:''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.
[1]
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.
Pathophysiology
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
[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. 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 diabetes
[3],[4]. About 55 percent of type 2 are
obese[5] —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.
[6]
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 aging
[7], high-fat diets
[8] and a less active lifestyle
[9].
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
[10]:
★ fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)
:or
★ With a
Glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/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"
[11][12], 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".
[13]
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
:
★
sensitivity about 50%
★
specificity greater than 95%
A ''random'' capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses ''current'' diabetes with
[14]:
★
sensitivity = 75%
★
specificity = 88%
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.
[15] 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 = 16.7%
★
specificity = 98.9%
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
[16].
Other studies have shown that life-style changes
[17] and
metformin[18] can delay the onset of diabetes.
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:
# 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). 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.
Dietary management
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".
[19]
Other evidence for modified diets treating and being beneficial include:
★ A vegan diet.
[20][21]
★ Caloric restriction.
[22]
★ Apple Pie spices.
[23]
Self monitoring of blood glucose
It is unclear if self-monitoring of blood glucose improves outcomes.
[24]
Antidiabetic drugs
Metformin 500mg tablets
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:
★
Thiazolidinediones (
TZDs) (
rosiglitazone,
pioglitazone, and
troglitazone) (withdrawn from the US market)
★
α-glucosidase inhibitors (
acarbose and
miglitol)
★
Meglitinides which stimulate insulin release (
nateglinide,
repaglinide, and their analogs)
★ Peptide analogs which work in a variety of ways:
★
★ Incretin mimetics act as insulin secretagogue among other effects. These includes the Glucagon-like peptide (GLP) analog
exenatide
★
★
Dipeptidyl peptidase-4 (DPP-4) inhibitors increase
Incretin levels (
sitagliptin)
★
★ Amylin agonist analog, which slows gastric emptying and suppresses glucagon (
pramlintide)
Selecting an antidiabetic drug
Oral drugs
A systematic review of randomized controlled trials found that
metformin and second-generation sulfonylureas are the preferred choices for most
[25] Failure of respose 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"
[26]. Of these, rosiglitazone had more weight gain and edema.
Rosiglitazone may increase risk of death from cardiovascular causes.
[27] Pioglitazone
[ MedWatch - 2007 Safety Information Alerts ]
Insulin preparations
If
antidiabetic drugs 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.
[28] Initially, adding nightly insulin to patients failing oral medications may be best.
[29]
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.
[30][31]. 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
Cochrane Collaboration found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2".
[32]
★
Insulin glargine
★
Insulin detemir
Alternative Medicines
Carnitine has been shown to increase insulin sensitivity and glucose storage in humans.
[33]. 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.
[34]
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.
Antihypertensive agents
Main articles: Antihypertensive
The goal blood pressure is 130/80 which is lower than in non-diabetic patients.
[35]
ACE inhibitors
The HOPE study suggests that diabetics should be treated with
ACE inhibitors (specifically
ramipril 10 mg/d) if they have one of the following
[36]:
★
hypertension
★
hypercholesterolemia or reduced low high-density lipoprotein cholesterol levels
★ cigarette smoking
★
microalbuminuria
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.
[37]
Hypolipidemic agents
Main articles: Hypercholesterolemia#Diabetic_patients
References
1. Diabetes - Disabling Disease to Double by 2050
2.
Zimmet, P., Alberti, K. G. M. M., Shaw, J. Global and societal implications of the
diabetes epidemic. ''Nature'' '2001', 414, 782-787.
3. 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
patients. ''Diabetes'' '1996', 45, 1279-1281.
4. Seino, S. S20G mutation of the amylin gene is associated with Type II diabetes in Japanese. ''Diabetologia'' '2001', 44, (7), 906-909.
5. Prevalence of Overweight and Obesity Among Adults with Diagnosed Diabetes --- United States, 1988--1994 and 1999--2002, , M. S., Eberhart, Morbidity and Mortality Weekly Report,
6. Effect of obesity and insulin resistance on resting and glucose-induced thermogenesis in man. EGIR (European Group for the Study of Insulin Resistance), Camastra S, Bonora E, Del Prato S, Rett K, Weck M, Ferrannini E, , , Int J Obes Relat Metab Disord, 1999
7. Jack, L., Jr., Boseman, L. & Vinicor, F. Aging Americans and diabetes. A public health and clinical response. ''Geriatrics'' '2004', 59, 14-17.
8. Lovejoy, J. C. The influence of dietary fat on insulin resistance. ''Curr Diab Rep'' '2002', 2,435-440.
9. Hu, F. B. Sedentary lifestyle and risk of obesity and type 2 diabetes. Lipids 2003, 38,103-108.
10. . Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus World Health Organization
11. Screening for type 2 diabetes mellitus in adults: recommendations and rationale, U.S. Preventive Services Task Force, , , Ann. Intern. Med., 2003 National Guidelines Clearinghouse: Complete Summary
12. Screening adults for type 2 diabetes: a review of the evidence for the U.S. Preventive Services Task Force, Harris R, Donahue K, Rathore SS, Frame P, Woolf SH, Lohr KN, , , Ann. Intern. Med., 2003
13. Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose, Santaguida PL, Balion C, Hunt D, ''et al'', , , Evidence report/technology assessment (Summary), 2005
14. Performance of recommended screening tests for undiagnosed diabetes and dysglycemia, Rolka DB, Narayan KM, Thompson TJ, ''et al'', , , Diabetes Care, 2001
15. Hemoglobin A1c predicts diabetes but not cardiovascular disease in nondiabetic women, Pradhan AD, Rifai N, Buring JE, Ridker PM, , , Am. J. Med., 2007
16. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial, Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, , , JAMA, 2003 ACP Journal Club review
17. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study, 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, , , Lancet, 2006 ACP Journal Club review
18. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, , , N. Engl. J. Med., 2002 ACP Journal Club review
19. Original Human 'Stone Age' Diet Is Good For People With Diabetes, Study Finds
20. Diabetes: Can a Vegan Diet Reverse Diabetes? Nicholson A
21. A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes, Barnard ND, Cohen J, Jenkins DJ, ''et al'', , , Diabetes Care, 2006
'Related news articles:'
★ Low-fat vegan diet treats type 2 diabetes more effectively than a standard diabetes diet
22. Low-carbohydrate diet in type 2 diabetes. Stable improvement of bodyweight and glycemic control during 22 months follow-up, Nielsen JV, Joensson E, , , Nutrition & metabolism, 2006
23. Insulin potentiating factor and chromium content of selected foods and spices, Khan A, Bryden NA, Polansky MM, Anderson RA, , , Biological trace element research, 1990
'Related news articles:'
★ Apple Pie Improves Blood Sugar Regulation and Insulin Sensitivity? -- Apple pie spices (typically cinnamon and nutmeg) were responsible for the beneficial effects.
24. Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial, Farmer A, Wade A, Goyder E, ''et al'', , , , 2007
25. Bolen S et al. Systematic Review: Comparative Effectiveness and Safety of Oral Medications for Type 2 Diabetes Mellitus. Ann Intern Med 2007;147:6
26. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy, Kahn SE, Haffner SM, Heise MA, ''et al'', , , N. Engl. J. Med., 2006
27. NEJM -- Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
28. Narrative review: a rational approach to starting insulin therapy, Mooradian AD, Bernbaum M, Albert SG, , , Ann. Intern. Med., 2006
29. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus, Yki-Järvinen H, Kauppila M, Kujansuu E, ''et al'', , , N. Engl. J. Med., 1992
30. Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs, Raskin P, Allen E, Hollander P, ''et al'', , , Diabetes Care, 2005
31. 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, Malone JK, Kerr LF, Campaigne BN, Sachson RA, Holcombe JH, , , Clinical therapeutics, 2004
32. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus, Horvath K, Jeitler K, Berghold A, Ebrahim Sh, Gratzer T, Plank J, Kaiser T, Pieber T, Siebenhofer A, , , Cochrane database of systematic reviews (Online), 2007
33. L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients, Geltrude Mingrone, Aldo V. Greco, Esmeralda Capristo, Giuseppe Benedetti, Annalisa Giancaterini, Andrea De Gaetano, and Giovanni Gasbarrini, , , Journal of the American College of Nutrition, 1999
34. Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes, , , , American Journal of Clinical Nutrition,
35. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report, Chobanian AV, Bakris GL, Black HR, ''et al'', , , JAMA, 2003
36. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G, , , N. Engl. J. Med., 2000
37. Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect?, Pilote L, Abrahamowicz M, Rodrigues E, Eisenberg MJ, Rahme E, , , Ann. Intern. Med., 2004
External links
★
Diabetes UK - Largest organisation in the UK working for people with diabetes
★
American Diabetes Association
★
National Diabetes Information Clearinghouse
★
Diabetes Section of
The Hormone Foundation
★
Diabetes Health Institute
★
Diabetes - Preventing Type 2 Diabetes video
★
Tu Diabetes - a global community for people touched by diabetes.
★
Tools and useful resources for diabetes patients
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