Advances in exercise, physical activity and diabetes mellitus

Diet and exercise form a solid foundation for the prevention and treatment of diabetes mellitus. Regular physical activity increases insulin sensitivity, improves pharmacotherapy, lowers blood sugar concentrations, reduces body fat content, builds muscle and improves cardiovascular fitness and function. A number of recent studies have demonstrated the effectiveness of regular exercise in improving metabolic control and overall health in persons with diabetes, although the clinical management of physically active patients with type 1 diabetes (T1D) remains a challenge. This year, we highlight a number of papers, published between 1 July and 30 June 2011, that are valuable contributions to the field of exercise and diabetes management. Mackenzie R 1 , Maxwell N 2 , Castle P 3 , Birckley G 2 , Watt P 2 1 School of Life Sciences, Department of Human and Health Sciences, University of Westminster, London, UK, 2 Chelsea School Research Centre, University of Brighton, Eastbourne, UK, and 3 Department of Sport and Exercise Science, University of Bedfordshire, Bedford, UK Diabetes Metab Res Rev 2011; 27 : 94–101 Aims: Similar to muscular contractions, hypoxia has been suggested to stimulate glucose uptake into skeletal muscle independent of insulin signalling. However, hypoxia has also been shown to cause insulin resistance in rodents, due to a sympathoadrenal-induced epinephrine release, thereby reducing glucose disposal. The aim of the study was to examine the effects of acute hypoxia, with and without exercise, on insulin sensitivity (SI2*), glucose effectiveness (SG2*) and β-cell function in individuals with type 2 diabetes mellitus (T2D). Methods: Eight sedentary males with T2D, who were not on exogenous insulin and who were diagnosed within the last 5 years, were recruited for this study. Following an overnight fast and baseline blood sampling, subjects completed the following in a randomised order (each visit separated by 7–14 days): (1) normoxic rest; (2) hypoxic rest (inspired O2 = 14.6%); (3) normoxic exercise; and (4) hypoxic exercise (inspired O2 = 14.6%). The exercise performed was at a work load equivalent to 90% of normoxic lactate threshold. Arterialised venous blood samples were taken every 10 min during the tests. A 4-h intravenous glucose tolerance test was administered immediately following each test under normoxic conditions. Results: The tests demonstrated increased insulin sensitivity following hypoxic rest compared with normoxic rest [SI2*= 2.25 ± 0.50 vs. 1.39 ± 0.08 × 10–4μU/ml (mean ± SEM), respectively] (p < 0.05), greater insulin sensitivity following hypoxic exercise compared with normoxic exercise (p < 0.05), and a lower acute insulin response to glucose following hypoxic rest compared with normoxic rest (p = 0.014). Blood lactic acid tests showed no differences between groups. Arterialised blood glucose tests showed a significantly greater decrease in glycaemia during hypoxic exercise (–1.82 ± 0.64 mmol/l) compared with normoxic exercise (–0.91 ± 0.35 mmol/l) (p < 0.05). With respect to insulin levels, hypoxic rest showed no change, while hypoxic exercise caused insulin levels to decrease from baseline but with no difference compared with normoxic exercise. The ability of glucose to use the muscle-contraction-stimulated pathway, as measured by glucose effectiveness (SG2*), showed no differences between conditions. Conclusion: Hypoxic conditions improve glucose tolerance, via insulin-mediated and non-insulin-mediated mechanisms, in the hours following exposure. Hypoxic exercise enhances insulin sensitivity over normoxic exercise in patients with T2D. Comment: Based on this study, acute hypoxia during rest and particularly during exercise provides improvements in short-term insulin sensitivity and glycaemic control for patients with T2D. While this study is an interesting and innovative approach to the treatment of diabetes, its applications and uses are limited with respect to economic and clinical practicality. Applying acute hypoxia to patients with T2D is expensive and cumbersome as a treatment. Research into long-standing hypoxia with respect to insulin sensitivity and glycaemic control may be useful in high elevation areas such as mountain climbing for those with diabetes. However, as a treatment for more sedentary diabetics on a wider scale, it is probably impractical at this stage of technological development (i.e. hypoxic environmental chambers). Moreover, a 2004 study that looked at 2658 participants in a sleep-disordered breathing state or sleep apnoea, which involves periods of hypoxia, found that sleep-related hypoxia was associated with glucose intolerance rather than improved insulin sensitivity, independent of age, gender, body mass index and waist circumference (1). Similarly, in a smaller study with 13 non-diabetic volunteers who underwent 5 h of intermittent hypoxia over 2 days, insulin sensitivity deteriorated (2). Thus, it remains unclear if hypoxia is good or bad for insulin sensitivity for patients with T2D. Balducci S, Zanuso S, Nicolucci A, De Feo P, Cavallo S, Cardelli P, Fallucca S, Alessa E, Fallucca F, Pugliese G; for the Italian Diabetes Exercise Study (IDES) Investigators Diabetes Division, Sant'Andrea Hospital, Rome , Italy Arch Intern Med 2010; 170 : 1794–803 Aims: Cardiorespiratory fitness is inversely related to rates of cardiovascular-related mortality in patients with T2D. The aim of this study was to assess the efficacy of an exercise intervention strategy combining supervised exercise with exercise counselling on increasing physical activity (PA) levels, lowering HbA1c levels and improving other cardiovascular risk factors in a large T2D cohort in Italy. Methods: In all, 606 eligible sedentary patients with T2D were enrolled in 22 outpatient diabetes clinics across Italy and were randomised to the exercise plus counselling group (EXE, n = 303) or the counselling-only group (CON, n = 303). The study period was 12 months and counselling was given every 3 months for both groups. The EXE group underwent mixed aerobic and resistance training twice a week for a total of 150 min of supervised exercise per week. Efficacy was measured primarily by HbA1c levels, while secondary outcomes were measures of other modifiable cardiovascular risk factors. Baseline PA levels were established by the Minnesota Leisure-time Physical Activity Questionnaire and PA levels were estimated in metabolic equivalents [1 MET = 1 kcal/(kg h); sleeping is 0.9 MET, running a 5.5 min mile is 18 METs]. Unsupervised PA levels were prospectively evaluated through daily diaries. Results: Compared with the CON group, the EXE group had double the total PA levels during the intervention (mean ± SD: 10.0 ± 8.7 vs. 20.0 ± 0.9 MET hours per week). The EXE group also had significant improvements in HbA1c levels [mean difference (95% confidence interval): –0.30% (–0.49% to –0.10%); p < 0.001], systolic [–4.2 mmHg (–6.9 to –1.6 mmHg); p = 0.002] and diastolic [–1.7 mmHg (–3.3 to –1.1 mmHg); p = 0.03) blood pressures; high-density lipoprotein levels [3.7 mg/dl (2.2–5.3 mg/dl); p < 0.001]; low-density lipoprotein levels [–9.6 mg/dl (–15.9 to –3.3 mg/dl); p = 0.003]; waist circumference [–3.6 cm (–4.4 to –2.9 cm); p < 0.001]; body mass index [–0.78 (–1.07 to –0.49); p < 0.001]; and C-reactive protein levels [–1.0 mg/l (–1.4 to –0.7 mg/l); p < 0.001]. Moreover, risk scores as measured by the 10-year Coronary Heart Disease UK Prospective Diabetes Study [–3.1 (–4.2 to –2.0); p < 0.001] and 10-year fatal algorithms [–2.4 (–3.3 to –1.5); p = 0.01] also improved in the EXE group. Conclusion: This type of exercise intervention (supervised and unsupervised together) is effective in improving exercise adherence, cardiorespiratory fitness and cardiovascular risk factors, while lowering HbA1c levels in patients with T2D. In contrast, although PA counselling alone may promote some increases in PA patterns, this is probably insufficient to reduce the cardiovascular risk profile in these high risk individuals. Comment: This large-scale study included several centres across Italy, thereby reducing the influence of local factors (e.g. urban vs. rural living) that are often thought to influence PA adherence. These results are promising for a 1-year intervention, with potentially better outcomes had the study continued. The study provides strong support for the combination of PA counselling with supervised training rather than counselling alone to lower HbA1c and other cardiovascular risk factors. The success in reinforcing PA through this mixed method may be applied to dietary counselling. What the study does not reveal are the social effects of interacting with other patients with diabetes on a regular basis in an exercise setting. In a large 2011 meta-analysis that compared PA counselling alone with structured exercise training with instruction, it was found that only the latter was associated with improvements in HbA1c while PA 'advice only' lowered HbA1c when combined with dietary advice (3). Another study that looked at 70 inactive T2D patients found that giving PA counselling at baseline, 6 and 9 months with follow-up calls at 1, 3, 6 and 9 months resulted in clinically significant decreases in HbA1c, blood pressure, fibrinogen and cholesterol levels (4). Thus, regular reinforcement of PA by a trained exercise counsellor, as opposed to intermittent advice during medical appointments, is probably of considerable benefit for patients with diabetes. When PA is not a familiar daily activity, we think it unreasonable to expect individuals to suddenly change sedentary behaviours after a 15-min medical appointment, once every 3 months. Kim MK, Baek KH, Song KH, Kwon HS, Lee JM, Kang MI, Yoon KH, Cha BY, Son HY, Lee KW Department of Internal Medicine, Catholic University of Korea School of Medicine, Seoul, Korea Diabetes Metab J 2011; 35 : 34–40 Background: In T2D patients, asymptomatic coronary artery disease (CAD) has higher cardiac mortality risk because CAD often becomes symptomatic at an advanced stage. In a large autopsy study of diabetic patients with asymptomatic CAD, about 50% less than 65 years and 75% older than 65 years had high-grade coronary atherosclerosis with no evidence prior to death (5). Although it is debatable whether to screen all T2D patients for asymptomatic CAD, appropriate screening criteria using an evidence-based diagnostic approach for high risk patients may identify individuals who could benefit from early detection. Aims: The aim of the study was to develop appropriate criteria for screening patients with T2D for asymptomatic CAD using a diagnostic approach of an exercise treadmill test (ETT) and then a coronary angiogram if the ETT was positive for myocardial ischaemia. Methods: T2D outpatients (n = 213) with no previous history of cardiovascular disease or severe systemic disease with poor prognosis were enrolled. The ETT was performed using the Bruce graded exercise protocol. The study also tested, using the ETT, T2D patients (n = 53) who had reported chest discomfort. Patients ceased taking beta blockers and calcium channel blockers 72 h prior to the test. A 12-lead electrocardiogram (ECG) was used during the test and blood pressure was monitored every 2 min during exercise and recovery. The ETT was considered positive when a horizontal or down-sloping ST segment with a depression ≥ 1 mm occurred 0.08 s after the J point at 85% of the predicted maximal heart rate for the patient's age. Coronary angiography was performed only when the ETT was positive. Positive asymptomatic was defined as objective evidence of ischaemia during the ETT. Flow-limiting CAD was defined as a stenosis of 70%+ on coronary angiography. Results: A total of 186 patients successfully completed the tests, with 31 (16.6%) patients with a positive ETT and 155 (83.3%) having a negative ETT. Of the 31, two had no defects on a thallium scan and six refused further evaluation. Within the remaining 23 patients, 11 patients were found to have coronary stenosis ≥ 70% via coronary angiogram. Both age (63.1 ± 9.4 years vs. 53.7 ± 10.1 years, p = 0.008) and duration of diabetes (16.0 ± 7.5 years vs. 5.5 ± 5.7 years, p < 0.001) predicted the results of the ETT and coronary angiography. When the authors analysed the results for 60+ years of age and a 10-year duration of diabetes, they found that a positive predictive value using the ETT was 87.5%. With respect to patients who presented with chest discomfort or exertional dyspnoea, 13 of the 17 patients with a positive ETT underwent coronary angiography; 10 of 13 (76.9%) of those had coronary stenosis >70%. Conclusion: The authors concluded that the ETT had a higher success rate and thus improved cost-effectiveness if used to screen for asymptomatic CAD, age ≥ 60 years with a duration of T2D ≥ 10 years. Comment: Despite some acknowledged limitations (sample size, retrospective design etc.), this study shows that the ETT is a cost-effective means for determining if CAD is present in older patients with T2D who have prolonged disease duration (>10 years). Indeed, the ETT demonstrates the heart's actual work capacity and health status more accurately than a pharmacological stress test, at least for those who can complete the exercise, and it does not expose the patient to ionising radiation. The European Society of Cardiology and International Olympic Committee recently endorsed a standardised screening evaluation method which utilises a 12-lead ECG along with a detailed history and physical examination to detect underlying causes of sudden cardiac death. The USA lacks a standardised screening system and is in need of well designed studies to demonstrate the effectiveness of the ECG for identifying underlying cardiovascular abnormalities in young athletes (6). In an assessment of appropriateness for stress echocardiography in detecting CAD in asymptomatic patients with high coronary heart disease risk, which includes anyone with diabetes, the study scored the diagnostic approach 6 out of 9 for appropriateness, with a score of 7 being considered as a generally acceptable approach (7). In a 1990 study with 136 diabetic patients, it was found that ETT for diabetic persons yielded angiographically demonstrable asymptomatic coronary heart disease in 9% (8). Based on this study's results, the use of ETT to diagnose asymptomatic CAD may be justified with its 48% success rate for all patients. As the paper notes, the best approach seems to redefine the screening protocol to patients' age ≥ 60 and with at least a decade long history of diabetes. Riddell MC, Milliken J School of Kinesiology and Health Science, Muscle Health Research Centre, Physical Activity and Diabetes Unit, York University, Toronto, ON, Canada Diabetes Technol Ther 2011; 13 : 819–25 Background: Physical activity for individuals with T1D is coupled with a risk of hypoglycaemia that can be difficult to predict, much less prevent. Symptoms of hypoglycaemia are often masked by physical activity. In order to better prevent a hypoglycaemic event, individuals with T1D must know the duration and intensity of activity beforehand to adjust insulin administration and carbohydrate intake. There are currently no guidelines on carbohydrate intake to prevent hypoglycaemia when glucose levels are within the appropriate range, but still dropping. Real-time continuous glucose monitoring (RT-CGM) offers a solution to reduce the likelihood of hypoglycaemic events for individuals during and after exercise, but only if appropriate amounts of carbohydrate are ingested during exercise. Aims: This study assessed the use of a novel carbohydrate intake algorithm to be used with RT-CGM, which takes into account both the interstitial glucose concentration and the rate at which glucose is dropping during exercise. Methods: At a youth sports camp in Canada, 25 youth (12 girls and 13 boys, 8–18 years old) with T1D participated in this field study. A baseline capillary glucose was taken each morning and intermittently throughout the day and interstitial glucose was measured with RT-CGM for 2–6 days of physical activity. The sports performed (basketball, tennis, soccer and track and field) varied from moderate to vigorous activity throughout the day. Using the RT-CGM algorithm, the researchers provided a dose of fast-acting oral carbohydrate (8 g, 16 g or 20 g) based on the measured glycaemia and the RT-CGM downward trend arrows predicting ensuing biochemical hypoglycaemia (glucose < 3.9 mml/l). Participants stopped their sporting activity if interstitial levels dropped below 5 mml/l or if they felt symptoms of hypoglycaemia. Results: Of the 25 participants, six were excluded because of sensor loss or insufficient data and one was excluded because of a hypoglycaemic event where he infused insulin on his own agency after a fast-acting oral carbohydrate intake. From the 18 volunteers included in the analyses, 35 algorithm events were captured with an average sensor use time of 2.9 days. When glucose levels were already below target (< 5.0 mmol/l) and carbohydrates were consumed, five out of 13 possible cases of mild hypoglycaemia occurred. Mild hypoglycaemia occurred only twice of 22 times when the RT-CGM alerted participants of dropping glucose levels during exercise and when the new carbohydrate intake algorithm was used. Conclusion: The use of RT-CGM with a novel carbohydrate intake algorithm that implements directional rate of change arrows appears to reduce the risk of hypoglycaemic events and helps maintain euglycaemia in physically active youth with T1D. This study also found fairly consistent glycaemic responses to fast-acting carbohydrates despite age and body size differences. of carbohydrates (8 g, 16 g) were to prevent while does g) had a more glucose response when the glucose was dropping. The algorithm is designed to glucose levels already in the In all cases when the algorithm was participants a state for 30 min carbohydrate intake and 60 min of a test group and of a control group, the are difficult to Comment: exercise have shown that patients with T1D a in interstitial glucose during and after physical exercise In the this study also more responses to higher amounts of ingested glucose g) and thus the need for glucose intake or a higher for hypoglycaemia in order to large of glucose that responses from to A June 2011 study on glucose on found that increasing the from to 5.5 the of hypoglycaemic events by with no cases of study not use a carbohydrate intake algorithm to prevent a hypoglycaemic event, but the in which the RT-CGM the may of mild hypoglycaemia for carbohydrates to be used rather than the fast-acting oral Based on this it may be that RT-CGM be to individuals with T1D with less in exercise and glycaemia or those who or change their exercise because of of with their response to exercise and glucose 1 , 1 , 1 , ST 2 , 3 , , 5 , 5 1 of Physical and University of Canada, 2 for and Health University, Canada, 3 Department of and Science, University of Canada, of Medicine, of University of Canada, and 5 of and Sciences, University of Canada Diabetes 2011; : Background: is with regular physical activity for the management of T2D. However, the studies on that with not an Both muscle and have been shown to protein and thus the oral has been an has also been shown to improve exercise tolerance in non-diabetic with clinically defined Aims: This study had (1) to examine the of on acute metabolic and responses to exercise; (2) to examine the of exercise on and (3) to examine the between and acute exercise on response to a standardised Methods: T2D volunteers and two were included in this study. The participants were between the of 30 and not taking or HbA1c blood pressure low-density lipoprotein and total high-density lipoprotein and consistent activity levels, and within the last 3 months with no to change over the of the study. The study used a design with each to (1) and no exercise; (2) and exercise; (3) and no exercise; and (4) and exercise. and conditions were given in the last 2 days of each participants were assessed for baseline glucose levels during a day by an exercise day. the participants at rest for the test exercise days, blood samples were taken during and after to 2 the exercise test. both days, metabolic outcomes such as and were measured and blood samples were Results: were higher on the exercise day compared with the day both ± vs. ± p = and after ± vs. ± p = exercise. increased heart rate and lactate levels during exercise (p and lowered the (p = 0.03) but not total response to the standardised was by but the was when exercise was (p = 0.05). In the and exercise levels were the all lactate were higher in the compared with the (p 0.05). Conclusion: and exercise increased heart higher and had no effects on the glycaemic response to the study exercise to with the of included increased and increased lactate during exercise. Comment: A study at the short-term treatment with also found that the combination of treatment with acute exercise not insulin sensitivity in insulin individuals. the combination of the two may reduce the positive effects of exercise alone While in this study it was found that increased heart a previous study with 17 participants found a significant in heart rate with The of that study are consistent that reduces (p < The authors state that the of in glucose on the exercise days not the use of exercise as a treatment While has no glycaemic benefit when used with exercise, this study that it may be to the of exercise and to glycaemic N Hospital, USA Diabetes 2011; : Aims: The aim of this study was to about the diabetes management of athletes with and then to these with the physical activity performed by individuals with T1D. Methods: A total of athletes and 18 and older with T1D participated in this study. Participants were to complete an that of their carbohydrate insulin insulin range, exercise and The were from on the of athletes with T1D and the own with athletes with diabetes. The of participants they guidelines on exercise and diabetes. A to the was on the Diabetes Exercise and from 20 to 20 Results: participants of of participants to to when their while reported not the guidelines and they not the With to clinical for athletes with participants reported following about of the or per of they the or of the When duration of exercise was into h and more than showed that the of blood glucose increased with duration of exercise (p = of blood glucose to the following 1, 3, of the h of exercise, this value was ± the value was ± more than h of exercise, the value increased to ± of the participants reported that they not decrease their insulin on exercise days. Of the athletes who reduce (n = it by at least However, data not reveal a between of insulin and the of blood who carbohydrate prior to exercise when their blood glucose was less than mg/dl reported of hypoglycaemia h after exercise compared with those who or However, these results were not significant (p = While of the participants for monitoring blood glucose and after exercise, only participants reported monitoring glucose during exercise. of athletes who completed the that they exercise when their blood glucose is mg/dl or one of the significant from this study was that duration of exercise increases the likelihood of blood glucose in individuals with T1D. This was given that during exercise glucose to glucose in patients with T1D who not lower their insulin data from this study that reducing insulin levels on days of exercise helps to decrease the of hypoglycaemia during the In to lowering insulin levels, the also of carbohydrates during and after exercise to prevent the of hypoglycaemia While the of this study are consistent with the results were not from those who not lower insulin of these athletes that they the to blood glucose during exercise, and of to with high blood glucose The that athletes exercise with blood glucose higher than mg/dl if are present in the and if are no present they exercise with a high of with high blood glucose may be by the that athletes with in order to prevent hypoglycaemia. Comment: While physical activity insulin sensitivity and improved metabolic it also which is a for the less insulin in response to prolonged aerobic exercise. However, athletes who on exogenous insulin often and hypoglycaemia as a of not lowering their insulin prior to exercise. The risk of hypoglycaemia may last for h due to increased insulin sensitivity that helps to muscle and

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