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- See diabetes mellitus for further general information on diabetes.
Diabetes mellitus type 2 (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.
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 organs, 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.
|Types of Diabetes|
|Diabetes mellitus type 1|
Diabetes mellitus type 2
Glucose tolerance test
- 1 Pathophysiology
- 2 Diagnosis
- 3 Screening and prevention
- 4 Treatment
- 5 References
- 6 External links
Genetic factors, usually polygenic, are present in most patients. However, environmental factors such as obesity, lack of exercise and a sedentary lifestyle are thought by most observers to lead to insulin resistance. Certainly not all type 2 diabetics have a family history of the condition.
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, 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. 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. About 55 percent of type 2 are obese —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.
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.
The World Health Organization definition of diabetes is for a single raised glucose reading with symptoms, otherwise raised values on two occassions,of either:
- fasting plasma glucose ≥ 7.0mmol/l (126mg/dl)
- With a Glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1mmol/l (200mg/dl)
Screening and prevention
Interest has arisen in preventing diabetes due to research on the benefits of treating patients before overt diabetes. Although the U.S. Preventive Services Task Force (USPSTF) concluded that "the evidence is insufficient to recommend for or against routinely screening asymptomatic adults for type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose", this was a grade I recommendation when published in 2003.
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".
Since publication of the USPSTF statement, a randomized controlled trial of prescribing acarboseto 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.
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 trials and is thus well established. The second goal is often addressed (in developed countries) by support and care from teams of diabetic health workers (physician. PA, nurse, dietitian or a certified diabetic educator). 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.
Diet and possible cure
Modifying the diet is known to help control glucose intake, and in response, blood glucose levels. However, a new study released shows, in a Paleolithic diet, all patients returned blood glucose levels to normal after the trial period (in excess of, or at 12 weeks) and improved glucose tolerance by ~26%. This is significant as this was the first Paleolithic diet study, the results were dramatic (compared to the Mediterranean diet also measured), and it shows there is a possible cure. This type of treatment (a modified diet) for curing is further supported by medical physicians and studies such as
Caloric restriction: http://www.nutritionandmetabolism.com/content/3/1/22
Physicians/doctors: Joseph Mercola, Vern S. Cherewatenko, MD, MEd , Richard K. Bernstein MD(more for diabetes type 1 than 2)
and from an excerpt of the book: Weight of the Evidence, by Regina Wilshire (site includes interview with Mercola and numerous studies)
Self monitoring of blood glucose
Is it unclear if self monitoring of blood glucose improves outcomes.
- Main article: antidiabetic drugs
The next step, if necessary, is treatment with a antidiabetic drugs (all are oral agents "OA"s, with the exception of the GLP analogues, which are injected). 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". Rosiglitazone had more weight gain and edema. Rosiglitazone may increase risk of death from cardiovascular causes. Pioglitazone and rosiglitazone may increase the risk of fractures. Antidiabetic drugs include:
- Biguanides include metformin and phenformin.
- Thiazolidinediones (TZDs) include rosiglitazone, pioglitazone, and troglitazone.
- α-glucosidase inhibitors include acarbose and miglitol.
- Meglitinides include nateglinide, repaglinide, and their analogs.
- Peptide analogs
- Incretin mimetics insulin secretagogues.
- Glucagon-like peptide (GLP) analogs (subcutaneous administration)
- liraglutide (not FDA approved)
- Gastric inhibitory peptide (GIP) analogs
- None are FDA approved
- Incretin enhancers
- Amylin agonist analog (slows gastric emptying and suppresses glucagon)
If antidiabetic drugs fail to help (or stop helping), insulin therapy may be necessary, usually as an adjunct to oral medication therapy, to maintain normal glucose levels.
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.. A guide to titrating fixed ratio insulin is available(http://www.annals.org/cgi/content/full/145/2/125/T4).
Long acting insulins
A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2".
- Insulin glargine
- Insulin detemir
Neither of these have shown permanent positive effects, nor a complete restoration to pre-diabetes conditions, only improvement.
- Main article: Antihypertensives
The goal blood pressure is 130/80 which is lower than in non-diabetic patients.
The HOPE study suggests that diabetics should be treated with ACE inhibitors (specifically ramipril 10 mg/d) if they have one of the following :
- hypercholesterolemia or reduced low high-density lipoprotein cholesterol levels
- cigarette smoking
- Main article: Hypercholesterolemia#Diabetic_patients
- Diabetes - Disabling Disease to Double by 2050
- Eberhart, M. S., Ogden, C, Engelgau, M, Cadwell, B, Hedley, A. A., Saydah, S. H., (November 19, 2004). Prevalence of Overweight and Obesity Among Adults with Diagnosed Diabetes --- United States, 1988--1994 and 1999--2002. Morbidity and Mortality Weekly Report 53 (45): 1066-1068.
- Camastra S, Bonora E, Del Prato S, Rett K, Weck M, Ferrannini E (1999). Effect of obesity and insulin resistance on resting and glucose-induced thermogenesis in man. EGIR (European Group for the Study of Insulin Resistance). Int J Obes Relat Metab Disord 23 (12): 1307-13. PMID 10643689.
- .World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus. URL accessed on 2007-05-29.
- U.S. Preventive Services Task Force (2003). Screening for type 2 diabetes mellitus in adults: recommendations and rationale. Ann. Intern. Med. 138 (3): 212-4. National Guidelines Clearinghouse: Complete Summary
- Harris R, Donahue K, Rathore SS, Frame P, Woolf SH, Lohr KN (2003). Screening adults for type 2 diabetes: a review of the evidence for the U.S. Preventive Services Task Force. Ann. Intern. Med. 138 (3): 215-29.
- Santaguida PL, Balion C, Hunt D, et al (2005). Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. Evidence report/technology assessment (Summary) (128): 1-11.
- Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M (2003). Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 290 (4): 486-94. ACP Journal Club review
- Lindström J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemiö K, Hämäläinen H, Härkönen P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Mannelin M, Paturi M, Sundvall J, Valle TT, Uusitupa M, Tuomilehto J (2006). Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 368 (9548): 1673-9.ACP Journal Club review
- Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002). Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346 (6): 393-403. ACP Journal Club review
- Farmer A, Wade A, Goyder E, et al (2007). Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial.
- Kahn SE, Haffner SM, Heise MA, et al (2006). Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N. Engl. J. Med. 355 (23): 2427-43.
- NEJM -- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes. URL accessed on 2007-05-21.
- MedWatch - 2007 Safety Information Alerts. URL accessed on 2007-05-21.
- MedWatch - 2007 Safety Information Alerts. URL accessed on 2007-05-21.
- Mooradian AD, Bernbaum M, Albert SG (2006). Narrative review: a rational approach to starting insulin therapy. Ann. Intern. Med. 145 (2): 125-34.
- Yki-Järvinen H, Kauppila M, Kujansuu E, et al (1992). Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. N. Engl. J. Med. 327 (20): 1426-33.
- Raskin P, Allen E, Hollander P, et al (2005). Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care 28 (2): 260-5.
- Malone JK, Kerr LF, Campaigne BN, Sachson RA, Holcombe JH (2004). Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy. Clinical therapeutics 26 (12): 2034-44.
- Horvath K, Jeitler K, Berghold A, Ebrahim Sh, Gratzer T, Plank J, Kaiser T, Pieber T, Siebenhofer A (2007). Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane database of systematic reviews (Online) (2): CD005613.
- Geltrude Mingrone, Aldo V. Greco, Esmeralda Capristo, Giuseppe Benedetti, Annalisa Giancaterini, Andrea De Gaetano, and Giovanni Gasbarrini (1999). L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients. Journal of the American College of Nutrition 18 (1): 77-82.
- Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. American Journal of Clinical Nutrition 71 (1): 54-58.
- Chobanian AV, Bakris GL, Black HR, et al (2003). The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289 (19): 2560-72.
- Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000). Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N. Engl. J. Med. 342 (3): 145-53.
- Pilote L, Abrahamowicz M, Rodrigues E, Eisenberg MJ, Rahme E (2004). Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect?. Ann. Intern. Med. 141 (2): 102-12.
- American Diabetes Association
- National Diabetes Information Clearinghouse
- (2007). Diabetes (Madhumeha). Ayurveda Encyclopedia. - see Ayurvedic Treatment for Diabetes section for list of herbs used.
- Diabetes Health Institute
- Diabetes - Preventing Type 2 Diabetes. NLM. URL accessed on 2007-04-28. video
- Tu Diabetes - a global community for people touched by diabetes.
Endocrine pathology of psychological interest (E00-35)
thyroid Hypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre) - Hyperthyroidism (Graves-Basedow disease, Toxic multinodular goitre) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis)
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