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Cited by 433Diabetes Management and ResearchPancreatic function and diabetesDiabetes and associated disorders

Abnormal Glucose Counterregulation in Insulin-dependent Diabetes Mellitus: Interaction of Anti-Insulin Antibodies and Impaired Glucagon and Epinephrine Secretion

Bolli, Geremia, Feo, Pierpaolo De, Compagnucci, Pietro, Cartechini, Maria G, Angeletti, Gabriella, Santeusanio, Fausto, Brunetti, Paolo, Gerich, John E·1983·Diabetes
DOI 10.2337/diab.32.2.134
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Abstract

To evaluate the roles of counterregulatory hormones and insulin antibodies in the impairment of plasma glucose recovery from hypoglycemia in diabetes mellitus, and to assess the relationship between the glucagon response and duration of the disease, 21 insulin-dependent diabetic patients and 10 nondiabetic subjects were studied. The diabetics consisted of 5 patients with recent onset of diabetes (< 1 mo); 11 with 2.6 ± 0.3 (mean ± SEM) yr duration of diabetes, 5 of whom had insulin antibodies; and 5 patients with long-term diabetes (21 ± 3 yr), insulin antibodies, and autonomic neuropathy. During insulin-induced hypoglycemia (28 mU/m2 × min for 60 min) in patients with recent-onset diabetes, plasma free insulin, glucose, and counterregulatory hormone concentrations did not differ from those of nondiabetic subjects. In patients with insulin antibodies, the disappearance of insulin after insulin infusion was delayed, and both restitution of normoglycemia and plasma glucagon response were blunted compared with patients without antibodies. When glucagon was infused (80–130 ng/m2 × min) during hypoglycemia in diabetics with impaired glucagon responses in order to simulate normal glucagon responses, plasma glucose recovery was normalized in patients without antibodies but not in those with antibodies. In patients with long-standing diabetes, restitution of normoglycemia was further impaired and this was associated with an absent plasma glucagon response and a diminished plasma epinephrine response. Plasma glucagon responses to hypoglycemia were inversely correlated to the duration of diabetes (r = −0.943; P < 0.0005). It is concluded that impaired A-cell secretion is the predominant mechanism for the delayed glucose recovery after hypoglycemia in diabetic patients without insulin antibodies and normal epinephrine responses. Slowed disappearance of insulin due to the presence of insulin antibodies further delays the restoration of normoglycemia. Patients with long-standing diabetes and autonomic neuropathy exhibit decreased epinephrine secretion, which leads to an additional retardation of glucose recovery. Since plasma glucagon and epinephrine responses to hypoglycemia were normal at the onset of diabetes but diminished in long-term diabetes, it appears that the impaired glucagon and epinephrine responses to hypoglycemia are acquired defects that develop subsequent to B-cell failure.

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  • The relevance of basing a biochemical definition for hypoglycaemia on the glycaemic threshold for secretion of glucagon can be disputed, as glucagon secretion becomes deficient at an early stage of type 1 diabetes and in type 2 diabetes when pancreatic beta cell failure is present.

    “The relevance of basing a biochemical definition for hypoglycaemia on the glycaemic threshold for secretion of glucagon can also be disputed, as this becomes deficient at an early stage of type 1 diabetes [12] and in type 2 diabetes when pancreatic beta cell failure is present [13].”

    From Defining hypoglycaemia: what level has clinical relevance? (2009) · cites this paper as [12]

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Authors
Bolli, G., Feo, P. D., Compagnucci, P., Cartechini, M. G., Angeletti, G., Santeusanio, F., Brunetti, P., & Gerich, J. E.
Affiliations
Mayo Clinic (US)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1983-02-01
Volume
32
Issue
2
Pages
134-141
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.32.2.134
OpenAlex
W2104564587
Cited by
433
References
0
Citations by year
2026: 3 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 4 · 2018: 10 · 2017: 5 · 2016: 11 · 2015: 11 · 2014: 9 · 2013: 13 · 2012: 11
FWCI
18.65
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
type 1 diabetes, glucose counterregulation, insulin antibodies, glucagon secretion, epinephrine secretion, hypoglycemia, glucose recovery, autonomic neuropathy, diabetes duration, insulin resistance, glucagon infusion, epinephrine infusion, beta-cell failure, type 1 diabetes autoimmunity
MeSH terms
Adolescent, Adult, Antibodies, Blood Glucose, Body Surface Area, Body Weight, C-Peptide, Diabetes Mellitus, Epinephrine, Glucagon, Humans, Hypoglycemia, Insulin, Islets of Langerhans

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