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INTRODUCTION: Ethnic minority populations experience significant health and social care disparities; despite experiencing a greater burden of diseases, these groups are underrepresented in health and social care research. Consequently, related research can be less applicable to these population groups. The REPRESENT study aims to explore the health and social care experiences of ethnic minorities and other minoritised populations, their research interests and appropriate research practices. METHODS: Focus groups and semistructured interviews were conducted between May and September 2022 with members of a number of ethnic minority communities in England. Data were audio recorded, transcribed and thematically coded using NVivo 12. Rigour was determined through extensive sampling, iterative data collection and analysis. FINDINGS: Fifty-two ethnic minority members were engaged in group interviews and one-to-one interviews. Participants included representatives of the following groups: African Caribbean, Eastern European, Gypsy Travellers, Lesbian, Gay, Bisexual, Transgender, Queer, Intersex and Asexual+, Refugee/Asylum Seekers, Somali and South Asian communities. Interviews were also conducted with ethnic minority healthcare providers and researchers. Three overarching categories were identified: health information, medical service experiences, health and social care concerns and health research. Health and social care services challenges were mostly attributed to discrimination, delayed services, poor cultural relevance and language and cultural barriers. The most influential information sources were local community organisations and word-of-mouth. The main health and social care concerns were chronic long-term health conditions, mental health, maternal health and child development. Recommendations for research involved understanding the motivations for participation, improving communication and empowering communities. Top research priorities were long-term health conditions, health promotion and education, early care interventions and understanding community needs. INTERPRETATION: Discrimination and bias in health and social care provision have severe implications for worsening ethnic health inequalities. Healthcare commissioning authorities and policymakers can leverage the preference of ethnic minority groups for pharmacy services and community organisations to improve access to care. Improving research interest and engagement requires understanding individual community needs, community sensitivity, research relevance and cultural appropriateness. PATIENT OR PUBLIC CONTRIBUTION: Members of ethnic minority Patient and Public Involvement and Engagement group and Community Advisory Board supported the REPRESENT study design, conceptualisation and report development.
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Grupos Focais , Humanos , Feminino , Masculino , Entrevistas como Assunto , Minorias Étnicas e Raciais , Adulto , Reino Unido , Etnicidade/psicologia , Grupos Minoritários/psicologia , Pessoa de Meia-Idade , Pesquisa Qualitativa , Disparidades em Assistência à Saúde/etnologia , InglaterraRESUMO
BACKGROUND: Insulin resistance (IR) increases vascular risk in individuals with Type 1 Diabetes (T1D). We aimed to investigate the relationship between dietary intake and IR, as well as vascular biomarkers in T1D. METHODS: Baseline data from three randomised controlled trials were pooled. Estimated glucose disposal rate (eGDR) was used as an IR marker. Employing multivariate nutrient density substitution models, we examined the association between macronutrient composition and IR/vascular biomarkers (tumour necrosis factor-α, fibrinogen, tissue factor activity, and plasminogen activator inhibitor-1). RESULTS: Of the 107 patients, 50.5% were male with mean age of 29 ± 6 years. Those with lower eGDR were older with a longer diabetes duration, higher insulin requirements, and an adverse vascular profile (p < 0.05). Patients with higher degrees of IR had higher total energy intake (3192 ± 566 vs. 2772 ± 268 vs. 2626 ± 395 kcal/d for eGDR < 5.1 vs. 5.1-8.6 vs. ≥ 8.7 mg/kg/min, p < 0.001) and consumed a higher absolute and proportional amount of fat (47.6 ± 18.6 vs. 30.4 ± 8.1 vs. 25.8 ± 10.4%, p < 0.001). After adjusting for total energy intake, age, sex, and diabetes duration, increased carbohydrate intake offset by an isoenergetic decrease in fat was associated with higher eGDR (ß = 0.103, 95% CI 0.044-0.163). In contrast, increased dietary fat at the expense of dietary protein intake was associated with lower eGDR (ß = - 0.119, 95% CI - 0.199 to - 0.040). Replacing fat with 5% isoenergetic amount of carbohydrate resulted in decreased vascular biomarkers (p < 0.05). CONCLUSION: Higher fat, but not carbohydrate, intake is associated with increased IR and an adverse vascular profile in patients with T1D.
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Diabetes Mellitus Tipo 1 , Resistência à Insulina , Humanos , Masculino , Adulto Jovem , Adulto , Feminino , Proteínas Alimentares , Glucose , Gorduras na Dieta , Glicemia/metabolismoRESUMO
AIM: To identify, appraise and synthesize the available evidence on the impact of the coronavirus disease 2019 (COVID-19) pandemic and lockdown (LD) on glycaemic control in people with diabetes. MATERIALS AND METHODS: We searched multiple databases up to 2 February 2021 for studies reporting HbA1c, time in range (TIR), average or fasting glucose, severe hypoglycaemia and diabetic ketoacidosis. Data were pooled using random effects meta-analysis and are presented as mean difference (MD) with 95% confidence intervals (CI). This review was preregistered on PROSPERO (CRD42020179319). RESULTS: We include 59 studies; 44 (n = 15 464) were included in quantitative syntheses and 15 were narratively synthesized. Pooled data were grouped by diabetes type. Results from 28 studies (n = 5048 type 1 diabetes [T1D] and combined diabetes participants) showed that TIR increased during LD compared with before LD (MD 2.74%, 95% CI 1.80% to 3.69%). Data from 10 studies (n = 1294 T1D participants) showed that TIR increased after LD compared with before LD (MD 5.14%, 95% CI 3.12% to 7.16%). Pooled results from 12 studies (n = 4810 T1D and type 2 diabetes participants) resulted in average glucose decreasing after LD compared with before LD (MD -6.86 mg/dl, 95% CI -8.54 to -5.18). Results for other outcomes, including HbA1c, were not statistically significantly different. CONCLUSIONS: The COVID-19 pandemic was associated with small improvements across multiple outcomes of glycaemic control, although there was insufficient evidence to suggest that this led to changes in HbA1c. Most evidence came from people with access to diabetes technologies in high-income countries; more research is needed in less advantaged populations.
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COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Glucose , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , PandemiasRESUMO
PURPOSE: Findings from randomized controlled trials (RCTs) evaluating the effect of pulse intake on glycemic control are inconsistent and conclusive evidence is lacking. The aim of this study was to systematically review the impact of pulse consumption on post-prandial and long-term glycemic control in adults with and without type 2 diabetes (T2D). METHODS: Databases were searched for RCTs, reporting outcomes of post-prandial and long-term interventions with different pulse types on parameters of glycemic control in normoglycemic and T2D adults. Effect size (ES) was calculated using random effect model and meta-regression was conducted to assess the impact of various moderator variables such as pulse type, form, dose, and study duration on ES. RESULTS: From 3334 RCTs identified, 65 studies were eligible for inclusion involving 2102 individuals. In acute RCTs, pulse intake significantly reduced peak post-prandial glucose concentration in participants with T2D (ES - 2.90; 95%CI - 4.60, - 1.21; p ≤ 0.001; I2 = 93%) and without T2D (ES - 1.38; 95%CI - 1.78, - 0.99; p ≤ 0.001; I2 = 86%). Incorporating pulse consumption into long-term eating patterns significantly attenuated fasting glucose in normoglycemic adults (ES - 0.06; 95%CI - 0.12, 0.00; p ≤ 0.05; I2 = 30%). Whereas, in T2D participants, pulse intake significantly lowered fasting glucose (ES - 0.54; 95%CI - 0.83, - 0.24; p ≤ 0.001; I2 = 78%), glycated hemoglobin A1c (HbA1c) (ES - 0.17; 95%CI - 0.33, 0.00; p ≤ 0.05; I2 = 78) and homeostatic model assessment of insulin resistance (HOMA-IR) (ES - 0.47; 95%CI - 1.25, - 0.31; p ≤ 0.05; I2 = 79%). CONCLUSION: Pulse consumption significantly reduced acute post-prandial glucose concentration > 1 mmol/L in normoglycemic adults and > 2.5 mmol/L in those with T2D, and improved a range of long-term glycemic control parameters in adults with and without T2D. PROSPERO REGISTRY NUMBER: (CRD42019162322).
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Diabetes Mellitus Tipo 2 , Controle Glicêmico , Adulto , Glicemia/análise , Hemoglobinas Glicadas/análise , Frequência Cardíaca , Humanos , Insulina , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND AIMS: Postprandial responses are influenced not only by the type and amount of fat ingested, but also lipid droplet size distribution. However, little research has investigated the impact of differential lipid size distributions within a mixed-macronutrient meal context on postprandial vascular health. Therefore, we examined whether manipulating the lipid droplet size distribution within a mixed-macronutrient meal impacts vascular-inflammatory and thrombotic parameters. METHODS AND RESULTS: In a randomised and counterbalanced fashion, sixteen adults (8 males; age 34 ± 7 years; BMI of 25.3 ± 4.5 kg/m2) completed three separate fasted morning-time feeding challenges, each separated by a minimum washout of 7-days. On each occasion, test-meals matched for carbohydrate and protein content differing only in fat amount and the lipid droplet size distribution were administered, such that participants consumed (1) a low-fat meal (LF) with negligible fat content, (2) an emulsified-high-fat meal with a fine lipid droplet size (FE), or (3) an emulsified-high-fat meal with a coarse lipid droplet size (CE). Periodic blood samples were retrospectively analysed for plasma triglycerides, tumour necrosis factor alpha (TNFα), tissue factor (TF), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). Triglyceride concentrations increased rapidly overtime under FE (P-time<0.05); this rise was attenuated under CE (P-time>0.05) and was comparable to LF (P-condition>0.05). Similarly, FE induced a significant rise in TNFα, TF, fibrinogen, and PAI-1 (P-time<0.05); these parameters remained unchanged under LF and CE (P-time>0.05). CONCLUSION: A high-fat mixed-macronutrient meal with a larger lipid droplet size distribution ameliorates the associated rise in vascular-inflammatory and thrombotic parameters. TRIAL REGISTRATION: ISRCTN88881254.
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Coagulação Sanguínea , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Mediadores da Inflamação/sangue , Inflamação/prevenção & controle , Gotículas Lipídicas , Período Pós-Prandial , Trombose/prevenção & controle , Adulto , Biomarcadores/sangue , Gorduras na Dieta/administração & dosagem , Inglaterra , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Trombose/sangue , Trombose/etiologia , Fatores de TempoRESUMO
BACKGROUND: The role of omega-3 polyunsaturated fatty acids (n-3PUFA), and the potential impact of n-3PUFA supplementation, in the treatment and management of type 1 diabetes (T1D) remains unclear and controversial. Therefore, this study aimed to examine the efficacy of daily high-dose-bolus n-3PUFA supplementation on vascular health, glycaemic control, and metabolic parameters in subjects with T1D. METHODS: Twenty-seven adults with T1D were recruited to a 6-month randomised, double-blind, placebo-controlled trial. Subjects received either 3.3 g/day of encapsulated n-3PUFA or encapsulated 3.0 g/day corn oil placebo (PLA) for 6-months, with follow-up at 9-months after 3-month washout. Erythrocyte fatty acid composition was determined via gas chromatography. Endpoints included inflammation-associated endothelial biomarkers (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], E-selectin, P-selectin, pentraxin-3, vascular endothelial growth factor [VEGF]), and their mediator tumor necrosis factor alpha [TNFα] analysed via immunoassay, vascular structure (carotid intima-media thickness [CIMT]) and function (brachial artery flow mediated dilation [FMD]) determined via ultrasound technique, blood pressure, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial metabolism. RESULTS: Twenty subjects completed the trial in full. In the n-3PUFA group, the mean ± SD baseline n-3PUFA index of 4.93 ± 0.94% increased to 7.67 ± 1.86% (P < 0.001) after 3-months, and 8.29 ± 1.45% (P < 0.001) after 6-months. Total exposure to n-3PUFA over the 6-months (area under the curve) was 14.27 ± 3.05% per month under n-3PUFA, and 9.11 ± 2.74% per month under PLA (P < 0.001). VCAM-1, ICAM-1, E-selectin, P-selectin, pentraxin-3, VEGF, TNFα, CIMT, FMD, blood pressure, HbA1c, FPG, and postprandial metabolism did not differ between or within groups after treatment (P > 0.05). CONCLUSIONS: This study indicates that daily high-dose-bolus of n-3PUFA supplementation for 6-months does not improve vascular health, glucose homeostasis, or metabolic parameters in subjects with T1D. The findings from this preliminary RCT do not support the use of therapeutic n-3PUFA supplementation in the treatment and management of T1D and its associated complications. Trial Registration ISRCTN, ISRCTN40811115. Registered 27 June 2017, http://www.isrctn.com/ISRCTN40811115 .
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Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Controle Glicêmico , Hemodinâmica/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Inglaterra , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Vasodilatação/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802.
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Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Síndrome Metabólica/tratamento farmacológico , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas/metabolismo , Humanos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoRESUMO
[This corrects the article DOI: 10.1016/j.eclinm.2022.101762.].
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Background: The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population. Methods: A systematic literature search was conducted using multiple electronic databases (MEDLINE and The Cochrane Library, Scopus, CINAHL, and medRxiv) until January 2022. Studies with at least 100 people with confirmed or self-reported COVID-19 symptoms at ≥28 days following infection onset were included. Patient-reported outcome measures and clinical investigations were both assessed. Results were analysed descriptively, and meta-analyses were conducted to derive prevalence estimates. This study was pre-registered (PROSPERO-ID: CRD42021238247). Findings: 194 studies totalling 735,006 participants were included, with five studies conducted in those <18 years of age. Most studies were conducted in Europe (n = 106) or Asia (n = 49), and the time to follow-up ranged from ≥28 days to 387 days. 122 studies reported data on hospitalised patients, 18 on non-hospitalised, and 54 on hospitalised and non-hospitalised combined (mixed). On average, at least 45% of COVID-19 survivors, regardless of hospitalisation status, went on to experience at least one unresolved symptom (mean follow-up 126 days). Fatigue was frequently reported across hospitalised (28.4%; 95% CI 24.7%-32.5%), non-hospitalised (34.8%; 95% CI 17.6%-57.2%), and mixed (25.2%; 95% CI 17.7%-34.6%) cohorts. Amongst the hospitalised cohort, abnormal CT patterns/x-rays were frequently reported (45.3%; 95% CI 35.3%-55.7%), alongside ground glass opacification (41.1%; 95% CI 25.7%-58.5%), and impaired diffusion capacity for carbon monoxide (31.7%; 95% CI 25.8%-3.2%). Interpretation: Our work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at â¼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies. Funding: No funding.
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The 'paediatric inactivity triad' (PIT) framework consists of three complex inter-related conditions that influence physical inactivity and related health risks. In those living with chronic kidney disease (CKD), a multi-factorial milieu of components likely confound the PIT elements, resulting in a cycle of decreased physical functioning and reduced physical activity. In this review, we explore and summarize previous research on each of the three principal PIT components (exercise deficit disorder, dynapenia, and physical illiteracy) in the pediatric CKD population. We found those living with CKD are significantly physically inactive compared to their peers. Physical inactivity occurs early in the disease process and progressively gets worse as disease burden increases. Although physical activity appears to increase post-transplantation, it remains lower compared to healthy controls. There is limited evidence on interventions to increase physical activity behaviour in this population, and those that have attempted have had negligible effects. Studies reported profound reductions in muscle strength, physical performance, and cardiorespiratory fitness. A small number of exercise-based interventions have shown favourable improvements in physical function and cardiorespiratory fitness, although small sample sizes and methodological issues preclude the generalization of findings. Physical activity must be adapted and individualized to the needs and goals of the children, particularly those with acute and chronic medical needs as is the case in CKD, and further work is needed to define optimal interventions across the life course in this population if we aim to prevent physical activity declining further.
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Purpose: The exact contribution of daily glucose exposure to HbA1c in people with type 1 diabetes (T1D) remains controversial. We examined the contribution of pre- and postprandial glycaemia, nocturnal and early-morning glycaemia, and glycaemic variability to HbA1c levels in T1D. In this analysis, we used clinical data, namely age, BMI and HbA1c, as well as glycaemic metrics (24-h glycaemia, postprandial, nocturnal, early-morning glycaemia, wake-up glucose, and glycaemic variability) obtained over a four-week period of continuous glucose monitoring (CGM) wear in thirty-two males with T1D. Methods: The trapezoid method was used estimate the incremental area under the glucose curve (iAUC) for 24-h, postprandial (3-h period following breakfast, lunch, and dinner, respectively), nocturnal (between 24:00-04:00 AM), and early-morning (2-h period 2-h prior to wake-up) glycaemia. Linear regression analysis was employed whereby CGM-derived glycaemic metrics were explanatory variables and HbA1c was the outcome. Results: Thirty-two T1D males (mean ± SD: age 29 ± 4 years; HbA1c 7.3 ± 0.9% [56 ± 13 mmol/mol]; BMI 25.80 ± 5.01 kg/m2) were included in this analysis. In linear models adjusted for age and BMI, HbA1c was associated with 24-h mean glucose (r 2 = 0.735, p < 0.001), SD (r 2 = 0.643, p = 0.039), and dinner iAUC (r 2 = 0.711, p = 0.001). CGM-derived metrics and non-glycaemic factors explained 77% of the variance in HbA1c, in which postprandial glucose accounted for 32% of the variance explained. The single greatest contributor to HbA1c was dinner iAUC resulting in 0.6%-point (~7 mmol/mol) increase in HbA1c per SD increase in dinner iAUC. Conclusions: Using comprehensive CGM profiling, we show that postprandial glucose, specifically evening-time postprandial glucose, is the single largest contributing factor to HbA1c in T1D. Trial registration number: NCT02204839 (July 30th 2014); NCT02595658 (November 3rd 2015).
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AIMS/HYPOTHESIS: We hypothesised that the detrimental effect of high glucose variability (GV) in people with type 1 diabetes is mainly evident in those with concomitant insulin resistance. METHODS: We conducted secondary analyses on continuous glucose monitoring (CGM) using baseline observational data from three randomised controlled trials and assessed the relationship with established vascular markers. We used standard CGM summary statistics and principal component analysis to generate individual glucose variability signatures for each participant. Cluster analysis was then employed to establish three GV clusters (low, intermediate, or high GV, respectively). The relationship with thrombotic biomarkers was then investigated according to insulin resistance, assessed as estimated glucose disposal rate (eGDR). RESULTS: Of 107 patients, 45%, 37%, and 18% of patients were assigned into low, intermediate, and high GV clusters, respectively. Thrombosis biomarkers (including fibrinogen, plasminogen activator inhibitor-1, tissue factor activity, and tumour necrosis factor-alpha) increased in a stepwise fashion across all three GV clusters; this increase in thrombosis markers was evident in the presence of low but not high eGDR and at a threshold of eGDR <5.1 mg/kg/min. CONCLUSION: Higher GV is associated with increased thrombotic biomarkers in type 1 diabetes but only in those with concomitant insulin resistance.
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Diabetes Mellitus Tipo 1 , Resistência à Insulina , Trombose , Biomarcadores , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Glucose , HumanosRESUMO
OBJECTIVES: Circulating insulin concentrations mediate vascular-inflammatory and prothrombotic factors. However, it is unknown whether interindividual differences in circulating insulin levels are associated with different inflammatory and prothrombotic profiles in type 1 diabetes (T1D). We applied an unsupervised machine-learning approach to determine whether interindividual differences in rapid-acting insulin levels associate with parameters of vascular health in patients with T1D. METHODS: We re-analyzed baseline pretreatment meal-tolerance test data from 2 randomized controlled trials in which 32 patients consumed a mixed-macronutrient meal and self-administered a single dose of rapid-acting insulin individualized by carbohydrate counting. Postprandial serum insulin, tumour necrosis factor (TNF)-alpha, plasma fibrinogen, human tissue factor (HTF) activity and plasminogen activator inhibitor-1 (PAI-1) were measured. Two-step clustering categorized individuals based on shared clinical characteristics. For analyses, insulin pharmacokinetic summary statistics were normalized, allowing standardized intraindividual comparisons. RESULTS: Despite standardization of insulin dose, individuals exhibited marked interpersonal variability in peak insulin concentrations (48.63%), time to peak (64.95%) and insulin incremental area under the curve (60.34%). Two clusters were computed: cluster 1 (n=14), representing increased serum insulin concentrations; and cluster 2 (n=18), representing reduced serum insulin concentrations (cluster 1: 389.50±177.10 pmol/L/IU h-1; cluster 2: 164.29±41.91 pmol/L/IU h-1; p<0.001). Cluster 2 was characterized by increased levels of fibrinogen, PAI-1, TNF-alpha and HTF activity; higher glycated hemoglobin; increased body mass index; lower estimated glucose disposal rate (increased insulin resistance); older age; and longer diabetes duration (p<0.05 for all analyses). CONCLUSIONS: Reduced serum insulin concentrations are associated with insulin resistance and a prothrombotic milieu in individuals with T1D, and therefore may be a marker of adverse vascular outcome.
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Diabetes Mellitus Tipo 1 , Resistência à Insulina , Glicemia/análise , Diabetes Mellitus Tipo 1/complicações , Fibrinogênio/uso terapêutico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Injeções Subcutâneas , Insulina/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Aprendizado de Máquina , Inibidor 1 de Ativador de Plasminogênio/uso terapêutico , Período Pós-PrandialRESUMO
OBJECTIVES: The aim of this study was to assess the relationship between specific erythrocyte fatty acid levels and vascular health in type 1 diabetes (T1D) with and without insulin resistance (IR). METHODS: We analyzed baseline pretreatment data in a subset of 23 patients with T1D from a previously published randomized controlled trial consisting of comprehensive erythrocyte-derived fatty acid profiles and a panel of inflammation-associated endothelial markers. Estimated glucose disposal rate was used to identify and categorize patients with IR. We utilized principal component analysis (PCA) to cluster vascular biomarkers to compute a single "vascular signal" and utilized univariate linear regression models to investigate the association with IR and fatty acid profiles. RESULTS: Subjects with IR displayed significantly higher levels of linoleic acid (p=0.001), lower levels of eicosapentaenoic acid (EPA) (p<0.001), lower levels of omega-3 polyunsaturated fatty acid (n-3PUFA) (p<0.006) and an increased omega-6 (n-6)PUFA:n-3PUFA ratio (p=0.001). IR was associated with significantly higher linoleic acid levels, total n-6PUFA and an increased ratio of n-6PUFA:n-3PUFA, and negatively associated with arachidonic acid and EPA levels, total saturated fatty acid and total n-3PUFA. The PCA-derived vascular biomarker cluster was positively associated with linoleic acid and n-6PUFA:n-3PUFA ratio, and inversely associated with EPA. CONCLUSIONS: Specific erythrocyte membrane fatty acid compositions are associated with impaired vascular health and IR in adults with T1D. These findings suggest that IR and risk of associated complications may be influenced by specific fatty acid profiles, and thus potentially modified by the selective targeting of dietary fatty acids.
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Diabetes Mellitus Tipo 1 , Ácidos Graxos Ômega-3 , Resistência à Insulina , Adulto , Biomarcadores , Estudos Transversais , Membrana Eritrocítica , Ácidos Graxos , Humanos , Ácidos LinoleicosRESUMO
Cross-sectional studies in younger adults have demonstrated a positive association between energy intake (EI) and fat-free mass (FFM), with this relationship seemingly mediated by resting metabolic rate (RMR). Establishing a causal effect longitudinally would be prudent in older adults suffering from loss of appetite. We investigated the effects of FFM on RMR, appetite and EI in 39 healthy older adults (age: 66 ± 4 years, BMI: 25.1 ± 3.5 kgâm2) assigned to either 12-week resistance training + protein supplementation group (RT + PRO) or control group (CON). Body composition, subjective appetite, leptin, insulin, RMR and laboratory-measured ad libitum EI were measured at baseline, weeks 6 and 12 of the intervention, while daily EI at baseline and week 12. FFM (+1.2 kg; p = 0.002), postprandial subjective appetite (+8 mm; p = 0.027), ad libitum EI (+119 kcal; p = 0.012) and daily EI (+133 kcal; p = 0.010) increased from baseline to week 12 in the RT + PRO. RMR, fasted subjective appetite, leptin and insulin concentrations remained unchanged (all p > 0.05). The increases ad libitum EI correlated with increases in FFM (r = 0.527, p = 0.001), with 54% of the change in EI attributed to FFM changes. In conclusion, FFM increases were associated with an increased ad libitum EI and postprandial appetite in older adults.