Hyperosmolar hyperglycemic state in advanced amyotrophic lateral sclerosis

Abstract

Our objective was to describe cases of hyperosmolar hyperglycemic state (HHS) in advanced amyotrophic lateral sclerosis (ALS) patients and discuss its pathophysiology. Five ventilator-dependent patients with ALS, with no previous history of diabetes, showed development of marked hyperglycemia (plasma glucose levels of 755–1544 mg/dl) after preceding infectious episodes. All patients had severe generalized muscle wasting and tetraplegia. The initial manifestations of HHS were fever, drowsiness, or polyuria. Hydration and intravenous insulin therapy were markedly effective, resulting in favorable recovery without the necessity of chronic medication for hyperglycemia in all cases. Seventy-five grams oral glucose tolerance tests performed via feeding tubes in two patients after the successful treatment of HHS revealed increased insulin resistance and diminished early-phase insulin secretion with preserved total insulin secretion. In conclusion, a marked loss of skeletal muscle, the largest glucose consumer of the human body, with background abnormality of early-phase insulin secretion, might be a causative factor of HHS in advanced ALS.

Key words::

• Amyotrophic lateral sclerosis
• hyperosmolar hyperglycemic state
• insulin resistance
• insulin secretion
• totally locked-in state

Acknowledgements

This work was supported in part by a grant-in-aid for Scientific Research on Pathomechanisms of ALS from the Tokyo Metropolitan Organization for Medical Research, and in part by a grant for research on the ‘Quality of Life for Patients with Intractable Diseases’ from the Ministry of Health, Labor and Welfare of Japan.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.