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Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia.
Open accessAbstract
We have used a continuous intravenous infusion of glucose (6 mg/kg/min), insulin (80 mU/min), epinephrine (6 mug/min), and propranolol (0.08 mg/min) to directly assess insulin resistance in 14 untreated adult onset diabetics with a mean (plus or minus SE) fasting plasma glucose level of 217 plus or minus 17 mg/100 ml. During the infusion endogenous insulin secretion is inhibited and steady-state plasma glucose and insulin levels are achieved after 90 min. Since similar steady-state levels of plasma insulin are achieved in all subjects, the plasma glucose concentration observed during the steady-state period is a measure of an individual's insulin resistance. Under these conditions, the mean (plus or minus SE) steady-state plasma glucose level of the 14 diabetic patients was 350 plus or minus 16 mg/100 ml, while that of 12 normal subjects was 121 plus or minus 4 mg/100 ml. Additional studies were performed in which control subjects and patients with diabetes had their fasting plasma glucose levels acutely raised or lowered to comparable levels before receiving the basic infusion mixture of glucose, insulin, epinephrine, and propranolol. The results of these studies indicated that differences in initial plasma glucose levels could not account for the different glucose responses of the two groups to the basic infusion. Finally, the mean (plus or minus SE) steady-state plasma glucose level of 104 plus or minus 17 mg/100 ml observed during the same basic infusion in five patients with fasting hyperglycemia (mean plus or minus SE, 142 plus or minus 12 mg/100 ml) secondary to chronic pancreatitis suggested that neither chronic hyperglycemia nor hypoinsulinemia per se necessarily lead to insulin resistance. These results demonstrate that marked insulin resistance exists in adult onset diabetics with fasting hyperglycemia. Since previous studies have documented the presence of insulin resistance in patients with chemical diabetes, the possibility exists that insulin resistance may be characteristic of adult onset diabetes mellitus.
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“Insulin resistance in skeletal muscle also has been reported in association with the normal ageing process [37], dyslipidemia (increased plasma triglyceride/decreased HDL cholesterol) [4, 26], and in association with many disease states including polycystic ovary syndrome (PCOs) [38], chronic kidney failure [39], heart failure [40], myotonic dystrophy [41], and lipodystrophy [42].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [26]
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Citations
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Is there a Delay in the Plasma Insulin Response of Patients with Chemical Diabetes Mellitus?
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Self-citationInsulin Patterns in Equivocal Glucose Tolerance Tests (Chemical Diabetes)
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Comparison of the Effects of Metabolic Acidosis and Acute Uremia on Carbohydrate Tolerance
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Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154
Self-citationMancia, G., Kreutz, R., Brunström, M., Burnier, M., Grassi, G., Januszewicz, A., Muiesan, M. L., Tsioufis, K., Agabiti-Rosei, E., Algharably, E. A. E., et al. (2023) · Journal of Hypertension · doi:10.1097/hjh.0000000000003480 · Cited by 3,473
The Metabolic Syndrome: Time for a Critical Appraisal
Kahn, R., Buse, J. B., Ferrannini, E., & Stern, M. P. (2005) · Diabetes Care · doi:10.2337/diacare.28.9.2289 · Cited by 2,400
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
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Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342
Metadata
- Authors
- Ginsberg, H., Kimmerling, G., Olefsky, J. M., & Reaven, G. M.
- Affiliations
- United States Department of Veterans Affairs (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1975-03-01
- Volume
- 55
- Issue
- 3
- Pages
- 454-461
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC301772
- OpenAlex
- W2055493265
- Cited by
- 225
- References
- 20
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 2 · 2012: 6
- FWCI
- 5.89
- 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 › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin resistance, adult-onset diabetes mellitus, fasting hyperglycemia, type 2 diabetes, steady-state plasma glucose, epinephrine, propranolol, chronic pancreatitis, hypoinsulinemia, endogenous insulin secretion
- MeSH terms
- Adult, Aged, Chronic Disease, Diabetes Mellitus, Epinephrine, Fasting, Female, Glucose, Humans, Hyperglycemia, Insulin, Insulin Resistance, Male, Middle Aged, Pancreatitis, Propranolol, Diabetes Complications
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