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Cited by 81Diabetes Management and ResearchPancreatic function and diabetesDiabetes Treatment and Management

Effect of Glycemic Control on Glucose Counterregulation During Hypoglycemia in NIDDM

Levy, Carol J, Kinsley, Brendan T, Bajaj, Mandeep, Simonson, Donald C·1998·Diabetes Care
DOI 10.2337/diacare.21.8.1330
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Abstract

OBJECTIVE: We examined the effect of glycemic control of NIDDM on counterregulatory hormone responses to hypoglycemia and compared the effect with that seen in patients with IDDM. RESEARCH DESIGN AND METHODS: Eleven subjects with NIDDM and eight age- and weight-matched control subjects and ten subjects with IDDM and ten age- and weight-matched control subjects were studied. All subjects underwent a stepped hypoglycemic-hyper-insulinemic clamp study during which plasma glucose levels were lowered in a stepwise manner from 5.0 to 2.2 mmol/l in steps of 0.6 mmol/l every 30 min. Counterregulatory hormones (epinephrine, norepinephrine, glucagon, ACTH, cortisol, and growth hormone [GH]) were measured, and a symptom survey was administered during the last 10 min of each 30-min interval. RESULTS: The threshold for release of epinephrine, norepinephrine, ACTH, and cortisol occurred at higher plasma glucose levels in NIDDM than in IDDM patients (P < 0.05–0.01). The glucose threshold for release of epinephrine and norepinephrine correlated with glycemic control as measured by glycosylated hemoglobin (P < 0.05–0.01). However, for a given level of glycemic control, the threshold for release of epinephrine and norepinephrine occurred at a higher glucose level in NIDDM versus IDDM patients (P < 0.05–0.01). At the nadir level of hypoglycemia, glucagon, ACTH, and cortisol levels were all higher in NIDDM compared with IDDM subjects, whereas GH levels were lower. CONCLUSIONS: Glycemic control alters counterregulatory responses to hypoglycemia in NIDDM as has been previously reported in IDDM. However, at similar levels of glycemic control, NIDDM patients release counterregulatory hormones at a higher plasma glucose level than patients with IDDM. In addition, subjects with NIDDM maintain their glucagon response to hypoglycemia. These data suggest that patients with NIDDM may be at reduced risk of severe hypoglycemia when compared with a group of IDDM patients in similar glycemic control, thus providing a more favorable risk-benefit ratio for intensive diabetes therapy in NIDDM.

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  • Improving glycemic control with insulin therapy shifts the threshold for the counterregulatory response to a lower blood glucose level; a similar phenomenon is observed in type 1 diabetes when glycemic control is intensified.

    “However, improving glycemic control with insulin therapy shifts the threshold for the counterregulatory response to a lower blood glucose level (37,38) (Fig. 3); a similar phenome-non is observed in type 1 diabetes when glycemic control is intensified (1,8,49).”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [38]

  • In type 2 diabetes, the glucagon response to hypoglycemia has been diversely reported as being either modestly diminished or preserved.

    “In type 2 diabetes, the glucagon response to hypoglycemia has been diversely reported as being either modestly diminished (16, 30,50) or preserved (33,34,37,38).”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [38]

  • Six of the subjects with type 2 diabetes required a high rate of insulin infusion (3-6 mU/kg/min) to achieve hypoglycemia.

    “Secondly, six of the subjects with type 2 diabetes required a high rate of insulin infusion (3-6 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) to achieve hypoglycemia.”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [38]

  • Most investigators reporting preservation of the glucagon response have studied people with type 2 diabetes who were unlikely to be insulin deficient, and, with one exception, all of these studies have examined counterregulatory responses in middle-aged subjects in their 5th or 6th decade.

    “Most investigators reporting preservation of the glucagon response have studied people with type 2 diabetes who were unlikely to be insulin deficient (33,34,36,38), and, with one exception (16), all of these studies have examined counterregulatory responses in middle-aged subjects in their 5th or 6th decade.”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [38]

  • In one study, counterregulatory hormones were secreted at higher blood glucose levels in subjects with type 2 diabetes than in those with type 1 diabetes.

    “Counterregulatory hormones were secreted at higher blood glucose levels in the subjects with type 2 than in those with type 1 diabetes (Fig. 3).”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [38]

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Authors
Levy, C. J., Kinsley, B. T., Bajaj, M., & Simonson, D. C.
Affiliations
  • Joslin Diabetes Center (US)
  • Brigham and Women's Hospital (US)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
1998-08-01
Volume
21
Issue
8
Pages
1330-1338
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/diacare.21.8.1330
OpenAlex
W2010613471
Cited by
81
References
0
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2022: 1 · 2021: 1 · 2019: 3 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 2
FWCI
2.46
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK36836, P30DK036836)
  • National Center for Research Resources (RR02635, M01RR002635)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 2 diabetes, type 1 diabetes, glycemic control, hypoglycemia, glucose counterregulation, counterregulatory hormones, epinephrine, norepinephrine, glucagon, ACTH, cortisol, growth hormone, HbA1c, hypoglycemia risk
MeSH terms
Adrenocorticotropic Hormone, Adult, Blood Glucose, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Epinephrine, Female, Glucagon, Glycated Hemoglobin, Homeostasis, Hormones, Humans, Hydrocortisone, Hypoglycemia, Male, Middle Aged, Norepinephrine, Reference Values, Regression Analysis, Time Factors, Human Growth Hormone

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