Effect of 48 Months of Closed-Loop Insulin Delivery on Residual C-Peptide Secretion and Glycemic Control in Newly Diagnosed Youth With Type 1 Diabetes: A Randomized Trial.

OBJECTIVE: We evaluated the effect of long-term intensive metabolic control with hybrid closed-loop (CL) on residual C-peptide secretion and glucose control compared with standard insulin therapy in youth with type 1 diabetes over 48 months. RESEARCH DESIGN AND METHODS: Following the 24-month primary phase of a multicenter, randomized, parallel trial of 96 newly diagnosed youth aged 10 to 16.9 years, participants were invited to an extension phase using treatment allocated at randomization. They continued with hybrid CL using the Cambridge algorithm or standard insulin therapy (control) until 48 months after diagnosis. Analysis was by intention-to-treat. RESULTS: At 24 months after diagnosis, 81 participants (mean ± SD age 14 ± 2 years) continued in the extension phase (47 CL, 34 control). There was no difference in fasting C-peptide corrected for fasting glucose at 48 months between groups (CL: 5 ± 9 vs. control: 6 ± 14 pmol/L per mmol/L; mean adjusted difference -2 [95% CI -7, 4; P = 0.54]). Central laboratory HbA1c remained lower in the CL group by 0.9% (10 mmol/mol [95% CI 0.2, 1.5; 3, 17 mmol/mol); P = 0.009). Time in target range of 3.9 to 10.0 mmol/L was 12 percentage points (95% CI 3, 20; P = 0.008) higher in the CL group compared with control. There were 11 severe hypoglycemic events (6 CL, 5 control) and 7 diabetic ketoacidosis events (3 CL, 4 control) during the extension phase. CONCLUSIONS: Improved glycemic control was sustained over 48 months after diagnosis with CL insulin delivery compared with standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion.

Using Artificial Intelligence to Improve the Accuracy of a Wrist-Worn, Noninvasive Glucose Monitor: A Pilot Study.

BACKGROUND: Self-monitoring of glucose is important to the successful management of diabetes; however, existing monitoring methods require a degree of invasive measurement which can be unpleasant for users. This study investigates the accuracy of a noninvasive glucose monitoring system that analyses spectral variations in microwave signals. METHODS: An open-label, pilot design study was conducted with four cohorts (N = 5/cohort). In each session, a dial-resonating sensor (DRS) attached to the wrist automatically collected data every 60 seconds, with a novel artificial intelligence (AI) model converting signal resonance output to a glucose prediction. Plasma glucose was measured in venous blood samples every 5 minutes for Cohorts 1 to 3 and every 10 minutes for Cohort 4. Accuracy was evaluated by calculating the mean absolute relative difference (MARD) between the DRS and plasma glucose values. RESULTS: Accurate plasma glucose predictions were obtained across all four cohorts using a random sampling procedure applied to the full four-cohort data set, with an average MARD of 10.3%. A statistical analysis demonstrates the quality of these predictions, with a surveillance error grid (SEG) plot indicating no data pairs falling into the high-risk zones. CONCLUSIONS: These findings show that MARD values approaching accuracies comparable to current commercial alternatives can be obtained from a multiparticipant pilot study with the application of AI. Microwave biosensors and AI models show promise for improving the accuracy and convenience of glucose monitoring systems for people with diabetes.

Comparability Evaluation of Three Benchtop Glucose Analyzers With the Recently Withdrawn YSI 2300 Stat Plus.

BACKGROUND: We compared the performance of three currently available laboratory benchtop glucose analyzers with the outgoing YSI 2300 Stat Plus. METHODS: Plasma samples (100), across a wide glucose concentration range were analysed on the YSI 2500, Randox daytona+ (glucose oxidase) and EKF Biosen in a single laboratory and compared to the YSI 2300 Stat Plus. RESULTS: All three analyzers showed good agreement with the YSI 2300 Stat Plus, and only a small bias (≤1% YSI 2500 and Randox daytona+, 4.6% EKF Biosen) was observed for each analyzer. None of the three comparator analyzers were affected by either proportional or constant bias, thus no significant differences between the YSI 2300 Stat Plus and the comparator methods were identified. CONCLUSIONS: The results from this study suggest all could be considered as suitable reference laboratory glucose analyzers and replacements for the recently withdrawn YSI 2300 Stat Plus.

The polyphenol epigallocatechin gallate lowers circulating catecholamine concentrations and alters lipid metabolism during graded exercise in man: a randomized cross-over study.

PURPOSE: Physical exercise is shown to mitigate catecholamine metabolites; however, it is unknown if exercise-induced increases in sympatho-adrenal activity or catecholamine metabolites are influenced by ingestion of specific catechins found within green tea. This study explored the impact of epigallocatechin gallate (EGCG) ingestion on catecholamine metabolism during graded cycle exercise in humans. METHODS: Eight males (22.4 ± 3.3 years, BMI:25.7 ± 2.4 kg.m2) performed a randomised, placebo-controlled, single-blind, cross-over trial after consumption (1450 mg) of either EGCG or placebo (PLAC) and performed graded cycling to volitional exhaustion. Venous bloods were taken at rest, 2 h post-ingestion and after every 3-min stage. Blood variables were analysed for catecholamines, catecholamine metanephrines and metabolic variables at rest, 2 h post-ingestion (POST-ING), peak rate of lipid oxidation (FATpeak), lactate threshold (LT) and peak rate of oxygen consumption (VO2peak). Data were analysed using SPSS (Version 26). RESULTS: Resting catecholamine and metanephrines were similar between trials. Plasma adrenaline (AD) was lower in ECGC treatment group between trials at FATpeak (P < 0.05), LT (P < 0.001) and VO2peak (P < 0.01). Noradrenaline (NA) was lower under EGCG at POST (P < 0.05), FATpeak (P < 0.05), LT (P < 0.01) and VO2peak (P < 0.05) compared to PLAC. Metanephrines, glucose and lactate increased similarly with exercise intensity in both trials. Lipid oxidation rate was 32% lower in EGCG at FATpeak (EGCG 0.33 ± 0.14 vs. PLAC 0.49 ± 0.11 g.min-1, P < 0.05). Cycle time to exhaustion was similar (NS). CONCLUSION: Acute EGCG supplementation reduced circulating catecholamines but not; metanephrine, glucose or lactates, response to graded exercise. Lower circulating catecholamines may explain a lower lipid oxidation rate.

Acute postprandial gut hormone, leptin, glucose and insulin responses to resistant starch in obese children: a single blind crossover study.

INTRODUCTION: Resistant starch (RS) has beneficial effects on postprandial glucose metabolism in both animals and adults. Hitherto, there have been no studies in children of the acute metabolic and hormonal effects of RS-containing meals. OBJECTIVES: We aimed to compare serial plasma glucose, insulin, gut hormone, leptin profiles and satiety scores in obese children after meals containing variable amounts of RS. METHODS: This was a single blind, non-randomised, crossover study of 20 obese children aged 10-14 years old without comorbidities. Three test meals containing rice (M1), rice cooked with coconut oil (M2), rice cooked in coconut oil with lentils (M3) were given in sequence after a 12-hour fast . Blood samples were analysed for glucose (PG), insulin, leptin, glucagon-like polypeptide (GLP) 1, ghrelin and peptide YY (PYY) at appropriate times between 0 and 180 min. RESULTS: Meal M2 resulted in significantly lower postprandial glucose values compared with meal M1 (maximal incremental glucose, ∆Cmax, p<0.05; area under the curve, ∆AUC0-3, p<0.01) and meal M3 (maximal concentration, Cmax, p<0.01; ∆Cmax, p<0.001, and ∆AUC0-3p<0.01). M2 also produced lower insulin values compared with M1 (p<0.05). Postprandial ghrelin was significantly higher after M1 compared with M3 (p<0.05). PYY, GLP1 and median satiety scores were not significantly different between the three meals. CONCLUSION: This study shows that M2, the meal containing RS alone, induced beneficial effects on acute postprandial glucose, insulin and ghrelin concentrations in obese children without diabetes. Acute postprandial satiety scores were not significantly affected by the three meals. TRIAL REGISTRATION NUMBER: SLCTR/2020/007.

Closed-Loop Therapy and Preservation of C-Peptide Secretion in Type 1 Diabetes.

BACKGROUND: Whether improved glucose control with hybrid closed-loop therapy can preserve C-peptide secretion as compared with standard insulin therapy in persons with new-onset type 1 diabetes is unclear. METHODS: In a multicenter, open-label, parallel-group, randomized trial, we assigned youths 10.0 to 16.9 years of age within 21 days after a diagnosis of type 1 diabetes to receive hybrid closed-loop therapy or standard insulin therapy (control) for 24 months. The primary end point was the area under the curve (AUC) for the plasma C-peptide level (after a mixed-meal tolerance test) at 12 months after diagnosis. The analysis was performed on an intention-to-treat basis. RESULTS: A total of 97 participants (mean [±SD] age, 12±2 years) underwent randomization: 51 were assigned to receive closed-loop therapy and 46 to receive control therapy. The AUC for the C-peptide level at 12 months (primary end point) did not differ significantly between the two groups (geometric mean, 0.35 pmol per milliliter [interquartile range, 0.16 to 0.49] with closed-loop therapy and 0.46 pmol per milliliter [interquartile range, 0.22 to 0.69] with control therapy; mean adjusted difference, -0.06 pmol per milliliter [95% confidence interval {CI}, -0.14 to 0.03]). There was not a substantial between-group difference in the AUC for the C-peptide level at 24 months (geometric mean, 0.18 pmol per milliliter [interquartile range, 0.06 to 0.22] with closed-loop therapy and 0.24 pmol per milliliter [interquartile range, 0.05 to 0.30] with control therapy; mean adjusted difference, -0.04 pmol per milliliter [95% CI, -0.14 to 0.06]). The arithmetic mean glycated hemoglobin level was lower in the closed-loop group than in the control group by 4 mmol per mole (0.4 percentage points; 95% CI, 0 to 8 mmol per mole [0.0 to 0.7 percentage points]) at 12 months and by 11 mmol per mole (1.0 percentage points; 95% CI, 7 to 15 mmol per mole [0.5 to 1.5 percentage points]) at 24 months. Five cases of severe hypoglycemia occurred in the closed-loop group (in 3 participants), and one occurred in the control group; one case of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In youths with new-onset type 1 diabetes, intensive glucose control for 24 months did not appear to prevent the decline in residual C-peptide secretion. (Funded by the National Institute for Health and Care Research and others; CLOuD ClinicalTrials.gov number, NCT02871089.).

Evaluating the impact of a prison smoking ban on the cardiovascular health of men in a UK prison.

PURPOSE: Smoking rates are known to be higher amongst those committed to prison than the general population. Those in prison suffer from high rates of comorbidities that are likely to increase their risk of cardiovascular disease (CVD), making it more difficult to manage. In 2016, a tobacco ban began to be implemented across prisons in England and Wales, UK. This study aims to measure the effect of the tobacco ban on predicted cardiovascular risk for those quitting smoking on admission to prison. DESIGN/METHODOLOGY/APPROACH: Using data from a prevalence study of CVD in prisons, the authors have assessed the effect of the tobacco ban on cardiovascular risk, using predicted age to CVD event, ten-year CVD risk and heart age, for those who previously smoked and gave up on admission to prison. FINDINGS: The results demonstrate measurable health gains across all age groups with the greatest gains found in those aged 50 years and older and who had been heavy smokers. Quitting smoking on admission to prison led to a reduced heart age of between two and seven years for all participants. ORIGINALITY/VALUE: The data supports tobacco bans in prisons as a public health measure to reduce risk of CVD. Interventions are needed to encourage maintenance of smoking cessation on release from prison for the full health benefits to be realised.

Brief lifestyle interventions for prediabetes in primary care: a service evaluation.

BACKGROUND: The increasing number of cases of prediabetes in the UK is concerning, particularly in Wales where there is no standard programme of support. The aim of the current service evaluation was to examine the effectiveness of brief lifestyle interventions on glucose tolerance in people at risk of developing type 2 diabetes. METHODS: In this pragmatic service evaluation clinical data on people deemed at risk of developing type 2 diabetes were evaluated from two GP clusters. Patients (n = 1207) received a single 15 to 30-min, face-to-face, consultation with a health care practitioner. Interventions were assessed by changes in HbA1c and distribution across the HbA1c ranges 12 months following intervention. Statistical significance of reversion to normoglycaemia and development of diabetes were assessed through comparison with expected rates without intervention. RESULTS: Between baseline and 12-month follow-up HbA1c fell from 43.85 ± 1.57 mmol/mol (6.16 ± 0.14%) to 41.63 ± 3.84 mmol/mol (5.96 ± 0.35%), a decrease of 2.22 mmol/mol (0.20%) (95% CI 2.01 (0.18%), 2.42 (0.22%); p < 0.0001). The proportion of people with normal glucose tolerance at 12 months (0.50 95%CI 0.47, 0.52) was significantly larger than the lower (0.06 (p < 0.0001) and the upper (0.19 (p < 0.0001)) estimates based on no intervention. CONCLUSION: Results indicate significant improvement in glucose tolerance across GP clusters. The brief intervention has the potential to offer a robust and effective option to support people at risk of developing type 2 diabetes. Further research in the form of a randomised trial is needed to confirm this and identify those likely to benefit most from this intervention.

The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM.

AIMS: The two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays. MATERIALS AND METHODS: A total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis. RESULTS: The MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function. CONCLUSION: This study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution.

Incidence of diabetic retinopathy in newly diagnosed subjects with type 2 diabetes mellitus over 5 years: Contribution of Β-cell function.

AIMS: Identifying and modulating risk factors is essential to prevent visual impairment due to diabetic retinopathy (DR). This study examines incident DR with metabolic and hormonal factors in newly-diagnosed, treatment naïve, individuals with Type2 Diabetes Mellitus (T2DM), over a 5 year period from diagnosis. METHODS: 233 T2DM subjects underwent serial DR screening using digital photography and standardised Meal Tolerance Tests at diagnosis and after 1, 2 and 5 years. Subjects (179) with no DR throughout the 5-year study period were compared with those who developed DR (54). RESULTS: Of 233 subjects, 54(23.2%) developed DR by 5 years, background DR in 50(93%) and exudative maculopathy in 4(7%) individuals. Of these subjects, 12(22%) developed DR after 1 year, 15(28%) after 2 years and 27(50%) after 5 years. At baseline, those with DR at 5 years had higher HbA1c (p = 0.017), higher fasting plasma glucose (PG) (p = 0.031) and postprandial PG (p = 0.009). They were associated with reduced basal ß-cell secretory function (M0) (p = 0.025), lower (p = 0.000) postprandial ß-cell responsiveness (M1) and ß-cell function (HOMA-B) (p = 0.044). CONCLUSIONS: There is an independent association between glycaemic control and ß-cell dysfunction at the time of diagnosis of T2DM, with incident DR over a follow-up period of 5 years.

Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol.

INTRODUCTION: Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%-20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis. METHODS AND ANALYSIS: This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12-18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work. ETHICS AND DISSEMINATION: This trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN14274380.

Estimating the burden of type 2 diabetes in the UK prison environment for the next decade.

Although limited, global evidence suggests that the cardiometabolic health of those in prison is poorer than their community peers. Type 2 diabetes (T2DM) is a public health challenge and community rates are continuing to rise. Given that cardiometabolic risk factors are prevalent amongst younger individuals within the prison population, it is reasonable to assume that the prison environment will also experience an increase in new cases of T2DM. Therefore, the aim of this study was, to predict in a current prison population, how many potential new cases of T2DM could develop in the next 10 years. This study used health data collected from a prison sample (n = 299) aged 25-84 years in HMP Parc, UK, and the Diabetes UK Risk Score was used to predict T2DM risk. In terms of projecting new cases, it was estimated that in the next decade 6.4 individuals per 100 would develop T2DM, and this value increased to 16.4 individuals per 100 in those aged 50 years and older. The development of new cases across all age groups is a concern, and it appears that the prison community are a 'target population' for prevention opportunities.

Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes.

AIM: To detail the extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin dose adjustments in individuals with type 1 diabetes (T1D) using multiple daily injections of insulins aspart (IAsp) and degludec (IDeg). METHODS AND RESULTS: Sixteen individuals with T1D, completed a single-centred, randomised, four-period crossover trial consisting of 23-h inpatient phases. Participants administered either a regular (100%) or reduced (50%) dose (100%; 5.1 ± 2.4, 50%; 2.6 ± 1.2 IU, p < 0.001) of individualised IAsp 1 h before and after 45-min of evening exercise at 60 ± 6% V̇O2max. An unaltered dose of IDeg was administered in the morning. Metabolic, physiological and hormonal responses during exercise, recovery and nocturnal periods were characterised. The primary outcome was the number of trial day occurrences of hypoglycemia (venous blood glucose ≤ 3.9 mmol L -1). Inclusion of a 50% IAsp dose reduction strategy prior to evening exercise reduced the occurrence of in-exercise hypoglycemia (p = 0.023). Mimicking this reductive strategy in the post-exercise period decreased risk of nocturnal hypoglycemia (p = 0.045). Combining this strategy to reflect reductions either side of exercise resulted in higher glucose concentrations in the acute post-exercise (p = 0.034), nocturnal (p = 0.001), and overall (p < 0.001) periods. Depth of hypoglycemia (p = 0.302), as well as ketonic and counter-regulatory hormonal profiles were similar. CONCLUSIONS: These findings demonstrate the glycemic safety of peri-exercise bolus dose reduction strategies in minimising the prevalence of acute and nocturnal hypoglycemia following evening exercise in people with T1D on MDI. Use of newer background insulins with current bolus insulins demonstrates efficacy and advances current recommendations for safe performance of exercise. CLINICAL TRIALS REGISTER: DRKS00013509.

Abundance of undiagnosed cardiometabolic risk within the population of a long-stay prison in the UK.

BACKGROUND: The health of people in prisons is a public health issue. It is well known that those in prison experience poorer health outcomes than those in the general community. One such example is the burden of non-communicable diseases, more specifically cardiovascular disease (CVD), stroke and type 2 diabetes (T2DM). However, there is limited evidence research on the extent of cardiometabolic risk factors in the prison environment in Wales, the wider UK or globally. METHODS: Risk assessments were performed on a representative sample of 299 men at HMP Parc, Bridgend. The risk assessments were 30 min in duration and men aged 25-84 years old and free from pre-existing CVD and T2DM were eligible. During the risk assessment, a number of demographic, anthropometric and clinical markers were obtained. The 10-year risk of CVD and T2DM was predicted using the QRISK2 algorithm and Diabetes UK Risk Score, respectively. RESULTS: The majority of the men was found to be either overweight (43.5%) or obese (37.5%) and/or demonstrated evidence of central obesity (40.1%). Cardiometabolic risk factors including systolic hypertension (25.1%), high cholesterol (29.8%), low HDL cholesterol (56.2%) and elevated total cholesterol: HDL ratios (23.1%) were observed in a considerable number of men. Ultimately, 15.4% were calculated at increased risk of CVD, and 31.8% predicted at moderate or high risk of T2DM. CONCLUSIONS: Overall, a substantial prevalence of previously undiagnosed cardiometabolic risk factors was observed and men in prison are at elevated risk of cardiometabolic disease at a younger age than current screening guidelines.

Metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes.

INTRODUCTION: This study sought to compare the metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Thirteen individuals with T1D (hemoglobin; 7.0%±1.3% (52.6±13.9 mmol/mol), age; 36±15 years, duration diabetes; 15±12 years) performed a maximum of 45 min submaximal exercise (60%±6% V̇O2max). Retrospectively identified exercise sessions that ended in hypoglycemia ((HypoEx) blood glucose (BG)≤3.9 mmol/L) were compared against a participant-matched euglycemic condition ((EuEx) BG≥4.0, BG≤10.0 mmol/L). Samples were compared for detailed physiological and hormonal parameters as well as metabolically profiled via large scale targeted ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Data were assessed using univariate and multivariate analysis techniques with false discovery rate adjustment. Significant results were considered at p≤0.05. RESULTS: Cardiorespiratory and counterregulatory hormone responses, whole-body fuel use and perception of fatigue during exercise were similar under conditions of hypoglycemia and euglycemia (BG 3.5±0.3 vs 5.8±1.1 mmol/L, respectively p<0.001). HypoEx was associated with greater adenosine salvage pathway activity (5'-methylthioadenosine, p=0.023 and higher cysteine and methionine metabolism), increased utilization of glucogenic amino acids (glutamine, p=0.021, alanine, aspartate and glutamate metabolism and homoserine/threonine, p=0.045) and evidence of enhanced ß-oxidation (lower carnitine p<0.001, higher long-chain acylcarnitines). CONCLUSIONS: Exposure to acute hypoglycemia during exercise potentiates alterations in subclinical indices of metabolic stress at the level of the metabolome. However, the physiological responses induced by dynamic physical exercise may mask the symptomatic recognition of mild hypoglycemia during exercise in people with T1D, a potential clinical safety concern that reinforces the need for diligent glucose management. TRIAL REGISTRATION NUMBER: DRKS00013509.

Omega-3 polyunsaturated fatty acid supplementation versus placebo on vascular health, glycaemic control, and metabolic parameters in people with type 1 diabetes: a randomised controlled preliminary trial.

BACKGROUND: The role of omega-3 polyunsaturated fatty acids (n-3PUFA), and the potential impact of n-3PUFA supplementation, in the treatment and management of type 1 diabetes (T1D) remains unclear and controversial. Therefore, this study aimed to examine the efficacy of daily high-dose-bolus n-3PUFA supplementation on vascular health, glycaemic control, and metabolic parameters in subjects with T1D. METHODS: Twenty-seven adults with T1D were recruited to a 6-month randomised, double-blind, placebo-controlled trial. Subjects received either 3.3 g/day of encapsulated n-3PUFA or encapsulated 3.0 g/day corn oil placebo (PLA) for 6-months, with follow-up at 9-months after 3-month washout. Erythrocyte fatty acid composition was determined via gas chromatography. Endpoints included inflammation-associated endothelial biomarkers (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], E-selectin, P-selectin, pentraxin-3, vascular endothelial growth factor [VEGF]), and their mediator tumor necrosis factor alpha [TNFα] analysed via immunoassay, vascular structure (carotid intima-media thickness [CIMT]) and function (brachial artery flow mediated dilation [FMD]) determined via ultrasound technique, blood pressure, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial metabolism. RESULTS: Twenty subjects completed the trial in full. In the n-3PUFA group, the mean ± SD baseline n-3PUFA index of 4.93 ± 0.94% increased to 7.67 ± 1.86% (P < 0.001) after 3-months, and 8.29 ± 1.45% (P < 0.001) after 6-months. Total exposure to n-3PUFA over the 6-months (area under the curve) was 14.27 ± 3.05% per month under n-3PUFA, and 9.11 ± 2.74% per month under PLA (P < 0.001). VCAM-1, ICAM-1, E-selectin, P-selectin, pentraxin-3, VEGF, TNFα, CIMT, FMD, blood pressure, HbA1c, FPG, and postprandial metabolism did not differ between or within groups after treatment (P > 0.05). CONCLUSIONS: This study indicates that daily high-dose-bolus of n-3PUFA supplementation for 6-months does not improve vascular health, glucose homeostasis, or metabolic parameters in subjects with T1D. The findings from this preliminary RCT do not support the use of therapeutic n-3PUFA supplementation in the treatment and management of T1D and its associated complications. Trial Registration ISRCTN, ISRCTN40811115. Registered 27 June 2017, http://www.isrctn.com/ISRCTN40811115 .

Temporal Effects of Bariatric Surgery on Adipokines, Inflammation and Oxidative Stress in Subjects with Impaired Glucose Homeostasis at 4 Years of Follow-up.

BACKGROUND: Previous studies have examined changes in plasma markers of inflammation and oxidative stress up to 24 months following bariatric surgery, but there is limited evidence on the long-term effects of bariatric surgery. OBJECTIVES: To examine the effects of bariatric surgery on adipokines (adiponectin, leptin), inflammatory cytokines [C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10(IL-10)] and global plasma measures of oxidative stress [thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAOS) 1 and 6 months, and 4 years post-surgery in subjects with obesity and impaired glucose regulation. METHODS: A prospective study comprising of 19 participants (13 females, mean age 50.4 ± 6.2 years, mean body mass index (BMI) 54 ± 14 kg/m2, 17 type 2 diabetes) undergoing bariatric surgery (10 sleeve gastrectomy, 6 biliopancreatic diversion, 2 Roux-en-Y gastric bypass and 1 laparoscopic adjustable gastric banding). Serial measurements of the above markers were made pre-operatively, 1 and 6 months and 4 years post-operatively. RESULTS: Compared to pre-operative levels, significant decreases were seen 4 years post-operatively in CRP (11.4 vs 2.8 ng/mL, p < 0.001), IL-6 (8.0 vs 2.1 pg/mL, p < 0.001) and leptin (60.7 vs 32.1 pg/mL, p = 0.001). At 4 years, both fasting and 120 min TAOS significantly increased by 35% and 19% respectively. However, fasting and 120 min TBARS did not show any significant changes. CONCLUSION: To our knowledge, no other studies have described changes in inflammation and oxidative stress at 4 years following bariatric surgery. This study contributes to the current literature supporting the longer-term beneficial effect of bariatric surgery on chronic inflammation and oxidative stress.

The impact of structured self-monitoring of blood glucose on glycaemic variability in non-insulin treated type 2 diabetes: The SMBG study, a 12-month randomised controlled trial.

BACKGROUND AND AIMS: There is inconsistent evidence supporting the self-monitoring of blood glucose (SMBG) in people with non-insulin treated type 2 diabetes (T2D). Structured SMBG protocols have a greater impact on glycaemic control than unstructured SMBG and may improve measures of glycaemic variability (GV), though few previous studies have reported on specific GV outcomes. Our aim was to determine the impact of structured SMBG on simple measures of GV in people with T2D. METHODS: Participants undertook structured SMBG over 12 months, with HbA1c recorded at baseline and at 3-monthly follow-up. For each participant, the mean blood glucose (MBG), fasting blood glucose (FBG), standard deviation BG (SD-BG), coefficient of variation of BG (CV-BG), mean absolute glucose change (MAG) and HbA1c were determined for each 3-month period. Responders were participants with an improvement in HbA1c of ≥5 mmol/mol (0.5%) over 12 months. RESULTS: Data from two hundred and thirty-one participants were included for analysis. Participants had a baseline median [interquartile range] HbA1c 68.0 [61.5-75.5] mmol/mol (8.4%). Participants demonstrated significant improvements in the MBG (-1.25 mmol/L), FBG (-0.97 mmol/L), SD-BG (-0.44 mmol/L), CV-BG (-1.43%), MAG (-0.97 mmol/L), and HbA1c (-7.0 mmol/mol) (all p < 0.001) at 12 months compared to these measures collected within the first 3 months of SMBG. Responders had a significantly higher baseline median [interquartile range] HbA1c of 70.0 [63.0-78.0] mmol/mol compared to 61.0 [56.5-66.0] mmol/mol in non-responders (P < 0.001). CONCLUSIONS: Structured SMBG improved all the observed measures of GV. These results support the use of structured SMBG in people with non-insulin treated T2D.

Effect of Laparoscopic Sleeve Gastrectomy on Static and Dynamic Measures of Glucose Homeostasis and Incretin Hormone Response 4-Years Post-Operatively.

INTRODUCTION: There is limited literature available on the long-term effect of bariatric surgery especially laparoscopic sleeve gastrectomy (LSG) on the incretin hormone response. AIM: Our primary aim was to investigate changes in glucose metabolism and incretin hormone responses in participants with impaired glucose regulation approximately 4 years after LSG. The secondary aim was to examine the long-term incretin hormone changes of biliopancreatic diversion (BPD). METHOD: A non-randomised prospective study comprising of 10 participants undergoing LSG and 6 participants undergoing BPD. Serial measurements of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were performed during an oral glucose tolerance test pre-operatively and 1 month, 6 months and at approximately 4-7 years post-operatively. Area under the curve (AUC) was examined at 60 and 120 min. RESULTS: In the LSG group, a significant reduction in 2-h plasma glucose (2 h PG), HbA1c and HOMA-IR was observed at 4 years. Compared with pre-operative levels, significant increases in post-glucose GLP-1 secretion were observed at 1 and 6 months, but not maintained at 4 years. A linear increase was seen in post-glucose GIP response at 1 month and 6 months and 4 years. Within the BPD group, a reduction in HbA1c along with an increase GLP-1 response was observed at 7 years. CONCLUSION: An increase in GLP-1 response was not preserved at 4 years, but a significant increase in GIP response was observed along with improved glycaemic control following LSG.

Temporal effects of laparoscopic sleeve gastrectomy on adipokines, inflammation, and oxidative stress in patients with impaired glucose homeostasis.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity and metabolic dysfunction. OBJECTIVES: The aim of this work was to examine the early temporal effects of laparoscopic sleeve gastrectomy (LSG) on adipokines (adiponectin, leptin), inflammatory cytokines (interleukin-6, C-reactive protein, interleukin-10), and global plasma measures of oxidative stress (thiobarbituric acid reactive substances and total antioxidant status) in a sample of 55 participants preoperatively, and 1 and 6 months postoperatively. The focus was on a sample of patients with impaired glucose tolerance and type 2 diabetes, which is associated with increased low-grade systemic inflammation and oxidative stress. SETTING: University hospital, United Kingdom. METHODS: This was a prospective study comprising 55 participants with impaired glucose homeostasis and type 2 diabetes undergoing LSG (mean body mass index 50.4 kg/m2, mean glycated hemoglobin 7.4%). Serial measurements of the above markers were made preoperatively, 1 and 6 months postoperatively (43 had measurable cytokines and oxidative stress at 1- and 6-mo follow-up). RESULTS: We observed a significant reduction in interleukin-6, C-reactive protein, leptin, and thiobarbituric acid reactive substances, along with an increase in adiponectin 6 months postoperatively. CONCLUSIONS: To our knowledge the effects of LSG on inflammatory cytokines and plasma markers of oxidative stress have not been examined temporally in a sizeable sample of participants who have undergone LSG. This present study supports the role of LSG for the treatment of the proinflammatory and pro-oxidant status associated with obesity-related glucose dysregulation.