Dr Ralph Manders


Lecturer in Exercise Physiology
+44 (0)1483 688668
29 PG 00
9am - 6pm

Biography

Areas of specialism

Exercise physiology; Glycemic control; Muscle metabolism; Nutrition; Sport science

University roles and responsibilities

  • Admissions Tutor for BSc (Hons) Sport and Exercise Science
  • Programme Leader for BSc (Hons) Sport and Exercise Science
  • Radiation Protection Supervisor FHMS

    Research

    Research interests

    Research projects

    Supervision

    Postgraduate research supervision

    Postgraduate research supervision

    My teaching

    My publications

    Highlights

    Rees Jordan L., Chang Courtney R., François Monique E., Marcotte-Chénard Alexis, Fontvieille Adeline, Klaprat Nika D., Dyck Rebecca A., Funk Deanna R., Snydmiller Gary, Bastell Kent, Godkin Florence E., Dubé Marie-Christine, Riesco Eléonor, McGavock Jon M., Yardley Jane E., Sigal Ronald J., Gibala Martin J., Weisnagel S. John, Prado Carla M., Jung Mary, Manders Ralph, Lee Terry, Singer Joel, Boulé Normand G., Little Jonathan P. (2019) Minimal effect of walking before dinner on glycemic responses in type 2 diabetes: outcomes from the multi-site E-PAraDiGM study, Acta Diabetologica 56 (7) pp. 755-765 Springer Verlag

    DOI: 10.1007/s00592-019-01358-x

    Darling A. L., Manders R. J. F., Sahni S., Zhu K., Hewitt C. E., Prince R. L., Millward D. J., Lanham-New S. A. (2019) Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years, Osteoporosis International 30 (4) pp. 741-761 Springer London

    DOI: 10.1007/s00198-019-04933-8

    Faithfull Sara, Turner Lauren, Poole Karen, Joy Mark, Manders Ralph, Weprin Jennifer, Winters-Stone Kerri, Saxton John (2019) Prehabilitation for adults diagnosed with cancer: A systematic review of long-term physical function, nutrition and patient-reported outcomes, European Journal of Cancer Care e13023 pp. 1-22 Wiley

    DOI: 10.1111/ecc.13023

    Publications

    Sara Faithfull, Lauren Turner, Karen Poole, Mark Joy, Ralph Manders, Jennifer Weprin, Kerri Winters-Stone, John Saxton (2019)Prehabilitation for adults diagnosed with cancer: A systematic review of long-term physical function, nutrition and patient-reported outcomes, In: European Journal of Cancer Caree13023pp. 1-22 Wiley

    Objective Prehabilitation is increasingly being used to mitigate treatment‐related complications and enhance recovery. An individual's state of health at diagnosis, including obesity, physical fitness and comorbidities, are influencing factors for the occurrence of adverse effects. This review explores whether prehabilitation works in improving health outcomes at or beyond the initial 30 days post‐treatment and considers the utility of prehabilitation before cancer treatment. Methods A database search was conducted for articles published with prehabilitation as a pre‐cancer treatment intervention between 2009 and 2017. Studies with no 30 days post‐treatment data were excluded. Outcomes post‐prehabilitation were extracted for physical function, nutrition and patient‐reported outcomes. Results Sixteen randomised controlled trials with a combined 2017 participants and six observational studies with 289 participants were included. Prehabilitation interventions provided multi‐modality components including exercise, nutrition and psychoeducational aspects. Prehabilitation improved gait, cardiopulmonary function, urinary continence, lung function and mood 30 days post‐treatment but was not consistent across studies. Conclusion When combined with rehabilitation, greater benefits were seen in 30‐day gait and physical functioning compared to prehabilitation alone. Large‐scale randomised studies are required to translate what is already known from feasibility studies to improve overall health and increase long‐term cancer patient outcomes.

    D Hansen, P Dendale, M Beelen, RAM Jonkers, R Manders, L Corluy, A Mullens, J Berger, R Meeusen, LJC van Loon (2008)Low Intensity Exercise Is Equally Effective As High Intensity Exercise Training To Improve Glycemic Control In Obese Type 2 Diabetes Patients, In: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE40(5)pp. S42-S42 LIPPINCOTT WILLIAMS & WILKINS
    D Hansen, P Dendale, M Beelen, R Jonkers, R Manders, L Corluy, A Mullens, R Meeusen, L van Loon (2008)Low intensity exercise is as effective as high intensity exercise to improve glycemic control in obese type 2 diabetes, In: ACTA CARDIOLOGICA63(1)pp. 94-94 ACTA CARDIOLOGICA
    C Punyadeera, AHG Zorenc, R Koopman, AJ McAinch, E Smit, R Manders, HA Keizer, D Cameron-Smith, LJC van Loon (2005)The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle, In: EUROPEAN JOURNAL OF ENDOCRINOLOGY152(3)pp. 427-436 BIO SCIENTIFICA LTD
    LJC van Loon, R Koopman, R Manders, W van der Weegen, GP van Kranenburg, HA Keizer (2004)Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes, In: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM287(3)pp. E558-E565 AMER PHYSIOLOGICAL SOC
    Jordan L. Rees, Courtney R. Chang, Monique E. François, Alexis Marcotte-Chénard, Adeline Fontvieille, Nika D. Klaprat, Rebecca A. Dyck, Deanna R. Funk, Gary Snydmiller, Kent Bastell, Florence E. Godkin, Marie-Christine Dubé, Eléonor Riesco, Jon M. McGavock, Jane E. Yardley, Ronald J. Sigal, Martin J. Gibala, S. John Weisnagel, Carla M. Prado, Mary Jung, Ralph Manders, Terry Lee, Joel Singer, Normand G. Boulé, Jonathan P. Little (2019)Minimal effect of walking before dinner on glycemic responses in type 2 diabetes: outcomes from the multi-site E-PAraDiGM study, In: Acta Diabetologica56(7)pp. 755-765 Springer Verlag

    Aim To examine the effect of walking before dinner on 24-h glycemic control in individuals with type 2 diabetes using the standardized multi-site Exercise-Physical Activity and Diabetes Glucose Monitoring (E-PAraDiGM) Protocol. Methods Eighty participants were studied under two conditions (exercise vs. non-exercise control) separated by 72 h in a randomized crossover design. Each condition lasted 2 days during which standardized meals were provided. Exercise consisted of 50 min of treadmill walking at 5.0 km/h before the evening meal, while control involved 50 min of sitting. The primary outcome measure was mean glucose during the 24-h period following exercise (or sitting) measured by continuous glucose monitoring. Results Of the 80 participants who were initially randomized, 73 completed both exercise and control. Sixty-three participants [29 males, 34 females; age = 64 ± 8 years, body mass index = 30.5 ± 6.5 kg/m2 and HbA1c = 51 ± 8 mmol/mol (6.8 ± 0.7%), mean ± SD] complied with the standardized diets and had complete continuous glucose monitoring data. Exercise did not affect mean 24-h glucose compared to control (0.03 mmol/L; 95% CI − 0.17, 0.22, P = 0.778) but individual differences between conditions ranged from − 2.8 to +1.8 mmol/L. Exercise did not affect fasting glucose, postprandial glucose or glucose variability. Glucose concentrations measured by continuous glucose monitoring were reduced during the 50 min of walking in exercise compared to sitting in control (− 1.56 mmol/L; 95% CI − 2.18, − 0.95, p ˂ 0.001). Conclusion Contrary to previous acute exercise studies, 50 min of walking before dinner in the E-PAraDiGM protocol did not affect 24-h glucose profiles. However, highly heterogeneous responses to exercise were observed.

    Agnieszka Lemanska, Karen Poole, Jonathan J. Aning, Bruce A. Griffin, Ralph Manders, John M. Saxton, Joe Wainwright, Sara Faithfull (2019)The Siconolfi step test: a valid and reliable assessment of cardiopulmonary fitness in older men with prostate cancer, In: European Review of Aging and Physical Activity16(1)pp. 1-10 BMC

    Background Assessing fitness and promoting regular physical activity can improve health outcomes and early recovery in prostate cancer. This is however, underutilised in clinical practice. The cardiopulmonary exercise test (CPET) is increasingly being used pre-treatment to measure aerobic capacity and peak oxygen consumption (VO2peak - a gold standard in cardiopulmonary fitness assessment). However, CPET requires expensive equipment and may not always be appropriate. The Siconolfi step test (SST) is simpler and cheaper, and could provide an alternative. The aim of this study was to evaluate the validity and reliability of SST for predicting cardiopulmonary fitness in men with prostate cancer. Men were recruited to this two-centre study (Surrey and Newcastle, United Kingdom) after treatment for locally advanced prostate cancer. They had one or more of three risk factors: elevated blood pressure, overweight (BMI ˃ 25), or androgen deprivation therapy (ADT). Cardiopulmonary fitness was measured using SST and cycle ergometry CPET, at two visits three months apart. The validity of SST was assessed by comparing it to CPET. The VO2peak predicted from SST was compared to the VO2peak directly measured with CPET. The reliability of SST was assessed by comparing repeated measures. Bland-Altman analysis was used to derive limits of agreement in validity and reliability analysis. Results Sixty-six men provided data for both SST and CPET. These data were used for validity analysis. 56 men provided SST data on both visits. These data were used for reliability analysis. SST provided valid prediction of the cardiopulmonary fitness in men ˃ 60 years old. The average difference between CPET and SST was 0.64 ml/kg/min with non-significant positive bias towards CPET (P = 0.217). Bland-Altman 95% limits of agreement of SST with CPET were ± 7.62 ml/kg/min. SST was reliable across the whole age range. Predicted VO2peak was on average 0.53 ml/kg/min higher at Visit 2 than at Visit 1 (P = 0.181). Bland-Altman 95% limits of agreement between repeated SST measures were ± 5.84 ml/kg/min. Conclusions SST provides a valid and reliable alternative to CPET for the assessment of cardiopulmonary fitness in older men with prostate cancer. Caution is advised when assessing men 60 years old or younger because the VO2peak predicted with SST was significantly lower than that measured with CPET.

    RJ Manders, JW Van Dijk, LJ van Loon (2010)Low-intensity exercise reduces the prevalence of hyperglycemia in type 2 diabetes., In: Med Sci Sports Exerc42(2)pp. 219-225

    INTRODUCTION: Glycemic instability is a severely underestimated problem in type 2 diabetes treatment. Therapeutic targets should aim to reduce postprandial blood glucose excursions. Exercise prescription can effectively improve glucose homeostasis and reduce the risk of cardiovascular complications. AIM: To assess the impact of a single, isoenergetic bout of low- (LI) and high-intensity (HI) exercise on the prevalence of hyperglycemia throughout the subsequent 24-h postexercise period in longstanding type 2 diabetes patients. METHODS: Nine sedentary, male type 2 diabetes patients (age = 57 +/- 2 yr, body mass index = 29.0 +/- 1.0 kg x m(-2), Wmax = 2.2 +/- 0.2 W x kg(-1) body weight) were selected to participate in a randomized crossover study. Subjects performed an isoenergetic bout of endurance-type exercise for 60 min at 35% Wmax (LI) or 30 min at 70% Wmax (HI) or no exercise at all (NE). Thereafter, glycemic control was assessed during the subsequent 24-h postexercise period by continuous glucose monitoring under strict dietary standardization but otherwise free-living conditions. RESULTS: Average 24-h glucose concentrations were reduced after the LI exercise bout (7.8 +/- 0.9 mmol x L(-1)) when compared with the control experiment (9.4 +/- 0.8 mmol x L(-1); P < 0.05). The HI exercise bout did not significantly lower mean glucose concentrations (8.7 +/- 0.7 mmol x L(-1); P = 0.14). Hyperglycemia was prevalent for as much as 35% +/- 9% throughout the day (NE). A single bout of exercise reduced the prevalence of hyperglycemia by 50% +/- 4% (P < 0.05) and 19% +/- 9% (P = 0.13) in the LI and HI exercise experiments, respectively. CONCLUSIONS: A single bout of LI, as opposed to HI, exercise substantially reduces the prevalence of hyperglycemia throughout the subsequent 24-h postexercise period in longstanding type 2 diabetes patients.

    JW Van Dijk, RJ Manders, EE Canfora, WV Mechelen, F Hartgens, CD Stehouwer, LJ Van Loon (2013)Exercise and 24-h glycemic control: equal effects for all type 2 diabetes patients?, In: Med Sci Sports Exerc45(4)pp. 628-635

    PURPOSE: We assessed the effect of a single bout of moderate-intensity exercise on subsequent 24-h glycemic control in 60 type 2 diabetes patients. Moreover, we examined whether individual responses to exercise were related to subjects' baseline characteristics, including age, body mass index, diabetes duration, exercise performance, medication, and HbA1c content. METHODS: Sixty type 2 diabetes patients (insulin-treated, n = 23) participated in a randomized crossover experiment. Patients were studied on two occasions for 3 d under strict dietary standardization but otherwise free-living conditions. Parameters of glycemic control (means [95% confidence interval]) were assessed by continuous glucose monitoring over the 24-h period after a single bout of moderate-intensity endurance-type exercise or no exercise at all (control). RESULTS: Type 2 diabetes patients experienced hyperglycemia (blood glucose >10 mmol·L) for as much as 8:16 h:min (6:44 to 9:48 h:min) per day. The prevalence of hyperglycemia was reduced by 31% to 5:38 h:min (3:17 to 7:00 h:min) over the 24-h period after the exercise bout (P < 0.001). Moreover, exercise lowered average blood glucose concentrations by 0.9 mmol·L (0.7 to 1.2) and reduced glycemic variability (P < 0.05). The response to exercise showed considerable variation between subjects and correlated positively with HbA1c levels (r = 0.38, P < 0.01). Nevertheless, even well-controlled patients with an HbA1c level below 7.0% (n = 28) achieved a 28% reduction in the daily prevalence hyperglycemia after exercise (P < 0.01). CONCLUSIONS: A single bout of moderate-intensity exercise substantially improves glycemic control throughout the subsequent day in insulin- and non-insulin-treated type 2 diabetes patients. Of all baseline characteristics, only subjects' HbA1c level is related to the magnitude of response to exercise. Nevertheless, the present study demonstrates that even well-controlled patients benefit considerably from the blood glucose-lowering properties of daily exercise.

    JW van Dijk, RJ Manders, F Hartgens, CD Stehouwer, SF Praet, LJ van Loon (2011)Postprandial hyperglycemia is highly prevalent throughout the day in type 2 diabetes patients., In: Diabetes Res Clin Pract93(1)pp. 31-37

    AIM: Although postprandial hyperglycemia is recognized as an important target in type 2 diabetes treatment, information on the prevalence of postprandial hyperglycemia throughout the day is limited. Therefore, we assessed the prevalence of hyperglycemia throughout the day in type 2 diabetes patients and healthy controls under standardized dietary, but otherwise free-living conditions. METHODS: 60 male type 2 diabetes patients (HbA(1c) 7.5±0.1% [58±1 mmol/mol]) and 24 age- and BMI-matched normal glucose tolerant controls were recruited to participate in a comparative study of daily glycemic control. During a 3-day experimental period, blood glucose concentrations throughout the day were assessed by continuous glucose monitoring. RESULTS: Type 2 diabetes patients experienced hyperglycemia (glucose concentrations >10 mmol/L) 38±4% of the day. Even diabetes patients with an HbA(1c) level below 7.0% (53 mmol/mol) experienced hyperglycemia for as much as 24±5% throughout the day. Hyperglycemia was negligible in the control group (3±1%). CONCLUSION: Hyperglycemia is highly prevalent throughout the day in type 2 diabetes patients, even in those patients with a HbA(1c) level well below 7.0% (53 mmol/mol). Standard medical care with prescription of oral blood glucose lowering medication does not provide ample protection against postprandial hyperglycemia.

    Sara Faithfull, Agnieszka Lemanska, Karen Poole, Jonathan Aning, Ralph Manders, John Marshall, John Saxton, Lauren Turner, Bruce Griffin (2021)Obesity and low levels of physical activity impact on cardiopulmonary fitness in older men after treatment for prostate cancer, In: European journal of cancer caree13476

    The purpose of this study was to compare fitness parameters and cardiovascular disease risk of older and younger men with prostate cancer (PCa) and explore how men's fitness scores compared to normative age values. 83 men were recruited post-treatment and undertook a cardiopulmonary exercise test (CPET), sit-to-stand, step-and-grip strength tests and provided blood samples for serum lipids and HbA1c. We calculated waist-to-hip ratio, cardiovascular risk (QRISK2), Charlson comorbidity index (CCI) and Godin leisure-time exercise questionnaire [GLTEQ]. Age-group comparisons were made using normative data. Men > 75 years, had lower cardiopulmonary fitness, as measured by VO2 Peak (ml/kg/min) 15.8 + 3.8 p < 0.001, and lower grip strength(28.6+5.2 kg p < 0.001) than younger men. BMI ≥30kg/m2 and higher blood pressure all contributed to a QRisk2 score indicative of 20% chance of cardiovascular risk within 10 years (mean: 36.9–6.1) p < 0.001. Age, BMI and perceived physical activity were significantly associated with lower cardiopulmonary fitness. Men with PCa > 75 years had more cardiovascular risk factors compared to normative standards for men of their age. Although ADT was more frequent in older men, this was not found to be associated with cardiopulmonary fitness, but obesity and low levels of physical activity were. Secondary prevention should be addressed in men with PCa to improve men's overall health.

    RJ Manders, R Koopman, M Beelen, AP Gijsen, WK Wodzig, WH Saris, LJ van Loon (2008)The muscle protein synthetic response to carbohydrate and protein ingestion is not impaired in men with longstanding type 2 diabetes., In: J Nutr138(6)pp. 1079-1085

    Protein ingestion stimulates muscle protein synthesis and improves net muscle protein balance. Insulin resistance has been suggested to result in a reduced muscle protein synthetic response to food intake. As such, we hypothesized that type 2 diabetes patients have a impaired muscle protein synthetic response to food ingestion. To test this hypothesis, 10 male type 2 diabetes patients using their normal oral glucose-lowering medication (68 +/- 2 y) and 10 matched, normoglycemic men (65 +/- 2 y) were randomly assigned to 2 crossover treatments in which whole body and muscle protein synthesis were measured following the consumption of either carbohydrate (CHO) or carbohydrate with a protein hydrolysate (CHO+PRO). Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied and blood and muscle samples were collected to assess whole-body protein balance and mixed muscle protein fractional synthetic rate over a 6-h period. Whole-body phenylalanine and tyrosine flux were higher after the CHO+PRO treatment compared with the CHO treatment in the diabetes and control group (P < 0.01). Protein balance was negative following CHO but positive following CHO+PRO treatment in both groups. Muscle protein synthesis rates were higher in both groups following the CHO+PRO (0.086 +/- 0.014%/h) treatment than in the CHO treatment (0.040 +/- 0.003%/h; P < 0.01) with no difference between the diabetes patients and normoglycemic controls. We conclude that the muscle protein synthetic response to CHO or CHO+PRO ingestion is not substantially impaired in longstanding, type 2 diabetes patients treated with oral blood glucose-lowering medication.

    AR Weseler, L Geraets, HJ Moonen, RJ Manders, LJ van Loon, HJ Pennings, EF Wouters, A Bast, GJ Hageman (2009)Poly (ADP-ribose) polymerase-1-inhibiting flavonoids attenuate cytokine release in blood from male patients with chronic obstructive pulmonary disease or type 2 diabetes., In: J Nutr139(5)pp. 952-957

    Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001]. Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.

    RJ Manders, SF Praet, RC Meex, R Koopman, AL de Roos, AJ Wagenmakers, WH Saris, LJ van Loon (2006)Protein hydrolysate/leucine co-ingestion reduces the prevalence of hyperglycemia in type 2 diabetic patients., In: Diabetes Care29(12)pp. 2721-2722
    R Koopman, L Verdijk, RJ Manders, AP Gijsen, M Gorselink, E Pijpers, AJ Wagenmakers, LJ van Loon (2006)Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men., In: Am J Clin Nutr84(3)pp. 623-632

    BACKGROUND: The progressive loss of skeletal muscle mass with aging is attributed to a disruption in the regulation of skeletal muscle protein turnover. OBJECTIVE: We investigated the effects on whole-body protein balance and mixed-muscle protein synthesis rates of the ingestion of carbohydrate with or without protein and free leucine after simulated activities of daily living. DESIGN: Eight elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to 2 crossover experiments in which they consumed either carbohydrate (CHO) or carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min of standardized activities of daily living. Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover and the protein fractional synthetic rate in the vastus lateralis muscle over a 6-h period. RESULTS: Whole-body phenylalanine and tyrosine flux were significantly higher in the young than in the elderly men (P < 0.01). Protein balance was negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both groups. Mixed-muscle protein synthesis rates were significantly greater in the CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and 0.060 +/- 0.005%/h, respectively; P < 0.01) and the elderly (0.072 +/- 0.006%/h and 0.043 +/- 0.003%/h, respectively; P < 0.01) subjects, with no significant differences between groups. CONCLUSIONS: Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men.

    BACKGROUND: Hyperglycemia forms a direct and independent risk factor for the development of cardiovascular comorbidities in type 2 diabetes. Consumption of sucrose-sweetened soft drinks might further increase the prevalence of hyperglycemic episodes. OBJECTIVE: The objective was to assess glycemic control in type 2 diabetic subjects and healthy lean and obese control subjects under strict dietary standardization but otherwise free-living conditions, with and without the consumption of soft drinks. DESIGN: Obese type 2 diabetic men (n = 11) and lean (n = 10) and obese (n = 10) normoglycemic male control subjects participated in a randomized crossover study. The subjects were provided with a standardized diet in 2 periods, during which they consumed 250 mL water with or without (control) sucrose (37.5 g) 2 h after breakfast and lunch. Blood glucose concentrations were assessed by continuous glucose monitoring. RESULTS: In the type 2 diabetic subjects, the mean 24-h glucose concentrations were significantly elevated (9.1 +/- 0.6 mmol/L), and hyperglycemia (glucose >10 mmol/L) was evident over 33 +/- 8% (8 +/- 2 h) of a 24-h period (P < 0.01). Hyperglycemia was rarely present in the normoglycemic lean and obese control subjects (5 +/- 2%/24 h for both). Consumption of 75 g sucrose, equivalent to 2 cans of a soft drink, did not further augment the prevalence of hyperglycemia throughout the day in any group. CONCLUSIONS: Type 2 diabetic subjects taking oral blood glucose-lowering medication experience hyperglycemia during most of the daytime. Moderate consumption of sucrose-sweetened beverages does not further increase the prevalence of hyperglycemia in type 2 diabetic subjects or in normoglycemic lean or obese men.

    SF Praet, RJ Manders, AG Lieverse, H Kuipers, CD Stehouwer, HA Keizer, LJ van Loon (2006)Influence of acute exercise on hyperglycemia in insulin-treated type 2 diabetes., In: Med Sci Sports Exerc38(12)pp. 2037-2044

    INTRODUCTION: The impact of exercise on blood glucose homeostasis has not been assessed in long-standing type 2 diabetes patients receiving exogenous insulin treatment. PURPOSE: To study the effects of an acute bout of exercise on the subsequent 24-h blood glucose excursions under free-living conditions in insulin-treated type 2 diabetes patients. METHODS: Eleven male type 2 diabetes patients (59 +/- 2 yr) performed an acute bout of exercise. One day before the exercise bout, a continuous glucose monitoring system (GlucoDay, A. Menarini Diagnostics) was inserted subcutaneously in the periumbilical region. The glucose sensor continuously measured glucose concentrations in the dialysate during a 48-h period. RESULTS: The prevalence of hyperglycemic glucose excursions was reduced by 39% during a 24-h period (equivalent to 3 h) after an acute bout of exercise (P < 0.05). Average glucose concentrations 24 h before and after the exercise bout did not differ (NS). Mean dialysate glucose concentrations and the prevalence of hyperglycemic periods correlated strongly with baseline blood HbA1c concentrations (Pearson's R = 0.69, P < 0.05). CONCLUSION: An acute bout of exercise effectively reduces the prevalence of hyperglycemia during a 24-h period under free-living conditions in long-standing type 2 diabetes patients on exogenous insulin therapy.

    RJ Manders, AJ Wagenmakers, R Koopman, AH Zorenc, PP Menheere, NC Schaper, WH Saris, LJ van Loon (2005)Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes., In: Am J Clin Nutr82(1)pp. 76-83

    BACKGROUND: Although insulin secretion after carbohydrate ingestion is severely impaired in patients with type 2 diabetes, amino acid and protein co-ingestion can substantially increase plasma insulin responses. OBJECTIVE: We investigated insulin responses and the subsequent plasma glucose disposal rates after the ingestion of carbohydrate alone (CHO) or with a protein hydrolysate and amino acid mixture (CHO+PRO) in patients with a long-term diagnosis of type 2 diabetes. DESIGN: Ten type 2 diabetic patients [mean (+/-SEM) age: 62 +/- 2 y; body mass index (kg/m(2)): 27 +/- 1] and 9 healthy control subjects (age: 58 +/- 1 y; body mass index: 27 +/- 1) participated in 2 trials in which the plasma insulin response was measured after the ingestion of 0.7 g carbohydrate . kg(-1) . h(-1) with or without 0.35 g . kg(-1) . h(-1) of a mixture that contained a protein hydrolysate, leucine, and phenylalanine. Continuous infusions with [6,6-(2)H(2)]glucose were then given to investigate plasma glucose disposal. RESULTS: Plasma insulin responses were higher by 299 +/- 64% and 132 +/- 63% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The subsequent plasma glucose responses were reduced by 28 +/- 6% and 33 +/- 3% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The reduced plasma glucose response in the diabetic patients was attributed to a 13 +/- 3% increase in glucose disposal (P < 0.01). CONCLUSIONS: The combined ingestion of carbohydrate with a protein hydrolysate and amino acid mixture significantly increases de novo insulin production in patients with a long-term diagnosis of type 2 diabetes. The increased insulin response stimulates plasma glucose disposal and reduces postprandial glucose concentrations.

    R Koopman, RJ Manders, RA Jonkers, GB Hul, H Kuipers, LJ van Loon (2006)Intramyocellular lipid and glycogen content are reduced following resistance exercise in untrained healthy males., In: Eur J Appl Physiol96(5)pp. 525-534

    Resistance exercise has recently been shown to improve whole-body insulin sensitivity in healthy males. Whether this is accompanied by an exercise-induced decline in skeletal muscle glycogen and/or lipid content remains to be established. In the present study, we determined fibre-type-specific changes in skeletal muscle substrate content following a single resistance exercise session. After an overnight fast, eight untrained healthy lean males participated in a approximately 45 min resistance exercise session. Muscle biopsies were collected before, following cessation of exercise, and after 30 and 120 min of post-exercise recovery. Subjects remained fasted throughout the test. Conventional light and (immuno)fluorescence microscopy were applied to assess fibre-type-specific changes in intramyocellular triacylglycerol (IMTG) and glycogen content. A significant 27+/-7% net decline in IMTG content was observed in the type I muscle fibres (P

    R Koopman, RJ Manders, AH Zorenc, GB Hul, H Kuipers, HA Keizer, LJ van Loon (2005)A single session of resistance exercise enhances insulin sensitivity for at least 24 h in healthy men., In: Eur J Appl Physiol94(1-2)pp. 180-187

    The aim of the present study was to determine whether a single session of resistance exercise improves whole-body insulin sensitivity in healthy men for up to 24 h. Twelve male subjects (23 +/- 1 years) were studied over a period of 4 days during which they consumed a standardized diet, providing 0.16 +/- 0.01 MJ.kg(-1).day(-1) containing 15 +/- 0.1 energy% (En%) protein, 29 +/ -0.1 En% fat and 55 +/- 0.3 En% carbohydrate. Insulin sensitivity was determined 24 h before and 24 h after a single resistance exercise session (8 sets of 10 repetitions at 75% of 1 repetition maximum for two leg exercise tasks) using an intravenous insulin tolerance test. Insulin sensitivity index was calculated by the decline in arterial blood glucose concentration following intravenous administration of a single bolus of human insulin (0.075 IU.kg(-1) fat free mass). Basal glucose and insulin concentrations were not changed up to 24 h after the resistance exercise. However, a substantial 13+/-5% improvement in whole-body insulin sensitivity was observed, 24 h after the resistance exercise (P < 0.05). This study shows that even a single session of resistance exercise improves whole-body insulin sensitivity for up to 24 h in healthy men, which is consistent with earlier observations following endurance exercise tasks.

    B Kaastra, RJ Manders, E Van Breda, A Kies, AE Jeukendrup, HA Keizer, H Kuipers, LJ Van Loon (2006)Effects of increasing insulin secretion on acute postexercise blood glucose disposal., In: Med Sci Sports Exerc38(2)pp. 268-275

    BACKGROUND: Coingestion of protein and/or free amino acids with carbohydrate has been reported to accelerate postexercise muscle glycogen synthesis due to an increase in the insulin response. PURPOSE: To determine the extent to which the combined ingestion of carbohydrate and a casein protein hydrolysate with or without additional free leucine can increase insulin levels during postexercise recovery in endurance-trained athletes. To determine how this affects whole-body plasma glucose disposal during postexercise recovery. METHODS: Fourteen male athletes (age: 24.3 +/- 0.8 yr; VO2max: 62.9 +/- 1.4 mL.kg.min) were subjected to three randomized crossover trials in which they performed 2 h of exercise (55% Wmax). Thereafter, subjects were studied for 3.5 h during which they ingested carbohydrate (CHO: 0.8 g.kg.h), carbohydrate and a protein hydrolysate (CHO-PRO: 0.8 and 0.4 g.kg.h, respectively), or carbohydrate, a protein hydrolysate, and free leucine (CHO-PRO-LEU: 0.8, 0.4, and 0.1 g.kg.h, respectively) in a double-blind fashion. Continuous infusions with [6,6-H2] glucose were applied to quantify plasma glucose appearance (Ra) and disappearance rates (Rd). RESULTS: Plasma insulin responses were 108 +/- 17 and 190 +/- 33% greater in the CHO-PRO and CHO-PRO-LEU trial, respectively, compared with the CHO-trial (P < 0.01). Plasma glucose responses were lower in the CHO-PRO and CHO-PRO-LEU trial compared with the CHO-trial (35 +/- 5 and 42 +/- 11% lower, respectively; P < 0.01). Plasma glucose Ra and Rd were greater in the CHO versus the CHO-PRO and CHO-PRO-LEU trials (P < 0.05). Glucose Rd represented 100 +/- 0.03% of Ra in all trials. CONCLUSIONS: The combined ingestion of a protein hydrolysate and/or free leucine with carbohydrate (0.8 g.kg.h) substantially augments insulin secretion, but does not affect plasma glucose disposal during the first 3.5 h of postexercise recovery in trained athletes.

    R Koopman, AJ Wagenmakers, RJ Manders, AH Zorenc, JM Senden, M Gorselink, HA Keizer, LJ van Loon (2005)Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects., In: Am J Physiol Endocrinol Metab288(4)pp. E645-E653

    The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.

    LJ van Loon, RJ Manders, R Koopman, B Kaastra, JH Stegen, AP Gijsen, WH Saris, HA Keizer (2005)Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients., In: Diabetologia48(10)pp. 2097-2107

    AIMS/HYPOTHESIS: In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients. MATERIALS AND METHODS: We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type. RESULTS: Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p

    SF Praet, RJ Manders, RC Meex, AG Lieverse, CD Stehouwer, H Kuipers, HA Keizer, LJ van Loon (2006)Glycaemic instability is an underestimated problem in Type II diabetes., In: Clin Sci (Lond)111(2)pp. 119-126

    The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA(1c) (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2+/-1% or 0.4+/-0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55+/-7% of the time (13+/-2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46+/-7%; P

    A. L. Darling, R. J. F. Manders, S. Sahni, K. Zhu, C. E. Hewitt, R. L. Prince, D. J. Millward, S. A. Lanham-New (2019)Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years, In: Osteoporosis International30(4)pp. 741-761 Springer London

    We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0–4% of areal BMC and areal BMD variance in adults and 0–14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2 = 32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed) = 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD(fixed) = 0.04 g/cm2 (0.00 to 0.08, P = 0.07), I2 = 0%) or FNBMD (total n = 435, MD(random) = 0.01 g/cm2 (−0.03 to 0.05, P = 0.59), I2 = 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8–1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.

    RJ Manders, R Koopman, WE Sluijsmans, R van den Berg, K Verbeek, WH Saris, AJ Wagenmakers, LJ van Loon (2006)Co-ingestion of a protein hydrolysate with or without additional leucine effectively reduces postprandial blood glucose excursions in Type 2 diabetic men., In: J Nutr136(5)pp. 1294-1299

    This study examined postprandial plasma insulin and glucose responses after co-ingestion of an insulinotropic protein (Pro) hydrolysate with and without additional free leucine with a single bolus of carbohydrate (Cho). Male patients with long-standing Type 2 diabetes (n = 10) and healthy controls (n = 10) participated in 3 trials in which plasma glucose, insulin, and amino acid responses were determined after the ingestion of beverages of different composition (Cho: 0.7 g/kg carbohydrate, Cho+Pro: 0.7 g/kg carbohydrate with 0.3 g/kg protein hydrolysate, or Cho+Pro+Leu: 0.7 g/kg carbohydrate, 0.3 g/kg protein hydrolysate and 0.1 g/kg free leucine). Plasma insulin responses [expressed as area under the curve (AUC)] were 141 and 204% greater in patients with Type 2 diabetes and 66 and 221% greater in the controls in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). The concomitant plasma glucose responses were 15 and 12% lower in the patients with Type 2 diabetes and 92 and 97% lower in the control group in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). Plasma leucine concentrations correlated with the insulin response in all subjects (r = 0.43, P < 0.001). We conclude that co-ingestion of a protein hydrolysate with or without additional free leucine strongly augments the insulin response after ingestion of a single bolus of carbohydrate, thereby significantly reducing postprandial blood glucose excursions in patients with long-standing Type 2 diabetes.

    Agnieszka Lemanska, Karen Poole, Bruce A. Griffin, Ralph Manders, John M Saxton, Lauren Turner, Joe Wainwright, Sara Faithfull (2019)Community pharmacy lifestyle intervention to increase physical activity and improve cardiovascular health of men with prostate cancer: a phase II feasibility study, In: BMJ Open9(6)e025114 BMJ Publishing group

    Objectives: To assess the feasibility and acceptability of a community pharmacy lifestyle intervention to improve physical activity and cardiovascular health of men with prostate cancer. To refine the intervention. Design: Phase II feasibility study of a complex intervention. Setting: Nine community pharmacies in the UK. Intervention: Community pharmacy teams were trained to deliver a health assessment including fitness, strength and anthropometric measures. A computer algorithm generated a personalised lifestyle prescription for a homebased programme accompanied by supporting resources. The health assessment was repeated 12 weeks later and support phone calls were provided at weeks 1 and 6. Participants: 116 men who completed treatment for prostate cancer. Outcome measures: The feasibility and acceptability of the intervention and the delivery model were assessed by evaluating study processes (rate of participant recruitment, consent, retention and adverse events), by analysing delivery data and semi-structured interviews with participants and by focus groups with pharmacy teams. Physical activity (measured with accelerometry at baseline, 3 and 6 months) and patient reported outcomes (activation, dietary intake and quality of life) were evaluated. Change in physical activity was used to inform the sample size calculations for a future trial. Results: Out of 403 invited men, 172 (43%) responded and 116 (29%) participated. Of these, 99 (85%) completed the intervention and 88 (76%) completed the 6-month follow-up (attrition 24%). Certain components of the intervention were feasible and acceptable (eg, community pharmacy delivery), while others were more challenging (eg, fitness assessment) and will be refined for future studies. By 3 months, moderate to vigorous physical activity increased on average by 34 min (95% CI 6 to 62, p=0.018), but this was not sustained over 6 months. Conclusions: The community pharmacy intervention was feasible and acceptable. Results are encouraging and warrant a definitive trial to assess the effectiveness of the refined intervention.

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