Timely research topics of Type I and Type II diabetes

Type I Diabetes

Complications of Type I Diabetes

Prevention of complications

Type II Diabetes

Chronic kidney disease


 

Timely research topics of Type I and Type II diabetes

While major global research activities are constantly trying to find clues to the causes and mechanisms to diabetes, many key issues still remain unknown.

For instance, while certain viral infections are associated with the onset of type I diabetes, how and why they lead to destruction of the insulin producing cells are widely unknown.

Advances in genetic analyses and techniques for massive and rapid genome wide analyses are pinpointing genes associating with diabetes. However, the exact set of genes responsible in various ethnic populations are yet to be identified. Similarly, why and how in Type II diabetes the actions of insulin are not mediated to the cells of muscles, brain and internal organs in need of constant energy supply from circulating glucose are not yet clear.

Background

Type I Diabetes

Type I diabetes is a metabolic disease of early childhood/youth leading to increased levels of blood glucose and a strong genetic component.

It is an autoimmune disease in which the body´s defence (immunological) system attacks its own insulin producing cells in the pancreas with loss of ability to secrete insulin when it is needed. Typically this happens after meals when blood glucose level rises and will need to be kept at the normal range.

Majority of new type I diabetics run in families but there are also a set of environmental components, most notably certain types of infections with viruses that are associated with the onset of the disease. Notably, there is presently a 1-2% prevalence of this disease with an increasing trend in globally.

Treatment of Type I diabetes: Type I diabetes patients need insulin replacement, typically with single-multiple daily insulin injections or administered with an insulin pump.

The key life-style factors beneficial to postpone complications of diabetes include regular exercise, avoidance of smoking, healthy diet rich in vegetables and certain kinds of fats. The medicinal treatment always includes optimised metabolic balance (insulin injections), lowering of cholesterol levels and control of elevated blood pressure.

Complications of Type I Diabetes

Complications of diabetes include those of the

  • Eye (retinopathy): gradual loss of visual acuity and other eye-symptoms
  • Kidney (nephropathy): Loss of kidney function
  • Nerves (neuropathy): Various symptoms from numbness to loss of pain sensation
  • Skin: Delayed healing of wounds
  • Cardiovascular system: increased atherosclerosis, heart complications (myocardial infarction)

Prevention of complications

Maintenace of optimal blood glucose levels by insulin is the key to all treatments. In addition, elevated blood pressure and serum cholesterol levels need to be treated. There are good pharmacological ways to manage these risk factors of diabetes. An active lifestyle with plenty of exercise, maintenance of body weight within normal limits and avoidance of smoking are the cornerstones of treatment and prevention of complications of diabetes.

Type II Diabetes

Disease background: Type II diabetes is rapidly increasing globally mostly for unknown reasons. It is a polygenic disease (with many genes playing together) while those genes responsible still remain to be verified. The catastrophic increase of diabetics worldwide is mostly associated with less physical activity, obesity and dietary deficits (excess of saturated fats and intake of calories). Notably, Type II diabetes (including prediabetes) already affects up to 6-10% of the general population, with a continuously increasing trend. In some vulnerable societies (African-American, Arab, areas in East Asia), Type II diabetes rate is already up to 17-20% and, notably, this disease increasingly affects younger people, even children.

Globally Type II diabetes is by far the biggest chronic health threat, with the same heart, eye, nerve and kidney complications as in Type I diabetes. Already at present stage an estimated 12-15% of ALL healthcare costs go to treat complications of diabetes, most importantly the kidney complications. It is estimated that up to 50% of African-American males born in the year 2000 will develop diabetes during their lifetime.

Special problems: A major problem is the “silent” diabetes: typically up to 60% of people with Type II / prediabetes go unaware of their elevated blood glucose. Consequently, in up to 70% of first myocardial infarctions, diabetes or prediabetes is found as the causative reason. Furthermore, Type II diabetes increasingly affects younger age groups, even children, with deleterious effects to their health expectations before middle age.

Treatment of Type II diabetes: The most important factor is early detection of elevated glucose levels and finding those individuals with prediabetes. This can be done by health screenings and with combination of tests from the blood and urine. The medical treatment aims at lowering glucose levels by a variety of medications already available. These work via different mechanisms: mainly to stimulate insulin production from the pancreas and to decrease the insulin resistance by peripheral tissues (e.g. the muscles). Treatment of elevated blood pressure and cholesterol is always important and have shown to postpone development of complications.

Prevention: As for Type I, also patients with Type II diabetes benefit dramatically from avoidance of smoking. Also, weight loss, increase of daily exercise and paying close attention to healthy diet (avoiding extra calories and saturated fats, increasing consumption of vegetables instead of e.g. pasta, rice and potatoes).

Chronic kidney disease

Chronic kidney disease (CKD) occurs when illness damages the kidneys which are no longer capable to adequately remove extra fluids and wastes from the body or to maintain the proper level of certain kidney-regulated chemicals in the bloodstream.

Progression of the disease leads to further loss of kidney function known as end stage 
kidney disease (ESKD). Currently millions of people suffer from EKSD worldwide. Diabetes is the major single cause for ESKD with up to 40% of all artificial kidney (dialysis) and transplantation patients due to diabetic kidney disease (nephropathy). The other main reasons for ESKD include direct immunologic, inflammatory and hereditary causes as well as chronic hypertension.

The existing therapies of ESKD (dialysis, transplantation) are unsatisfactory: expensive, not curative and “blind” (they do not correct the underlining pathology).

Symptoms of CKD are subtle and difficult to detect in an early stage and will necessitate a set of laboratory tests, mainly from the blood and urine. In fact the kidney is able to compensate a lack of functionality for a long time. Thus CKD may progress to ESKD essentially without prominent symptoms.

Often the very first detection of kidney impairment occurs by chance following routine blood and urine test requested by the general practitioner for other purposes. However, in the late stage and with respect to the severity and aggressiveness of the underlined kidney condition, symptoms can manifest in different ways. This is due to the multi-functionality of the kidney whose role covers important aspects in the body homeostasis. Among the most common symptoms suggesting of kidney damage include:

  • Leakage of circulating plasma protein in the urine (Proteinuria)
  • Frequent need of urination especially at night
  • Swelling of the legs (Edema)
  • High blood pressure (Hypertension)
  • Fatigue and weakness caused by anemia and progressive accumulation of waste products in the body
  • Loss of appetite and weight

It is widely accepted that, independently of any underlying kidney conditions, the first event leading to kidney failure is associated with alterations of the kidney glomerular filtration barrier, especially the glomerular epithelial cell layer made of highly specialised cells called podocytes.

Podocytes play a pivotal role both in the maintenance of the glomerular filtration barrier and its structural integrity. Podocyte damage contributes to proteinuria and progressive kidney damage including scarring.

Newly discovered molecules are known to constitute a unique cellular apparatus for maintaining the filtration barrier. Nevertheless, the full structure and modification of it in response to disease is not known in detail.

Currently, diagnostics of CKD is based on the estimation of glomerular filtration rate (eGFR) and proteinuria (as measured from the urine). However, proteinuria has serious limitations as a biomarker of CKD progression.

Chronic diseases pose a significant challenge to health management worldwide. The growing prevalence of chronic kidney disease particularly, has severe implications on public health and the economic output.

The European Kidney Patients’ Federation has estimated that up to 400.000 European citizens suffer from end-stage kidney disease (ESKD) and require approximately €12.6 billion worth of direct interventions per year.

The number of ESKD patients, furthermore, is increasing by 4% per year. In the USA, Medicare spending on more than 550.000 patients with ESKD reached $26.8 billion in 2008, representing 5.9% of total Medicare spending.

These alarming statistics highlight the importance of better understanding of the molecular and cellular mechanisms leading to End Stage Kidney Disease (ESKD).

Finding early diagnostic biomarkers will enable to a timely intervention with appropriate medications and will delay the need of hemodialysis treatment and all its wide implications.
Patients often experience physical pain, such as joint pain, as well as discomfort from being immobile during the several hours of hemodialysis, typically 3-4 times per week in a hospital setting.

Depression and anxiety are among the most common symptoms and side-effects in patients with ESKD. A general feeling of unwell and discomfort; along with major disruptions in lifestyle such as the need to comply with treatment regimens, including dialysis schedules, diet prescription, water restriction, hospitalizations; the fear of disability and shortened lifespan can further aggravate the psychological reactions to disease.

Depression has been studied extensively in patients on maintenance dialysis, and much effort has been done to validate the proper screening tools to diagnose depression and to define the treatment options for patients on maintenance dialysis with depression. Anxiety is less well studied in this population of patients. Evidence indicates that also anxiety symptoms are common in maintenance dialysis.


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