Metabolic Effects of High Altitude Trekking in Patients With Type 2 Diabetes

Thirteen complication-free, nonsmoking subjects (8 men, 5 women) with type 2 diabetes participated in a 12-day trekking expedition to Mount Toubkal (altitude, 4,167 m), Morocco (4). Participants’ characteristics were age, 48.2 ± 9.7 years; diabetes duration, 6.3 ± 3.9 years; HbA_1c, 6.6 ± 0.8%; and BMI, 27.5 ± 4.1 kg/m². Antihyperglycemic medication consisted of metformin (n = 8), a sulfonylurea derivant (n = 4), dipeptidyl peptidase-4 (n = 1), thiazolidinedione (n = 1), and insulin (n = 3).

Participants underwent a physical examination, maximal cycle ergometer testing, electrocardiography, echocardiography, and laboratory tests at baseline (day −270) and received a written training program at the start of the training period (day −180). Cycle ergometer and laboratory tests were repeated at day 0.

Participants recorded energy expenditure (SenseWear Pro Armband, Bodymedia) and fasting capillary glucose (AccuChek Compact Plus, Roche Diagnostics), and used a continuous blood glucose monitoring system (Paradigm MiniMed, Medtronic) during 1 week every month (from day −60 onwards) at sea level and continuously at altitude.

Fasting glucose and plasma insulin were determined on days −150, 0, 9, and 12, and homeostasis model assessment of insulin sensitivity (HOMA-IR) was calculated (5). Insulin users were excluded from HOMA-IR and fasting glucose analyses. HbA_1c and lipids were determined on days −270, −150, 0, and 12.

At altitude, acute mountain sickness (AMS) symptoms were scored daily using the Lake Louise Questionnaire.

The research protocol was approved by the Isala Clinics ethics committee, Zwolle, the Netherlands. Subjects gave written informed consent.

SPSS software (SPSS, Inc.) was used for statistical analysis. A P value of <0.05 was considered statistically significant.

During the training period, the dose of antihyperglycemic medication (insulin or tablets) was stopped in two subjects (one sulfonylurea derivant and one thiazolidinedione) and reduced in five subjects. Energy expenditure increased from 2,997 ± 386 to 3,361 ± 358 kcal/day (day −180 vs. −60, P = 0.01; Fig. 1). Fasting glucose decreased from 7.6 ± 1.5 to 6.9 ± 1.2 mmol/L (P = 0.026), whereas maximal workload increased from 2.6 ± 0.8 to 2.9 ± 0.8 W/kg (day −180 vs. 3, P = 0.003).

Fasting plasma triglycerides decreased from 2.2 ± 0.9 to 1.6 ± 0.6 mmol/L (day −270 vs. day 0, P = 0.025), whereas LDL (2.3 ± 1.0 mmol/L), HDL (1.4 ± 0.6 mmol/L), and total cholesterol (4.6 ± 1.1 mmol/L) did not change. HbA_1c, HOMA-IR, and body weight remained unchanged (P = 0.27; day −180 vs. day 0).

All participants summited Mount Toubkal (altitude, 4,167 m), and AMS scores remained low (Fig. 1). During the expedition, mean fasting glucose was lower in the second half compared with the first half at altitude (7.1 ± 1.2 vs. 6.6 ± 0.9 mmol/L, P = 0.022) but did not differ from sea level (6.9 ± 1.2 mmol/L; Fig. 1).

The area under the curve for glucose and the time (median ± interquartile range) at sea level versus altitude in hyperglycemia (74 ± 251 vs. 147 ± 388 min/day, P = 0.20) and hypoglycemia (0 ± 29 vs. 0 ± 66, P = 0.43) remained unchanged.

HOMA-IR at 3,200-m altitude (day 9: 1.9 ± 0.8) was decreased compared with lower altitudes (day 12: 2.7 ± 1.2, P = 0.024; day 0: 3.8 ± 1.8, P = 0.013).

High altitude trekking led to decreased cholesterol (4.5 ± 1.3 vs. 3.8 ± 1.8; P = 0.008) and LDL cholesterol (2.5 ± 1.0 vs. 1.9 ± 0.7 mmol/L; P = 0.007) on day 0 vs. day 12; triglycerides and HDL remained unchanged.

Energy expenditure increased at altitude and peaked on days of largest altitude gain (Fig. 1). Body weight remained stable.

Our study indicates that patients with complication-free type 2 diabetes can safely take part in high altitude trekking after adequate preparation.

The results of the training period showed reductions in triglycerides and fasting glucose, while workload capacity increased and body weight remained stable. These effects are generally in line with previous studies (6–8) and most likely associated with the increase in physical activity, as reflected by the energy expenditure. That HbA_1c did not change is probably explained by the already low values at inclusion and the reduction in medication. These facts and the small sample size might also explain the unchanged HOMA-IR at sea level.

During the expedition, HOMA-IR and lipids decreased, while body weight, blood glucose, and food intake (data not shown) remained stable.

Exposure to high altitude can initially lead to higher levels of insulin, glucose, and counter-regulatory hormones, possibly related to AMS (9–11), which typically occurs at altitudes above 3,000 m (12,13). In our study, mean glucose and time in hyper- and hypoglycemia remained stable, consistent with absent glycemic deregulation at altitude. The gradual ascent, and the fact that we only resided at altitudes above 3,000 m on days 8–11, could explain the stable glucose profiles and low AMS scores.

The lower HOMA-IR at 3,200 m was driven by a drop in fasting insulin. Because insulin users were excluded from analyses and antihyperglycemic medication and dietary intake remained unchanged, the most likely explanation is increased exercise-stimulated glucose uptake. However, in the absence of a direct measure of insulin sensitivity, increased insulin- or hypoxia-stimulated glucose uptake cannot be excluded (14).

Our study implies that there are no objections for subjects with complication-free type 2 diabetes and normal results on cardiac exercise tests to participate in high altitude trekking. Regarding glycemic control, we would consider any subject with type 2 diabetes capable of safely exercising at high altitude, irrespective of the type of hypoglycemic medication.

This study has limitations. Because of the uncontrolled study design, it is not clear whether the improved fasting glucose and HOMA-IR were due to the increased energy expenditure, to the hypoxic conditions at altitude, or to other factors. HOMA-IR is validated for studies with large samples (15), so these results should be interpreted with caution. The research setting precluded the use of direct measures of insulin sensitivity and limited the number of patients.

In conclusion, high altitude trekking is feasible for subjects with type 2 diabetes after a preparatory training phase. Beyond the objective improvement in blood glucose, lipids, and fasting insulin, the successful accomplishment of a summit may have substantial beneficial psychologic effects.

The Bas van de Goor Foundation, the Netherlands, provided support and funding of the expedition. Medtronic, Heerlen, the Netherlands, and APC Cardiovascular, Belfeld, the Netherlands, provided glucose and energy-expenditure monitoring equipment.

P.d.M. wrote the study protocol, researched the data, and wrote the manuscript. M.J.F. and S.T.d.V. contributed to the study design and data collection, researched the data, and reviewed the manuscript. E.J.P.d.K. and H.J.G.B. contributed to the study design and reviewed and edited the manuscript. B.D.D. contributed to the study design, researched the data, and reviewed and edited the manuscript. R.O.B.G. contributed to the study design and reviewed and edited the manuscript. C.J.T. contributed to, reviewed, and edited the manuscript. P.d.M. is the guarantor of this work and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors thank Snow Leopard Travels, the Netherlands, and local porters and guides for expedition logistics and support, and all participants for their participation in this study.

Some results of this study were presented in abstract form as poster presentation at and appear in the abstract book of the 47th European Association for the Study of Diabetes Annual Meeting, Lisbon, Portugal, 12–16 September 2011.