The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index.
The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus
Open accessAbstract
The pathogenesis of type 2 diabetes involves abnormalities in insulin action, insulin secretion, and endogenous glucose output (EGO). However, the sequence with which these abnormalities develop and their relative contributions to the deterioration in glucose tolerance remain unclear in the absence of a detailed longitudinal study. We measured insulin action, insulin secretion, and EGO longitudinally in 17 Pima Indians, in whom glucose tolerance deteriorated from normal (NGT) to impaired (IGT) to diabetic over 5.1 +/- 1.4 years. Transition from NGT to IGT was associated with an increase in body weight, a decline in insulin-stimulated glucose disposal, and a decline in the acute insulin secretory response (AIR) to intravenous glucose, but no change in EGO. Progression from IGT to diabetes was accompanied by a further increase in body weight, further decreases in insulin-stimulated glucose disposal and AIR, and an increase in basal EGO. Thirty-one subjects who retained NGT over a similar period also gained weight, but their AIR increased with decreasing insulin-stimulated glucose disposal. Thus, defects in insulin secretion and insulin action occur early in the pathogenesis of diabetes. Intervention to prevent diabetes should target both abnormalities.
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In the citing paper
“Insulin resistance and concurrent relative insulin deficiency and glucagon dysregulation underlie T2D pathophysiology.33–35”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [34]
Experimental — accuracy not yet measuredIn the citing paper
“These findings derived from cross-sectional data are supported by a longitudinal study in Pima Indians that has also shown the importance of accounting for the hyperbolic relationship between insulin sensitivity and insulin secretion and demonstrated the presence of impaired beta-cell function in those destined to progress to Type 2 diabetes [95].”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [95]
In the citing paper
“Seventeen (35%) of these subjects progressed from NGT to IGT and then to diabetes during follow up.”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [95]
In the citing paper
“Our finding of a hyperbolic relationship between insulin sensitivity and insulin secretion in healthy subjects has been confirmed in large cohorts of Danish [94] and Pima Indian subjects [95].”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [95]
In the citing paper
“During follow up, insulin secretion declined progressively by 78% while insulin sensitivity decreased by only 14%.”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [95]
In the citing paper
“Based on the UKPDS [18] and the longitudinal assessment in Pima Indians [95], the major reason for the decline in glucose tolerance seems to be a progressive loss of beta-cell function.”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [95]
In the citing paper
“Further progressive deterioration of β-cell function accounts for the evolving natural history of the disease from impaired glucose tolerance to type 2 diabetes10,11.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [10]
In the citing paper
“Our results may help explain the aforementioned association between N3 lack and T2DM, as a loss in first-phase insulin secretion is both an early marker of T2DM and part of its pathogenesis (20).”
From Sleep architecture and glucose and insulin homeostasis in obese adolescents (2011) · cites this paper as [20]
In the citing paper
“IGT and T2DM ensue when beta cell function fails to compensate.”
From The Vasculature in Prediabetes (2018) · cites this paper as [16]
In the citing paper
“Insulin resistance precedes the development of hyperglycemia and T2DM and results in compensatory hyperinsulinemia.”
From The Vasculature in Prediabetes (2018) · cites this paper as [16]
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Citations
Cites
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“It is well known that there is a hyperbolic relationship between early insulin secretion and insulin action in individuals with NGT, meaning that, cross-sectionally, insulin secretion increases with decreasing insulin action and vice versa (51, 52).”
BackgroundMethodInfluentialTechniques for Measuring Body Composition
National Research Council (1961) · National Academies Press eBooks · doi:10.17226/21603 · Cited by 1,620
Flagged first, then by citations
1 of the 68 references couldn’t be matched to a known paper.
Research works printed but not linked: 6
- 1998, Diabetes Care, 21(Suppl. 1), S5
- DeFronzo, 1997, Diabetes Reviews, 5, 177
- Abbott, 1990, Am J Physiol, 258, E347
- Bogardus, 1984, J Clin Invest, 78, 1568
- Schwartz, 1995, J Clin Endocrinol Metab, 80, 1571
- Luzi, 1989, Am J Physiol, 257, E241
Cited by
Sorted by citations
Items 1,001–1,002 of 1,002
Heikkilä, H. M., Krachler, B., Rauramaa, R., & Schwab, U. S. (2014) · British Journal of Nutrition · doi:10.1017/s0007114514002426 · Cited by 12
Razavi, L. N., Ebenibo, S., Edeoga, C., Wan, J., & Dagogo-Jack, S. (2020) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2020.03.005 · Cited by 4
Metadata
- Authors
- Weyer, C., Bogardus, C., Mott, D. M., & Pratley, R. E.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Weyer, Christian
- Venue
- Journal of Clinical Investigation
- Published
- 1999-09-15
- Volume
- 104
- Issue
- 6
- Pages
- 787-794
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC408438
- OpenAlex
- W2077149049
- Cited by
- 1,940
- References
- 68
- Citations by year
- 2026: 24 · 2025: 53 · 2024: 53 · 2023: 74 · 2022: 63 · 2021: 80 · 2020: 64 · 2019: 64 · 2018: 61 · 2017: 72 · 2016: 88 · 2015: 81 · 2014: 91 · 2013: 85 · 2012: 83
- FWCI
- 44.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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
- type 2 diabetes, insulin resistance, insulin secretion, impaired glucose tolerance, Pima Indians, insulin-stimulated glucose disposal, weight gain, diabetes prevention, pathogenesis
- MeSH terms
- Insulin Secretion, Adult, Anthropometry, Diabetes Mellitus, Type 2, Female, Glucose, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Obesity, Sex Factors
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