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Abstract

Aims

To determine the effects of insulin sensitization (IS) and insulin provision (IP) treatment strategies on adipokines associated with cardiovascular disease in patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (BARI 2D).

Methods and results

Changes in adipokine levels were compared in patients with type 2 diabetes mellitus and coronary artery disease randomized to IS (n = 1037) versus IP (n = 1019) treatment strategies in BARI 2D. Circulating concentrations of leptin, adiponectin, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin 6 and C-reactive protein were evaluated at baseline and one year. IS and IP treatment strategies exerted significant (p < 0.0001) differential effects on: leptin (IS: 0.02% decrease, p = 0.01; IP: 13% increase, p < 0.0001); adiponectin (IS: 73% increase, p < 0.0001; IP: no change, p = 0.52); interleukin 6 (IS: 14% decrease, p < 0.0001; IP: no change, p = 0.68). Changes in monocyte chemoattractant protein-1 and tumor necrosis factor-alpha were not statistically different between groups. C-reactive protein decreased, but the effect was significantly greater in the IS group (–32%, p < 0.0001) than in the IP group (–5%, p = 0.0005).

Conclusion

The IS and IP treatment strategies exerted divergent effects on adipokine and inflammatory profile in patients with type 2 diabetes mellitus and coronary artery disease. The IS treatment strategy-induced changes may be more favorable than the IP treatment strategy regarding cardiovascular pathophysiology.

Keywords

Diabetes mellitus coronary disease risk factors adipokines

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References

Haffner

Taegtmeyer

. Epidemic obesity and the metabolic syndrome. Circulation 2003; 108: 1541–1545.

Reaven

. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am 2004; 33: 283–303.

Agewall

Fagerberg

Attvall

. Carotid artery wall intima-media thickness is associated with insulin-mediated glucose disposal in men at high and low coronary risk. Stroke 1995; 26: 956–960.

Bressler

Bailey

Matsuda

. Insulin resistance and coronary artery disease. Diabetologia 1996; 39: 1345–1350.

Howard

O’Leary

Zaccaro

. Insulin sensitivity and atherosclerosis. The Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Circulation 1996; 93: 1809–1817.

McGuire

Newby

Bhapkar

. Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes. Am Heart J 2004; 147: 246–252.

Frye

August

Brooks

. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009; 360: 2503–2515.

Chaitman

Hardison

Adler

. The Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial of different treatment strategies in type 2 diabetes mellitus with stable ischemic heart disease: Impact of treatment strategy on cardiac mortality and myocardial infarction. Circulation 2009; 120: 2529–2540.

Galic

Oakhill

Steinberg

. Adipose tissue as an endocrine organ. Mol Cell Endocrinol 2010; 316: 129–139.

10.

Antuna-Puente

Feve

Fellahi

. Adipokines: The missing link between insulin resistance and obesity. Diabetes Metab 2008; 34: 2–11.

11.

Barnes

Yang

. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112: 1821–1830.

12.

Brooks

Frye

Genuth

. Hypotheses, design, and methods for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Am J Cardiol 2006; 97: 9G–19G.

13.

Sobel

Hardison

Genuth

. Profibrinolytic, antithrombotic, and antiinflammatory effects of an insulin-sensitizing strategy in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Circulation 2011; 124: 695–703.

14.

Yang

Jeng

. Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 2002; 25: 376–380.

15.

Javorschi

Hevener

. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 2002; 51: 2968–2974.

16.

Patel

Holder

Smith

. Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. Diabetes 2003; 52: 43–50.

17.

Kolaczynski

Nyce

Considine

. Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro. Diabetes 1996; 45: 699–701.

18.

Motoshima

Sinha

. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: Effects of insulin and rosiglitazone. J Clin Endocrinol Metab 2002; 87: 5662–5667.

19.

Niswender

Schwartz

. Insulin and leptin revisited: Adiposity signals with overlapping physiological and intracellular signaling capabilities. Front Neuroendocrinol 2003; 24: 1–10.

20.

Kahn

Flier

. Obesity and insulin resistance. J Clin Invest 2000; 106: 473–481.

21.

Singh

Sahakyan

Sert-Kuniyoshi

. Leptin induces adiponectin expression: Implications in obesity. FASEB J 2013; 27: 1192.7–1192.7.

22.

Wolk

Somers

. Leptin and vascular function: Friend or foe? Eur Heart J 2006; 27: 2263–2265.

23.

Wallace

McMahon

Packard

. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation 2001; 104: 3052–3056.

24.

Wolk

Berger

Lennon

. Plasma leptin and prognosis in patients with established coronary atherosclerosis. J Am Coll Cardiol 2004; 44: 1819–1824.

25.

Pischon

Girman

Hotamisligil

. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291: 1730–1737.

26.

Wolk

Berger

Lennon

. Association between plasma adiponectin levels and unstable coronary syndromes. Eur Heart J 2007; 28: 292–298.

27.

Ridker

Rifai

Stampfer

. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101: 1767–1772.

28.

Lindmark

Diderholm

Wallentin

. Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: Effects of an early invasive or noninvasive strategy. JAMA 2001; 286: 2107–2113.

29.

Verma

Szmitko

Ridker

. C-reactive protein comes of age. Nat Clin Pract Cardiovasc Med 2005; 2: 29–36; quiz 58.

30.

Niswender

. Early and aggressive initiation of insulin therapy for type 2 diabetes: What is the evidence? Clin Diabetes 2009; 27: 60–68.

31.

Inzucchi

Bergenstal

Buse

. Management of hyperglycemia in type 2 diabetes: A patient-centered approach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35: 1364–1379.

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Differential effects of insulin sensitization and insulin provision treatment strategies on concentrations of circulating adipokines in patients with diabetes and coronary artery disease in the BARI 2D trial

Abstract

Aims

Methods and results

Conclusion

Keywords

Get full access to this article

References

Supplementary Material