Type 2 diabetes: The role of basal insulin therapy

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Type 2 diabetes: The role of basal insulin therapy

J Fam Pract. 2004 March;53(3):215-222

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References

1. American Diabetes Association. Economic costs of diabetes in the U.S. in 2002. Diabetes Care. 2003;26:917-932.

2. National Institute of Diabetes and Digestive and Kidney Diseases. National diabetes statistics fact sheet: general information and national estimates on diabetes in the United States, 2000. Bethesda, Md: U.S. Department of Health and Human Services, National Institutes of Health, 2002. National Institute of Diabetes and Digestive and Kidney Diseases, 2002.

3. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229-234.

4. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. 2003;289:2254-2264.

5. Dagogo-Jack S, Santiago JV. Pathophysiology of type 2 diabetes and modes of action of therapeutic interventions. Arch Intern Med. 1997;157:1802-1817.

6. Stratton IM, Adler AI, Neil HAW, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Br Med J. 2000;321:405-412.

7. Gaede P, Vedel P, Parving H-H, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno-2 randomised study. Lancet. 1999;353:617-622.

8. Gaede P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383-393.

9. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Br Med J. 1998;317:703-713.

10. American Diabetes Association. Clinical practice recommendations 2003. Diabetes Care. 2003;26(suppl 1):S1-S156.

11. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

12. National Institutes of Health, National Heart Lung and Blood Institute. JNC 7 Express: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, Md: US Dept of Health and Human Services; May 2003. NIH publication 03-5233. Available at: http://www.nhlbi.nih.gov/guidelines/hypertension/express. Accessed November 14, 2003.

13. American Association of Clinical Endocrinologists medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management: 2000 update. Endocr Pract. 2000;8(suppl 1):40-82.

14. Woolf SH, Davidson MB, Greenfield S, et al. Controlling blood glucose levels in patients with type 2 diabetes mellitus: an evidence-based policy statement by the American Academy of Family Physicians and American Diabetes Association. J Fam Pract. 2000;49:453-460.

15. National Committee for Quality Assurance. The State of Health Care Quality: 2003. Washington, DC: NCQA; 2003;1-34.

16. Saaddine JB, Engelgau MM, Beckles GL, Gregg EW, Thompson TJ, Venkat Narayan KMV. A diabetes report card for the United States: quality of care in the 1990s. Ann Intern Med. 2002;136:565-574.

17. Suwattee P, Lynch JC, Pendergrass ML. Quality of care for diabetic patients in a large urban public hospital. Diabetes Care. 2003;26:563-568.

18. Fleming BB, Greenfield S, Engelgau MM, Pogach LM, Clauser SB, Parrott MA. The Diabetes Quality Improvement Project: moving science into health policy to gain an edge on the diabetes epidemic. Diabetes Care. 2001;24:1815-1820.

19. American Diabetes Association. Screening for type 2 diabetes. Diabetes Care. 2004;27:S11-S14.

20. U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: recommendations and rationale. Ann Intern Med. 2003;138:212-214.

21. Genuth S, Alberti KG, Bennett P, et al. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003;26:3160-3167.

22. Centers for Disease Control and Prevention. Prevalence of diabetes and impaired fasting glucose in adults: United States, 1999-2000. Morb Mortal Wkly Rep. 2003;52:833-837.

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

24. 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.

25. Feld S. AACE diabetes guidelines. Endocr Pract. 2002;8(suppl 1):41-65.

26. Wright A, Burden AC, Paisey RB, Cull CA, Holman RR. Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the UK Prospective Diabetes Study (UKPDS 57). Diabetes Care. 2002;25:330-336.

27. Riddle MC. The underuse of insulin therapy in North America. Diabetes Metab Res Rev. 2002;18:S42-S49.

28. Rosenstock J. Insulin therapy: optimizing control in type 1 and type 2 diabetes. Clin Cornerstone. 2001;4:50-64.

29. Avilés-Santa L, Sinding J, Raskin P. Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;131:182-188.

30. Ratner RE, Hirsch IB, Neifing JL, Garg SK, Mecca TE, Wilson CA. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes. Diabetes Care. 2000;23:639-643.

31. Yki-Jarvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner 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.

32. 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.

33. Scarlett JA, Gray RS, Griffin J, Olefsky JM, Kolterman OG. Insulin treatment reverses the insulin resistance of type II diabetes mellitus. Diabetes Care. 1982;5:353-363.

34. Malmberg K. and the DIGAMI (Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction) Study Group Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. Br Med J. 1997;314:1512-1515.

35. Hunt LM, Valenzuela MA, Pugh JA. NIDDM patients’ fears and hopes about insulin therapy: the basis of patient reluctance. Diabetes Care. 1997;20:292-298.

36. Fritsche A, Schweitzer MA, Haring HU. Glimepiride combined with morning insulin glargine, bedtime neutral protamine Hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2003;138:952-959.

37. Lepore M, Pampanelli S, Fanelli C, et al. Pharmacokinetics and pharmacodynamics 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.

38. Full U.S. Prescribing Information for Lantus. Available at: http://www.lantus.com/professional/home.jsp .Accessed March 5, 2003.

39. DeWitt DE, Dugdale DC. Using new insulin strategies in the outpatient treatment of diabetes: clinical applications. JAMA. 2003;289:2265-2269.

40. Rosenstock J, Schwartz SL, Clark CM, Jr.,, Park GD, Donley DW, Edwards MB. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care. 2001;24:631-636.

41. Raut M, Sung JCY, Law AW. Cost of treating hypoglycemia among patients with diabetes [abstract]. Diabetes Care. 2003;26(suppl 2):A1152.-

Disclosures: Dr LeRoith serves as a consultant to Aventis Pharmaceuticals, Pfizer Inc, and Novo Nordisk Pharmaceuticals, Inc. and on the speakers’ bureaus of Aventis Pharmaceuticals, Pfizer Inc, and Eli Lilly and Co. Dr Levetan serves as a consultant to Eli Lilly and Co. and Novo Nordisk Pharmaceuticals, Inc. and on the speakers’ bureaus of Aventis Pharmaceuticals and Novo Nordisk Pharmaceuticals, Inc. Dr Hirsch serves as a consultant to Eli Lilly and Co., Novo Nordisk Pharmaceuticals, Inc., Aventis Pharmaceuticals, and Medtronic MiniMed. Dr Riddle has received grant/research support from Amylin Pharmaceuticals, Aventis Pharmaceuticals, and Pfizer Inc. He serves as a consultant to and is on the speakers’ bureaus of Amylin Pharmaceuticals, Aventis Pharmaceuticals, GlaxoSmithKline, and Novo Nordisk Pharmaceuticals, Inc. Corresponding author: Derek Le Roith, MD, PhD, Room 8D12, Bldg 10, National Institutes of Health, MSC 1758, Bethesda MD 20892-1758. E-mail: leroith@comcast.net.

Routine screening for type 1 diabetes among healthy children is not expected to yield many cases and is not recommended. However, because the incidence of type 2 diabetes is increasing among children, it has been suggested that those who are overweight (defined as weight for height >85th percentile or weight >120% of ideal for height) with 2 or more additional risk factors should be screened every 2 years, beginning at age 10 years or at the onset of puberty.¹⁹

The ADA criteria for diagnosis of diabetes are listed in Table 1 . Whichever criterion is used, diagnostic test results must be confirmed on a subsequent day.¹⁹

Patients who do not meet the diagnostic criteria but have either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) are considered to have prediabetes (see Table 1 ).^19,21 Based on recent estimates, more than 12 million adults in the United States have prediabetes.²² Of great importance is regular monitoring of patients with IGT or IFG because in addition to diabetes, they are at a heightened risk of MI or stroke compared with normoglycemic persons.

TABLE 1
Diagnostic criteria for prediabetes and diabetes

Prediabetes	Diabetes
One or both of the following:	One or more of the following:
Impaired fasting glucose (fasting plasma glucose ≥100 mg/dL and <126 mg/dL) Impaired glucose tolerance (2-hour postload plasma glucose ≥140 mg/dL and <200 mg/dL)*	Fasting plasma glucose ≥126 mg/dL 2-hour postload plasma glucose ≥200 mg/dL* Symptoms of diabetes (eg, polyuria, polydipsia, weight loss, blurred vision) plus random plasma glucose ≥200 mg/dL
*Oral glucose tolerance test should use glucose load containing equivalent of 75 g anhydrous glucose dissolved in water.
Adapted from American Diabetes Association.¹⁹

Intensive management

The UKPDS showed that intensive glycemic control in type 2 diabetes significantly reduced the risk of microvascular complications.^23,24 In UKPDS 33, patients with newly diagnosed type 2 diabetes whose disease remained uncontrolled after completing 3 months of dietary management were initially randomized to intensive treatment (goal: FPG <108 mg/dL) with sulfonylurea or insulin monotherapy or to conventional treatment (goal: FPG <270 mg/dL) that began with diet. After 10 years, the median A1C was 7.0% in the intensive group and 7.9% in the conventional group.²³ The reduction in A1C was associated with a 25% reduction of microvascular endpoints, mainly a reduced need for retinal photocoagulation (relative risk [RR] for intensive therapy, 0.75; 95% CI, 0.60–0.93; P<.01). While there was a 16% reduction in the risk of MI, this difference was not statistically significant (RR, 0.84; 95% CI, 0.71–1.00; P=.052). The UKPDS 35, which was an epidemiologic analysis of data (ie, not a direct comparison of the 2 treatment arms), demonstrated that each 1% reduction in mean A1C was associated with a 21% decrease in risk for any diabetes-related endpoint (95% CI, 17%–24%; P<.0001), a 21% decrease in diabetes-related deaths (95% CI, 15%–27%; P<.0001), a 37% decrease in the risk for microvascular complications (95% CI, 33%–41%; P<.0001), and a 14% decrease in the risk of MI (95% CI, 8%–21%; P<.0001) ( Figure 1 ).⁶

Another study that supports intensive management of type 2 diabetes is the Steno-2 study, a randomized controlled trial of 160 patients with type 2 diabetes and microalbuminuria.⁸ After 7.8 years of follow-up, 54% of conventionally treated and 57% of intensively treated patients were receiving insulin. Decreases in risk factors (eg, A1C, blood pressure, lipids, and albumin excretion) were significantly greater in patients receiving intensive therapy ( Figure 2 ). Significant reductions also were seen in the risk of cardiovascular disease (RR, 0.47; 95% CI, 0.24–0.73), nephropathy (RR, 0.39; 95% CI, 0.17–0.87), retinopathy (RR, 0.42; 95% CI, 0.21–0.86), and autonomic neuropathy (RR, 0.37; 95% CI, 0.18–0.79). Overall, intensive therapy in the Steno-2 study reduced risk of cardiovascular and microvascular events by about 50%.

FIGURE 1
UKPDS 35: Risk reductions associated with each 1% decrease in updated mean A1C

Adapted from Stratton et al.⁶

FIGURE 2 Percentage of patients in Steno-2 who reached treatment goals at mean follow-up of 7.8 years

Adapted from Gaede et al.⁸

Role of insulin in achieving targets

Another finding of the UKPDS was that type 2 diabetes is routinely progressive and that treatment with a single agent is unlikely to be successful for more than 5 years. Such observations mirror the physiologic progression from insulin resistance to absolute insulin deficiency. Thus, lifestyle modification often needs to be supplemented with oral antihyperglycemic therapy. In some cases, early treatment with insulin is preferable to relieve symptoms of hyperglycemia (eg, blurred vision, frequent thirst), which are suggestive of glucotoxicity and deteriorating β-cell function. As absolute insulin deficiency occurs, multiple oral agents, with or without insulin, may be required for optimal control of the disease.^4,25