This study investigated the relationships among daily insulin doses, glucose profiles, and AMS symptoms in response to exercise at very high altitude in subjects with complication-free type 1 diabetes. As anticipated, insulin doses initially tended to decrease while glucose levels remained fairly stable at altitude. However, during the final ascent (day 12), glucose levels increased sharply in parallel to an increase in AMS scores but insulin doses did not change. Taken together, these results are in accordance with an increased insulin requirement when extreme altitudes (>5,000 m) are reached (day 12). On the final ascent, the increments in AMS symptoms and mean glucose are borderline significant. However, the significant increase in time in hyperglycemia and the positive relations between AMS and mean glucose levels, and AMS and insulin doses, support the notion of increased insulin requirements at extreme altitude, possibly related to AMS.
The increased glucose levels (day 12) cannot be attributed to an increased carbohydrate intake, because higher anorexia scores on the Lake Louise Questionnaire suggested markedly reduced caloric intake at altitudes >4,500 m (data not shown). In addition, reduced exercise-stimulated glucose uptake is unlikely because energy expenditure increased in response to exercise at altitude. The fact that increments in glucose, together with unchanged insulin doses, were accompanied by parallel increments in AMS scores suggests a shared causative factor.
Even after partial restoration of glucoregulatory hormone levels because of acclimatization, ascent to higher altitudes will elicit increments in gluco-counterregulatory hormones (3
). Furthermore, AMS in itself is related to increments of counter regulatory hormones (7
). Therefore, it seems likely that after an initial acclimatization to altitudes of up to ± 4,500 m, increments in AMS and altitude on day 12, again, induced a state of insulin resistance by increments in counterregulatory hormones.
Previous expeditions with individuals with type 1 diabetes have shown diverging results (8
). Moore et al. (10
) have reported decrements in insulin doses on Mount Kilimanjaro of up to 50%. This expedition had a very low summit success rate and was complicated by cases with keto-acidosis. This suggests insulin underdosing. In our study, insulin dose was initially decreased by approximately 15–20% (). However, it is likely that above a critical altitude of approximately 5,000 m this decreased insulin dose becomes inadequate as glucose levels increase. A critical altitude of approximately 5,000 m might also explain why for Mount Meru we did not find a relation between AMS and glucose levels.
Admettla et al. (9
) found increased insulin requirements at altitudes above 5,000 m when adjusting for carbohydrate intake in a group of type 1 diabetic climbers on Mount Aconcagua (6,962 m). Pavan et al. (8
) reported increased insulin requirements in eight climbers with type 1 diabetes on Mount Cho Oyu (8,201 m) and increased HbA1c
levels in type 1 diabetic subjects and healthy controls after this 39-day expedition. Thus, most reported studies seem to be in line with the concept that at extreme (>5,500 m) and even very high (3,500–5,000 m) altitudes, glucose levels and insulin requirements increase despite the high energy expenditure and lower carbohydrate intake.
Our study has clinical implications. At very high altitude, we would recommend climbers with type 1 diabetes to maintain or only slightly decrease insulin doses despite strenuous exercise and reduced caloric intake. Also, if more symptoms of AMS occur, one should expect to see an increase in insulin requirements.
Although the use of acetazolamide is not recommended in patients with type 1 diabetes because of the perceived risk for keto-acidosis (9
), six of eight subjects with diabetes in our study used the drug without any complications.
This study has limitations. First, we did not monitor caloric intake because we were not informed in advance what type of food would be provided. Also, it was difficult to estimate carbohydrate contents of local foods. However, higher anorexia scores on the Lake Louise Questionnaire suggests markedly reduced caloric intake at altitudes >4,500 m. Furthermore, because of ethical and financial constraints, it was not feasible to use CGM devices to measure glucose continuously in the control group. Insulin requirements can hardly be determined in subjects without diabetes while exercising at very high altitude. Therefore, it was not possible to compare between groups for insulin requirements and glucose levels.
Second, acetazolamide, which was used by ±75% of all subjects in both groups, could have influenced AMS scores and insulin doses at very high altitude. Acetazolamide helps to prevent AMS and thus could attenuate counterregulatory hormonal responses associated with high altitude and AMS. As far as we know, this has not been investigated in humans, so the degree of interference remains speculative. Because of the small number of subjects who did not use acetazolamide (), we could not statistically analyze whether acetazolamide use influenced insulin requirements or not. However, we could not discover any consistent pattern between acetazolamide users and nonusers regarding insulin requirements. Finally, we were unable to measure counterregulatory hormone levels because of local limitations of blood sampling, handling, and storage.
One strength of our study is the use of continuous measurement of energy expenditure and glucose monitoring at very high and extreme altitudes, which provides detailed information on glucose trends and exercise intensity. Furthermore, CGM proved to function well at very high altitudes and provides the subjects with diabetes with instant access of actual glucose levels and trends.
In summary, in individuals with type 1 diabetes, insulin requirements tend to increase during very high altitude trekking despite high energy expenditure and reduced caloric intake. This change may be explained, at least partly, by AMS. The role of AMS and counterregulatory hormones warrants further investigation.