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1.
Arch Toxicol ; 97(2): 329-358, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36592197

RESUMO

In much of the world, currently employed upper limits of tolerable intake and acceptable excretion of cadmium (Cd) (ECd/Ecr) are 0.83 µg/kg body weight/day and 5.24 µg/g creatinine, respectively. These figures were derived from a risk assessment model that interpreted ß2-microglobulin (ß2MG) excretion > 300 µg/g creatinine as a "critical" endpoint. However, current evidence suggests that Cd accumulation reduces glomerular filtration rate at values of ECd/Ecr much lower than 5.24 µg/g creatinine. Low ECd/Ecr has also been associated with increased risks of kidney disease, type 2 diabetes, osteoporosis, cancer, and other disorders. These associations have cast considerable doubt on conventional guidelines. The goals of this paper are to evaluate whether these guidelines are low enough to minimize associated health risks reliably, and indeed whether permissible intake of a cumulative toxin like Cd is a valid concept. We highlight sources and levels of Cd in the human diet and review absorption, distribution, kidney accumulation, and excretion of the metal. We present evidence for the following propositions: excreted Cd emanates from injured tubular epithelial cells of the kidney; Cd excretion is a manifestation of current tissue injury; reduction of present and future exposure to environmental Cd cannot mitigate injury in progress; and Cd excretion is optimally expressed as a function of creatinine clearance rather than creatinine excretion. We comprehensively review the adverse health effects of Cd and urine and blood Cd levels at which adverse effects have been observed. The cumulative nature of Cd toxicity and the susceptibility of multiple organs to toxicity at low body burdens raise serious doubt that guidelines concerning permissible intake of Cd can be meaningful.


Assuntos
Diabetes Mellitus Tipo 2 , Exposição Ambiental , Humanos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Cádmio/toxicidade , Creatinina , Diabetes Mellitus Tipo 2/induzido quimicamente , Rim
2.
Am J Physiol Heart Circ Physiol ; 324(2): H241-H257, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607798

RESUMO

Left ventricular (LV) dysfunction is an early, clinically detectable sign of cardiomyopathy in type 2 diabetes mellitus (T2DM) that precedes the development of symptomatic heart failure. Preclinical models of diabetic cardiomyopathy are essential to develop therapies that may prevent or delay the progression of heart failure. This study examined the molecular, structural, and functional cardiac phenotype of two rat models of T2DM induced by a high-fat diet (HFD) with a moderate- or high-sucrose content (containing 88.9 or 346 g/kg sucrose, respectively), plus administration of low-dose streptozotocin (STZ). At 8 wk of age, male Sprague-Dawley rats commenced a moderate- or high-sucrose HFD. Two weeks later, rats received low-dose STZ (35 mg/kg ip for 2 days) and remained on their respective diets. LV function was assessed by echocardiography 1 wk before end point. At 22 wk of age, blood and tissues were collected postmortem. Relative to chow-fed sham rats, diabetic rats on a moderate- or high-sucrose HFD displayed cardiac reactive oxygen species dysregulation, perivascular fibrosis, and impaired LV diastolic function. The diabetes-induced impact on LV adverse remodeling and diastolic dysfunction was more apparent when a high-sucrose HFD was superimposed on STZ. In conclusion, a high-sucrose HFD in combination with low-dose STZ produced a cardiac phenotype that more closely resembled T2DM-induced cardiomyopathy than STZ diabetic rats subjected to a moderate-sucrose HFD.NEW & NOTEWORTHY Left ventricular dysfunction and adverse remodeling were more pronounced in diabetic rats that received low-dose streptozotocin (STZ) and a high-sucrose high-fat diet (HFD) compared with those on a moderate-sucrose HFD in combination with STZ. Our findings highlight the importance of sucrose content in diet composition, particularly in preclinical studies of diabetic cardiomyopathy, and demonstrate that low-dose STZ combined with a high-sucrose HFD is an appropriate rodent model of cardiomyopathy in type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Ratos , Masculino , Animais , Estreptozocina/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Experimental/induzido quimicamente , Ratos Sprague-Dawley , Dieta Hiperlipídica/efeitos adversos , Fenótipo
3.
JAMA Netw Open ; 6(1): e2251177, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36648944

RESUMO

Importance: Patients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted. Objective: This study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes. Design, Setting, and Participants: This retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics. Exposures: Patients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator). Main Outcomes and Measures: The main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022. Results: This study included 30 385 patients. The propensity score-matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P < .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis. Conclusions and Relevance: The findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Doença Pulmonar Obstrutiva Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Hong Kong/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hipoglicemiantes/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/complicações , Dipeptidil Peptidases e Tripeptidil Peptidases , Glucose , Sódio
4.
Environ Res ; 204(Pt B): 112129, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34597662

RESUMO

BACKGROUND: Positive associations have been reported between persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM); however, causality has not been established. Over the last decades, environmental exposure to legacy POPs has decreased, complicating epidemiological studies. In addition, physiological risk factors for T2DM may also influence POP concentrations, contributing to a complex network of factors that could impact associations with T2DM. Longitudinal studies on this topic are lacking, and few have assessed prospective and cross-sectional associations between repeated POP measurements and T2DM in the same individuals, which may shed light on causality. OBJECTIVES: To compare longitudinal trends in concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in T2DM cases and controls, and to examine prospective and cross-sectional associations between PCBs, OCPs and T2DM at different time-points before and after T2DM diagnosis in cases. METHODS: We conducted a longitudinal, nested case-control study (1986-2016) of 116 T2DM cases and 139 controls from the Tromsø Study. All participants had three blood samples collected before T2DM diagnosis in cases, and up to two samples thereafter. We used linear mixed-effect models to assess temporal changes of POPs within and between T2DM cases and controls, and logistic regression models to investigate the associations between different POPs and T2DM at different time-points. RESULTS: PCBs, trans-nonachlor, cis-nonachlor, oxychlordane, cis-heptachlor epoxide, p,p'-DDE, and p,p'-DDT declined more slowly in cases than controls, whereas ß-HCH and HCB declined similarly in both groups. Most POPs showed positive associations between both pre- and post-diagnostic concentrations and T2DM, though effect estimates were imprecise. These associations were most consistent for cis-heptachlor epoxide. DISCUSSION: The observed positive associations between certain POPs and T2DM may be because of higher POP concentrations within prospective T2DM cases, due to slower temporal declines as compared to controls.


Assuntos
Diabetes Mellitus Tipo 2 , Poluentes Ambientais , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hidrocarbonetos Clorados/análise , Poluentes Orgânicos Persistentes , Bifenilos Policlorados/análise , Estudos Prospectivos
5.
Front Endocrinol (Lausanne) ; 13: 1007980, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36545339

RESUMO

Purpose: To explore the risk of stroke (including ischemic and hemorrhagic stroke) in type 2 diabetes mellitus treated with glucagon-like peptide 1 receptor agonist (GLP-1RA) medication according to data from the Cardiovascular Outcome Trials(CVOT). Methods: Randomized controlled trials (RCT) on GLP-1RA therapy and cardiovascular outcomes in type 2 diabetics published in full-text journal databases such as Medline (via PubMed), Embase, Clinical Trials.gov, and the Cochrane Library from establishment to May 1, 2022 were searched. We assess the quality of individual studies by using the Cochrane risk of bias algorithm. RevMan 5.4.1 software was use for calculating meta- analysis. Results: A total of 60,081 randomized participants were included in the data of these 8 GLP-1RA cardiovascular outcomes trials. Pooled analysis reported statistically significant effect on total stroke risk[RR=0.83, 95%CI(0.73, 0.95), p=0.005], and its subtypes such as ischemic Stroke [RR=0.83, 95%CI(0.73, 0.95), p=0.008] from treatment with GLP-1RA versus placebo, and have no significant effect on the risk of hemorrhagic stroke[RR=0.83, 95%CI(0.57, 1.20), p=0.31] and retinopathy [RR=1.54, 95%CI(0.74, 3.23), p=0.25]. Conclusion: GLP-1RA significantly reduces the risk of ischemic stroke in type 2 diabetics with cardiovascular risk factors.


Assuntos
Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Doenças Retinianas , Acidente Vascular Cerebral , Humanos , Hipoglicemiantes/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Acidente Vascular Cerebral Hemorrágico/induzido quimicamente , Acidente Vascular Cerebral Hemorrágico/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Front Endocrinol (Lausanne) ; 13: 1043789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568085

RESUMO

Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have significantly improved clinical effects on glycemic control. However, real-world data concerning the difference in gastrointestinal adverse events (AEs) among different GLP-1 RAs are still lacking. Our study aimed to characterize and compare gastrointestinal AEs among different marketed GLP-1 RAs (exenatide, liraglutide, dulaglutide, lixisenatide, and semaglutide) based on real-world data. Methods: Disproportionality analysis was used to evaluate the association between GLP-1 RAs and gastrointestinal adverse events. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database between January 2018 and September 2022. Clinical characteristics, the time-to-onset, and the severe proportion of GLP-1 RAs-associated gastrointestinal AEs were further analyzed. Results: A total of 21,281 reports of gastrointestinal toxicity were analyzed out of 81,752 adverse event reports, and the median age of the included patients was 62 (interquartile range [IQR] 54-70) years old. Overall GLP-1 RAs were associated with increased risk of gastrointestinal system disorders (ROR, 1.46; 95% CI, 1.44-1.49), which were further attributed to liraglutide (ROR, 2.39; 95% CI, 2.28-2.51), dulaglutide (ROR, 1.39; 95% CI, 1.36-1.42), and semaglutide (ROR, 3.00; 95% CI, 2.89-3.11). Adverse events uncovered in the labels included gastroesophageal reflux disease, gastritis, bezoar, breath odor, intra-abdominal hematoma, etc. Furthermore, it was observed that semaglutide had the greatest risk of nausea (ROR, 7.41; 95% CI, 7.10-7.74), diarrhea (ROR, 3.55; 95% CI, 3.35-3.77), vomiting (ROR, 6.67; 95% CI, 6.32-7.05), and constipation (ROR, 6.17; 95% CI, 5.72-6.66); liraglutide had the greatest risk of abdominal pain upper (ROR, 4.63; 95% CI, 4.12-5.21) and pancreatitis (ROR, 32.67; 95% CI, 29.44-36.25). Most gastrointestinal AEs tended to occur within one month. Liraglutide had the highest severe rate of gastrointestinal AEs (23.31%), while dulaglutide had the lowest, with a severe rate of 12.29%. Conclusion: GLP-1 RA were significantly associated with gastrointestinal AEs, and the association was further attributed to liraglutide, dulaglutide, and semaglutide. In addition, semaglutide had the greatest risk of nausea, diarrhea, vomiting, constipation, and pancreatitis, while liraglutide had the greatest risk of upper abdominal pain. Our study provided valuable evidence for selecting appropriate GLP-1 RAs to avoid the occurrence of GLP-1 RA-induced gastrointestinal AEs.


Assuntos
Diabetes Mellitus Tipo 2 , Gastroenteropatias , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Idoso , Humanos , Pessoa de Meia-Idade , Dor Abdominal , Constipação Intestinal/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Diarreia/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/efeitos adversos , Liraglutida/efeitos adversos , Náusea/induzido quimicamente , Pancreatite/induzido quimicamente , Vômito/induzido quimicamente , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Estados Unidos/epidemiologia , United States Food and Drug Administration/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos
7.
Cardiovasc Diabetol ; 21(1): 242, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380358

RESUMO

Several randomized controlled trials have demonstrated the benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic stroke in patients with diabetes. In this review, we summarize and discuss the potential mechanisms of stroke protection by GLP-1RAs. GLP-1RAs exert multiple anti-atherosclerotic effects contributing to stroke prevention such as enhanced plaque stability, reduced vascular smooth muscle proliferation, increased nitric oxide, and improved endothelial function. GLP-1RAs also lower the risk of stroke by reducing traditional stroke risk factors including hyperglycemia, hypertension, and dyslipidemia. Independently of these peripheral actions, GLP-1RAs show direct cerebral effects in animal stroke models, such as reduction of infarct volume, apoptosis, oxidative stress, neuroinflammation, excitotoxicity, blood-brain barrier permeability, and increased neurogenesis, neuroplasticity, angiogenesis, and brain perfusion. Despite these encouraging findings, further research is still needed to understand more thoroughly the mechanisms by which GLP-1RAs may mediate stroke protection specifically in the human diabetic brain.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Acidente Vascular Cerebral , Animais , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/induzido quimicamente , Hiperglicemia/induzido quimicamente
8.
J Diabetes Complications ; 36(12): 108332, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36375235

RESUMO

The objective of this article is to review the efficacy and safety of tirzepatide and discuss its potential role in the treatment of type 2 diabetes. Tirzepatide is a novel once-weekly dual GIP and GLP-1 receptor agonist which has been studied in the SURPASS clinical trials in doses of 5 mg, 10 mg, and 15 mg. Tirzepatide phase III clinical trials, SURPASS-1 through SURPASS-5, demonstrate that this medication is safe and effective in treating type 2 diabetes both with and without a variety of background medications versus placebo, semaglutide, insulin degludec, and insulin glargine in different patient populations. Most adverse events were gastrointestinal in nature, with a relatively low withdrawal rate in the active treatment arms. It seems likely that tirzepatide will be recommended as a preferred option in the American Diabetes Association treatment algorithm for high glucose lowering effects in patients with a compelling need for low hypoglycemia risk and weight loss. However, the positioning of tirzepatide in the treatment algorithm will ultimately be dependent on the results of the cardiovascular outcomes trial (CVOT) or other outcome-based trials. Tirzepatide is effective for treating type 2 diabetes by lowering glycated hemoglobin and contributing to significant weight loss.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Polipeptídeo Inibidor Gástrico/efeitos adversos , Redução de Peso
9.
Front Endocrinol (Lausanne) ; 13: 1000872, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339411

RESUMO

Metformin is the first-line oral treatment for type 2 diabetes mellitus and is prescribed to more than 150 million people worldwide. Metformin's effect as a glucose-lowering drug is well documented but the precise mechanism of action is unknown. A recent finding of an association between paternal metformin treatment and increased numbers of genital birth defects in sons and a tendency towards a skewed secondary sex ratio with less male offspring prompted us to focus on other evidence of reproductive side effects of this drug. Metformin in humans is documented to reduce the circulating level of testosterone in both men and women. In experimental animal models, metformin exposure in utero induced sex-specific reproductive changes in adult rat male offspring with reduced fertility manifested as a 30% decrease in litter size and metformin exposure to fish, induced intersex documented in testicular tissue. Metformin is excreted unchanged into urine and feces and is present in wastewater and even in the effluent of wastewater treatment plants from where it spreads to rivers, lakes, and drinking water. It is documented to be present in numerous freshwater samples throughout the world - and even in drinking water. We here present the hypothesis that metformin needs to be considered a potential reproductive toxicant for humans, and probably also for wildlife. There is an urgent need for studies exploring the association between metformin exposure and reproductive outcomes in humans, experimental animals, and aquatic wildlife.


Assuntos
Diabetes Mellitus Tipo 2 , Água Potável , Metformina , Humanos , Masculino , Feminino , Ratos , Animais , Metformina/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Reprodução , Fertilidade
10.
Nutrients ; 14(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364937

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with type 2 diabetes (T2D). Semaglutide, a glucagon-like peptide 1 receptor agonist, may have a therapeutic role by targeting common mechanisms involved in the pathophysiology of T2D and NAFLD. The study aimed to assess the effectiveness of Semaglutide on NAFLD in patients with T2D. METHODS: Forty-eight patients were treated with subcutaneous Semaglutide in add-on to metformin for 52 weeks. After the baseline visit (T0), follow-up was scheduled quarterly (T3, and T6) and then at 12 months of therapy (T12). During each visit, body composition was analyzed by phase-sensitive bio-impedance, and NAFLD was diagnosed and staged by Ultrasound (US) imaging. Surrogate biomarkers of NAFLD were also calculated and followed over time. RESULTS: A significant decrease in anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and laboratory indices of hepatic steatosis was observed during treatment. Similarly, fat mass and visceral adipose tissue (VAT) decreased over time more than skeletal muscle and free-fat mass. US-assessed VAT thickness and the 12-point steatosis score also declined at T3 up to T12. Liver steatosis improved in most patients (70%), showing a reduction by at least one class in the semiquantitative US staging. CONCLUSION: Besides glucose control and body composition improvements, Semaglutide was effective in ameliorating the clinical appearance and severity of NAFLD in T2D patients.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Estudos Prospectivos , Peptídeos Semelhantes ao Glucagon/efeitos adversos
11.
Diabetes Metab Syndr ; 16(11): 102633, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36279701

RESUMO

BACKGROUND AND AIMS: To explore efficacy and safety of empagliflozin in people with type2 diabetes during Ramadan fasting METHODS: People with type2 diabetes (T2DM) who were taking empagliflozin and sulphonylurea with or without a metformin and dipeptidyl peptidase inhibitors (DPP4) recruited a month before Ramadan. Glycated hemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR) were recorded pre- and post-Ramadan. A predesigned diary was given to the participants to keep track of their T2DM status during Ramadan. The proportion of the people who had hypoglycaemia, or any adverse event related to the study drug was assessed after-Ramadan. RESULTS: A total of 116 participants completed the study. Symptomatic episodes of hypoglycaemia were more common among people who used sulphonylurea (i.e., 8.6%). Genitourinary infections and volume depletion events were recorded more in people on empagliflozin i.e., (6.9% and 5.17%, respectively). A significant reduction in body mass index (BMI), and HbA1c was noted among people on empagliflozin post Ramadan. A significant reduction in eGFR was noted only in people who were taking empagliflozin in combination with metformin. CONCLUSION: Empagliflozin was found to be safe and effective in fasting people with T2DM. Further large-scale studies are needed to validate our findings.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Jejum , Hipoglicemiantes/efeitos adversos , Islamismo , Compostos de Sulfonilureia/efeitos adversos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Metformina/efeitos adversos , Glicemia
12.
Diabetes Metab Syndr ; 16(11): 102640, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36274410

RESUMO

BACKGROUND AND AIMS: This study aims to explore the efficacy and safety of tirzepatide for patients with type 2 diabetes (T2D). METHODS: Using specific keywords, we comprehensively go through the potential articles on Europe PMC, Scopus, PubMed, and ClinicalTrials.gov sources until July 12th, 2022. We collected all clinical trials that compare tirzepatide 5, 10, or 15 mg once-weekly with placebo or other glucose lowering agents in adult patients with T2D. RESULTS: Nine clinical trials were included. Our pooled analysis revealed the dose-dependent superiority of tirzepatide in reducing HbA1c, ranging from -1.50% with 5 mg to -1.80% with 15 mg when compared with placebo, -0.61% with 5 mg to -0.95% with 15 mg when compared with GLP-1 receptor agonist, and -0.70% with 5 mg to 1.09% with 15 mg when compared with basal insulin. The dose-dependent superiority of tirzepatide was also seen in the bodyweight reduction effect with all comparators. These superiorities were not accompanied by increased odds of hypoglycemia, but there is an increase in gastrointestinal adverse events incidence. CONCLUSIONS: Tirzepatide has shown superiority in glycemic control and bodyweight reduction with a good safety profile in patients with T2D. Tirzepatide may become a future potential drug in the management of T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Polipeptídeo Inibidor Gástrico/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas
13.
Int J Chron Obstruct Pulmon Dis ; 17: 2635-2652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36274995

RESUMO

Purpose: We analyzed population-level administrative claims data for Medicare fee-for-service (FFS) beneficiaries to provide insights on systemic oral corticosteroid (OCS) use patterns and associated health conditions and acute events among patients newly diagnosed with chronic obstructive pulmonary disease (COPD). Background: COPD is a progressive inflammatory disease of the lungs, characterized by acute exacerbations that may lead to increased mortality. Short courses of systemic corticosteroids (SCS) are recommended to reduce recovery time from exacerbations, although SCS use has been associated with increased risk of adverse events. Methods: This study used 2013-2019 Medicare 100% FFS research identifiable files, which contain all Medicare Parts A, B, and D paid claims incurred by 100% of Medicare FFS beneficiaries. Descriptive statistics for patients newly diagnosed with COPD were analyzed, including OCS use, select health conditions and acute events, and COPD exacerbations. Statistical models were used to analyze the relationship between the incidence of select health conditions and events and cumulative OCS dosage. Results: Of Medicare FFS patients newly diagnosed with COPD, 36% received OCS in the 48 months following diagnosis, and 38% of OCS episodes lasted longer than the recommended 5-7 days. Patients had a variety of health conditions or acute events in the 24-month period prior to new COPD diagnosis, such as hypertension, depression/anxiety, type 2 diabetes, or osteoporosis, that could heighten the risks of OCS use. Patients treated with >1000 mg of prednisolone equivalent OCS in the 48 months following COPD diagnosis had a higher incidence of new conditions or events, including cardiovascular disease, heart failure, hypertension, obesity, dyspepsia, infections, and depression/anxiety, than patients with no OCS use. Conclusion: These results highlight the potential risks of OCS in COPD treatment, including prolonged use among complex Medicare patients, and reinforce the importance of preventive treatment strategies and therapy optimization early in the disease course.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Estados Unidos/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Medicare , Revisão da Utilização de Seguros , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/induzido quimicamente , Corticosteroides/efeitos adversos , Prednisolona
14.
J Diabetes Investig ; 13(12): 1971-1980, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36222597

RESUMO

AIMS/INTRODUCTION: The etiology and treatment of type 2 diabetes might differ between specific populations. This post-hoc exploratory analysis assessed the efficacy and safety of once-weekly subcutaneous semaglutide vs comparators in Japanese individuals with type 2 diabetes in comparison with the total population from four phase III studies in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN) program. MATERIALS AND METHODS: This analysis was carried out with data from the SUSTAIN 1, 2, 5 and 9 trials. Post-hoc analyses were carried out to assess outcomes in all participants and in Japanese participants in each study. The primary end-point was the change from baseline to end of study in glycated hemoglobin (%). The confirmatory secondary end-point was change from baseline to end of study in bodyweight (kg). RESULTS: Change from baseline to end of study in glycated hemoglobin with once-weekly semaglutide ranged from -1.32 to -1.85% points in the overall populations, and -1.69 to -2.49% points in Japanese participants. With once-weekly semaglutide, relative bodyweight was reduced from baseline to end of study by 4.0-7.3% in the overall populations, and 2.7-10.4% in Japanese participants. In the Japanese subpopulation, no new safety concerns were identified with once-weekly semaglutide, and there were no adverse events leading to death or severe hypoglycemic episodes. CONCLUSIONS: In this post-hoc analysis, participants with type 2 diabetes initiating once-weekly semaglutide experienced improvements in glycated hemoglobin and bodyweight in both the overall and Japanese population, and no new safety concerns were identified among Japanese participants, supporting the efficacy of once-weekly semaglutide in this population.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Japão , Hipoglicemiantes/efeitos adversos , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peso Corporal , Resultado do Tratamento
15.
Diabetes Metab Syndr ; 16(10): 102638, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36223666

RESUMO

BACKGROUND & AIMS: Finerenone is a novel non-steroidal mineralocorticoid antagonist (MRA) recently approved for the treatment of chronic kidney disease (CKD) in people with type 2 diabetes (T2D). We aim to conduct a systematic review of finerenone to know the efficacy and safety of finerenone in CKD with or without T2D. METHODS: A systematic search in the electronic database of PubMed and Google Scholar was made from inception until September 09, 2022, using several MeSH keywords related to finerenone. Ongoing trials were additionally searched from ClinicalTrials.Gov. RESULTS: Five phase 2 and three phase 3, randomized, double-blind, placebo- or active-controlled studies of finerenone have been published to date and several other randomized and real-world studies of finerenone are currently undergoing. CONCLUSIONS: In short-term studies in patients with CKD and reduced ejection heart failure, with or without T2D, finerenone 20 mg appears to have a better renal outcome compared with spironolactone and a better mortality outcome compared with eplerenone, with significantly lesser hyperkalemia compared to both spironolactone and finerenone. In long-term studies in patients with CKD and T2D, finerenone 10/20 mg significantly reduces the progression of renal disease and reduced CV endpoints (especially heart failure hospitalization) compared to placebo. Finerenone has no effect on HbA1c, body weight, and sexual side effects including gynecomastia, and has only a modest effect on blood pressure. However, hyperkalemia leading to drug withdrawal was significantly higher with finerenone compared to placebo. Safety data in real-world settings is a pressing priority.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Cardíaca , Hiperpotassemia , Insuficiência Renal Crônica , Masculino , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/induzido quimicamente , Eplerenona/uso terapêutico , Espironolactona/efeitos adversos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
BMJ Open ; 12(10): e066491, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302574

RESUMO

INTRODUCTION: Participants in randomised controlled trials (trials) are generally younger and healthier than many individuals encountered in clinical practice. Consequently, the applicability of trial findings is often uncertain. To address this, results from trials can be calibrated to more representative data sources. In a network meta-analysis, using a novel approach which allows the inclusion of trials whether or not individual-level participant data (IPD) is available, we will calibrate trials for three drug classes (sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor analogues and dipeptidyl peptidase-4 (DPP4) inhibitors) to the Scottish diabetes register. METHODS AND ANALYSIS: Medline and EMBASE databases, the US clinical trials registry (clinicaltrials.gov) and the Chinese Clinical Trial Registry (chictr.org.cn) will be searched from 1 January 2002. Two independent reviewers will apply eligibility criteria to identify trials for inclusion. Included trials will be phase 3 or 4 trials of SGLT2 inhibitors, GLP1 receptor analogues or DPP4 inhibitors, with placebo or active comparators, in participants with type 2 diabetes, with at least one of glycaemic control, change in body weight or major adverse cardiovascular event as outcomes. Unregistered trials will be excluded.We have identified a target population from the population-based Scottish diabetes register. The chosen cohort comprises people in Scotland with type 2 diabetes who either (1) require further treatment due to poor glycaemic control where any of the three drug classes may be suitable, or (2) who have adequate glycaemic control but are already on one of the three drug classes of interest or insulin. ETHICS AND DISSEMINATION: Ethical approval for IPD use was obtained from the University of Glasgow MVLS College Ethics Committee (Project: 200160070). The Scottish diabetes register has approval from the Scottish A Research Ethics Committee (11/AL/0225) and operates with Public Benefit and Privacy Panel for Health and Social Care approval (1617-0147). PROSPERO REGISTRATION NUMBER: CRD42020184174.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes/uso terapêutico , Metanálise como Assunto , Metanálise em Rede , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Revisões Sistemáticas como Assunto
17.
BMJ Open ; 12(10): e060655, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36241355

RESUMO

OBJECTIVES: To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. METHODS: We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI. RESULTS: We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m2/year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion. CONCLUSIONS: Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD. PROSPERO REGISTRATION NUMBER: CRD42021239807.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Sódio/uso terapêutico , Transportador 2 de Glucose-Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
18.
Rinsho Shinkeigaku ; 62(10): 801-804, 2022 Oct 22.
Artigo em Japonês | MEDLINE | ID: mdl-36184416

RESUMO

A 79-year-old-man with a clinical history of type 2 diabetes and hypertension was admitted to our hospital for recurrent right hemiparesis. He was referred to our department with left internal carotid artery stenosis. Cerebral angiography with a slight contrast agent revealed NASCET 86% stenosis at the left internal carotid bifurcation. Although no neurological deficit was observed, he had a renal dysfunction with an estimated glomerular filtration rate of 32.2 ml/min/1.73 m2. We used a 3D fusion image obtained from the initial angiography with B-mode and intravascular ultrasound to avoid aggravating renal function instead of using a contrast medium. Following the procedure, favorable expansion of the stenotic region was achieved, and no evidence of recurrence was seen during the follow-up period. 3D fusion imaging is a valuable and safe method for endovascular treatment of carotid artery stenosis for patients with renal dysfunction.


Assuntos
Estenose das Carótidas , Diabetes Mellitus Tipo 2 , Nefropatias , Masculino , Humanos , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Stents , Meios de Contraste/efeitos adversos , Angiografia Cerebral , Diabetes Mellitus Tipo 2/induzido quimicamente , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/cirurgia , Nefropatias/induzido quimicamente , Artéria Carótida Interna
19.
J Am Heart Assoc ; 11(20): e026743, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36250658

RESUMO

Background Although endocrine therapy is an effective treatment for breast cancer, its antiestrogen effects are associated with increased risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the association between endocrine therapy and the risk of cardiovascular diseases and type 2 diabetes among breast cancer survivors in Korea, in consideration of various age groups. Methods and Results In the National Health Insurance Service database of Korea, a total of 133 171 patients with breast cancer aged ≥20 years were included in the current study. Endocrine therapy was treated as time-varying exposure, and patients were categorized as nonusers, selective estrogen receptor modulator users, aromatase inhibitor users, and both users. Time-dependent Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs. Age at diagnosis, socioeconomic status, histological type, other treatments, and comorbidities were adjusted in the model. Compared with nonusers, selective estrogen receptor modulator users were associated with higher risks of stroke (HR, 1.20 [95% CI, 1.04-1.40]) and venous thromboembolism (HR, 1.47 [95% CI, 1.13-1.90]), whereas aromatase inhibitor users were associated with a higher risk of coronary heart disease (HR, 1.22 [95% CI, 1.06-1.41]). The risk of type 2 diabetes was associated with selective estrogen receptor modulator users (HR, 1.13 [95% CI, 1.05-1.21]), aromatase inhibitor users (HR, 1.14 [95% CI, 1.05-1.23]), and both users (HR, 1.24 [95% CI, 1.10-1.39]). In particular, the risk of a composite of cardiovascular diseases was higher in younger or premenopausal patients. Conclusions In breast cancer survivors in Korea, endocrine therapy is associated with a higher risk of cardiovascular diseases and type 2 diabetes. Monitoring of cancer comorbidities after endocrine therapy is needed in younger and older patients.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Feminino , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Tamoxifeno/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Moduladores Seletivos de Receptor Estrogênico , Programas Nacionais de Saúde
20.
Metabolism ; 137: 155332, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36240884

RESUMO

Type 2 diabetes (T2D) is a widely prevalent disease with substantial economic and social impact for which multiple conventional and novel pharmacotherapies are currently available; however, the landscape of T2D treatment is constantly changing as new therapies emerge and the understanding of currently available agents deepens. This review aims to provide an updated summary of the pharmacotherapeutic approach to T2D. Each class of agents is presented by mechanism of action, details of administration, side effect profile, cost, and use in certain populations including heart failure, non-alcoholic fatty liver disease, obesity, chronic kidney disease, and older individuals. We also review targets of novel therapeutic T2D agent development. Finally, we outline an up-to-date treatment approach that starts with identification of an individualized goal for glycemic control then selection, initiation, and further intensification of a personalized therapeutic plan for T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
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