Plasma pancreatic polypeptide response to insulin-induced hypoglycemia as a marker for defective glucose counterregulation in insulin-dependent diabetes mellitus.
Defective glucose counterregulation occurs in some insulin-dependent diabetic subjects (IDDMs) as a result of a combined deficiency of glucagon (IRG) and epinephrine (EPI) secretion in response to insulin-induced hypoglycemia. To determine whether the deficient glucagon response, the deficient epinephrine response, or both are manifestations of autonomic dysfunction, we used the pancreatic polypeptide (PP) secretory response to insulin-induced hypoglycemia as a marker for autonomic neuropathy. Seven nondiabetic controls and 21 IDDMs were given insulin at 40 mU/kg/h after overnight euglycemia. Eight of the IDDMs had defective counterregulation (-CR), and 13 had adequate counterregulation (+CR) by our previously published criteria. Those with -CR had a blunted EPI (delta EPI = 102 +/- 16 pg/ml; mean +/- SEM) and PP (delta PP = 12 +/- 13 pg/ml) response as compared with controls (delta EPI = 310 +/- 49; delta PP = 498 +/- 43) and IDDMs with +CR (delta EPI = 291 +/- 32; delta PP = 521 +/- 86). In controls, IRG rose by 31 +/- 6 pg/ml; in IDDMs, IRG failed to rise significantly above baseline regardless of counterregulatory status. Although the PP and EPI responses correlated well (r = 0.626, P less than 0.001), the IRG response failed to correlate with either the EPI or the PP response. We conclude that the deficient epinephrine, but not glucagon, secretory response to hypoglycemia in diabetic subjects is a result of autonomic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
White
N H
NH
Gingerich
R L
RL
Levandoski
L A
LA
Cryer
P E
PE
Santiago
J V
JV
D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010191:Pancreatic Polypeptide / Q000097:blood*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism
D007328:Insulin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine