Loss of beta cell function as fasting glucose increases in the non-diabetic range
Open accessAbstract
Aims/hypothesis Our aim was to define the level of glycaemia at which pancreatic insulin secretion, particularly first-phase insulin release, begins to decline.Methods Plasma glucose and insulin concentrations were measured during an IVGTT in 553 men with non-diabetic fasting plasma glucose concentrations. In 466 of the men C-peptide was also estimated. IVGTT insulin secretion in first and late phases was assessed by: (i) the circulating insulin response; (ii) population parameter deconvolution analysis of plasma C-peptide concentrations; and (iii) a combined model utilising both insulin and C-peptide concentrations. Measurements of insulin sensitivity and elimination were also derived by modelling analysis.Results As fasting plasma glucose (FPG) increased, IVGTT first-phase insulin secretion declined by 73%, 71% and 68% for the three methods respectively. The FPG values at which this decline began, determined by change point regression, were 4.97, 5.16 and 5.42 mmol/l respectively. The sensitivity of late-phase insulin secretion to glucose declined at FPG concentrations above 6.0 mmol/l. Insulin elimination, but not insulin sensitivity, varied with FPG.Conclusions/interpretation The range of FPG over which progressive loss of the first-phase response begins may be as low as 5.0 to 5.4 mmol/l, with late-phase insulin responses declining at FPG concentrations above 6.0 mmol/l.
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Both IFG and IGT have insulin resistance and beta-cell defect.
“Both IFG and IGT have both insulin resistance and beta-cell defect.”
From Postprandial Reactive Hypoglycemia (2019) · cites this paper as [16]
The Results (page unavailable) show declining first-phase insulin secretion as glucose homeostasis deteriorated, supporting the beta-cell-defect component. They report no marked trend in insulin sensitivity, however, and the Discussion (page unavailable) says participants were not classified by impaired glucose tolerance (IGT). The paper therefore does not establish that both IFG and IGT have both defects. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIndividuals with IFG have insulin sensitivity close to normal in muscle with severe hepatic insulin resistance in liver, whereas individuals with IGT have moderate insulin resistance in liver but severe insulin resistance in muscle.
“Individuals with IFG have insulin sensitivity close to normal/normal in the muscle with severe hepatic insulin resistance in the liver whereas individuals with IGT have moderate insulin resistance in the liver, but severe insulin resistance in the muscle.[9, 15-19]”
From Postprandial Reactive Hypoglycemia (2019) · cites this paper as [16]
The Results report no marked trend in overall insulin sensitivity across categories of deteriorating glucose homeostasis, but do not separate sensitivity in muscle from resistance in the liver. The Discussion notes that some participants may have had impaired glucose tolerance, without comparing IFG and IGT on tissue-specific insulin resistance. Searches for hepatic and muscle insulin resistance did not locate the claimed comparison. (LLM, conf=0.76)
Experimental — accuracy not yet measuredPrevious prospective randomized trials have shown lifestyle modifications and pharmacological agents significantly reduce risk of developing Type 2 DM and cardiovascular risk factors in prediabetic patients.
“Previous prospective randomized trials have shown that lifestyle modifications and pharmacological agents significantly reduce the risk of developing Type 2 DM and cardiovascular risk factors in prediabetic patients.[16]”
From Postprandial Reactive Hypoglycemia (2019) · cites this paper as [16]
The Design section describes an observational cohort analysis of fasting glucose and insulin responses, not a randomized intervention trial. The Introduction discusses diabetes risk, but our copy does not report whether lifestyle changes or pharmacological agents reduce diabetes incidence or cardiovascular risk factors in prediabetic patients. Searches for lifestyle interventions, drugs, and prevention trials found no supporting passage; page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredA low or inadequate first-phase beta cell response appears to occur due to glucose toxicity.
“A low or inadequate first-phase b cell response is one of the first signs of impaired b cell function (39) and appears to occur due to glucose toxicity (40)(41)(42)(43).”
From A Lower-Carbohydrate, Higher-Fat Diet Reduces Abdominal and Intermuscular Fat and Increases Insulin Sensitivity in Adults at Risk of Type 2 Diabetes (2015) · cites this paper as [40]
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“diovascular risk factors in prediabetic patients.[16] Thus, it is important to look for new prediabetes indicators.”
Background
- Authors
- Godsland, I. F., Jeffs, J. A. R., & Johnston, D. G.
- Affiliations
- St Mary's Hospital (GB)
- Corresponding author
- Godsland, I. F.
- Venue
- Diabetologia
- Published
- 2004-07
- Volume
- 47
- Issue
- 7
- Pages
- 1157-1166
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W1992505070
- Cited by
- 131
- References
- 47
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 7 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 9 · 2014: 9 · 2013: 10 · 2012: 6
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- beta-cell function, fasting blood glucose, first-phase insulin secretion, insulin sensitivity, C-peptide, intravenous glucose tolerance test, non-diabetic men, prediabetes
- MeSH terms
- Insulin Secretion, Adult, Aged, Blood Glucose, Blood Pressure, C-Peptide, Fasting, Glucose Tolerance Test, Humans, Insulin, Islets of Langerhans, Male, Models, Biological, Reference Values, Risk Factors, Smoking, Cohort Studies, Body Mass Index
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