Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

PURPOSE: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. MATERIALS AND METHODS: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. RESULTS: Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). CONCLUSION: A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study.

ELITE: rationale and design of a longitudinal elite athlete, extreme cardiovascular phenotyping, prospective cohort study.

Introduction: The cardiovascular benefits of physical exercise are well-known. However, vigorous exercise has also been associated with adverse cardiac effects. To improve our understanding of cardiovascular adaptation to exercise versus maladaptation and pathology, the limits of adaptation should be firmly established using state-of-the-art diagnostic modalities. We therefore initiated the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise (ELITE) cohort to investigate the longitudinal (beneficial and pathological) cardiovascular effects of intensive elite sports and exercise. Methods and analysis: ELITE is a prospective, multicentre, longitudinal cohort study. Elite athletes, from the age of sixteen, are recruited in The Netherlands. The primary objective is to determine the association between elite sports and exercise-induced cardiac remodelling, cardiac pathology, and health benefits over time. Secondary objectives include determining and identifying genetic profiles of elite athletes, and how these are associated with cardiac indices. ELITE will collect data from consultations, electrocardiography, echocardiography and cardiac magnetic resonance imaging, and training- and injury data. ELITE will also collect blood for biobanking and cardiogenetics. Follow-up will take place at intervals of two to five years, and after the elite athletes' professional careers have ended. In addition, a subcohort of ELITE has been established to investigate cardiac sequelae following infections associated with myocardial involvement, including SARS-CoV-2. ELITE is a prospective observational study; therefore, analyses will be primarily explorative. Ethics and dissemination: This study has been approved by the Medical Ethics Review Board of the Amsterdam University Medical Centers (NL71682.018.19). The results of the study will be disseminated by publication in peer-reviewed journals (Netherlands Trial Register number: NL9328).

Physical activity at altitude: challenges for people with diabetes: a review.

BACKGROUND: A growing number of subjects with diabetes take part in physical activities at altitude such as skiing, climbing, and trekking. Exercise under conditions of hypobaric hypoxia poses some unique challenges on subjects with diabetes, and the presence of diabetes can complicate safe and successful participation in mountain activities. Among others, altitude can alter glucoregulation. Furthermore, cold temperatures and altitude can complicate accurate reading of glucose monitoring equipment and storage of insulin. These factors potentially lead to dangerous hyperglycemia or hypoglycemia. Over the last years, more information has become available on this subject. PURPOSE: To provide an up-to-date overview of the pathophysiological changes during physical activity at altitude and the potential problems related to diabetes, including the use of (continuous) blood glucose monitors and insulin pumps. To propose practical recommendations for preparations and travel to altitude for subjects with diabetes. DATA SOURCES AND SYNTHESIS: We researched PubMed, medical textbooks, and related Internet sites, and extracted human studies and data based on relevance for diabetes, exercise, and altitude. LIMITATIONS: Given the paucity of controlled trials regarding diabetes and altitude, we composed a narrative review and filled in areas lacking diabetes-specific studies with data obtained from nondiabetic subjects. CONCLUSIONS: Subjects with diabetes can take part in activities at high, and even extreme, altitude. However, careful assessment of diabetes-related complications, optimal preparation, and adequate knowledge of glycemic regulation at altitude and altitude-related complications is needed.

Metabolic effects of high altitude trekking in patients with type 2 diabetes.

OBJECTIVE: Limited information is available regarding the metabolic effects of high altitude trekking in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirteen individuals with type 2 diabetes took part in a 12-day expedition to the summit of Mount Toubkal (altitude, 4,167 m), Morocco, after 6 months of exercise training. Energy expenditure, body weight, blood glucose, fasting insulin, lipids, and HbA(1c) were assessed. RESULTS: Training reduced fasting glucose (-0.7 ± 0.9 mmol/L, P = 0.026) and increased exercise capacity (+0.3 ± 0.3 W/kg, P = 0.005). High altitude trekking decreased fasting insulin concentrations (-3.8 ± 3.2 µU/L, P = 0.04), total cholesterol (-0.7 ± 0.8 mmol/L, P = 0.008), and LDL cholesterol (-0.5 ± 0.6 mmol/L, P = 0.007). CONCLUSIONS: High altitude trekking preceded by exercise training is feasible for patients with type 2 diabetes. It improves blood glucose, lipids, and fasting insulin concentrations, while glucose control is maintained.

Increased insulin requirements during exercise at very high altitude in type 1 diabetes.

OBJECTIVE: Safe, very high altitude trekking in subjects with type 1 diabetes requires understanding of glucose regulation at high altitude. We investigated insulin requirements, energy expenditure, and glucose levels at very high altitude in relation to acute mountain sickness (AMS) symptoms in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eight individuals with complication-free type 1 diabetes took part in a 14-day expedition to Mount Meru (4,562 m) and Mount Kilimanjaro (5,895 m) in Tanzania. Daily insulin doses, glucose levels, energy expenditure, and AMS symptoms were determined. Also, energy expenditure and AMS symptoms were compared with a healthy control group. RESULTS: We found a positive relation between AMS symptoms and insulin requirements (r = 0.78; P = 0.041) and AMS symptoms and glucose levels (r = 0.86; P = 0.014) for Mount Kilimanjaro. Compared with sea level, insulin doses tended to decrease by 14.2% (19.7) (median [interquartile range]) (P = 0.41), whereas glucose levels remained stable up to 5,000 m altitude. However, at altitudes >5,000 m, insulin dose was unchanged (36.8 ± 17 vs. 37.6 ± 19.1 international units [mean ± SD] P = 0.75), but glucose levels (7.5 ± 0.6 vs. 9.5 ± 0.8 mmol/L [mean ± SD] P = 0.067) and AMS scores (1.3 ± 1.6 vs. 4.4 ± 4 points [mean ± SD] P = 0.091) tended to increase. Energy expenditure and AMS symptoms were comparable in both groups (P = 0.84). CONCLUSIONS: Our data indicate that in complication-free individuals with type 1 diabetes, insulin requirements tend to increase during altitudes above 5,000 m despite high energy expenditure. This change may be explained, at least partly, by AMS.

Accuracy of handheld blood glucose meters at high altitude.

BACKGROUND: Due to increasing numbers of people with diabetes taking part in extreme sports (e.g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior studies reported bias in blood glucose measurements using different BGMs at high altitude. We hypothesized that glucose-oxidase based BGMs are more influenced by the lower atmospheric oxygen pressure at altitude than glucose dehydrogenase based BGMs. METHODOLOGY/PRINCIPAL FINDINGS: Glucose measurements at simulated altitude of nine BGMs (six glucose dehydrogenase and three glucose oxidase BGMs) were compared to glucose measurement on a similar BGM at sea level and to a laboratory glucose reference method. Venous blood samples of four different glucose levels were used. Moreover, two glucose oxidase and two glucose dehydrogenase based BGMs were evaluated at different altitudes on Mount Kilimanjaro. Accuracy criteria were set at a bias <15% from reference glucose (when >6.5 mmol/L) and <1 mmol/L from reference glucose (when <6.5 mmol/L). No significant difference was observed between measurements at simulated altitude and sea level for either glucose oxidase based BGMs or glucose dehydrogenase based BGMs as a group phenomenon. Two GDH based BGMs did not meet set performance criteria. Most BGMs are generally overestimating true glucose concentration at high altitude. CONCLUSION: At simulated high altitude all tested BGMs, including glucose oxidase based BGMs, did not show influence of low atmospheric oxygen pressure. All BGMs, except for two GDH based BGMs, performed within predefined criteria. At true high altitude one GDH based BGM had best precision and accuracy.

A comparison of two invasive strategies in patients with non-ST elevation acute coronary syndromes: results of the Early or Late Intervention in unStable Angina (ELISA) pilot study. 2b/3a upstream therapy and acute coronary syndromes.

BACKGROUND: Only few studies specifically addressed the effect of timing of angiography and/or pre-treatment with a glycoprotein 2b/3a receptor blocker in patients with non-ST elevation acute coronary syndromes (ACS) who undergo invasive treatment. METHODS: In a 2-year period, 220 patients with non-ST elevation ACS, were randomized to early angiography without tirofiban pre-treatment (Early strategy) or to delayed angiography after 24-48h pre-treatment with tirofiban (Late strategy). The first 48h after admission, CKmb levels were measured and enzymatic infarct size (LDHQ(48)) was assessed by the area under the LDH release curve. When PCI was performed beyond 48h, CKmb was measured 6 and 12h afterwards. RESULTS: Median time to angiography was 6 (Early) and 50 (Late) hours. PCI was performed in 130 patients (59%). In these patients, a patent (TIMI 2 or 3 flow) culprit vessel was more often present in the Late group compared to the Early group (66% vs 82% p=0.05). In patients with an elevated CKmb (n=96, 44%), LDHQ(48)was significantly lower in patients who underwent angiography after pre-treatment with tirofiban (629+/-503U/L (Early) vs 432+/-441U/L (Late), p=0.02). No difference in clinical outcome between the groups was observed at 30 days follow-up. CONCLUSION: This pilot study showed that a strategy of delayed angiography with concomitant pre-treatment with tirofiban is associated with improved angiographic outcomes and less initial enzyme release, compared to a strategy of immediate angiography without 2b/3a inhibitor pre-treatment. The use of an end point parameter, which assess total enzyme release over a given period of time, might be of special value in patients with non-ST elevation ACS, who undergo very early invasive treatment.