Cholinergic-induced sweat rate during hypo- and hyperglycemia.

ABSTRACT

The purpose of this study was to measure the in vivo cholinergic-induced sweat rate during hypoglycemia, euglycemia and hyperglycemia. A healthy 49-year-old, male with type 1 diabetes served as the subject. During a two-month period, he reported to the laboratory on 18 separate days. Six times he reported with his blood glucose in the euglycemic range (4.4-6.6 mmol x [L.sup.-1]), six times in the hypoglycemic range (< 4.0 mmol x [L.sup.-1]), and six times in the hyperglycemic range (>11.0 mmol x [L.sup.-1]). Peripheral sweat rate was measured each visit using pilocarpine iontophoresis. The mean [+ or -] SD cholinergic-induced sweat rates were 9.0 [+ or -] 1.4, 7.3 [+ or -] 1.0, and 10.4 [+ or -] 1.4 mg x [m.sup.2] x [min.sup.-1] for the euglycemic, hypoglycemic, and hyperglycemic trials, respectively. These values were all significantly (p < .05) different from each other. The results suggest that blood glucose concentration can affect sweat capacity. However, even during hypoglycemia, there appears to be enough glucose to maintain a relatively high sweat production. This supports previous clinical observations that hypoglycemia can be accompanied by excessive sweating.

Keywords: hypoglycemia, sweat rate, pilocarpine, hyperhydrosis

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It has been shown that the major energy source used by the eccrine sweat gland is glucose. For example, cholinergic-induced sweating in isolated monkey eccrine sweat glands is reduced 97% when stimulated in a glucose-free medium vs. the control condition (6). Furthermore fatty acids and citric acid cycle intermediates do not support sweat production in vitro (5). The above findings, however, are somewhat contradictory with clinical observations that hypoglycemia is universally accompanied by excessive sweating (1,2,4). It would seem reasonable to hypothesize that hypoglycemia should depress sweating by reducing the primary energy source of the eccrine glands. In light of the above findings, it was the purpose of this study to measure the in vivo pilocarpine-induced sweat rate during hypoglycemia, euglycemia, and hyperglycemia. This technique allowed us to measure sweat gland function independent of the increased sympathetic stimulation usually associated with hypoglycemia.

METHODS

The subject for this study was a healthy 49-year-old male with type 1 diabetes. He was 170 cm tall and weighed 72 kg. He had been a type 1 diabetic for the last 26 years and currently used an insulin pump (MiniMed-508) to regulate his blood glucose. The study was approved by the San Diego State University IRB.

During a 2-month period the subject reported to the laboratory on 18 separate days at approximately 9 am. Six times he reported with his blood glucose in the euglycemic range (4.4-6.6 mmol x [L.sup.-1]), six times in the hypoglycemic range (< 4.0 mmol x [L.sup.-1]), and six times in the hyperglycemic range (>11 mmol x [L.sup.-1]). The order was randomized. Manipulation of the blood glucose level was achieved by the subject via increasing or decreasing his insulin dose. Blood glucose was measured using a glucometer (Lifescan Ultra) immediately prior to sweat collection.

Peripheral sweat rate was determined using pilocarpine iontophoresis on the flexor surface of both arms and the two values were averaged. The iontophoresis current was fixed as 1.5 mA for 5 minutes. Pilocarpine was delivered via reagent-impregnated (0.5%) solid agar gel discs using a Wescor (Logan, UT) model 3700 inducer. Sweat was collected for 15 minutes immediately following iontophoresis using macroduct sweat collectors (Wescor) according to the procedures outlined by Webster (7). Sweat rate was expressed in mg x [m.sup.2] x [min.sup.-1].

Mean blood glucose and peripheral sweat rate for the three trials were statistically compared using a repeated measures ANOVA and Tukey's post hoc comparisons. Significance was set at the p < .05 level.

RESULTS

The mean [+ or -] SD blood glucose concentration during the euglycemic, hypoglycemic, and hyperglycemic trials was 5.9 [+ or -] 0.7, 3.3 [+ or -] 0.4, and 12.6 [+ or -] 1.8 mmol x [L.sup.-1], respectively. These values were all significantly different. The mean peripheral sweat rate for the euglycemic, hypoglycemic and hyperglycemic conditions was 9.0 [+ or -] 1.4, 7.3 [+ or -] 1.0, and 10.4 [+ or -] 1.4 mg x [m.sup.2] x [min.sup.-1], respectively. Again all three values were significantly different.

DISCUSSION

The major finding of the current study was that hypoglycemia significantly reduced cholinergic-induced sweat rate in the one subject tested. This supports previous findings that blood glucose is a major energy source used by eccrine sweat glands (5,6). Surprising, however, was the fact that a 44% reduction in blood glucose during the hypoglycemic trial vs. the euglycemic trial (from 5.9 to 3.3 mmol x [L.sup.-1]) reduced peripheral sweat rate by only 19%. This suggests that the relationship between blood glucose concentration and sweat production is not linear. Thus, although the current study reduced blood glucose to 3.3 mmol x [L.sup.-1] (60 mg x d[L.sup.-1]), it appears that was sufficient to maintain a relatively high sweat production. It is hypothesized that more severe levels of hypoglycemia might significantly depress sweating by reducing the primary energy source.

The results of the current study also support the clinical observations that hypoglycemia is usually associated with excessive sweating. For example, Maggs et al. (3) reported that insulin-induced hypoglycemia (2.5 mmol x [L.sup.-1]) caused a significant four-fold increase in abdominal sweat rate. In that study, hypoglycemia increased sympathetic stimulation as evidenced by a significant elevation in plasma epinephrine levels.

The following scenario seems plausible concerning sweat production during hypoglycemia. The reduced blood glucose levels negatively affect sweating capacity; however, there is still sufficient fuel to produce a significant sweat rate in response to intense sympathetic stimulation.

Another interesting finding of the current study was that pilocarpine-induced sweat rate was significantly increased during hyperglycemia. To our knowledge this is the first time this has been reported in the literature. Such a result suggests that blood glucose is a limiting factor for sweat production during euglycemia. Since it is assumed that glucose uptake in eccrine sweat glands is the result of facilitated diffusion, hyperglycemia could increase delivery to the interior of the cells. Further work to examine if hyperglycemia would increase sweat production during exercise would seem warranted.

In conclusion, the current study suggests that even during hypoglycemia, there appears to be enough glucose to maintain a relatively high sweat production. Thus, glucose starvation at the level of the eccrine sweat gland should probably not be a concern for clinicians working with diabetic populations. However, as this was a case study, further work with additional subjects is needed before generalization is possible to the population of people with type 1 diabetes.

REFERENCES

(1.) Ebihara, A., K. Konda, K.Ohashi, K. Kosaka, T. Kuzuya, and A. Matsuda. Comparative clinical pharmacology of human insulin and porcine insulin in normal subjects. Diabetes Care 6(Suppl. 1):17-22, 1983.

(2.) Harris, N. D., S. B. Baykoucher, J. L. Marques, T. Cochrane, E. George, S. R. Heller, S. R., and J. D. Ward. A portable system for monitoring physiological responses to hypoglycemia. J. Med. Eng. Technol. 20:196-202, 1996.

(3.) Maggs, D. G., A. R. Scott, and I. A. MacDonald. Thermoregulatory responses to hyperinsulinemic hypoglycemia and euglycemia in humans. Am. J. Physiol. 267:R1266-R1272, 1994.

(4.) Robertshaw, D. Hyperhydrosis and the sympatho-adrenal system. Med. Hypothesis. 5:317-322, 1979.

(5.) Sato, K. The mechanism of eccrine sweat secretion. In: Perspectives in Exercise Science and Sports Medicine. Vol. 6. C. V. Gisolfi, D. R. Lamb, and E. R. Nadel. eds. Carmel, IN: Cooper Publishing Group, 1993:85-117.

(6.) Sato, K., and R. L. Dobson. Glucose metabolism of the isolated eccrine sweat gland. J. Clin. Invest. 52:2166-2174, 1973.

(7.) Webster, H. L. Laboratory diagnosis of cystic fibrosis. In: CRC Critical Reviews in Clinical Laboratory Sciences. Boca Raton, FL: CRC, 1983:313-338

Michael J. Buono and Larry S. Verity

Exercise and Nutritional Sciences Department, San Diego State University, San Diego, CA 92182

Address Correspondence to:

Michael J. Buono, Ph.D.

MC-7251

San Diego State University

San Diego, CA 92182

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