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1.
Obes Surg ; 34(6): 2216-2226, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38668820

RESUMO

Since a previous systematic review published in 2016, there have been further studies investigating the association of changes in cognitive function following bariatric surgery. All studies since the original review that reported at least one element of cognitive function before and after bariatric surgery were eligible. A total of 137 additional studies were identified; 13 were included in addition to the 18 studies previously. Almost all studies reported improvements in at least one domain. Most revealed improvements were limited to a few domains and were not universal. Further findings investigated cognitive function improvement in relation to procedure choice, and mental health or quality of life post-surgery. Further high-powered studies are still necessary, but these findings support the impact of bariatric surgery on cognitive function in obesity.


Assuntos
Cirurgia Bariátrica , Cognição , Obesidade Mórbida , Qualidade de Vida , Humanos , Cirurgia Bariátrica/psicologia , Cognição/fisiologia , Obesidade Mórbida/cirurgia , Obesidade Mórbida/psicologia , Feminino , Masculino , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade
2.
Diabetes Obes Metab ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602398

RESUMO

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs. CONTROL: SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1. CONCLUSIONS: Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.

3.
J Diabetes Metab Disord ; 22(2): 1763-1768, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37975098

RESUMO

Background: Bariatric surgery is well-established to support long-term metabolic health benefits associated with considerable weight loss. Here, we aim to determine the longer-term impact of bariatric surgery on liver enzymes and associations with other metabolic improvements. Methods: One hundred patients who underwent bariatric surgery between 2007 and 2014 were included, and changes in liver enzymes, anthropometric measures and other parameters were observed over a mean 9.8 years. Results: At the time of surgery, the mean age was 45.4 ± 9.6 years, weight 141.2 ± 31.6 kg, and body mass index (BMI) 50.2 ± 10.1 kg/m2. Most patients underwent sleeve gastrectomy [n = 71] with a mean follow-up duration 9.8 ± 2.3 years. From baseline, alanine transaminase (ALT) reduced by 41.3% within 12 months post-operatively (36.6 ± 29.2 U/L to 21.5 ± 14.9 U/L, p < 0.001), which was sustained at recent follow-up (20.2 ± 10.7 U/L, p < 0.001). There were associated reductions in body weight, BMI, HbA1c, blood pressure and triglycerides. Patients with greater baseline ALT had the greatest reduction in ALT over follow-up. Conclusions: Bariatric surgery is associated with rapid and sustained improvements in routine liver enzymes at 10 years, and sustained improvements in features of the metabolic syndrome. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01311-4.

4.
Eur Geriatr Med ; 14(5): 1105-1110, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37612537

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2D) is associated with poor health outcomes whilst tight glycaemic targets are questionable in those aged over 70 years with increased frailty. Our aim was to examine whether people with T2D admitted to hospital with a fall, were more likely to have greater frailty, increased mortality and co-morbidity burden, or risk factors for falls than people without T2D, and whether these differences were associated with medications used for the treatment of T2D. METHODS: The Older Persons Assessment Service (OPAS) is a local emergency department (ED) service, which accepts patients on frailty criteria. The OPAS accepts patients primarily aged over 70 years who present with frailty and geriatric syndromes such as falls, with retrieval from the ED department directly to the service from triage. The OPAS databank was analysed for people with T2D admitted with a fall between June 2020-September 2022. We examined clinical outcomes relating to medication, age, Charlson co-morbidity index (CCI) and clinical frailty score (CFS). RESULTS: 1081 patients were included: 294 (27.2%) with T2D and a mean HbA1c of 53.9 (± 15.8) mmol/mol [7.1%]. People with T2D had a similar mean CFS and age compared to those without T2D, but higher mean CCI (7.0 ± 2.2 vs 5.9 ± 2.1, p < 0.001). Of those people with T2D, 175 (59.5%) and 240 (81.6%) had a HbA1c ≤ 53 mmol/mol [7.0%] and ≤ 64 mmol/mol [8.0%], respectively. In total, 48 (16.3%) people with T2D were identified to have a capillary blood glucose below 4.0 mmol/L on admission to the ED. At 12 months' follow-up, 831 (76.9%) patients were alive and 250 (23.1%) had died. People with T2D treated with insulin and/or gliclazide had a greater 1-year mortality (36.6% vs 23.6%, p < 0.05), greater frequency of hypoglycaemia (35.4% vs 11.8%, p < 0.001), and greater HbA1c (65.5 ± 17.2 mmol/mol [8.2] vs 48.9 ± 12.1 mmol/mol [6.6%]) compared to those who used other agents. Logistic regression confirmed a diagnosis of T2D was associated with 1-year mortality, but mortality was not significantly associated with hypoglycaemic-inducing agents. People with T2D were not more likely to live in deprived areas. CONCLUSIONS: A diagnosis of T2D is associated with greater 1-year mortality, and may be influenced by use of hypoglycaemia-inducing diabetes medications. Clinician awareness can support de-prescribing for patients with frailty and HbA1c < 64 mmol/mol.

5.
Postgrad Med J ; 99(1172): 595-598, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37319160

RESUMO

BACKGROUND AND AIMS: Pituitary apoplexy (PA) is a rare neurosurgical emergency, associated with deficiency of one or more pituitary hormones. Few studies have explored the relative outcomes associated with conservative and neurosurgical intervention. METHODS: A retrospective evaluation of all patients with PA reviewed at Morriston Hospital was undertaken and diagnosis was obtained from Morriston database (Leicester Clinical Workstation database) between 1998 and 2019 from clinic letters and discharge summaries. RESULTS: Thirty-nine patients with PA were identified with a mean age of 74.5 years and 20 (51.3%) patients were women. Patients were followed up for a mean±SD 68.1±61.7 months. Twenty-three (59.0%) patients had a known pituitary adenoma. Commoner clinical presentations of PA were ophthalmoplegia or visual field loss. Following PA, 34 (87.2%) patients were noted to have a non-functioning pituitary adenoma (either pre-existing or new), while 5 (12.8%) patients had a pre-existing functional macroadenoma. Neurosurgical intervention was taken in 15 (38.5%) patients of which 3 (20.0%) patients also received radiotherapy, 2 (13.3%) patients had radiotherapy alone and the remainder managed conservatively. External ophthalmoplegia recovered in all cases. Visual loss remained in all cases. One (2.6%) patient with chromophobe adenoma had a significant second episode of PA requiring repeat surgery. CONCLUSION: PA often occurs in patients with undiagnosed adenoma. Hypopituitarism commonly occurred following conservative or surgical treatment. External ophthalmoplegia resolved in all cases, however, visual loss did not recover. Pituitary tumour recurrence and further PA episodes are rare.


Assuntos
Adenoma , Oftalmoplegia , Apoplexia Hipofisária , Neoplasias Hipofisárias , Humanos , Feminino , Idoso , Masculino , Apoplexia Hipofisária/diagnóstico , Apoplexia Hipofisária/terapia , Apoplexia Hipofisária/complicações , Estudos Retrospectivos , Seguimentos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/terapia , Recidiva Local de Neoplasia , Transtornos da Visão/etiologia , Adenoma/complicações , Adenoma/cirurgia , Oftalmoplegia/complicações
6.
Int J Cardiol ; 377: 104-111, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36764610

RESUMO

AIM: To assess compliance with European Society of Cardiology (ESC) secondary prevention recommendations in a nationwide contemporary population with diabetes mellitus (DM) and coronary artery disease. METHOD: We conducted a retrospective observational study using linked health data in patients across Wales with DM undergoing percutaneous coronary intervention (2012-2017). The follow-up was for one year. We analysed the clinical characteristics, medications, target levels for HbA1c, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and blood pressure against the ESC prevention guidelines. RESULTS: Overall, 3478 patients with diabetes had available data at 1-year post-PCI. Only 43% had HbA1c levels <53 mmol/L, but 81% had blood pressure < 140/80 (current ESC targets). Prescribing frequency of the newer hypoglycaemic agents (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors) was suboptimal, with a higher rate in patients with HbA1c ≥53 mmol/mol. Only 51% & 27% of the patients had LDL-C levels <1.8 &1.4 mmol/L (2016 & 2019 guidelines recommendations respectively), and 55% & 34% had non-HDL-C levels <2.6 & 2.2 mmol/L (2016 & 2019 guidelines respectively). Of the uncontrolled LDL-C patients, 42% (2016 target) and 35% (2019 target) were prescribed high-intensity statins. Females were more likely to have LDL-C targets above the recommended level. CONCLUSION: Achievement of ESC treatment goals in this very-high risk cohort for DM and hyperlipidaemia was far from optimal, with a low prescription rate of the guidelines-recommended therapy. Target goals for hypertension were met more frequently. An up-to-date analysis reflecting the current practice against the most recent guidelines is warranted.


Assuntos
Cardiologia , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Intervenção Coronária Percutânea , Feminino , Humanos , LDL-Colesterol , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Prevenção Secundária , Hemoglobinas Glicadas , Fatores de Risco , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Colesterol , Estudos de Coortes , Fatores de Risco de Doenças Cardíacas
8.
Diabetes Metab Syndr ; 16(12): 102658, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36371968

RESUMO

BACKGROUND AND AIMS: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are associated with diabetic ketoacidosis (DKA), however limited case series are published. METHODS: We evaluated the characteristics of patients admitted with SGLT-2i associated DKA. RESULTS: Over 4 months, 22 patients were identified; 45.5% of DKA was not associated with concurrent illness. CONCLUSION: DKA is not uncommonly associated with SGLT2i with no clear patient factors associated with severity.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/complicações , Atenção Secundária à Saúde , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
9.
Pract Neurol ; 22(6): 532-539, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35907634

RESUMO

Diabetes mellitus is a common condition associated with numerous complications and comorbidities. The diabetes spectrum includes type 1, type 2 and other forms of diabetes, which may be associated with medical therapies and genetic factors. Type 2 diabetes is managed with lifestyle, oral therapies, non-insulin-based injectables and subsequently insulin. Type 1 diabetes requires insulin from the time of diagnosis. In recent years, there have been considerable developments in the therapies available to treat type 2 diabetes and some of these also afford cardiorenal protection. This review summarises the nature, complications and therapeutic advances in the field of diabetes and provides a concise review for neurologists. Managing diabetes optimally prevents complications and all medical specialties need a basic understanding of the principles involved in diabetes care.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neurologistas , Insulina/uso terapêutico , Comorbidade
12.
Diabetes Metab Syndr Obes ; 15: 281-295, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153495

RESUMO

Previous guidelines for the treatment of people with type 2 diabetes mellitus (T2D) have relied heavily upon rigid algorithms for the sequential addition of pharmacotherapies to achieve target glycemic control. More recent guidelines advocate a personalized approach for diabetes treatment, to improve patient satisfaction, quality of life, medication adherence and overall health outcomes. Clinicians should work with patients to develop personalized goals for their treatment, including targeted glycemic control, weight management, prevention and treatment of associated comorbidities and avoidance of complications such as hypoglycemia. Factors that affect the intensity of treatment and choice of pharmacotherapy should include medical and patient influences. Medical considerations include the diabetes phenotype, biomarkers including genetic tests, and the presence of comorbidities such as cardiovascular, renal, or hepatic disease. Patient factors include their treatment preference, age and life expectancy, diabetes duration, hypoglycemia fear and unawareness, psychological and social circumstances. The use of a personalized approach in the management of people with T2D can reduce the cost and failure associated with the algorithmic "one-size-fits-all" approach, to anticipate disease progression, improve the response to diabetes pharmacotherapy and reduce the incidence of diabetes-associated complications. Ultimately, the use of personalized medicine in people with T2D should improve medication adherence, patient satisfaction and quality of life to reduce diabetes distress and improve physical health outcomes.

13.
Diabetes Obes Metab ; 23(8): 1806-1822, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830637

RESUMO

AIM: To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes. METHODS: Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation: C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m2 and diabetes duration 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference -0.54 mg/L [-0.75, -0.34]; standard mean difference [SMD] -0.39 [-0.62, -0.15]; SMD -0.84 [-1.61, -0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. CONCLUSIONS: There is strong evidence supporting clinically relevant anti-inflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Biomarcadores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Diabetes Ther ; 12(3): 801-811, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33565043

RESUMO

INTRODUCTION: The glucagon-like peptide-1 receptor analogue (GLP-1RA) semaglutide is associated with improvements in glycaemia and cardiovascular risk factors in clinical trials. The aim of this study was to examine the real-world impact of semaglutide administered by injection in people with type 2 diabetes (T2D) across three secondary care sites in Wales. METHODS: A retrospective evaluation of 189 patients with T2D initiated on semaglutide between January 2019 and June 2020 with at least one follow-up visit was undertaken. RESULTS: At baseline, participants had a mean age of 61.1 years, mean glycated haemoglobin (HbA1c) of 77.8 mmol/mol (9.3%) and mean body weight of 101.8 kg. At 6 and 12 months of follow-up, mean HbA1c reductions of 13.3 mmol/mol (1.2%) and 16.4 mmol/mol (1.5%), respectively, were observed, and mean weight loss at 6 months was 3.0 kg (all p < 0.001). At 12 months, there were significant reductions in total cholesterol (0.5 mmol/L) and alanine transaminase (4.8 IU/L). Patients naïve to GLP-1RAs or with higher baseline HbA1c at baseline had greater glycaemic reductions, although clinically significant HbA1c reductions were also observed in those who switched from other GLP-1RAs, whose body mass index was < 35.0 and > 35.0 kg/m2 or who had lower baseline HbA1c. Semaglutide was generally well tolerated, although adverse-effects limited use in 18 patients (9.5%). CONCLUSION: Semaglutide provided clinically and statistically significant reductions in HbA1c, body weight, lipids and liver enzymes.

15.
Clin Hemorheol Microcirc ; 77(2): 183-194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32925001

RESUMO

BACKGROUND: Diabetic ketoacidosis (DKA) is a medical emergency with a high mortality rate and is associated with severe metabolic acidosis and dehydration. DKA patients have an increased risk of arterial and venous thromboembolism, however little is known about this metabolic derangement in the first 24 hours of admission and to assess its effect on coagulation. We therefore utilised a novel functional marker of clot microstructure (fractal dimension - df) to assess these changes within the first 24 hours. METHODS: Prospective single centre observational study to demonstrate whether the tendency of blood clot formation differs in DKA patients. RESULTS: 15 DKA patients and 15 healthy matched controls were recruited. Mean df in the healthy control group was 1.74±0.03. An elevated df of 1.78±0.07 was observed in patients with DKA on admission. The mean pH on admission was 7.14±0.13 and the lactate was 3.6±2.0. df changed significantly in response to standard treatment and was significantly reduced to 1.68±0.09 (2-6& h) and to 1.66±0.08 at 24& h (p < 0.01 One-way ANOVA). df also correlated significantly with lactate and pH (Pearson correlation coefficient 0.479 and -0.675 respectively, p < 0.05). CONCLUSIONS: DKA patients at presentation have a densely organising less permeable thrombogenic clot microstructure as evidenced by high df. These structural changes are due to a combination of dehydration and a profound metabolic acidosis, which was reversed with treatment. These changes were not mirrored in standard clinical markers of thromboge-nicity.


Assuntos
Biomarcadores/sangue , Cetoacidose Diabética/tratamento farmacológico , Hemorreologia/fisiologia , Trombose/tratamento farmacológico , Estudos de Casos e Controles , Cetoacidose Diabética/sangue , Feminino , Fractais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Diabetes Res Clin Pract ; 168: 108368, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32800932

RESUMO

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a protective cardiorenal effect in type 2 diabetes. This systematic review examines the effects of SGLT2is on clinical biomarkers of inflammation and oxidative stress. METHODS: A search of Medline, Embase, Web of Science, and The Cochrane Library was performed examining changes in selected clinical biomarkers for inflammation: c-reactive protein (CRP), adiponectin, interleukin-6 (IL6), tumour necrosis factor-alpha (TNF-α), and oxidative stress: 8-iso-prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Quality of evidence was evaluated using the GRADEpro tool and risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools. RESULTS: A total of 23 (15 randomised, 8 observational) heterogeneously-designed clinical studies were identified (1654 patients, 24 weeks median follow-up). Consistent reductions were observed for CRP (10/12 studies), IL6 (5/5 studies), TNFα (3/4 studies), 8-iso-PGF2α (3/4 studies) and 8-OHdG (2/2 studies), and a consistent increase in adiponectin (6/8 studies). Change in serum CRP following SGLT2is appear to be independent of change in HbA1c and other study design and clinically relevant variables. CONCLUSIONS: There is heterogeneous, yet consistent data supporting the beneficial effects of SLGT2is on inflammatory and oxidative stress. Change in serum CRP appears to be independent of change in HbA1c.


Assuntos
Biomarcadores/sangue , Inflamação/sangue , Estresse Oxidativo/fisiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
17.
Lancet HIV ; 7(6): e389-e400, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32504574

RESUMO

BACKGROUND: In the primary week-48 analyses of two phase 3 studies, coformulated bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to a dolutegravir-containing regimen in treatment-naive people with HIV. We report week-144 efficacy and safety results from these studies. METHODS: We did two double-blind, active-controlled studies (now in open-label extension phase). Study 1 randomly assigned (1:1) HLA-B*5701-negative adults without hepatitis B virus co-infection to receive coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, or coformulated dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg once daily. Study 2 randomly assigned (1:1) adults to bictegravir, emtricitabine, and tenofovir alafenamide, or dolutegravir 50 mg given with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg. We previously reported non-inferiority at the primary endpoint. Here, we report the week-144 secondary outcome of proportion of participants with plasma HIV-1 RNA less than 50 copies per mL at week 144, by US Food and Drug Administration Snapshot algorithm, analysed in the same manner. These studies were registered with ClinicalTrials.gov, NCT02607930 and NCT02607956. FINDINGS: 629 participants were randomly assigned and treated in study 1 (314 to bictegravir, emtricitabine, and tenofovir alafenamide, and 315 to dolutegravir, abacavir, and lamivudine) and 645 in study 2 (327 to bictegravir, emtricitabine, and tenofovir alafenamide, 325 to dolutegravir, emtricitabine, tenofovir alafenamide). At week 144, bictegravir, emtricitabine, and tenofovir alafenamide was non-inferior to both dolutegravir-containing regimens for efficacy. In study 1, 256 (82%) of 314 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 265 (84%) of 315 in the dolutegravir, abacavir, and lamivudine group (difference -2·6%, 95% CI -8·5 to 3·4). In study 2, 262 (82%) of 320 participants had plasma HIV-1 RNA less than 50 copies per mL in the bictegravir, emtricitabine, and tenofovir alafenamide group and 273 (84%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (difference -1·9%, -7·8 to 3·9). In both studies, no participant had treatment-emergent resistance to study drugs up to week 144. All treatment regimens were well tolerated with additional exposure. Adverse events that led to study drug discontinuation were reported for no participants in the bictegravir, emtricitabine, and tenofovir alafenamide group versus five (2%) of 315 in the dolutegravir, abacavir, and lamivudine group (study 1), and six (2%) of 320 in the bictegravir, emtricitabine, and tenofovir alafenamide versus six (2%) of 325 in the dolutegravir, emtricitabine, and tenofovir alafenamide group (study 2). In study 1, statistically significant differences were observed in median changes from baseline in fasting total cholesterol (14 mg/dL vs 10 mg/dL; p=0·034), direct LDL (21 mg/dL vs 14 mg/dL; p=0·004), and total cholesterol to HDL ratio (-0·1 vs -0·3; p=0·007) at week 144; no differences were observed between groups in study 2. Weight gain was seen across all treatment groups in both studies, with no differences in median changes from baseline in weight at week 144 for either study. INTERPRETATION: These long-term data support the use of bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people with HIV, with no emergent resistance. FUNDING: Gilead Sciences.


Assuntos
Adenina/análogos & derivados , Didesoxinucleosídeos/administração & dosagem , Emtricitabina/administração & dosagem , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Lamivudina/administração & dosagem , Tenofovir/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Idoso , Alanina , Didesoxinucleosídeos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Emtricitabina/efeitos adversos , Feminino , Infecções por HIV/virologia , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , RNA Viral/sangue , Tenofovir/efeitos adversos , Resultado do Tratamento , Adulto Jovem
18.
Diabetes Metab Syndr ; 14(3): 237-239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247210

RESUMO

BACKGROUND AND AIMS: We examined HbA1c and cardiovascular risk factors with a median follow-up of 44 months therapy with dapagliflozin. METHODS: We undertook a clinical practice evaluation of 101 patients attending our clinic. RESULTS: Dapagliflozin resulted in a significant reduction in HbA1c 82.6 ± 15.7 v 68.7 ± 17.8 mmol/mol. CONCLUSION: Dapagliflozin maintains glycaemic control along with sustained improvements in weight and no decline in renal function.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Redução de Peso/efeitos dos fármacos , Idoso , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Secundária à Saúde , Resultado do Tratamento , Reino Unido
19.
Diabetes Obes Metab ; 22 Suppl 1: 32-45, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32267078

RESUMO

This review examines the current literature relating to diabetes related kidney disease (DKD) and the optimal management of cardio-renal risk. DKD develops in approximately 40% of patients with type 2 diabetes mellitus. The mainstay of therapy is to reduce the progression of DKD by optimising hyperglycaemia, blood pressure, lipids and lifestyle. Evidence supports the role for renin-angiotensin system blockade in limiting the progression of DKD. Recent data from diabetes related cardiovascular outcome trials and renal specific trials have provided a novel insight on the additional benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing the progression of DKD as well as cardiovascular risk. Lessons have been learnt from CREDENCE and there are expectations that DAPA-CKD and EMPA-KIDNEY will further support the benefits of SGLT2 inhibition in relation to DKD. As a consequence, international guidelines have been updated to reflect the positive benefits. In addition, novel steroidal mineralocorticoid receptor antagonists offer a potential role in future years. The review examines the current evidence and future approach to optimising outcomes for renal protection in patients with diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Controle Glicêmico , Humanos , Rim , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
20.
Diabetes Metab Syndr ; 14(2): 101-106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995784

RESUMO

BACKGROUND AND AIMS: There is inconsistent evidence supporting the self-monitoring of blood glucose (SMBG) in people with non-insulin treated type 2 diabetes (T2D). Structured SMBG protocols have a greater impact on glycaemic control than unstructured SMBG and may improve measures of glycaemic variability (GV), though few previous studies have reported on specific GV outcomes. Our aim was to determine the impact of structured SMBG on simple measures of GV in people with T2D. METHODS: Participants undertook structured SMBG over 12 months, with HbA1c recorded at baseline and at 3-monthly follow-up. For each participant, the mean blood glucose (MBG), fasting blood glucose (FBG), standard deviation BG (SD-BG), coefficient of variation of BG (CV-BG), mean absolute glucose change (MAG) and HbA1c were determined for each 3-month period. Responders were participants with an improvement in HbA1c of ≥5 mmol/mol (0.5%) over 12 months. RESULTS: Data from two hundred and thirty-one participants were included for analysis. Participants had a baseline median [interquartile range] HbA1c 68.0 [61.5-75.5] mmol/mol (8.4%). Participants demonstrated significant improvements in the MBG (-1.25 mmol/L), FBG (-0.97 mmol/L), SD-BG (-0.44 mmol/L), CV-BG (-1.43%), MAG (-0.97 mmol/L), and HbA1c (-7.0 mmol/mol) (all p < 0.001) at 12 months compared to these measures collected within the first 3 months of SMBG. Responders had a significantly higher baseline median [interquartile range] HbA1c of 70.0 [63.0-78.0] mmol/mol compared to 61.0 [56.5-66.0] mmol/mol in non-responders (P < 0.001). CONCLUSIONS: Structured SMBG improved all the observed measures of GV. These results support the use of structured SMBG in people with non-insulin treated T2D.


Assuntos
Automonitorização da Glicemia , Glicemia , Controle Glicêmico/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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