Effects of Glycemic Control on Protective Responses Against Hypoglycemia in Type 2 Diabetes
Abstract
OBJECTIVE: To determine the effects of glycemic control on the counterregulatory responses to hypoglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: Seven poorly controlled type 2 diabetes patients (mean HbA1c, 11.3 ± 1.1%) were studied by stepped hyperinsulinemic hypoglycemic clamp (nadir, 2.4 mmol/1) before and after improving glycemic control with insulin treatment. Counterregulatory hormones, symptoms, and four-choice reaction time were measured at each glucose plateau. RESULTS: In patients with poorly controlled type 2 diabetes, counterregulatory hormone responses began at higher plasma glucose levels than did those in healthy subjects (epinephrine, 4.4 ± 0.2 vs. 3.7 ± 0.2 mmol/1, P = 0.011). After significant improvement in glycemic control (mean HbA1c, 8.1 ± 0.9%, P < 0.001) was achieved without severe hypoglycemia, hormonal responses started at much lower plasma glucose levels (e.g., epinephrine, 3.5 ± 0.3 mmol/1, P = 0.005) and were significantly reduced in magnitude (e.g., area under epinephrine response curve, 306 ± 93 vs. 690 ± 107 nmol · min−1 · l−1, P = 0.012). This was accompanied by a change in the plasma glucose threshold at which hypoglycemic symptoms first developed from 3.6 ± 0.2 to 3.0 ± 0.2 mmol/1 (P = 0.019). In contrast, the plasma glucose threshold at which four-choice reaction time deteriorated did not change significantly (3.1 ±0.1 vs. 2.9 ± 0.1 mmol/1, P = 0.125). CONCLUSIONS: Counterregulatory responses begin at normoglycemia in poorly controlled type 2 diabetes. Improving glycemic control with insulin therapy normalizes hormonal responses but lowers the plasma glucose levels at which hypoglycemic symptoms develop to levels associated with impairment of four-choice reaction time, a marker of cognitive function. This process potentially increases the risk of severe hypoglycemia, but to a lesser extent than occurs in type 1 disease.
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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 [37]
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 [37]
Type 2 diabetes may therefore confer greater protection against hypoglycemia, particularly when glycemic control is suboptimal, because the counterregulatory responses commence at higher blood glucose levels than observed in the nondiabetic state or in people with type 1 diabetes.
“Type 2 diabetes may therefore confer greater protection against hypoglycemia, particularly when glycemic control is suboptimal, because the counterregulatory responses commence at higher blood glucose levels than observed in the nondiabetic state or in people with type 1 diabetes (37,38).”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [37]
Three studies of counterregulatory responses to hypoglycemia in people with type 2 diabetes treated with either diet or oral medication have shown that counterregulatory hormonal release occurs at higher blood glucose levels than in nondiabetic control subjects and people with type 1 diabetes.
“Three studies of counterregulatory responses to hypoglycemia in people with type 2 diabetes, treated with either diet or oral medication, have shown that counterregulatory hormonal release occurs at higher blood glucose levels than in nondiabetic control subjects (36,37) and people with type 1 diabetes (38).”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [37]
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References 47 · Cited by 71
- Authors
- Korzon-Burakowska, A., Hopkins, D., Matyka, K., Lomas, J., Pernet, A., Macdonald, I., & Amiel, S.
- Affiliations
- King's College London (GB)
- University of Nottingham (GB)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1998-02-01
- Volume
- 21
- Issue
- 2
- Pages
- 283-290
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2158597424
- Cited by
- 71
- References
- 47
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 2 diabetes, glycemic control, hypoglycemia, counterregulatory hormones, epinephrine, hypoglycemic symptoms, insulin therapy, cognitive function, reaction time, HbA1c
- MeSH terms
- Blood Glucose, Diabetes Mellitus, Type 2, Epinephrine, Female, Glucagon, Glucose, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Middle Aged, Norepinephrine, Psychomotor Performance, Reaction Time, Growth Hormone, Glucose Clamp Technique
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