Awakening and Counterregulatory Response to Hypoglycemia During Early and Late Sleep

  1. Kamila Jauch-Chara1,
  2. Manfred Hallschmid2,
  3. Steffen Gais2,
  4. Kerstin M. Oltmanns3,
  5. Achim Peters1,
  6. Jan Born2 and
  7. Bernd Schultes14
  1. 1Department of Internal Medicine I, University of Luebeck, Luebeck, Germany
  2. 2Department of Neuroendocrinology, University of Luebeck, Luebeck, Germany
  3. 3Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany
  4. 4Interdisciplinary Obesity Center, Kantonsspital St. Gallen, St. Gallen, Switzerland
  1. Address correspondence and reprint requests to Bernd Schultes, MD, Interdisciplinary Obesity Center, Kantonsspital St. Gallen, Heidenerstr. 11, 9400 Rorschach, Switzerland. E-mail: schultes{at}


OBJECTIVE—Nocturnal hypoglycemia represents an important problem for diabetic patients, which has been primarily attributed to an attenuated hormonal counterregulation during sleep. So far, hypoglycemia counterregulation has been exclusively examined during early nocturnal sleep, although early sleep differs markedly in sleep stage architecture from late sleep. Here, we investigated whether awakening and counterregulatory responses differ between early and late sleep.

RESEARCH DESIGN AND METHODS—Sixteen healthy subjects were tested on three occasions. On two nights, a linear fall in plasma glucose to a nadir of 2.2 mmol/l within 60 min was induced by insulin infusion. On one night, this was done immediately after sleep onset and on the other night after ∼3.5 h of sleep. In a further control night, no hypoglycemia was induced.

RESULTS—During early sleep, 10 subjects awoke in response to hypoglycemia, whereas no subject awoke during the corresponding interval of the control night (P < 0.004). During late sleep, all subjects awoke upon hypoglycemia, and four subjects awoke spontaneously during the corresponding control interval (P < 0.001). The pattern indicates that the frequency of awakenings caused by hypoglycemia is similar for early and late sleep. Increases in epinephrine, norepinephrine, ACTH, cortisol, and growth hormone were distinctly weaker during late than early hypoglycemia (all P < 0.05).

CONCLUSIONS—Diminished hormonal counterregulation during late sleep could be one factor contributing to the clinically observed accumulation of hypoglycemic episodes in the later part of the night in patients with diabetes.


  • Published ahead of print at on 27 March 2007. DOI: 10.2337/db07-0044.

  • Additional information for this article can be found in an online appendix at

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 19, 2007.
    • Received January 11, 2007.
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