Diabetes mellitus type 2

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Diagnosis

The World Health Organization definition of diabetes is for a single raised glucose reading with symptoms, otherwise raised values on two occassions,of either[1]:

  • fasting plasma glucose ≥ 7.0mmol/l (126mg/dl)
or

Screening and prevention

Interest has arisen in preventing diabetes due to research on the benefits of treating patients before overt diabetes. Although the U.S. Preventive Services Task Force (USPSTF) concluded that "the evidence is insufficient to recommend for or against routinely screening asymptomatic adults for type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose"[2][3], this was a grade I recommendation when published in 2003.

In 2005, an evidence report by the Agency for Healthcare Research and Quality concluded that "there is evidence that combined diet and exercise, as well as drug therapy (metformin, acarbose), may be effective at preventing progression to DM in IGT subjects".[4]

Accuracy of tests for early detection

If a 2-hour postload glucose level of at least 11.1 mmol/L (≥ 200 mg/dL) is used as the reference standard, the fasting plasma glucose > 7.0 mmol/L (126 mg/dL) has[3]:

A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) has[5]:

Benefit of early detection

Since publication of the USPSTF statement, a randomized controlled trial of prescribing acarbose to patients with "high-risk population of men and women between the ages of 40 and 70 years with a body mass index (BMI), calculated as weight in kilograms divided by the square of height in meters, between 25 and 40. They were eligible for the study if they had IGT according to the World Health Organization criteria, plus impaired fasting glucose (a fasting plasma glucose concentration of between 100 and 140 mg/dL or 5.5 and 7.8 mmol/L) found a number needed to treat of 44 (over 3.3 years) to prevent a major cardiovascular event[6].

Other studies have shown that life-style changes[7] and metformin[8] can delay the onset of diabetes.

Treatment

Self monitoring of blood glucose

Is it unclear if self monitoring of blood glucose improves outcomes in type 2 diabetes.[9]

Available classes of antidiabetic drugs

Sulfonylureas

For more information, see: Sulfonylureas.


Biguanides

Biguanides include metformin and phenformin.

Thiazolidinediones

Thiazolidinediones (TZDs) include rosiglitazone, pioglitazone, and troglitazone.

α-glucosidase inhibitors

α-glucosidase inhibitors include acarbose and miglitol.

Meglitinides

Meglitinides stimulate insulin release. Examples include nateglinide, repaglinide, and their analogs.

Peptide analogs

Insulins

For more information, see: insulin.


Selecting an antidiabetic drug

Oral drugs

If dietary changes are not successful, medication is needed. A systematic review of randomized controlled trials found that metformin and second-generation sulfonylureas and are excellent choices.[10] Confirming the role of metformin, the initial choice of anti-diabetic drug has been compared in a randomized controlled trial which found "cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide"[11]. Rosiglitazone had more weight gain and edema.[11] Rosiglitazone may increase risk of death from cardiovascular causes.[12] Pioglitazone[13] and rosiglitazone may increase the risk of fractures.[14]

Insulin preparations

If antidiabetic drugs fail to help (or stop helping), insulin therapy may be necessary, usually as an adjunct to oral medication therapy, to maintain normal glucose levels.

The initial insulin regimen can be chosen based on the patient's blood glucose profile.[15] Initially, adding nightly insulin to patients failing oral medications may be best.[16]

When nightly insulin is insufficient, insulin can be premixed with a fixed ratio of short and intermediate acting insulin; this may be better than using long acting insulin.[17][18]. A guide to titrating fixed ratio insulin is available(http://www.annals.org/cgi/content/full/145/2/125/T4).[15]

Long acting insulins

A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2".[19]

Antihypertensive agents

The goal blood pressure is 130/80 which is lower than in non-diabetic patients.[20]

ACE inhibitors

The HOPE study suggests that diabetics should be treated with ACE inhibitors (specifically ramipril 10 mg/d) if they have one of the following [21]:

After treatment with ramipril for 5 years the number needed to treat was 50 patients to prevent one cardiovascular death. Other ACE inhibitors may not be as effective.[22]

Hypolipidemic agents

Various clinical practice guidelines have addressed the treatment of hypercholesterolemia. The American College of Physicians has addressed hypercholesterolemia in patients with diabetes [23]. Their recommendations are:

  • Recommendation 1: Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type 2 diabetes.
  • Recommendation 2: Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type 2 diabetes and other cardiovascular risk factors.
  • Recommendation 3: Once lipid-lowering therapy is initiated, patients with type 2 diabetes mellitus should be taking at least moderate doses of a statin (the accompanying evidence report states "simvastatin, 40 mg/d; pravastatin, 40 mg/d; lovastatin, 40 mg/d; atorvastatin, 20 mg/d; or an equivalent dose of another statin")[24].
  • Recommendation 4: For those patients with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes is not recommended except in specific circumstances.

Complications

Diabetic neuropathy

For more information, see: Diabetic neuropathy.

References

  1. ↑ .World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus. Retrieved on 2007-05-29.
  2. ↑ U.S. Preventive Services Task Force (2003). "Screening for type 2 diabetes mellitus in adults: recommendations and rationale". Ann. Intern. Med. 138 (3): 212-4. PMID 12558361. National Guidelines Clearinghouse: Complete Summary
  3. ↑ 3.0 3.1 Harris R, Donahue K, Rathore SS, Frame P, Woolf SH, Lohr KN (2003). "Screening adults for type 2 diabetes: a review of the evidence for the U.S. Preventive Services Task Force". Ann. Intern. Med. 138 (3): 215-29. PMID 12558362.
  4. ↑ Santaguida PL, Balion C, Hunt D, et al (2005). "Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose". Evidence report/technology assessment (Summary) (128): 1-11. PMID 16194123. [e]
  5. ↑ Rolka DB, Narayan KM, Thompson TJ, et al (2001). "Performance of recommended screening tests for undiagnosed diabetes and dysglycemia". Diabetes Care 24 (11): 1899-903. PMID 11679454. [e]
  6. ↑ Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M (2003). "Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial". JAMA 290 (4): 486-94. DOI:10.1001/jama.290.4.486. PMID 12876091. Research Blogging. ACP Journal Club review
  7. ↑ Lindström J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemiö K, Hämäläinen H, Härkönen P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Mannelin M, Paturi M, Sundvall J, Valle TT, Uusitupa M, Tuomilehto J (2006). "Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study". Lancet 368 (9548): 1673-9. DOI:10.1016/S0140-6736(06)69701-8. PMID 17098085. Research Blogging. ACP Journal Club review
  8. ↑ Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002). "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin". N. Engl. J. Med. 346 (6): 393-403. DOI:10.1056/NEJMoa012512. PMID 11832527. Research Blogging. ACP Journal Club review
  9. ↑ Farmer A, Wade A, Goyder E, et al (2007). "Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial". DOI:10.1136/bmj.39247.447431.BE. PMID 17591623. Research Blogging. PMID 17591623
  10. ↑ Bolen S et al. Systematic Review: Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus. Ann Intern Med 2007;147:6
  11. ↑ 11.0 11.1 Kahn SE, Haffner SM, Heise MA, et al (2006). "Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy". N. Engl. J. Med. 355 (23): 2427-43. DOI:10.1056/NEJMoa066224. PMID 17145742. Research Blogging.
  12. ↑ NEJM -- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. Retrieved on 2007-05-21.
  13. ↑ MedWatch - 2007 Safety Information Alerts. Retrieved on 2007-05-21.
  14. ↑ MedWatch - 2007 Safety Information Alerts. Retrieved on 2007-05-21.
  15. ↑ 15.0 15.1 Mooradian AD, Bernbaum M, Albert SG (2006). "Narrative review: a rational approach to starting insulin therapy". Ann. Intern. Med. 145 (2): 125-34. PMID 16847295. [e]
  16. ↑ Yki-Järvinen H, Kauppila M, Kujansuu E, et al (1992). "Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus". N. Engl. J. Med. 327 (20): 1426-33. PMID 1406860. [e]
  17. ↑ Raskin P, Allen E, Hollander P, et al (2005). "Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs". Diabetes Care 28 (2): 260-5. PMID 15677776. [e]
  18. ↑ Malone JK, Kerr LF, Campaigne BN, Sachson RA, Holcombe JH (2004). "Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy". Clinical therapeutics 26 (12): 2034-44. DOI:10.1016/j.clinthera.2004.12.015. PMID 15823767. Research Blogging.
  19. ↑ Horvath K, Jeitler K, Berghold A, Ebrahim Sh, Gratzer T, Plank J, Kaiser T, Pieber T, Siebenhofer A (2007). "Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus". Cochrane database of systematic reviews (Online) (2): CD005613. PMID 17443605.
  20. ↑ Chobanian AV, Bakris GL, Black HR, et al (2003). "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report". JAMA 289 (19): 2560-72. DOI:10.1001/jama.289.19.2560. PMID 12748199. Research Blogging.
  21. ↑ Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000). "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators". N. Engl. J. Med. 342 (3): 145-53. PMID 10639539. [e]
  22. ↑ Pilote L, Abrahamowicz M, Rodrigues E, Eisenberg MJ, Rahme E (2004). "Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect?". Ann. Intern. Med. 141 (2): 102-12. PMID 15262665. [e]
  23. ↑ Snow V, Aronson M, Hornbake E, Mottur-Pilson C, Weiss K (2004). "Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians". Ann Intern Med 140 (8): 644-9. PMID 15096336.
  24. ↑ Vijan S, Hayward RA (2004). "Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians". Ann. Intern. Med. 140 (8): 650-8. PMID 15096337. [e]
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