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1.
Diabetes Obes Metab ; 26(6): 2439-2445, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558524

RESUMO

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).


Assuntos
Biomarcadores , Estudos Cross-Over , Diabetes Mellitus Tipo 1 , Inibidor 1 de Ativador de Plasminogênio , Período Pós-Prandial , Caminhada , Humanos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Período Pós-Prandial/fisiologia , Masculino , Adulto , Caminhada/fisiologia , Biomarcadores/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Fator de Necrose Tumoral alfa/sangue , Interleucina-1beta/sangue , Fibrinogênio/metabolismo , Fibrinogênio/análise , Adulto Jovem , Resistência à Insulina , Comportamento Sedentário , Inflamação/sangue , Glicemia/metabolismo , Glicemia/análise
2.
Diabetes Obes Metab ; 25(12): 3589-3598, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37622406

RESUMO

AIM: To examine the impact of interrupting prolonged sitting with frequent short bouts of light-intensity activity on glycaemic control in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In total, 32 inactive adults with T1D [aged 27.9 ± 4.7 years, 15 men, diabetes duration 16.0 ± 6.9 years and glycated haemoglobin 8.4 ± 1.4% (68 ± 2.3 mmol/mol)] underwent two 7-h experimental conditions in a randomised crossover fashion with >7-day washout consisting of: uninterrupted sitting (SIT), or, interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals (SIT-LESS). Standardised mixed-macronutrient meals were administered 3.5 h apart during each condition. Blinded continuous glucose monitoring captured interstitial glucose responses during the 7-h experimental period and for a further 48-h under free-living conditions. RESULTS: SIT-LESS reduced total mean glucose (SIT 8.2 ± 2.6 vs. SIT-LESS 6.9 ± 1.7 mmol/L, p = .001) and increased time in range (3.9-10.0 mmol/L) by 13.7% (SIT 71.5 ± 9.5 vs. SIT-LESS 85.1 ± 7.1%, p = .002). Hyperglycaemia (>10.0 mmol/L) was reduced by 15.0% under SIT-LESS (SIT 24.2 ± 10.8 vs. SIT-LESS 9.2 ± 6.4%, p = .002), whereas hypoglycaemia exposure (<3.9 mmol/L) (SIT 4.6 ± 3.0 vs. SIT-LESS 6.0 ± 6.0%, p = .583) was comparable across conditions. SIT-LESS reduced glycaemic variability (coefficient of variation %) by 7.8% across the observation window (p = .021). These findings were consistent when assessing discrete time periods, with SIT-LESS improving experimental and free-living postprandial, whole-day and night-time glycaemic outcomes (p < .05). CONCLUSIONS: Interrupting prolonged sitting with frequent short bouts of light-intensity activity improves acute postprandial and 48-h glycaemia in adults with T1D. This pragmatic strategy is an efficacious approach to reducing sedentariness and increasing physical activity levels without increasing risk of hypoglycaemia in T1D.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Masculino , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico , Automonitorização da Glicemia , Glicemia , Estudos Cross-Over , Postura/fisiologia , Exercício Físico/fisiologia , Caminhada/fisiologia , Hipoglicemia/prevenção & controle , Período Pós-Prandial/fisiologia
3.
Eur J Nutr ; 62(3): 1231-1238, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36495341

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1 , Resistência à Insulina , Humanos , Masculino , Adulto Jovem , Adulto , Feminino , Proteínas Alimentares , Glucose , Gorduras na Dieta , Glicemia/metabolismo
4.
Diab Vasc Dis Res ; 19(3): 14791641221103217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35657731

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1 , Resistência à Insulina , Trombose , Biomarcadores , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Glucose , Humanos
5.
Can J Diabetes ; 46(3): 225-232.e2, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35568422

RESUMO

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.


Assuntos
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-Prandial
6.
Diab Vasc Dis Res ; 19(1): 14791641211067415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35089082

RESUMO

BACKGROUND: Severe hypoglycaemia may pose significant risk to individuals with type 2 diabetes (T2D), and evidence surrounding strategies to mitigate this risk is lacking. METHODS: Data was re-analysed from a previous randomised controlled trial studying the impact of nurse-led intervention on mortality following severe hypoglycaemia in the community. A Cox-regression model was used to identify baseline characteristics associated with mortality and to adjust for differences between groups. Kaplan-Meier curves were created to demonstrate differences in outcome between groups across different variables. RESULTS: A total of 124 participants (mean age = 75, 56.5% male) were analysed. In univariate analysis, Diabetes Severity Score (DSS), age and insulin use were baseline factors found to correlate to mortality, while HbA1C and established cardiovascular disease showed no significant correlations. Hazard ratio favoured the intervention (0.68, 95% CI: 0.38-1.19) and in multivariate analysis, only DSS demonstrated a relationship with mortality. Comparison of Kaplan-Meier curves across study groups suggested the intervention is beneficial irrespective of HbA1c, diabetes severity score or age. CONCLUSION: While DSS predicts mortality following severe community hypoglycaemia in individuals with T2D, a structured nurse-led intervention appears to reduce the risk of death across a range of baseline parameters.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Hipoglicemiantes/efeitos adversos , Masculino , Fatores de Risco
7.
Diabet Med ; 38(5): e14529, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33502032

RESUMO

AIMS: To understand the relationship between insulin resistance (IR), assessed as estimated glucose disposal rate (eGDR), and microvascular/macrovascular complications in people with type 1 diabetes. MATERIALS AND METHODS: Individuals with a confirmed diagnosis of type 1 diabetes were included in this cross-sectional study. BMI was categorised into normal weight (18.0-24.9 kg m-2 ), overweight (25.0-29.9 kg m-2 ) and obese groups (≥30.0 kg m-2 ). We categorised eGDR into four groups: eGDR >8, 6-7.9, 4-5.9 and <4 mg kg-1  min-1 . Multiple logistic regression was used to identify associations with vascular complications, after adjusting for relevant confounders. RESULTS: A total of 2151 individuals with type 1 diabetes were studied. Median [interquartile range (IQR)] age was 41.0 [29.0, 55.0] with diabetes duration of 20.0 [11, 31] years. Odds ratio (OR) for retinopathy and nephropathy in obese compared with normal weight individuals was 1.64 (95% CI: 1.24-2.19; p = 0.001) and 1.62 (95% CI: 1.10-2.39; p = 0.015), while the association with cardiovascular disease just failed to reach statistical significance (OR 1.66 [95% CI: 0.97-2.86; p = 0.066]). Comparing individuals with eGDR ≥8 mg kg-1  min-1 and <4 mg kg-1  min-1 showed OR for retinopathy, nephropathy and macrovascular disease of 4.84 (95% CI: 3.36-6.97; p < 0.001), 8.35 (95% CI: 4.86-14.34; p < 0.001) and 13.22 (95% CI: 3.10-56.38; p < 0.001), respectively. Individuals with the highest eGDR category (≥8 mg kg-1  min-1 ) had the lowest complication rates irrespective of HbA1c levels. CONCLUSIONS: Obesity is prevalent in type 1 diabetes and diabetes complications are not only related to glucose control. IR, assessed as eGDR, is strongly associated with both microvascular and macrovascular complications, regardless of HbA1c levels.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 1/metabolismo , Angiopatias Diabéticas/etiologia , Glucose/metabolismo , Adulto , Metabolismo Basal , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/epidemiologia , Sobrepeso/metabolismo , Fatores de Risco , Reino Unido/epidemiologia
8.
Cardiovasc Diabetol ; 20(1): 18, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435992

RESUMO

BACKGROUND: Mortality in individuals with diabetes with severe hypoglycemia requiring ambulance services intervention is high and it is unclear whether this is modifiable. Our aim was to characterise this high-risk group and assess the impact of nurse-led intervention on mortality. METHODS: In this single centre study, patients with diabetes and hypoglycemia requiring ambulance call out were randomized to nurse led support (intensive arm) or managed using existing pathways (standard arm). A third group agreed to have their data collected longitudinally (observational arm). The primary outcome was all-cause mortality comparing intensive with combined standard and observational arms as well as standard arm alone. RESULTS: Of 828 individuals identified, 323 agreed to participate with 132 assigned to intensive, 130 to standard and 61 to observational arms. Mean follow up period was 42.6 ± 15.6 months. Mortality in type 1 diabetes (n = 158) was similar across study arms but in type 2 diabetes (n = 160) this was reduced to 33% in the intensive arm compared with 51% in the combined arm (p = 0.025) and 50% in the standard arm (p = 0.06). Cardiovascular deaths, the leading cause of mortality, was lower in the intensive arm compared with combined and standard study arms (p < 0.01). CONCLUSIONS: Medium-term mortality following severe hypoglycemia requiring the assistance of emergency services is high in those with type 2 diabetes. In individuals with type 2 diabetes, nurse-led individualized intervention reduces cardiovascular mortality compared with standard care. Large-scale multicentre studies are warranted to further investigate this approach. Trial registration The trial was retrospectively registered on http://www.clinicaltrials.gov with reference NCT04422145.


Assuntos
Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/enfermagem , Hipoglicemiantes/efeitos adversos , Serviço Hospitalar de Enfermagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ambulâncias , Biomarcadores/sangue , Glicemia/metabolismo , Automonitorização da Glicemia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/mortalidade , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Projetos Piloto , Índice de Gravidade de Doença , Fatores de Tempo
9.
Cardiovasc Diabetol ; 19(1): 3, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910903

RESUMO

BACKGROUND: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. MATERIALS AND METHODS: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. RESULTS: Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20µmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 µmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 µg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). CONCLUSIONS: Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.


Assuntos
Aspirina/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Clopidogrel/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Cloridrato de Prasugrel/uso terapêutico , Trombose/prevenção & controle , Idoso , Aspirina/efeitos adversos , Biomarcadores/sangue , Clopidogrel/efeitos adversos , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Método Duplo-Cego , Feminino , Fibrina/metabolismo , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Selectina-P/sangue , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Prevenção Primária , Prevenção Secundária , Trombose/sangue , Trombose/diagnóstico , Fatores de Tempo , Resultado do Tratamento
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