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Horm Metab Res 2007; 39(10): 734-738
DOI: 10.1055/s-2007-990271
Review

© Georg Thieme Verlag KG Stuttgart · New York

Adipose Tissue and Diabetes Therapy: Do We Hit the Target?

A. F. H. Pfeiffer 1
  • 1German Institute of Human Nutrition, Department of Clinical Nutrition - Potsdam Rehbrücke and Charité University Medicine Berlin, Campus Benjamin Franklin, Department of Endocrinology, Diabetes and Nutrition, Berlin, Germany
Further Information

Publication History

received 16.10.2006

accepted 10.08.2007

Publication Date:
22 October 2007 (online)

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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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 9 Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism.  Trends Endocrinol Metab. 2002;  13 84-89
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 19 Yki-Jarvinen H, Westerbacka J. The fatty liver and insulin resistance.  Curr Mol Med. 2005;  5 287-295
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 31 Weickert MO, Pfeiffer AF. Signalling mechanisms linking hepatic glucose and lipid metabolism.  Diabetologia. 2006;  49 1732-1741
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 39 Astrup A. Effect of rimonabant on weight reduction and cardiovascular risk.  Lancet. 2005;  366 368 , author's reply 369-370
    PubMedGoogle Scholar

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

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