Insulin Resistance and Hyperinsulinemia
Open accessAbstract
Insulin resistance, recently recognized as a strong predictor of disease in adults, has become the leading element of the metabolic syndrome and renewed as a focus of research. The condition exists when insulin levels are higher than expected relative to the level of glucose. Thus, insulin resistance is by definition tethered to hyperinsulinemia. The rising prevalence of medical conditions where insulin resistance is common has energized research into the causes. Many causes and consequences have been identified, but the direct contributions of insulin itself in causing or sustaining insulin resistance have received little sustained attention. We examine situations where insulin itself appears to be a proximate and important quantitative contributor to insulin resistance. 1) Mice transfected with extra copies of the insulin gene produce basal and stimulated insulin levels that are two to four times elevated. The mice are of normal weight but show insulin resistance, hyperglycemia, and hypertriglyceridemia. 2) Somogyi described patients with unusually high doses of insulin and hyperglycemia. Episodes of hypoglycemia with release of glucose-raising hormones, postulated as the culprits in early studies, have largely been excluded by studies including continuous glucose monitoring. 3) Rats and humans treated with escalating doses of insulin show both hyperinsulinemia and insulin resistance. 4) The pulsatile administration of insulin (rather than continuous) results in reduced requirements for insulin. 5) Many patients with insulinoma who have elevated basal levels of insulin have reduced (but not absent) responsiveness to administered insulin. In summary, hyperinsulinemia is often both a result and a driver of insulin resistance.
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Insulin resistance leads to basal-fasting hyperinsulinemia, which may result in insensitivity of beta-cell secretion, leading to lower first-phase insulin secretion to rising postprandial glucose but a subsequent exaggerated compensatory second-phase insulin secretion, which might result in hypoglycemia.
“As indicated by several studies, insulin resistance leads to basal-fasting hyperinsulinemia, which may result in the insensitivity of beta-cell secretion. This insensitivity leads to a lower first-phase insulin secretion to the rising postprandial glucose but a subsequent exaggerated compensatory second-phase insulin secretion, which might result in hypoglycemia [2, 3].”
From Associated Factors with Biochemical Hypoglycemia during an Oral Glucose Tolerance Test in a Chinese Population (2017) · cites this paper as [2]
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- Authors
- Shanik, M. H., Xu, Y., Škrha, J., Dankner, R., Zick, Y., & Roth, J.
- Affiliations
- Northwell Health (US)
- Department of Internal Medicine 3, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- Cardiovascular Epidemiology Unit, Gertner Institute for Epidemiology and Health Policy Research, Tel-Hashomer, Israel
- Weizmann Institute of Science (IL)
- Albert Einstein College of Medicine (US)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2008-02-01
- Volume
- 31
- Issue
- Supplement_2
- Pages
- S262-S268
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2025578932
- Cited by
- 791
- References
- 3
- Citations by year
- 2026: 24 · 2025: 46 · 2024: 41 · 2023: 46 · 2022: 57 · 2021: 68 · 2020: 84 · 2019: 49 · 2018: 56 · 2017: 51 · 2016: 50 · 2015: 42 · 2014: 50 · 2013: 38 · 2012: 32
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin resistance, hyperinsulinemia, metabolic syndrome, hypertriglyceridemia, Somogyi effect, hypoglycemia, insulinoma, insulin responsiveness
- MeSH terms
- Insulin Secretion, Animals, Diabetes Mellitus, Type 2, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Mice, Transgenic, Obesity, Incidence, Mice
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