Diabetes mellitus type 2

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Differentiating Diabetes Mellitus Type 2 from other Diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Cafer Zorkun, M.D., Ph.D. [3]

Overview

Historical Perspective

Pathophysiology

Risk Factors

Screening

Epidemiology and demographics

Natural history, Complications, and Prognosis

Classification

Causes

Differentiating Type page name here from other Disorders

Diagnosis

History and Symptoms | Physical Examination | Laboratory Tests | Electrocardiogram | Chest X Ray | MRI | CT | Echocardiography | Other Imaging Findings | Other Diagnostic Studies

Treatment

Medical: Medical Therapy

Surgical: Surgery

Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies|Social issues

See also

References

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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"[1][2], this was a grade I recommendation when published in 2003. However, the USPSTF does recommend screening for diabetics in adults with hypertension or hyperlipidemia (grade B recommendation).

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".[3]

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) diagnoses current diabetes with[2]:

A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses current diabetes with[4]:

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.[5] 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

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

Diabetes mellitus type 2 is a chronic, progressive disease that has no medically proven cure. There are two main goals of treatment of the disease:

  1. reduction of mortality and concomitant morbidity (from assorted diabetic complications)
  2. preservation of quality of life

The first goal can be achieved through close glycemic control (i.e., blood glucose levels); the reduction effect in diabetic complications has been well demonstrated in several extensive clinical trials and is thus well established. The second goal is often addressed (in developed countries) by support and care from teams of diabetic health workers (physician, PA, nurse, dietitian or a certified diabetic educator). Endocrinologists, family practitioners, and general internists are the types of physicians most likely to treat people with diabetes. Knowledgeable patient participation is vital and so patient education is a crucial aspect of this effort.

Type 2 is initially treated by adjustment in diet and exercise, and by weight loss, especially in obese patients. The amount of weight loss which improves the clinical picture is sometimes modest (2-5 kg or 4.4-11 lb); this is almost certainly due to currently poorly understood aspects of fat tissue chemical signaling (especially in visceral fat tissue in and around abdominal organs). In many cases, such initial efforts can substantially restore insulin sensitivity.

Treatment goals

For most patients, clinical practice guidelines recommend a goal Hba1c of 6.0%[9] to 7.0%[10].

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".[11]

Self monitoring of blood glucose

Main article: Blood glucose monitoring

It is unclear if self-monitoring of blood glucose improves outcomes among "reasonably well controlled non-insulin treated patients with type 2 diabetes".[12]

Dietary management

Modifying the diet is known to help control glucose intake, and in response, blood glucose levels.

One 2007 study will report that in a Paleolithic diet, all 14 patients returned blood glucose levels to normal after the trial period of 12 weeks, and improved glucose tolerance (26% less blood glucose rise following a carbohydrate intake compared to 7% reduction for control group on a Mediterranean diet). This was the first Paleolithic diet study, and suggested that "it may be more efficient to avoid some of our modern foods than to count calories or carbohydrate".[13]

Other evidence for modified diets treating and being beneficial include:

  • A vegan diet.[14][15]
  • Caloric restriction.[16]
  • Cinnamon and Nutmeg (spices commonly found in apple pie).[17]

Exercise

In September 2007, a joint randomized controlled trial by the University of Calgary and the University of Ottawa found that "Either aerobic or resistance training alone improves glycemic control in type 2 diabetes, but the improvements are greatest with combined aerobic and resistance training than either alone."[18][19] The combined program reduced the HbA1c by 0.5 percentage point.

Antidiabetic drugs

Metformin 500mg tablets
Main article: anti-diabetic drug

The most important drug now used in Type 2 Diabetes is the Biguanide metformin which works primarily by reducing liver release of blood glucose from glycogen stores as well as some increase in uptake of glucose by the body's tissues. Both historically and currently commonly used are the Sulfonylurea group, of which several members (including glibenclamide and gliclazide) are widely used; these increase glucose stimulated insulin secretion by the pancreas.

Newer drug classes include:

Selecting an antidiabetic drug

Oral drugs

A systematic review of randomized controlled trials found that metformin and second-generation sulfonylureas are the preferred choices for most.[20] Failure of response after a time is not unknown with most of these agents: 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".[21] Of these, rosiglitazone had more weight gain and edema.[21] Rosiglitazone may increase risk of death from cardiovascular causes.[22] Pioglitazone and rosiglitazone may increase the risk of fractures.[23][24]

For patients who also have heart failure, metformin may be the best drug.[25]

Insulin preparations
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.[26] More complicated estimations to guide initial dosage of insulin are:[27]

  • 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.[28] Initially, adding nightly insulin to patients failing oral medications may be best.[29] Nightly insulin combines better with metformin that with sulfonylureas.[26] 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.[30]

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.[31][32][33]. 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".[32] A guide to titrating fixed ratio insulin is available (http://www.annals.org/cgi/content/full/145/2/125/T4).[28]

Alternative Medicines

Carnitine has been shown to increase insulin sensitivity and glucose storage in humans. [35]. It is important to note that this was with a constant blood infusion, not an oral dose, and that the clinical significance of this result is unclear.

Taurine has also shown significant improvement in insulin sensitivity and hyperlipidemia in rats.[36]

Neither of these have shown permanent positive effects, nor a complete restoration to pre-diabetes conditions, only improvement. Their clinical importance in humans remains unclear.

Antihypertensive agents

Main article: Antihypertensive

The goal blood pressure is 130/80 which is lower than in non-diabetic patients.[37]

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 [38]:

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.[39]

Hypolipidemic agents

Main article: Hypercholesterolemia § Diabetic_patients

References

  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
  2. ↑ 2.0 2.1 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  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. 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.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. ACP Journal Club review
  9. ↑ "Standards of medical care in diabetes--2006". Diabetes Care. 29 Suppl 1: S4–42. 2006. PMID 16373931.
  10. ↑ 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
  11. ↑ Brown AF, Mangione CM, Saliba D, Sarkisian CA (2003). "Guidelines for improving the care of the older person with diabetes mellitus" (PDF). Journal of the American Geriatrics Society. 51 (5 Suppl Guidelines): S265–80. doi:10.1046/j.1532-5415.51.5s.1.x. PMID 12694461.
  12. ↑ 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.
  13. ↑ "Original Human 'Stone Age' Diet Is Good For People With Diabetes, Study Finds". ScienceDaily.com. June 28, 2007.
  14. ↑ Nicholson A (02/15/05). "Diabetes: Can a Vegan Diet Reverse Diabetes?". Physicians Committee for Responsible Medicine. Check date values in: |date= (help)
  15. ↑ Barnard ND, Cohen J, Jenkins DJ; et al. (2006). "A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes". Diabetes Care. 29 (8): 1777–83. doi:10.2337/dc06-0606. PMID 16873779.
    Related news articles:
  16. ↑ Nielsen JV, Joensson E (2006). "Low-carbohydrate diet in type 2 diabetes. Stable improvement of bodyweight and glycemic control during 22 months follow-up". Nutrition & metabolism. 3: 22. doi:10.1186/1743-7075-3-22. PMID 16774674.
  17. ↑ Khan A, Bryden NA, Polansky MM, Anderson RA (1990). "Insulin potentiating factor and chromium content of selected foods and spices". Biological trace element research. 24 (3): 183–8. PMID 1702671.
    Related news articles:
  18. ↑ Sigal RJ, Kenny GP, Boulé NG; et al. (2007). "Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial". Ann. Intern. Med. 147 (6): 357–69. PMID 17876019. Non-technical summary
  19. ↑ Song S. "Study: The Best Exercise for Diabetes". Time Inc.
  20. ↑ Bolen S et al. Systematic Review: Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus. Ann Intern Med 2007;147:6
  21. ↑ 21.0 21.1 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.
  22. ↑ "NEJM -- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes".
  23. ↑ "MedWatch - 2007 Safety Information Alerts (Actos (pioglitazone))".
  24. ↑ "MedWatch - 2007 Safety Information Alerts (Rosiglitazone)".
  25. ↑ 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.
  26. ↑ 26.0 26.1 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.
  27. ↑ Holman RR, Turner RC (1985). "A practical guide to basal and prandial insulin therapy". Diabet. Med. 2 (1): 45–53. PMID 2951066.
  28. ↑ 28.0 28.1 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 31.0 31.1 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.
  32. ↑ 32.0 32.1 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.
  33. ↑ 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.
  34. ↑ 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.
  35. ↑ Geltrude Mingrone, Aldo V. Greco, Esmeralda Capristo, Giuseppe Benedetti, Annalisa Giancaterini, Andrea De Gaetano, and Giovanni Gasbarrini (1999). "L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients". Journal of the American College of Nutrition. 18 (1): 77–82.
  36. ↑ Yutaka Nakaya, Asako Minami, Nagakatsu Harada, Sadaichi Sakamoto, Yasuharu Niwa and Masaharu Ohnaka. "Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes". American Journal of Clinical Nutrition. 71 (1): 54–58. Text "date January 2000 " ignored (help)
  37. ↑ 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.
  38. ↑ 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.
  39. ↑ 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.

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