Plasma pancreatic polypeptide response to insulin-induced hypoglycemia as a marker for defective glucose counterregulation in insulin-dependent diabetes mellitus

N. H. White, R. L. Gingerich, L. A. Levandoski, P. E. Cryer, J. V. Santiago

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38 Scopus citations

Abstract

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 (ΔEPI = 102 ± 16 pg/ml; mean ± SEM) and PP (ΔPP = 12 ± 13 pg/ml) response as compared with controls (ΔEPI = 12 ± 13 pg/ml) response as compared with controls (ΔEPI = 310 ± 49; ΔPP = 498 ± 43) and IDDMs with +CR (ΔEPI = 291 ± 32; ΔPP = 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 < 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. The pancreatic polypeptide response may be helpful in evaluating the counterregulatory status of IDDMs before attempts at normalization of blood glucose using intensive therapeutic regimens, since a deficient pancreatic polypeptide response identifies patients with defective glucose counterregulation who have been shown previously to be at increased risk of severe hypoglycemia during intensive therapy.

Original languageEnglish
Pages (from-to)870-875
Number of pages6
JournalDiabetes
Volume34
Issue number9
DOIs
StatePublished - Jan 1 1985

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