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

Impaired fasting glucose

Impaired fasting glucose is defined as:[1][2]

  • Fasting glucose level > 5.6 mmol/l (100 mg/dl) and < 6.9 mmol/l (125mg/dl).

Impaired glucose tolerance

Impaired glucose tolerance is defined as[1][2]:

Screening and prevention

Regarding the mass screening for diabetes, the U.S. Preventive Services Task Force (USPSTF) concluded:[3][4]

  • "The evidence is insufficient to recommend for or against routinely screening asymptomatic adults for type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose" (italics by CZ), this was a grade I recommendation when published in 2003.
  • "The USPSTF recommends screening for type 2 diabetes in adults with hypertension or hyperlipidemia." This was a grade B recommendation

Screening obese patients may also be beneficial.[5]

Accuracy of tests for early detection

Various testing strategies are available.[6][7] The fasting plasma glucose > 7.0 mmol/L (126 mg/dL), compared to a 2-hour postload glucose level of at least 11.1 mmol/L (≥ 200 mg/dL) as a reference standard, has[4]:

A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) has[8]:

Glycosylated hemoglobin values that are elevated (over 5%), but not in the diabetic range (not over 7.0%) are predictive of subsequent clinical diabetes in US female health professionals.[9] In this study, 177 of 1061 patients with glycosylated hemoglobin value less than 6% became diabetic within 5 years compared to 282 of 26281 patients with a glycosylated hemoglobin value of 6.0% or more. This equates to a glycosylated hemoglobin value of 6.0% or more having:

Benefit of early detection

According to the USPSTF[3][4], the benefits are:

  • In hypertensive patients, identifying diabetes would lower the goal diastolic pressure to ≤ 80 mm Hg.
  • In hypercholesterolemia patients, identifying diabetes would affect decision making due to changes in calculating cardiovascular risk in the ATP3 clinical practice guideline.[10]

Since publication of the USPSTF statement, a randomized controlled trial of prescribing acarbose to patients who do not have overt diabetes, but are a "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[11].

Subsequently in 2005, an evidence report by the Agency for Healthcare Research and Quality (AHRQ) 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".[12]

Other studies have shown that life-style changes[13] and metformin[14] can delay the onset of diabetes. Life-style changes can reduce cardiovascular risk factors.[15]

The DREAM study has reported that rosiglitazone[16] but not ramipril[17] can delay the onset of diabetes. Although the DREAM study performed carotid ultrasounds on 20% of patients, these results have not been reported.[18]

Treatment

Treatment goals

Practice guidelines

For most patients, clinical practice guidelines recommend a goal Hba1c of 6.0%[19] to 7.0%[20].

In older patients, clinical practice guidelines by the American Geriatrics Society states "for frail older adults, persons with life expectancy of less than 5 years, and others in whom the risks of intensive glycemic control appear to outweigh the benefits, a less stringent target such as 8% is appropriate".[21]

Evidence from trials

The UK Prospective Diabetes Study (UKPDS 33) randomized controlled trial found that intensively treating patients with diabetes type II for 10 years reduced diabetic complications in one out of every 20 patients (number needed to treat = 20).[22]

Self monitoring of blood glucose

It is unclear if self-monitoring of blood glucose improves outcomes among "reasonably well controlled non-insulin treated patients with type 2 diabetes".[23]

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.[24] 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"[25]. Rosiglitazone had more weight gain and edema.[25] Rosiglitazone may increase risk of death from cardiovascular causes.[26] Pioglitazone[27] and rosiglitazone may increase the risk of fractures.[28]

For patients with heart failure, metformin may be the best choice.[29]

Starting insulin

If antidiabetic drugs fail (or stop helping), insulin therapy may be necessary -- usually in addition to oral medication therapy -- to maintain normal glucose levels.

Typical total daily dosage of insulin is 0.6 U/kg.[30] More complicated estimations to guide initial dosage of insulin are:[31]

  • For men, [(fasting plasma glucose [mmol/liter]–5)x2] x (weight [kg]÷(14.3xheight [m])–height [m])
  • For women, [(fasting plasma glucose [mmol/liter]–5)x2] x (weight [kg]÷(13.2xheight [m])–height [m])

The initial insulin regimen can be chosen based on the patient's blood glucose profile.[32] Initially, adding nightly insulin to patients failing oral medications may be best.[33] Nightly insulin combines better with metformin that with sulfonylureas.[30] The initial dose of nightly insulin (measured in IU/d) should be equal to the fasting blood glucose level (measured in mmol/L). If the fasting glucose is reported in mg/dl, multiple by 0.05551 to convert to mmol/L.[34]

When nightly insulin is insufficient, choices include:

  • Premixed insulin with a fixed ratio of short and intermediate acting insulin; this tends to be more effective than long acting insulin, but is associated with more hypoglycemia.[35][36][37]. Initial total daily dosage of biphasic insulin can be 10 units if the fasting plasma glucose values are less than 180 mg/dl or 12 units when the fasting plasma glucose is above 180 mg/dl".[36] A guide to titrating fixed ratio insulin is available (http://www.annals.org/cgi/content/full/145/2/125/T4).[32]

Antihypertensive agents

The goal blood pressure is 130/80 which is lower than in non-diabetic patients.[39]

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 [40]:

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.[41]

Hypolipidemic agents

Various clinical practice guidelines have addressed the treatment of hypercholesterolemia. The American College of Physicians has addressed hypercholesterolemia in patients with diabetes [42]. 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")[43].
  • 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

Neuropathy

For more information, see: Diabetic neuropathy.


Nephropathy

References

  1. ↑ 1.0 1.1 1.2 .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. Cite error: Invalid <ref> tag; name "who-99" defined multiple times with different content Cite error: Invalid <ref> tag; name "who-99" defined multiple times with different content
  2. ↑ 2.0 2.1 (2005) "Diagnosis and classification of diabetes mellitus". Diabetes Care 28 Suppl 1: S37-42. PMID 15618111. [e]
  3. ↑ 3.0 3.1 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
  4. ↑ 4.0 4.1 4.2 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.
  5. ↑ Hoerger TJ, Hicks KA, Sorensen SW, et al (2007). "Cost-effectiveness of screening for pre-diabetes among overweight and obese U.S. adults". Diabetes Care 30 (11): 2874–9. DOI:10.2337/dc07-0885. PMID 17698614. Research Blogging.
  6. ↑ (2005) "Strategies to identify adults at high risk for type 2 diabetes: the Diabetes Prevention Program". Diabetes Care 28 (1): 138–44. PMID 15616247. [e]
  7. ↑ Icks A, Haastert B, Gandjour A, et al (2004). "Cost-effectiveness analysis of different screening procedures for type 2 diabetes: the KORA Survey 2000". Diabetes Care 27 (9): 2120–8. PMID 15333472. [e]
  8. ↑ 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]
  9. ↑ Pradhan AD, Rifai N, Buring JE, Ridker PM (2007). "Hemoglobin A1c predicts diabetes but not cardiovascular disease in nondiabetic women". Am. J. Med. 120 (8): 720-7. DOI:10.1016/j.amjmed.2007.03.022. PMID 17679132. Research Blogging.
  10. ↑ 10-year CVD Risk Calculator (Risk Assessment Tool for Estimating 10-year Risk of Developing Hard CHD (Myocardial Infarction and Coronary Death) Version). Retrieved on 2007-11-14.
  11. ↑ 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
  12. ↑ 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]
  13. ↑ 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
  14. ↑ 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
  15. ↑ Thoolen B, De Ridder D, Bensing J, et al (2007). "Effectiveness of a self-management intervention in patients with screen-detected type 2 diabetes". Diabetes Care 30 (11): 2832–7. DOI:10.2337/dc07-0777. PMID 17666461. Research Blogging.
  16. ↑ Gerstein HC, Yusuf S, Bosch J, et al (2006). "Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial". Lancet 368 (9541): 1096–105. DOI:10.1016/S0140-6736(06)69420-8. PMID 16997664. Research Blogging.
  17. ↑ Bosch J, Yusuf S, Gerstein HC, et al (2006). "Effect of ramipril on the incidence of diabetes". N. Engl. J. Med. 355 (15): 1551–62. DOI:10.1056/NEJMoa065061. PMID 16980380. Research Blogging.
  18. ↑ Gerstein HC, Yusuf S, Holman R, Bosch J, Pogue J (2004). "Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial". Diabetologia 47 (9): 1519–27. DOI:10.1007/s00125-004-1485-5. PMID 15322749. Research Blogging.
  19. ↑ (2006) "Standards of medical care in diabetes--2006". Diabetes Care 29 Suppl 1: S4–42. PMID 16373931. [e]
  20. ↑ Qaseem A, Vijan S, Snow V, Cross JT, Weiss KB, Owens DK, et al. Glycemic Control and Type 2 Diabetes Mellitus: The Optimal Hemoglobin A1c Targets. A Guidance Statement from the American College of Physicians. Ann Intern Med. 2007 Sep 18;147(6):417-422. Full text
  21. ↑ Brown AF, Mangione CM, Saliba D, Sarkisian CA (2003). "Guidelines for improving the care of the older person with diabetes mellitus". Journal of the American Geriatrics Society 51 (5 Suppl Guidelines): S265–80. DOI:10.1046/j.1532-5415.51.5s.1.x. PMID 12694461. Research Blogging.
  22. ↑ (1998) "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 352 (9131): 837–53. DOI:10.1016/S0140-6736(98)07019-6. PMID 9742976. Research Blogging. Review by ACP Journal Club
  23. ↑ 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.
  24. ↑ Bolen S et al. Systematic Review: Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus. Ann Intern Med 2007;147:6
  25. ↑ 25.0 25.1 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.
  26. ↑ NEJM -- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. Retrieved on 2007-05-21.
  27. ↑ MedWatch - 2007 Safety Information Alerts. Retrieved on 2007-05-21.
  28. ↑ MedWatch - 2007 Safety Information Alerts. Retrieved on 2007-05-21.
  29. ↑ Eurich DT, McAlister FA, Blackburn DF, et al (2007). "Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review". BMJ 335 (7618): 497. DOI:10.1136/bmj.39314.620174.80. PMID 17761999. Research Blogging.
  30. ↑ 30.0 30.1 Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M (1999). "Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial". Ann. Intern. Med. 130 (5): 389–96. PMID 10068412. [e]
  31. ↑ Holman RR, Turner RC (1985). "A practical guide to basal and prandial insulin therapy". Diabet. Med. 2 (1): 45–53. PMID 2951066. [e]
  32. ↑ 32.0 32.1 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]
  33. ↑ 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]
  34. ↑ Kratz A, Lewandrowski KB (1998). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Normal reference laboratory values". N. Engl. J. Med. 339 (15): 1063–72. PMID 9761809. [e]
  35. ↑ 35.0 35.1 Holman RR, Thorne KI, Farmer AJ, et al (2007). "Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes". N. Engl. J. Med. 357. DOI:10.1056/NEJMoa075392. PMID 17890232. Research Blogging.
  36. ↑ 36.0 36.1 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]
  37. ↑ 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.
  38. ↑ 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.
  39. ↑ 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.
  40. ↑ 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]
  41. ↑ 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]
  42. ↑ 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.
  43. ↑ 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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