Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to, symptoms of, and defense against subsequent hypoglycemia.

Dagogo-Jack, S E; Craft, S; Cryer, P E

doi:10.1172/jci116302

Cited by 471Diabetes Management and ResearchCardiovascular Syncope and Autonomic DisordersDiabetes and associated disorders

Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to, symptoms of, and defense against subsequent hypoglycemia.

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Dagogo-Jack, S E, Craft, S, Cryer, P E·1993·Journal of Clinical Investigation

DOI 10.1172/jci116302PMC PMC288033

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Abstract

We hypothesize that in patients with insulin-dependent diabetes mellitus (IDDM), recent antecedent iatrogenic hypoglycemia is a major cause of hypoglycemia-associated autonomic failure, a disorder distinct from classical diabetic autonomic neuropathy (CDAN), and that hypoglycemia-associated autonomic failure, by reducing both symptoms of and defense against developing hypoglycemia, results in recurrent iatrogenic hypoglycemia, thus creating a vicious cycle. We used the hyperinsulinemic (12.0 pmol.kg-1.min-1) stepped hypoglycemic clamp technique to assess autonomic and symptomatic responses to hypoglycemia and the insulin infusion test (4.0 pmol.kg-1.min-1) to assess defense against hypoglycemia on mornings before and after clamped afternoon hypoglycemia (approximately 2.8 mmol/liter) and hyperglycemia (approximately 11.1 mmol/liter) in patients with IDDM. Compared with nondiabetic subjects, IDDM with or without CDAN exhibited reduced epinephrine (P = 0.0222 and 0.0040) and pancreatic polypeptide (P = 0.0083 and 0.0056) responses to hypoglycemia. After afternoon hypoglycemia, lower plasma glucose concentrations were required to elicit autonomic and symptomatic responses during morning hypoglycemic clamps in patients without CDAN. At the 2.8 mmol/liter step, mean (+/- SE) epinephrine levels were 1,160 +/- 270 and 2,040 +/- 270 pmol/liter (P = 0.0060), pancreatic and total symptom scores were 22 +/- 3 and 41 +/- 7 (P = 0.0475) after afternoon hypoglycemia and hyperglycemia, respectively. During morning insulin infusion tests after afternoon hypoglycemia, nadir plasma glucose concentrations were 2.6 +/- 0.2 mmol/liter compared with 3.3 +/- 0.3 mmol/liter (P < 0.001) at the corresponding time points after afternoon hyperglycemia. Thus, we conclude: (a) elevated glycemic thresholds for autonomic responses to hypoglycemia are a feature of IDDM per se, not classical diabetic autonomic neuropathy; and (b) a single episode of afternoon hypoglycemia results in both elevated glycemic thresholds for autonomic and symptomatic responses to hypoglycemia and impaired physiological defense against hypoglycemia the next morning in IDDM.

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The concept of hypoglycemia-associated autonomic failure in diabetes is based on pivotal findings in nondiabetic individuals and patients with type 1 diabetes and was first documented in type 1 diabetes.
“The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes is based on pivotal findings in nondiabetic individuals (97) and patients with T1DM (101) and was first documented in T1DM (89).”
From Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline (2009) · cites this paper as [89]
The Discussion (page unavailable) says the study’s data document that recent antecedent hypoglycemia can induce HAAF in patients with insulin-dependent diabetes mellitus (type 1 diabetes). The paper does not establish that this was the first documentation of HAAF in that population. (LLM, conf=0.78)
Experimental — accuracy not yet measured
All of these defenses, not just insulin secretion, are compromised in type 1 diabetes mellitus and in long-standing type 2 diabetes mellitus.
“All of these defenses, not just insulin secretion, are compromised in T1DM and in long-standing T2DM (12,16,89,90).”
From Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline (2009) · cites this paper as [89]
The Introduction (page not available in our copy) says that insulin, glucagon, and epinephrine responses are abnormal in insulin-dependent diabetes mellitus, supporting the T1DM portion. The paper does not establish the same claim for long-standing T2DM. (LLM, conf=0.87)
Experimental — accuracy not yet measured
The concept of hypoglycemia-associated autonomic failure in diabetes is based on pivotal findings in nondiabetic individuals and patients with type 1 diabetes mellitus and was first documented in type 1 diabetes mellitus.
“The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes is based on pivotal findings in nondiabetic individuals (97) and patients with T1DM (101) and was first documented in T1DM (89).”
From Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline (2009) · cites this paper as [89]
The Discussion reports that this study documented hypoglycemia-associated autonomic failure induced by recent antecedent hypoglycemia in patients with insulin-dependent diabetes mellitus (T1DM). It does not establish the historical priority implied by “first documented.” The findings in nondiabetic individuals are attached to a different citation in the citing sentence. (LLM, conf=0.83)
Experimental — accuracy not yet measured
The glycemic threshold for sympathoadrenal activation is shifted to lower plasma glucose concentrations by recent antecedent hypoglycemia, prior exercise, and sleep.
“Through mechanisms yet to be clearly defined but generally thought to reside in the brain (12, 16, 85, 95), the glycemic threshold for sympathoadrenal activation is shifted to lower plasma glucose concentrations by recent antecedent hypoglycemia, as well as by prior exercise and by sleep (12, 16, 89, 90, 95-97).”
From Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline (2009) · cites this paper as [89]
The Discussion (p. 823) reports that recent antecedent hypoglycemia shifted autonomic-response thresholds in patients with insulin-dependent diabetes: lower plasma glucose was needed to elicit a comparable epinephrine response. The paper does not establish the claimed effects of prior exercise or sleep. (LLM, conf=0.88)
Experimental — accuracy not yet measured
The concept of HAAF has been extended to patients with long-standing type 2 diabetes mellitus and absolute insulin deficiency.
“More recently, the concept of HAAF (12,16,89) has been extended to patients with long-standing T2DM and absolute insulin deficiency (90).”
From Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline (2009) · cites this paper as [89]
The Introduction describes HAAF in insulin-dependent diabetes mellitus (IDDM), and the Discussion concludes that antecedent hypoglycemia can induce it in patients with IDDM. The paper does not report an extension to patients with long-standing type 2 diabetes and absolute insulin deficiency; searches for type 2 diabetes and NIDDM found no such passage. No page number was supplied for these passages. (LLM, conf=0.86)
Experimental — accuracy not yet measured

The glycaemic thresholds at which counterregulatory responses occur are not fixed, showing inter- and intra-individual variability, and are influenced by prior exposure to hypo- and hyperglycaemia, as well as by age and duration of diabetes.
“Although reported to be organised hierarchically, the glycaemic thresholds at which these responses occur are not fixed, showing inter- and intra-individual variability, and are influenced by prior exposure to hypo- and hyperglycaemia, as well as by age and duration of diabetes [5, 6].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [6]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
These data are in line with studies showing that prior exposure to recurrent hypoglycaemia, which often is the rule in people with impaired awareness, shifts the glycaemic thresholds for counterregulatory responses to lower glucose levels.
“These data are in line with studies showing that prior exposure to recurrent hypoglycaemia, which often is the rule in people with impaired awareness, shifts the glycaemic thresholds for counterregulatory responses to lower glucose levels [6, 15].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [6]
The Discussion reports that after antecedent hypoglycemia, lower plasma glucose concentrations were required to elicit comparable epinephrine responses, supporting a shift in the threshold for a counterregulatory response. However, the study tested a recent, short-term episode in patients with insulin-dependent diabetes, not recurrent prior exposure in people with impaired awareness; the paper presents a link to recurrent hypoglycemia as a hypothesis. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Merely directing people with type 1 diabetes to allow their HbA1c to increase is not expected to alter glycaemic thresholds or the associated burden of hypoglycaemia unless the rate of hypoglycaemia drops considerably.
“Our data underscore, however, that merely directing people with type 1 diabetes to allow their HbA1c to increase is not expected to alter glycaemic thresholds or the associated burden of hypoglycaemia unless the rate of hypoglycaemia drops considerably [6, 32, 60].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [6]
The Discussion (page not available in our copy) reports that recent antecedent hypoglycaemia reduces responses to subsequent hypoglycaemia and physiological defence against it, supporting the importance of hypoglycaemia exposure. But this short-term experiment did not test advice to raise HbA1c, whether thresholds would remain unchanged, or how much the rate of hypoglycaemia must fall to reduce its burden. (LLM, conf=0.84)
Experimental — accuracy not yet measured
In fully developed type 1 diabetes mellitus, circulating insulin levels do not decrease as plasma glucose levels decline.
“In fully developed T1DM, circulating insulin levels do not decrease as plasma glucose levels decline.”
From Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline (2009) · cites this paper as [89]
Glycemic thresholds for symptoms of hypoglycemia shift to lower plasma glucose concentrations after recent antecedent hypoglycemia.
“glycemic thresholds for symptoms of hypoglycemia (among other responses) shift to lower plasma glucose concentrations after recent antecedent hypoglycemia (9–12)”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
A single threshold plasma glucose concentration defining hypoglycemia in diabetes cannot be assigned.
“A single threshold value for plasma glucose concentration that defines hypoglycemia in diabetes cannot be assigned because glycemic thresholds for symptoms of hypoglycemia (among other responses) shift to lower plasma glucose concentrations after recent antecedent hypoglycemia (9–12) and to higher plasma glucose concentrations in patients with poorly controlled diabetes and infrequent hypoglycemia”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
Recurrent hypoglycemia reduces the glucose level that precipitates the counterregulatory response necessary to restore euglycemia during a subsequent episode of hypoglycemia.
“Recurrent hypoglycemia has been shown to reduce the glucose level that precipitates the counterregulatory response necessary to restore euglycemia during a subsequent episode of hypoglycemia (10–12).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
A total of 25 studies (40%) provided data to either calculate or extract the glycaemic threshold for symptom responses to hypoglycaemia.
“A total of 25 studies (40%) provided data to either calculate or extract the glycaemic threshold for symptom responses to hypoglycaemia [6, 13, 16–18, 20, 23, 24, 26, 29, 31, 33–37, 46, 51–53, 56, 57, 58, 63, 68].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [6]
In published studies, avoiding frequent hypoglycemia required frequent (almost daily) contact between clinician and patient, and adjustments to caloric intake and insulin regimen based on blood glucose values.
“In published studies, this has required frequent (almost daily) contact between clinician and patient, and adjustments to caloric intake and insulin regimen based on blood glucose values (10,119,120).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
The Introduction describes the paper’s inpatient glucose-clamp studies and intravenous insulin management, not published hypoglycemia-avoidance programs. Searches for almost-daily clinician–patient contact and blood-glucose-based adjustments to caloric intake and insulin regimens found no passage addressing those requirements. Page numbers were not available for the indexed passages. (LLM, conf=0.74)
Experimental — accuracy not yet measured
With this approach, complete reversal of hypoglycemia unawareness was achieved by 3 months.
“With this approach, restoration of autonomic symptoms of hypoglycemia occurred within 2 weeks, and complete reversal of hypoglycemia unawareness was achieved by 3 months.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
The experimental-design passage (Introduction; page not provided) describes a five-day study of responses to recent hypoglycemia, not a three-month intervention. A search of our copy for reversal of unawareness and a three-month outcome found no passage reporting complete reversal by that time. (LLM, conf=0.78)
Experimental — accuracy not yet measured
With this approach, restoration of autonomic symptoms of hypoglycemia occurred within 2 weeks.
“With this approach, restoration of autonomic symptoms of hypoglycemia occurred within 2 weeks, and complete reversal of hypoglycemia unawareness was achieved by 3 months.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
The Introduction describes a five-day experiment comparing responses after afternoon hypoglycemia and hyperglycemia; it does not describe an approach that restored symptoms. Searches for restoration, avoidance of hypoglycemia, and a two-week timeframe found no passage reporting restoration of autonomic symptoms within two weeks. (LLM, conf=0.75)
Experimental — accuracy not yet measured
All but one of the studies (98%) provided data to either calculate or extract the glycaemic threshold for counterregulatory hormone responses to hypoglycaemia.
“All but one [6] of the studies (98%) provided data to either calculate or extract the glycaemic threshold for counterregulatory hormone responses to hypoglycaemia.”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [6]
The citation is attached to the one study said not to provide usable threshold data. The Introduction describes stepped hypoglycemic clamps, and the Discussion describes threshold abnormalities, but neither passage establishes whether the paper supplied data that the citing authors could calculate or extract as a glycaemic threshold. The paper also does not address the citing review’s count of studies. (LLM, conf=0.70)
Experimental — accuracy not yet measured
Recurrent hypoglycemia reduces the glucose level that precipitates the counterregulatory response necessary to restore euglycemia during a subsequent episode of hypoglycemia.
“Recurrent hypoglycemia has been shown to reduce the glucose level that precipitates the counterregulatory response necessary to restore euglycemia during a subsequent episode of hypoglycemia (10 -12).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
In published studies, avoiding frequent hypoglycemia required frequent (almost daily) contact between clinician and patient, and adjustments to caloric intake and insulin regimen based on blood glucose values.
“In published studies, this has required frequent (almost daily) contact between clinician and patient, and adjustments to caloric intake and insulin regimen based on blood glucose values (10,119,120).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]
With this approach, restoration of autonomic symptoms of hypoglycemia occurred within 2 weeks, and complete reversal of hypoglycemia unawareness was achieved by 3 months.
“With this approach, restoration of autonomic symptoms of hypoglycemia occurred within 2 weeks, and complete reversal of hypoglycemia unawareness was achieved by 3 months.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [10]

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Effect of Ischemia on Known Substrates and Cofactors of the Glycolytic Pathway in Brain
Lowry, O. H., Passonneau, J. V., Hasselberger, F. X., & Schulz, D. W. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51740-3 · Cited by 2,222 · see citing works
Hormone-fuel interrelationships during fasting.
Cahill, G. F., Herrera, M. G., Morgan, A. P., Soeldner, J. S., Steinke, J., Levy, P. L., Reichard, G. A., & Kipnis, D. M. (1966) · Journal of Clinical Investigation · doi:10.1172/jci105481 · Cited by 1,036 · see citing works
Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial
(1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)90605-w · Cited by 807 · see citing works
Epidemiology of severe hypoglycemia in the diabetes control and complications trial
(1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)80085-z · Cited by 807 · see citing works
Lack of Glucagon Response to Hypoglycemia in Diabetes: Evidence for an Intrinsic Pancreatic Alpha Cell Defect
Gerich, J. E., Langlois, M., Noacco, C., Karam, J. H., & Forsham, P. H. (1973) · Science · doi:10.1126/science.182.4108.171 · Cited by 688 · see citing works
A Sensitive Double Antibody Immunoassay for Human Growth Hormone in Plasma
Schalch, P., & PARKER, M. L. (1964) · Nature · doi:10.1038/2031141a0 · Cited by 635 · see citing works
Determination of Free and Total Insulin and C-Peptide in Insulin-treated Diabetics
Kuzuya, H., BLIX, P. M., Horwitz, D. L., Steiner, D. F., & Rubenstein, A. H. (1977) · Diabetes · doi:10.2337/diab.26.1.22 · Cited by 603 · see citing works
Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction
Mitrakou, A., Ryan, C., Veneman, T., Mokan, M., Jenssen, T., Kiss, I., Durrant, J., Cryer, P., & Gerich, J. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.260.1.e67 · Cited by 558 · see citing works
Self-citation
Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans.
Heller, S. R., & Cryer, P. E. (1991) · Diabetes · doi:10.2337/diab.40.2.223 · Cited by 531 · see citing works
Self-citation
Abnormal Glucose Counterregulation in Insulin-dependent Diabetes Mellitus: Interaction of Anti-Insulin Antibodies and Impaired Glucagon and Epinephrine Secretion
Bolli, G., Feo, P. D., Compagnucci, P., Cartechini, M. G., Angeletti, G., Santeusanio, F., Brunetti, P., & Gerich, J. E. (1983) · Diabetes · doi:10.2337/diab.32.2.134 · Cited by 433 · see citing works
Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms.
Schwartz, N. S., Clutter, W. E., Shah, S. D., & Cryer, P. E. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112884 · Cited by 394 · see citing works
Self-citation
Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release.
Amiel, S. A., Sherwin, R. S., Simonson, D. C., & Tamborlane, W. V. (1988) · Diabetes · doi:10.2337/diab.37.7.901 · Cited by 393 · see citing works
Identification of type I diabetic patients at increased risk for hypoglycemia during intensive therapy.
White, N. H., Skor, D. A., Cryer, P. E., Levandoski, L. A., Bier, D. M., & Santiago, J. V. (1983) · New England Journal of Medicine · doi:10.1056/nejm198303033080903 · Cited by 391 · see citing works
Self-citation
Symptomatic Hypoglycaemia in 411 Type 1 Diabetic Patients
Pramming, S., Thorsteinsson, B., Bendtson, I., & Binder, C. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01575.x · Cited by 336 · see citing works
Defective glucose counterregulation after strict glycemic control of insulin-dependent diabetes mellitus
Amiel, S. A., Tamborlane, W. V., Simonson, D. C., & Sherwin, R. S. (1987) · New England Journal of Medicine · doi:10.1056/nejm198705283162205 · Cited by 309 · see citing works
Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics.
Boyle, P. J., Schwartz, N. S., Shah, S. D., Clutter, W. E., & Cryer, P. E. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806093182302 · Cited by 258 · see citing works
Self-citation
Iatrogenic Hypoglycemia as a Cause of Hypoglycemia-Associated Autonomic Failure in IDDM: A Vicious Cycle
Cryer, P. E. (1992) · Diabetes · doi:10.2337/diab.41.3.255 · Cited by 222 · see citing works
Self-citation
Enzymic assay of glycerol, dihydroxyacetone, and glyceraldehyde
Pinter, J. K., Hayashi, J. A., & Watson, J. A. (1967) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(67)90094-x · Cited by 190 · see citing works
Unawareness of Hypoglycaemia in Insulin‐treated Diabetic Patients: Prevalence and Relationship to Autonomic Neuropathy
Hepburn, D. A., Patrick, A. W., Eadington, D. W., Ewing, D. J., & Frier, B. M. (1990) · Diabetic Medicine · doi:10.1111/j.1464-5491.1990.tb01475.x · Cited by 179 · see citing works
Chronic hypoglycemia increases brain glucose transport
McCall, A. L., Fixman, L. B., Fleming, N., Tornheim, K., Chick, W., & Ruderman, N. B. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.4.e442 · Cited by 174 · see citing works
Plasma Cortisol Determination: Radioimmunoassay and Competitive Protein Binding Compared
Farmer, R. W., & Pierce, C. E. (1974) · Clinical Chemistry · doi:10.1093/clinchem/20.4.411 · Cited by 170 · see citing works
Correlation Between Minimal Secretory Capacity of Pancreatic β-Cells and Stability of Diabetic Control
Fukuda, M., Tanaka, A., Tahara, Y., Ikegami, H., Yamamoto, Y., Kumahara, Y., & Shima, K. (1988) · Diabetes · doi:10.2337/diab.37.1.81 · Cited by 145 · see citing works
Counterregulatory adaptation to recurrent hypoglycemia in normal humans
DAVIS, M. R., & SHAMOON, H. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-73-5-995 · Cited by 143 · see citing works
Glycemic Control and Neuropsychologic Function during Hypoglycemia in Patients with Insulin-Dependent Diabetes Mellitus
Widom, B., & Simonson, D. C. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-112-12-904 · Cited by 131 · see citing works
A reliable and reproducible test for adequate glucose counterregulation in type I diabetes mellitus.
Bolli, G. B., Feo, P. D., Cosmo, S. D., Perriello, G., Ventura, M. M., Benedetti, M. M., Santeusanio, F., Gerich, J. E., & Brunetti, P. (1984) · Diabetes · doi:10.2337/diab.33.8.732 · Cited by 124 · see citing works
External and internal standards in the single-isotope derivative (radioenzymatic) measurement of plasma norepinephrine and epinephrine.
SHAH, S. D., Clutter, W. E., & Cryer, P. E. (1985) · PubMed · Cited by 119 · see citing works
Self-citation
Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion
Bolli, G. B., Feo, P. D., Compagnucci, P., et al. (1983) · Diabetes · doi:10.2337/diabetes.32.2.134 · Cited by 118 · see citing works
Role of Epinephrine-mediated β-Adrenergic Mechanisms in Hypoglycemic Glucose Counterregulation and Posthypoglycemic Hyperglycemia in Insulin-dependent Diabetes Mellitus
Popp, D. A., Shah, S. D., & Cryer, P. E. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110455 · Cited by 112 · see citing works
Self-citation
RR‐variation: The autonomic test of choice in diabetes
Genovely, H., & Pfeifer, M. A. (1988) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610040305 · Cited by 110 · see citing works
Intermittent Hypoglycemia Impairs Glucose Counterregulation
Widom, B., & Simonson, D. C. (1992) · Diabetes · doi:10.2337/diab.41.12.1597 · Cited by 109 · see citing works
INFLUENCE OF SYMPATHETIC NERVOUS SYSTEM ON HYPOGLYCAEMIC WARNING SYMPTOMS
Heller, S. R., Herbert, M., Macdonald, I. A., & Tattersall, R. B. (1987) · The Lancet · doi:10.1016/s0140-6736(87)92382-8 · Cited by 109 · see citing works
Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy.
Ryder, R. E. J., Owens, D. R., Hayes, T. M., Ghatei, M. A., & Bloom, S. R. (1990) · BMJ · doi:10.1136/bmj.301.6755.783 · Cited by 108 · see citing works
Hormonal, Metabolic, and Cardiovascular Responses to Hypoglycemia in Diabetic Autonomic Neuropathy
Hilsted, J., Madsbad, S., Krarup, T., Sestoft, L., Christensen, N. J., Tronier, B., & Galbo, H. (1981) · Diabetes · doi:10.2337/diab.30.8.626 · Cited by 104 · see citing works
Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release
Amiel, S. A., Sherwin, R. S., Simonson, D. C., et al. (1988) · Diabetes · doi:10.2337/diabetes.37.7.901 · Cited by 99 · see citing works
Further defects in counterregulatory responses induced by recurrent hypoglycemia in IDDM.
Davis, M. R., Mellman, M., & Shamoon, H. (1992) · Diabetes · doi:10.2337/diab.41.10.1335 · Cited by 98 · see citing works
Effect of Antecedent Glucose Control on Cerebral Function During Hypoglycemia
Amiel, S. A., Pottinger, R. C., Archibald, H. R., Chusney, G. D., Cunnah, D., Prior, P. F., & Gale, E. A. (1991) · Diabetes Care · doi:10.2337/diacare.14.2.109 · Cited by 96 · see citing works
Multifactorial Origin of Hypoglycemic Symptom Unawareness in IDDM: Association With Defective Glucose Counterregulation and Better Glycemic Control
Clarke, W. L., Gonder-Frederick, L. A., Richards, F. E., & Cryer, P. E. (1991) · Diabetes · doi:10.2337/diab.40.6.680 · Cited by 76 · see citing works
Self-citation
Regional Pancreatic Concentration and In-vitro Secretion of Canine Pancreatic Polypeptide, Insulin, and Glucagon
Gingerich, R. L., Lacy, P. E., Chance, R. E., & Johnson, M. G. (1978) · Diabetes · doi:10.2337/diab.27.2.96 · Cited by 75 · see citing works
Brain glucose utilization and transport and cortical function in chronic vs. acute hypoglycemia
Pelligrino, D. A., Segil, L. J., & Albrecht, R. F. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.5.e729 · Cited by 73 · see citing works
Immunoassays for Glucagon
Ensinck, J. W. (1983) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-68866-9_10 · Cited by 72 · see citing works
Hypoglycaemia Unawareness in Type 1 Diabetes: A Lower Plasma Glucose is Required to Stimulate Sympathoadrenal Activation
Hepburn, D. A., Patrick, A. W., Brash, H. M., Thomson, I., & Frier, B. M. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01533.x · Cited by 68 · see citing works
A New Colorimetric Method for the Determination of Free Fatty Acids with Acyl-CoA Synthetase and Acyl-CoA Oxidase1
Hosaka, K., Kikuchi, T., Mitsuhida, N., & Kawaguchi, A. (1981) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a133380 · Cited by 65 · see citing works
The human sympathochromaffin system
Shah, S. D., Tse, T. F., Clutter, W. E., & Cryer, P. E. (1984) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1984.247.3.e380 · Cited by 64 · see citing works
Self-citation
Defective Epinephrine and Growth Hormone Responses in Type I Diabetes Are Stimulus Specific
Hirsch, B. R., & Shamoon, H. (1987) · Diabetes · doi:10.2337/diab.36.1.20 · Cited by 56 · see citing works
Cholinergic Stimulation of Norepinephrine Release in Man
Leveston, S. A., SHAH, S. D., & Cryer, P. E. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109471 · Cited by 50 · see citing works
Self-citation
Higher Glycemic Thresholds for Symptoms During β-Adrenergic Blockade in IDDM
Hirsch, I. B., Boyle, P. J., Craft, S., & Cryer, P. E. (1991) · Diabetes · doi:10.2337/diab.40.9.1177 · Cited by 50 · see citing works
Self-citation
The prevalence of impaired glucose counter-regulation during an insulin-infusion test in insulin-treated diabetic patients prone to severe hypoglycaemia
Sj�bom, N. C., Adamson, U., & Lins, P. E. (1989) · Diabetologia · doi:10.1007/bf00264914 · Cited by 35 · see citing works
A reliable and reproducible test for adequate glucose counterregulation in type I diabetes mellitus
Bolli, G. B., Feo, P. D., Cosmo, S. D., et al. (1984) · Diabetes · doi:10.2337/diabetes.33.8.732 · Cited by 34 · see citing works
Intermittent hypoglycemia impairs glucose counterregulation
Widom, B., & Simonson, D. C. (1992) · Diabetes · doi:10.2337/diabetes.41.12.1597 · Cited by 34 · see citing works
Regional pancreatic concentration and in-vitro secretion of canine pancreatic polypeptide, insulin, and glucagon
Gingerich, R. L., Lacy, P. E., Chance, R. E., et al. (1978) · Diabetes · doi:10.2337/diabetes.27.2.96 · Cited by 32 · see citing works
Does Central Nervous System Adaptation to Antecedent Glycemia Occur in Patients with Insulin-Dependent Diabetes Mellitus?
Cryer, P. E. (1985) · Annals of Internal Medicine · doi:10.7326/0003-4819-103-2-284 · Cited by 28 · see citing works
Self-citation
Hypoinsulinemia is not critical to glucose recovery from hypoglycemia in humans
Heller, S. R., & Cryer, P. E. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.261.1.e41 · Cited by 26 · see citing works
Self-citation
Unawareness of Hypoglycemia by Insulin-Dependent Diabetics
Grimaldi, A., Bosquet, F., Davidoff, P., Digy, J. P., Sachon, C., Landault, C., Thervet, F., Zoghbi, F., & Legrand, J. C. (1990) · Hormone and Metabolic Research · doi:10.1055/s-2007-1004858 · Cited by 25 · see citing works
Decreased Sympathochromaffin Activity in IDDM
Cryer, P. E. (1989) · Diabetes · doi:10.2337/diab.38.4.405 · Cited by 23 · see citing works
Self-citation
Counterregulatory Hormone Responses Preserved After Long-Term Intravenous Insulin Infusion Compared to Continuous Subcutaneous Insulin Infusion
Gulan, M., Perlman, K., Sole, M. J., Albisser, A. M., & Zinman, B. (1988) · Diabetes · doi:10.2337/diab.37.5.526 · Cited by 18 · see citing works
Defective epinephrine and growth hormone responses in type I diabetes are stimulus specific
Hirsch, B. R., & Shamoon, H. (1987) · Diabetes · doi:10.2337/diabetes.36.1.20 · Cited by 17 · see citing works
Decreased sympathochromaffin activity in IDDM
Cryer, P. E. (1989) · Diabetes · doi:10.2337/diabetes.38.4.405 · Cited by 12 · see citing works
Self-citation
Noradrenaline response to edrophonium (Tensilon) and its relation to other autonomic tests in diabetic subjects.
Dm, M., Cn, M., Ra, R., et al. (1987) · PubMed · Cited by 4 · see citing works

Flagged first, then by citations

Research works printed but not linked: 2

[1]1. Cryer, P. E., and J. E. Gerich. 1990. Hypoglycemia in insulin dependent diabetes mellitus: insulin excess and defective glucose counterregulation. In El- lenberg and Rifkin's Diabetes Mellitus, Theory and Practice. 4th ed. H. Rifkin and D. Porte, editors. Elsevier Science Publishing, NY. 526-546.
[40]40. Cryer, P. E. 1987. Diseases ofthe sympathochromaffin system. In Endocri- nology and Metabolism. 2nd ed. P. Felig, J. Baxter, A. Broadus, and L. Frohman, editors. McGraw-Hill, NY. 651-692.

Sorted by citations

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Vinik, A. I., Maser, R. E., Mitchell, B. D., & Freeman, R. (2003) · Diabetes Care · doi:10.2337/diacare.26.5.1553 · Cited by 2,044 · see citing works
Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society
Seaquist, E. R., Anderson, J., Childs, B., Cryer, P., Dagogo-Jack, S., Fish, L., Heller, S. R., Rodriguez, H., Rosenzweig, J., & Vigersky, R. (2013) · Diabetes Care · doi:10.2337/dc12-2480 · Cited by 1,389 · see citing works
“In published studies, this has required frequent (almost daily) contact between clinician and patient, and adjustments to caloric intake and insulin regimen based on blood glucose values (10,119,120).”
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Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline
Cryer, P. E., Axelrod, L., Grossman, A. B., Heller, S. R., Montori, V. M., Seaquist, E. R., & Service, F. J. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1410 · Cited by 1,277 · see citing works
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Defining and Reporting Hypoglycemia in Diabetes
American Diabetes Association Workgroup on Hypoglycemia (2005) · Diabetes Care · doi:10.2337/diacare.28.5.1245 · Cited by 1,146 · see citing works
Hypoglycemia in Diabetes
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Hypoglycaemia: the limiting factor in the glycaemic management of type I and type II diabetes.
Cryer, P. (2002) · Diabetologia · doi:10.1007/s00125-002-0822-9 · Cited by 794 · see citing works
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The barrier of hypoglycemia in diabetes
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Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: A joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes
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Self-citation
Diverse causes of hypoglycemia-associated autonomic failure in diabetes.
Cryer, P. E. (2004) · New England Journal of Medicine · doi:10.1056/nejmra031354 · Cited by 411 · see citing works
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Meticulous prevention of hypoglycemia normalizes the glycemic thresholds and magnitude of most of neuroendocrine responses to, symptoms of, and cognitive function during hypoglycemia in intensively treated patients with short-term IDDM.
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Hypoglycemia-associated autonomic failure in advanced type 2 diabetes.
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Symptoms of hypoglycaemia in people with diabetes
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Reversibility of unawareness of hypoglycemia in patients with insulinomas.
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Self-citation
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Long-term recovery from unawareness, deficient counterregulation and lack of cognitive dysfunction during hypoglycaemia, following institution of rational, intensive insulin therapy in IDDM.
Fanelli, C., Pampanelli, S., Epifano, L., Rambotti, A. M., Di Vincenzo, A., Modarelli, F., Ciofetta, M., Lepore, M., Annibale, B., Torlone, E., et al. (1994) · Diabetologia · doi:10.1007/bf00399801 · Cited by 212 · see citing works
Adaptation in brain glucose uptake following recurrent hypoglycemia.
Boyle, P. J., Nagy, R. J., O'Connor, A. M., Kempers, S. F., Yeo, R. A., & Qualls, C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.20.9352 · Cited by 208 · see citing works
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Self-citation
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Neuroendocrine responses to hypoglycemia
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Hypoglycemia and the sympathoadrenal system: neurogenic symptoms are largely the result of sympathetic neural, rather than adrenomedullary, activation
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Mini-review: Impact of recurrent hypoglycemia on cognitive and brain function
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Proinflammatory effects of hypoglycemia in humans with or without diabetes
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Effects of differing durations of antecedent hypoglycemia on counterregulatory responses to subsequent hypoglycemia in normal humans.
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Self-citation
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Hypoglycaemia.
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Philip E. Cryer, MD: seminal contributions to the understanding of hypoglycemia and glucose Counterregulation and the discovery of HAAF (Cryer Syndrome)
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Self-citation
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Self-citation
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Carey, M., Gospin, R., Goyal, A., Tomuta, N., Sandu, O., Mbanya, A., Lontchi-Yimagou, E., Hulkower, R., Shamoon, H., Gabriely, I., et al. (2017) · Diabetes · doi:10.2337/db16-1478 · Cited by 23 · see citing works
Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine
Dagogo‐Jack, S., Askari, H., Morrill, B., Lehner, L. L., Kim, B., & Sha, X. (2000) · Diabetes, Obesity and Metabolism · doi:10.1046/j.1463-1326.2000.00109.x · Cited by 23 · see citing works
Self-citation
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Frier, B. M. (2007) · Hypoglycaemia in Clinical Diabetes · doi:10.1002/9780470516270.ch7 · Cited by 22 · see citing works
Hypoglycaemia and its management in primary care setting
Ibrahim, M., Baker, J., Cahn, A., Eckel, R. H., El Sayed, N. A., Fischl, A. H., Gaede, P., Leslie, R. D., Pieralice, S., Tuccinardi, D., et al. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3332 · Cited by 21 · see citing works
Increased risk of severe hypoglycemic events with increasing frequency of non-severe hypoglycemic events in patients with type 1 and type 2 diabetes
Sreenan, S., Andersen, M., Thorsted, B. L., Wolden, M. L., & Evans, M. (2014) · Diabetes Therapy · doi:10.1007/s13300-014-0075-x · Cited by 21 · see citing works
Plasma metanephrine levels are decreased in type 1 diabetic patients with a severely impaired epinephrine response to hypoglycemia, indicating reduced adrenomedullary stores of epinephrine.
de Galan, B. E., Tack, C. J., Willemsen, J. J., Sweep, C. G. J. (., Smits, P., & Lenders, J. W. M. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031289 · Cited by 17 · see citing works
Effect of short-term glucose control on glycemic thresholds for epinephrine and hypoglycemic symptoms
Burge, M. R., Sobhy, T. A., Qualls, C. R., & Schade, D. S. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.11.7993 · Cited by 17 · see citing works
Residual insulin secretion is not coupled to a maintained glucagon response to hypoglycaemia in long‐term type 1 diabetes
Sjöberg, S., Ahrén, B., & Bolinder, J. (2002) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2002.01043.x · Cited by 13 · see citing works
Significance of the CGM metric of time in range in children and adolescents with type 1 diabetes
Urakami, T. (2022) · Endocrine Journal · doi:10.1507/endocrj.ej22-0257 · Cited by 11 · see citing works
Hypoglycemia
Cryer, P. E., & Frier, B. M. (2004) · International Textbook of Diabetes Mellitus · doi:10.1002/0470862092.d0707 · Cited by 1 · see citing works
Self-citation

Hypoglycemia-Induced Autonomic Failure in IDDM is Specific for Stimulus of Hypoglycemia and Is Not Attributable to Prior Autonomic Activation
Rattarasarn, C., Dagogo-Jack, S. E., Zachwieja, J. J., & Cryer, P. E. (1994) · Diabetes · doi:10.2337/diab.43.6.809 · Cited by 59 · see citing works
Self-citation
Dose-Response Study of Somatostatin on Meal-Stimulated Levels of Pancreatic Polypeptide and Insulin in the Dog
Feurle, G. E., Spoleanschi, P., Stauder, M., et al. (2009) · Digestion · doi:10.1159/000198700 · Cited by 9 · see citing works
Regional distribution of pancreatic polypeptide and other hormones in chicken pancreas: Reciprocal relationship between pancreatic polypeptide and glucagon
Tomita, T., Doull, V., POLLOCK, H. G., et al. (1985) · General and Comparative Endocrinology · doi:10.1016/0016-6480(85)90346-6 · Cited by 28 · see citing works
Pancreatic polypeptide and other hormones in pancreas of obese (ob/ob) mice
Tomita, T., Doull, V., KIMMEL, J. R., et al. (1984) · Diabetologia · doi:10.1007/bf00273910 · Cited by 18 · see citing works
Immunolocalization of insulin, glucagon, pancreatic polypeptide, and somatostatin in the pancreatic islets of the possum, Trichosurus vulpecula
Reddy, S., Bibby, N. J., Fisher, S. L., et al. (1986) · General and Comparative Endocrinology · doi:10.1016/0016-6480(86)90042-0 · Cited by 15 · see citing works

Authors: Dagogo-Jack, S. E., Craft, S., & Cryer, P. E.
Affiliations: Washington University in St. Louis (US)
ORCID: Dagogo-Jack, S E
Craft, S
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1993-03-01
Volume: 91
Issue: 3
Pages: 819-828
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci116302
PMC: PMC288033
OpenAlex: W2166004381
Semantic Scholar: 430f5983ed19fcf70d0f068aeb6ca2c17add0002
Cited by: 471
References: 58
Citations by year: 2026: 9 · 2025: 8 · 2024: 14 · 2023: 11 · 2022: 16 · 2021: 13 · 2020: 18 · 2019: 11 · 2018: 18 · 2017: 17 · 2016: 18 · 2015: 18 · 2014: 13 · 2013: 27 · 2012: 17
FWCI: 6.31
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
U.S. Public Health Service
National Institute of Diabetes and Digestive and Kidney Diseases (DK-44235, DK20579, DK27085)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords: hypoglycemia-associated autonomic failure, type 1 diabetes, iatrogenic hypoglycemia, autonomic neuropathy, epinephrine response, pancreatic polypeptide, hypoglycemic symptoms, hypoglycemic counterregulation, vicious circle
MeSH terms: Adult, Blood Glucose, Blood Pressure, Cognition, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Epinephrine, Fatty Acids, Nonesterified, Female, Glucagon, Glycated Hemoglobin, Humans, Hydroxybutyrates, Hyperinsulinism, Hypoglycemia, Iatrogenic Disease, Insulin, Lactates, Male, Time Factors, Glucose Clamp Technique, 3-Hydroxybutyric Acid

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Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to, symptoms of, and defense against subsequent hypoglycemia.

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