Skip to main content

Glycemic Variability in Type 2 Diabetes Mellitus

Oxidative Stress and Macrovascular Complications

  • Chapter
  • First Online:
Diabetes

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 771))

Abstract

Diabetes mellitus is a world-wide health issue with potential for significant negative health outcomes, including microvascular and macrovascular complications. The relationship of hemoglobin HbA1c and other glycosylation end products (AGEs) to these complications, particularly microvascular disease, is well understood. More recent evidence suggests that glycemic variability may be associated with diabetes macrovascular complications. As HbA1c is better representative of average glucose levels and does not account as well for glycemic variability, hence new methods to assess and treat this variability is needed to reduce incidence of complications. In this chapter, the relationship of glycemic control to diabetes complications will be explored with focus on the mechanisms of tissue damage from this variability along with the oxidative stress. Additionally, treatment strategies to optimize HbA1c and glycemic variability with the goal of reducing risk of complications in persons with diabetes are reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. International Diabetes Federation. Diabetes Atlas, http://www.diabetesatlas.org/content/diabetes-and-impairedglucose-tolerance. Accessed 2011.

  2. Narayan KM, Boyle JP, Geiss LS et al. Impact of recent increase in incidence on future diabetes burden: U.S., 2005–2050. Diabetes Care 2006; 29:2114–2116.

    Article  PubMed  Google Scholar 

  3. Temelkova-Kurktschiev TS, Koehler C, Henkel E et al. Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care 2000; 23:1830–1834.

    Article  CAS  PubMed  Google Scholar 

  4. Monnier L, Mas E, Ginet C et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006; 295:1681–1687.

    Article  CAS  PubMed  Google Scholar 

  5. Bonora E, Muggeo M. Postprandial blood glucose as a risk factor for cardiovascular disease in Type II diabetes: the epidemiological evidence. Diabetologia 2001; 44:2107–2114.

    Article  CAS  PubMed  Google Scholar 

  6. Chiasson JL, Josse RG, Gomis R et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 2003; 290:486–494.

    Article  CAS  PubMed  Google Scholar 

  7. Meigs JB, Nathan DM, D’Agostino RB et al. Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study. Diabetes Care 2002; 25:1845–1850.

    Article  PubMed  Google Scholar 

  8. Hu Y, Liu W, Huang R et al. Postchallenge plasma glucose excursions, carotid intima-media thickness, and risk factors for atherosclerosis in Chinese population with type 2 diabetes. Atherosclerosis 2010; 210(1):302–306.

    Article  CAS  PubMed  Google Scholar 

  9. Balkau B, Shipley M, Jarrett RJ et al. High blood glucose concentration is a risk factor for mortality in middle-aged nondiabctic men. 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study. Diabetes Care 1998; 21:360–367.

    Article  CAS  PubMed  Google Scholar 

  10. Hanefeld M, Fischer S, Julius U et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia 1996; 39:1577–1583.

    Article  CAS  PubMed  Google Scholar 

  11. Donahue RP, Abbott RD, Reed DM et al. Postchallenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program. Diabetes 1987; 36:689–692.

    Article  CAS  PubMed  Google Scholar 

  12. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe. Lancet 1999; 354:617–621.

    Article  Google Scholar 

  13. Balkau B, Hu G, Qiao Q et al. Prediction of the risk of cardiovascular mortality using a score that includes glucose as a risk factor. The DECODE Study. Diabetologia 2004; 47:2118–2128.

    Article  CAS  PubMed  Google Scholar 

  14. Preis SR, Hwang SJ, Coady S et al. Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the Framingham Heart Study, 1950 to 2005. Circulation 2009; 119:1728–1735.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tzoulaki I, Molokhia M, Curcin V et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ 2009; 339:b4731.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Emerging Risk Factors Collaboration. Sarwar N, Gao P, Kondapally S et al. Fasting glucose concentration, diabetes mellitus, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375:2215–2222.

    Article  CAS  Google Scholar 

  17. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329:977–986.

    Article  Google Scholar 

  18. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352(9131):837–853.

    Article  Google Scholar 

  19. The Diabetes Control and Complications Trial (DCCT) Research Group, 1995 The Diabetes Control and Complications Trial (DCCT) Research Group, The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial, Diabetes 1995; 44;968–983.

    Article  Google Scholar 

  20. Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control? J Diabetes Complications 2005; 19:178–181.

    Article  PubMed  Google Scholar 

  21. Polak JF, Backlund JY, Cleary PA et al. DCCT/EDIC Research Group. Progression of carotid artery intima-media thickness during 12 years in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Diabetes 2011; 60(2):607–613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nathan DM, Zinman B, Cleary PA et al. Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983–2005). Arch Intern Med 2009; 169(14):1307–1301.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Stratton IM, Adler AI, Neil HA et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:405–412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Holman RR, Paul SK, Bethel MA et al. 10-year follow-up of intensive glucose control in type 2 diabetes. NE.IM 2008; 359(15):1577–1589.

    CAS  Google Scholar 

  25. Skyler JS, Bergenstal R, Bonow RO et al. American Diabetes Association; American College of Cardiology Foundation; American Heart Association. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care 2009; 32(1):187–192.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Selvin E, Marinopoulos S, Berkenblit G et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 2004; 141:421–431.

    Article  CAS  PubMed  Google Scholar 

  27. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358:2545–2559.

    Article  Google Scholar 

  28. ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358:2560–2572.

    Article  Google Scholar 

  29. Duckworth W, Abraira C, Moritz T et al. Intensive glucose control and complications in American veterans with type 2 diabetes. N Engl J Med 2009; 360(2):129–139.

    Article  CAS  PubMed  Google Scholar 

  30. Greenfield S, Billimek J, Pellegrini F et al. Comorbidity affects the relationship between glycemic control and cardiovascular outcomes in diabetes: a cohort study. Ann Intern Med 2009; 151:854–860.

    Article  PubMed  Google Scholar 

  31. Schernthaner G. Diabetes and Cardiovascular Disease: Is intensive glucose control beneficial or deadly? Lessons from ACCORD, ADVANCE, VADT, UKPDS, PROactivc and NICE-SUGAR. Wien Med Wochenschr 2010; 160(1–2):8–19.

    Article  PubMed  Google Scholar 

  32. Ray KK, Seshasai SR, Wijesuriya S et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet 2009; 373(9677):1765–1772.

    Article  CAS  PubMed  Google Scholar 

  33. Johnston SS, Conner C, Aagren M et al. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care 2011; 34(5):1164–70.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zaccardi F, Pitocco D, Ghirlanda G. Glycemic risk factors of diabetic vascular complications: the role of glycemic variability. Diabetes Metab Res Rev 2009; 25(3):199–207.

    Article  CAS  PubMed  Google Scholar 

  35. Johnson EL. Glycemic variability: too often overlooked in type 2 diabetes? J Fam Prac 2010; 59(8):E1–E8.

    Google Scholar 

  36. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58(4):773–795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ginsberg UN. Insulin resistance and cardiovascular disease. J Clin Invest 2000; 106:453–458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54:1615–1625.

    Article  CAS  PubMed  Google Scholar 

  39. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414:813–820.

    Article  CAS  PubMed  Google Scholar 

  40. Cericllo A, Quagliaro L, Catone B et al. Role of hyperglycemia in nitrotyrosinc postprandial generation. Diabetes Care 2002; 25:1439–1443.

    Article  Google Scholar 

  41. Williams SB, Cusco JA, Roddy MA et al. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 1996; 27:567–574.

    Article  CAS  PubMed  Google Scholar 

  42. Ceriello A. Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects. Diabetologia 1993; 36:1119–1125.

    Article  CAS  PubMed  Google Scholar 

  43. Quagliaro L, Piconi L, Assaloni R et al. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 2003; 52:2795–2804.

    Article  CAS  PubMed  Google Scholar 

  44. Risso A, Mercuri F, Quagliaro L et al. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab 2001; 281:E924–E930.

    Article  CAS  PubMed  Google Scholar 

  45. Jones SC, Saunders HJ, Qi W et al. Intermittent high glucose enhances cell growth and collagen synthesis in cultured human tubulointerstitial cells. Diabetologia 1999; 42:1113–1119.

    Article  CAS  PubMed  Google Scholar 

  46. Buscemi S, Re A, Batsis JA et al. Glycaemic variability using continuous glucose monitoring and endothelial function in the metabolic syndrome and in Type 2 diabetes. Diabet Med. 2010; 27(8): 872–878.

    Article  CAS  PubMed  Google Scholar 

  47. Su G, Mi S, Tao II et al. Association of glycemic variability and the presence and severity of coronary artery disease in type 2 diabetes. Cardiovascular Diabetology 2011; 25:10–19.

    Google Scholar 

  48. 48. Clinical Practice Recommendations. Diabetes Care 2011; 34(S1).

    Google Scholar 

  49. American Association of Clinical Endocrinologists Medical Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan, http://www.aace.com/sites/default/filcs/DMGuidelinesCCP_OnlinePDF.pdf. Accessed online 2011.

  50. Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin Ale-independent risk factor for diabetic complications. J Am Med Assoc 2006; 295:1707–1708.

    Article  CAS  Google Scholar 

  51. Koro CE, Bowlin SJ, Bourgeois N et al. Glycemic control from 1988 to 2000 among U.S. adults diagnosed with type 2 diabetes: a preliminary report. Diabetes Care 2004; 27:17–20.

    Article  PubMed  Google Scholar 

  52. Barnett AH. Treating to goal: challenges of current management Eur J Endocrinol 2004; 151(Suppl 2): T3–T7; discussion T29–T30.

    Article  CAS  PubMed  Google Scholar 

  53. Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Diabetes Care 2004; 27:1535–1540.

    Article  PubMed  Google Scholar 

  54. Garg SK, Voelmle MK, Beatson CR et al. Use of continuous glucose monitoring in subjects with type 1 diabetes onmultiple daily injections versus continuous subcutaneous insulin infusion therapy: a prospective 6-month study. Diabetes Care 2011; 34(3):574–579. Epub 2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chase HP, Beck RW, Xing D et al. Continuous glucose monitoring in youth with type 1 diabetes: 12-month follow-up of the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized trial. Diabetes Technol Ther 2010; 12(7):507–515.

    Article  CAS  PubMed  Google Scholar 

  56. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Effectiveness of continuous glucose monitoring in a clinical care environment: evidence from the Juvenile Diabetes Research Foundation continuous glucose monitoring (JDRF-CGM) trial. Diabetes Care 2010; 33(1):17–22.

    Article  CAS  Google Scholar 

  57. Zheng F, Lu W, Jia C et al. Relationships between glucose excursion and the activation of oxidative stress in patients with newly diagnosed type 2 diabetes or impaired glucose regulation. Endocrine 2010; 37(1):201–208.

    Article  CAS  PubMed  Google Scholar 

  58. Hoeks LB, Greven WL, de Valk HW. Real-time continuous glucose monitoring system for treatment of diabetes: a systematic review. Diabet Med 2011; 28(4):386–394.

    Article  CAS  PubMed  Google Scholar 

  59. Chaudhuri A, Janicke D, Wilson MF et al. Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction. Circulation 2004; 109:849–854.

    Article  CAS  PubMed  Google Scholar 

  60. Rask-Madsen C, Ihlemann N, Krarup T et al. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease. Diabetes 2001; 50:2611–2618.

    Article  CAS  PubMed  Google Scholar 

  61. Chaudhuri A, Kanjwal Y, Mohanty P et al. Insulin-induced vasodilatation of internal carotid artery. Metabolism 1999; 48:1470–1473.

    Article  CAS  PubMed  Google Scholar 

  62. Melidonis A, Stefanidis A, Tournis S et al. The role of strict metabolic control by insulin infusion on fibrinolytic profile during an acute coronary event in diabetic patients. Clin Cardiol 2000; 23:160–164.

    Article  CAS  PubMed  Google Scholar 

  63. Garvey WT, Olefsky JM, Griffin J et al. The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes 1985; 34:222–234.

    Article  CAS  PubMed  Google Scholar 

  64. Rolla A. The pathophysiological basis for intensive insulin replacement. Int J Obes Relat Metab Disord 2004; 28Suppl 2:S3–S7.

    Article  CAS  PubMed  Google Scholar 

  65. Alvarsson M, Sundkvist G, Lager I et al. Beneficial effects of insulin versus sulphonylureaon insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care 2003; 26:2231–2237.

    Article  CAS  PubMed  Google Scholar 

  66. Glaser B, Leibovich G, Nesher R et al. Improved beta-cell function after intensive insulin treatment in severe non-insulin-dependent diabetes. Acta Endocrinol (Copenh) 1988; 118:365–373.

    Article  CAS  Google Scholar 

  67. Andrews WJ, Vasque/ B, Nagulesparan M et al. Insulin therapy in obese, non-insulin-dependent diabetes induces improvements in insulin action and secretion that are maintained for two weeks after insulin withdrawal. Diabetes 1984; 33:634–642.

    Article  CAS  PubMed  Google Scholar 

  68. Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care 2004; 27:1028–1032.

    Article  CAS  PubMed  Google Scholar 

  69. Malmberg K, Ryden L, Efendic S et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995; 26:57–65.

    Article  CAS  PubMed  Google Scholar 

  70. Banting FG, Best CH, Collip IB et al. Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. 1922. Cmaj 1991; 145:1281–1286.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Heise T, Heinemann L. Rapid and long-acting analogues as an approach to improve insulin therapy: an evidence-based medicine assessment. Curr Pharm Des 2001; 7:1303–1325.

    Article  CAS  PubMed  Google Scholar 

  72. Brems DN, Alter LA, Beckage MJ et al. Altering the association properties of insulin by ammo acid replacement. Protein Eng 1992; 5:527–533.

    Article  CAS  PubMed  Google Scholar 

  73. Bolli GB, Di Marchi RD, Park GD et al. Insulin analogues and their potential in the management of diabetes mellitus. Diabetologia 1999; 42:1151–1167.

    Article  CAS  PubMed  Google Scholar 

  74. Garber AJ. Pharmacologic modifications of hormones to improve their therapeutic potential for diabetes management. Diabetes Obes Metab 2005; 7:666–674.

    Article  CAS  PubMed  Google Scholar 

  75. Hansen BF, Danielsen GM, Drejer K et al. Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. Biochem J 1996; 315(Pt 1):271–279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Slieker LJ, Brooke GS, DiMarchi RD et al. Modifications in the B10 and B26–30 regions of the B chain of human insulin alter affinity for the human IGF-I receptor more than for the insulin receptor. Diabetologia 1997; 40(Suppl 2):S54–61.

    Article  CAS  PubMed  Google Scholar 

  77. Dimitriadis GD, Gerich JE. Importance of timing of preprandial subcutaneous insulin administration in the management of diabetes mellitus. Diabetes Care 1983; 6:374–377.

    Article  CAS  PubMed  Google Scholar 

  78. Roy B, Chou MC, Field JB. Time-action characteristics of regular and NPH insulin in insulin-treated diabetics. J Clin Endocrinol Metab 1980; 50:475–479.

    Article  CAS  PubMed  Google Scholar 

  79. Kang S, Creagh FM, Peters JR et al. Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9; GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects. Diabetes Care 1991; 14:571–577.

    Article  CAS  PubMed  Google Scholar 

  80. Hirsch IB. Insulin analogues. N Engl J Med 2005; 352:174–183.

    Article  CAS  PubMed  Google Scholar 

  81. Becker RH, Frick AD, Burger F et al. A comparison ofthe steady-state phannacokinetics and pharmacodyuamics of a novel rapid-acting insulin analog, insulin glulisine and regular human insulin in healthy volunteers using the euglycemic clamp technique. Exp Clin Endocrinol Diabetes 2005; 113:292–297.

    Article  CAS  PubMed  Google Scholar 

  82. Brunelle BL, Llewelyn J, Anderson JH et al. Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes. Diabetes Care 1998; 21:1726–1731.

    Article  CAS  PubMed  Google Scholar 

  83. Home PD, Lindholm A, Hylleberg B et al. Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group. Diabetes Care 1998; 21:1904–1909.

    Article  CAS  PubMed  Google Scholar 

  84. Lindholm A, McEwen J, Riis AP. Improved postprandial glycemic control with insulin aspart. A randomized double-blind cross-over trial in type 1 diabetes. Diabetes Care 1999; 22:801–805.

    Article  CAS  PubMed  Google Scholar 

  85. Binder C, Lauritzen T, Faber O et al. Insulin pharmacokinetics. Diabetes Care 1984; 7:188–199.

    Article  PubMed  Google Scholar 

  86. Rosenstock J, Park G, Zimmerman J. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group. Basal insulin glargine (HOE 901) versus NP1I insulin in patients with type 1 diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group. Diabetes Care 2000; 23(8):1137–1142.

    Article  CAS  PubMed  Google Scholar 

  87. Rosenstock J, Schwartz SL, Clark CM Jr et al. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001; 24(4):631–636. Diab Obcs Metab,2007.

    Article  CAS  PubMed  Google Scholar 

  88. Klein O, Lynge J. Endahl L et al. Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes. Diabetes Obes Mctab 2007; 9:290-299.

    Article  CAS  Google Scholar 

  89. Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003; 26:3080–3086.

    Article  CAS  PubMed  Google Scholar 

  90. Yki-Jarvinen H, Dressier A, Ziemen M. Less nocturnal hypoglycemia and better postdinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care 2000; 23:1130–1136.

    Article  CAS  PubMed  Google Scholar 

  91. Hermansen K, Davies M, Derezinski T et al. A 26-week, randomi zed, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care 2006; 29:1269–1274.

    Article  CAS  PubMed  Google Scholar 

  92. Philis-Tsimikas A, Charpentier G, Clauson P et al. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther 2006; 28:1569–1581.

    Article  CAS  PubMed  Google Scholar 

  93. Haak T, Tiengo A, Draeger E et al Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes. Diabetes Obes Metab 2005; 7:56–64.

    Article  CAS  PubMed  Google Scholar 

  94. Lepore M, Pampanelli S, Fanelli C et al. Pharmacokinetics andpharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 2000; 49:2142–2148.

    Article  CAS  PubMed  Google Scholar 

  95. Hermansen K, Madsbad S. Perrild H et al. Comparison of the soluble basal insulin analog insulin detemir with NPH insulin: a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy. Diabetes Care 2001; 24:296–301.

    Article  CAS  PubMed  Google Scholar 

  96. Heise T, Nosek L, Ronn BB et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes 2004; 53:1614–1620.

    Article  CAS  PubMed  Google Scholar 

  97. Su IB, Wang XQ, Chen JF et al. Glycemic variability in insulin treated type 2 diabetes with well-controlled hemoglobin Alc and its responsetofurthertreatment with acarbose. Chin Med J (Eugl) 2011; 124(1): 144–147.

    CAS  Google Scholar 

  98. Blonde L, Klein EJ, Han J et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006; 8(4):436–447.

    Article  CAS  PubMed  Google Scholar 

  99. Vilsbøll T, Zdravkovic M, Le-Thi T et al. Liraglutide, a long-acting human glucagou-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007; 1608–1610.

    Article  PubMed  CAS  Google Scholar 

  100. Raz I, Hanefeld M, Xu L et al. Sitagliptin Study 023 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabctologia 2006; 49(11):2564–2571.

    Article  CAS  Google Scholar 

  101. Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drag-naive patients with type 2 diabetes. Diabetes Obes Metab 2008; 10(5):376–386.

    Article  CAS  PubMed  Google Scholar 

  102. Singh-Franco D, Perez A, Harrington C. The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 2011; 13(2):169–168.

    Article  CAS  PubMed  Google Scholar 

  103. Hollander PA, Levy P, Fineman MS et al. Pramlinitide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-yearrandomized controlled trial. Diabetes Care 2003; 26(3):784–790.

    Article  CAS  PubMed  Google Scholar 

  104. Okerson T, Chilton RJ. The Cardiovascular Effects of GLP-1 Receptor Agonists. Cardiovasc Ther 2010 doi: 10.1111/j.1755-5922.2010.00256.X. [Epub ahead of print].

    Article  PubMed  CAS  Google Scholar 

  105. Horton es, silberman c, davis kl et al. Glycemic control and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care 2010; 33(8):1759–1765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Mellbin LG, Malmberg K, Norhammar A et al; for the DIGAMI 2 Investigators. Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. Diabetologia 2011; 54(6):1308–1317.

    Article  CAS  PubMed  Google Scholar 

  107. Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 2010; 170(14):1191–1201.

    Article  CAS  PubMed  Google Scholar 

  108. Matschinsky FM, Zelent B, Doliba NM et al. Research and development of glucokinase activators for diabetes therapy: theoretical and practical aspects. Ilandb Exp Pharmacol 2011; (203):357–401.

    Article  CAS  Google Scholar 

  109. Neumiller JJ, White JR Jr, Campbell RK. Sodium-glucose cotransport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs 2010; 70(4)377–385.

    Article  CAS  PubMed  Google Scholar 

  110. Capes SE, Hunt D, Malmberg K et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000; 355:773–778.

    Article  CAS  PubMed  Google Scholar 

  111. Bolk J, van der Ploeg T, Cornel JH et al. Impaired glucose metabolism predicts mortality after a myocardial infarction. Int J Cardiol 2001; 79:207–214.

    Article  CAS  Google Scholar 

  112. Furnary AP, Gao G, Grunkemeier GL et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003; 125:1007–1021.

    Article  CAS  PubMed  Google Scholar 

  113. Van den Berghe G, Wouters PJ, Bouillon R et al. Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control. Crit Care Med 2003; 31:359–366.

    Article  PubMed  CAS  Google Scholar 

  114. Van den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345:1359–1367.

    Article  PubMed  Google Scholar 

  115. Pulsinelli WA, Levy DE, Sigsbee B et al. Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med 1983; 74:540–544.

    Article  CAS  PubMed  Google Scholar 

  116. Williams LS, Rotich J, Qi R et al. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurology 2002; 59:67–71.

    Article  CAS  PubMed  Google Scholar 

  117. Umpierrez GE, Isaacs SD, Bazargan N et al. Hyperglycemia: an independent marker of in-hospital mortal ity in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002; 87:978–982.

    Article  CAS  PubMed  Google Scholar 

  118. Clement S, Braithwaite S, Magee M et al. Management of Diabetes and Hyperglycemia in Hospitals. Diabetes Care 2004; 27:553–591.

    Article  PubMed  Google Scholar 

  119. Furnary AP, Zerr KJ, Grunkemeier GL et al. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999; 67:352–360; discussion 360–352.

    Article  CAS  PubMed  Google Scholar 

  120. Garber AJ, Moghissi ES, Bransome ED et al. American College of Endocrinology position statement on inpatient diabetes and metabolic control. Endocr Pract 2004; 10 Suppl 2:4–9.

    PubMed  Google Scholar 

  121. Testa MA, Simonson DC. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, double-blind trial. JAMA 1998; 280:1490–1496.

    Article  CAS  PubMed  Google Scholar 

  122. Qaseem A, Humphrey LL, Chou R. et al. Clinical Guidelines Committee of the American College of Physicians. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2011; 154(4):260–267.

    Article  PubMed  Google Scholar 

  123. Buse JB, Ginsberg HN, Bakris GL et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: A scientific statement from the American Heart Association and the American Diabetes Association. Circulation 2007; 115:114–126.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Johnson, E.L. (2013). Glycemic Variability in Type 2 Diabetes Mellitus. In: Ahmad, S.I. (eds) Diabetes. Advances in Experimental Medicine and Biology, vol 771. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5441-0_13

Download citation

Publish with us

Policies and ethics