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Models and simulation techniques for discovering diabetes influence factors

Diabetes and commorbidites

Diabetes Mellitus is a chronic metabolic disturbance that has no cure. It is characterized by increased blood glucose concentrations and decreased insulin secretion and/or action. T2DM is the most common form of diabetes. Sometimes called non-insulin dependent diabetes or adult-onset diabetes, it accounts for at least 90% of all cases of diabetes. The WHO estimates that by 2030 there will be about 550 million people suffering this disease. It is characterized by insulin resistance and relative insulin deficiency, either of which may be present at the time that diabetes becomes clinically manifest. The diagnosis of T2DM usually occurs after the age of 40 but even earlier, especially in populations with high prevalence of this disease. It is often associated with obesity, which itself can cause insulin resistance and lead to elevated blood glucose levels.

This disease can remain undetected for many years because hyperglycemia (consequence of the above insulin defects) develops gradually and at earlier stages is not severe enough for the patient to notice any of the classic symptoms of diabetes. Nevertheless, such patients are at increased risk of developing macrovascular (mainly stroke and acute coronary syndromes) and microvascular (mainly retinopathy, neuropathy, nephropathy, and limb ischemia) complications and diagnosis is often made from associated complications or incidentally through an abnormal blood or urine glucose test.

The major environmental risk factors for developing T2DM mellitus are obesity and a sedentary lifestyle lack of physical activity. It occurs more frequently in women with prior gestational diabetes mellitus and in individuals with hypertension or dyslipidemia, and its frequency varies in different ethnic subgroups. It is often associated with a strong genetic predisposition, even more than the autoimmune form of type 1 diabetes. However, the genetics of this form of diabetes are complex and not clearly defined.

As insulin resistance worsens, more global defects in insulin secretion occur and together these defects lead to further elevations in fasting blood glucose. The American Diabetes Association has encouraged the use of the term impaired fasting glucose (IFG) to denote this stage. IFG is defined as having a fasting plasma glucose level between 110 and 126 mg/dl. IGT is defined as 2-h postload glucose 140–199 mg/dl range.

Clinically, IFG and IGT represent intermediate stages between normal glucose tolerance and final diabetes: an essentially asymptomatic but still potentially pathological stage characterized by mild hyperglycemia. Both IGT and IFG serve as markers for those who are at greatest risk for developing T2DM. However, it still has not been possible to predict, which of the subjects with IFG and/or IGT progress to diabetes.

Diabetes Chronic Complications

Cardiac Disease

According to the American Diabetes Association, 65% (until 70% according to Toronto University) of diabetics die due to coronary diseases or Heart Failure. DM is associated to a considerable increase in the risk of developing a cardiovascular disease (CVD) in comparison to healthy persons: double for men and 5 times higher for women in ages between 47 – 65 years. The figures rise up to 4 – 8 in the elderly. This susceptibility is seen in both T1DM and T2DM. The development of arterial diseases fastens in the case of T1DM is often present in the diagnosis of T2DM. 77% of hospitalizations for diabetes in US are related to CVD. Glycemic control has proved to improve cardiac metabolism and myocardial function. Patients with cardiac disorders suffer a change in their drugs, nutrients and insulin patterns → absorption = blood flow function.

Retinopathy

Diabetic rethinopathy is the 1st cause of non-reversable blindness in the western world. The appearance and progression of this complication is strictly dependent upon glycemic control and blood pressure level, although a genetic predisposition is also involved. A person with diabetes has 10– to 20-fold increased risk of blindness.

Nephropathy

Diabetes is the leading cause of end-stage renal disease. Although renal disease has several known risk factors (above all hyperglycemia and hypertension), the genetic component behind development and progression of nephropathy may play a significant role, especially in type 1 diabetics. Nephropathy increases cardiovascular morbidity and mortality.

Diabetic Neuropathy

It usually occurs in patients with long-standing and often poorly controlled diabetes. Diabetic neuropathy may affect the peripheral nervous system – leading to neuropathic pain, loss of limb sensitivity (a major risk factor for food ulceration) and loss of muscular strength – , but also the autonomic system leading to development of cardiovascular symptoms (orthostatic hypotension, syncope, arrhythmias, etc.), gastrointenstinal disturbances (including chronic abdominal pain, diarrhoea with loss of sphincterial competence, vomit, hypo-nutrition, etc.), urinary incompetence, or male impotence. Patients with CVD may not experiment angina symptoms as others → increase in morbidity for “silent“ myocardial ischemia → possible relation with the neuropathy.

Foot Ulceration

It is the first cause of lower limb amputation in the western world. Commonest Risk factor is chronic sensorimotor neuropathy and/or impaired blood supply.

Others

Diabetes is also associated with an increased incidence of infections (especially dermatological, dental and urinary) and skin diseases. Chronic cerebrovascular disturbances and liver disease have also been associated with diabetes.

Copyright © 2013 MOSAIC project. All rights reserved.

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