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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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In the citing paper
“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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Differential effect of weight loss on insulin resistance in surgically treated obese patients
Muscelli, E., Mingrone, G., Camastra, S., Manco, M., Pereira, J. A., Pareja, J. C., & Ferrannini, E. (2005) · The American Journal of Medicine · doi:10.1016/j.amjmed.2004.08.017 · Cited by 130
Self-citationBansal, T. C., Guay, A. T., Jacobson, J., Woods, B. O., & Nesto, R. W. (2005) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2005.20120.x · Cited by 132
Gender differences in lipid and glucose kinetics during short-term fasting.
Mittendorfer, B., Horowitz, J. F., & Klein, S. (2001) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.6.e1333 · Cited by 129
“Although several studies have reported that insulin sensitivity with respect to glucose metabolism was similar in men and women (2, 10), other investigators have found that insulin sensitivity, assessed by an oral glucose tolerance test (7, 9) or a hyperinsulinemic euglycemic clamp (8, 39, 41, 49), was greater in wome…”
ResultRelationship between changes in neck circumference and cardiovascular risk factors.
Ben-Noun, L. L., & Laor, A. (2006) · PubMed Central · Cited by 132
Stanická, S., Vondra, K., Pelikánová, T., Vlček, P., Hill, M., & Zamrazil, V. (2005) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2005.121 · Cited by 128
“An important and yet unreported observation is the finding that H is associated with an inverse correlation between insulin secretion (expressed as PHD) and insulin sensitivity markers (M), which has been reported in the healthy population without impaired glucose tolerance (18).”
BackgroundResultMetabolically healthy but obese individuals: relationship with hepatic enzymes
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Diabetes incidence and glucose intolerance prevalence increase with higher outdoor temperature
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“In fact, not only is IR strongly related to insulin secretion in a reciprocal manner (10), but the compensatory hyperinsulinemia feeds back negatively on insulin action.”
BackgroundSelf-citationPlatelets and diabetes mellitus
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Impact of obesity on the risk of heart failure and survival after the onset of heart failure
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Isokuortti, E., Zhou, Y., Peltonen, M., Bugianesi, E., Clement, K., Bonnefont-Rousselot, D., Lacorte, J.-M., Gastaldelli, A., Schuppan, D., Schattenberg, J. M., et al. (2017) · Diabetologia · doi:10.1007/s00125-017-4340-1 · Cited by 120
“This is particularly relevant for HOMA-IR, as obesity is highly prevalent and perhaps the single most important cause of variation in insulin [13].”
BackgroundA blunted cortisol awakening response and hippocampal atrophy in type 2 diabetes mellitus
Bruehl, H., Wolf, O. T., & Convit, A. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.12.010 · Cited by 142
“Risk factors for developing T2DM include age (Panagiotakos et al., 2008), physical inactivity (Dyck et al., 2008), obesity (Ferrannini et al., 1997) and genetic predisposition (Busch and Hegele, 2001).”
Hwang, L. C., Bai, C. H., Sun, C. A., & Chen, C. (2012) · PubMed · Cited by 116
Increased Fat Mass Compensates for Insulin Resistance in Abdominal Obesity and Type 2 Diabetes
Virtanen, K. A., Iozzo, P., Hällsten, K., Huupponen, R., Parkkola, R. K., Janatuinen, T., Lönnqvist, F., Viljanen, T., Rönnemaa, T., Lönnroth, P., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2720 · Cited by 116
“This phenomenon has been previously surmised to occur in obese subjects (27) in whom insulin-stimulated glucose uptake, when expressed not per unit fat-free mass but as total M, declined only at BMIs in the range of morbid obesity.”
Self-citationGower, B. A., Granger, W. M., Franklin, F., Shewchuk, R. M., & Goran, M. I. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.5.8498 · Cited by 114
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“There is a negative linear relationship between body mass index and whole-body insulin sensitivity (Ferrannini et al. 1997).”
BackgroundGuo, F., & Garvey, W. T. (2015) · Obesity · doi:10.1002/oby.21344 · Cited by 112
“Although obesity can exacerbate insulin resistance and impel the progression of cardiometabolic disease, lean individuals can be afflicted with insulin resistance and cardiometabolic disease, albeit with relative fat distribution to the intra-abdominal compartment, and individuals with obesity can be relatively insuli…”
BackgroundResultInfluentialAndrogen excess is the key element in polycystic ovary syndrome
Azziz, R. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(03)00735-0 · Cited by 109
Insulin Resistance: the Link Between Obesity and Cardiovascular Disease
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St-Pierre, D. H., Karelis, A. D., Coderre, L., Malita, F. M., Fontaine, J., Mignault, D., Brochu, M., Bastard, J., Cianflone, K., Doucet, É., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1603 · Cited by 110
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Insulin: in search of a syndrome
Ferrannini, E., & Balkau, B. (2002) · Diabetic Medicine · doi:10.1046/j.1464-5491.2002.00794.x · Cited by 107
Self-citation
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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