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Insulin resistance and hypersecretion in obesity: European Group for the Study of Insulin Resistance (EGIR)
Open accessAbstract
Insulin resistance and insulin hypersecretion are established features of obesity. Their prevalence, however, has only been inferred from plasma insulin concentrations. We measured insulin sensitivity (as the whole-body insulin-mediated glucose uptake) and fasting posthepatic insulin delivery rate (IDR) with the use of the euglycemic insulin clamp technique in a large group of obese subjects in the database of the European Group for the Study of Insulin Resistance (1,146 nondiabetic, normotensive Caucasian men and women aged 18-85 yr, with a body mass index (BMI) ranging from 15 to 55 kg.m-2). Insulin resistance, defined as the lowest decile of insulin sensitivity in the lean subgroup (608 subjects with a mean BMI of 29 kg.m-2). Insulin sensitivity declined linearly with BMI at an age- and sex-adjusted rate of 1.2 micromol.min-1.kg FFM-1 per BMI unit (95% confidence intervals = 1.0-1.4). Insulin hypersecretion, defined as the upper decile of IDR, was significantly (P<0.0001) more prevalent (38%) than insulin resistance in the obese group. In the whole dataset, IDR rose as a function of both BMI and insulin resistance in a nonlinear fashion. Neither the waist circumference nor the waist-to-hip ratio, indices of body fat distribution, was related to insulin sensitivity after adjustment for age, gender, and BMI; both, however, were positively associated (P<0.001) with insulin hypersecretion, particularly in women. In nondiabetic, normotensive obese subjects, the prevalence of insulin resistance is relatively low, and is exceeded by the prevalence of insulin hypersecretion, particularly in women with central obesity. In the obese with preserved insulin sensitivity, risk for diabetes, cardiovascular risk, and response to treatment may be different than in insulin resistant obesity.
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“Because the great majority of glucose disposal after intravenous glucose administration occurs in muscle, these results provide strong evidence that insulin resistance in muscle is the earliest demonstrable defect in the natural history of type 2 diabetes, but that the development of overt type 2 diabetes occurs only in those individuals whose β-cells are unable to compensate for the defect in”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [48]
Experimental — accuracy not yet measuredIn the citing paper
“Given the strong association between BMI and insulin sensitivity (8), groups with large differences in insulin sensitivity are generally difficult to match for BMI and fat mass, complicating data interpretation.”
From Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity (2018) · cites this paper as [8]
In the citing paper
“A similar relationship also exists between BMI and the degree of insulin resistance.22”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [22]
In the citing paper
“one study reported that 19, 34 and 60% of individuals with a BMI of <30, ≥30–35 and >35, respectively, were insulin resistant.22”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [22]
In the citing paper
“It is well established that there is a generally directly proportional relationship between BMI and both fasting and postprandial insulin levels.21,22”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [22]
In the citing paper
“The hyperinsulinemia associated with rising BMI is necessary to overcome insulin resistance and maintain normoglycemia.22”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [22]
In the citing paper
“Insulin hypersecretion also becomes more frequent with increasing BMI;24 28, 49 and 80% of individuals with a BMI of <30, >30–35 and >35, respectively, exhibited insulin hypersecretion.22”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [22]
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“The relationship between obesity and insulin resistance, while well recognized for many years, has nonetheless been confusing since not all obese individuals have insulin resistance (1) and because insulin resistance occurs in individuals who have BMIs that are within the normal or mildly overweight categories (2).”
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“The prevalence rates of type 2 diabetes mellitus (T2DM), a metabolic disorder associated with obesity (Ferrannini et al., 1997) and age (Morley, 2008), have risen markedly in recent years (Wild, Roglic, Green, Sicree, and King, 2004).”
Metadata
- Authors
- Ferrannini, E., Natali, A., Bell, P., Cavallo-Perin, P., Lalic, N., & Mingrone, G.
- Affiliations
- Istituto di Fisiologia Clinica (IT)
- Venue
- Journal of Clinical Investigation
- Published
- 1997-09-01
- Volume
- 100
- Issue
- 5
- Pages
- 1166-1173
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508292
- OpenAlex
- W2036400933
- Cited by
- 898
- References
- 53
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 20 · 2023: 13 · 2022: 20 · 2021: 28 · 2020: 32 · 2019: 26 · 2018: 32 · 2017: 26 · 2016: 26 · 2015: 36 · 2014: 30 · 2013: 36 · 2012: 43
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- Università degli Studi di Napoli Federico II
- Helsingin Yliopisto
- Universität Heidelberg
- Lunds Universitet
- Università degli Studi di Padova
- National and Kapodistrian University of Athens
- Université de Genève
- Università degli Studi di Torino
- Università degli Studi di Verona
- 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 › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin resistance, insulin hypersecretion, obesity, insulin sensitivity, body mass index, waist circumference, waist-to-hip ratio, abdominal obesity, sex differences, hyperinsulinemic-euglycemic clamp, type 2 diabetes risk
- MeSH terms
- Insulin Secretion, Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Body Mass Index
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