Abstract
Ten patients with type 2 diabetes were enrolled in an isoglycemic glucose clamp study to determine the impact of intra-abdominal fat, subcutaneous abdominal fat and total abdominal fat on the metabolic effect of a single bolus (0.2 IU/kg) of sc-injected human regular insulin. The maximum metabolic effect associated highly and negatively with intra-abdominal fat (r = - 0.72, p < 0.02) and with the homeostasis model assessment insulin resistance score (HOMA, r = - 0.71, p < 0.03). Likewise, the total metabolic effect of sc-injected insulin correlated strongly and negatively with intra-abdominal fat (r = - 0.77, p < 0.01), HOMA (r = - 0.74, p < 0.02) and HbA1c (r = - 0.70, p < 0.03). Stepwise multiple regression analyses showed that the highest metabolic effect was only significantly predicted by intra-abdominal fat, indicating a high negative correlation with the maximum effect (β = - 0.72) whereas time to maximum metabolic effect showed a strong (β = 0.72) and positive correlation with HOMA. In combination with the HOMA, it is intra-abdominal fat, and not subcutaneous abdominal fat, which explains 50 - 75 % of the variability of the effect of sc human regular insulin in patients with type 2 diabetes.
Key words
Visceral fat - Insulin action - Adipose tissue - Anthropology - Abdominal imaging
References
-
1
Yamashita S, Nakamura T, Shimomura I, Nishida M, Yoshida S, Kotani K, Kameda-Takemuara K, Tokunaga K, Matsuzawa Y.
Insulin resistance and body fat distribution.
Diab Care.
1996;
19
287-291
-
2
Hernandez-Ono A, Monter-Carreola G, Zamora-Gonzalez J, Cardoso-Saldana G, Posadas-Sanchez R, Torres-Tamayo M, Posadas-Romero C.
Association of visceral fat with coronary risk factors in a population-based sample of postmenopausal women.
Int J Obes Relat Metab Disord.
2002;
26
33-39
-
3
Brochu M, Starling R D, Tchernof A, Matthews D E, Garcia-Rubi E, Poehlman E T.
Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women.
J Clin Endocrinol Metab.
2000;
85
2378-2384
-
4
Banerji M A, Faridi N, Atluri R, Chaiken R L, Lebovitz H E.
Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men.
J Clin Endocrinol Metab.
1999;
84
137-144
-
5
Atzmon G, Yang X M, Muzumdar R, Ma X H, Gabriely I, Barzilai N.
Differential gene expression between visceral and subcutaneous fat depots.
Horm Metab Res.
2002;
34
622-628
-
6
.
Report of the Expert Committee on the Diagnosisand Classification of Diabetes Mellitus.
Diab Care.
1998;
21
5-19
-
7
Poll L W, Wittsack H J, Koch J A, Willers R, Scherer A, Kapitza C, Heinemann L, Modder U.
Quantification of total abdominal fat volumes using magnetic resonance imaging.
Eur J Med Res.
2002;
7
347-352
-
8
Lancaster J L, Ghiatas A A, Alyassin A, Kilcoyne R F, Bonora E, DeFronzo R A.
Measurement of abdominal fat with T1-weighted MR images.
J Magn Reson Imaging.
1991;
1
363-369
-
9
Durnin J V, Womersley J.
Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years.
Br J Nutr.
1974;
32
77-97
-
10
Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C.
Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
Diabetologia.
1985;
28
412-419
-
11
Rave K, Heise T, Pfutzner A, Heinemann L, Sawicki P T.
Impact of diabetic nephropathy on pharmacodynamic and pharmacokinetic properties of insulin in type 1 diabetic patients.
Diabetes Care.
2001;
24
886-890
-
12
Ross R, Dagnone D, Jones P J, Smith H, Paddags A, Hudson R, Janssen I.
Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial.
Ann Intern Med.
2000;
133
92-103
-
13
Vora J P, Burch A, Peters J R, Owens D R.
Relationship between absorption of radiolabeled soluble insulin, subcutaneous blood flow, and anthropometry.
Diab Care.
1992;
15
1484-1493
-
14
Sjostrand M, Gudbjornsdottir S, Holmang A, Lonn L, Strindberg L, Lonnroth P.
Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects.
Diab.
2002;
51
2742-2748
-
15
Caprio S, Hyman L D, Limb C, McCarthy S, Lange R, Sherwin R S, Shulman G, Tamborlane W V.
Central adiposity and its metabolic correlates in obese adolescent girls.
Am J Physiol.
1995;
269
E118-E126
-
16
Gautier J F, Mourier A, de Kerviler E, Tarentola A, Bigard A X, Villette J M, Guezennec C Y, Cathelineau G.
Evaluation of abdominal fat distribution in noninsulin-dependent diabetes mellitus: relationship to insulin resistance.
J Clin Endocrinol Metab.
1998;
83
1306-1311
-
17
Carey D G, Jenkins A B, Campbell L V, Freund J, Chisholm D J.
Abdominal fat and insulin resistance in normal and overweight women: Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM.
Diab.
1996;
45
633-638
-
18
Gastaldelli A, Miyazaki Y, Pettiti M, Matsuda M, Mahankali S, Santini E, DeFronzo R A, Ferrannini E.
Metabolic effects of visceral fat accumulation in type 2 diabetes.
J Clin Endocrinol Metab.
2002;
87
5098-5103
-
19
Goodpaster B H, Thaete F L, Simoneau J A, Kelley D E.
Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat.
Diab.
1997;
46
1579-1585
-
20
Park K S, Rhee B D, Lee K U, Kim S Y, Lee H K, Koh C S, Min H K.
Intra-abdominal fat is associated with decreased insulin sensitivity in healthy young men.
Metabolism.
1991;
40
600-603
-
21
Abate N, Garg A, Peshock R M, Stray-Gundersen J, Grundy S M.
Relationships of generalized and regional adiposity to insulin sensitivity in men.
J Clin Invest.
1995;
96
88-98
-
22
Lovejoy J C, de la Bretonne J A, Klemperer M, Tulley R.
Abdominal fat distribution and metabolic risk factors: effects of race.
Metabolism.
1996;
45
1119-1124
-
23
Gautier J F, Milner M R, Elam E, Chen K, Ravussin E, Pratley R E.
Visceral adipose tissue is not increased in Pima Indians compared with equally obese Caucasians and is not related to insulin action or secretion.
Diabetologia.
1999;
42
28-34
-
24
Thomas E L, Saeed N, Hajnal J V, Brynes A, Goldstone A P, Frost G, Bell J D.
Magnetic resonance imaging of total body fat.
J Appl Physiol.
1998;
85
1778-1785
-
25
Shen W, Wang Z, Punyanita M, Lei J, Sinav A, Kral J G, Imielinska C, Ross R, Heymsfield S B.
Adipose tissue quantification by imaging methods: a proposed classification.
Obes Res.
2003;
11
5-16
K. Rave, M. D.
Profil Institute for Metabolic Research
Hellersbergstr. 9 · 41460 Neuss · Germany ·
Phone: +49(2131)4018-403
Fax: +49(2131)4018-503
Email: klaus.rave@profil-research.de