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2.
Artigo em Inglês | MEDLINE | ID: mdl-36332974

RESUMO

BACKGROUND AND OBJECTIVES: Individuals with type 2 diabetes are at a higher risk of developing kidney failure. The objective of this study was to develop and validate a decision support tool for estimating 10-year and lifetime risks of kidney failure in individuals with type 2 diabetes as well as estimating individual treatment effects of preventive medication. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prediction algorithm was developed in 707,077 individuals with prevalent and incident type 2 diabetes from the Swedish National Diabetes Register for 2002-2019. Two Cox proportional regression functions for kidney failure (first occurrence of kidney transplantation, long-term dialysis, or persistent eGFR <15 ml/min per 1.73 m2) and all-cause mortality as respective end points were developed using routinely available predictors. These functions were combined into life tables to calculate the predicted survival without kidney failure while using all-cause mortality as the competing outcome. The model was externally validated in 256,265 individuals with incident type 2 diabetes from the Scottish Care Information Diabetes database between 2004 and 2019. RESULTS: During a median follow-up of 6.8 years (interquartile range, 3.2-10.6), 8004 (1%) individuals with type 2 diabetes in the Swedish National Diabetes Register cohort developed kidney failure, and 202,078 (29%) died. The model performed well, with c statistics for kidney failure of 0.89 (95% confidence interval, 0.88 to 0.90) for internal validation and 0.74 (95% confidence interval, 0.73 to 0.76) for external validation. Calibration plots showed good agreement in observed versus predicted 10-year risk of kidney failure for both internal and external validation. CONCLUSIONS: This study derived and externally validated a prediction tool for estimating 10-year and lifetime risks of kidney failure as well as life years free of kidney failure gained with preventive treatment in individuals with type 2 diabetes using easily available clinical predictors. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2022_11_04_CJN05020422.mp3.

3.
Diabet Med ; : e15010, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36398460

RESUMO

AIMS: As sustained weight loss is vital for achieving remission of type 2 diabetes we explored whether randomisation to weight loss plus maintenance in the DiRECT trial was associated with physical activity, inactivity or sleep. METHODS: Participants were randomised to either a dietary weight management programme or best-practice care. The weight management group were encouraged to increase daily physical activity to their sustainable maximum. Objective measurement was achieved using a wrist-worn GENEActiv accelerometer for 7 days at baseline, 12 and 24 months in both groups. RESULTS: Despite average weight loss of 10 kg at 12 months in the intervention (n=66) group there were no differences in total physical activity or inactivity compared with control (n=104) at any time point. However, in our exploratory analysis, those who lost more than 10% of their baseline body weight performed on average 11 mins/day more light activity than the <10% group at 24 months (p=0.033) and had significantly lower bouts of Inactivity30min (interaction, p=0.005) across 12 and 24 months. At 24 months, the ≥10% group had higher daily acceleration (38.5 ± 12.1 vs. 33.2 ± 11.1 mg, p=0.020), and higher accelerations in the most active 5 hour period (59.4 ± 21.8 vs. 50.6 ± 18.3 mg, p=0.023). Wakefulness after sleep onset decreased in the intervention group compared with the control group and also in the ≥10% weight loss group at 12 and 24 months. CONCLUSIONS: Randomisation to a successful intensive weight loss intervention, including regular physical activity encouragement, was not associated with increased physical activity although sleep parameters improved. Physical activity was greater and night time waking reduced in those who maintained >10% weight loss at 12 and 24 months.

6.
BMC Womens Health ; 22(1): 473, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434722

RESUMO

BACKGROUND: Whether women's physical function in mid-life is related to their reproductive age is not known. The objectives of this study were to examine and compare changes in physical function in women by reproductive age, measured as time since final menstrual period (FMP), and chronological age, and to explore associations with repeatedly assessed levels of reproductive hormones. METHODS: We used data from 2319 UK women with up to three repeated measurements of physical function (median length of follow up: 2 years), focusing on changes occurring in women experiencing a natural menopausal transition. The main outcome was a composite physical function score that incorporated assessments of strength (grip strength), balance (one-leg stand) and cardiorespiratory fitness (timed chair rises). Associations with time since FMP, age, and time-updated measures of anti-Müllerian hormone, follicle-stimulating hormone and luteinizing hormone were assessed by multilevel models and generalised estimating equations models adjusted for the underlying effects of chronological age and confounding by education, age at first birth and smoking. RESULTS: The results showed that, adjusted for these confounders, time since FMP (- 0.21 SD per 10 years, 95% CI - 0.37, - 0.06) and chronological age (- 0.31 SD per 10 years, 95% CI - 0.46, - 0.15) were inversely associated with the physical function composite score. Grip strength seemed to be the main contributor to the decline in the composite score by time since FMP. There was no strong evidence of associations between any of the three reproductive hormones and the composite score. CONCLUSIONS: Physical function in women in mid-life declined with both chronological and reproductive age. The decline with reproductive age was independent of chronological age but did not seem to be driven by changes in reproductive hormones.

7.
Diabet Med ; : e15016, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36440921

RESUMO

AIMS: People with type 2 diabetes can enter remission but may relapse or develop legacy complications. This analysis assesses whether people with remission from type 2 diabetes continue receiving annual care processes recommended in national guidelines and potential impacts of formal recognition of remission. METHODS: People with type 2 diabetes with and without formal recognition (diagnostic code) of remission, and with and without evidence of remission (HbA1c <48 mmol/mol without prescription for glucose-lowering drugs in preceding 26 weeks), included in the 2018/19 National Diabetes Audit (NDA) for England and Wales were followed up to identify care processes received between 1st January 2019 and 31st March 2020. RESULTS: Of the 2,822,145 people with type 2 diabetes in the cohort, 16,460 (0.58%) were coded with remission in the 2018/19 NDA. After adjustment for age, sex, socioeconomic deprivation and ethnicity, people coded with remission were less likely to receive each care process than those without such coding irrespective of HbA1c measurements (relative risk (RR) of receiving all 8 care processes 0.70 (95% CI 0.69-0.72)). For the 339,235 people with evidence of remission irrespective of diagnostic coding compared to those without such evidence the RR for receiving all 8 care processes was 0.94 (95% CI 0.93-0.94). CONCLUSIONS: People coded with remission of type 2 diabetes were less likely to receive diabetes care processes than those without such coding. People with evidence of remission had only slightly reduced likelihood of receiving care processes. Formal recognition of remission may affect provision or uptake of care processes.

8.
Lancet Digit Health ; 4(12): e873-e883, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36427949

RESUMO

BACKGROUND: Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies. METHODS: In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD). We excluded those who received SGLT2 or DPP-4 inhibitors as first-line treatment or insulin at the same time, had estimated glomerular filtration rate (eGFR) of less than 45 mL/min per 1·73 m2, or did not have a valid baseline glycated haemoglobin (HbA1c) measure (<53 or ≥120 mmol/mol). The primary efficacy outcome was the HbA1c value reached 6 months after drug initiation, adjusted for baseline HbA1c. Clinical features associated with differential HbA1c outcome on the two therapies were identified in CPRD (n=26 877), and replicated in reanalysis of 14 clinical trials (n=10 414). An algorithm to predict individual-level differential HbA1c outcome on the two therapies was developed in CPRD (derivation; n=14 069) and validated in head-to-head trials (n=2499) and CPRD (independent validation; n=9376). In CPRD, we further explored heterogeneity in 6-month weight change and treatment discontinuation. FINDINGS: Among 10 253 patients initiating SGLT2 inhibitors and 16 624 patients initiating DPP-4 inhibitors in CPRD, baseline HbA1c, age, BMI, eGFR, and alanine aminotransferase were associated with differential HbA1c outcome with SGLT2 inhibitor and DPP-4 inhibitor therapies. The median age of participants was 62·0 years (IQR 55·0-70·0). 10 016 (37·3%) were women and 16 861 (62·7%) were men. An algorithm based on these five features identified a subgroup, representing around four in ten CPRD patients, with a 5 mmol/mol or greater observed benefit with SGLT2 inhibitors in all validation cohorts (CPRD 8·8 mmol/mol [95% CI 7·8-9·8]; CANTATA-D and CANTATA-D2 trials 5·8 mmol/mol [3·9-7·7]; BI1245.20 trial 6·6 mmol/mol [2·2-11·0]). In CPRD, predicted differential HbA1c response with SGLT2 inhibitor and DPP-4 inhibitor therapies was not associated with weight change. Overall treatment discontinuation within 6 months was similar in patients predicted to have an HbA1c benefit with SGLT2 inhibitors over DPP-4 inhibitors (median 15·2% [13·2-20·3] vs 14·4% [12·9-16·7]). A smaller subgroup predicted to have greater HbA1c reduction with DPP-4 inhibitors were twice as likely to discontinue SGLT2 inhibitors than DPP-4 inhibitors (median 26·8% [23·4-31·0] vs 14·8% [12·9-16·8]). INTERPRETATION: A validated treatment selection algorithm for SGLT2 inhibitor and DPP-4 inhibitor therapies can support decisions on optimal treatment for people with type 2 diabetes. FUNDING: BHF-Turing Cardiovascular Data Science Award and the UK Medical Research Council.

10.
Eur J Heart Fail ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36325584

RESUMO

AIMS: Baseline body mass index (BMI) and weight loss promoted by sodium-glucose cotransporter 2 inhibitors may impact outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We assessed in the EMPEROR-Reduced population treated with empagliflozin versus placebo the relationship between baseline BMI, weight loss and effects on the primary (time to first hospitalization for heart failure [HHF] or cardiovascular death) and key secondary outcomes. METHODS AND RESULTS: We categorized patients according to their baseline BMI: <20 kg/m2 (n = 180); 20 to <25 kg/m2 (n = 1038); 25 to <30 kg/m2 (n = 1345); 30 to <35 kg/m2 (n = 774) and ≥35 kg/m2 (n = 393). The treatment effect of empagliflozin on the primary outcome was consistent across all BMI categories (hazard ratios in subgroups 0.66-0.88, interaction trend p = 0.32), as was the effect on total (first plus recurrent) HHF (interaction trend p = 0.31). Empagliflozin reduced the rate of estimated glomerular filtration rate decline consistently across the BMI categories (interaction trend p = 0.67). Overall, incidence rates of any or serious adverse events were comparable between the treatment groups across all BMI categories. A total of 313 (17.4%) patients treated with empagliflozin experienced a weight loss of more than 5% at week 52 versus 230 (12.8%) in placebo. When analysed separately within each treatment group, presence of weight loss was similarly associated with an increased risk of all-cause mortality. CONCLUSION: The benefits of empagliflozin versus placebo were consistently present across all BMI categories in HFrEF patients. Weight loss was associated with higher risk of all-cause mortality, regardless of treatment group.

11.
Diabetes Care ; 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36256925

RESUMO

OBJECTIVE: Patients with type 2 diabetes undergoing coronary artery bypass grafting (CABG) are at risk for cardiovascular events. Sodium-glucose cotransporter 2 receptor inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) are effective cardioprotective agents; however, their prescription among CABG patients is uncertain. The aims of this study were 1) to evaluate the overall use of SGLT2i/GLP-1RA after CABG and explore longitudinal trends and 2) to examine patient-related factors associated with the use of SGLT2i or GLP-1RA. RESEARCH DESIGN AND METHODS: We analyzed the nationwide Veterans Affairs (VA) database (2016-2019) to report trends and factors associated with SGLT2i or GLP-1RA prescription after CABG. RESULTS: Among 5,109 patients operated on at 40 different VA medical centers, 525 of 5,109 (10.4%), 352 of 5,109 (6.8%), and 91 of 5,109 (1.8%) were prescribed SGLT2i, GLP-1RA, and both, respectively. A substantial increase in the quarterly SGLT2i prescription rates (1.6% [first quarter of 2016 (2016Q1)], 33% [2019Q4]) was present but was lower for GLP-1RA (0.8% [2016Q1], 11.2% [2019Q4]). SGLT2i use was less likely with preexisting vascular disease (odd ratio [OR] 0.75, 95% CI 0.75, 0.94) or kidney disease (OR 0.72, 95% CI 0.58, 0.88), while GLP-1RA use was associated with obesity (OR 1.91, 95% CI 1.50, 2.46). CONCLUSIONS: The overall utilization of SGLT2i or GLP-1RA drugs in U.S. veterans with type 2 diabetes undergoing CABG is low, with SGLT2i preferred over GLP-1RA.

12.
Diabetologia ; 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36224274

RESUMO

AIMS/HYPOTHESIS: South Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors. METHODS: We performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries ( https://osf.io/w5bf9 ). RESULTS: We summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5-0.7 kg/m2 lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55; I2=83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98; I2=93%) more liver fat, but nine studies had similar VAT (-0.03 SMD; 95% CI -0.24, 0.19; I2=85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m2 lower BMI but 0.31 SMD (95% CI 0.14, 0.48; I2=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI -0.17, 0.23; I2=72%) and VAT levels (0.04 SMD; 95% CI -0.16, 0.24; I2=71%) did not differ significantly between ethnic groups in eight studies of women. CONCLUSIONS/INTERPRETATION: South Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians. FUNDING: There was no primary direct funding for undertaking the systematic review and meta-analysis.

13.
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
14.
RMD Open ; 8(2)2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36260501

RESUMO

OBJECTIVES: Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases. METHODS: A systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and observational studies. Meeting abstracts from ACR, EULAR conferences and results on clinicaltrials.gov were taken into consideration. RESULTS: 187 articles fulfilled the inclusion criteria. Evidence for positive effect of IL-6 inhibition was available in various inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, cytokine release syndrome due to chimeric antigen receptor T cell therapy and systemic sclerosis-associated interstitial lung disease. Newcomers like satralizumab and anti-IL-6 ligand antibody siltuximab have expanded therapeutic approaches for Castleman's disease and neuromyelitis optica, respectively. IL-6 inhibition did not provide therapeutic benefits in psoriatic arthritis, ankylosing spondylitis and certain connective tissue diseases. In COVID-19, tocilizumab (TCZ) has proven to be therapeutic in advanced disease. Safety outcomes did not differ from other bDMARDs, except higher risks of diverticulitis and lower gastrointestinal perforations. Inconsistent results were observed in several studies investigating the risk for infections when comparing TCZ to TNF-inhibitors. CONCLUSION: IL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.


Assuntos
Antirreumáticos , COVID-19 , Receptores de Antígenos Quiméricos , Adulto , Humanos , Antirreumáticos/efeitos adversos , COVID-19/tratamento farmacológico , Interleucina-6 , Ligantes
16.
Artigo em Inglês | MEDLINE | ID: mdl-36315474

RESUMO

ABSTRACT: 2018 AHA guidelines provide criteria to identify patients at very high-risk (VHR) for adverse vascular events and recommend an LDL-C level < 1.8 mmol/L. Data regarding the 10-year risk for adverse vascular events in CABG patients at VHR and the need for non-statin therapies in the VHR cohort are limited.We queried a national cohort of CABG patients to answer these questions. The projected reduction of LDL-C from stepwise escalation of lipid lowering therapy (LLT) was simulated; Monte Carlo methods were used to account for patient-level heterogeneity in treatment effects. Data on preoperative statin therapy and LDL-C levels were obtained. In the first scenario, all eligible patients not at target LDL-C received high intensity statins, followed by ezetimibe and then alirocumab; alternatively, bempedoic acid was also utilized. The 10-year risk for an adverse vascular event was estimated using a validated risk score. Potential risk reduction was estimated after simulating maximal LLT. Before CABG, 8,948/27,443 patients [(median LDL-C 85 mg/dl) were VHR. In the whole cohort, 31% were receiving high intensity statins. With stepwise LLT escalation, the proportion of patients at target were 60%, 78%, 86% and 97% after high intensity statins, ezetimibe, bempedoic acid and alirocumab respectively. The projected 10-year risk to suffer a vascular event reduced by 4.6%.A large proportion of CABG patients who are at VHR for vascular events fail to meet 2018 AHA LDL-C targets. A stepwise approach, particularly with the use of bempedoic acid, can significantly reduce the need for more expensive PCSK9 inhibitors.

17.
BMJ Open ; 12(10): e063046, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36223968

RESUMO

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.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Insulina Glargina , Pessoa de Meia-Idade , Naftalenossulfonatos , Escócia/epidemiologia
18.
Diabet Med ; 39(12): e14982, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36256488

RESUMO

The role of diabetes in developing microvascular and macrovascular complications has been subject to extensive research. Despite multiple observational and genetic studies, the causal inference of diabetes (and associated risk factors) on those complications remains incomplete. In this review, we focused on type 2 diabetes, as the major form of diabetes, and investigated the evidence of causality provided by observational and genetic studies. We found that genetic studies based on Mendelian randomization provided consistent evidence of causal inference of type 2 diabetes on macrovascular complications; however, the evidence for causal inference on microvascular complications has been somewhat limited. We also noted high BMI could be causal for several diabetes complications, notable given high BMI is commonly upstream of type 2 diabetes and the recent calls to target weight loss more aggressively. We emphasize the need for further studies to identify type 2 diabetes components that mostly drive the risk of those complications. Even so, the genetic evidence summarized broadly concurs with the need for a multifactorial risk reduction approach in type 2 diabetes, including addressing excess adiposity.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Análise da Randomização Mendeliana , Adiposidade/genética , Fatores de Risco , Obesidade/complicações , Obesidade/genética
19.
BMC Med ; 20(1): 318, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36138475

RESUMO

BACKGROUND: The type 2 diabetes risk after gestational diabetes mellitus (GDM) is twice as high in South Asian compared to European women. Current guidelines differ regarding which test to use as a screening-tool post-GDM. We aimed to identify ethnic differences in the prevalence rates and early predictors for actionable HbA1c (defined as prediabetes and diabetes) short time after GDM. METHODS: This cross-sectional study, enrolling South Asian and Nordic women 1-3 years after a diagnosis of GDM, was undertaken at three hospitals in Norway. We performed a clinical and laboratory evaluation including an oral glucose tolerance test (OGTT). Medical records were used to retrieve data during pregnancy. Prediabetes was classified with HbA1c alone or combined with OGTT glucose measurements according to the WHO, WHO-IEC, and ADA criteria (fasting plasma glucose (FPG) 6.1-6.9 mmol/L, FPG 6.1-6.9 mmol/L and/or HbA1c 42-47 mmol/mol (6.0-6.4%), and FPG 5.6-6.9 mmol/L and/or HbA1c 39-47 mmol/mol (5.7-6.4%)). Ethnic differences in prevalence and predictors of glucose deterioration were assed by χ2 (Pearson) tests and logistic regression models. RESULTS: We included 163 South Asian and 108 Nordic women. Actionable HbA1c levels were highly prevalent and more so among South Asian than Nordic women (WHO-IEC-HbA1c: 25.8% vs. 6.5% (p ≤ 0.001), ADA-HbA1c: 58.3% vs. 22.2% (p ≤ 0.001)). Although adding OGTT-data gave higher combined prevalence rates of prediabetes and diabetes (WHO: 65.6% vs. 47.2% (p ≤ 0.05), WHO-IEC: 70.6% vs. 47.2% (p ≤ 0.001), ADA: 87.8% vs. 65.7% (p ≤ 0.001)), the excess risk in the South Asian women was best captured by the HbA1c. Important predictors for glucose deterioration after GDM were: South Asian ethnicity, GDM before the index pregnancy, use of glucose-lowering drugs in pregnancy, higher age, and higher in-pregnancy fasting glucose levels. CONCLUSIONS: In women with GDM 1-3 year previously, we found high prevalence and significant ethnic differences in actionable ADA-HbA1c levels, with South Asian ethnicity, GDM before the index pregnancy, and the use of glucose-lowering drugs in pregnancy as the most important risk factors. This study reinforces the importance of annual screening-preferably with HbA1c measurements-to facilitate early intervention after GDM.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Estado Pré-Diabético , Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Gravidez , Prevalência
20.
J Am Heart Assoc ; 11(18): e025551, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36073669

RESUMO

Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Anticolesterolemiantes/efeitos adversos , Apolipoproteínas , Colesterol , LDL-Colesterol , Ácidos Dicarboxílicos , Método Duplo-Cego , Ezetimiba/efeitos adversos , Ácidos Graxos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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