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OBJECTIVE The objective is to characterize the presence of malnutrition, examine the association between malnutrition and baseline functional capacity (FC), and the extent to which patients benefit from preoperative multimodal prehabilitation in patients undergoing lung resection for cancer. METHODS Data from 162 participants enrolled in multimodal prehabilitation or control before lung cancer surgery were analyzed. Malnutrition was measured using the Patient-Generated Subjective Global Assessment (PG-SGA) according to triage levels: low-nutrition-risk (PG-SGA 0-3), moderate-nutrition-risk (4-8) and high-nutrition-risk (≥9). Baseline differences in FC, measured by the 6-minute walk test (6MWT), were compared. Factorial analysis of covariance (ANCOVA) was conducted to examine the effect of nutrition status and intervention on mean change in 6MWT preoperatively. RESULTS 51.2% patients were considered low-nutrition-risk, 37.7% moderate-nutrition-risk, and 11.1% high-nutrition-risk. Low-nutrition-risk patients had significantly higher 6MWT at baseline (mean of 484 m [standard deviation (SD) = 88]) compared with moderate-nutrition-risk (432 m [SD = 107], P = .005) and high-nutrition-risk groups (416 m [SD = 90], P = .022). The adjusted mean change in 6MWT between prehabilitation vs control was 18.1 (95% confidence interval, 3.8 to 32.3) vs 5.6 m (-14.1 to 25.4) in low-nutrition-risk (P = .309), 28.5 (11 to 46) vs -4 m (-31.3 to 23.4) in moderate-nutrition-risk (P = .053), and 58.9 (16.7 to 101.2) vs -39.7 m (-80.2 to 0.826) in high-nutrition-risk group (P = .001). CONCLUSIONS Lung cancer patients at high-nutrition-risk awaiting surgery had significantly lower baseline FC compared with low-nutrition-risk patients but experienced significant improvements in preoperative FC upon receiving multimodal prehabilitation.

To determine the effect of preoperative nutrition and multimodal prehabilitation on clinical and functional outcomes in surgical lung cancer patients. We searched MEDLINE, Cochrane Library and CENTRAL, EMBASE, Scopus, and clinical trial registries ( clinicaltrials.gov , International Clinical Trials Registry Platform and Google Scholar) to identify studies involving a preoperative nutrition-based intervention or multimodal prehabilitation (nutrition with exercise) of at least 7 days, in lung cancer patients awaiting surgery. Studies must have reported results on at least one of the following outcomes: functional capacity, pulmonary function, postoperative complications, and length of hospital stay. The quality of included studies was assessed using the Cochrane risk of bias assessment tool for randomized trials and the modified Newcastle-Ottawa scale for non-controlled trials. Five studies were included (1 nutrition-only and 4 multimodal prehabilitation studies). Due to substantial heterogeneity in the interventions across studies, a meta-analysis was not conducted. Findings suggest that multimodal prehabilitation, compared with standard hospital care, is associated with improvements in both functional walking capacity and pulmonary function during the preoperative period; however it does not appear to have an effect on postoperative outcomes. Rather, the finding of significantly lower rates of postoperative complications in the intervention group was unique to the nutrition-only study. Multimodal prehabilitation programs that combine nutrition and exercise may have beneficial effects on various physical function outcomes in patients with lung cancer awaiting surgery. Optimizing preoperative nutrition may have postoperative benefits which remain to be confirmed.

Background The enhancement of post-operative care is under constant evolution and, with the addition of enhanced recovery programs, is changing the traditional in-hospital paradigm. Despite these advances, there is a clear lack of focus regarding early post-surgical mobilization, which has been identified as an important aspect of recovery. This pilot study investigates the feasibility of initiating resistance exercise to promote early mobilization in colorectal cancer patients during the in-hospital period. Method Patients participated in a supervised progressive resistance exercise program, adapted to their physical ability (either in bed, seated or standing), within the first 24 h following surgery. They were seen each day during the hospital stay and encouraged to continue exercising upon discharge. All patients were asked to return to the lab at four weeks after surgery for re-evaluation to establish recovery. Results Patient compliance to the in-hospital program was high, with 90% of patients engaging in exercise on the first post-operative day (POD 1) and no adverse effects reported during study. By POD 2, over 70% of patients met enhanced recovery after surgery (ERAS) recommendations. Conclusion It is feasible to initiate a progressive post-operative resistance exercise program in patients undergoing colorectal resection. The results suggest the positive aspects of incorporating resistance exercise into post-operative care. This may facilitate a clear and easy to implement exercise intervention that can take into consideration patient physical status and limited facility space in the hospital environment.

Objective To investigate, in lung cancer patients awaiting elective surgery, the feasibility of delivering a novel four-week multimodal prehabilitation intervention and its effects on preoperative functional capacity and health-related quality of life (HRQoL), compared to standard hospital care. Methods Adult patients awaiting elective thoracotomy for lung cancer stages I, II or IIIa, were approached to participate in an open-label, randomized controlled trial of two parallel arms: multimodal prehabilitation combining a mixed-nutrient supplement with structured supervised and home-based exercise training, and relaxation-strategies (Prehab) or standard hospital care (Control). Feasibility was assessed based on recruitment and adherence rates to the intervention and study outcome assessment. Functional capacity, measured by the 6-min walk test (6MWT), and HRQoL were measured at baseline and after four weeks (preoperative). Results Within 5 months, 34 patients were enrolled and randomized (2:1) to Prehab (n = 24; median age = 67 years) or Control (n = 10; median age = 69 years); recruitment rate of 58.6%. The study was interrupted by the COVID-19 pandemic. Adherence to the prescribed intensity of the supervised exercise program was 84.1% (SD 23.1). Self-reported adherence to the home-based exercise program was 88.2% (SD 21) and to the nutritional supplement, 93.2% (SD 14.2). Adherence to patients’ preoperative assessment was 82% and 88% in Prehab and Control, respectively. The mean adjusted difference in 4-week preoperative 6MWT between groups was 37.7 m (95% CI, −6.1 to 81.4), p = 0.089. There were no differences in HRQoL between groups. Conclusion Within a preoperative timeframe, it was feasible to deliver this novel multimodal prehabilitation intervention in lung cancer patients awaiting surgery.

Prehabilitation has been previously shown to be more effective in enhancing postoperative functional capacity than rehabilitation alone. The purpose of this study was to determine whether a weekly supervised exercise session could provide further benefit to our current prehabilition program, when comparing to standard post-surgical rehabilitation.A parallel-arm single-blind randomized control trial was conducted in patients scheduled for non-metastatic colorectal cancer resection. Patients were assigned to either a once weekly supervised prehabilitation (PREHAB+, n = 41) or standard rehabilitation (REHAB, n = 39) program. Both multimodal programs were home-based program and consisted of moderate intensity aerobic and resistance exercise, nutrition counseling with daily whey protein supplementation and anxiety-reduction strategies. Perioperative care was standardized for both groups as per enhanced recovery after surgery (ERASBoth groups were comparable for baseline walking capacity (PREHAB+: 448 m [IQR 375-525] vs. REHAB: 461 m [419-556], p=.775) and included a similar proportion of patients who improved walking capacity (20 m) during the preoperative period (PREHAB+: 54% vs. REHAB: 38%, p = .222). After surgery, changes in 6MWD were also similar in both groups. In PREHAB+, however, there was a significant association between physical activity energy expenditure and 6MWD (p .01). Previously inactive patients were more likely to improve functional capacity due to PREHAB+ (OR 7.07 [95% CI 1.10-45.51]).The addition of a weekly supervised exercise session to our current prehabilitation program did not further enhance postoperative walking capacity when compared to standard REHAB care. Sedentary patients, however, seemed more likely to benefit from PREHAB+. An association was found between energy spent in physical activity and 6MWD. This information is important to consider when designing cost-effective prehabilitation programs.

Colorectal cancer surgery results in considerable postoperative morbidity, mortality and reduced quality of life. As many patients will undergo additional (neo)adjuvant therapy, it is imperative that each individual optimize their physical function. To elucidate the potential of exercise in patient optimization, we investigated the evidence for an exercise program before and after surgical treatment in colorectal cancer patients. A systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions, the guidelines of the Physical Therapy Journal and the PRISMA guidelines. No literature pertaining to exercise training during preoperative neoadjuvant treatment was found. Seven studies, investigating the effects of regular exercise during adjuvant chemotherapy for patients with colorectal cancer or a mixed population, were identified. A small effect (effect size (ES) 0.4) of endurance/interval training and strength training (ES 0.4) was found in two studies conducted in patients with colorectal and gastrointestinal cancer. In five studies that included a mixed population of cancer patients, interval training resulted in a large improvement (ES 1.5; P≤.05). Endurance training alone was found to increase both lower extremity strength and endurance capacity. The effects of strength training in the lower extremity are moderate, whereas, in the upper extremity, the increase is small. There is limited evidence available on exercise training during treatment in colorectal cancer patients. One study concluded exercise therapy may be beneficial for colorectal cancer patients during adjuvant treatment. The possible advantages of training during neoadjuvant treatment may be explored by prehabilitation trials.

Objective Depression and poor functional status (FS) frequently co-occur. Though both predict adverse surgical outcomes, research examining preoperative functional performance (FP; self-reported) and functional capacity (FC; performance-based) measures in depressed cancer patients is lacking. Prehabilitation, a preoperative intervention including exercise, nutrition, and stress-reduction, may improve FC; however, whether depressed patients benefit from this intervention remains unknown. The primary objectives were to (a) assess differences in FP and FC and (b) explore the impact of prehabilitation on FC in individuals with depressive symptoms versus those without. Method A secondary analysis was conducted on 172 colorectal cancer patients enrolled in three studies comparing prehabilitation with a control group (rehabilitation). Measures were collected at 4 weeks pre- and 8 weeks postoperatively. FP, FC, and psychological symptoms were assessed using the 36-Item Short Form Health Survey, Six-Minute Walk Distance (6MWD), and Hospital Anxiety and Depression Scale (HADS), respectively. Subjects were divided into three groups according to baseline psychological symptoms: no psychological-symptoms (HADS-N), anxiety-symptoms (HADS-A), or depressive-symptoms (HADS-D). Main objectives were tested using analyses of variance, chi-square tests, and multivariate logistic regression. Results At baseline, HADS-D reported lower FP, had shorter 6MWD, and a greater proportion walked ≤ 400 m. Prehabilitation was associated with significant improvements in 6MWD in HADS-D group but not in HADS-N or HADS-A groups. Conclusion Poorer FS was observed in subjects with depressive symptoms, and these subjects benefited most from prehabilitation intervention. Future research could examine whether severity of depression and co-occurrence of anxiety differentially impact FS and whether prehabilitation can improve psychological symptoms and quality of life. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This review by a 10-member panel of experts in surgical prehabilitation addresses processes that may improve oncologic care. Surgical prehabilitation is the process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of surgical treatment. The panel focused on the current state-of-the-science and recommended future research that would help to identify the elements that enhance preoperative physical, nutritional, and psychological health in anticipation of surgery, mitigate the burden of disease, facilitate the return of patient health status to baseline values, decrease postoperative morbidity, and reduce health care costs.

High complication rates following colorectal surgery render many patients unable to fully regain functional capacity, thus seriously compromising quality of life. The aim of this study was to assess whether a 4-week trimodal prehabilitation program (exercise, nutritional supplementation, and counseling on relaxation techniques), implemented during the preoperative period, is sufficient to modify exercise behaviors and improve functional capacity of elderly patients scheduled for colorectal cancer surgery. Patients were assigned to either a prehabilitation (PREHAB; n = 57) or matched time control group (CTRL; n = 59). Over the 4-week period prior to surgery, patients in PREHAB participated in a trimodal prehabilitation program. Patients in CTRL received the same program but only postoperatively. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to measure physical activity levels, while the 6-min walk test (6MWT) was used for assessment of functional walking capacity. Measurements were collected at baseline and at the time of surgery. Over the preoperative period, patients in PREHAB significantly increased the amount of moderate- and vigorous-intensity physical activities that they performed. PREHAB patients also demonstrated a greater improvement in 6MWT compared to CTRL. At the time of surgery, a greater proportion of patients in PREHAB met current physical activity guidelines, as compared to CTRL. These findings highlight the positive effects of a trimodal prehabilitation program on patients’ physical activity levels and functional walking capacity and demonstrate that modifying exercise behaviors and improving physical function within the 4-week preoperative period are an achievable goal.

BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients' functional capacity and postoperative complications.METHODS/DESIGN: This international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis.DISCUSSION: Multimodal prehabilitation is expected to enhance patients' functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer.TRIAL REGISTRATION: Trial Registry: NTR5947 - date of registration: 1 August 2016.

Background: Poor functional capacity (FC) is an independent predictor of postoperative morbidity. However, there is still a lack of evidence as to whether enhancing FC before surgery has a protective effect on postoperative complications. The purpose of this study was to determine whether an improvement in preoperative FC impacted positively on surgical morbidity. Methods: This was a secondary analysis of a cohort of patients who underwent colorectal resection for cancer under Enhanced Recovery After Surgery care. FC was assessed with the 6-min walk test, which measures the distance walked in 6 min (6MWD), at 4 weeks before surgery and again the day before. The study population was classified into two groups depending on whether participants achieved a significant improvement in FC preoperatively (defined as a preoperative 6MWD change ≥19 meters) or not (6MWD change Results: A total of 179 eligible adults were studied: 80 (44.7%) improved in 6MWD by ≥19 m preoperatively, and 99 (55.3%) did not. Subjects whose FC increased had lower CCI (0 [0–8.7] versus 8.7 [0–22.6], p = .022). Furthermore, they were less likely to have a severe complication (adjusted OR 0.28 (95% CI 0.11–0.74), p = .010), and to have an ED visit. Conclusion: Improved preoperative FC was independently associated with a lower risk of severe postoperative complications. Further investigation is required to establish a causative relationship conclusively.

Low-carbohydrate diets are considered to be an effective approach to weight loss and have, subsequently, grown in popularity. Despite the apparent health benefits that these diets may provide for insulin resistance, hypertension, and dyslipidemia, their implications on cardiomyocyte oxidative capacity have yet to be investigated. To evaluate the adaptations induced by a 6-week low-carbohydrate, high-fat (LCHF) diet on mitochondrial respiration, two groups of male mice were investigated: Apolipoprotein E-deficient mice on a LCHF diet (L-DIET) and apolipoprotein E-deficient mice on a regular rodent diet (CON). Heart tissue was extracted and used for high-resolution respirometry (HRR), while immunoblotting was performed to quantify mitochondrial density and complexes. The results demonstrate increased expression of all five mitochondrial subunits in the L-DIET group compared to control condition. Furthermore, HRR revealed increased efficiency of substrate consumption, implying augmented oxidative capacity in the L-DIET group. These findings further support the notion that cardiomyocytes prefer lipids as a primary fuel source, by demonstrating that the shift in metabolism caused by a LCHF diet facilitates such an environment. This provides important information regarding the effects of a LCHF on cardiomyocytes, especially when considering free radical production and heart dysfunction.

Objective: The incidence of childhood obesity in North America and around the world has risen significantly over the past decade leaving clinicians constantly searching for effective weight loss strategies. Despite the growing popularity or carbohydrate restricted diets, consequences of long term use remain widely unknown. The objective of the current investigation is to evaluate the effects of LCHF diets on heart size and cardiac glycogen content in young mice. Methods: Young mice (age 21 d, n = 24) and mature mice (age 84 d, n = 18) were placed on either a LCHF diet, a WD diet or a control diet for 12 weeks. Activity levels, body weight, and glucose values were measured during the investigation. At the competition of the dietary intervention, wet heart weights were measured to compute the heart weight-to-tibia length ratio, cross sectional area was calculated and sections of cardiac tissue were stained with periodic acid and Schiff reagent to visualize glycogen. Results: No differences in activity levels or glucose measures were noted between groups. Mice following the LCHF diet displayed a smaller heart weight-to-tibia length ratio when compared to controls. The trend was observed in both young (p = 0.012) and mature (p = 0.024) mice. No differences in cross sectional area were detected. Cardiac tissue from mice consuming the LCHF diet had a reduced percentage of total area stained positive for glycogen when compared to mice following the WD diet (p = 0.016). Conclusions: A LCHF diet can lead to the development of a smaller heart in young and mature mice. Alterations in intercellular cardiac glycogen content may contribute to differences observed in heart weight. Cardiac restricted diets should be recommended with caution as long term cardiac developmental impairments are unknown.

Multimodal prehabilitation is a preoperative conditioning intervention in form of exercise, nutritional assessment, whey protein supplementation, and anxiety-coping technique. Despite recent evidence suggesting that prehabilitation could improve functional capacity in patients undergoing colorectal surgery for cancer, all studies were characterized by a relatively small sample size. The aim of this study was to confirm what was previously found in three small population trials.Data of 185 participants enrolled in a pilot single group study and two randomized control trials conducted at the McGill University Health Center from 2010 to 2015 were reanalyzed. Subjects performing trimodal prehabilitation (exercise, nutrition, and coping strategies for anxiety) were compared to the patients who underwent the trimodal program only after surgery (rehabilitation/control group). Functional capacity was assessed with the six-minute walk test (6MWT), a measure of the distance walked over six minutes (6MWD). A significant functional improvement was defined as an increase in 6MWD from baseline by at least 19 m. Changes in 6MWD before surgery, at four and eight weeks were compared between groups.Of the total study population, 113 subjects (61%) underwent prehabilitation. Changes in 6MWD in the prehabilitation group were higher compared to the rehabilitation/control group during the preoperative period {30.0 [standard deviation (SD) 46.7] m vs. -5.8 (SD 40.1) m, p 0.001}, at four weeks [-11.2 (SD 72) m vs. -72.5 (SD 129) m, p 0.01], and at eight weeks [17.0 (SD 84.0) m vs. -8.8 (SD 74.0) m, p = 0.047]. The proportion of subjects experiencing a significant preoperative improvement in physical fitness was higher in those patients who underwent prehabilitation [68 (60%) vs. 15 (21%), p 0.001].In large secondary analysis, multimodal prehabilitation resulted in greater improvement in walking capacity throughout the whole perioperative period when compared to rehabilitation started after surgery.

Traditional rehabilitative approaches to perioperative cancer care have focused on the postoperative period to facilitate the return to presurgical baseline conditions. However, there is some realization that the preoperative period can be a very effective time for intervention as the patients are more amenable to target their physiological condition to prepare to overcome the metabolic cost of the surgical stress.We undertook a narrative review of the current literature on surgical prehabilitation and discussed the current evidence of preoperative interventions before cancer surgery in order to increase physiological reserve before surgery and accelerate postoperative recovery.Published data indicate the positive impact of prehabilitation on postoperative functional capacity and return to daily activities. However, the current evidence on the impact on short- and long-term clinical outcome is limited, and more research needs to be conducted.Preliminary findings indicate that a group of interventions such as exercise, nutrition and anxiety reduction in the preoperative period can complement the enhanced recovery program and facilitate the return to baseline activities of daily living. It is not clear at this stage whether the preoperative increase in functional capacity mitigates the burden of postoperative morbidities and subsequent cancer therapies. Therefore, more research is warranted.

summary Background & aims: Despite the descriptive presence of cancer cachexia (CC) in clinical practice, the underlying mechanisms and diagnostic definition have not been clearly identified. Recent work, attempting to establish diagnostic and staging criteria for CC, has identified IL-6 as a biomarker. This study aimed to investigate the clinical relevance of plasma levels of four pro-inflammatory cytokines (IL6, IL-1b, IL-8 and TNF-a) in advanced cancer patients (ACP) to further establish their potential in the diagnostic definition of CC. Methods: Blood was obtained from 83 ACP (47 male and 36 female, aged 34e85 years) and analyzed for white blood cells, lymphocytes, C-reactive protein, albumin and cytokines. Subjects completed questionnaires to establish weakness, loss of appetite, fatigue, quality of life and weight loss; completed tests to determine strength, body composition and sarcopenia; and consented to chart review to calculate survival and total days admitted to hospital. Results: This study shows that, in ACP, IL-1 b is better associated with clinical features of the cachectic condition, such as weakness, loss of appetite, weight loss and sarcopenia, than IL-6. Conclusion: IL-6 may not best represent the clinical correlates of CC in ACP. Additional cytokines should be considered in the definition of this condition.

Patients with type 2 diabetes (T2DM) have an increased risk for cardiovascular disease. We examined the effects of 8 weeks of home-based rowing training (heart rate corresponding to 65-70% of VO(2 peak) ) on endothelial function and glucose clearance (local and systemic effects) in male subjects with T2DM (n=9) and matched controls (n=8). Before and after training (30 min every other day), all subjects underwent sequential graded brachial artery infusions of non-insulin vasodilators (acetylcholine; sodium nitroprusside; adenosine). Forearm blood flow was improved by training in controls (without and with insulin: P=0.003 and 0.05, respectively) but not in subjects with T2DM. Likewise, whole body glucose clearance increased in response to training in controls (P=0.05) but not in T2DM. However, in both groups, the capacity for local forearm glucose extraction (controls: P=0.001; T2DM: P=0.002) and clearance (controls: P

Aims: The objective was to re-examine endothelial function, insulin mediated vasodilation and glucose extraction in the forearm of patients with type 2 diabetes (T2DM) and matched control subjects (CON) to investigate whether blood flow impairments result from diabetes per se or from concurrent disease. Methods: 18 subjects (10 with T2DM, 8 CON) had graded brachial artery infusions of endothelial dependent (acetylcholine: 15, 30, 60 mg/min), endothelial independent (sodium nitroprusside: 1, 3, 10 mg/min) and partially endothelial mediated (adenosine: 50, 150, 500 mg/min) vasodilators. The protocol was repeated during a hyperinsulinemic clamp. Forearm blood flow and glucose extraction were measured at each dose of vasodilator (with/ without insulin). Measurements were also taken in the control arm, reflecting systemic insulin infusion only. Results: Non-insulin mediated increases in bulk forearm blood flow were similar in T2DM and CON. However, insulin mediated forearm blood flow responses and glucose extraction were lower in T2DM versus CON. Conclusion: The vasodilatory effect of insulin is impaired in T2DM although bulk flow capacity is maintained. Insulin mediated glucose extraction is reduced during concomitant maximal stimulation of forearm blood flow with endothelial-dependent vasodilators, despite maintaining flow. This is consistent with previous work that associates T2DM with impaired insulin mediated capillary recruitment.

Patients with T2DM have an increased risk of CVD. Prevention of CVD represents the major goal of all treatment of T2DM, and early intervention in those patients at particularly high risk is important.We measured the insulin sensitivity and plasma biomarkers of CVD to determine whether a home-based exercise training program improves biomarker levels and insulin sensitivity. Patients with T2DM (n=12), IGT (n=4) and healthy control subjects (n=9) were studied before and after eight weeks of exercise training by rowing ergometry at 65—70% of peak oxygen uptake. Conclusions: 1) patients with T2DM have elevated plasma concentrations of CVD biomarkers compared to the matched control and IGT groups; 2) a moderate to vigorous intensity home-based training program did not reduce plasma concentrations of these CVD markers; 3) insulin sensitivity improved as a result of exercise training in the control group, but not in the T2DM group.

ObjectiveIn obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during a hyperinsulinemic–euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor the intramyocellular lipid deposition has been compared directly in obese females and males.DesignWe studied eight obese females and eight obese males (body mass index (BMI): 32.6±1.4 and 32.8±0.8 respectively, non significant (NS)) matched for cardiorespiratory fitness relative to lean body mass (43.7±1.6 and 47.6±1.3 ml/kg min respectively, NS).MethodsEach subject underwent two hyperinsulinemic–euglycemic clamps with infusion of lipid or saline respectively. Furthermore, the subjects exercised during the last half an hour of each clamp.ResultsThe lipid-induced reduction in glucose disposal during the clamp was similar in females and males (46±10 and 60±4% respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (PP=0.01 respectively). Muscle ceramide, triacylglycerol (TAG), diacylglycerol (DAG), and glycogen content were similar between sexes and remained unchanged during the clamp and when exercise was superimposed.ConclusionsThe lipid-induced inhibition of glucose disposal is similar in obese females and males. However, obese females are more insulin sensitive compared with obese males (both during saline and lipid infusion), which is not due to differences in the concentration of the muscle lipid intermediates such as ceramide and DAG.

Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences. To date, the significance of endogenous antioxidants such as metallothioneins I and II (MT-I+II) in type 2 diabetes remains unclear. To examine the MT-I+II-mediated antioxidant capacity and its response to exercise training in the skeletal muscle of patients with type 2 diabetes, biopsies and blood samples were taken from 13 matched subjects (type 2 diabetes n = 8, control subjects n = 5) both before and after 8 weeks of exercise training. Immunohistochemical analysis revealed reduced MT-I+II levels in the skeletal muscle of type 2 diabetic subjects compared with control subjects. Control subjects produced a robust increase of MT-I+II in response to training; however, in type 2 diabetes, MT-I+II levels remained essentially unchanged. Significantly lower levels of MT-I+II were also detected in the plasma of type 2 diabetic subjects compared with control subjects. These results suggest that, in control subjects, the MT-I+II defense system is active and inducible within skeletal muscle tissue and plasma. In type 2 diabetes, reduced levels of MT-I+II in muscle and plasma, as well as the deficient MT-I+II response to exercise, indicate that this antioxidant defense is impaired. This study presents a novel candidate in the pathogenesis of complications related to oxidative stress in type 2 diabetes.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) play a critical role during vascular remodelling, in both health and disease. Impaired MMP regulation is associated with many diabetes-related complications. This study examined whether exercise-induced regulation of MMPs is maintained in the skeletal muscle of patients with uncomplicated type 2 diabetes (T2DM). Subjects [12 T2DM, 9 healthy control subjects (CON)] underwent 8 weeks of physical training. Messenger RNA (mRNA) was measured at baseline, during and after 8 weeks of training. Protein was measured pre- and post-training. At baseline, there were no effects of diabetes on MMP or TIMP mRNA or protein. mRNA and protein response to training was similar in both groups, except active MMP-2 protein was elevated post training in T2DM only. Our results indicate that exercise-induced stimulation of MMPs is preserved in skeletal muscle of patients with T2DM. This early stage of diabetes may provide an opportunity for intervention and prevention of complications.

There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukemia (ALL), have increased rates of long-term skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strongly implicated. Normal skeletal muscle growth, development, and function are dependent on correctly functioning muscle satellite cells, muscle motor neurons, and muscle mitochondria. Each of these key components is potentially susceptible to damage by chemotherapy in childhood, particularly prolonged courses including repeated administration of combination chemotherapy. If this chemotherapy-induced damage is not fully reversible, impairment of satellite cells, muscle motor innervation, and mitochondria could, either singly or together, lead to the emergence of delayed or persistent skeletal muscle dysfunction many years later. The known effects of individual drugs used in the treatment of ALL are outlined and the need for specific targeted studies to investigate the mechanisms underlying persistent muscle dysfunction in survivors of ALL and other childhood cancers is highlighted.

The term “endothelial dysfunction” refers to the inability or attenuated effect of the endothelial cells in participating in the relaxation of the adjacent smooth muscle, thus causing less vasodilation. Although endothelial dysfunction is often seen in patients with type 2 diabetes, it does not necessarily follow that insulin resistance and (or) hyperglycemia is causing the inability to respond properly to vasodilatory stimuli. Rather, this could be related to the impact of concomitant cardiovascular risk factors that are almost invariably present in patients with type 2 diabetes. The impact of physical training — or the opposite, inactivity — on endothelial function is not fully elucidated. Some studies have shown positive effects of physical training, whereas others have not. In general, physical training can improve endothelial function when this is impaired. However, physical training does not seem to have any effect on endothelial function when this is normal.