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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February 01 1983
Abnormal Glucose Counterregulation in Insulin-dependent Diabetes Mellitus: Interaction of Anti-Insulin Antibodies and Impaired Glucagon and Epinephrine Secretion
Geremia Bolli;
Geremia Bolli
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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Pierpaolo De Feo;
Pierpaolo De Feo
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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Pietro Compagnucci;
Pietro Compagnucci
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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Maria G Cartechini;
Maria G Cartechini
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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Gabriella Angeletti;
Gabriella Angeletti
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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Fausto Santeusanio;
Fausto Santeusanio
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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Paolo Brunetti;
Paolo Brunetti
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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John E Gerich
John E Gerich
From the Institutes of Medical Pathology and Clinical Medicine, Perugia University School of Medicine
06100 Perugia, Italy
Diabetes and Metabolism Research Laboratory, Endocrine Research Unit, Departments of Medicine and Physiology, Mayo Clinic and Medical School
Rochester, Minnesota 55901
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Address reprint requests to Paolo Brunetti, Instituto Patologia Medica Università, Via del Giochetto, 06100 Perugia, Italy.
Diabetes 1983;32(2):134–141
Article history
Received:
June 16 1982
Revision Received:
August 23 1982
PubMed:
6337896
Citation
Geremia Bolli, Pierpaolo De Feo, Pietro Compagnucci, Maria G Cartechini, Gabriella Angeletti, Fausto Santeusanio, Paolo Brunetti, John E Gerich; Abnormal Glucose Counterregulation in Insulin-dependent Diabetes Mellitus: Interaction of Anti-Insulin Antibodies and Impaired Glucagon and Epinephrine Secretion. Diabetes 1 February 1983; 32 (2): 134–141. https://doi.org/10.2337/diab.32.2.134
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