Diabetes mellitus type 2 is a chronic, progressive disease that has no established cure, but does have well-established treatments which can delay or prevent entirely the formerly inevitable consequences of the condition. Often, the disease 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 disease is effectively cured - that is, patients are at no heightened risk for neuropathy, blindness, or any other high blood sugar complication. 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 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. Among adults with diagnosed diabetes, 12% take both insulin and oral medications,19% take insulin only, 53% take oral medications only, and 15% do not take either insulin or oral medications.
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:
* HbA1c of 6%[29] to 7.0%[30]
* Preprandial blood glucose: 4.0 to 6.0 mmol/L (72 to 108 mg/dl)[31]
* 2-hour postprandial blood glucose: 5.0 to 8.0 mmol/L (90 to 144 mg/dl)
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".
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." 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. Though they have different structures, they both perform the same function of increasing intake of glucose into the cell from the blood serum. Exercise also allows for the uptake of glucose independently of insulin, ie 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 disease's progression. Additionally, weight loss is recommended and is often helpful in persons suffering from type 2 diabetes for the reasons discussed above.
Several dietary modifications using dietary supplements are sometimes recommended to those with type 2; there are studies suggesting that there is some beneficial effect for some of these. See the discussion below.
[edit] Monitoring of blood glucose
Main article: Blood glucose monitoring
Self-monitoring of blood glucose may not improve outcomes in some cases, that is among "reasonably well controlled non-insulin treated patients with type 2 diabetes". Nevertheless, it is very strongly recommended for patients in whom it can assist in maintaining proper glycemic control, 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.
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.[36] 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.
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. 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.
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:
o Incretin mimetics which increase insulin output from the beta cells among other effects. These includes the Glucagon-like peptide (GLP) analog exenatide, sometimes referred to as lizard spit as it was first identified in Gila monster saliva
o Dipeptidyl peptidase-4 (DPP-4) inhibitors increase Incretin levels (sitagliptin) by decreasing their deactivation rates
o Amylin agonist analog, which slows gastric emptying and suppresses glucagon (pramlintide)
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 disease. 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 Of these, rosiglitazone users showed more weight gain and edema than did non-users. Rosiglitazone may increase risk of death from cardiovascular causes though the causal connection is unclear. Pioglitazone and rosiglitazone may also increase the risk of fractures.
For patients who also have heart failure, metformin may be the best tolerated drug.
The variety of available agents can be confusing, and the clinical differences among type 2 diabetics 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 lowered A1c by 0.74%, comparable to other antidiabetic drugs. GLP-1 analogs resulted in weight loss and had more gastrointestinal side effects, while DPP-4 inhibitors were weight neutral and increased risk for infection and headache, but both classes appear to present an alternative to other antidiabetic drugs.
[edit] Insulin
If antidiabetic drugs fail (ie, the clinical benefit stops), insulin therapy may be necessary – usually in addition to oral medication therapy – to maintain normal or near normal glucose levels.
Typical total daily dosage of insulin is 0.6 U/kg. 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:[47]
* 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. Initially, adding nightly insulin to patients failing oral medications may be best. Nightly insulin combines better with metformin than with sulfonylureas. 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.
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. 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". A guide to titrating fixed ratio insulin is available.
* 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". More recently, a randomized controlled trial found that although long acting insulins were less effective, they were associated with reduced hypoglycemic episodes.
* Insulin Pump therapy in Type 2 diabetes is gradualy 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.
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 Institute 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.[56] More 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).
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.
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. 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). Click here to adjust these results for patients at higher or lower risk of type 2 diabetics.
These results have not yet produced a clinical standard for surgical treatment of diabetic patients, as the mechanism, if any, is currently obscure. Surgical cure of Type 2 diabetes must be, as a result, considered currently experimental.