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(formerly called diabetes mellitus type II, non
Insulin -dependent diabetes (NIDDM), obesity related diabetes, or adult-onset diabetes) is a
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
CDC has characterized the increase as an
Epidemic .
Diabetes - Disabling Disease to Double by 2050
Unlike
Type 1 diabetes, there is little tendency toward
Ketoacidosis in Type 2 diabetes, though it is not unknown. One effect that can occur is
Nonketonic Hyperglycemia . Complex and multifactorial metabolic changes lead to damage and function impairment of many
Organ s, most importantly the
Cardiovascular system in both types. This leads to substantially increased
Morbidity and
Mortality in both Type 1 and Type 2 patients, but the two have quite different origins and treatments despite the similarity in complications.
Insulin Resistance means that body
Cells do not respond appropriately when insulin is present.
Other important contributing factors:
- increased hepatic glucose production (e.g., from glycogen degradation), especially at inappropriate times
- decreased insulin-mediated Glucose transport in (primarily) Muscle and adipose tissues (receptor and post-receptor defects)
- impaired beta-cell function—loss of early phase of insulin release in response to hyperglycemic stimuli
- 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.
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
Later Life .
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).
About 90–95% of all North American cases of diabetes are type 2
Zimmet, P., Alberti, K. G. M. M., Shaw, J. Global and societal implications of the
diabetes epidemic. ''Nature'' , 414, 782-787., 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. There is also a strong inheritable
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 a earlier onset, more severe form of diabetesSakagashira, 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
-->
2
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
Endocrinological disorders. Additional factors found to increase risk of type 2 diabetes include agingJack, L., Jr., Boseman, L. & Vinicor, F. Aging Americans and diabetes. A public health and clinical response. ''Geriatrics'' , 59, 14-17., high-fat dietsLovejoy, J. C. The influence of dietary fat on insulin resistance. ''Curr Diab Rep'' '''2002''', 2,435-440. and a less active lifestyleHu, F. B. Sedentary lifestyle and risk of obesity and type 2 diabetes. Lipids 2003, 38,103-108..
The World Health Organization definition of diabetes is for a single raised glucose reading with symptoms, otherwise raised values on two occasions,of either.
3:
- fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)
:or
Interest has arisen in preventing diabetes due to research on the benefits of treating patients before overt diabetes. Although the
U.S. Preventive Services Task Force (USPSTF) concluded that "the evidence is insufficient to recommend for or against routinely screening asymptomatic adults for type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose"
4 National Guidelines Clearinghouse: Complete Summary 5, this was a
grade I recommendation when published in 2003. However, the USPSTF does recommend screening for diabetics in adults with hypertension or hyperlipidemia (
grade B recommendation ).
In 2005, an
evidence report by the
Agency For Healthcare Research And Quality concluded that "there is evidence that combined diet and exercise, as well as drug therapy (metformin, acarbose), may be effective at preventing progression to DM in IGT subjects".
6
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:
A ''random'' capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses ''current'' diabetes with
7:
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.
8 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:
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
9 ACP Journal Club review .
Other studies have shown that life-style changes
10[http://www.acpjc.org/Content/146/2/issue/ACPJC-2007-146-2-037.htm ACP Journal Club review] and
Metformin 11 ACP Journal Club review can delay the onset of diabetes.
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:
# reduction of mortality and concomitant morbidity (from assorted diabetic complications)
# preservation of quality of life
The first goal can be achieved through close glycemic control (i.e., blood glucose levels); the reduction effect in diabetic complications has been well demonstrated in several extensive
Clinical 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.
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 (5–10 lb); this is almost certainly due to currently poorly understood aspects of fat tissue chemical signalling (especially in visceral fat tissue in and around abdominal organs). In many cases, such initial efforts can substantially restore insulin sensitivity.
Modifying the diet is known to help control glucose intake, and in response, blood glucose levels.
One 2007 study will report that in a
Paleolithic Diet , all 14 patients returned blood glucose levels to normal after the trial period of 12 weeks, and improved glucose tolerance (26% less blood glucose rise following a carbohydrate intake compared to 7% reduction for control group on a Mediterranean diet). This was the first Paleolithic diet study, and suggested that "it may be more efficient to avoid some of our modern foods than to count calories or carbohydrate".
12
Other evidence for modified diets treating and being beneficial include:
- A vegan diet.1314
- 15
- Caloric restriction.16
- Apple Pie spices.17
- 18
It is unclear if self-monitoring of blood glucose improves outcomes.
19
See Also: antidiabetic drugs
The most important drug now used in Type 2 Diabetes is the
Biguanide Metformin which works primarily by reducing liver release of blood glucose from glycogen stores as well as some increase in uptake of glucose by the body's tissues. Both historically and currently commonly used are the
Sulfonylurea group, of which several members (including
Glibenclamide and
Gliclazide ) are widely used; these increase glucose stimulated
Insulin Secretion by the pancreas.
Newer drug classes include:
A systematic review of randomized controlled trials found that which found "cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide"
20. Of these, rosiglitazone had more weight gain and edema. Rosiglitazone may increase risk of death from cardiovascular causes.
21 Pioglitazone
22 and rosiglitazone may increase the risk of fractures.
23
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.
The initial insulin regimen can be chosen based on the patient's blood glucose profile.
24 Initially, adding nightly insulin to patients failing oral medications may be best.
25
When nightly insulin is insufficient, insulin can be premixed with a fixed ratio of short and intermediate acting insulin; this may be better than using long acting insulin.
2627. A guide to titrating fixed ratio insulin is available(http://www.annals.org/cgi/content/full/145/2/125/T4).
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".
28
Carnitine has been shown to increase insulin sensitivity and glucose storage in humans.
29. It is important to note that this was with a constant blood infusion, not an oral dose, and that the clinical significance of this result is unclear.
Taurine has also shown significant improvement in
Insulin Sensitivity and
Hyperlipidemia in rats.
30
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.
See Also: Antihypertensive
The goal blood pressure is 130/80 which is lower than in non-diabetic patients.
31
The HOPE study suggests that diabetics should be treated with
ACE Inhibitors (specifically
Ramipril 10 mg/d) if they have one of the following
32:
See Also: Hypercholesterolemia#Diabetic_patients
