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DOI: 10.1055/s-2007-990271
© Georg Thieme Verlag KG Stuttgart · New York
Adipose Tissue and Diabetes Therapy: Do We Hit the Target?
Publication History
received 16.10.2006
accepted 10.08.2007
Publication Date:
22 October 2007 (online)
Abstract
Factors derived from adipose tissue are believed to play a central role in the development and progression of diabetes and its vascular complications. Insulin resistance and vascular function are directly affected these factors, i.e., by free fatty acids, inflammatory adipocytokines, thrombotic and antifibrinolytic factors and by adiponectin, and adipokine with insulin sensitizing and anti-inflammatory actions. Targeting these factors by antidiabetic agents should result in improved metabolism and in a reduction of vascular risk. We therefore analyzed antidiabetic treatment strategies with regard to improvements of adipose tissue derived risk factors. This shows that weight loss remains an extremely powerful tool to reduce all of these risk factors. Thiazolidinediones and rimonabant are most potent in improving numerous adipose derived risk factors but studies demonstrating reduced mortality are not yet available. Metformin has little effect on any of the adipose tissue derived factors but appears to reduce diabetes related mortality according to limited evidence. Sulfonylureas and insulin have rather limited effects on adipose tissue derived factors and are likely to exert beneficial effects mainly by improved glucose metabolism and its consequences.
Key words
diabetes therapy - adipocytokines - adipose tissue
References
- 1 Savage DB, Petersen KF, Shulman GI. Mechanisms of insulin resistance in humans and possible links with inflammation. Hypertension. 2005; 45 828-833
- 2 Regitz-Zagrosek V, Lehmkuhl E, Weickert MO. Gender differences in the metabolic syndrome and their role for cardiovascular disease. Clin Res Cardiol. 2006; 95 136-147
- 3 Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004; 114 1752-1761
- 4 Barbieri M, Rizzo MR, Ragno E, Grella R, Manzella D, Carbonella M, Saccomanno F, Paolisso G. Insulin resistance, plasma PAI-1 levels and PAI-1 gene polymorphism in healthy centenarians. J Endocrinol Invest. 2002; 25 110-112
- 5 Anderwald C, Bernroider E, Krssak M, Stingl H, Brehm A, Bischof MG, Nowotny P, Roden M, Waldhausl W. Effects of insulin treatment in type 2 diabetic patients on intracellular lipid content in liver and skeletal muscle. Diabetes. 2002; 51 3025-3032
- 6 Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1 H NMR spectroscopy study. Diabetologia. 1999; 42 113-116
- 7 Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes. 2002; 51 2005-2011
- 8 Mohlig M, Freudenberg M, Bobbert T, Ristow M, Rochlitz H, Weickert MO, Pfeiffer AF, Spranger J. Acetylsalicylic acid improves lipid-induced insulin resistance in healthy men. J Clin Endocrinol Metab. 2006; 91 964-967
- 9 Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab. 2002; 13 84-89
- 10 Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003; 361 226-228
- 11 Mohlig M, Wegewitz U, Osterhoff M, Isken F, Ristow M, Pfeiffer AF, Spranger J. Insulin decreases human adiponectin plasma levels. Horm Metab Res. 2002; 34 655-658
- 12 Heidemann C, Hoffmann K, Spranger J, Klipstein-Grobusch K, Mohlig M, Pfeiffer AF, Boeing H. A dietary pattern protective against type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study cohort. Diabetologia. 2005; 48 1126-1134
- 13 Rochlitz H, Akpulat S, Bobbert T, Mai K, Mohlig M, Osterhoff M, Weickert MO, Pfeiffer AF, Spranger J. Significance of biomarkers for metabolic syndrome during weight reduction. Dtsch Med Wochenschr. 2005; 130 1061-1066
- 14 Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert MO, Mohlig M, Pfeiffer AF, Spranger J. Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes. 2005; 54 2712-2719
- 15 Fisher FF, Trujillo ME, Hanif W, Barnett AH, MacTernan PG, Scherer PE, Kumar S. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia. 2005; 48 1084-1087
- 16 Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, Wagner JA, Wu M, Knopps A, Xiang AH, Utzschneider KM, Kahn SE, Olefsky JM, Buchanan TA, Scherer PE. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem. 2004; 279 12152-12162
- 17 UK Prospective Diabetes Study (UKPDS) Group . Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352 854-865
- 18 Phillips SA, Ciaraldi TP, Kong AP, Bandukwala R, Aroda V, Carter L, Baxi S, Mudaliar SR, Henry RR. Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes. 2003; 52 667-674
- 19 Yki-Jarvinen H, Westerbacka J. The fatty liver and insulin resistance. Curr Mol Med. 2005; 5 287-295
- 20 Dandona P, Aljada A, Ghanim H, Mohanty P, Tripathy C, Hofmeyer D, Chaudhuri A. Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. J Clin Endocrinol Metab. 2004; 89 5043-5047
- 21 Di Gregorio GB, Yao-Borengasser A, Rasouli N, Varma V, Lu T, Miles LM, Ranganathan G, Peterson CA, MacGehee RE, Kern PA. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. Diabetes. 2005; 54 2305-2313
- 22 Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes. 2004; 53 2169-2176
- 23 Boden G, Cheung P, Mozzoli M, Fried SK. Effect of thiazolidinediones on glucose and fatty acid metabolism in patients with type 2 diabetes. Metabolism. 2003; 52 753-759
- 24 Tonelli J, Li W, Kishore P, Pajvani UB, Kwon E, Weaver C, Scherer PE, Hawkins M. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes. 2004; 53 1621-1629
- 25 Ek J, Andersen G, Urhammer SA, Hansen L, Carstensen B, Borch-Johnsen K, Drivsholm T, Berglund L, Hansen T, Lithell H, Pedersen O. Studies of the Pro12Ala polymorphism of the peroxisome proliferator- activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians. Diabetologia. 2001; 44 1170-1176
- 26 Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med. 1998; 339 953-959
- 27 Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman RR. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006; 368 1096-1105
- 28 Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006; 355 2427-2443
- 29 Rudovich NN, Leyck Dieken MG, Rochlitz H, Pfeiffer AF. Enhancement of early- and late-phase insulin secretion and insulin sensitivity by the combination of repaglinide and metformin in type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2004; 112 395-400
- 30 Chen G, Liang G, Ou J, Goldstein JL, Brown MS. Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Procd Natl Acad Sci USA. 2004; 101 11245-11250
- 31 Weickert MO, Pfeiffer AF. Signalling mechanisms linking hepatic glucose and lipid metabolism. Diabetologia. 2006; 49 1732-1741
- 32 Takebayashi K, Aso Y, Inukai T. Initiation of insulin therapy reduces serum concentrations of high-sensitivity C-reactive protein in patients with type 2 diabetes. Metabolism. 2004; 53 693-699
- 33 Yudkin JS, Panahloo A, Stehouwer C, Emeis JJ, Bulmer K, Mohamed-Ali V, Denver AE. The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects. Diabetologia. 2000; 43 1099-1106
- 34 Hauner H. The impact of pharmacotherapy on weight management in type 2 diabetes. Int J Obes Relat Metab Disord. 1999; 23 ((Suppl 7)) S12-S17
- 35 Jbilo O, Ravinet-Trillou C, Arnone M, Buisson I, Bribes E, Peleraux A, Penarier G, Soubrie P, Fur G Le, Galiegue S, Casellas P. The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. Faseb J. 2005; 19 1567-1569
- 36 Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 2006; 295 761-775
- 37 Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005; 353 2121-2134
- 38 Gaal LF Van, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005; 365 1389-1397
- 39 Astrup A. Effect of rimonabant on weight reduction and cardiovascular risk. Lancet. 2005; 366 368 , author's reply 369-370
Correspondence
A. F.H. Pfeiffer
Abteilung Klinische Ernährung
Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Arthur-Scheunert-Allee 114-116
14558 Nuthetal
Germany
Phone: +49/33200/88 77 1
Fax: +49/33200/88 77 7
Email: AFHP@dife.de