The relationship between fasting hyperglycemia and insulin secretion in subjects with normal or impaired glucose tolerance
Open accessAbstract
To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT (n = 293) and IGT (n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as DeltaISR/DeltaG / IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(-0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0-30 min) was correlated with the increase in FPG in both NGT and IGT (r = -0.43, P < 0.0001 and r = -0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60-120 min) and FPG was not significant. In conclusion, small increments in FPG, within the "normal" range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.
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A low or inadequate first-phase beta cell response is one of the first signs of impaired beta cell function.
“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 [39]
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- Authors
- Abdul-Ghani, M. A., Matsuda, M., Jani, R., Jenkinson, C. P., Coletta, D. K., Kaku, K., & DeFronzo, R. A.
- Affiliations
- Kawasaki Medical School (JP)
- The University of Texas at San Antonio Health Science Center (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-08
- Volume
- 295
- Issue
- 2
- Pages
- E401-E406
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC4043181
- OpenAlex
- W1994299902
- Cited by
- 91
- References
- 51
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 5
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067690, R01DK079195)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- fasting blood glucose, insulin secretion, impaired glucose tolerance, normal glucose tolerance, disposition index, first-phase insulin secretion, Matsuda index, C-peptide, oral glucose tolerance test, non-diabetic patients
- MeSH terms
- Insulin Secretion, Blood Glucose, C-Reactive Protein, Fasting, Female, Glucose Tolerance Test, Humans, Hyperglycemia, Insulin, Insulin Resistance, Male, Middle Aged, Glucose Intolerance, Area Under Curve
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