Effect of near physiologic insulin therapy on hypoglycemia counterregulation in type-1 diabetes.
OBJECTIVE
The aim of this study was to examine hormonal counterregulation during insulin-induced hypoglycemia in type-1 diabetic patients during long-term near normoglycemic insulin therapy and intensive clinical care.


METHODS
Type-1 diabetic patients (age 35.3 +/- 2 years, body mass index 22.8 +/- 1 kg x m(-2), mean diabetes duration 13.6 (11-17 years), mean HbA1c during the last year 6.6 +/- 0.1%) and nondiabetic subjects were studied during (0-120 min) and after (120-240 min) hypoglycemic (3.05 mmol/l) hyperinsulinemic (approximately 330 pmol/l) clamp tests.


RESULTS
During hypoglycemia peak plasma concentrations of glucagon (199 +/- 16 vs. 155 +/- 11 ng/l, p < 0.05), epinephrine (4,514 +/- 644 vs. 1,676 +/- 513 pmol/l, p < 0.001), norepinephrine (2.21 +/- 0.14 vs. 1.35 +/- 0.19 nmol/l, p < 0.01) and cortisol (532 +/- 44 vs. 334 +/- 61 nmol/l) were reduced in the diabetic patients. Plasma lactate did not change from baseline values (0.51 +/- 0.06 mmol/l) in diabetic but doubled in healthy subjects (1.13 +/- 0.111 mmol/l, p < 0.001 vs. control). During the posthypoglycemic recovery period plasma concentrations of free fatty acids were higher in diabetic patients at 240 min (1.34 +/- 0.12 vs. 2.01 +/- 0.23 mmol/l, p < 0.05).


CONCLUSIONS
Despite long-term near physiologic insulin substitution and the low incidence of hypoglycemia, hormonal hypoglycemia counterregulation was impaired in type-1 diabetic patients after a diabetes duration of more than 10 years.
Bischof
M G
MG
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Vienna, Austria.
Bernroider
E
E
Ludwig
C
C
Kurzemann
S
S
Kletter
K
K
Waldhäusl
W
W
Roden
M
M
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006728:Hormones / Q000097:blood*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D005947:Glucose; D020155:3-Hydroxybutyric Acid