inhibitor (iSGLT2) therapy (OR =0.64, 95% CI: 0.46-0.88). Vaccination was the most important protective factor in both types of DM: DM1 OR =0.19, 95% CI: 0.06-0.59;SD2 OR =0.20, 95% CI: 0.16-0.26. CONCLUSION(S): The common risk factor for fatal outcome in both DM1 and DM2 was age >=65 years;in DM1 - history of hypertension and DFS, in DM2 - male sex, diabetes duration >=10 years, BMI >=30 kg/m2, history of ASCVD/CKD and diabetic coma, disability. In T2DM, significant differences in risk were observed depending on the type of ADT: insulin and SU therapy were factors that increased the risk of death, whereas therapy with iDPP-4 and iSGLT2 reduced the risk of death. Vaccination reduced the risk of death in DM1 and DM2 by 5.2 and 5-fold, respectively. Copyright © Endocrinology Research Centre, 2022.

Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms.

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a class of drugs which lower glucose by promoting its elimination through urine, thus inducing a net loss of calories. This effect promotes a metabolic shift at the systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, and is accompanied by a modulation of major nutrient-sensing pathways held to drive aging, e.g., mTOR and the inflammasome, overall resembling major features of caloric restriction. In addition, preliminary experimental data suggest that SGLT-2i might also have intrinsic activities independent of their systemic effects, such as the inhibition of cellular senescence. Consistently, evidence from both preclinical and clinical studies have also suggested a marked ability of SGLT-2i to ameliorate low-grade inflammation in humans, a relevant driver of aging commonly referred to as inflammaging. Considering also the amount of data from clinical trials, observational studies, and meta-analyses suggesting a tangible effect on age-related outcomes, such as cardiovascular diseases, heart failure, kidney disease, and all-cause mortality also in patients without diabetes, here we propose a framework where at least part of the benefit provided by SGLT-2i is mediated by their ability to blunt the drivers of aging. To support this postulate, we synthesize available data relative to the effect of this class on: 1- animal models of healthspan and lifespan; 2- selected molecular pillars of aging in preclinical models; 3- biomarkers of aging and especially inflammaging in humans; and 4- COVID-19-related outcomes. The burden of evidence might prompt the design of studies testing the potential employment of this class as anti-aging drugs.

NEPHROLOGY E-CONSULTS: A NOVEL APPROACH TO KIDNEY CARE IN A SAFETY-NET HOSPITAL

STATEMENT OF PROBLEM/QUESTION: With Chronic Kidney Disease (CKD) on the rise, Grady Health System (GHS) implemented a novel Electronic-Consultation (E-Consult) Service for outpatient Nephrology and we sought to determine the characteristics and outcomes of these patients to better recognize the utility in our new approach to kidney care. DESCRIPTION OF PROGRAM/INTERVENTION: The Nephrology EConsult service was launched in September 2020 across all primary care clinics at GHS, which is located in downtown Atlanta, GA, and serves a population of mainly Medicare/Medicaid and uninsured patients. With this service, Primary Care Providers (PCPs) submit an E- Consult and a single Nephrologist reviews the chart to communicate closed-loop recommendations via the patient's Electronic Health Record (EHR). If high-complexity factors are discovered (including nephrotic-range proteinuria, acute kidney injury (AKI), or CKD 4/5), the patient is scheduled for an in-person clinic visit with Nephrology. MEASURES OF SUCCESS: We retrospectively analyzed the charts of 200 randomly-selected E-Consults placed 09/2020-12/2021 to determine disease complexity, A1c and albuminuria screening rates, DM2 control, common comorbidities, renoprotective medication use, as well as the percentage of PCPs who completed the consultation recommendations. We identified the number of in-person Nephrology clinic visits that were prevented with this virtual service and compared waitlist times against a traditional referral to outpatient Nephrology. FINDINGS TO DATE: The majority of patients (55%) have low-complexity kidney disease, and nearly half of all E- Consults are managed entirely virtually, avoiding an in-person visit to Nephrology. Fewer E-Consults have high- complexity disease (45%), most of which involve AKI (60%) and/or CKD4 (35%), warranting an in-person Nephrology evaluation, and with this service an in-person visit occurs in 1/3 the time of traditionally-placed referrals. The most common comorbidities are hypertension (80%) and DM2 (51%), and interestingly, the majority of patients with DM2 have relative control of their disease with an A1c <7% (63%). However, the rate of screening A1c differs from albuminuria: most patients have a recent A1c (70%) while less than half of patients have a recent urine albumin. Very few patients are prescribed an SGLT2-inhibitor (5%) and more than a quarter of eligible patients are not on any renoprotective medications. Nearly a quarter of PCPs do not complete the e-consult recommendations, representing an area where EMR automatization may be useful. KEY LESSONS FOR DISSEMINATION: Our Nephrology E-Consult Service improves access to kidney care for all patients, reduces clinic wait times for those with high-complexity disease, and may play an important role during the Covid-19 pandemic by reducing healthcare-associated exposures. By providing a closed-loop method of communication between PCP and Nephrologist, guideline-based recommendations for routine screening and renoprotective strategies can be exchanged for the patient's benefit.