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Published in: Diabetologia 10/2005

01-10-2005 | Article

Visceral fat and beta cell function in non-diabetic humans

Authors: A. Gastaldelli, A. M. Sironi, D. Ciociaro, V. Positano, E. Buzzigoli, D. Giannessi, M. Lombardi, A. Mari, E. Ferrannini

Published in: Diabetologia | Issue 10/2005

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Abstract

Aims/hypothesis

Preferential visceral adipose tissue (VAT) accumulation has been clearly associated with insulin resistance. In contrast, the impact of visceral obesity on beta cell function is controversial.

Methods

In 62 non-diabetic women and men (age 24–69 years, BMI 21–39 kg/m2), we measured VAT and subcutaneous adipose tissue (SAT) fat mass by magnetic resonance imaging. We also measured insulin secretion and beta cell function by C-peptide deconvolution and physiological modelling of data from a frequently sampled, 75-g, 3-h OGTT, respectively.

Results

VAT (range 0.1–3.1 kg) was strongly related to sex, age and BMI; SAT was related to sex and BMI. Controlling for sex, age, BMI and SAT by multivariate analysis, excess VAT was associated with a clinical phenotype comprising higher plasma glucose levels, BP, heart rate and serum transaminases. The corresponding metabolic phenotype consisted of insulin resistance (partial r=−0.38) and hyperinsulinaemia (partial r=0.29). The latter, however, was appropriate for the degree of insulin resistance regardless of obesity and abdominal fat distribution. Moreover, none of the model-derived parameters describing beta cell function (glucose sensitivity, rate sensitivity and potentiation) was independently associated with excess VAT.

Conclusions/interpretation

In non-diabetic Caucasian adults of either sex, preferential visceral fat deposition in itself is part of an insulin-resistant phenotype. The insulin secretory response to a physiological challenge is increased to fully compensate for the insulin resistance, but the dynamics of beta cell function (glucose sensitivity, rate sensitivity and potentiation) are largely preserved.
Literature
1.
go back to reference Despres JP (1998) The insulin resistance-dyslipidemic syndrome of visceral obesity: effect on patients’ risk. Obes Res 16(Suppl 1):8S–17S Despres JP (1998) The insulin resistance-dyslipidemic syndrome of visceral obesity: effect on patients’ risk. Obes Res 16(Suppl 1):8S–17S
2.
go back to reference Goodpaster BH, Krishnaswami S, Resnick H et al (2003) Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 26:372–379PubMed Goodpaster BH, Krishnaswami S, Resnick H et al (2003) Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 26:372–379PubMed
3.
go back to reference Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19PubMed Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19PubMed
4.
go back to reference Ferrannini E, Camastra S, Gastaldelli A et al (2004) Beta-cell function in obesity: effects of weight loss. Diabetes 53(Suppl 3):S26–S33 Ferrannini E, Camastra S, Gastaldelli A et al (2004) Beta-cell function in obesity: effects of weight loss. Diabetes 53(Suppl 3):S26–S33
5.
go back to reference Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, De Fronzo RA (2005) Beta-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab 90:493–500PubMed Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, De Fronzo RA (2005) Beta-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab 90:493–500PubMed
6.
go back to reference Ferrannini E, Gastaldelli A, Miyazaki Y et al (2003) Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia 46:1211–1219PubMed Ferrannini E, Gastaldelli A, Miyazaki Y et al (2003) Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia 46:1211–1219PubMed
7.
go back to reference Kohrt WM, Kirwan JP, Staten MA, Bourey RE, King DS, Holloszy JO (1993) Insulin resistance in aging is related to abdominal obesity. Diabetes 42:273–281PubMed Kohrt WM, Kirwan JP, Staten MA, Bourey RE, King DS, Holloszy JO (1993) Insulin resistance in aging is related to abdominal obesity. Diabetes 42:273–281PubMed
8.
go back to reference Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Jarvinen H, Ferrannini E (1999) Independent influence of age on basal insulin secretion in nondiabetic humans. European group for the study of insulin resistance. J Clin Endocrinol Metab 84:863–868PubMed Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Jarvinen H, Ferrannini E (1999) Independent influence of age on basal insulin secretion in nondiabetic humans. European group for the study of insulin resistance. J Clin Endocrinol Metab 84:863–868PubMed
9.
go back to reference Goran MI, Bergman RN, Gower BA (2001) Influence of total vs. visceral fat on insulin action and secretion in African American and white children. Obes Res 9:423–431PubMed Goran MI, Bergman RN, Gower BA (2001) Influence of total vs. visceral fat on insulin action and secretion in African American and white children. Obes Res 9:423–431PubMed
10.
go back to reference Sumner AE, Farmer NM, Cochran CS et al (2001) Obese premenopausal African–American women with normal and impaired glucose tolerance have a similar degree of insulin resistance but differ in beta-cell function. Diabetes Care 24:1978–1983PubMed Sumner AE, Farmer NM, Cochran CS et al (2001) Obese premenopausal African–American women with normal and impaired glucose tolerance have a similar degree of insulin resistance but differ in beta-cell function. Diabetes Care 24:1978–1983PubMed
11.
go back to reference Cruz ML, Bergman RN, Goran MI (2002) Unique effect of visceral fat on insulin sensitivity in obese Hispanic children with a family history of type 2 diabetes. Diabetes Care 25:1631–1636PubMed Cruz ML, Bergman RN, Goran MI (2002) Unique effect of visceral fat on insulin sensitivity in obese Hispanic children with a family history of type 2 diabetes. Diabetes Care 25:1631–1636PubMed
12.
go back to reference Wagenknecht LE, Langefeld CD, Scherzinger AL et al (2003) Insulin sensitivity, insulin secretion, and abdominal fat. The Insulin Resistance Atherosclerosis Study (IRAS) family study. Diabetes 52:2490–2496PubMed Wagenknecht LE, Langefeld CD, Scherzinger AL et al (2003) Insulin sensitivity, insulin secretion, and abdominal fat. The Insulin Resistance Atherosclerosis Study (IRAS) family study. Diabetes 52:2490–2496PubMed
13.
go back to reference Utzschneider KM, Carr DB, Hull RL et al (2004) Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell function. Diabetes 53:2867–2872PubMed Utzschneider KM, Carr DB, Hull RL et al (2004) Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell function. Diabetes 53:2867–2872PubMed
14.
go back to reference Van Cauter E, Mestrez F, Sturis J, Polonsky KS (1992) Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 41:368–377PubMed Van Cauter E, Mestrez F, Sturis J, Polonsky KS (1992) Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 41:368–377PubMed
15.
go back to reference Mari A, Schmitz O, Gastaldelli A, Oestergaard T, Nyholm B, Ferrannini E (2002) Meal and oral glucose tests for assessment of beta-cell function: modeling analysis in normal subjects. Am J Physiol Endocrinol Metab 283:E1159–E1166PubMed Mari A, Schmitz O, Gastaldelli A, Oestergaard T, Nyholm B, Ferrannini E (2002) Meal and oral glucose tests for assessment of beta-cell function: modeling analysis in normal subjects. Am J Physiol Endocrinol Metab 283:E1159–E1166PubMed
16.
go back to reference Gabir MM, Hanson RL, Dabelea D et al (2000) The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes. Diabetes Care 23:1108–1112PubMed Gabir MM, Hanson RL, Dabelea D et al (2000) The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes. Diabetes Care 23:1108–1112PubMed
17.
go back to reference Ross R, Leger L, Morris D, de Guise J, Guardo R (1992) Quantification of adipose tissue by MRI: relationship with anthropometric variables. J Appl Physiol 72:787–795PubMed Ross R, Leger L, Morris D, de Guise J, Guardo R (1992) Quantification of adipose tissue by MRI: relationship with anthropometric variables. J Appl Physiol 72:787–795PubMed
18.
go back to reference Positano V, Gastaldelli A, Sironi AM, Santarelli MF, Lombardi M, Landini L (2004) An accurate and robust method for unsupervised assessment of abdominal fat by MRI. J Magn Reson Imaging 20:684–689PubMed Positano V, Gastaldelli A, Sironi AM, Santarelli MF, Lombardi M, Landini L (2004) An accurate and robust method for unsupervised assessment of abdominal fat by MRI. J Magn Reson Imaging 20:684–689PubMed
19.
go back to reference Snyder W, Cooke M, Mnassett E, Larhansen L, Howells G, Tipton I (1975) Report of the task group on reference man. Pergamon Press, Oxford Snyder W, Cooke M, Mnassett E, Larhansen L, Howells G, Tipton I (1975) Report of the task group on reference man. Pergamon Press, Oxford
20.
go back to reference Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ (2001) A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548PubMed Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ (2001) A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548PubMed
21.
go back to reference Kobayashi J, Tadokoro N, Watanabe M, Shinomiya M (2002) A novel method of measuring intra-abdominal fat volume using helical computed tomography. Int J Obes Relat Metab Disord 26:398–402PubMed Kobayashi J, Tadokoro N, Watanabe M, Shinomiya M (2002) A novel method of measuring intra-abdominal fat volume using helical computed tomography. Int J Obes Relat Metab Disord 26:398–402PubMed
22.
go back to reference Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738PubMed Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738PubMed
23.
go back to reference Ferrannini E, Mari A (2004) Beta cell function and its relation to insulin action in humans: a critical appraisal. Diabetologia 47:943–956PubMed Ferrannini E, Mari A (2004) Beta cell function and its relation to insulin action in humans: a critical appraisal. Diabetologia 47:943–956PubMed
24.
go back to reference Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19PubMed Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19PubMed
25.
go back to reference Robertson RP, Harmon J, Tran PO, Poitout V (2004) Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 53(Suppl 1):S119–S124PubMed Robertson RP, Harmon J, Tran PO, Poitout V (2004) Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 53(Suppl 1):S119–S124PubMed
26.
go back to reference Wajchenberg BL, Giannella-Neto D, Da Silva ME, Santos RF (2002) Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Horm Metab Res 34:616–621PubMed Wajchenberg BL, Giannella-Neto D, Da Silva ME, Santos RF (2002) Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Horm Metab Res 34:616–621PubMed
27.
go back to reference Kabir M, Catalano KJ, Ananthnarayan S et al (2005) Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance. Am J Physiol Endocrinol Metab 288:E454–E461CrossRef Kabir M, Catalano KJ, Ananthnarayan S et al (2005) Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance. Am J Physiol Endocrinol Metab 288:E454–E461CrossRef
28.
go back to reference Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588PubMed Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD (2004) Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588PubMed
Metadata
Title
Visceral fat and beta cell function in non-diabetic humans
Authors
A. Gastaldelli
A. M. Sironi
D. Ciociaro
V. Positano
E. Buzzigoli
D. Giannessi
M. Lombardi
A. Mari
E. Ferrannini
Publication date
01-10-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1891-3

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