Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 224
Filter
1.
Probl Endokrinol (Mosk) ; 68(2): 56-65, 2022 02 22.
Article in Russian | MEDLINE | ID: covidwho-2203926

ABSTRACT

BACKGROUND: There is a lack of data on the features of dysglycemia in hospitalized patients with COVID-19 and concomitant diabetes mellitus (DM) confirmed by continuous glucose monitoring (CGM). AIM: to study the glycemic profile in hospitalized patients with COVID-19 and type 2 diabetes mellitus by continuous glucose monitoring and the role of steroid therapy in dysglycemiadevelopment. MATERIALS AND METHODS: We examined 21 patients with COVID-19 and DM 2 and 21 patients with DM 2 without COVID-19 (control group) using a professional 4-7-day CGM. We also compared two subgroups of patients with COVID-19 and DM 2: 1) patients received systemic glucocorticosteroids (GCS) during CGM and 2) patients in whomCGMwas performed after discontinuation of GCS. RESULTS: Compared with controls, patients with COVID-19 and DM2 had lesser values of glycemic «time in range¼ (32.7 ± 20.40 vs 48.0 ± 15.60%, p = 0.026) andhigher parameters of mean glycemia (p <0.05) but similar proportion of patients with episodes of hypoglycemia (33.3% vs 38.1%, p = 0.75). Patients who received dexamethasone during CGM were characterized by higher hyperglycemia and the absence of episodes of hypoglycemia. In patients who hadCGM after dexamethasone discontinuation, hyperglycemia was less pronounced, but 60% of them had episodes of hypoglycemia, often nocturnal, clinically significant and not detected by routine methods. CONCLUSION: Patients with COVID-19 and DM 2had severe and persistent hyperglycemia but a third of them hadalso episodes of hypoglycemia. During therapy with dexamethasone, they had the most pronounced hyperglycemia without episodes of hypoglycemia. In patients who underwent CGM after discontinuation of dexamethasone, hyperglycemia was less pronounced but 60% of them have episodes of hypoglycemia, often nocturnal, clinically significant and not diagnosed by routine methods. It would be advisable to recommend at least a 5-6-fold study of the blood glucose level (with its obligatory assessment at night) even for stable patients with COVID-19 and DM 2after the end of GCS treatment.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Hyperglycemia , Hypoglycemia , Blood Glucose , Blood Glucose Self-Monitoring , COVID-19/complications , COVID-19/drug therapy , Dexamethasone/adverse effects , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Humans , Hyperglycemia/drug therapy , Hypoglycemia/chemically induced , Steroids
2.
J Diabetes Sci Technol ; 16(4): 955-961, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2194856

ABSTRACT

BACKGROUND: Hospitalization of persons with diabetes in an inpatient diabetes unit is challenging, notably for patients having different profiles. We aimed to evaluate the feasibility and the benefit of a continuous glucose monitoring (CGM) telemetry system to control glucose excursions in hospitalized patients with diabetes, according to their diabetes type and the reasons for their hospitalization. METHOD: A prospective pilot study was conducted in 53 insulin-requiring diabetes patients hospitalized in the general ward. Glucose was monitored using Guardian Connect (GC, Medtronic) to adopt insulin therapy. The time in range (TIR, target 70-180 mg/dL), the time below range (TBR), and the time above range (TAR) were recorded by GC between the start of hospitalization (SH) and end of hospitalization (EH), and analyzed according to the diabetes type (type 1 diabetes n = 28, type 2 diabetes n = 25) and the reasons for hospitalization (acute complications n = 35, therapeutic education n = 18). Patient and caregiver satisfaction was also assessed. RESULTS: In patients with type 2 diabetes and those hospitalized for acute complications, TIR significantly increased between the SH and EH, from 75.7% (95%CI 48.5-84.6) to 82.2% (95%CI 63.2-91.8) P = 0.043 and from 58.3% (95%CI 46.3-69.7) to 66.4% (95%CI 55.6-75.5) P = 0.031, respectively, and TAR significantly decreased, with no change in TBR. In patients with diabetes hospitalized for therapeutic education, TBR significantly decreased from 3.4% (95%CI 0-9.4) to 0% (95%CI 0-3.8) P = 0.037. Finally, 94% of patients and caregivers deemed the GC system useful. CONCLUSIONS: CGM telemetry system use is feasible and well accepted in patients hospitalized in diabetes care unit and could be useful to improve therapeutic education and metabolic control, especially for specific homogenous populations with diabetes.


Subject(s)
Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 2 , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Feasibility Studies , Humans , Inpatients , Insulin/therapeutic use , Pilot Projects , Prospective Studies , Telemetry
3.
Lancet ; 400(10365): 1803-1820, 2022 11 19.
Article in English | MEDLINE | ID: covidwho-2159959

ABSTRACT

Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. The number affected is increasing rapidly with alarming trends in children and young adults (up to age 40 years). Early detection and proactive management are crucial for prevention and mitigation of microvascular and macrovascular complications and mortality burden. Access to novel therapies improves person-centred outcomes beyond glycaemic control. Precision medicine, including multiomics and pharmacogenomics, hold promise to enhance understanding of disease heterogeneity, leading to targeted therapies. Technology might improve outcomes, but its potential is yet to be realised. Despite advances, substantial barriers to changing the course of the epidemic remain. This Seminar offers a clinically focused review of the recent developments in type 2 diabetes care including controversies and future directions.


Subject(s)
Diabetes Mellitus, Type 2 , Epidemics , Humans , Child , Young Adult , Adult , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Pharmacogenetics , Precision Medicine , Technology
4.
Am Fam Physician ; 106(1): 61-69, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2156674

ABSTRACT

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.


Subject(s)
COVID-19 , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Low Back Pain , Physicians, Primary Care , Sodium-Glucose Transporter 2 Inhibitors , Aged , Analgesics, Opioid , Anti-Bacterial Agents , COVID-19/complications , Child , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Duloxetine Hydrochloride , Female , Humans , Male , Pandemics , Physicians, Primary Care/education
5.
N Engl J Med ; 385(6): 503-515, 2021 08 05.
Article in English | MEDLINE | ID: covidwho-2160403

ABSTRACT

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Gastric Inhibitory Polypeptide/administration & dosage , Glucagon-Like Peptides/administration & dosage , Hypoglycemic Agents/administration & dosage , Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Gastric Inhibitory Polypeptide/adverse effects , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptides/adverse effects , Glycated Hemoglobin A/analysis , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Injections, Subcutaneous , Male , Metformin/therapeutic use , Middle Aged , Nausea/chemically induced , Weight Loss/drug effects
6.
Front Endocrinol (Lausanne) ; 13: 1002834, 2022.
Article in English | MEDLINE | ID: covidwho-2141737

ABSTRACT

Introduction: Diabetes mellitus is a common comorbidity among patients with coronavirus disease 2019 (COVID-19). Diabetic patients with COVID-19 have a two-fold increased risk of death and tend to have more severe infection compared to the general population. Metformin, a first-line medication for diabetes management, has anti-inflammatory and immunomodulatory effects. Previous studies focusing on metformin and COVID-19 clinical outcomes have had mixed results, with some showing a mortality benefit or decreased complications with metformin use. To date, few studies have analyzed such outcomes among a diverse, multiracial community. Methods: This was a retrospective review of patients with Type 2 diabetes and a confirmed COVID-19 infection admitted to an urban academic medical center from January 1, 2020 to May 7, 2020. Baseline characteristics were collected. The primary outcomes of the study were in-hospital mortality and length of stay (LOS). Results: A total of 4462 patients with Type 2 diabetes and confirmed COVID-19 were identified. 41.3% were Black, and 41.5% were Hispanic. There were 1021 patients in the metformin group and 3441 in the non-metformin group. Of note, more participants in the metformin group had comorbid disease and/or advanced diabetes. We found no statistically significant differences between the metformin and non-metformin group in in-hospital mortality (28.1% vs 25.3%, P=0.08) or length of hospital stay in days (7.3 vs. 7.5, P=0.59), even after matching patients on various factors (29.3% vs. 29.6%, P=0.87; 7.7 vs. 8.1, P=0.23). Conclusion: While patients had more comorbid disease and advanced diabetes in the metformin group, there were no significant differences with regard to in-hospital mortality or length of stay due to COVID-19 compared to the non-metformin group. Prospective studies are needed to determine if there is clinical benefit for initiating, continuing, or re-initiating metformin in patients hospitalized with COVID-19.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Humans , Metformin/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Length of Stay , COVID-19/complications , COVID-19/drug therapy , Hypoglycemic Agents/therapeutic use
7.
Cell Physiol Biochem ; 56(6): 685-691, 2022 Nov 25.
Article in English | MEDLINE | ID: covidwho-2146449

ABSTRACT

BACKGROUND/AIMS: Corona virus disease 2019 (COVID-19) has become a deadly infectious disease, especially for those with co-morbidities such as diabetes. People with diabetes developing a viral infection, seem to have harder treatments due to fluctuations in blood glucose levels therefore, effective therapeutic approaches need to be considered for them. Statins are well-known lipid-lowering drugs; they also have anti-inflammatory and immunomodulatory effects and can impact on expression of microRNAs (miRNAs). METHODS: In this study we investigate the effects of simvastatin on the expression of miR-150-5p as a famous regulator of inflammation and its association with multiple cancers in 30 patients with Type 2 diabetes mellitus (T2DM) and COVID-19 compared to the COVID-19 hospitalized patients before and after treatment with simvastatin with real-time-PCR after 2month, and evaluate its targets gens and functions with the help of bioinformatics and GO enrichment analysis respectively. RESULTS: Our results showed that simvastatin can increase miR-150-5p and therefore down regulate expression of its target genes involving in immune stimulation and decrease lipid profile including LDL-C, total cholesterol, and ApoB, especially in the group with type 2 diabetes mellitus (T2DM) and COVID-19 compared to the patients with only COVID-19. CONCLUSION: Simvastatin as an anti-inflammatory agent can modulate miRNAs expression; it can be suggested as an adjunct therapy especially for T2DM patients with COVID-19. Further studies may help us for developing better treatments about therapeutic manipulation of miRNAs in vivo.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , MicroRNAs , Humans , Simvastatin/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , COVID-19/drug therapy , MicroRNAs/metabolism , Lipids
8.
PLoS One ; 17(11): e0271574, 2022.
Article in English | MEDLINE | ID: covidwho-2119192

ABSTRACT

BACKGROUND: While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size. METHODS: Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome. RESULTS: 6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28-0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33-0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control. CONCLUSIONS: There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Adult , Child , Male , Humans , Middle Aged , Aged , Female , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Retrospective Studies , COVID-19/drug therapy , RNA, Viral/therapeutic use , SARS-CoV-2 , Treatment Outcome , Sulfonylurea Compounds/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Metformin/therapeutic use , Cohort Studies
9.
Prim Care Diabetes ; 16(6): 753-759, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2113826

ABSTRACT

AIMS: To analyse if antidiabetic treatment was associated with better COVID-19 outcomes in type 2 diabetic patients, measured by hospital admission and mortality rates as severe outcomes. METHODS: Cohort study including COVID-19 patients registered in the Primary Care electronic records, in March-June 2020, comparing exposed to metformin in monotherapy with exposed to any other antidiabetic. DATA SOURCE: SIDIAP (Information System for Research in Primary Care), which captures clinical information of 5,8 million people from Catalonia, Spain. RESULTS: We included 31,006 diabetic patients infected with COVID-19, 43.7% previously exposed to metformin, 45.5% of them in monotherapy. 16.4% were admitted to hospital and 15.1% died. Users of insulin in monotherapy (OR 1.29, 95% CI 1.11-1.50), combined with metformin (OR 1.38, 1.13-1.69) or IDPP4 alone (OR 1.29, 1.03-1.63) had higher risk of severe outcomes than those in metformin monotherapy. Users of any insulin (OR 1.61, 1.32-1.97) or combined with metformin (OR 1.69, 1.30-2.20) had a higher risk of mortality. CONCLUSIONS: Patients receiving metformin monotherapy in our study showed a lower risk of hospitalization and death in comparison to those treated with other frequent antidiabetic agents. We cannot distinguish if better outcomes are related with the antidiabetic therapy or with other factors, such as metabolic control or interventions applied during the hospital admission.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Humans , Hypoglycemic Agents/adverse effects , Spain/epidemiology , Pandemics , Cohort Studies , COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Metformin/adverse effects , Insulin/adverse effects , Primary Health Care
11.
JAMA Netw Open ; 5(10): e2236123, 2022 10 03.
Article in English | MEDLINE | ID: covidwho-2084938

ABSTRACT

Importance: Patients with chronic kidney disease and type 2 diabetes have a higher risk of developing pneumonia as well as an increased risk of severe COVID-19-associated adverse events and mortality. Therefore, the anti-inflammatory effects of mineralocorticoid receptor antagonists via blockade of the mineralocorticoid receptor may alter the risk of pneumonia and COVID-19-associated adverse events in patients with chronic kidney disease and type 2 diabetes. Objective: To evaluate whether the selective, nonsteroidal mineralocorticoid receptor antagonist finerenone is associated with protection against pneumonia and COVID-19 adverse events in patients with type 2 diabetes and chronic kidney disease. Design, Setting, and Participants: This secondary analysis used patient-level data from FIDELITY, a prespecified pooled analysis of 2 multicenter, double-blind, placebo-controlled, event-driven, phase 3 randomized clinical trials: FIDELIO-DKD and FIGARO-DKD, conducted between September 2015 and February 2021. Patients in FIDELIO-DKD or FIGARO-DKD with type 2 diabetes and chronic kidney disease (urine albumin to creatine ratio, 30-5000 mg/g, estimated glomerular filtration rate ≥25 mL/min/1.73 m2) were assessed. Data were analyzed from May 15, 2021, to July 28, 2022. Exposure: Patients were randomized to finerenone (10 or 20 mg once daily) or matching placebo. Main Outcomes and Measures: The main outcomes were investigator-reported incidences of treatment-emergent infective pneumonia adverse events and serious adverse events (during and up to 3 days after treatment) and any COVID-19 adverse events. Results: Of 13 026 randomized patients (mean [SD] age, 64.8 [9.5] years; 9088 [69.8%] men), 12 999 were included in the FIDELITY safety population (6510 patients receiving finerenone; 6489 patients receiving placebo). Over a median (range) treatment duration of 2.6 (0-5.1) years, finerenone was consistently associated with reduced risk of pneumonia and serious pneumonia vs placebo. Overall, 307 patients (4.7%) treated with finerenone and 434 patients (6.7%) treated with placebo experienced pneumonia (hazard ratio [HR], 0.71; 95% CI, 0.64-0.79; P < .001). Serious pneumonia occurred in 171 patients (2.6%) treated with finerenone and 250 patients (3.9%) treated with placebo (HR, 0.69; 95% CI, 0.60-0.79; P < .001). Incidence proportions of COVID-19 adverse events were 86 patients (1.3%) in the finerenone group and 118 patients (1.8%) in the placebo group (HR, 0.73; 95% CI, 0.60-0.89; P = .002). Conclusions and Relevance: These findings suggest that mineralocorticoid receptor blockade with finerenone was associated with protection against pneumonia and COVID-19 adverse events in patients with type 2 diabetes and chronic kidney disease. Further clinical studies may be warranted. Trial Registration: ClinicalTrials.gov identifiers: FIDELIO-DKD: NCT02540993; FIGARO-DKD: NCT02545049.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Renal Insufficiency, Chronic , Female , Humans , Male , Middle Aged , Albumins/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Creatine/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/complications , Mineralocorticoid Receptor Antagonists/therapeutic use , Receptors, Mineralocorticoid/therapeutic use , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/chemically induced
12.
Int J Mol Sci ; 23(20)2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2071511

ABSTRACT

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.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Animals , Humans , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Inflammasomes , Drug Repositioning , Diabetes Mellitus, Type 2/drug therapy , Aging , Glucose/therapeutic use , TOR Serine-Threonine Kinases , Sodium , Ketones/therapeutic use , Fatty Acids/therapeutic use
13.
BMJ Open ; 12(10): e063046, 2022 10 12.
Article in English | MEDLINE | ID: covidwho-2064161

ABSTRACT

PURPOSE: The Scottish Diabetes Research Network (SDRN)-diabetes research platform was established to combine disparate electronic health record data into research-ready linked datasets for diabetes research in Scotland. The resultant cohort, 'The SDRN-National Diabetes Dataset (SDRN-NDS)', has many uses, for example, understanding healthcare burden and socioeconomic trends in disease incidence and prevalence, observational pharmacoepidemiology studies and building prediction tools to support clinical decision making. PARTICIPANTS: We estimate that >99% of those diagnosed with diabetes nationwide are captured into the research platform. Between 2006 and mid-2020, the cohort comprised 472 648 people alive with diabetes at any point in whom there were 4 million person-years of follow-up. Of the cohort, 88.1% had type 2 diabetes, 8.8% type 1 diabetes and 3.1% had other types (eg, secondary diabetes). Data are captured from all key clinical encounters for diabetes-related care, including diabetes clinic, primary care and podiatry and comprise clinical history and measurements with linkage to blood results, microbiology, prescribed and dispensed drug and devices, retinopathy screening, outpatient, day case and inpatient episodes, birth outcomes, cancer registry, renal registry and causes of death. FINDINGS TO DATE: There have been >50 publications using the SDRN-NDS. Examples of recent key findings include analysis of the incidence and relative risks for COVID-19 infection, drug safety of insulin glargine and SGLT2 inhibitors, life expectancy estimates, evaluation of the impact of flash monitors on glycaemic control and diabetic ketoacidosis and time trend analysis showing that diabetic ketoacidosis (DKA) remains a major cause of death under age 50 years. The findings have been used to guide national diabetes strategy and influence national and international guidelines. FUTURE PLANS: The comprehensive SDRN-NDS will continue to be used in future studies of diabetes epidemiology in the Scottish population. It will continue to be updated at least annually, with new data sources linked as they become available.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Diabetic Ketoacidosis , Sodium-Glucose Transporter 2 Inhibitors , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Humans , Insulin Glargine , Middle Aged , Naphthalenesulfonates , Scotland/epidemiology
15.
JAMA ; 328(9): 861-871, 2022 09 06.
Article in English | MEDLINE | ID: covidwho-2058978

ABSTRACT

Importance: Novel therapies for type 2 diabetes can reduce the risk of cardiovascular disease and chronic kidney disease progression. The equitability of these agents' prescription across racial and ethnic groups has not been well-evaluated. Objective: To investigate differences in the prescription of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) among adult patients with type 2 diabetes by racial and ethnic groups. Design, Setting, and Participants: Cross-sectional analysis of data from the US Veterans Health Administration's Corporate Data Warehouse. The sample included adult patients with type 2 diabetes and at least 2 primary care clinic visits from January 1, 2019, to December 31, 2020. Exposures: Self-identified race and self-identified ethnicity. Main Outcomes and Measures: The primary outcomes were prevalent SGLT2i or GLP-1 RA prescription, defined as any active prescription during the study period. Results: Among 1 197 914 patients (mean age, 68 years; 96% men; 1% American Indian or Alaska Native, 2% Asian, Native Hawaiian, or Other Pacific Islander, 20% Black or African American, 71% White, and 7% of Hispanic or Latino ethnicity), 10.7% and 7.7% were prescribed an SGLT2i or a GLP-1 RA, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 8.4% among American Indian or Alaska Native patients; 11.8% and 8% among Asian, Native Hawaiian, or Other Pacific Islander patients; 8.8% and 6.1% among Black or African American patients; and 11.3% and 8.2% among White patients, respectively. Prescription rates for SGLT2i and GLP-1 RA, respectively, were 11% and 7.1% among Hispanic or Latino patients and 10.7% and 7.8% among non-Hispanic or Latino patients. After accounting for patient- and system-level factors, all racial groups had significantly lower odds of SGLT2i and GLP-1 RA prescription compared with White patients. Black patients had the lowest odds of prescription compared with White patients (adjusted odds ratio, 0.72 [95% CI, 0.71-0.74] for SGLT2i and 0.64 [95% CI, 0.63-0.66] for GLP-1 RA). Patients of Hispanic or Latino ethnicity had significantly lower odds of prescription (0.90 [95% CI, 0.88-0.93] for SGLT2i and 0.88 [95% CI, 0.85-0.91] for GLP-1 RA) compared with non-Hispanic or Latino patients. Conclusions and Relevance: Among patients with type 2 diabetes in the Veterans Health Administration system during 2019 and 2020, prescription rates of SGLT2i and GLP-1 RA medications were low, and individuals of several different racial groups and those of Hispanic ethnicity had statistically significantly lower odds of receiving prescriptions for these medications compared with individuals of White race and non-Hispanic ethnicity. Further research is needed to understand the mechanisms underlying these differences in rates of prescribing and the potential relationship with differences in clinical outcomes.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Healthcare Disparities , Prescriptions , Sodium-Glucose Transporter 2 Inhibitors , Veterans Health , Adult , Aged , Cross-Sectional Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/ethnology , Ethnicity/statistics & numerical data , Female , Glucagon-Like Peptide-1 Receptor/agonists , Health Equity/statistics & numerical data , Healthcare Disparities/ethnology , Healthcare Disparities/statistics & numerical data , Humans , Hypoglycemic Agents/therapeutic use , Male , Practice Patterns, Physicians'/statistics & numerical data , Prescriptions/statistics & numerical data , Professional Practice/statistics & numerical data , Racial Groups/statistics & numerical data , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , United States/epidemiology , Veterans Health/ethnology , Veterans Health/statistics & numerical data
16.
S Afr Fam Pract (2004) ; 64(1): e1-e5, 2022 Sep 22.
Article in English | MEDLINE | ID: covidwho-2055673

ABSTRACT

BACKGROUND:  Coronavirus disease 2019 (COVID-19) is associated with an increased prevalence and mortality from diabetic ketoacidosis (DKA) globally. With limited access to specialised care, most patients with DKA in South Africa are managed at district hospital level. This study describes the profile of patients admitted to a district hospital in South Africa with DKA and COVID-19 and examines associated risk factors encountered. METHODS:  This was a case series of all patients presenting to a district hospital with DKA and COVID-19 infection between July 2020 and July 2021. Data extracted included patients' demographic profiles, biochemical results, comorbidities and clinical outcomes. RESULTS:  The median age of the 10 patients admitted during the study period was 39 years old (±12), six of whom were male. The hemoglobin A1c (HbA1c) values on admission ranged from 9.7 to 13.8. Five of the patients had pre-existing type 2 diabetes mellitus (DM). Four of the known DM patients were on metformin only, and one was on biphasic insulin. Three patients had other pre-existing comorbidities, two patients with hypertension and one with human immunodeficiency virus (HIV). Three patients demised, two of whom were hypoxic on admission. CONCLUSION:  Diabetic ketoacidosis appears more commonly in COVID-19 infected patients with type 2 DM and at a young age. Suboptimal glycaemic control was associated with DKA, and hypoxia was a strong predictor for mortality. Treatment inertia was evident in the known DM group, who were on monotherapy despite persistent hyperglycaemia. Greater vigilance is required to detect ketosis in type 2 DM and intensify therapy to improve glycaemic control.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Diabetic Ketoacidosis , Metformin , Adult , Biphasic Insulins/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/epidemiology , Diabetic Ketoacidosis/therapy , Female , Glycated Hemoglobin A/analysis , Glycated Hemoglobin A/therapeutic use , Hospitals, District , Humans , Male , Metformin/therapeutic use , Retrospective Studies , South Africa/epidemiology
17.
N Engl J Med ; 387(12): 1089-1098, 2022 09 22.
Article in English | MEDLINE | ID: covidwho-2036975

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).


Subject(s)
Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Stroke Volume , Ventricular Function, Left , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucosides/adverse effects , Glucosides/therapeutic use , Heart Failure/complications , Heart Failure/drug therapy , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume/drug effects , Ventricular Function, Left/drug effects
18.
Endocr Pract ; 28(8): 811-821, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2031274

ABSTRACT

OBJECTIVE: The health and economic burden of type 2 diabetes is of global significance. Many people with type 2 diabetes eventually need insulin to help reduce their risk of serious associated complications. However, barriers to the initiation and/or optimization of insulin expose people with diabetes to sustained hyperglycemia. In this review, we investigated how new and future technologies may provide opportunities to help overcome these barriers to the initiation and/or optimization of insulin. METHODS: A focused literature search of PubMed and key scientific congresses was conducted. Software tools and devices developed to support the initiation and/or optimization of insulin were identified by manually filtering >300 publications and conference abstracts. RESULTS: Most software tools have been developed for smartphone platforms. At present, published data suggest that the use of these technologies is associated with equivalent or improved glycemic outcomes compared with standard care, with additional benefits such as reduced time burden and improved knowledge of diabetes among health care providers. However, there remains paucity of good-quality evidence. Most new devices to support insulin therapy help track the dose and timing of insulin. CONCLUSION: New digital health tools may help to reduce barriers to optimal insulin therapy. An integrated solution that connects glucose monitoring, dose recording, and titration advice as well as records comorbidities and lifestyle factors has the potential to reduce the complexity and burden of treatment and may improve adherence to titration and treatment, resulting in better outcomes for people with diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin , Blood Glucose , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin, Regular, Human/therapeutic use
19.
Int J Mol Sci ; 23(16)2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-2023733

ABSTRACT

Glucocorticoids (GCs), which are secreted by the adrenal cortex, are important regulators in the metabolism of carbohydrates, lipids, and proteins. For the proper functioning of the body, strict control of their release is necessary, as increased GCs levels may contribute to the development of obesity, type 2 diabetes mellitus, hypertension, cardiovascular diseases, and other pathological conditions contributing to the development of metabolic syndrome. 11ß-hydroxysteroid dehydrogenase type I (11ß-HSD1) locally controls the availability of the active glucocorticoid, namely cortisol and corticosterone, for the glucocorticoid receptor. Therefore, the participation of 11ß-HSD1 in the development of metabolic diseases makes both this enzyme and its inhibitors attractive targets in the pharmacotherapy of the above-mentioned diseases.


Subject(s)
Diabetes Mellitus, Type 2 , Metabolic Diseases , Metabolic Syndrome , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , Diabetes Mellitus, Type 2/drug therapy , Glucocorticoids/metabolism , Glucocorticoids/therapeutic use , Humans , Metabolic Diseases/drug therapy
SELECTION OF CITATIONS
SEARCH DETAIL