TY - JOUR
T1 - Insulin-mediated hypokalemia and paralysis in familial hypokalemic periodic paralysis
AU - Minaker, Kenneth L.
AU - Meneilly, Graydon S.
AU - Flier, Jeffrey S.
AU - Rowe, John W.
N1 - Funding Information:
From the Charles A. Dana Research Institute and the Harvard Thorndike Laboratory of the Beth Israel Hospital, Department of Medicine, Beth Israel Hospital, Division of Aging, Harvard Medical School, and the Geriatric Research Education Clinical Center, West RoxburyIBrockton Veterans Administration Medical Center, Boston, Massachusetts. This work was supported in part by United States Public Health Service Grant AG-00599, National Institutes of Health Grant AM-28082-03, and General Clinical Research Centers Grant RR-01032. Dr. Minaker is the recipient of the Greenwall Foundation Award from the American Federation for Aging Research. Dr. Flier is the recipient of Research Career Development Award AM-00856-02 from the National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases. Dr. Meneilly is a fellow of the Medical Research Council of Canada. Dr. Rowe is the recipient of an award from the John D. and Catherine T. MacArthur Foundation. Requests for reprints should be addressed to Dr. Kenneth L. Minaker, Gerontology Division, Beth Israel Hospital, 330 Brookline Avenue, Boston, Massachusetts 02215. Manuscript submitted October 15, 1987, and accepted in revised form March 28, 1988.
PY - 1988/6
Y1 - 1988/6
N2 - To elucidate a potential role for insulin-mediated extra-renal potassium disposal in the clinical syndrome of hypokalemic periodic paralysis, an obese affected man was studied using the euglycemic insulin clamp, which, in normal and obese subjects, produces predictable, insulin dose-dependent declines in plasma potassium levels. During a 20 mU/m2/minute euglycemic clamp (insulin level, 88 μU/ml) procedure, while the patient with hypokalemic periodic paralysis demonstrated severe resistance to insulin-mediated glucose uptake (glucose uptake 50 percent of that of normal control subjects, n = 17), his plasma potassium declined to a degree similar to that seen in normal subjects. During a subsequent higher dose, 200 mU/m2/minute insulin infusion (insulin level, 914 μU/ml), plasma potassium declined to 2.5 meq/liter, a value significantly below that seen in normal (n = 19) (3.3 ± 0.1 meq/liter) and obese (n = 6) (3.2 ± 0.1 meq/liter) subjects. During this study, paralysis began in the patient's hand and forearm at the potassium nadir and lasted three hours, despite restoration of normokalemia 30 minutes after paralysis began. Glucose disposal rates during this high-dose insulin infusion were one-half that seen in lean control subjects (n = 19) and similar to those in obese control subjects. If these findings are representative of hypokalemic periodic paralysis and can be generalized to larger numbers of patients, they indicate several new features of this syndrome. The ability of insulin to induce hypokalemia is enhanced in this syndrome even in the presence of marked coexistent obesity-related resistance to the action of insulin to promote glucose utilization. Enhanced sensitivity of potassium uptake systems to activation by insulin (and other factors) may be a central feature of this syndrome. Additionally, paralytic hypokalemia can be induced during a euglycemic insulin clamp procedure, which could be utilized as a diagnostic test for this syndrome.
AB - To elucidate a potential role for insulin-mediated extra-renal potassium disposal in the clinical syndrome of hypokalemic periodic paralysis, an obese affected man was studied using the euglycemic insulin clamp, which, in normal and obese subjects, produces predictable, insulin dose-dependent declines in plasma potassium levels. During a 20 mU/m2/minute euglycemic clamp (insulin level, 88 μU/ml) procedure, while the patient with hypokalemic periodic paralysis demonstrated severe resistance to insulin-mediated glucose uptake (glucose uptake 50 percent of that of normal control subjects, n = 17), his plasma potassium declined to a degree similar to that seen in normal subjects. During a subsequent higher dose, 200 mU/m2/minute insulin infusion (insulin level, 914 μU/ml), plasma potassium declined to 2.5 meq/liter, a value significantly below that seen in normal (n = 19) (3.3 ± 0.1 meq/liter) and obese (n = 6) (3.2 ± 0.1 meq/liter) subjects. During this study, paralysis began in the patient's hand and forearm at the potassium nadir and lasted three hours, despite restoration of normokalemia 30 minutes after paralysis began. Glucose disposal rates during this high-dose insulin infusion were one-half that seen in lean control subjects (n = 19) and similar to those in obese control subjects. If these findings are representative of hypokalemic periodic paralysis and can be generalized to larger numbers of patients, they indicate several new features of this syndrome. The ability of insulin to induce hypokalemia is enhanced in this syndrome even in the presence of marked coexistent obesity-related resistance to the action of insulin to promote glucose utilization. Enhanced sensitivity of potassium uptake systems to activation by insulin (and other factors) may be a central feature of this syndrome. Additionally, paralytic hypokalemia can be induced during a euglycemic insulin clamp procedure, which could be utilized as a diagnostic test for this syndrome.
UR - https://www.scopus.com/pages/publications/0023894157
U2 - 10.1016/0002-9343(88)90304-X
DO - 10.1016/0002-9343(88)90304-X
M3 - Article
C2 - 3287913
AN - SCOPUS:0023894157
SN - 0002-9343
VL - 84
SP - 1001
EP - 1006
JO - American Journal of Medicine
JF - American Journal of Medicine
IS - 6
ER -