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.

Nutritional intake when cycling under racing and training conditions in professional male cyclists with type 1 diabetes.

This study sought to detail and compare the in-ride nutritional practices of a group of professional cyclists with type 1 diabetes (T1D) under training and racing conditions. We observed seven male professional road cyclists with T1D (Age: 28 ± 4 years, HbA1c: 6.4 ± 0.4% [46 ± 4 mmol.mol-1], VO2max: 73.9 ± 4.3 ml.kg -1.min-1) during pre-season training and during a Union Cycliste Internationale multi-stage road cycling race (Tour of Slovenia). In-ride nutritional, interstitial glucose, and performance variables were quantified and compared between the two events.    The in-ride energy intake was similar between training and racing conditions     (p = 0.909), with carbohydrates being the major source of fuel in both events during exercise at a rate of 41.9 ± 6.8 g.h-1 and 45.4 ± 15.5 g.h-1 (p = 0.548), respectively. Protein consumption was higher during training (2.6 ± 0.6 g.h-1) than race rides (1.9 ± 0.9 g.h-1; p = 0.051).   A similar amount of time was spent within the euglycaemic range (≥70-≤180 mg.dL-1): training 77.1 ± 32.8% vs racing 73.4 ± 3.9%; p = 0.818. These data provide new information on the in-ride nutritional intake in professional cyclists with T1D during different stages of the competitive season.

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.

Different type 2 diabetes risk assessments predict dissimilar numbers at 'high risk': a retrospective analysis of diabetes risk-assessment tools.

BACKGROUND: Use of a validated risk-assessment tool to identify individuals at high risk of developing type 2 diabetes is currently recommended. It is under-reported, however, whether a different risk tool alters the predicted risk of an individual. AIM: This study explored any differences between commonly used validated risk-assessment tools for type 2 diabetes. DESIGN AND SETTING: Cross-sectional analysis of individuals who participated in a workplace-based risk assessment in Carmarthenshire, South Wales. METHOD: Retrospective analysis of 676 individuals (389 females and 287 males) who participated in a workplace-based diabetes risk-assessment initiative. Ten-year risk of type 2 diabetes was predicted using the validated QDiabetes(®), Leicester Risk Assessment (LRA), FINDRISC, and Cambridge Risk Score (CRS) algorithms. RESULTS: Differences between the risk-assessment tools were apparent following retrospective analysis of individuals. CRS categorised the highest proportion (13.6%) of individuals at 'high risk' followed by FINDRISC (6.6%), QDiabetes (6.1%), and, finally, the LRA was the most conservative risk tool (3.1%). Following further analysis by sex, over one-quarter of males were categorised at high risk using CRS (25.4%), whereas a greater percentage of females were categorised as high risk using FINDRISC (7.8%). CONCLUSION: The adoption of a different valid risk-assessment tool can alter the predicted risk of an individual and caution should be used to identify those individuals who really are at high risk of type 2 diabetes.

Association between the preoperative fasting and postprandial C-peptide AUC with resolution of type 2 diabetes 6 months following bariatric surgery.

BACKGROUND AND AIMS: Bariatric surgery results in the remission of type 2 diabetes mellitus (T2DM) in morbidly obese subjects. The aim of the study was to investigate the predictive value of both static and dynamic measures of C-peptide in relation to T2DM resolution 6 months after bariatric surgery regardless of the operation type. METHODS AND RESULTS: A non-randomized prospective study of 24 participants with T2DM undergoing bariatric surgery. Measurements of fasting and 2-hour plasma glucose, insulin, C-peptide and measures of insulin sensitivity were recorded temporally during an oral glucose tolerance test pre-operatively and 6 months post-operatively. A responder was defined with a fasting glucose <5.6 mmol/L and HbA1c <6.0% postoperatively. Within the sample there were 11 responders and 13 non-responders at 6 months. There was a significant difference in the duration of diabetes between the groups. Fasting C-peptide (P≤0.05) and 2-hour C-peptide (P≤0.05) were higher in responders compared to non-responders. Significantly higher C-peptide levels were observed preoperatively at all time points for responders, with significantly higher area under the curve (AUC0-60 and AUC0-120). Using the lower quartiles for C-peptide levels, both fasting C-peptide (>2.5 ng/mL [0.83 nmol/L]) and 2-hour C-peptide (>5.2 ng/mL [1.73 nmol/L]) had a sensitivity and negative predictive value of 100% to predict T2DM remission. Logistic regression showed that C-peptide, duration of diabetes and BMI were associated with response. The area under the ROC curve was 0.94 and a regression model predicted diabetes remission with a sensitivity of 85.7% and a specificity of 88.9%. CONCLUSIONS: This study demonstrated that static (fasting) and dynamic (AUC, 2-hour) C-peptide measurements predict T2DM resolution 6 months following bariatric surgery. This work provides insight into C-peptide dynamics as a predictor of response to bariatric surgery.

Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial.

INTRODUCTION: Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes. METHODS: Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, ß-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise. RESULTS: Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar. CONCLUSIONS: Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances. CLINICAL TRIALS NUMBER: NCT02204839, ClinicalTrials.gov.

Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis.

AIM: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. METHODS: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). RESULTS: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). CONCLUSION: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.

Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial.

AIM: To examine the metabolic, gluco-regulatory-hormonal and inflammatory cytokine responses to large reductions in rapid-acting insulin dose administered prandially before and after intensive running exercise in male type 1 diabetes patients. METHODS: This was a single centre, randomised, controlled open label study. Following preliminary testing, 8 male patients (24±2 years, HbA1c 7.7±0.4%/61±4 mmol.l-1) treated with insulin's glargine and aspart, or lispro attended the laboratory on two mornings at ∼08:00 h and consumed a standardised breakfast carbohydrate bolus (1 g carbohydrate.kg-1BM; 380±10 kcal) and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.1±0.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg-1BM; 660±21 kcal) and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, ß-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-α concentrations were measured for 180 minutes post-meal. RESULTS: All participants were analysed. All glycaemic, metabolic, hormonal, and cytokine responses were similar between conditions up to 60 minutes following exercise. Following the post-exercise meal, serum insulin concentrations were lower under 50% (p<0.05) resulting in 75% of patients experiencing hyperglycaemia (blood glucose ≥8.0 mmol.l-1; 50% n = 6, Full n = 3). ß-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-α concentrations remained similar to fasting levels under 50% but declined under Full. Under 50% IL-6 concentrations were inversely related with serum insulin concentrations (r = -0.484, p = 0.017). CONCLUSIONS: Heavily reducing rapid-acting insulin dose with a carbohydrate bolus before, and a meal after intensive running exercise may cause hyperglycaemia, but does not augment ketonaemia, raise inflammatory cytokines TNF-α and IL-6 above fasting levels, or cause other adverse metabolic or hormonal disturbances. TRIAL REGISTRATION: ClinicalTrials.gov NCT01531855.

Prevalence of undiagnosed cardiovascular risk factors and 10-year CVD risk in male steel industry workers.

OBJECTIVE: To assess the prevalence of undiagnosed cardiovascular disease (CVD) in a cohort of male steelworkers in South Wales, UK. METHODS: Male steel industry workers (n = 221) with no prior diagnosis of CVD or diabetes accepted a CVD risk assessment within the work environment. Demographic, anthropometric, family, and medical histories were all recorded and capillary blood samples obtained. The 10-year CVD risk was predicted using the QRISK2-2012 algorithm. RESULTS: Up to 81.5% of workers were either overweight or obese. More than 20% of workers were found to have diastolic hypertension, high total cholesterol, and/or a total cholesterol/high-density lipoprotein ratio of six or more. Over one quarter of workers assessed had an increased 10-year CVD risk. CONCLUSIONS: Despite a physically demanding occupation, risk assessment in the workplace uncovered significant occult factors in CVD risk in a sample of male heavy industry workers.

A low-glycemic index meal and bedtime snack prevents postprandial hyperglycemia and associated rises in inflammatory markers, providing protection from early but not late nocturnal hypoglycemia following evening exercise in type 1 diabetes.

OBJECTIVE: To examine the influence of the glycemic index (GI) of foods consumed after evening exercise on postprandial glycemia, metabolic and inflammatory markers, and nocturnal glycemic control in type 1 diabetes. RESEARCH DESIGN AND METHODS: On two evenings (∼1700 h), 10 male patients (27 ± 5 years of age, HbA1c 6.7 ± 0.7% [49.9 ± 8.1 mmol/mol]) were administered a 25% rapid-acting insulin dose with a carbohydrate bolus 60 min before 45 min of treadmill running. At 60 min postexercise, patients were administered a 50% rapid-acting insulin dose with one of two isoenergetic meals (1.0 g carbohdyrate/kg body mass [BM]) matched for macronutrient content but of either low GI (LGI) or high GI (HGI). At 180 min postmeal, the LGI group ingested an LGI snack and the HGI group an HGI snack (0.4 g carbohdyrate/kg BM) before returning home (∼2300 h). Interval samples were analyzed for blood glucose and lactate; plasma glucagon, epinephrine, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); and serum insulin, cortisol, nonesterified fatty acid, and ß-hydroxybutyrate concentrations. Interstitial glucose was recorded for 20 h postlaboratory attendance through continuous glucose monitoring. RESULTS: Following the postexercise meal, an HGI snack induced hyperglycemia in all patients (mean ± SD glucose 13.5 ± 3.3 mmol/L) and marked increases in TNF-α and IL-6, whereas relative euglycemia was maintained with an LGI snack (7.7 ± 2.5 mmol/L, P < 0.001) without inflammatory cytokine elevation. Both meal types protected all patients from early hypoglycemia. Overnight glycemia was comparable, with a similar incidence of nocturnal hypoglycemia (n = 5 for both HGI and LGI). CONCLUSIONS: Consuming LGI food with a reduced rapid-acting insulin dose following evening exercise prevents postprandial hyperglycemia and inflammation and provides hypoglycemia protection for ∼8 h postexercise; however, the risk of late nocturnal hypoglycemia remains.

Rapid core measure improvement through a "business case for quality".

Incentives to improve performance are emerging as revenue or financial penalties are linked to the measured quality of service provided. The HCA "Getting to Green" program was designed to rapidly increase core measure performance scores. Program components included (1) the "business case for quality"-increased awareness of how quality drives financial performance; (2) continuous communication of clinical and financial performance data; and (3) evidence-based clinical protocols, incentives, and tools for process improvement. Improvement was measured by comparing systemwide rates of adherence to national quality measures for heart failure (HF), acute myocardial infarction (AMI), pneumonia (PN), and surgical care (SCIP) to rates from all facilities reporting to the Centers for Medicare and Medicaid Services (CMS). As of the second quarter of 2011, 70% of HCA total measure set composite scores were at or above the 90th percentile of CMS scores. A test of differences in regression coefficients between the CMS national average and the HCA average revealed significant differences for AMI (p = .001), HF (p = .012), PN (p < .001), and SCIP (p = .015). This program demonstrated that presentation of the financial implications of quality, transparency in performance data, and clearly defined goals could cultivate the desire to use improvement tools and resources to raise performance.