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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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| __NOTOC__ | | __NOTOC__ |
| {{Infobox_Disease | | {{Diabetes mellitus type 2}} |
| | Name = Diabetes mellitus
| | '''For patient information, click [[{{PAGENAME}} (patient information)|here]]''' |
| | Image = Blue circle for diabetes.svg
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| | Caption = United Nations blue circle symbol for diabetes.<ref>{{cite web| title=IDF Chooses Blue Circle to Represent UN Resolution Campaign |url=http://www.unitefordiabetes.org/news/campaign/idf_chooses_blue_circle_to_represent_un_resolution_campaign/index.html |date=17 March 2006 |publisher=Unite for Diabetes}}</ref>
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| | ICD10 = {{ICD10|E|10||e|10}}–{{ICD10|E|14||e|10}}
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| | ICD9 = {{ICD9|250}}
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| | ICDO =
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| | OMIM = 222100 |
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| | MedlinePlus = 001214
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| | eMedicineSubj = med
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| | eMedicineTopic = 546
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| | eMedicine_mult = {{eMedicine2|emerg|134}}
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| | MeshName = Diabetes
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| | MeshNumber = C18.452.394.750
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| }}
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| {{SI}}
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| {{CMG}}
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| {{Editor Join}} | | {{CMG}}; {{AE}}{{MehdiP}},{{TarekNafee}}, {{Anahita}} |
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| ==Overview==
| | {{SK}}:DM, Diabetes, NIDDM |
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| '''Diabetes mellitus type 2''' (formerly called non [[insulin]]-dependent diabetes (NIDDM), obesity related diabetes, or adult-onset diabetes) is a [[metabolism|metabolic]] disorder that is primarily characterized by [[insulin resistance]], relative insulin deficiency, and [[hyperglycemia]]. It is often managed by engaging in exercise and modifying one's diet. It is rapidly increasing in the developed world, and there is some evidence that this pattern will be followed in much of the rest of the world in coming years. The [[Centers for Disease Control and Prevention|CDC]] has characterized the increase as an [[epidemic]].<ref>{{Citation
| | ==[[Diabetes mellitus type 2 overview|Overview]]== |
| | last =Gerberding
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| | first =Julie Louise
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| | title =Diabetes, Disabling Disease to Double by 2050
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| | date =2007-05-24
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| | year =2007
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| | publisher =CDC
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| | url =http://www.cdc.gov/nccdphp/publications/aag/ddt.htm }}</ref>
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| Unlike [[Diabetes mellitus type 1|Type 1]] diabetes, there is little tendency toward [[ketoacidosis]] in Type 2 diabetes, though it is not unknown. One effect that can occur is [[Non Ketonic Hyperglycemic coma|nonketonic hyperglycemia]]. Complex and multifactorial metabolic changes lead to damage and function impairment of many [[organ (anatomy)|organ]]s, most importantly the [[cardiovascular]] system in both types. This leads to substantially increased [[morbidity]] and [[death|mortality]] in both Type 1 and Type 2 patients, but the two have quite different origins and treatments despite the similarity in complications.
| | ==[[Diabetes mellitus type 2 historical perspective|Historical Perspective]]== |
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| ==Pathophysiology== | | ==[[Diabetes mellitus type 2 pathophysiology |Pathophysiology]]== |
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| [[Insulin resistance]] means that body [[cell (biology)|cells]] do not respond appropriately when insulin is present. | | ==[[Diabetes mellitus type 2 causes|Causes]]== |
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| Other important contributing factors:
| | ==[[Differentiating Diabetes mellitus type 2 from other diseases|Differentiating Diabetes Mellitus Type 2 from other Diseases]]== |
| * increased hepatic glucose production (e.g., from glycogen degradation), especially at inappropriate times
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| * decreased insulin-mediated [[glucose]] transport in (primarily) [[muscle]] and adipose tissues (receptor and post-receptor defects)
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| * impaired beta-cell function—loss of early phase of insulin release in response to hyperglycemic stimuli
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| * Cancer survivors who received allogenic Hematopoeitic Cell Transplantation (HCT) are 3.65 times more likely to report type 2 diabetes than their siblings. Total body irradiation (TBI) is also associated with a higher risk of developing diabetes.
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| This is a more complex problem than type 1, but is sometimes easier to treat, especially in the initial years when insulin is often still being produced internally. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. However, severe complications can result from unnoticed type 2 diabetes, including [[renal failure]], blindness, wounds that fail to heal, and [[coronary artery disease]]. The onset of the disease is most common in [[middle age]] and [[old age|later life]].
| | ==[[Diabetes mellitus type 2 epidemiology and demographics|Epidemiology and Demographics]]== |
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| Diabetes mellitus type 2 is presently of unknown [[etiology]] (i.e., origin). Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus. Examples include diabetes mellitus caused by [[hemochromatosis]], pancreatic insufficiency, or certain types of medications (e.g. long-term [[steroid]] use).
| | ==[[Diabetes mellitus type 2 risk factors|Risk Factors]]== |
| {{Diabetes}}
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| About 90–95% of all North American cases of diabetes are type 2<ref name="nature">Zimmet, P., Alberti, K. G. M. M., Shaw, J. Global and societal implications of the diabetes epidemic. ''Nature'' '''2001''', 414, 782-787.</ref>, and about 20% of the population over the age of 65 has diabetes mellitus type 2. The fraction of type 2 diabetics in other parts of the world varies substantially, almost certainly for environmental and lifestyle reasons, though these are not known in detail. Diabetes affects over 150 million people worldwide with this number expected to double by 2025<ref name="nature"/>. There is also a strong inheritable [[genetics|genetic]] connection in type 2 diabetes: having relatives (especially first degree) with type 2 is a considerable risk factor for developing type 2 diabetes. In addition there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe form of diabetes<ref>Sakagashira, S., Sanke, T., Hanabusa, T., Shimomura, H., Ohagi, S., Kumagaye, K. Y.,Nakajima, K. & Nanjo, K. Missense mutation of amylin gene (S20G) in Japanese NIDDM
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| patients. ''Diabetes'' '''1996''', 45, 1279-1281.</ref><sup>,</sup><ref>Seino, S. S20G mutation of the amylin gene is associated with Type II diabetes in Japanese. ''Diabetologia'' '''2001''', 44, (7), 906-909.</ref>. About 55 percent of type 2 are [[obesity|obese]]<ref>{{cite journal
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| | last = Eberhart
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| | first = M. S.
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| | coauthors = Ogden, C, Engelgau, M, Cadwell, B, Hedley, A. A., Saydah, S. H.,
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| | title = Prevalence of Overweight and Obesity Among Adults with Diagnosed Diabetes --- United States, 1988--1994 and 1999--2002
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| | journal = Morbidity and Mortality Weekly Report
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| | volume = 53
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| | issue = 45
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| | pages = 1066-1068
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| | publisher = Centers for Disease Control and Prevention
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| | date = November 19, 2004
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| | url = http://www.cdc.gov/mmwR/preview/mmwrhtml/mm5345a2.htm
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| }}</ref> —chronic obesity leads to increased insulin resistance that can develop into diabetes, most likely because [[adipose tissue]] is a (recently identified) source of chemical signals (hormones and [[cytokines]]). Other research shows that type 2 diabetes causes obesity.<!--
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| --><ref name="IntJObes.1999-Camastra">{{cite journal | author=Camastra S, Bonora E, Del Prato S, Rett K, Weck M, Ferrannini E | title=Effect of obesity and insulin resistance on resting and glucose-induced thermogenesis in man. EGIR (European Group for the Study of Insulin Resistance) | journal=Int J Obes Relat Metab Disord | year=1999 | pages=1307-13 | volume=23 | issue=12 | id=PMID 10643689}}</ref>
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| Diabetes mellitus type 2 is often associated with [[obesity]] and [[hypertension]] and elevated [[cholesterol]] ([[combined hyperlipidemia]]), and with the condition [[Metabolic syndrome]] (also known as Syndrome X, Reavan's syndrome, or CHAOS). It is also associated with [[acromegaly]], [[Cushing's syndrome]] and a number of other[[endocrinology|endocrinological]] disorders. Additional factors found to increase risk of type 2 diabetes include aging<ref>Jack, L., Jr., Boseman, L. & Vinicor, F. Aging Americans and diabetes. A public health and clinical response. ''Geriatrics'' '''2004''', 59, 14-17.</ref>, high-fat diets<ref>Lovejoy, J. C. The influence of dietary fat on insulin resistance. ''Curr Diab Rep'' '''2002''', 2,435-440.</ref> and a less active lifestyle<ref>Hu, F. B. Sedentary lifestyle and risk of obesity and type 2 diabetes. Lipids 2003, 38,103-108.</ref>. | | ==[[Diabetes mellitus type 2 screening|Screening]]== |
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| | ==[[Diabetes mellitus type 2 natural history, complications, and prognosis|Natural history, Complications and Prognosis]]== |
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| ==Diagnosis== | | ==Diagnosis== |
| The World Health Organization definition of diabetes is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either<ref name="who-99">.{{cite web |url=http://www.who.int/diabetes/publications/en/ |author=World Health Organization | title= Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus |format= |work=}}</ref>:
| | [[Diabetes mellitus type 2 diagnostic study of choice|Diagnostic Study of Choice]] |[[Diabetes mellitus type 2 history and symptoms|History and Symptoms]] | [[Diabetes mellitus type 2 physical examination|Physical Examination]] | [[Diabetes mellitus type 2 laboratory findings|Laboratory Findings]] | [[Diabetes mellitus type 2 electrocardiogram|Electrocardiogram]] | [[Diabetes mellitus type 2 chest x ray|X-Ray]] | [[Diabetes mellitus type 2 CT|CT scan]] | [[Diabetes mellitus type 2 MRI|MRI]] | [[Diabetes mellitus type 2 echocardiography or ultrasound |Echocardiography and Ultrasound]] | [[Diabetes mellitus type 2 other imaging findings|Other Imaging Findings]] | [[Diabetes mellitus type 2 other diagnostic studies|Other Diagnostic Studies]] |
| * fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)
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| :or
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| * With a [[Glucose tolerance test]], two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl)
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| ==Screening and prevention==
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| Interest has arisen in preventing diabetes due to research on the benefits of treating patients before overt diabetes. Although the [http://www.ahrq.gov/clinic/uspstfix.htm 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"<ref name="pmid12558361">{{cite journal |author=U.S. Preventive Services Task Force |title=Screening for type 2 diabetes mellitus in adults: recommendations and rationale |journal=Ann. Intern. Med. |volume=138 |issue=3 |pages=212-4 |year=2003 |pmid=12558361 |url=http://www.annals.org/cgi/content/full/138/3/212}} [http://www.ngc.gov/summary/summary.aspx?ss=15&doc_id=3523 National Guidelines Clearinghouse: Complete Summary]</ref><ref name="pmid12558362">{{cite journal |author=Harris R, Donahue K, Rathore SS, Frame P, Woolf SH, Lohr KN |title=Screening adults for type 2 diabetes: a review of the evidence for the U.S. Preventive Services Task Force |journal=Ann. Intern. Med. |volume=138 |issue=3 |pages=215-29 |year=2003 |pmid=12558362|url=http://www.annals.org/cgi/content/full/138/3/215}}</ref>, this was a [http://www.ahrq.gov/clinic/3rduspstf/ratings.htm grade I recommendation] when published in 2003. However, the USPSTF does recommend screening for diabetics in adults with hypertension or hyperlipidemia ([http://www.ahrq.gov/clinic/3rduspstf/ratings.htm grade B recommendation]).
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| In 2005, an [http://www.ahrq.gov/clinic/epcindex.htm 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".<ref name="pmid16194123">{{cite journal |author=Santaguida PL, Balion C, Hunt D, ''et al'' |title=Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose |journal=Evidence report/technology assessment (Summary) |volume= |issue=128 |pages=1-11 |year=2005 |pmid=16194123 |doi= | url=http://www.ahrq.gov/clinic/epcsums/impglusum.htm}}</ref>
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| ===Accuracy of tests for early detection===
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| 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<ref name="pmid12558362"/>:
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| * [[sensitivity (tests)|sensitivity]] about 50%
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| * [[specificity (tests)|specificity]] greater than 95%
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| A ''random'' capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses ''current'' diabetes with<ref name="pmid11679454">{{cite journal |author=Rolka DB, Narayan KM, Thompson TJ, ''et al'' |title=Performance of recommended screening tests for undiagnosed diabetes and dysglycemia |journal=Diabetes Care |volume=24 |issue=11 |pages=1899-903 |year=2001 |pmid=11679454 |doi=}}</ref>:
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| * [[sensitivity (tests)|sensitivity]] = 75%
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| * [[specificity (tests)|specificity]] = 88%
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| [[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.<ref name="pmid17679132">{{cite journal |author=Pradhan AD, Rifai N, Buring JE, Ridker PM |title=Hemoglobin A1c predicts diabetes but not cardiovascular disease in nondiabetic women |journal=Am. J. Med. |volume=120 |issue=8 |pages=720-7 |year=2007 |pmid=17679132 |doi=10.1016/j.amjmed.2007.03.022}}</ref> 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: | |
| * [[sensitivity (tests)|sensitivity]] = 16.7%
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| * [[specificity (tests)|specificity]] = 98.9%
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| ===Benefit of early detection===
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| 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 [[Impaired glucose tolerance|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<ref name="pmid12876091">{{cite journal |author=Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M |title=Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial |journal=JAMA |volume=290 |issue=4 |pages=486-94 |year=2003 |pmid=12876091 |doi=10.1001/jama.290.4.486}} [http://www.acpjc.org/Content/140/1/issue/ACPJC-2004-140-1-002.htm ACP Journal Club review]</ref>.
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| Other studies have shown that life-style changes<ref name="pmid17098085">{{cite journal |author=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 |title=Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study |journal=Lancet |volume=368 |issue=9548 |pages=1673-9 |year=2006 |pmid=17098085|doi=10.1016/S0140-6736(06)69701-8}}[http://www.acpjc.org/Content/146/2/issue/ACPJC-2007-146-2-037.htm ACP Journal Club review]</ref> and [[metformin]]<ref name="pmid11832527">{{cite journal |author=Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM |title=Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin |journal=N. Engl. J. Med. |volume=346 |issue=6 |pages=393-403 |year=2002 |pmid=11832527|doi=10.1056/NEJMoa012512}} [http://www.acpjc.org/Content/137/2/issue/ACPJC-2002-137-2-055.htm ACP Journal Club review]</ref> can delay the onset of diabetes.
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| ==Treatment== | | ==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: | | ===Medical therapy=== |
| # reduction of mortality and concomitant morbidity (from assorted diabetic complications)
| | : '''[[Diabetes mellitus type 2 medical therapy|Pharmacotherapy]]''' (outpatients) |
| # preservation of quality of life
| | : '''[[Diabetes mellitus type 2 medical therapy of inpatients|Pharmacotherapy]]''' (inpatients) |
| 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 trial]]s 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.
| | : '''[[Diabetes mellitus type 2 Glycemic control|Glycemic Control]]''' |
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| 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.
| | ===Non-medical therapy=== |
| | : '''[[Diabetes mellitus type 2 Life style modification|Life Style Modification]]''' |
| | : '''[[Diabetes mellitus type 2 Patient education|Patient education]]''' |
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| ===Treatment goals=== | | ===Surgical therapy=== |
| For most patients, [[clinical practice guideline]]s recommend a goal [[Glycosylated hemoglobin|Hba1c]] of 6.0%<ref name="pmid16373931">{{cite journal |author= |title=Standards of medical care in diabetes--2006 |journal=Diabetes Care |volume=29 Suppl 1 |issue= |pages=S4–42 |year=2006 |pmid=16373931 |doi=}}</ref> to 7.0%<ref name="pmidpending">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. [http://www.annals.org/cgi/content/full/147/6/417 Full text]</ref>.
| | : '''[[Diabetes mellitus type 2 surgery|Surgery]]''' |
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| In older patients, [[clinical practice guideline]]s 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".<ref name="pmid12694461">{{cite journal |author=Brown AF, Mangione CM, Saliba D, Sarkisian CA |title=Guidelines for improving the care of the older person with diabetes mellitus |journal=Journal of the American Geriatrics Society |volume=51 |issue=5 Suppl Guidelines |pages=S265–80 |year=2003 |pmid=12694461 |doi=10.1046/j.1532-5415.51.5s.1.x|url=http://www.americangeriatrics.org/products/positionpapers/JAGSfinal05.pdf}}</ref>
| | ===Patient Care Management interventions=== |
| | : '''[[Mobile_health#Diabetes | Mobile health]]''' |
| | : '''[[Patient Care Teams]]''' |
| | : '''[[Patient navigators]]''' |
| | : '''[[Shared decision making]]''' |
| | : '''[[Telemedicine]]''' |
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| ===Self monitoring of blood glucose=== | | ===Prevention=== |
| {{main|Blood glucose monitoring}}
| | : '''[[Diabetes mellitus type 2 primary prevention|Primary Prevention]]''' |
| It is unclear if self-monitoring of blood glucose improves outcomes among "reasonably well controlled non-insulin treated patients with type 2 diabetes".<ref name="pmid17591623">{{cite journal |author=Farmer A, Wade A, Goyder E, ''et al'' |title=Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial |journal= |volume= |issue= |pages= |year=2007 |pmid=17591623 |doi=10.1136/bmj.39247.447431.BE}}</ref>
| | : '''[[Diabetes mellitus type 2 secondary prevention|Secondary Prevention]]''' |
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| ===Dietary management=== | | ==Related Chapters== |
| Modifying the diet is known to help control glucose intake, and in response, blood glucose levels.
| | *[[List of terms associated with diabetes]] |
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| 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".<ref>{{cite news |title=Original Human 'Stone Age' Diet Is Good For People With Diabetes, Study Finds |url=http://www.sciencedaily.com/releases/2007/06/070627225459.htm |date=June 28, 2007 |publisher=ScienceDaily.com}}</ref>
| | ==External Links== |
| | | {{refbegin|2}} |
| Other evidence for modified diets treating and being beneficial include:
| | *[http://www.who.int/nutrition/topics/dietnutrition_and_chronicdiseases/en/ Diet, Nutrition and the prevention of chronic diseases] (including diabetes) by a Joint [[WHO]]/[[FAO]] Expert consultation (2003) |
| * A vegan diet.<ref>{{cite web |title=Diabetes: Can a Vegan Diet Reverse Diabetes? |url=http://www.pcrm.org/health/clinres/diabetes.html |author=Nicholson A| date=02/15/05 |publisher=Physicians Committee for Responsible Medicine}}</ref><ref>{{cite journal |author=Barnard ND, Cohen J, Jenkins DJ, ''et al'' |title=A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes |journal=Diabetes Care |volume=29 |issue=8 |pages=1777-83 |year=2006 |pmid=16873779 |doi=10.2337/dc06-0606 |url=http://care.diabetesjournals.org/cgi/content/full/29/8/1777}}<br/>'''Related news articles:'''
| | *[http://www.cdc.gov/diabetes/ Centers for Disease Control Diabetes Section] |
| *{{cite news |title=Low-fat vegan diet treats type 2 diabetes more effectively than a standard diabetes diet |url=http://www.news-medical.net/?id=19351 |date=8-Aug-2006 |publisher=News-Medical.Net}}</ref>
| | *[http://www.nlm.nih.gov/medlineplus/diabetes.html MedlinePlus Diabetes from the U.S. National Library of Medicine] |
| * Caloric restriction.<ref>{{cite journal |author=Nielsen JV, Joensson E |title=Low-carbohydrate diet in type 2 diabetes. Stable improvement of bodyweight and glycemic control during 22 months follow-up |journal=Nutrition & metabolism |volume=3 |issue= |pages=22 |year=2006 |pmid=16774674 |doi=10.1186/1743-7075-3-22 |url=http://www.nutritionandmetabolism.com/content/3/1/22}}</ref> | | *[http://ndep.nih.gov/ National Diabetes Education Program] |
| * Cinnamon and Nutmeg (spices commonly found in apple pie).<ref>{{cite journal |author=Khan A, Bryden NA, Polansky MM, Anderson RA |title=Insulin potentiating factor and chromium content of selected foods and spices |journal=Biological trace element research |volume=24 |issue=3 |pages=183-8 |year=1990 |pmid=1702671 |doi=}}<br/>'''Related news articles:'''
| | *[http://www.diabetes.niddk.nih.gov/ National Diabetes Information Clearinghouse] |
| *{{cite news |title=Apple Pie Improves Blood Sugar Regulation and Insulin Sensitivity? -- Apple pie spices (typically cinnamon and nutmeg) were responsible for the beneficial effects. |url=http://www.diabetesincontrol.com/issue118/item8.shtml |date=August, 2001 |publisher=Diabetes In Control}}</ref>
| | *[http://www.who.int/mediacentre/factsheets/fs312/en/ World Health Organization fact sheet on diabetes] |
| | | *[http://www.who.int/diabetes/en/ World Health Organization—The Diabetes Programme] |
| ===Exercise===
| | *[http://diabetes.niddk.nih.gov/ National Diabetes Information Clearinghouse] |
| 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."<ref name="pmid17876019">{{cite journal |author=Sigal RJ, Kenny GP, Boulé NG, ''et al'' |title=Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial |journal=Ann. Intern. Med. |volume=147 |issue=6 |pages=357–69 |year=2007 |pmid=17876019 |doi=|url=http://www.annals.org/cgi/content/full/147/6/357}} [http://www.annals.org/cgi/content/summary/147/6/357 Non-technical summary]</ref><ref>{{cite web |url=http://www.time.com/time/health/article/0,8599,1662683,00.html?xid=newsletter-weekly |title=Study: The Best Exercise for Diabetes|publisher=Time Inc|
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| author=Song S|format= |work=}}</ref> The combined program reduced the [[Glycosylated hemoglobin|HbA1c]] by 0.5 percentage point.
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| ===Antidiabetic drugs===
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| [[Image:Metformin 500mg Tablets.jpg|200px|thumb|Metformin 500mg tablets]]
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| {{main|anti-diabetic drug}}
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| 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 [[secretagogue|insulin secretion]] by the pancreas.
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| Newer drug classes include:
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| * [[Thiazolidinedione]]s ([[TZD]]s) ([[rosiglitazone]], [[pioglitazone]], and [[troglitazone]]) (withdrawn from the US market) | |
| * [[Alpha-glucosidase inhibitor|α-glucosidase inhibitors]] ([[acarbose]] and [[miglitol]])
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| * [[Meglitinide]]s which stimulate insulin release ([[nateglinide]], [[repaglinide]], and their analogs)
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| * Peptide analogs which work in a variety of ways:
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| ** Incretin mimetics act as insulin secretagogue among other effects. These includes the Glucagon-like peptide (GLP) analog [[exenatide]]
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| ** [[Dipeptidyl peptidase-4 inhibitors|Dipeptidyl peptidase-4 (DPP-4) inhibitors]] increase [[Incretin]] levels ( [[sitagliptin]]) | |
| ** Amylin agonist analog, which slows gastric emptying and suppresses glucagon ([[pramlintide]])
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| ====Selecting an antidiabetic drug====
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| =====Oral drugs=====
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| A systematic review of randomized controlled trials found that [[metformin]] and second-generation sulfonylureas are the preferred choices for most.<ref>Bolen S et al. Systematic Review: [http://www.annals.org/cgi/content/full/0000605-200709180-00178v1 Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus]. Ann Intern Med 2007;147:6
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| </ref> 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".<ref name="pmid17145742">
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| {{cite journal |author=Kahn SE, Haffner SM, Heise MA, ''et al'' |title=Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy |journal=N. Engl. J. Med. |volume=355 |issue=23 |pages=2427-43 |year=2006 |pmid=17145742 |doi=10.1056/NEJMoa066224}}
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| </ref> Of these, rosiglitazone had more weight gain and edema.<ref name="pmid17145742"/> Rosiglitazone may increase risk of death from cardiovascular causes.<ref name="nejm-rosiglitazone">
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| {{cite web |url=http://content.nejm.org/cgi/content/full/NEJMoa072761 |title=NEJM -- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes}}
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| </ref> Pioglitazone and rosiglitazone may increase the risk of fractures.<ref name="fda-actos>
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| {{cite web |url=http://www.fda.gov/medwatch/safety/2007/safety07.htm#actos |title=MedWatch - 2007 Safety Information Alerts (Actos (pioglitazone))}}
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| </ref><ref name="fda-rosiglitazone">{{cite web |url=http://www.fda.gov/medwatch/safety/2007/safety07.htm#rosiglitazone |title=MedWatch - 2007 Safety Information Alerts (Rosiglitazone)}}
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| </ref>
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| For patients who also have heart failure, [[metformin]] may be the best drug.<ref name="pmid17761999">{{cite journal |author=Eurich DT, McAlister FA, Blackburn DF, ''et al'' |title=Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review |journal=BMJ |volume=335 |issue=7618 |pages=497 |year=2007 |pmid=17761999 |doi=10.1136/bmj.39314.620174.80}}</ref>
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|
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|
| =====Insulin preparations=====
| | {{refend}} |
| =====Starting insulin=====
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| If [[antidiabetic drug]]s fail (or stop helping), [[insulin]] therapy may be necessary -- usually in addition to oral medication therapy -- to maintain normal glucose levels.
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| Typical total daily dosage of insulin is 0.6 U/kg.<ref name="pmid10068412"/> More complicated estimations to guide initial dosage of insulin are:<ref name="pmid2951066">{{cite journal |author=Holman RR, Turner RC |title=A practical guide to basal and prandial insulin therapy |journal=Diabet. Med. |volume=2 |issue=1 |pages=45–53 |year=1985 |pmid=2951066 |doi=}}</ref>
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| * For men, [(fasting plasma glucose [mmol/liter]–5)x2] x (weight [kg]÷(14.3xheight [m])–height [m])
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| * For women, [(fasting plasma glucose [mmol/liter]–5)x2] x (weight [kg]÷(13.2xheight [m])–height [m])
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| The initial insulin regimen can be chosen based on the patient's blood glucose profile.<ref name="pmid16847295">{{cite journal |author=Mooradian AD, Bernbaum M, Albert SG |title=Narrative review: a rational approach to starting insulin therapy |journal=Ann. Intern. Med. |volume=145 |issue=2 |pages=125-34 |year=2006 |pmid=16847295 |doi=|url=http://www.annals.org/cgi/content/full/145/2/125}}</ref> Initially, adding nightly insulin to patients failing oral medications may be best.<ref name="pmid1406860">{{cite journal |author=Yki-Järvinen H, Kauppila M, Kujansuu E, ''et al'' |title=Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus |journal=N. Engl. J. Med. |volume=327 |issue=20 |pages=1426-33 |year=1992 |pmid=1406860 |doi=}}</ref> Nightly insulin combines better with [[metformin]] that with [[sulfonylurea]]s.<ref name="pmid10068412">{{cite journal |author=Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M |title=Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial |journal=Ann. Intern. Med. |volume=130 |issue=5 |pages=389–96 |year=1999 |pmid=10068412 |doi=|url=http://www.annals.org/cgi/content/full/130/5/389}}</ref> 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.<ref name="pmid9761809">{{cite journal |author=Kratz A, Lewandrowski KB |title=Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Normal reference laboratory values |journal=N. Engl. J. Med. |volume=339 |issue=15 |pages=1063–72 |year=1998 |pmid=9761809 |doi=}}</ref>
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| When nightly insulin is insufficient, choices include:
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| * 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.<ref name="pmid17890232">{{cite journal |author=Holman RR, Thorne KI, Farmer AJ, ''et al'' |title=Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes |journal=N. Engl. J. Med. |volume=357 |issue= |pages= |year=2007 |pmid=17890232 |doi=10.1056/NEJMoa075392}}</ref><ref name="pmid15677776">{{cite journal |author=Raskin P, Allen E, Hollander P, ''et al'' |title=Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs |journal=Diabetes Care |volume=28 |issue=2 |pages=260-5 |year=2005 |pmid=15677776 |doi=|url=http://care.diabetesjournals.org/cgi/content/full/28/2/260}}</ref><ref name="pmid15823767">{{cite journal |author=Malone JK, Kerr LF, Campaigne BN, Sachson RA, Holcombe JH |title=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 |journal=Clinical therapeutics |volume=26 |issue=12 |pages=2034-44 |year=2004 |pmid=15823767 |doi=10.1016/j.clinthera.2004.12.015}}</ref>. 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".<ref name="pmid15677776"/> A guide to titrating fixed ratio insulin is available (http://www.annals.org/cgi/content/full/145/2/125/T4).<ref name="pmid16847295"/>
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| * Long acting insulins such as [[insulin glargine]] and [[insulin detemir]]. A [[meta-analysis]] of [[randomized controlled trials]] by the [[Cochrane Collaboration]] found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2".<ref name="pmid17443605">{{cite journal |author=Horvath K, Jeitler K, Berghold A, Ebrahim Sh, Gratzer T, Plank J, Kaiser T, Pieber T, Siebenhofer A |title=Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus |journal=Cochrane database of systematic reviews (Online) |volume= |issue=2 |pages=CD005613 |year=2007 |pmid=17443605}}</ref> More recently, a [[randomized controlled trial]] found that although long acting insulins were less effective, they were associated with less hypoglycemia.<ref name="pmid17890232"/>
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| ===Alternative Medicines===
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| [[Carnitine]] has been shown to increase insulin sensitivity and glucose storage in humans. <ref name="AMC study">{{cite journal | title=L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients| journal=Journal of the American College of Nutrition| author=Geltrude Mingrone, Aldo V. Greco, Esmeralda Capristo, Giuseppe Benedetti, Annalisa Giancaterini, Andrea De Gaetano, and Giovanni Gasbarrini |year=1999 |volume=18 |issue=1 |pages=77-82 |url=http://www.jacn.org/cgi/content/full/18/1/77}}</ref>. 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.
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| [[Taurine]] has also shown significant improvement in [[insulin sensitivity]] and [[hyperlipidemia]] in rats.<ref name="Japanese rats">{{cite journal | title=Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes |authors=Yutaka Nakaya, Asako Minami, Nagakatsu Harada, Sadaichi Sakamoto, Yasuharu Niwa and Masaharu Ohnaka |date January 2000 |journal=American Journal of Clinical Nutrition |volume= 71 |issue= 1 |pages=54-58 |url=http://www.ajcn.org/cgi/content/full/71/1/54}}</ref>
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| 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.
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| ===Antihypertensive agents===
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| {{main|Antihypertensive}}
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| The goal blood pressure is 130/80 which is lower than in non-diabetic patients.<ref name="pmid12748199">{{cite journal |author=Chobanian AV, Bakris GL, Black HR, ''et al'' |title=The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report |journal=JAMA |volume=289 |issue=19 |pages=2560-72 |year=2003 |pmid=12748199 |doi=10.1001/jama.289.19.2560}}</ref>
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| ===ACE inhibitors===
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| The HOPE study suggests that diabetics should be treated with [[ACE inhibitors]] (specifically [[ramipril]] 10 mg/d) if they have one of the following <ref name="pmid10639539">{{cite journal |author=Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G |title=Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators |journal=N. Engl. J. Med. |volume=342 |issue=3 |pages=145-53 |year=2000 |pmid=10639539 |doi=}}</ref>:
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| * [[hypertension]]
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| * [[hypercholesterolemia]] or reduced low high-density lipoprotein cholesterol levels
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| * cigarette smoking
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| * [[microalbuminuria]]
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| 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.<ref name="pmid15262665">{{cite journal |author=Pilote L, Abrahamowicz M, Rodrigues E, Eisenberg MJ, Rahme E |title=Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect? |journal=Ann. Intern. Med. |volume=141 |issue=2 |pages=102-12 |year=2004 |pmid=15262665 |doi=}}</ref>
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|
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| ===Hypolipidemic agents===
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| {{main|Hypercholesterolemia#Diabetic_patients}}
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| ==References==
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| {{reflist|2}}
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| ==External links ==
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| *[http://www.diabetes.org.uk/ Diabetes UK - Largest organisation in the UK working for people with diabetes]
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| *[http://www.diabetes.org/home.jsp American Diabetes Association]
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| *[http://diabetes.niddk.nih.gov/ National Diabetes Information Clearinghouse]
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| *[http://www.hormone.org/public/diabetes.cfm Diabetes Section] of [[The Hormone Foundation]]
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| *[http://www.dhealth.org/ Diabetes Health Institute]
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| *[http://www.tabixir.com/ Diabetes]
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| *[http://diabetescorner.blogspot.com/2007/09/type-2-diabetes-mellitus-adult-onset.html Adult Onset Diabetes]
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| *[http://healthydiabeticmeals.com/dangerous-myths-about-diabetes Dangerous Myths About Diabetes]
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| {{Endocrine pathology}} | | {{Endocrine pathology}} |
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