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1.
Am J Physiol Endocrinol Metab ; 326(3): E277-E289, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38231001

ABSTRACT

Although the mechanisms underpinning short-term muscle disuse atrophy and associated insulin resistance remain to be elucidated, perturbed lipid metabolism might be involved. Our aim was to determine the impact of acipimox administration [i.e., pharmacologically lowering circulating nonesterified fatty acid (NEFA) availability] on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age: 22 ± 1 years; body mass index: 24.0 ± 0.6 kg·m-2) underwent 2 days forearm immobilization with placebo (PLA; n = 9) or acipimox (ACI; 250 mg Olbetam; n = 9) ingestion four times daily. Before and after immobilization, whole body glucose disposal rate (GDR), forearm glucose uptake (FGU; i.e., muscle insulin sensitivity), and amino acid kinetics were measured under fasting and hyperinsulinemic-hyperaminoacidemic-euglycemic clamp conditions using forearm balance and l-[ring-2H5]-phenylalanine infusions. Immobilization did not affect GDR but decreased insulin-stimulated FGU in both groups, more so in ACI (from 53 ± 8 to 12 ± 5 µmol·min-1) than PLA (from 52 ± 8 to 38 ± 13 µmol·min-1; P < 0.05). In ACI only, and in contrast to our hypothesis, fasting arterialized NEFA concentrations were elevated to 1.3 ± 0.1 mmol·L-1 postimmobilization (P < 0.05), and fasting forearm NEFA balance increased approximately fourfold (P = 0.10). Forearm phenylalanine net balance decreased following immobilization (P < 0.10), driven by an increased rate of appearance [from 32 ± 5 (fasting) and 21 ± 4 (clamp) preimmobilization to 53 ± 8 and 31 ± 4 postimmobilization; P < 0.05] while the rate of disappearance was unaffected by disuse or acipimox. Disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.NEW & NOTEWORTHY We demonstrate that 2 days of forearm cast immobilization in healthy young volunteers leads to the rapid development of insulin resistance, which is accompanied by accelerated muscle amino acid efflux in the absence of impaired muscle amino acid uptake. Acutely elevated fasting nonesterified fatty acid (NEFA) availability as a result of acipimox supplementation worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance.


Subject(s)
Insulin Resistance , Pyrazines , Humans , Young Adult , Amino Acids/metabolism , Fatty Acids, Nonesterified/metabolism , Forearm , Glucose/metabolism , Hypolipidemic Agents/metabolism , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Insulin/metabolism , Muscles/metabolism , Phenylalanine/metabolism , Polyesters/metabolism , Volunteers
2.
Diabet Med ; 40(9): e15169, 2023 09.
Article in English | MEDLINE | ID: mdl-37381170

ABSTRACT

AIMS: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: A 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.


Subject(s)
Biomedical Research , Diabetes Mellitus , Humans , Exercise , Diabetes Mellitus/therapy , Health Personnel , United Kingdom/epidemiology
3.
Diabetes Spectr ; 36(2): 114-126, 2023 May.
Article in English | MEDLINE | ID: mdl-37193206

ABSTRACT

This article provides practical tips for advising people with type 2 diabetes on how to engage in regular exercise safely and effectively. Its focus is on individuals who wish to exceed the minimum physical activity recommendation of 150 minutes/week of moderate-intensity exercise or even compete in their chosen sport. Health care professionals who work with such individuals must have a basic understanding of glucose metabolism during exercise, nutritional requirements, blood glucose management, medications, and sport-related considerations. This article reviews three key aspects of individualized care for physically active people with type 2 diabetes: 1) initial medical assessment and pre-exercise screenings, 2) glucose monitoring and nutritional considerations, and 3) the combined glycemic effects of exercise and medications.

4.
BMC Med ; 19(1): 184, 2021 08 20.
Article in English | MEDLINE | ID: mdl-34412655

ABSTRACT

BACKGROUND: Type 2 diabetes (T2D) is common and increasing in prevalence. It is possible to prevent or delay T2D using lifestyle intervention programmes. Entry to these programmes is usually determined by a measure of glycaemia in the 'intermediate' range. This paper investigated the relationship between HbA1c and future diabetes risk and determined the impact of varying thresholds to identify those at high risk of developing T2D. METHODS: We studied 4227 participants without diabetes aged ≥ 40 years recruited to the Exeter 10,000 population cohort in South West England. HbA1c was measured at study recruitment with repeat HbA1c available as part of usual care. Absolute risk of developing diabetes within 5 years, defined by HbA1c ≥ 48 mmol/mol (6.5%), according to baseline HbA1c, was assessed by a flexible parametric survival model. RESULTS: The overall absolute 5-year risk (95% CI) of developing T2D in the cohort was 4.2% (3.6, 4.8%). This rose to 7.1% (6.1, 8.2%) in the 56% (n = 2358/4224) of participants classified 'high-risk' with HbA1c ≥ 39 mmol/mol (5.7%; ADA criteria). Under IEC criteria, HbA1c ≥ 42 mmol/mol (6.0%), 22% (n = 929/4277) of the cohort was classified high-risk with 5-year risk 14.9% (12.6, 17.2%). Those with the highest HbA1c values (44-47 mmol/mol [6.2-6.4%]) had much higher 5-year risk, 26.4% (22.0, 30.5%) compared with 2.1% (1.5, 2.6%) for 39-41 mmol/mol (5.7-5.9%) and 7.0% (5.4, 8.6%) for 42-43 mmol/mol (6.0-6.1%). Changing the entry criterion to prevention programmes from 39 to 42 mmol/mol (5.7-6.0%) reduced the proportion classified high-risk by 61%, and increased the positive predictive value (PPV) from 5.8 to 12.4% with negligible impact on the negative predictive value (NPV), 99.6% to 99.1%. Increasing the threshold further, to 44 mmol/mol (6.2%), reduced those classified high-risk by 59%, and markedly increased the PPV from 12.4 to 23.2% and had little impact on the NPV (99.1% to 98.5%). CONCLUSIONS: A large proportion of people are identified as high-risk using current thresholds. Increasing the risk threshold markedly reduces the number of people that would be classified as high-risk and entered into prevention programmes, although this must be balanced against cases missed. Raising the entry threshold would allow limited intervention opportunities to be focused on those most likely to develop T2D.


Subject(s)
Diabetes Mellitus, Type 2 , Blood Glucose , Cohort Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , England/epidemiology , Glycated Hemoglobin , Humans
5.
Exerc Immunol Rev ; 25: 64-82, 2019.
Article in English | MEDLINE | ID: mdl-30753130

ABSTRACT

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that targets and destroys insulin-secreting pancreatic beta cells. Beta cell specific T cells are highly differentiated and show evidence of previous antigen exposure. Exerciseinduced mobilisation of highly-differentiated CD8+ T cells facilitates immune surveillance and regulation. We aimed to explore exercise-induced T cell mobilisation in T1D. In this study, we compared the effects of a single bout of vigorous intensity exercise on T cell mobilisation in T1D and control participants. N=12 T1D (mean age 33.2yrs, predicted VO2 max 32.2 mL/(kg·min), BMI 25.3Kg/m2) and N=12 control (mean age 29.4yrs, predicted VO2 max 38.5mL(kg.min), BMI 23.7Kg/m2) male participants completed a 30-minute bout of cycling at 80% predicted VO2 max in a fasted state. Peripheral blood was collected at baseline, immediately post-exercise, and 1 hour post-exercise. Exercise-induced mobilisation was observed for T cells in both T1D and control groups. Total CD8+ T cells mobilised to a similar extent in T1D (42.7%; p=0.016) and controls (39.7%; p=0.001). CD8 effector memory CD45RA+ (EMRA) subset were the only T cell lineage subset to be significantly mobilised in both groups though the percentage increase of CD8+ EMRA was blunted in T1D (T1D (26.5%) p=0.004, control (66.1%) p=0.010). Further phenotyping of these subsets revealed that the blunting was most evident in CD8+ EMRA that expressed adhesion (CD11b: T1D 37.70%, Control 91.48%) and activation markers (CD69: T1D 29.87%, Control 161.43%), and appeared to be the most differentiated (CD27-CD28-: T1D 7.12%, Control 113.76%). CD4+ T cells mobilised during vigorous intensity exercise in controls (p=0.001), but not in T1D. The blunted mobilisation response of particular T cell subsets was not due to CMV serostatus or apparent differences in exertion during the exercise bout as defined by heart rate and RPE. Predicted VO2 max showed a trend to be lower in the T1D group than the control group but is unlikely to contribute to this blunted response. We postulate the reasons for a blunted mobilisation of differentiated CD8+ EMRA cells includes differences in blood glucose, adrenaline receptor density, and sequestration of T cells in the pancreas of T1D participants. In conclusion, mobilisation of CD8+ EMRA and CD4+ subsets T cells is decreased in people with T1D during acute exercise.


Subject(s)
CD8-Positive T-Lymphocytes/cytology , Diabetes Mellitus, Type 1/immunology , Exercise , Adult , CD4-Positive T-Lymphocytes/cytology , Humans , Male
6.
Mol Cell ; 37(4): 457-68, 2010 Feb 26.
Article in English | MEDLINE | ID: mdl-20188665

ABSTRACT

MeCP2 is a nuclear protein with an affinity for methylated DNA that can recruit histone deacetylases. Deficiency or excess of MeCP2 causes severe neurological problems, suggesting that the number of molecules per cell must be precisely regulated. We quantified MeCP2 in neuronal nuclei and found that it is nearly as abundant as the histone octamer. Despite this high abundance, MeCP2 associates preferentially with methylated regions, and high-throughput sequencing showed that its genome-wide binding tracks methyl-CpG density. MeCP2 deficiency results in global changes in neuronal chromatin structure, including elevated histone acetylation and a doubling of histone H1. Neither change is detectable in glia, where MeCP2 occurs at lower levels. The mutant brain also shows elevated transcription of repetitive elements. Our data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner.


Subject(s)
Chromatin/metabolism , Histones/metabolism , Methyl-CpG-Binding Protein 2/metabolism , Neurons/metabolism , Protein Multimerization , Animals , Brain/cytology , Brain/metabolism , Cell Nucleus/metabolism , CpG Islands , DNA Methylation , Genome , Methyl-CpG-Binding Protein 2/deficiency , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurons/cytology , Nucleosomes/metabolism , Protein Binding , Transcription, Genetic
7.
Public Health Nutr ; 20(2): 191-199, 2017 02.
Article in English | MEDLINE | ID: mdl-27609314

ABSTRACT

OBJECTIVE: Dietary advice is fundamental in the prevention and management of type 2 diabetes (T2DM). Advice is improved by individual assessment but existing methods are time-consuming and require expertise. We developed a twenty-five-item questionnaire, the UK Diabetes and Diet Questionnaire (UKDDQ), for quick assessment of an individual's diet. The present study examined the UKDDQ's repeatability and relative validity compared with 4 d food diaries. DESIGN: The UKDDQ was completed twice with a median 3 d gap (interquartile range=1-7 d) between tests. A 4 d food diary was completed after the second UKDDQ. Diaries were analysed and food groups were mapped on to the UKDDQ. Absolute agreement between total scores was examined using intra-class correlation (ICC). Agreement for individual items was tested with Cohen's weighted kappa (κ w). SETTING: South West of England. SUBJECTS: Adults (n 177, 50·3 % women) with, or at high risk for, T2DM; mean age 55·8 (sd 8·6) years, mean BMI 34·4 (sd 7·3) kg/m2; participants were 91 % White British. RESULTS: The UKDDQ showed excellent repeatability (ICC=0·90 (0·82, 0·94)). For individual items, κ w ranged from 0·43 ('savoury pastries') to 0·87 ('vegetables'). Total scores from the UKDDQ and food diaries compared well (ICC=0·54 (0·27, 0·70)). Agreement for individual items varied and was good for 'alcohol' (κ w=0·71) and 'breakfast cereals' (κ w=0·70), with no agreement for 'vegetables' (κ w=0·08) or 'savoury pastries' (κ w=0·09). CONCLUSIONS: The UKDDQ is a new British dietary questionnaire with excellent repeatability. Comparisons with food diaries found agreements similar to those for international dietary questionnaires currently in use. It targets foods and habits important in diabetes prevention and management.


Subject(s)
Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/prevention & control , Diet Surveys/methods , Glucose Intolerance/diet therapy , Surveys and Questionnaires/standards , Adult , Aged , Diabetes Mellitus, Type 2/etiology , Diet Records , Diet Surveys/standards , Female , Glucose Intolerance/complications , Humans , Male , Middle Aged , Reproducibility of Results , United Kingdom
8.
Nature ; 464(7291): 1082-6, 2010 Apr 15.
Article in English | MEDLINE | ID: mdl-20393567

ABSTRACT

CpG islands (CGIs) are prominent in the mammalian genome owing to their GC-rich base composition and high density of CpG dinucleotides. Most human gene promoters are embedded within CGIs that lack DNA methylation and coincide with sites of histone H3 lysine 4 trimethylation (H3K4me3), irrespective of transcriptional activity. In spite of these intriguing correlations, the functional significance of non-methylated CGI sequences with respect to chromatin structure and transcription is unknown. By performing a search for proteins that are common to all CGIs, here we show high enrichment for Cfp1, which selectively binds to non-methylated CpGs in vitro. Chromatin immunoprecipitation of a mono-allelically methylated CGI confirmed that Cfp1 specifically associates with non-methylated CpG sites in vivo. High throughput sequencing of Cfp1-bound chromatin identified a notable concordance with non-methylated CGIs and sites of H3K4me3 in the mouse brain. Levels of H3K4me3 at CGIs were markedly reduced in Cfp1-depleted cells, consistent with the finding that Cfp1 associates with the H3K4 methyltransferase Setd1 (refs 7, 8). To test whether non-methylated CpG-dense sequences are sufficient to establish domains of H3K4me3, we analysed artificial CpG clusters that were integrated into the mouse genome. Despite the absence of promoters, the insertions recruited Cfp1 and created new peaks of H3K4me3. The data indicate that a primary function of non-methylated CGIs is to genetically influence the local chromatin modification state by interaction with Cfp1 and perhaps other CpG-binding proteins.


Subject(s)
Chromatin Assembly and Disassembly , Chromatin/genetics , Chromatin/metabolism , CpG Islands/genetics , Trans-Activators/metabolism , Alleles , Animals , Brain/cytology , Cell Line , Chromatin Immunoprecipitation , DNA Methylation , Genome/genetics , Histone-Lysine N-Methyltransferase/metabolism , Histones/chemistry , Histones/metabolism , Methylation , Mice , NIH 3T3 Cells , Promoter Regions, Genetic , Trans-Activators/chemistry , Trans-Activators/deficiency , Trans-Activators/genetics , Zinc Fingers
9.
Diabetologia ; 58(1): 10-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25367458

ABSTRACT

Type 1 diabetes is characterised by immune-mediated destruction of insulin-producing beta cells. Significant beta cell function is usually present at the time of diagnosis with type 1 diabetes, and preservation of this function has important clinical benefits. The last 30 years have seen a number of largely unsuccessful trials for beta cell preservation, some of which have been of therapies that have potential for significant harm. There is a need to explore new, more tolerable approaches to preserving beta cell function that can be implemented on a large clinical scale. Here we review the evidence for physical exercise as a therapy for the preservation of beta cell function in patients with newly diagnosed type 1 diabetes. We highlight possible mechanisms by which exercise could preserve beta cell function and then present evidence from other models of diabetes that demonstrate that exercise preserves beta cell function. We conclude by proposing that there is now a need for studies to explore whether exercise can preserve beta cell in patients newly diagnosed with type 1 diabetes.


Subject(s)
Cytoprotection , Diabetes Mellitus, Type 1/therapy , Exercise/physiology , Insulin-Secreting Cells/physiology , Animals , Apoptosis/physiology , Cell Count , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/physiopathology , Exercise Therapy , Humans , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/pathology
10.
Br J Nutr ; 114(10): 1656-66, 2015 Nov 28.
Article in English | MEDLINE | ID: mdl-26411958

ABSTRACT

Weight loss is crucial for treating type 2 diabetes mellitus (T2DM). It remains unclear which dietary intervention is best for optimising glycaemic control, or whether weight loss itself is the main reason behind observed improvements. The objective of this study was to assess the effects of various dietary interventions on glycaemic control in overweight and obese adults with T2DM when controlling for weight loss between dietary interventions. A systematic review of randomised controlled trials (RCT) was conducted. Electronic searches of Medline, Embase, Cinahl and Web of Science databases were conducted. Inclusion criteria included RCT with minimum 6 months duration, with participants having BMI≥25·0 kg/m2, a diagnosis of T2DM using HbA1c, and no statistically significant difference in mean weight loss at the end point of intervention between dietary arms. Results showed that eleven studies met the inclusion criteria. Only four RCT indicated the benefit of a particular dietary intervention over another in improving HbA1c levels, including the Mediterranean, vegan and low glycaemic index (GI) diets. However the findings from one of the four studies showing a significant benefit are questionable because of failure to control for diabetes medications and poor adherence to the prescribed diets. In conclusion there is currently insufficient evidence to suggest that any particular diet is superior in treating overweight and obese patients with T2DM. Although the Mediterranean, vegan and low-GI diets appear to be promising, further research that controls for weight loss and the effects of diabetes medications in larger samples is needed.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/diet therapy , Diet , Obesity/diet therapy , Overweight/diet therapy , Weight Loss , Diabetes Mellitus, Type 2/complications , Diet, Mediterranean , Diet, Vegan , Glycated Hemoglobin/analysis , Glycemic Index , Humans , MEDLINE , Obesity/complications , Overweight/complications , Randomized Controlled Trials as Topic
11.
Endocr Connect ; 13(5)2024 05 01.
Article in English | MEDLINE | ID: mdl-38451861

ABSTRACT

Post bariatric hypoglycaemia (PBH) is typically a post-prandial hypoglycaemia occurring about 2-4 hours after eating in people who have undergone bariatric surgery. PBH develops relatively late after surgery and often after discharge from post-surgical follow-up by bariatric teams, leading to variability in diagnosis and management in non-specialist centres. AIM: to improve and standardise clinical practice in the diagnosis and management of PBH. OBJECTIVES: (1) to undertake an up-to-date review of the current literature; (2) to formulate practical and evidence-based guidance with regards on the diagnosis and treatment of PBH; (3) to recommend future avenues for research in this condition. METHOD: A scoping review was undertaken after an extensive literature search. A consensus on the guidance and confidence in the recommendations was reached by the steering group authors prior to review by key stakeholders. OUTCOME: We make pragmatic recommendations for the practical diagnosis and management of PBH including criteria for diagnosis and recognition, as well as recommendations for research areas that should be explored.

12.
PLOS Glob Public Health ; 3(9): e0001263, 2023.
Article in English | MEDLINE | ID: mdl-37756263

ABSTRACT

Sub-Saharan Africa is projected to have the highest increase in the number of people with diabetes worldwide. However, the drivers of diabetes in this region have not been clearly elucidated. The aim of this study was to evaluate the incidence of diabetes and the predictors of progression in a population-based cohort with impaired fasting glucose (IFG) in Malawi. We used data from an extensive rural and urban non-communicable disease survey. One hundred seventy-five, of 389 individuals with impaired fasting glucose (IFG) at baseline, age 48 ±15 years and body mass index 27.5 ±5.9 kg/m2 were followed up for a median of 4.2 years (714 person-years). Incidence rates were calculated, and predictors of progression to diabetes were analysed using multivariable logistic regression models, with overall performance determined using receiver operator characteristics (ROC) curves. The median follow-up was 4.2 (IQR 3.4-4.7) years. Forty-five out of 175 (26%) progressed to diabetes. Incidence rates of diabetes were 62.9 per 1000 person-years 95% CI, 47.0-84.3. The predictors of progression were higher; age (odds ratio [OR] 1.48, P = 0.046), BMI (OR 1.98, P = 0.001), waist circumference (OR 2.50,P<0.001), waist-hip ratio (OR 1.40, P = 0.03), systolic blood pressure (OR 1.56, P = 0.01), fasting plasma glucose (OR 1.53, P = 0.01), cholesterol (OR 1.44, P = 0.05) and low-density lipoprotein cholesterol (OR 1.80, P = 0.002). A simple model combining fasting plasma glucose and waist circumference was predictive of progression to diabetes (ROC area under the curve = 0.79). The incidence of diabetes in people with IFG is high in Malawi and predictors of progression are like those seen in other populations. Our data also suggests that a simple chart with probabilities of progression to diabetes based on waist circumference and fasting plasma glucose could be used to identify those at risk of progression in clinical settings in sub-Saharan Africa.

13.
bioRxiv ; 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37873346

ABSTRACT

The mechanisms underpinning short-term muscle disuse atrophy remain to be elucidated, but perturbations in lipid metabolism may be involved. Specifically, positive muscle non-esterified fatty acid (NEFA) balance has been implicated in the development of disuse-induced insulin and anabolic resistance. Our aim was to determine the impact of acipimox administration (i.e. pharmacologically lowering circulating NEFA availability) on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age 22±1 years, BMI 24.0±0.6 kg·m-2) underwent 2 days of forearm cast immobilization with placebo (PLA; n=9, 5M/4F) or acipimox (ACI; 250 mg Olbetam; n=9, 4M/5F) ingestion four times daily. Before and after immobilization, whole-body glucose disposal rate (GDR), forearm glucose uptake (FGU, i.e. muscle insulin sensitivity), and amino acid kinetics were measured under fasting and hyperinsulinaemic-hyperaminoacidaemic-euglycaemic clamp conditions using arteriovenous forearm balance and intravenous L-[ring-2H5]phenylalanine infusions. Immobilization did not affect GDR but decreased insulin-stimulated FGU in both groups, but to a greater degree in ACI (from 53±8 to 12±5 µmol·min-1) than in PLA (from 52±8 to 38±13 µmol·min-1; P<0.05). In ACI only, fasting arterialised NEFA concentrations were elevated to 1.3±0.1 mmol·L-1 post-immobilization (P<0.05), and fasting forearm NEFA balance increased ~4-fold (P=0.10). Forearm phenylalanine net balance tended to decrease following immobilization (P<0.10), driven by increases in phenylalanine rates of appearance (from 32±5 (fasting) and 21±4 (clamp) pre-immobilization to 53±8 and 31±4 post-immobilization; P<0.05) while rates of disappearance were unaffected and no effects of acipimox observed. Altogether, we show disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting muscle amino acid kinetics, suggesting that disuse-associated increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not represent an early mechanism causing anabolic resistance.

14.
J Diabetes Investig ; 14(12): 1378-1382, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37602910

ABSTRACT

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are thought to be the main drivers of insulin secretion in individuals with sulfonylurea (SU)-treated KCNJ11 permanent neonatal diabetes. The aim of this study was to assess for the first time the incretin hormone response to carbohydrate and protein/fat in adults with sulfonylurea-treated KCNJ11 permanent neonatal diabetes compared with that of controls without diabetes. Participants were given a breakfast high in carbohydrate and an isocaloric breakfast high in protein/fat on two different mornings. Incremental area under the curve and total area under the curve (0-240 minutes) for total GLP-1 and GIP were compared between groups, using non-parametric statistical methods. Post-meal GLP-1 and GIP secretion were similar in cases and controls, suggesting this process is adenosine triphosphate-sensitive potassium channel-independent. Future research will investigate whether treatments targeting the incretin pathway are effective in individuals with KCNJ11 permanent neonatal diabetes who do not have good glycemic control on sulfonylurea alone.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes Mellitus , Infant, Newborn , Adult , Humans , Incretins/therapeutic use , Glucagon/metabolism , Insulin/metabolism , Blood Glucose/metabolism , Gastric Inhibitory Polypeptide , Glucagon-Like Peptide 1 , Diabetes Mellitus, Type 2/metabolism
15.
PLoS One ; 17(2): e0264432, 2022.
Article in English | MEDLINE | ID: mdl-35226681

ABSTRACT

INTRODUCTION: Sodium fluoride (NaF) tubes are the recommended tubes for glucose measurements, but these are expensive, have limited number of uses, and are not always available in low resource settings. Alternative sample handling techniques are thus needed. We compared glucose stability in samples collected in various tubes exposed to different pre-analytical conditions in Uganda. METHODS: Random (non-fasted) blood samples were drawn from nine healthy participants into NaF, Ethylenediaminetetraacetic acid (EDTA), and plain serum tubes. The samples were kept un-centrifuged or centrifuged with plasma or serum pipetted into aliquots, placed in cool box with ice or at room temperature and were stored in a permanent freezer after 0, 2, 6, 12 and 24 hours post blood draw before glucose analysis. RESULTS: Rapid decline in glucose concentrations was observed when compared to baseline in serum (declined to 64%) and EDTA-plasma (declined to 77%) after 6 hours when samples were un-centrifuged at room temperature whilst NaF-plasma was stable after 24 hours in the same condition. Un-centrifuged EDTA-plasma kept on ice was stable for up to 6 hours but serum was not stable (degraded to 92%) in the same conditions. Early centrifugation prevented glucose decline even at room temperature regardless of the primary tube used with serum, EDTA-plasma and NaF-plasma after 24 hours. CONCLUSION: In low resource settings we recommend use of EDTA tubes placed in cool box with ice and analysed within 6 hours as an alternative to NaF tubes. Alternatively, immediate separation of blood with manual hand centrifuges will allow any tube to be used even in remote settings with no electricity.


Subject(s)
Blood Glucose/metabolism , Blood Specimen Collection , Edetic Acid/pharmacology , Sodium Fluoride/pharmacology , Adult , Female , Humans , Male , Middle Aged
16.
Patient Educ Couns ; 74(2): 258-63, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18848413

ABSTRACT

OBJECTIVES: To explore patients newly diagnosed with Type 2 Diabetes Mellitus (T2DM) experiences of making single (diet) or multiple (diet and physical activity) changes in order to (1) assess whether patients experienced increases in physical activity as supporting or hindering dietary changes and vice versa, and (2) whether patients found making multiple lifestyle changes counterproductive or beneficial. METHODS: In-depth interviews with 30 individuals taking part in a randomised controlled trial that aimed to determine the effect of diet and physical activity on T2DM. Interviewees had been randomised to receive usual care, intensive dietary advice, or intensive dietary advice plus information on physical activity. Respondents were interviewed 6 and 9 months post-randomisation. They were asked about their experiences of making lifestyle changes. Data were analysed thematically. RESULTS: Findings suggest providing diet and physical activity information together encourages patients to use physical activity in strategic ways to aid disease management and that most patients find undertaking multiple lifestyle changes helpful. CONCLUSION: Increasing physical activity can act as a gateway behaviour, i.e. behaviour that produces positive effects in other behaviours. PRACTICE IMPLICATIONS: Practitioners should provide diet and physical activity information together to encourage patients to use physical activity strategically to maintain dietary changes.


Subject(s)
Adaptation, Psychological , Attitude to Health , Diabetes Mellitus, Type 2/psychology , Life Style , Patient Education as Topic/methods , Adult , Aged , Aged, 80 and over , Curriculum , Diabetes Mellitus, Type 2/prevention & control , England , Exercise , Feeding Behavior , Female , Health Services Needs and Demand , Humans , Life Change Events , Male , Middle Aged , Motivation , Qualitative Research , Randomized Controlled Trials as Topic , Self Care , Surveys and Questionnaires
17.
Article in English | MEDLINE | ID: mdl-30837947

ABSTRACT

Objective: One way of improving the prognosis for the growing numbers of people with type 1 diabetes (T1D) is to increase their frequency of exercise. One known barrier to this is the lack of cohesive support and information from care providers. To better understand the issues around existing support for patients wishing to exercise and inform the design of an education package specifically to facilitate safe exercise we interviewed care providers and patients about the existing provision of support. Research Design and Methods: The study was based within two large UK teaching hospitals where four focus groups were undertaken two consisting of patients diagnosed with T1D who undertook regular exercise, and two with health care providers (HCPs) that were part of the diabetes care team. In all 14 patients and 11 staff were involved. These were complemented by two 1:1 interviews with staff unable to attend group discussions. Results: We found the successful provision of education and advice was influenced by factors relating to the individual patient and their service provider. Patient factors included the type of activity and complexity of the exercise regime, the level of engagement with their condition and care and health literacy. Service-related factors included inconsistent training, a lack of capacity and continuity, and limited coherence of information from across their care team. Conclusions: Any education package developed to support exercise in patients with type 1 diabetes should be offered at a time following diagnosis in accordance with patients' preferences and priorities, contain information on how to manage regular and irregular bouts of exercise. Patients described how they related more closely to the stories of their peers than famous sports stars and one way this can be facilitated is by group delivery. The content and relevance of any supporting materials should be closely considered. Training in the delivery of a novel education package should be made available to staff across the care team to enable them to either deliver the course or increase their confidence in offering salient advice as part of routine care.

18.
J Clin Endocrinol Metab ; 104(2): 604-612, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30281094

ABSTRACT

Context: We investigated whether 6 weeks of high-intensity interval training (HIT) induced improvements in cardiometabolic health markers similar to moderate-intensity continuous training (MICT) in people with type 1 diabetes (T1D), and whether HIT abolished acute reductions in plasma glucose levels observed after MICT sessions. Methods: Two groups of sedentary individuals with T1D (n = 7 per group) completed 6 weeks of thrice weekly HIT or MICT. Pre- and post-training measurements were made of 24-hour interstitial glucose profiles, using continuous glucose monitors, and cardiometabolic health markers [peak oxygen consumption (V˙o2peak), blood lipid profile, and aortic pulse wave velocity (aPWV)]. Capillary blood glucose (BG) concentrations were assessed before and after exercise to investigate changes in BG levels during exercise in the fed state. Results: Six weeks of HIT or MICT increased V˙o2peak by 14% and 15%, respectively (P < 0.001), and aPWV by 12% (P < 0.001), with no difference between groups. There was no difference in incidence or percentage of time spent in hypoglycemia after training in either group (P > 0.05). In the fed state, the mean change (±SEM) in capillary BG concentration during the HIT sessions was -0.2 ± 0.5 mmol/L, and -5.5 ± 0.4 mmol/L during MICT. Conclusions: Six weeks of HIT improved V˙o2peak and aPWV to a similar extent as MICT. That BG levels remained stable during HIT in the fed state but consistently fell during MICT suggests HIT may be the preferred training mode for some people with T1D.


Subject(s)
Blood Glucose/analysis , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 1/rehabilitation , Exercise Therapy/methods , High-Intensity Interval Training/methods , Adult , Blood Glucose/physiology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Cross-Over Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Exercise Therapy/adverse effects , Fasting , Female , High-Intensity Interval Training/adverse effects , Humans , Male , Oxygen Consumption/physiology , Pulse Wave Analysis , Time Factors , Treatment Outcome
19.
Diabetes Care ; 42(12): 2330-2333, 2019 12.
Article in English | MEDLINE | ID: mdl-31530660

ABSTRACT

OBJECTIVE: Adopt a multidisciplinary approach to evaluate a virtually supervised home-based high-intensity interval training (Home-HIT) intervention in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eleven individuals with type 1 diabetes (seven women; age 30 ± 3 years; [Formula: see text] 2.5 ± 0.2 L/min; duration of diabetes 10 ± 2 years) completed 6 weeks of Home-HIT. A heart rate monitor and mobile phone application were used to provide feedback to the participants and research team on exercise intensity (compliance) and adherence. RESULTS: Training adherence was 95 ± 2%, and compliance was 99 ± 1%. Home-HIT increased [Formula: see text] by 7% (P = 0.017) and decreased insulin dose by 13% (P = 0.012). Blood glucose concentration did not change from baseline to immediately or 1 h post Home-HIT. Qualitative perceptions of Home-HIT and the virtual-monitoring system were positive, supporting that the intervention successfully removed exercise barriers in people with type 1 diabetes. CONCLUSIONS: Virtually monitored Home-HIT resulted in high adherence alongside increased [Formula: see text] and decreased insulin dose.


Subject(s)
Diabetes Mellitus, Type 1/therapy , High-Intensity Interval Training/methods , Patient Compliance/statistics & numerical data , Telemetry/methods , Adult , Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/psychology , Female , High-Intensity Interval Training/psychology , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Male , Mobile Applications , Patient Care Team , Patient Compliance/psychology , Telemetry/psychology , Treatment Outcome
20.
J Clin Endocrinol Metab ; 104(1): 111-117, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30252054

ABSTRACT

Aims: To compare the effect of a bout of high-intensity interval training (HIT) with a bout of moderate-intensity continuous training (MICT) on glucose concentrations over the subsequent 24-hour period. Methods: Fourteen people with type 1 diabetes [T1D (duration of T1D, 8.2 ± 1.4 years)], all on a basal-bolus regimen, completed a randomized, counterbalanced, crossover study. Continuous glucose monitoring was used to assess glycemic control after a single bout of HIT (six 1-minute intervals) and 30 minutes of MICT on separate days compared with a nonexercise control day (CON). Exercise was undertaken after an overnight fast with omission of short-acting insulin. Capillary blood glucose samples were recorded before and after exercise to assess the acute changes in glycemia during HIT and MICT. Results: There was no difference in the incidence of or percentage of time spent in hypoglycemia, hyperglycemia, or target glucose range over the 24-hour and nocturnal period (12:00 am to 6:00 am) between CON, HIT, and MICT (P > 0.05). Blood glucose concentrations were not significantly (P = 0.49) different from pre-exercise to post-exercise, with HIT (0.39 ± 0.42 mmol/L) or MICT (-0.39 ± 0.66 mmol/L). There was no difference between exercise modes (P = 1.00). Conclusions: HIT or 30 minutes of MICT can be carried out after an overnight fast with no increased risk of hypoglycemia or hyperglycemia. If the pre-exercise glucose concentration is 7 to 14 mmol/L, no additional carbohydrate ingestion is necessary to undertake these exercises. Because HIT is a time-efficient form of exercise, the efficacy and safety of long-term HIT should now be explored.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Exercise/physiology , High-Intensity Interval Training/organization & administration , Adult , Cross-Over Studies , Exercise Therapy , Female , Humans , Hyperglycemia/blood , Hypoglycemia/blood , Male , Young Adult
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