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AIMS/HYPOTHESIS: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear. METHODS: In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19). Pre-hepatic insulin secretion rates were determined by the deconvolution of C-peptide, and insulin clearance was calculated using a single-pool model. Insulin sensitivity was measured by an oral minimal model. RESULTS: There were divergent time course changes in insulin clearance between groups. In the Lean-NGT group, there was an immediate post-meal increase in insulin clearance compared with pre-meal values (p<0.05), whereas insulin clearance remained stable at baseline values in Obese-NGT or declined slightly in the type 2 diabetes group (p<0.05). The mean AUC for insulin clearance during the test was ~40% lower in the Obese-NGT (1.3 ± 0.4 l min-1 m-2) and type 2 diabetes (1.4 ± 0.7 l min-1 m-2) groups compared with Lean-NGT (1.9 ± 0.5 l min-1 m-2; p<0.01), with no difference between the Obese-NGT and type 2 diabetes groups. HOMA-IR and glucagon AUC emerged as predictors of insulin clearance AUC, independent of BMI, age or insulin sensitivity (adjusted R2=0.670). Individuals with increased glucagon AUC had a 40% reduction in insulin clearance AUC (~ -0.75 l min-1 m-2; p<0.001). CONCLUSIONS/INTERPRETATION: The ingestion of a mixed-macronutrient meal augments differing temporal profiles in insulin clearance among individuals without type 2 diabetes, which is associated with HOMA-IR and the secretion of glucagon. Further research investigating the role of hepatic glucagon signalling in postprandial insulin kinetics is warranted. TRIAL REGISTRATION: ISRCTN17563146 and ISRCTN95281775.
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PURPOSE: To determine how COVID-19 lockdown impacted physical activity (PA) levels, wellbeing, and diabetes management in children (aged 0-17 years) with type 1 diabetes (T1D), from the perspectives of their parent/guardian. DESIGN AND METHODS: This qualitative descriptive study is part of a larger, parallel mixed-methods design study, which incorporated a cross-sectional survey and semi-structured one-to-one interviews. Interviewees were recruited from the survey, which was distributed to parents of children/adolescents with T1D in the UK. Interviews explored diabetes management, mental and physical wellbeing, changes in PA levels, sleep quality before/during lockdown, and the effects of lockdown on the individual and their family. The interviews were transcribed and the data were analysed thematically. RESULTS: 14 interviews were conducted with parents. Thematic analysis generated a central theme of routine disruption, with four further themes on diabetes management routines, harnessing the opportunities of lockdown, weighing up risk, and variable impact on wellbeing. CONCLUSIONS: Maintaining or increasing PA during COVID-19 lockdown was associated with better diabetes management, sleep, and wellbeing for children/adolescents with T1D, despite significant disruption to established routines. Use of technology during the pandemic contributed positively to wellbeing. PRACTICE IMPLICATIONS: It is crucial to emphasize the significance of maintaining a well-structured routine when treating patients with type 1 diabetes. A consistent routine, incorporating regular physical exercise and good sleep hygiene, will help with managing overall diabetes control.
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COVID-19 , Diabetes Mellitus Tipo 1 , Ejercicio Físico , Padres , Investigación Cualitativa , Humanos , Diabetes Mellitus Tipo 1/psicología , COVID-19/prevención & control , COVID-19/epidemiología , Niño , Masculino , Adolescente , Femenino , Reino Unido , Padres/psicología , Estudios Transversales , Preescolar , Adaptación Psicológica , SARS-CoV-2 , Cuarentena/psicología , LactanteRESUMEN
AIMS/HYPOTHESIS: Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by V Ë O 2peak . METHODS: Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3-200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by V Ë O 2peak test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% V Ë O 2peak ) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity ( V Ë O 2peak ) during exercise in health and type 1 diabetes. RESULTS: Maximal aerobic capacity ( V Ë O 2peak ) inversely correlated with HbA1c in the type 1 diabetes group (r2=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23×10-5) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity ( V Ë O 2peak ) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]). CONCLUSIONS/INTERPRETATION: The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Ejercicio Físico , Metaboloma , Humanos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatología , Masculino , Femenino , Adulto , Metaboloma/fisiología , Ejercicio Físico/fisiología , Consumo de Oxígeno/fisiología , Prueba de Esfuerzo , Metabolómica/métodos , Adulto Joven , Péptido C/sangre , Persona de Mediana Edad , Células Secretoras de Insulina/metabolismoRESUMEN
BACKGROUND: NAFLD is associated with activation of fibroblasts and hepatic fibrosis. Substantial patient heterogeneity exists, so it remains challenging to risk-stratify patients. We hypothesized that the amount of fibroblast activity, as assessed by circulating biomarkers of collagen formation, can define a "high-risk, high-fibrogenesis" patient endotype that exhibits greater fibroblast activity and potentially more progressive disease, and this endotype may be more amendable to dietary intervention. METHODS: Patients with clinically confirmed advanced NAFLD were prescribed a very low-calorie diet (VLCD) intervention (â¼800 kcal/d) to induce weight loss, achieved using total diet replacement. Serum markers of type III (PRO-C3) and IV collagen (PRO-C4) fibrogenesis were assessed at baseline every second week until the end of the VLCD, and 4 weeks post-VLCD and at 9 months follow-up. RESULTS: Twenty-six subjects had a mean weight loss of 9.7% with VLCD. This was associated with significant improvements in liver biochemistry. When stratified by baseline PRO-C3 and PRO-C4 into distinct fibrosis endotypes, these predicted substantial differences in collagen fibrogenesis marker dynamics in response to VLCD. Patients in the high activity group (PRO-C3 >11.4 ng/mL and/or PRO-C4 >236.5 ng/mL) exhibited a marked reduction of collagen fibrogenesis, ranging from a 40%-55% decrease in PRO-C3 and PRO-C4, while fibrogenesis remained unchanged in the low activity group. The biochemical response to weight loss was substantially greater in patients a priori exhibiting a high fibroblast activity endotype in contrast to patients with low activity. CONCLUSIONS: Thus, the likelihood of treatment response may be predicted at baseline by quantification of fibrogenesis biomarkers.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Complemento C3 , Complemento C4 , Colágeno , Biomarcadores , Pérdida de PesoRESUMEN
CONTEXT: Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on ß-cell function and insulin kinetics remains unclear. OBJECTIVE: To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and ß-cell function. METHODS: This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and ß-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured. RESULTS: ß-cell function was 40% greater after WP (P = .001) and was accompanied with a -22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (-1.5 mmol/L and -16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133). CONCLUSION: In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in ß-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further ß-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146 Website link: www.isrctn.com/ISRCTN17563146.
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Diabetes Mellitus Tipo 2 , Insulina , Adulto , Humanos , Insulina/metabolismo , Proteína de Suero de Leche , Cinética , Método Simple Ciego , Glucemia/metabolismo , Periodo Posprandial/fisiología , Estudios CruzadosRESUMEN
Beetroot (BR) is a rich source of nitrate (NO3-) that has been shown to reduce blood pressure (BP). Yet, no studies have examined the vascular benefits of BR in whole-food form and whether the effects are modified by age. This study was a four-arm, randomised, open-label, cross-over design in twenty-four healthy adults (young n 12, age 27 ± 4 years, old n 12, age 64 ± 5 years). Participants consumed whole-cooked BR at portions of (NO3- content in brackets) 100 g (272 mg), 200 g (544 mg) and 300 g (816 mg) and a 200-ml solution containing 1000 mg of potassium nitrate (KNO3) on four separate occasions over a 4-week period (≥7-d washout period). BP, plasma NO3- and nitrite (NO2-) concentrations, and post-occlusion reactive hyperaemia via laser Doppler, were measured pre- and up to 5-h post-intervention. Data were analysed by repeated-measures ANOVA. Plasma NO2- concentrations were higher in the young v. old at baseline and post-intervention (P < 0·05). All NO3- interventions decreased systolic and diastolic BP in young participants (P < 0·05), whereas only KNO3 (at 240-300 min post-intake) significantly decreased systolic (-4·8 mmHg, -3·5 %, P = 0·024) and diastolic (-5·4 mmHg, -6·5 %, P = 0·007) BP in older participants. In conclusion, incremental doses of dietary NO3- reduced systolic and diastolic BP in healthy young adults whereas in the older group a significant decrease was only observed with the highest dose. The lower plasma NO2- concentrations in older participants suggest that there may be mechanistic differences in the production of NO from dietary NO3- in young and older populations.
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Beta vulgaris , Nitratos , Adulto Joven , Humanos , Anciano , Adulto , Persona de Mediana Edad , Presión Sanguínea , Estudios Cruzados , Dióxido de Nitrógeno/farmacología , Nitritos , Envejecimiento , Verduras , Suplementos DietéticosRESUMEN
PURPOSE: We examined the effects of collagen peptides (CP) supplementation on exercise-induced gastrointestinal (GI) stress. METHODS: In a randomized, crossover design, 20 volunteers (16 males: [Formula: see text]O2max, 53.4 ± 5.9 ml·kg-1) completed 3 trials: a non-exercise rest trial, with no supplement (REST) and then an exercise trial with CP (10 g·day-1) or placebo control (CON) supplements, which were consumed for 7 days prior to, and 45 min before, a 70 min run at 70-90% of [Formula: see text]O2max. Outcome measures included urinary lactulose and rhamnose (L/R), intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), anti-LPS antibody, monocyte-chemoattractant protein-1 (MCP-1), interleukin (IL) 6 and 8, cortisol, alkaline phosphatase (ALP) (measured pre, 10 min post and 2 h post) and subjective GI symptoms. RESULTS: There were no differences in heart rate, perceived exertion, thermal comfort, or core temperature during exercise in the CP and CON trials (all P > 0.05). I-FABP was higher in CP (2538 ± 1221 pg/ml) and CON (2541 ± 766 pg/ml) vs. REST 2 h post (1893 ± 1941 pg/ml) (both P < 0.05). LPS increased in CON vs. REST 2 h post (+ 71.8 pg/ml; P < 0.05). Anti-LPS antibody decreased in CON and CP vs. REST at post (both P < 0.05). There were no differences in MCP-1, IL-6, and IL-8 between the CP and CON trials (all P > 0.05), and no differences in L/R or GI symptoms between CON and CP (all P > 0.05). CONCLUSION: Collagen peptides did not modify exercise-induced changes in inflammation, GI integrity or subjective GI symptoms but LPS was higher in CON 2 h post-exercise and thus future studies may be warranted.
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Ejercicio Físico , Tracto Gastrointestinal , Masculino , Humanos , Tracto Gastrointestinal/metabolismo , Ejercicio Físico/fisiología , Inflamación/metabolismo , Interleucina-6/metabolismo , ColágenoRESUMEN
INTRODUCTION: During acute feeding trials, consuming a large dose of whey protein (WP) before meals improves postprandial glucose regulation in people with type 2 diabetes. It is unclear if the reported benefits of premeal WP supplementation are translatable to everyday care or are associated with clinically meaningful, real-world glycemic outcomes. This study examined the application of a novel, premeal shot containing a low dose of WP on parameters of free-living glycemic control in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized, placebo-controlled, single-blind crossover design, 18 insulin naive individuals with type 2 diabetes ((mean±SD) age, 50±6 years; HbA1c (glycated hemoglobin), 7.4%±0.8%; duration of diabetes, 6±5 years) consumed a ready-to-drink WP shot (15 g of protein) or a nutrient-depleted placebo beverage 10 min before breakfast, lunch, and dinner over a 7-day free-living period. Free-living glucose control was measured by blinded continuous glucose monitoring and determined by the percentage of time spent above range (>10 mmol/L), in euglycemic range (3.9-10.0 mmol/L), below range (<3.9 mmol/L) and mean glucose concentrations. RESULTS: Mealtime WP supplementation reduced the prevalence of daily hyperglycemia by 8%±19% (30%±25% vs 38%±28%, p<0.05), thereby enabling a 9%±19% (~2 hours/day) increase in the time spent in euglycemia (p<0.05). Mean 24-hour blood glucose concentrations were 0.6±1.2 mmol/L lower during WP compared with placebo (p<0.05). Similar improvements in glycemic control were observed during the waken period with premeal WP supplementation (p<0.05), whereas nocturnal glycemic control was unaffected (p>0.05). Supplemental compliance/acceptance was high (>98%), and no adverse events were reported. CONCLUSIONS: Consuming a novel premeal WP shot containing 15 g of protein before each main meal reduces the prevalence of daily hyperglycemia, thereby enabling a greater amount of time spent in euglycemic range per day over 7 days of free-living in people with type 2 diabetes. TRIAL REGISTRATION NUMBER: ISRCTN17563146; www.isrctn.com/ISRCTN17563146.
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Diabetes Mellitus Tipo 2 , Hiperglucemia , Adulto , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Estudios Cruzados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hiperglucemia/prevención & control , Persona de Mediana Edad , Método Simple Ciego , Proteína de Suero de Leche/uso terapéuticoRESUMEN
Background: Many individuals with type 1 diabetes retain residual beta-cell function. Sustained endogenous insulin and C-peptide secretion is associated with reduced diabetes related complications, but underlying mechanisms remain unclear. Lower circulating numbers of endothelial and hematopoietic progenitor cells (EPCs and HPCs), and the inability to increase the count of these cells in response to exercise, are also associated with increased diabetes complications and cardiovascular disease. It is unknown whether residual beta-cell function influences HPCs and EPCs. Thus, this study examined the influence of residual beta-cell function in type 1 diabetes upon exercise-induced changes in haematopoietic (HPCs) and endothelial progenitor cells (EPCs). Methods: Participants with undetectable stimulated C-peptide (n=11; Cpepund), 10 high C-peptide (Cpephigh; >200 pmol/L), and 11 non-diabetes controls took part in this observational exercise study, completing 45 minutes of intensive walking at 60% VËO2peak . Clinically significant HPCs (CD34+) and EPCs (CD34+VEGFR2+) phenotypes for predicting future adverse cardiovascular outcomes, and subsequent cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), were enumerated at rest and immediately post-exercise by flow cytometry. Results: Exercise increased HPCs and EPCs phenotypes similarly in the Cpephigh and control groups (+34-121% across phenotypes, p<0.04); but Cpepund group did not significantly increase from rest, even after controlling for diabetes duration. Strikingly, the post-exercise Cpepund counts were still lower than Cpephigh at rest. Conclusions: Residual beta-cell function is associated with an intact exercise-induced HPCs and EPCs mobilisation. As key characteristics (age, fitness, HbA1c) were similar between groups, the mechanisms underpinning the absent mobilisation within those with negative C-peptide, and the vascular implications, require further investigation.
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Capacidad Cardiovascular , Diabetes Mellitus Tipo 1 , Células Progenitoras Endoteliales , Diabetes Mellitus Tipo 1/metabolismo , Células Progenitoras Endoteliales/metabolismo , Ejercicio Físico/fisiología , Hemoglobina Glucada/metabolismo , HumanosRESUMEN
AIMS: Many individuals with type 1 diabetes retain residual ß-cell function, with increased endogenous insulin secretion associated with reduced hyperglycaemia, hypoglycaemia and glycaemic variability. However, it is unknown when these improvements occur during the day. Dysglycaemia is common in overnight and postprandial periods and associated with diabetes complications. Therefore, this study aimed to determine the influence of residual ß-cell function upon nocturnal and postprandial glycaemic control in established type 1 diabetes. METHODS: Under free-living conditions, 66 participants wore a blinded continuous glucose monitor (CGM), kept a food diary, and completed a stimulated urine C-peptide creatinine (UCPCR) test. Nocturnal, and postprandial CGM outcomes (participant means and discrete event analysis) were compared between UCPCR groups: undetectable (Cpepund ), low (Cpeplow : 0.001-0.19 nmol/mmol) and high (Cpephigh : ≥0.2 nmol/mmol). RESULTS: Greater ß-cell function was associated with incremental improvements in glycaemia. Cpephigh spent significantly greater time in normoglycaemia than Cpepund overnight (76 ± 20% vs. 58 ± 20%, p = 0.005) and 0-300 mins postprandially (68 ± 22% vs. 51 ± 22%, p = 0.045), while also having reducing nocturnal variability (SD 1.12 ± 0.41 vs. 1.52 ± 0.43 mmol/L, p = 0.010). Analysis of individual events, controlling for diabetes duration, BMI, basal insulin, use of a continuous or flash glucose monitor and (for postprandial) meal type, carbohydrate and bolus insulin intake, replicated the group findings, additionally demonstrating Cpepund had increased hyperglycaemia versus Cpeplow overnight and increased postprandial hypoglycaemic events compared with Cpephigh . For all participants, breakfast had a significantly higher incremental area under the curve than lunch and dinner. CONCLUSIONS: Residual ß-cell function is associated with improved nocturnal and postprandial glycaemic control. These data may be of clinical importance for identifying specific periods and individuals where further glycaemic management strategies would be beneficial.
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Diabetes Mellitus Tipo 1 , Hiperglucemia , Hipoglucemia , Glucemia/análisis , Estudios Cruzados , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Progresión de la Enfermedad , Humanos , Hiperglucemia/prevención & control , Insulina , Periodo PosprandialRESUMEN
BACKGROUND: Dietary nitrate consumption can increase concentrations of nitrate and nitrite in blood, saliva, and urine. Whether the change in concentrations is influenced by age is currently unknown. OBJECTIVES: We aimed to measure changes in nitrate and nitrite concentrations in plasma, urine, and saliva and exhaled NO concentrations after single incremental doses of dietary nitrate in young and older healthy adults. METHODS: Twelve young (18-35 y old) and 12 older (60-75 y old) healthy, nonsmoking participants consumed single doses of 100 g, 200 g, 300 g whole beetroot (BR) and 1000 mg potassium nitrate (positive control) ≥7 d apart in a crossover, randomized clinical trial. Plasma nitrate and nitrite concentrations and exhaled NO concentrations were measured over a 5-h period. Salivary nitrate and nitrite concentrations were measured over a 12-h period and urinary nitrate over a 24-h period. Time, intervention, age, and interaction effects were measured with repeated-measures ANOVAs. RESULTS: Dose-dependent increases were seen in plasma, salivary, and urinary nitrate after BR ingestion (all P ≤ 0.002) but there were no differences between age groups at baseline (all P ≥ 0.56) or postintervention (all P ≥ 0.12). Plasma nitrite concentrations were higher in young than older participants at baseline (P = 0.04) and after consumption of 200 g (P = 0.04; +25.7 nmol/L; 95% CI: 0.97, 50.3 nmol/L) and 300 g BR (P = 0.02; +50.3 nmol/L; 95% CI: 8.57, 92.1 nmol/L). Baseline fractional exhaled NO (FeNO) concentrations were higher in the younger group [P = 0.03; +8.60 parts per billion (ppb); 95% CI: 0.80, 16.3 ppb], and rose significantly over the 5-h period, peaking 5 h after KNO3 consumption (39.4 ± 4.5 ppb; P < 0.001); however, changes in FeNO were not influenced by age (P = 0.276). CONCLUSIONS: BR is a source of bioavailable dietary nitrate in both young and older adults and can effectively raise nitrite and nitrate concentrations. Lower plasma nitrite and FeNO concentrations were found in older subjects, confirming the impact of ageing on NO bioavailability across different systems.This trial was registered at www.isrctn.com as ISRCTN86706442.
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Beta vulgaris , Nitratos , Anciano , Envejecimiento , Presión Sanguínea , Estudios Cruzados , Humanos , Nitritos , VerdurasRESUMEN
INTRODUCTION: There are 3.9 million people in the UK with diabetes. Sarcopenia, increased frailty and loss of independence are often unappreciated complications of diabetes. Resistance exercise shows promise in reducing these complications in older adult diabetes patients. The aim of this feasibility randomised controlled trial is to (1) characterise the physical function, cardiovascular health and the health and well-being of older adults with mild frailty with/without diabetes treated with insulin, (2) to understand the feasibility and acceptability of a 4-week resistance exercise training programme in improving these parameters for those with diabetes and (3) to test the feasibility of recruiting and randomising the diabetic participant group to a trial of resistance training. METHODS AND ANALYSIS: Thirty adults aged ≥60 years with insulin-treated diabetes mellitus (type 1 or 2), and 30 without, all with mild frailty (3-4 on the Rockwood Frailty Scale) will be recruited. All will complete blood, cardiovascular and physical function testing. Only the diabetic group will then proceed into the trial itself. They will be randomised 1:1 to a 4-week semisupervised resistance training programme, designed to increase muscle mass and strength, or to usual care, defined as their regular physical activity, for 4 weeks. This group will then repeat testing. Primary outcomes include recruitment rate, attrition rate, intervention fidelity and acceptability, and adherence to the training programme. A subset of participants will be interviewed before and after the training programme to understand experiences of resistance training, impact on health and living with diabetes (where relevant) as they have aged. Analyses will include descriptive statistics and qualitative thematic analysis. ETHICS AND DISSEMINATION: The North East-Newcastle and North Tyneside 2 Research Ethics Committee (20/NE/0178) approved the study. Outputs will include feasibility data to support funding applications for a future definitive trial, conference and patient and public involvement presentations, and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN13193281.
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Diabetes Mellitus , Fragilidad , Anciano , Diabetes Mellitus/tratamiento farmacológico , Ejercicio Físico , Terapia por Ejercicio , Estudios de Factibilidad , Fragilidad/prevención & control , Humanos , Insulina , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Purpose: Elevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes. Methods: In a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5-10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen. Results: WP reduced PPG area under the curve [AUC0-60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects. Conclusion: Pre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual's insulin resistance, their obese state, or other obesity-related ailments needs further investigation. Clinical Trial Registration: ISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.
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Glucemia/metabolismo , Hormonas Gastrointestinales/metabolismo , Obesidad Abdominal/dietoterapia , Proteína de Suero de Leche/farmacología , Adulto , Glucemia/efectos de los fármacos , Péptido C/sangre , Estudios Cruzados , Ingestión de Alimentos , Inglaterra , Alimentos Formulados , Vaciamiento Gástrico/fisiología , Polipéptido Inhibidor Gástrico/sangre , Polipéptido Inhibidor Gástrico/efectos de los fármacos , Glucagón/sangre , Péptido 1 Similar al Glucagón/sangre , Péptido 1 Similar al Glucagón/efectos de los fármacos , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Obesidad Abdominal/sangre , Obesidad Abdominal/metabolismo , Periodo Posprandial/efectos de los fármacos , Delgadez/sangre , Delgadez/metabolismo , Proteína de Suero de Leche/administración & dosificación , Adulto JovenRESUMEN
OBJECTIVE: Clinical guidelines recommend weight loss to manage non-alcoholic fatty liver disease (NAFLD). However, the majority of patients find weight loss a significant challenge. We identified factors associated with engagement and adherence to a low-energy diet (LED) as a treatment option for NAFLD. DESIGN: 23 patients with NAFLD enrolled in a LED (~800 kcal/day) were individually interviewed. Transcripts were thematically analysed. RESULTS: 14/23 patients achieved ≥10% weight loss, 18/23 achieved ≥7% weight loss and 19/23 achieved ≥5% weight loss. Six themes were generated from the data. A desire to achieve rapid weight loss to improve liver health and prevent disease progression was the most salient facilitator to engagement. Early and significant weight loss, accountability to clinicians and regular appointments with personalised feedback were facilitators to engagement and adherence. The desire to receive positive reinforcement from a consultant was a frequently reported facilitator to adherence. Practical and emotional support from friends and family members was critically important outside of the clinical setting. Irregular working patterns preventing attendance at appointments was a barrier to adherence and completion of the intervention. CONCLUSIONS: Engagement and adherence to a LED in patients with NAFLD were encouraged by early and rapid weight loss, personalised feedback and positive reinforcement in the clinical setting combined with ongoing support from friends and family members. Findings support those identified in patients who completed a LED to achieve type 2 diabetes remission and highlight the importance of behaviour change support during the early stages of a LED to promote adherence.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Restricción Calórica , Humanos , Estilo de Vida , Enfermedad del Hígado Graso no Alcohólico/terapia , Pérdida de PesoRESUMEN
Exercise mobilizes angiogenic cells, which stimulate vascular repair. However, limited research suggests exercise-induced increase of endothelial progenitor cell (EPCs) is completely lacking in type 1 diabetes (T1D). Clarification, along with investigating how T1D influences exercise-induced increases of other angiogenic cells (hematopoietic progenitor cells; HPCs) and cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), is needed. Thirty T1D patients and 30 matched non-diabetes controls completed 45 min of incline walking. Circulating HPCs (CD34+, CD34+CD45dim) and EPCs (CD34+VEGFR2+, CD34+CD45dimVEGFR2+), and subsequent expression of CXCR4 and CXCR7, were enumerated by flow cytometry at rest and post-exercise. Counts of HPCs, EPCs and expression of CXCR4 and CXCR7 were significantly lower at rest in the T1D group. In both groups, exercise increased circulating angiogenic cells. However, increases was largely attenuated in the T1D group, up to 55% lower, with CD34+ (331 ± 437 Δcells/mL vs. 734 ± 876 Δcells/mL p = 0.048), CD34+VEGFR2+ (171 ± 342 Δcells/mL vs. 303 ± 267 Δcells/mL, p = 0.006) and CD34+VEGFR2+CXCR4+ (126 ± 242 Δcells/mL vs. 218 ± 217 Δcells/mL, p = 0.040) significantly lower. Exercise-induced increases of angiogenic cells is possible in T1D patients, albeit attenuated compared to controls. Decreased mobilization likely results in reduced migration to, and repair of, vascular damage, potentially limiting the cardiovascular benefits of exercise.Trial registration: ISRCTN63739203.
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Diabetes Mellitus Tipo 1/sangre , Células Progenitoras Endoteliales/fisiología , Ejercicio Físico/fisiología , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Adulto , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Células Madre Hematopoyéticas/fisiología , Humanos , Masculino , Persona de Mediana Edad , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
INTRODUCTION: Exercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this population is prudent. We assessed bone turnover responses to acute exercise in individuals with long-duration type 1 diabetes and matched controls. RESEARCH DESIGN AND METHODS: Participants with type 1 diabetes (n=15; age: 38.7±13.3; glycosylated hemoglobin: 60.5±6.7 mmol/mol; diabetes duration: 19.3±11.4 years) and age-matched, fitness-matched, and body mass index-matched controls (n=15) completed 45 min of incline walking (60% peak oxygen uptake). Blood samples were collected at baseline and immediately, 30 min, and 60 min postexercise. Markers of bone resorption (ß-C-terminal cross-linked telopeptide of type 1 collagen, ß-CTx) and formation (procollagen type-1 amino-terminal propeptide, P1NP), parathyroid hormone (PTH), phosphate, and calcium (albumin-adjusted and ionized) were measured. Data (mean±SD) were analyzed by a mixed-model analysis of variance. RESULTS: Baseline concentrations of P1NP and ß-CTx were comparable between participants with type 1 diabetes and controls. P1NP did not change with exercise (p=0.20) but ß-CTx decreased (p<0.001) in both groups, but less so in participants with type 1 diabetes compared with controls (-9.2±3.7%; p=0.02). PTH and phosphate increased immediately postexercise in both groups; only PTH was raised at 30 min postexercise (p<0.001), with no between-group differences (p>0.39). Participants with type 1 diabetes had reduced albumin and ionized calcium at all sample points (p<0.01). CONCLUSIONS: Following exercise, participants with type 1 diabetes displayed similar time-course changes in markers of bone formation and associated metabolites, but an attenuated suppression in bone resorption. The reduced albumin and ionized calcium may have implications for future bone health. Further investigation of the interactions between type 1 diabetes, differing modalities and intensities of exercise, and bone health is warranted.
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Remodelación Ósea , Diabetes Mellitus Tipo 1 , Ejercicio Físico , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona ParatiroideaRESUMEN
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common liver condition worldwide. A weight loss goal of ≥10% is the recommended treatment for NAFLD; however, only a minority of patients achieve this level of weight reduction with standard dietary approaches. This study aimed to determine whether a very low calorie diet (VLCD) is an acceptable and feasible therapy to achieve and maintain a ≥10% weight loss in patients with clinically significant NAFLD. METHODS: Patients with clinically significant NAFLD were recruited to a VLCD (â¼800 kcal/d) intervention using meal replacement products. Anthropometrics, blood tests (liver and metabolic), liver stiffness, and cardiovascular disease risk were measured at baseline, post-VLCD, and at 9-month follow-up. RESULTS: A total of 45 patients were approached of which 30 were enrolled 27 (90%) completed the VLCD intervention, and 20 (67%) were retained at 9-month follow-up. The VLCD was acceptable to patients and feasible to deliver. Intention-to-treat analysis found that 34% of patients achieved and sustained ≥10% weight loss, 51% achieved ≥7% weight loss, and 68% achieved ≥5% weight loss at 9-month follow-up. For those completing the VLCD, liver health (liver enzymes and liver stiffness), cardiovascular disease risk (blood pressure and QRISK2), metabolic health (fasting glucose, HbA1c, and insulin), and body composition significantly improved post-VLCD and was maintained at 9 months. DISCUSSION: VLCD offers a feasible treatment option for some patients with NAFLD to enable a sustainable ≥10%, weight loss, which can improve liver health, cardiovascular risk, and quality of life in those completing the intervention.
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Restricción Calórica , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Pérdida de Peso , Adulto , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/psicología , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the impact of residual ß-cell function on continuous glucose monitoring (CGM) outcomes following acute exercise in people with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Thirty participants with T1D for ≥3 years were recruited. First, participants wore a blinded CGM unit for 7 days of free-living data capture. Second, a 3-h mixed-meal test assessed stimulated C-peptide and glucagon. Peak C-peptide was used to allocate participants into undetectable (Cpepund <3 pmol/L), low (Cpeplow 3-200 pmol/L), or high (Cpephigh >200 pmol/L) C-peptide groups. Finally, participants completed 45 min of incline treadmill walking at 60% VO2peak followed by a further 48-h CGM capture. RESULTS: CGM parameters were comparable across groups during the free-living observation week. In the 12- and 24-h postexercise periods (12 h and 24 h), the Cpephigh group had a significantly greater amount of time spent with glucose 3.9-10 mmol/L (12 h, 73.5 ± 27.6%; 24 h, 76.3 ± 19.2%) compared with Cpeplow (12 h, 43.6 ± 26.1%, P = 0.027; 24 h, 52.3 ± 25.0%, P = 0.067) or Cpepund (12 h, 40.6 ± 17.0%, P = 0.010; 24 h, 51.3 ± 22.3%, P = 0.041). Time spent in hyperglycemia (12 h and 24 h glucose >10 and >13.9 mmol/L, P < 0.05) and glycemic variability (12 h and 24 h SD, P < 0.01) were significantly lower in the Cpephigh group compared with Cpepund and Cpeplow. Change in CGM outcomes from pre-exercise to 24-h postexercise was divergent: Cpepund and Cpeplow experienced worsening (glucose 3.9-10 mmol/L: -9.1% and -16.2%, respectively), with Cpephigh experiencing improvement (+12.1%) (P = 0.017). CONCLUSIONS: Residual ß-cell function may partially explain the interindividual variation in the acute glycemic benefits of exercise in individuals with T1D. Quantifying C-peptide could aid in providing personalized and targeted support for exercising patients.
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Diabetes Mellitus Tipo 1/sangre , Ejercicio Físico/fisiología , Control Glucémico , Células Secretoras de Insulina/fisiología , Adolescente , Adulto , Anciano , Glucemia/análisis , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea/métodos , Péptido C/análisis , Péptido C/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Control Glucémico/métodos , Control Glucémico/estadística & datos numéricos , Humanos , Hipoglucemia/sangre , Hipoglucemia/epidemiología , Hipoglucemia/fisiopatología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: This study examined whether a higher protein diet following strenuous exercise can alter markers of muscle damage and inflammation in older adults. METHODS: Using a double-blind, independent group design, 10 males and eight females (age 57 ± 4 years; mass 72.3 ± 5.6 kg; height 1.7 ± 6.5 m) were supplied with a higher protein (2.50 g·kg-1·day-1) or moderate protein (1.25 g·kg-1·day-1) diet for 48 hr after 140 squats with 25% of their body mass. Maximal isometric voluntary contractions, muscle soreness, creatine kinase, Brief Assessment of Mood Adapted, and inflammatory markers were measured preexercise, and 24 hr and 48 hr postexercise. RESULTS: The maximal isometric voluntary contractions decreased postexercise (p = .001, ηp2=.421), but did not differ between groups (p = .822, ηp2=.012). Muscle soreness peaked at 24 hr post in moderate protein (44 ± 30 mm) and 48 hr post in higher protein (70 ± 46 mm; p = .005; ηp2=.282); however, no group differences were found (p = .585; ηp2=.083). Monocytes and lymphocytes significantly decreased postexercise, and eosinophils increased 24 hr postexercise (p < 0.05), but neutrophils, creatine kinase, interleukin-6, C-reactive protein, monocyte chemotactic protein-1, and Brief Assessment of Mood Adapted were unchanged by exercise or the intervention (p > .05). CONCLUSION: In conclusion, 2.50 g·kg-1·day-1 of protein is not more effective than 1.25 g·kg-1·day-1 for attenuating indirect markers of muscle damage and inflammation following strenuous exercise in older adults.