Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans
Open accessAbstract
OBJECTIVE: To compare the pathophysiology of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a more comprehensive and standardized fashion than has hitherto been done. RESEARCH DESIGN AND METHODS: We studied 21 individuals with isolated IFG (IFG/normal glucose tolerance [NGT]), 61 individuals with isolated IGT (normal fasting glucose [NFG]/IGT), and 240 healthy control subjects (NFG/NGT) by hyperglycemic clamps to determine first- and second-phase insulin release and insulin sensitivity. Homeostasis model assessment (HOMA) indexes of beta-cell function (HOMA-%B) and insulin resistance (HOMA-IR) were calculated from fasting plasma insulin and glucose concentrations. RESULTS: Compared with NFG/NGT, IFG/NGT had similar fasting insulin concentrations despite hyperglycemia; therefore, HOMA-IR was increased approximately 30% (P < 0.05), but clamp-determined insulin sensitivity was normal (P > 0.8). HOMA-%B and first-phase insulin responses were reduced approximately 35% (P < 0.002) and approximately 30% (P < 0.02), respectively, but second-phase insulin responses were normal (P > 0.5). NFG/IGT had normal HOMA-IR but approximately 15% decreased clamp-determined insulin sensitivity (P < 0.03). Furthermore, HOMA-%B was normal but both first-phase (P < 0.0003) and second-phase (P < 0.0001) insulin responses were reduced approximately 30%. IFG/NGT differed from NFG/IGT by having approximately 40% lower HOMA-%B (P < 0.012) and approximately 50% greater second-phase insulin responses (P < 0.005). CONCLUSIONS: Since first-phase insulin responses were similarly reduced in IFG/NGT and NFG/IGT, we conclude that IFG is due to impaired basal insulin secretion and preferential resistance of glucose production to suppression by insulin, as reflected by fasting hyperglycemia despite normal plasma insulin concentrations and increased HOMA-IR, whereas IGT mainly results from reduced second-phase insulin release and peripheral insulin resistance, as reflected by reduced clamp-determined insulin sensitivity.
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Individuals 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 [19]
The Hyperglycemic clamp discussion says IFG may involve preferential hepatorenal insulin resistance with normal or near-normal muscle sensitivity, while IGT may involve preferential muscle resistance. It does not establish the claimed severe-versus-moderate degrees: it describes IGT hepatorenal sensitivity as normal or near-normal, and the Abstract reports only an approximately 15% decrease in clamp-determined sensitivity for IGT. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBoth 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 [19]
Both fasting and postprandial glucose measures are predictive of type 2 diabetes, and may represent two distinct risk factors that contribute to diabetes via different physiological mechanisms.
“There is evidence that both fasting and postprandial glucose measures are predictive of type 2 diabetes, and these may represent two distinct risk factors that may contribute to diabetes via different physiological mechanisms (43).”
From Social jetlag, chronotype, and cardiometabolic risk (2015) · cites this paper as [43]
IFG is characterized primarily by impaired hepatic insulin sensitivity and a decrease in the first-phase insulin response.
“IFG is characterized primarily by impaired hepatic insulin sensitivity and a decrease in the first-phase insulin response”
From The Vasculature in Prediabetes (2018) · cites this paper as [14]
IGT is characterized by impaired muscle insulin sensitivity as well as early and late phase insulin responses.
“IGT is characterized by impaired muscle insulin sensitivity as well as early and late phase insulin responses.”
From The Vasculature in Prediabetes (2018) · cites this paper as [14]
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References 23 · Cited by 308
Research works printed but not linked: 1
- Bratusch-Marrain PR: [The euglycemic insulin and hyperglycemic clamp technic: methods for the determination of insulin sensitivity of tissues and glucose sensitiv- ity of the B cell: a review.] Infusionsther Klin Ernahr 11:4 -10, 1984 [article in German]
- Authors
- Meyer, C., Pimenta, W., Woerle, H. J., Van Haeften, T., Szoke, E., Mitrakou, A., & Gerich, J.
- Affiliations
- Carl T. Hayden Veterans Affairs Medical Center (US)
- Universidade de São Paulo (BR)
- Ludwig-Maximilians-Universität München (DE)
- Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
- University of Rochester Medicine (US)
- Henry Dunant Hospital (GR)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2006-08-01
- Volume
- 29
- Issue
- 8
- Pages
- 1909-1914
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2165152751
- Cited by
- 308
- References
- 23
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 17 · 2023: 21 · 2022: 12 · 2021: 16 · 2020: 15 · 2019: 16 · 2018: 12 · 2017: 13 · 2016: 16 · 2015: 8 · 2014: 16 · 2013: 19 · 2012: 15
- FWCI
- 19.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- American Diabetes Association
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-20411)
- National Center for Research Resources (M01RR000044)
- 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
- impaired fasting glucose, impaired glucose tolerance, insulin secretion, first-phase insulin response, second-phase insulin response, insulin sensitivity, insulin resistance, beta-cell function, hyperglycemia
- MeSH terms
- Adult, Blood Glucose, Diet, Female, Glucose Tolerance Test, Humans, Hyperglycemia, Insulin, Male, Body Mass Index, Waist-Hip Ratio
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