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People with a confirmed diagnosis of diabetes are tested routinely for complications. This includes yearly urine testing for [[microalbuminuria]] and examination of the [[retina]] of the eye for [[diabetic retinopathy|retinopathy]].
People with a confirmed diagnosis of diabetes are tested routinely for complications. This includes yearly urine testing for [[microalbuminuria]] and examination of the [[retina]] of the eye for [[diabetic retinopathy|retinopathy]].

The [[U.S. Preventive Services Task Force]] 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=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 |month=February |pmid=12558362 |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=12558362 |accessdate=19 July 2008}}</ref><ref name=pmid12558361>{{cite journal |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 |month=February |pmid=12558361 |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=12558361 |accessdate=19 July 2008 |author1=U.S. Preventive Services Task Force}}</ref> this was a grade I recommendation<ref>[http://www.ahrq.gov/clinic/3rduspstf/ratings.htm Grade I recommendation]</ref> when published in 2003. However, the USPSTF does recommend screening for diabetics in adults with hypertension or hyperlipidemia.<ref>[http://www.ahrq.gov/clinic/3rduspstf/ratings.htm grade B recommendation]</ref>


==Prevention==
==Prevention==
{{Main|Prevention of diabetes mellitis type 2}}
Onset of type 2 diabetes can often be delayed through proper nutrition and regular exercise.<ref>{{cite journal |author=Raina Elley C, Kenealy T |title=Lifestyle interventions reduced the long-term risk of diabetes in adults with impaired glucose tolerance |journal=Evid Based Med |volume=13 |issue=6 |pages=173 |year=2008 |month=December |pmid=19043031 |doi=10.1136/ebm.13.6.173 }}</ref>
Onset of type 2 diabetes can often be delayed through proper nutrition and regular exercise.<ref>{{cite journal |author=Raina Elley C, Kenealy T |title=Lifestyle interventions reduced the long-term risk of diabetes in adults with impaired glucose tolerance |journal=Evid Based Med |volume=13 |issue=6 |pages=173 |year=2008 |month=December |pmid=19043031 |doi=10.1136/ebm.13.6.173 }}</ref>


A 2005 report concluded that "there is evidence that combined diet and exercise, as well as drug therapy (metformin, acarbose), may be effective at preventing progression to diabetes 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=Evid Rep Technol Assess (Summ) |issue=128 |pages=1–11 |year=2005 |month=August |pmid=16194123 |url=http://www.ahrq.gov/downloads/pub/evidence/pdf/impglucose/impglucose.pdf |format=PDF|accessdate=19 July 2008}}</ref><ref>[http://www.ahrq.gov/clinic/epcindex.htm evidence report]</ref>
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]] 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=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 |month=February |pmid=12558362 |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=12558362 |accessdate=19 July 2008}}</ref><ref name=pmid12558361>{{cite journal |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 |month=February |pmid=12558361 |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=12558361 |accessdate=19 July 2008 |author1=U.S. Preventive Services Task Force}}</ref> this was a grade I recommendation<ref>[http://www.ahrq.gov/clinic/3rduspstf/ratings.htm Grade I recommendation]</ref> when published in 2003. However, the USPSTF does recommend screening for diabetics in adults with hypertension or hyperlipidemia.<ref>[http://www.ahrq.gov/clinic/3rduspstf/ratings.htm grade B recommendation]</ref>

In 2005, an evidence report<ref>[http://www.ahrq.gov/clinic/epcindex.htm evidence report]</ref> 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 diabetes 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=Evid Rep Technol Assess (Summ) |issue=128 |pages=1–11 |year=2005 |month=August |pmid=16194123 |url=http://www.ahrq.gov/downloads/pub/evidence/pdf/impglucose/impglucose.pdf |format=PDF|accessdate=19 July 2008}}</ref>

[[Milk]] has also been associated with the prevention of diabetes. A questionnaire study was done by Choi et al. of 41,254 men which including a twelve year follow up showed this association. In this study, it was found that diets high in low-fat [[dairy]] might lower the risk of type 2 diabetes in men. Even though these benefits are being considered linked to milk consumption, the effect of diet is only one factor that is affecting the body's overall health.<ref>
{{cite journal
|author = Choi HK, Willett WC, Stampfer P, Vasson MP, Maubois JL, Beaufrere B
|title = Dairy consumption and risk of type 2 diabetes mellitus in men
|journal = Archives of Internal Medicine
|volume = 165
|pages = 997–1003
|year = 2005
|accessdate = 2009-10-29
|doi = 10.1001/archinte.165.9.997
|pmid = 15883237
|issue = 9
}}</ref>

===Lifestyle===
Type&nbsp;2 diabetes risk can be reduced in many cases by making changes in diet and increasing physical activity.<ref name=pmid17098085 /><ref name="Knowler">{{cite journal |author=Knowler WC, Barrett-Connor E, Fowler SE, ''et al.'' |title=Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin |journal=[[The New England Journal of Medicine]] |volume=346 |issue=6 |pages=393–403 |year=2002 |month=February |pmid=11832527 |pmc=1370926 |doi=10.1056/NEJMoa012512}}</ref><ref>{{cite doi|10.1016/S0140-6736(09)61457-4}}</ref> The [[American Diabetes Association]] (ADA) recommends maintaining a healthy weight, getting at least 2½ hours of exercise per week (several brisk sustained walks appear sufficient), having a modest fat intake, and eating sufficient fiber (e.g., from whole grains).

There is inadequate evidence that eating foods of low [[glycemic index]] is clinically helpful despite recommendations and suggested diets emphasizing this approach.<ref>{{cite journal |author=Bantle JP, Wylie-Rosett J, Albright AL, ''et al.'' |title=Nutrition recommendations and interventions for diabetes—2006: a position statement of the American Diabetes Association |journal=Diabetes Care |volume=29 |issue=9 |pages=2140–57 |year=2006 |month=September |pmid=16936169 |doi=10.2337/dc06-9914}}</ref>

Diets that are very low in saturated fats reduce the risk of becoming insulin resistant and diabetic.<ref name="Barnard 2007">{{Cite book|last=Barnard|first=Neal|coauthors=|year=2007|chapter=13|title=Dr. Neal Barnard's Program for Reversing Diabetes: The Scientifically Proven System for Reversing Diabetes Without Drugs|publisher=Rodale/Holtzbrinck Publishers|location=New York, NY|isbn=978-1-59486-528-2|isbn-status=May be invalid – please double check}}</ref><ref name=pmid19386029>{{cite journal |author=Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G |title=Vegetarian and vegan diets in type 2 diabetes management |journal=Nutrition Reviews |volume=67 |issue=5 |pages=255–63 |year=2009 |month=May |pmid=19386029 |doi=10.1111/j.1753-4887.2009.00198.x}}</ref> Study group participants whose "physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes."<ref name="Mozaffarian D, Kamineni A, Carnethon M, Djoussé L, Mukamal KJ, Siscovick D 2009 798–807"/> In another study of dietary practice and incidence of diabetes, "foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized."<ref name="Fat2009"/> However, in 2010, scientists at the [[Harvard School of Public Health]] and collaborators from other institutions identified a natural substance in dairy fat that may substantially reduce the risk of type 2 diabetes. The compound, trans-palmitoleic acid, is a fatty acid found in milk and other dairy products. It is not produced by the body and so only comes from the diet. The researchers examined participants who have been followed for 20 years in an observational study to evaluate risk factors for cardiovascular diseases in older adults. During follow-up it was found that individuals with higher circulating levels of trans-palmitoleic acid had a much lower risk of developing diabetes, with about a 60% lower risk among participants in the highest quintile (fifth) of trans-palmitoleic acid levels, compared to individuals in the lowest quintile, almost a three-fold difference in risk of developing diabetes among individuals with the highest blood levels of trans-palmitoleic acid.<ref>http://www.sciencedaily.com/releases/2010/12/101220200000.htm</ref>

There are numerous studies which suggest connections between some aspects of type 2 diabetes with ingestion of certain foods or with some drugs. Breastfeeding may also be associated with the prevention of type&nbsp;2 diabetes in mothers.<ref name="JAMA2005-Stuebe">{{cite journal |author=Stuebe AM, Rich-Edwards JW, [[Walter Willett|Willett WC]], [[JoAnn E. Manson|Manson JE]], Michels KB |title=Duration of lactation and incidence of type 2 diabetes |journal=JAMA |volume=294 |issue=20 |pages=2601–10 |year=2005 |month=November |pmid=16304074 |doi=10.1001/jama.294.20.2601}}</ref>

Lowering meat intake may help prevent diabetes, as several studies have found lower incidence among [[vegetarians]].<ref>{{cite pmid|3985239}}</ref><ref>{{Cite journal
| last1 = Jenkins | first1 = DJA
| last2 = Kendall | first2 = CWC
| last3 = Marchie | first3 = A
| last4 = Jenkins | first4 = AL
| last5 = Augustin | first5 = LSA
| last6 = Ludwig | first6 = DS
| last7 = Barnard | first7 = ND
| last8 = Anderson | first8 = JW
| display-authors = 2
| title = Type 2 diabetes and the vegetarian diet
| journal = Am J Clin Nutr
| volume = 78
| issue = 3 Suppl
| pages = 610S–616S
| year = 2003
| month = September
| pmid = 12936955
}}</ref><ref>{{cite pmid|10446033}}</ref>

===Medications===
Some studies have shown delayed progression to diabetes in predisposed patients through prophylactic use of [[metformin]],<ref name="Knowler" /> [[rosiglitazone]],<ref>{{cite journal |author=Gerstein HC, Yusuf S, Bosch J, ''et al.'' |title=Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial |journal=Lancet |volume=368 |issue=9541 |pages=1096–105 |year=2006 |month=September |pmid=16997664 |doi=10.1016/S0140-6736(06)69420-8}}</ref> or [[valsartan]].<ref>{{cite journal |author=Kjeldsen SE, Julius S, Mancia G, ''et al.'' |title=Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: the VALUE trial |journal=Journal of Hypertension |volume=24 |issue=7 |pages=1405–12 |year=2006 |month=July |pmid=16794491 |doi=10.1097/01.hjh.0000234122.55895.5b}}</ref> In patients on [[hydroxychloroquine]] for [[rheumatoid arthritis]], incidence of diabetes was reduced by 77% though causal mechanisms are unclear.<ref>{{cite journal |author=Wasko MC, Hubert HB, Lingala VB, ''et al.'' |title=Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis |journal=JAMA |volume=298 |issue=2 |pages=187–93 |year=2007 |month=July |pmid=17622600 |doi=10.1001/jama.298.2.187}}</ref> Lifestyle interventions are however more effective than metformin at preventing diabetes regardless of weightloss.<ref>{{cite journal |author=Knowler WC, Fowler SE, Hamman RF, ''et al.'' |title=10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study |journal=Lancet |volume=374 |issue=9702 |pages=1677–86 |year=2009 |month=November |pmid=19878986 |doi=10.1016/S0140-6736(09)61457-4 |url=}}</ref>


==Management==
==Management==

Revision as of 23:06, 23 December 2010

Type 2 diabetes
SpecialtyFamily medicine, endocrinology Edit this on Wikidata

Diabetes mellitus type 2–formerly non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes–is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.[2] Diabetes is often initially managed by increasing exercise and dietary modification. As the condition progresses, medications may be needed.

Unlike type 1 diabetes, there is very little tendency toward ketoacidosis though it is not unheard of.[3] One effect that can occur is nonketonic hyperglycemia. Long-term complications from high blood sugar can include increased risk of heart attacks, strokes, amputation, and kidney failure.

Signs and symptoms

The classical symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), fatigue and weight loss.[4]

Cause

Type 2 diabetes is due primarily to lifestyle factors and genetics.[5] It was also found that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1β production in vitro.[6]

Lifestyle

A number of lifestyle factors are known to be important to the development of type 2 diabetes. In one study, those who had high levels of physical activity, a healthy diet, did not smoke, and consumed alcohol in moderation had an 82% lower rate of diabetes. When a normal weight was included the rate was 89% lower. In this study a healthy diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, and a lower mean glycemic index.[7] Obesity has been found to contribute to approximately 55% of cases of type 2 diabetes,[8] and decreasing consumption of saturated fats and trans fatty acids while replacing them with unsaturated fats may decrease the risk.[5] The increased rate of childhood obesity in between the 1960s and 2000s is believed to have led to the increase in type 2 diabetes in children and adolescents.[9]

Environmental toxins may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of some plastics, and the incidence of type 2 diabetes.[10]

Medical conditions

There are many factors which can potentially give rise to or exacerbate type 2 diabetes. These include obesity, hypertension, elevated cholesterol (combined hyperlipidemia), and with the condition often termed metabolic syndrome (it is also known as Syndrome X, Reavan's syndrome, or CHAOS). Other causes include acromegaly, Cushing's syndrome, thyrotoxicosis, pheochromocytoma, chronic pancreatitis, cancer and drugs. Additional factors found to increase the risk of type 2 diabetes include aging,[11] high-fat diets[12] and a less active lifestyle.[13]

Subclinical Cushing's syndrome (cortisol excess) may be associated with type 1 diabetes.[14] The percentage of subclinical Cushing's syndrome in the diabetic population is about 9%.[15] Diabetic patients with a pituitary microadenoma can improve insulin sensitivity by removal of these microadenomas.[16]

Hypogonadism is often associated with cortisol excess, and testosterone deficiency is also associated with type 2 diabetes,[17][18] even if the exact mechanism by which testosterone improve insulin sensitivity is still not known.

Genetics

There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 increases risks of developing type 2 diabetes very substantially. In addition, there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes.[19][20]

About 55 percent of type 2 diabetes patients are obese at diagnosis[21] —chronic obesity leads to increased insulin resistance that can develop into type 2 diabetes, most likely because adipose tissue (especially that in the abdomen around internal organs) is a (recently identified) source of several chemical signals to other tissues (hormones and cytokines).

Other research shows that type 2 diabetes causes obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance.[22]

However, environmental factors (almost certainly diet and weight) play a large part in the development of type 2 diabetes in addition to any genetic component. This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment as compared to the same genetic pool who have not. Immigrants to Western developed countries, for instance, as compared to lower incidence countries of origins.[23]

There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 diabetes have a much higher risk of developing type 2 diabetes, increasing with the number of those relatives. Concordance among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX.[24][25] KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates proglucagon gene expression and thus the production of glucagon-like peptide-1.[26] Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.[27]

Monogenic forms, e.g., MODY, constitute 1–5 % of all cases.[28]

Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich's ataxia. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.[29]

Gene expression promoted by a diet of fat and glucose as well as high levels of inflammation related cytokines found in the obese results in cells that "produce fewer and smaller mitochondria than is normal," and are thus prone to insulin resistance.[30]

Medications

Some drugs, used for any of several conditions, can interfere with the insulin regulation system, possibly producing drug induced hyperglycemia. Some examples follow, giving the biochemical mechanism in each case:

  • Atypical Antipsychotics - Alter receptor binding characteristics, leading to increased insulin resistance.
  • Beta-blockers - Inhibit insulin secretion.
  • Calcium Channel Blockers - Inhibits secretion of insulin by interfering with cytosolic calcium release.
  • Corticosteroids - Cause peripheral insulin resistance and gluconeogenesis.
  • Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive potassium channels.
  • Niacin - causes increased insulin resistance due to increased free fatty acid mobilization.
  • Phenothiazines - Inhibit insulin secretion.
  • Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.
  • Somatropin - May decrease sensitivity to insulin, especially in those susceptible.
  • Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also cause increased insulin resistance due to increased free fatty acid mobilization.

Pathophysiology

Insulin resistance means that body cells do not respond appropriately when insulin is present. Unlike type 1 diabetes mellitus, insulin resistance is generally "post-receptor", meaning it is a problem with the cells that respond to insulin rather than a problem with the production of insulin.

This is a more complex problem than type 1, but is sometimes easier to treat, especially in the early years when insulin is often still being produced internally. Severe complications can result from improperly managed type 2 diabetes, including renal failure, erectile dysfunction, blindness, slow healing wounds (including surgical incisions), and arterial disease, including coronary artery disease. The onset of type 2 diabetes has been most common in middle age and later life, although it is being more frequently seen in adolescents and young adults due to an increase in child obesity and inactivity. A type of diabetes called MODY is increasingly seen in adolescents, but this is classified as a diabetes due to a specific cause and not as type 2 diabetes.

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 or diabetes due to a specific cause. Examples include diabetes mellitus such as MODY or those caused by hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g., long-term steroid use).

Diagnosis

WHO diabetes diagnostic criteria[31][32]  edit
Condition 2-hour glucose Fasting glucose HbA1c
Unit mmol/L mg/dL mmol/L mg/dL mmol/mol DCCT %
Normal < 7.8 < 140 < 6.1 < 110 < 42 < 6.0
Impaired fasting glycaemia < 7.8 < 140 6.1–7.0 110–125 42–46 6.0–6.4
Impaired glucose tolerance ≥ 7.8 ≥ 140 < 7.0 < 126 42–46 6.0–6.4
Diabetes mellitus ≥ 11.1 ≥ 200 ≥ 7.0 ≥ 126 ≥ 48 ≥ 6.5

The World Health Organization definition of diabetes is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:[33]

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

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[34]:

A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses current diabetes with[35]:

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 United States female health professionals.[36] 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.[37]

Other studies have shown that lifestyle changes,[38] orlistat[39] and metformin[40] can delay the onset of diabetes.

Screening

Diabetes screening is recommended for many people at various stages of life, and for those with any of several risk factors. The screening test varies according to circumstances and local policy, and may be a random blood glucose test, a fasting blood glucose test, a blood glucose test two hours after 75 g of glucose, or an even more formal glucose tolerance test. Many healthcare providers recommend universal screening for adults at age 40 or 50, and often periodically thereafter. Earlier screening is typically recommended for those with risk factors such as obesity, family history of diabetes, history of gestational diabetes, high-risk ethnicity (Hispanic, Native American, Afro-Caribbean, Pacific Islander, or Māori).[41][42]

Many medical conditions are associated with diabetes and warrant screening. A partial list includes: subclinical Cushing's syndrome,[14] testosterone deficiency,[17] high blood pressure, past gestational diabetes, polycystic ovary syndrome, chronic pancreatitis, fatty liver, cystic fibrosis, several mitochondrial neuropathies and myopathies (such as MIDD), myotonic dystrophy, Friedreich's ataxia, some of the inherited forms of neonatal hyperinsulinism. The risk of diabetes is higher with chronic use of several medications, including long term corticosteroids, some chemotherapy agents (especially L-asparaginase), as well as some of the antipsychotics and mood stabilizers (especially phenothiazines and some atypical antipsychotics).

People with a confirmed diagnosis of diabetes are tested routinely for complications. This includes yearly urine testing for microalbuminuria and examination of the retina of the eye for retinopathy.

The U.S. Preventive Services Task Force 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,"[34][43] this was a grade I recommendation[44] when published in 2003. However, the USPSTF does recommend screening for diabetics in adults with hypertension or hyperlipidemia.[45]

Prevention

Onset of type 2 diabetes can often be delayed through proper nutrition and regular exercise.[46]

A 2005 report concluded that "there is evidence that combined diet and exercise, as well as drug therapy (metformin, acarbose), may be effective at preventing progression to diabetes in IGT subjects".[47][48]

Management

Left untreated, type 2 diabetes is a chronic, progressive condition, but there are well-established treatments which can delay or prevent entirely the formerly inevitable consequences of the condition. Often, the condition is viewed as progressive since poor management of blood sugar leads to a myriad of steadily worsening complications. However, if blood sugar is properly maintained, then the condition is, in a limited sense, cured - that is, patients are at no heightened risk for neuropathy, blindness, or any other high blood sugar complication, though the underlying isssue, a tendency to hyperglycemia has not been addressed directly. A study at UCLA in 2005 showed that the Pritikin Program of diet and exercise brought dramatic improvement to a group of diabetics and pre-diabetics in only three weeks, so that about half no longer met the criteria for the condition.[49][50]

There are two main goals of treatment:

  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., to near 'normal' blood glucose levels); the reduction in severity of diabetic side effects has been very well demonstrated in several large clinical trials and is established beyond controversy. The second goal is often addressed (in developed countries) by support and care from teams of diabetic health workers (usually physician, PA, nurse, dietitian or a certified diabetic educator). Endocrinologists, family practitioners, and general internists are the physician specialties most likely to treat people with diabetes. Knowledgeable patient participation is vital to clinical success, and so patient education is a crucial aspect of this effort.

Type 2 diabetes is initially treated by adjustments in diet and exercise, and by weight loss, most 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 activity, for instance chemical signaling (especially in visceral fat tissue in and around abdominal organs). In many cases, such initial efforts can substantially restore insulin sensitivity. In some cases strict diet can adequately control the glycemic levels.

Diabetes education is an integral component of medical care. A Cochrane Review of studies concluded that using community-based health advocates to deliver information within same-gender groups or adapting dietary and lifestyle advice to fit a particular community's likely diet can help people with type 2 diabetes control their blood sugar levels, certainly for up to six months, following health education. This conclusion was reached by a team of Cochrane Researchers after they considered the data in 11 trials that involved 1,603 people.[51]. However, a further Cochrane review of studies found that there is no indication that dietary advice alone can prevent type 2 diabetes.[52]

Goals

Treatment goals for type 2 diabetic patients are related to effective control of blood glucose, blood pressure and lipids to minimize the risk of long-term consequences associated with diabetes. They are suggested in clinical practice guidelines released by various national and international diabetes agencies.

The targets are:

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 HbA1c of 8% is appropriate".[56]

Lifestyle modification

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."[57][58] The combined program reduced the HbA1c by 0.5 percentage point. Other studies have established that the amount of exercise needed is not large or extreme, but must be consistent and continuing. Examples might include a brisk 45 minute walk every other day.

Theoretically, exercise does have benefits in that exercise would stimulate the release of certain ligands that cause GLUT4 to be released from internal endosomes to the cell membrane. Insulin though, which no longer works effectively in those afflicted with type 2 diabetes, causes GLUT1 to be placed into the membrane. Exercise also allows for the uptake of glucose independently of insulin, i.e. by adrenaline.

Dietary management

Modifying the diet to limit and control glucose (or glucose equivalent, e.g., starch) intake, and in consequence, blood glucose levels, is known to assist type 2 patients, especially early in the course of the condition's progression. Additionally, weight loss is recommended and is often helpful in persons suffering from type 2 diabetes (see above).

Monitoring of blood glucose

Self-monitoring of blood glucose may not improve outcomes in some cases, especially those of "reasonably well controlled non-insulin treated patients with type 2 diabetes".[59] Nevertheless, it is very strongly recommended for patients in whom it can assist in maintaining proper glycemic control[60], and is well worth the cost (sometimes considerable) if it does. It is the only source of current information on the glycemic state of the body, as changes are rapid and frequent, depending on food, exercise, and medication (dosage and timing with respect to both diet and exercise), and secondarily, on time of day, stress (mental and physical), infection, etc. However, patient adherence to self-monitoring routines is often sporadic and prone to fluctuation, with patients often self-monitoring very regularly near to check-up times and very little during other times.[60]Ensuring due compliance is an ongoing issue which may well affect research results into efficacy and benefits of self-monitoring.

The Reaction Project (EU R&D project) aims to research and develop an intelligent service platform that can provide professional, remote monitoring and therapy management to diabetes patients in different healthcare regimes across Europe. The platform, with emphasis on blood pressure control and lifestyle factors combined with new technology supporting tight glucose control measuring will enable a constant flow of readings sent automatically to medical staff without the need for the patients' physical appearance at the hospital. It will contribute to improve the risk profile of most diabetes related complications.

The National Institute for Health and Clinical Excellence (NICE), UK released updated diabetes recommendations on 30 May 2008. They indicate that self-monitoring of blood glucose levels for people with newly diagnosed type 2 diabetes should be part of a structured self-management education plan.[61] However, a recent study found that a treatment strategy of intensively lowering blood sugar levels (below 6%) in patients with additional cardiovascular disease risk factors poses more harm than benefit, and so there appear to be limits to benefit of intensive blood glucose control in some patients.[62][63]

Medications

Metformin 500mg tablets

There are several drugs available for type 2 diabetics—most are unsuitable or even dangerous for use by type 1 diabetics. They fall into several classes and are not equivalent, nor can they be simply substituted one for another. All are prescription drugs.

One of the most widely used drugs now used for type 2 diabetes is the biguanide metformin; it works primarily by reducing liver release of blood glucose from glycogen stores and secondarily by provoking some increase in cellular uptake of glucose in body tissues. Metformin also reduces insulin resistance and is preferred in obese patients as it promotes weight loss. Both historically and currently the most commonly used drugs are in the Sulfonylurea group, of which several members (including glibenclamide and gliclazide) are widely used; these increase glucose stimulated insulin secretion by the pancreas and so lower blood glucose even in the face of insulin resistance. Their chief adverse effect is increased chance of hypoglycemic episodes.

Newer drug classes include:

  • Thiazolidinediones (TZDs) (rosiglitazone, pioglitazone, and troglitazone -- the last, as Rezulin, was withdrawn from the US market because of an increased risk of systemic acidosis). These increase tissue insulin sensitivity by affecting gene expression
  • α-glucosidase inhibitors (acarbose and miglitol) which interfere with absorption of some glucose containing nutrients, reducing (or at least slowing) the amount of glucose absorbed
  • Meglitinides which stimulate insulin release (nateglinide, repaglinide, and their analogs) quickly; they can be taken with food, unlike the sulfonylureas which must be taken prior to food (sometimes some hours before, depending on the drug)
  • Peptide analogs which work in a variety of ways:

Oral

A systematic review of randomized controlled trials found that metformin and second-generation sulfonylureas are the preferred choices for most with type 2 diabetes, especially those early in the course of the condition.[64] 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 to be 15% with rosiglitazone, 21% with metformin, and 34% with glyburide".[65] Of these, rosiglitazone users showed more weight gain and edema than did non-users.[65] Rosiglitazone may increase risk of death from cardiovascular causes though the causal connection is unclear.[66] Pioglitazone and rosiglitazone may also increase the risk of fractures.[67][68]

For patients who also have heart failure, metformin may be the best tolerated drug.[69]

The variety of available agents can be confusing, and the clinical differences among type 2 diabetes patients compounds the problem. At present, choice of drugs for type 2 diabetics is rarely straightforward and in most instances has elements of repeated trial and adjustment.

Injectable peptide analogs

DPP-4 inhibitors (also known as glyptins) lowered HbA1c by 0.74% (points), comparable to other antidiabetic drugs.[70] GLP-1 analogs resulted in weight loss and had more gastrointestinal side effects, while DPP-4 inhibitors were generally weight neutral and increased risk for infection and headache, but both classes appear to present an alternative to other antidiabetic drugs. However, weight gain and/or hypoglycaemia have been observed when DPP-4 inhibitors were used with sulfonylureas; effect on long-term health and morbidity rates are still unknown.[71]

Insulin

In rare cases, if antidiabetic drugs fail (i.e., the clinical benefit stops), insulin therapy may be necessary – usually in addition to oral medication therapy – to maintain normal or near normal glucose levels.[72][73]

Typical total daily dosage of insulin is 0.6 U/kg.[74] But, of course, best timing and indeed total amounts depend on diet (composition, amount, and timing) as well the degree of insulin resistance. More complicated estimations to guide initial dosage of insulin are:[75]

  • 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 are often chosen based on the patient's blood glucose profile.[76] Initially, adding nightly insulin to patients failing oral medications may be best.[77] Nightly insulin combines better with metformin than with sulfonylureas.[74] 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, multiply by 0.05551 to convert to mmol/L.[78]

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 increased hypoglycemia.[79][80][81] 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".[80] A guide to titrating fixed ratio insulin is available.[76]
  • 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".[82] More recently, a randomized controlled trial found that although long acting insulins were less effective, they were associated with reduced hypoglycemic episodes.[79]
  • Insulin Pump therapy in type 2 diabetes is gradually becoming popular.In an original published study, in addition to reduction of blood sugars, there is evidence of profound benefits in resistant neuropathic pain and also improvements in sexual performance.[83]

Gastric bypass surgery

Gastric Bypass procedures are currently considered an elective procedure with no universally accepted algorithm to decide who should have the surgery. In the diabetic patient, certain types result in 99-100% prevention of insulin resistance and 80-90% clinical resolution or remission of type 2 diabetes. In 1991, the NIH (National Institutes of Health) Consensus Development Conference on Gastrointestinal Surgery for Obesity proposed that the body mass index (BMI) threshold to consider surgery should drop from 40 to 35 in the appropriate patient. More recently, the American Society for Bariatric Surgery (ASBS) and the ASBS Foundation suggested that the BMI threshold be lowered to 30 in the presence of severe co-morbidities.[84] Debate has flourished about the role of gastric bypass surgery in type 2 diabetics since the publication of The Swedish Obese Subjects Study. The largest prospective series showed a large decrease in the occurrence of type 2 diabetes in the post-gastric bypass patient at both 2 years (odds ratio was 0.14) and at 10 years (odds ratio was 0.25).[85]

A study of 20-years of Greenville (US) gastric bypass patients found that 80% of those with type 2 diabetes before surgery no longer required insulin or oral agents to maintain normal glucose levels. Weight loss occurred rapidly in many people in the study who had had the surgery. The 20% who did not respond to bypass surgery were, typically, those who were older and had had diabetes for over 20 years.[86]

In January 2008, the Journal of the American Medical Association (JAMA) published the first randomized controlled trial comparing the efficacy of laparoscopic adjustable gastric banding against conventional medical therapy in the obese patient with type 2 diabetes. Laparoscopic Adjustable Gastric Banding results in remission of type 2 diabetes among affected patients diagnosed within the previous two years according to a randomized controlled trial.[87] The relative risk reduction was 69.0%. For patients at similar risk to those in this study (87.0% had type 2), this leads to an absolute risk reduction of 60%. 1.7 patients must be treated for one to benefit (number needed to treat = 1.7).[original research?][88] to adjust these results for patients at higher or lower risk of type 2 diabetes.

These results have not yet produced a clinical standard for surgical treatment of type 2 diabetes, as the mechanism, if any, is currently obscure. Surgical cure of type 2 diabetes must be, as a result, considered currently experimental.

Epidemiology

There are an estimated 23.6 million people in the United States (7.8% of the population) with diabetes with 17.9 million being diagnosed,[89] 90% of whom are type 2.[90] With prevalence rates doubling between 1990 and 2005, CDC has characterized the increase as an epidemic.[91] Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates [92] due to alterations in dietary patterns as well as in life styles during childhood.[93]

About 90–95% of all North American cases of diabetes are type 2,[94] and about 20% of the population over the age of 65 has type 2 diabetes. The incidence of type 2 diabetes in other parts of the world varies substantially, almost certainly because of environmental and lifestyle factors, though these are not known in detail. Diabetes affects over 150 million people worldwide and this number is expected to double by 2025.[94]

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