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Journal of Diabetes Research
Volume 2015 (2015), Article ID 834903, 7 pages
http://dx.doi.org/10.1155/2015/834903
Clinical Study

Impact of Bromocriptine-QR Therapy on Glycemic Control and Daily Insulin Requirement in Type 2 Diabetes Mellitus Subjects Whose Dysglycemia Is Poorly Controlled on High-Dose Insulin: A Pilot Study

1University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
2Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA

Received 30 January 2015; Accepted 28 March 2015

Academic Editor: Bernard Portha

Copyright © 2015 Erin D. Roe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. A. Defronzo, “From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus,” Diabetes, vol. 58, no. 4, pp. 773–795, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. E. Ferrannini, A. Gastaldelli, Y. Miyazaki, M. Matsuda, A. Mari, and R. A. DeFronzo, “β-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 1, pp. 493–500, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Khunti, M. Davies, A. Majeed, B. L. Thorsted, M. L. Wolden, and S. K. Paul, “Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study,” Diabetes Care, vol. 38, no. 2, pp. 316–322, 2015. View at Publisher · View at Google Scholar
  4. S. R. Heller, P. Choudhary, C. Davies et al., “Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration,” Diabetologia, vol. 50, no. 6, pp. 1140–1147, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. E. C. McNay, J. A. Teske, C. M. Kotz et al., “Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy,” American Journal of Physiology—Endocrinology and Metabolism, vol. 304, no. 2, pp. E131–E138, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. A. E. Pontiroli, L. Miele, and A. Morabito, “Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: Systematic review and meta-analysis,” Diabetes, Obesity and Metabolism, vol. 13, no. 11, pp. 1008–1019, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Russell-Jones and R. Khan, “Insulin-associated weight gain in diabetes—causes, effects and coping strategies,” Diabetes, Obesity and Metabolism, vol. 9, no. 6, pp. 799–812, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. S. A. Ross, H. D. Tildesley, and J. Ashkenas, “Barriers to effective insulin treatment: the persistence of poor glycemic control in type 2 diabetes,” Current Medical Research and Opinion, vol. 27, no. 3, pp. 13–20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. P. Hildebrandt, “Subcutaneous absorption of insulin in insulin-dependent diabetic patients. Influence of species, physico-chemical properties of insulin and physiological factors,” Danish Medical Bulletin, vol. 38, no. 4, pp. 337–346, 1991. View at Google Scholar · View at Scopus
  10. L. Heinemann, “Variability of insulin absorption and insulin action,” Diabetes Technology and Therapeutics, vol. 4, no. 5, pp. 673–682, 2002. View at Publisher · View at Google Scholar · View at Scopus
  11. C. Binder, T. Lauritzen, O. Faber, and S. Pramming, “Insulin pharmacokinetics,” Diabetes Care, vol. 7, no. 2, pp. 188–199, 1984. View at Publisher · View at Google Scholar · View at Scopus
  12. V. Mattoo, D. Eckland, M. Widel et al., “Metabolic effects of pioglitazone in combination with insulin in patients with type 2 diabetes mellitus whose disease is not adequately controlled with insulin therapy: results of a six-month, randomized, double-blind, prospective, multicenter, parallel-group study,” Clinical Therapeutics, vol. 27, no. 5, pp. 554–567, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. J. A. Davidson, A. Perez, J. Zhang, and Pioglitazone 343 Study Group, “Addition of pioglitazone to stable insulin therapy in patients with poorly controlled type 2 diabetes: results of a double-blind, multicentre, randomized study,” Diabetes, Obesity and Metabolism, vol. 8, no. 2, pp. 164–174, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. B. Charbonnel, R. DeFronzo, J. Davidson et al., “Pioglitazone use in combination with insulin in the prospective pioglitazone clinical trial in macrovascular events study (PROactive19),” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 5, pp. 2163–2171, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Clar, P. Royle, and N. Waugh, “Adding pioglitazone to insulin containing regimens in type 2 diabetes: systematic review and meta-analysis,” PLoS ONE, vol. 4, no. 7, Article ID e6112, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. D. M. Hartung, D. R. Touchette, N. C. Bultemeier, and D. G. Haxby, “Risk of hospitalization for heart failure associated with thiazolidinedione therapy: a medicaid claims-based case-control study,” Pharmacotherapy, vol. 25, no. 10, pp. 1329–1336, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. P. S. Chaggar, S. M. Shaw, and S. G. Williams, “Thiazolidinediones and heart failure,” Diabetes and Vascular Disease Research, vol. 6, no. 3, pp. 146–152, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. T. D. Giles, A. B. Miller, U. Elkayam, M. Bhattacharya, and A. Perez, “Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction,” Journal of Cardiac Failure, vol. 14, no. 6, pp. 445–452, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. A. J. Scheen, “Combined thiazolidinedione-insulin therapy: should we be concerned about safety?” Drug Safety, vol. 27, no. 12, pp. 841–856, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. Actos (pioglitazone hydrochloride) prescribing information, http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021073s043s044lbl.pdf, http://www.actos.com/pi.pdf.
  21. J. M. Gaziano, A. H. Cincotta, C. M. O'Connor et al., “Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes,” Diabetes Care, vol. 33, no. 7, pp. 1503–1508, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. J. M. Gaziano, A. H. Cincotta, A. Vinik, L. Blonde, N. Bohannon, and R. Scranton, “Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects,” Journal of the American Heart Association, vol. 1, no. 5, Article ID e002279, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. A. I. Vinik, A. H. Cincotta, R. E. Scranton, N. Bohannon, M. Ezrokhi, and J. M. Gaziano, “Effect of Bromocriptine-QR on glycemic control in subjects with uncontrolled hyperglycemia on one or two oral anti-diabetes agents,” Endocrine Practice, vol. 18, no. 6, pp. 931–943, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. R. Scranton and A. Cincotta, “Bromocriptine—unique formulation of a dopamine agonist for the treatment of type 2 diabetes,” Expert Opinion on Pharmacotherapy, vol. 11, no. 2, pp. 269–279, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. H. Pijl, S. Ohashi, M. Matsuda et al., “Bromocriptine: a novel approach to the treatment of type 2 diabetes,” Diabetes Care, vol. 23, no. 8, pp. 1154–1161, 2000. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Ezrokhi, S. Luo, Y. Trubitsyna, and A. H. Cincotta, “Weighted effects of bromocriptine treatment on glucose homeostasis during hyperglycemic versus euglycemic clamp conditions in insulin resistant hamsters: bromocriptine as a unique postprandial insulin sensitizer,” Journal of Diabetes & Metabolism, vol. S2, no. 1, 2012. View at Publisher · View at Google Scholar
  27. M. C. Moore, M. Smith, B. Farmer, and A. D. Cherrington, “Timed daily bromocriptine mesylate (BC) administration improves glucose disposal in a canine diet-induced model of impaired glucose tolerance,” Diabetologia, vol. 57, supplement 1, p. S350, 2014. View at Google Scholar
  28. S. Luo, J. Luo, and A. H. Cincotta, “Suprachiasmatic nuclei monoamine metabolism of glucose tolerant versus intolerant hamsters,” NeuroReport, vol. 10, no. 10, pp. 2073–2077, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Luo, J. Luo, A. H. Meier, and A. H. Cincotta, “Dopaminergic neurotoxin administration to the area of the suprachiasmatic nuclei induces insulin resistance,” NeuroReport, vol. 8, no. 16, pp. 3495–3499, 1997. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Ezrokhi, S. Luo, Y. Trubitsyna, and A. H. Cincotta, “Neuroendocrine and metabolic components of dopamine agonist amelioration of metabolic syndrome in SHR rats,” Diabetology & Metabolic Syndrome, vol. 6, article 104, 2014. View at Publisher · View at Google Scholar
  31. A. H. Cincotta, “Hypothalamic role in insulin resistance and insulin resistance syndrome,” in Frontiers in Animal Diabetes Research, B. Hansen and E. Shafrir, Eds., pp. 271–312, Taylor & Francis, London, UK, 2002. View at Google Scholar
  32. S. Luo, J. Luo, and A. H. Cincotta, “Chronic ventromedial hypothalamic infusion of norepinephrine and serotonin promotes insulin resistance and glucose intolerance,” Neuroendocrinology, vol. 70, no. 6, pp. 460–465, 1999. View at Publisher · View at Google Scholar · View at Scopus
  33. A. H. Cincotta, S. Luo, Y. Zhang et al., “Chronic infusion of norepinephrine into the VMH of normal rats induces the obese glucose-intolerant state,” The American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 278, no. 2, pp. R435–R444, 2000. View at Google Scholar · View at Scopus
  34. S. Luo, M. Ezrokhi, Y. Trubitsyna, and A. H. Cincotta, “Intrahypothalamic circuitry regulating hypothalamic fuel sensing to induce insulin sensitivity or insulin resistance,” Diabetologia, vol. 51, supplement 1, p. S59, 2008. View at Google Scholar
  35. J. M. Monti and D. Monti, “The involvement of dopamine in the modulation of sleep and waking,” Sleep Medicine Reviews, vol. 11, no. 2, pp. 113–133, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. A. H. Cincotta, T. A. MacEachern, and A. H. Meier, “Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsulinemic state in Syrian hamsters,” The American Journal of Physiology—Endocrinology and Metabolism, vol. 264, no. 2, pp. E285–E293, 1993. View at Google Scholar · View at Scopus
  37. S. Luo, A. H. Meier, and A. H. Cincotta, “Bromocriptine reduces obesity, glucose intolerance and extracellular monoamine metabolite levels in the ventromedial hypothalamus of Syrian hamsters,” Neuroendocrinology, vol. 68, no. 1, pp. 1–10, 1998. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Ezrokhi, S. Luo, T. Trubitsyna, and A. H. Cincotta, “Synergism of dopamine agonist plus GLP-1 analog therapy on improvement of glucose intolerance in Syrian hamsters,” Diabetes, vol. 60, supplement 1, article A445, 2011. View at Google Scholar
  39. A. Pocai, T. K. T. Lam, S. Obici et al., “Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats,” Journal of Clinical Investigation, vol. 116, no. 4, pp. 1081–1091, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. T. K. T. Lam, “Neuronal regulation of homeostasis by nutrient sensing,” Nature Medicine, vol. 16, no. 4, pp. 392–395, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. D. M. Breen, C. S. Yang, and T. K. T. Lam, “Gut-brain signalling: how lipids can trigger the gut,” Diabetes/Metabolism Research and Reviews, vol. 27, no. 2, pp. 113–119, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. S. D. Jordan, A. C. Könner, and J. C. Brüning, “Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis,” Cellular and Molecular Life Sciences, vol. 67, no. 19, pp. 3255–3273, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. K. Morgan, S. Obici, and L. Rossetti, “Hypothalamic responses to long-chain fatty acids are nutritionally regulated,” The Journal of Biological Chemistry, vol. 279, no. 30, pp. 31139–31148, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Luo, Y. Zhang, M. Ezrokhi, Y. Trubitsyna, and A. H. Cincotta, “High-fat feeding abolishes the insulin-sensitizing peak in circadian dopamine activity at the biological clock,” Diabetes, vol. 63, supplement 1, p. A470, 2014. View at Google Scholar
  45. S. Luo, Y. Liang, and A. H. Cincotta, “Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant/glucose-intolerant state in hamsters,” Neuroendocrinology, vol. 69, no. 3, pp. 160–166, 1999. View at Publisher · View at Google Scholar · View at Scopus
  46. K. G. Bina and A. H. Cincotta, “Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice,” Neuroendocrinology, vol. 71, no. 1, pp. 68–78, 2000. View at Publisher · View at Google Scholar · View at Scopus
  47. B. M. Geiger, M. Haburcak, N. M. Avena, M. C. Moyer, B. G. Hoebel, and E. N. Pothos, “Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity,” Neuroscience, vol. 159, no. 4, pp. 1193–1199, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. A. G. Roseberry, T. Painter, G. P. Mark, and J. T. Williams, “Decreased vesicular somatodendritic dopamine stores in leptin-deficient mice,” Journal of Neuroscience, vol. 27, no. 26, pp. 7021–7027, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. J. F. Davis, A. L. Tracy, J. D. Schurdak et al., “Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat,” Behavioral Neuroscience, vol. 122, no. 6, pp. 1257–1263, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. B. M. Geiger, G. G. Behr, L. E. Frank et al., “Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats,” FASEB Journal, vol. 22, no. 8, pp. 2740–2746, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. P. Rada, M. E. Bocarsly, J. R. Barson, B. G. Hoebel, and S. F. Leibowitz, “Reduced accumbens dopamine in Sprague-Dawley rats prone to overeating a fat-rich diet,” Physiology and Behavior, vol. 101, no. 3, pp. 394–400, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. N. D. Volkow, G.-J. Wang, F. Telang et al., “Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors,” NeuroImage, vol. 42, no. 4, pp. 1537–1543, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Mendoza and E. Challet, “Circadian insights into dopamine mechanisms,” Neuroscience, vol. 282, pp. 230–242, 2014. View at Publisher · View at Google Scholar