Hypoglycaemic counter-regulation at normal blood glucose concentrations in patients with well controlled type-2 diabetes
Abstract
Background Intensive treatment to achieve good glycaemic control in diabetic patients is limited by a high frequency of hypoglycaemia. The glucose concentrations at which symptoms and release of counter-regulatory hormones takes place have not been studied in patients with well controlled type-2 diabetes.Methods We studied seven well controlled, non-insulin treated, type-2 diabetic patients (mean HbA1c [corrected according to Diabetes Control and Complications Trial] 7.4%, SD 1.0) and seven healthy controls matched for age, sex, and body mass index with a stepped hyperinsulinaemic hypoglycaemic glucose clamp. Symptoms, cognitive function, and counter-regulatory hormone concentrations were measured at each glucose plateau, and the glucose value at which there was a significant change from baseline was calculated.Findings Symptom response took place at higher whole-blood glucose concentrations in diabetic patients than in controls. Counter-regulatory release of epinephrine, norepinephrine, growth hormone, and cortisol showed a similar pattern--eg, at blood glucose concentrations of 3.8 mmol/L [SD 0.4] vs 2.6 [0.3] for epinephrine.Interpretation Glucose thresholds for counter-regulatory hormone secretion are altered in well controlled type-2 diabetic patients, so that both symptoms and counter-regulatory hormone release can take place at normal glucose values. This effect might protect type-2 diabetic patients against episodes of profound hypoglycaemia and make the achievement of normoglycaemia more challenging in clinical practice.
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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 [36]
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 [36]
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References 16 · Cited by 126
- Authors
- Spyer, G., Hattersley, A. T., MacDonald, I., Amiel, S., & MacLeod, K. M.
- Affiliations
- University of Exeter (GB)
- King's College London (GB)
- Corresponding author
- MacLeod, Kenneth M
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 356
- Issue
- 9246
- Pages
- 1970-1974
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2146404839
- Cited by
- 126
- References
- 16
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 5 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 7 · 2012: 4
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Diabetes UK
- Novo Nordisk
- 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
- hypoglycemia, counterregulation, type 2 diabetes, well-controlled diabetes, counterregulatory hormones, epinephrine, norepinephrine, growth hormone, cortisol, hypoglycaemic symptoms, glucose threshold, normoglycemia
- MeSH terms
- Adult, Blood Glucose, Diabetes Mellitus, Type 2, Epinephrine, Female, Glucagon, Humans, Hydrocortisone, Hypoglycemia, Male, Middle Aged, Norepinephrine, Pancreatic Polypeptide, Case-Control Studies, Human Growth Hormone
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