Sunday, June 30, 2013

What is Asthma? What Causes Asthma?

Asthma is a disease affecting the airways that carry air to and from your lungs. People who suffer from this chronic condition (long-lasting or recurrent) are said to be asthmatic.
doctor examining a lung x-ray
The inside walls of an asthmatic's airways are swollen or inflamed. This swelling or inflammation makes the airways extremely sensitive to irritations and increases your susceptibility to an allergic reaction.
As inflammation causes the airways to become narrower, less air can pass through them, both to and from the lungs. Symptoms of the narrowing include wheezing (a hissing sound while breathing), chest tightness, breathing problems, and coughing. Asthmatics usually experience these symptoms most frequently during the night and the early morning.
For information on the different causes of asthma (allergy, colds, stress, exercise, etc) please see page 4 (causes of asthma).

Asthma is Incurable

Asthma is an incurable illness. However, with good treatment and management there is no reason why a person with asthma cannot live a normal and active life.

What is an Asthma Episode / Attack?

An asthma episode, or an asthma attack, is when symptoms are worse than usual. They can come on suddenly and can be mild, moderate or severe.
What happens during an asthma attack?
  • The muscles around your airways tighten up, narrowing the airway.
  • Less air is able to flow through the airway.
  • Inflammation of the airways increases, further narrowing the airway.
  • More mucus is produced in the airways, undermining the flow of air even more.

Asthma Attacks Vary

patient using oxygen
In some asthma attacks, the airways are blocked such that oxygen fails to enter the lungs. This also prevents oxygen from entering the blood stream and traveling to the body's vital organs. Asthma attacks of this type can be fatal, and the patient may require urgent hospitalization.
Asthma attacks can be mild, moderate, severe and very severe. At onset, an asthma attack does allow enough air to get into the lungs, but it does not let the carbon dioxide leave the lungs at a fast enough rate. Carbon dioxide - poisonous if not expelled - can build up in the lungs during a prolonged attack, lowering the amount of oxygen getting into your bloodstream.

See Your Doctor

If you suffer from asthma you should see your doctor. He/she will help you find out what triggers your asthma symptoms and how to avoid them. You will also be prescribed medications which will help you manage your asthma.
With experience you will learn to keep away from things that irritate your airways, know when to take your medication, and better control your asthma. Effective asthma control allows you to take part in normal everyday activities.

Consequences of Not Controlling Your Asthma

If you don't control your asthma you will miss school or work more often and you will be less likely to be able to take part in some activities you enjoy. In the USA and Western Europe, asthma is one of the leading causes of school absenteeism.

Menstrual Cycle Affects Asthma Severity

A woman’s respiratory symptoms, including those of asthma, tend to worsen between day 10 to 22 of her menstrual cycle, researchers from Haukeland University Hospital in Bergen, Norway, found. They reported their findings in the American Journal of Respiratory and Critical Care Medicine (November 2012 issue).
The authors added that wheezing symptom severity dipped during ovulation (days 14 to 16). Patients with asthma, regular smokers and those with a BMI (body mass index) of more than 23 tend to experience more coughs immediately after ovulation.
Head researcher, Ferenc Macsali, MD, said "The effects of the menstrual cycle on respiratory symptoms in the general population have not been well studied. In a cohort of nearly 4,000 women, we found large and consistent changes in respiratory symptoms according to menstrual cycle phase, and, in addition, these patterns varied according to body mass index, asthma, and smoking status."

What is Asthma - Video

A video that explains what asthma is and the medications available to help relieve it. (by Altana Pharma)

What Is Cancer? What Causes Cancer?

Cancer is a class of diseases characterized by out-of-control cell growth. There are over 100 different types of cancer, and each is classified by the type of cell that is initially affected.
Cancer harms the body when damaged cells divide uncontrollably to form lumps or masses of tissue called tumors (except in the case of leukemia where cancer prohibits normal blood function by abnormal cell division in the blood stream). Tumors can grow and interfere with the digestive, nervous, and circulatory systems, and they can release hormones that alter body function. Tumors that stay in one spot and demonstrate limited growth are generally considered to be benign.
Cancer cell
More dangerous, or malignant, tumors form when two things occur:
  1. a cancerous cell manages to move throughout the body using the blood or lymph systems, destroying healthy tissue in a process called invasion
  2. that cell manages to divide and grow, making new blood vessels to feed itself in a process called angiogenesis.
When a tumor successfully spreads to other parts of the body and grows, invading and destroying other healthy tissues, it is said to have metastasized. This process itself is called metastasis, and the result is a serious condition that is very difficult to treat.
How cancer spreads - scientists reported in Nature Communications (October 2012 issue) that they have discovered an important clue as to why cancer cells spread. It has something to do with their adhesion (stickiness) properties. Certain molecular interactions between cells and the scaffolding that holds them in place (extracellular matrix) cause them to become unstuck at the original tumor site, they become dislodged, move on and then reattach themselves at a new site.
The researchers say this discovery is important because cancer mortality is mainly due to metastatic tumors, those that grow from cells that have traveled from their original site to another part of the body. Only 10% of cancer deaths are caused by the primary tumors.
The scientists, from the Massachusetts Institute of Technology, say that finding a way to stop cancer cells from sticking to new sites could interfere with metastatic disease, and halt the growth of secondary tumors.
In 2007, cancer claimed the lives of about 7.6 million people in the world. Physicians and researchers who specialize in the study, diagnosis, treatment, and prevention of cancer are called oncologists.
Malignant cells are more agile than non-malignant ones - scientists from the Physical Sciences-Oncology Centers, USA, reported in the journal Scientific Reports (April 2013 issue) that malignant cells are much “nimbler” than non-malignant ones. Malignant cells can pass more easily through smaller gaps, as well as applying a much greater force on their environment compared to other cells.
Professor Robert Austin and team created a new catalogue of the physical and chemical features of cancerous cells with over 100 scientists from 20 different centers across the United States.
The authors believe their catalogue will help oncologists detect cancerous cells in patients early on, thus preventing the spread of the disease to other parts of the body
Prof. Austin said "By bringing together different types of experimental expertise to systematically compare metastatic and non-metastatic cells, we have advanced our knowledge of how metastasis occurs."

What causes cancer?

Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis, and when this process breaks down, cancer begins to form. Unlike regular cells, cancer cells do not experience programmatic death and instead continue to grow and divide. This leads to a mass of abnormal cells that grows out of control.

What is cancer? - Video

A short, 3D, animated introduction to cancer. This was originally created by BioDigital Systems and used in the Stand Up 2 Cancer telethon.

Genes - the DNA type

Cells can experience uncontrolled growth if there are damages or mutations to DNA, and therefore, damage to the genes involved in cell division. Four key types of gene are responsible for the cell division process: oncogenes tell cells when to divide, tumor suppressor genes tell cells when not to divide, suicide genes control apoptosis and tell the cell to kill itself if something goes wrong, and DNA-repair genes instruct a cell to repair damaged DNA.
Cancer occurs when a cell's gene mutations make the cell unable to correct DNA damage and unable to commit suicide. Similarly, cancer is a result of mutations that inhibit oncogene and tumor suppressor gene function, leading to uncontrollable cell growth.

Carcinogens

Carcinogens are a class of substances that are directly responsible for damaging DNA, promoting or aiding cancer. Tobacco, asbestos, arsenic, radiation such as gamma and x-rays, the sun, and compounds in car exhaust fumes are all examples of carcinogens. When our bodies are exposed to carcinogens, free radicals are formed that try to steal electrons from other molecules in the body. Theses free radicals damage cells and affect their ability to function normally.

Genes - the family type

Cancer can be the result of a genetic predisposition that is inherited from family members. It is possible to be born with certain genetic mutations or a fault in a gene that makes one statistically more likely to develop cancer later in life.

Other medical factors

Holding hands
As we age, there is an increase in the number of possible cancer-causing mutations in our DNA. This makes age an important risk factor for cancer. Several viruses have also been linked to cancer such as: human papillomavirus (a cause of cervical cancer), hepatitis B and C (causes of liver cancer), and Epstein-Barr virus (a cause of some childhood cancers). Human immunodeficiency virus (HIV) - and anything else that suppresses or weakens the immune system - inhibits the body's ability to fight infections and increases the chance of developing cancer.

What are the symptoms of cancer?

Cancer symptoms are quite varied and depend on where the cancer is located, where it has spread, and how big the tumor is. Some cancers can be felt or seen through the skin - a lump on the breast or testicle can be an indicator of cancer in those locations. Skin cancer (melanoma) is often noted by a change in a wart or mole on the skin. Some oral cancers present white patches inside the mouth or white spots on the tongue.
Other cancers have symptoms that are less physically apparent. Some brain tumors tend to present symptoms early in the disease as they affect important cognitive functions. Pancreas cancers are usually too small to cause symptoms until they cause pain by pushing against nearby nerves or interfere with liver function to cause a yellowing of the skin and eyes called jaundice. Symptoms also can be created as a tumor grows and pushes against organs and blood vessels. For example, colon cancers lead to symptoms such as constipation, diarrhea, and changes in stool size. Bladder or prostate cancers cause changes in bladder function such as more frequent or infrequent urination.
As cancer cells use the body's energy and interfere with normal hormone function, it is possible to present symptoms such as fever, fatigue, excessive sweating, anemia, and unexplained weight loss. However, these symptoms are common in several other maladies as well. For example, coughing and hoarseness can point to lung or throat cancer as well as several other conditions.
When cancer spreads, or metastasizes, additional symptoms can present themselves in the newly affected area. Swollen or enlarged lymph nodes are common and likely to be present early. If cancer spreads to the brain, patients may experience vertigo, headaches, or seizures. Spreading to the lungs may cause coughing and shortness of breath. In addition, the liver may become enlarged and cause jaundice and bones can become painful, brittle, and break easily. Symptoms of metastasis ultimately depend on the location to which the cancer has spread.

How is cancer classified?

There are five broad groups that are used to classify cancer.
  1. Carcinomas are characterized by cells that cover internal and external parts of the body such as lung, breast, and colon cancer.
  2. Sarcomas are characterized by cells that are located in bone, cartilage, fat, connective tissue, muscle, and other supportive tissues.
  3. Lymphomas are cancers that begin in the lymph nodes and immune system tissues.
  4. Leukemias are cancers that begin in the bone marrow and often accumulate in the bloodstream.
  5. Adenomas are cancers that arise in the thyroid, the pituitary gland, the adrenal gland, and other glandular tissues.
Cancers are often referred to by terms that contain a prefix related to the cell type in which the cancer originated and a suffix such as -sarcoma, -carcinoma, or just -oma. Common prefixes include:
  • Adeno- = gland
  • Chondro- = cartilage
  • Erythro- = red blood cell
  • Hemangio- = blood vessels
  • Hepato- = liver
  • Lipo- = fat
  • Lympho- = white blood cell
  • Melano- = pigment cell
  • Myelo- = bone marrow
  • Myo- = muscle
  • Osteo- = bone
  • Uro- = bladder
  • Retino- = eye
  • Neuro- = brain

How is cancer diagnosed and staged?

Early detection of cancer can greatly improve the odds of successful treatment and survival. Physicians use information from symptoms and several other procedures to diagnose cancer. Imaging techniques such as X-rays, CT scans, MRI scans, PET scans, and ultrasound scans are used regularly in order to detect where a tumor is located and what organs may be affected by it. Doctors may also conduct an endoscopy, which is a procedure that uses a thin tube with a camera and light at one end, to look for abnormalities inside the body.
Cancer testing
Extracting cancer cells and looking at them under a microscope is the only absolute way to diagnose cancer. This procedure is called a biopsy. Other types of molecular diagnostic tests are frequently employed as well. Physicians will analyze your body's sugars, fats, proteins, and DNA at the molecular level. For example, cancerous prostate cells release a higher level of a chemical called PSA (prostate-specific antigen) into the bloodstream that can be detected by a blood test. Molecular diagnostics, biopsies, and imaging techniques are all used together to diagnose cancer.

After a diagnosis is made, doctors find out how far the cancer has spread and determine the stage of the cancer. The stage determines which choices will be available for treatment and informs prognoses. The most common cancer staging method is called the TNM system. T (1-4) indicates the size and direct extent of the primary tumor, N (0-3) indicates the degree to which the cancer has spread to nearby lymph nodes, and M (0-1) indicates whether the cancer has metastasized to other organs in the body. A small tumor that has not spread to lymph nodes or distant organs may be staged as (T1, N0, M0), for example.
TNM descriptions then lead to a simpler categorization of stages, from 0 to 4, where lower numbers indicate that the cancer has spread less. While most Stage 1 tumors are curable, most Stage 4 tumors are inoperable or untreatable.

How is cancer treated?

Cancer treatment depends on the type of cancer, the stage of the cancer (how much it has spread), age, health status, and additional personal characteristics. There is no single treatment for cancer, and patients often receive a combination of therapies and palliative care. Treatments usually fall into one of the following categories: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, or gene therapy.

Surgery

Surgery is the oldest known treatment for cancer. If a cancer has not metastasized, it is possible to completely cure a patient by surgically removing the cancer from the body. This is often seen in the removal of the prostate or a breast or testicle. After the disease has spread, however, it is nearly impossible to remove all of the cancer cells. Surgery may also be instrumental in helping to control symptoms such as bowel obstruction or spinal cord compression.

Radiation

Radiotherapy treatment
Radiation treatment, also known as radiotherapy, destroys cancer by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide. Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or high-energy x-rays that are created in a special machine. Early radiation treatments caused severe side-effects because the energy beams would damage normal, healthy tissue, but technologies have improved so that beams can be more accurately targeted. Radiotherapy is used as a standalone treatment to shrink a tumor or destroy cancer cells (including those associated with leukemia and lymphoma), and it is also used in combination with other cancer treatments.

Chemotherapy

Chemotherapy utilizes chemicals that interfere with the cell division process - damaging proteins or DNA - so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not necessarily just cancer cells), but normal cells usually can recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is generally used to treat cancer that has spread or metastasized because the medicines travel throughout the entire body. It is a necessary treatment for some forms of leukemia and lymphoma. Chemotherapy treatment occurs in cycles so the body has time to heal between doses. However, there are still common side effects such as hair loss, nausea, fatigue, and vomiting. Combination therapies often include multiple types of chemotherapy or chemotherapy combined with other treatment options.

Immunotherapy

Immunotherapy aims to get the body's immune system to fight the tumor. Local immunotherapy injects a treatment into an affected area, for example, to cause inflammation that causes a tumor to shrink. Systemic immunotherapy treats the whole body by administering an agent such as the protein interferon alpha that can shrink tumors. Immunotherapy can also be considered non-specific if it improves cancer-fighting abilities by stimulating the entire immune system, and it can be considered targeted if the treatment specifically tells the immune system to destroy cancer cells. These therapies are relatively young, but researchers have had success with treatments that introduce antibodies to the body that inhibit the growth of breast cancer cells. Bone marrow transplantation (hematopoetic stem cell transplantation) can also be considered immunotherapy because the donor's immune cells will often attack the tumor or cancer cells that are present in the host.

Hormone therapy

Several cancers have been linked to some types of hormones, most notably breast and prostate cancer. Hormone therapy is designed to alter hormone production in the body so that cancer cells stop growing or are killed completely. Breast cancer hormone therapies often focus on reducing estrogen levels (a common drug for this is tamoxifen) and prostate cancer hormone therapies often focus on reducing testosterone levels. In addition, some leukemia and lymphoma cases can be treated with the hormone cortisone.

Gene therapy

The goal of gene therapy is to replace damaged genes with ones that work to address a root cause of cancer: damage to DNA. For example, researchers are trying to replace the damaged gene that signals cells to stop dividing (the p53 gene) with a copy of a working gene. Other gene-based therapies focus on further damaging cancer cell DNA to the point where the cell commits suicide. Gene therapy is a very young field and has not yet resulted in any successful treatments.

Using cancer-specific immune system cells to treat cancer

Scientists from the RIKEN Research Centre for Allergy and Immunology in Yokohama, Japan, explained in the journal Cell Stem Cell (January 2013 issue) how they managed to make cancer-specific immune system cells from iPSCs (induced pluripotent stem cells) to destroy cancer cells.
The authors added that their study has shown that it is possible to clone versions of the patients’ own cells to enhance their immune system so that cancer cells could be destroyed naturally.
Hiroshi Kawamoto and team created cancer-specific killer T-lymphocytes from iPSCs. They started off with mature T-lymphocytes which were specific for a type of skin cancer and reprogrammed them into iPSCs with the help of “Yamanaka factors”. The iPSCs eventually turned into fully active, cancer-specific T-lymphocytes - in other words, cells that target and destroy cancer cells.

How can cancer be prevented?

Cancers that are closely linked to certain behaviors are the easiest to prevent. For example, choosing not to smoke tobacco or drink alcohol significantly lower the risk of several types of cancer - most notably lung, throat, mouth, and liver cancer. Even if you are a current tobacco user, quitting can still greatly reduce your chances of getting cancer.
Skin cancer can be prevented by staying in the shade, protecting yourself with a hat and shirt when in the sun, and using sunscreen. Diet is also an important part of cancer prevention since what we eat has been linked to the disease. Physicians recommend diets that are low in fat and rich in fresh fruits and vegetables and whole grains.
Certain vaccinations have been associated with the prevention of some cancers. For example, many women receive a vaccination for the human papillomavirus because of the virus's relationship with cervical cancer. Hepatitis B vaccines prevent the hepatitis B virus, which can cause liver cancer.
Some cancer prevention is based on systematic screening in order to detect small irregularities or tumors as early as possible even if there are no clear symptoms present. Breast self-examination, mammograms, testicular self-examination, and Pap smears are common screening methods for various cancers.
Researchers from Northwestern University Feinberg School of Medicine in Chicago reported in the journal Circulation that the 7 steps recommended for protection against heart disease can also reduce the risk of developing cancer,. They include being physically active, eating a healthy diet, controlling cholesterol, managing blood pressure, reducing blood sugar and not smoking.

Targeting cancers for new drug therapies

Researchers at The Institute of Cancer Research reported in the journal Nature Reviews Drug Discovery (January 2013 issue) that they have found a new way of rapidly prioritizing the best druggable targets online. They managed to identify 46 previously overlooked targets.
The researchers used the canSAR database together with a tool and were able to compare up to 500 drug targets in a matter of minutes. With this method, it is possible to analyze huge volumes of data to discover new drug targets, which can lead to the development of effective cancer medications.
The scientists analyzed 479 cancer genes to determine which ones were potential targets for medications. Their approach was effective - they found 46 new potentially “druggable” cancer proteins.
Not only will this approach lead to much more targeted cancer drugs, but also considerably cheaper ones, the authors added.

How to eat to prevent cancer - video

A guide to some everyday foods that contain nutrients that may help reduce your risk of getting cancer. Video by Howcast.

Cancer / Oncology news

Medical News Today is a leading resource for the latest news on cancer. You can find ourcancer news section here.

Diabetes mellitus

Diabetes mellitus
Classification and external resources

Universal blue circle symbol for diabetes.[1]
ICD-10E10E14
ICD-9250
MedlinePlus001214
eMedicinemed/546 emerg/134
MeSHC18.452.394.750
Diabetes mellitus, or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin, or because cells do not respond to the insulin that is produced.[2] This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).
There are three main types of diabetes mellitus (DM).
  • Type 1 DM results from the body's failure to produce insulin, and currently requires the person to inject insulin or wear an insulin pump. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes".
  • Type 2 DM results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. This form was previously referred to as non insulin-dependent diabetes mellitus (NIDDM) or "adult-onset diabetes".
  • The third main form, gestational diabetes occurs when pregnant women without a previous diagnosis of diabetes develop a high blood glucose level. It may precede development of type 2 DM.
Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes.
Untreated, diabetes can cause many complications. Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long-term complications include cardiovascular diseasechronic renal failure, and diabetic retinopathy (retinal damage). Adequate treatment of diabetes is thus important, as well as blood pressure control and lifestyle factors such as stopping smoking and maintaining a healthy body weight.
All forms of diabetes have been treatable since insulin became available in 1921, and type 2 diabetes may be controlled with medications. Insulin and some oral medications can cause hypoglycemia (low blood sugars), which can be dangerous if severe. Both types 1 and 2 are chronic conditions that cannot be cured. Pancreas transplants have been tried with limited success in type 1 DM; gastric bypass surgery has been successful in many withmorbid obesity and type 2 DM. Gestational diabetes usually resolves after delivery.

Classification

Comparison of type 1 and 2 diabetes[3]
FeatureType 1 diabetesType 2 diabetes
OnsetSuddenGradual
Age at onsetMostly in childrenMostly in adults
Body habitusThin or normal[4]Often obese
KetoacidosisCommonRare
AutoantibodiesUsually presentAbsent
Endogenous insulinLow or absentNormal, decreased
or increased
Concordance
in identical twins
50%90%
Prevalence~10%~90%
Diabetes mellitus is classified into four broad categories: type 1type 2gestational diabetes and "other specific types".[2] The "other specific types" are a collection of a few dozen individual causes.[2] The term "diabetes", without qualification, usually refers to diabetes mellitus. The rare disease diabetes insipidus has similar symptoms as diabetes mellitus, but without disturbances in the sugar metabolism (insipidus means "without taste" in Latin) and does not involve the same disease mechanisms.
The term "type 1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM). Likewise, the term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature.

Type 1 diabetes

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in which beta cell loss is a T-cell-mediated autoimmune attack.[5] There is no known preventive measure against type 1 diabetes, which causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults, but was traditionally termed "juvenile diabetes" because a majority of these diabetes cases were in children.
"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.[6] There are many reasons for type 1 diabetes to be accompanied by irregular and unpredictable hyperglycemia, frequently with ketosis, and sometimes serious hypoglycemia, including an impaired counterregulatory response to hypoglycemia, occult infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[6] These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.[7]

Type 2 diabetes

Type 2 diabetes mellitus is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.[2] The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type.
In the early stage of type 2, the predominant abnormality is reduced insulin sensitivity. At this stage, hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver.

Gestational diabetes

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%–5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type 2 diabetes later in life.
Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndromeHyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A Caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.
A 2008 study completed in the U.S. found the number of American women entering pregnancy with pre-existing diabetes is increasing. In fact, the rate of diabetes in expectant mothers has more than doubled in the past six years.[8] This is particularly problematic as diabetes raises the risk of complications during pregnancy, as well as increasing the potential for the children of diabetic mothers to become diabetic in the future.

Other types

Prediabetes indicates a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 DM. Many people destined to develop type 2 DM spend many years in a state of prediabetes which has been termed "America's largest healthcare epidemic."[9]:10–11
Latent autoimmune diabetes of adults (LADA) is a condition in which type 1 DM develops in adults. Adults with LADA are frequently initially misdiagnosed as having type 2 DM, based on age rather than etiology.
Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization when the current taxonomy was introduced in 1999.[10]

Signs and symptoms

Overview of the most significant symptoms of diabetes
The classic symptoms of untreated diabetes are loss of weight, polyuria (frequent urination), polydipsia (increased thirst) and polyphagia(increased hunger).[11] Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.
Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Blurred vision is a common complaint leading to a diabetes diagnosis. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Diabetic emergencies

People (usually with type 1 diabetes) may also present with diabetic ketoacidosis, a state of metabolic dysregulation characterized by the smell of acetone, a rapid, deep breathing known as Kussmaul breathing, nausea, vomiting and abdominal pain, and altered states of consciousness.
A rare but equally severe possibility is hyperosmolar nonketotic state, which is more common in type 2 diabetes and is mainly the result of dehydration.

Complications

All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20), but may be the first symptom in those who have otherwise not received a diagnosis before that time. The major long-term complications relate to damage toblood vessels. Diabetes doubles the risk of cardiovascular disease.[12] The main "macrovascular" diseases (related to atherosclerosis of larger arteries) are ischemic heart disease (angina andmyocardial infarction), stroke and peripheral vascular disease.
Diabetes also damages the capillaries (causes microangiopathy).[13] Diabetic retinopathy, which affects blood vessel formation in the retina of the eye, can lead to visual symptoms including reduced vision and potentially blindnessDiabetic nephropathy, the impact of diabetes on the kidneys, can lead to scarring changes in the kidney tissue, loss of small or progressively largeramounts of protein in the urine, and eventually chronic kidney disease requiring dialysis.
Another risk is diabetic neuropathy, the impact of diabetes on the nervous system — most commonly causing numbness, tingling and pain in the feet, and also increasing the risk of skin damage due to altered sensation. Together with vascular disease in the legs, neuropathy contributes to the risk of diabetes-related foot problems (such as diabetic foot ulcers) that can be difficult to treat and occasionally require amputation. As well, proximal diabetic neuropathy causes painful muscle wasting and weakness.
Several studies suggest[14] a link between cognitive deficit and diabetes. Compared to those without diabetes, the research showed that those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function, and are at greater risk.

Causes

The cause of diabetes depends on the type.
Type 1 diabetes is partly inherited, and then triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. A genetic element in individual susceptibility to some of these triggers has been traced to particular HLA genotypes (i.e., the genetic "self" identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 DM seems to require an environmental trigger. The onset of type 1 diabetes is unrelated to lifestyle.
Type 2 diabetes is due primarily to lifestyle factors and genetics.[15]
The following is a comprehensive list of other causes of diabetes:[16]

Pathophysiology

The fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day with three meals - one of the effects of a sugar-rich vs a starch-rich meal is highlighted.
Mechanism of insulin release in normal pancreatic beta cells - insulin production is more or less constant within the beta cells. Its release is triggered by food, chiefly food containing absorbable glucose.
Insulin is the principal hormone that regulates uptake of glucose from the blood into most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore, deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.
Humans are capable of digesting some carbohydrates, in particular those most common in food; starch, and some disaccharides such as sucrose, are converted within a few hours to simpler forms, most notably the monosaccharide glucose, the principal carbohydrate energy source used by the body. The rest are passed on for processing by gut flora largely in the colon. Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage.
Insulin is also the principal control signal for conversion of glucose to glycogen for internal storage in liver and muscle cells. Lowered glucose levels result both in the reduced release of insulin from the β-cells and in the reverse conversion of glycogen to glucose when glucose levels fall. This is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin. Glucose thus forcibly produced from internal liver cell stores (as glycogen) re-enters the bloodstream; muscle cells lack the necessary export mechanism. Normally, liver cells do this when the level of insulin is low (which normally correlates with low levels of blood glucose).
Higher insulin levels increase some anabolic ("building up") processes, such as cell growth and duplication, protein synthesis, and fat storage. Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, a low insulin level is the trigger for entering or leaving ketosis (the fat-burning metabolic phase).
If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, then glucose will not have its usual effect, so it will not be absorbed properly by those body cells that require it, nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.
When the glucose concentration in the blood is raised to about 9-10 mmol/L (except certain conditions, such as pregnancy), beyond its renal threshold(i.e. when glucose level surpasses the transport maximum of glucose reabsorption), reabsorption of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing dehydration and increased thirst.

Diagnosis

Diabetes diagnostic criteria[18][19]  edit
Condition2 hour glucoseFasting glucoseHbA1c
mmol/l(mg/dl)mmol/l(mg/dl)%
Normal<7.8 (<140)<6.1 (<110)<6.0
Impaired fasting glycaemia<7.8 (<140)≥ 6.1(≥110) & <7.0(<126)6.0–6.4
Impaired glucose tolerance≥7.8 (≥140)<7.0 (<126)6.0–6.4
Diabetes mellitus≥11.1 (≥200)≥7.0 (≥126)≥6.5
Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:[10]
  • Fasting plasma glucose level ≥ 7.0 mmol/l (126 mg/dl)
  • Plasma glucose ≥ 11.1 mmol/l (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test
  • Symptoms of hyperglycemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)
  • Glycated hemoglobin (Hb A1C) ≥ 6.5%.[20]
A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test.[21] According to the current definition, two fasting glucose measurements above 126 mg/dl (7.0 mmol/l) is considered diagnostic for diabetes mellitus.
People with fasting glucose levels from 110 to 125 mg/dl (6.1 to 6.9 mmol/l) are considered to have impaired fasting glucose.[22] Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease.[23]
Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.[24]

Management

Diabetes mellitus is a chronic disease, for which there is no known cure except in very specific situations. Management concentrates on keeping blood sugar levels as close to normal ("euglycemia") as possible, without causing hypoglycemia. This can usually be accomplished with diet, exercise, and use of appropriate medications (insulin in the case of type 1 diabetes; oral medications, as well as possibly insulin, in type 2 diabetes).
Patient education, understanding, and participation is vital, since the complications of diabetes are far less common and less severe in people who have well-managed blood sugar levels.[25][26]The goal of treatment is an HbA1C level of 6.5%, but should not be lower than that, and may be set higher.[27] Attention is also paid to other health problems that may accelerate the deleterious effects of diabetes. These include smokingelevated cholesterol levels, obesityhigh blood pressure, and lack of regular exercise.[27] Specialised footwear is widely used to reduce the risk of ulceration, or re-ulceration, in at-risk diabetic feet. Evidence for the efficacy of this remains equivocal, however.[28]

Lifestyle

There are roles for patient education, dietetic support, sensible exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.[29]

Medications

Metformin is generally recommended as a first line treatment for type 2 diabetes, as there is good evidence that it decreases mortality.[30] Routine use of aspirin, however, has not been found to improve outcomes in uncomplicated diabetes.[31]
Type 1 diabetes is typically treated with a combinations of regular and NPH insulin, or synthetic insulin analogs. When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.[30] Doses of insulin are then increased to effect.[30]

Support

In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care of a patient in a team approach. Home telehealth support can be an effective management technique.[32]

Epidemiology

Prevalence of diabetes worldwide in 2000 (per 1,000 inhabitants) - world average was 2.8%.
  no data
  ≤ 7.5
  7.5–15
  15–22.5
  22.5–30
  30–37.5
  37.5–45
  45–52.5
  52.5–60
  60–67.5
  67.5–75
  75–82.5
  ≥ 82.5
Disability-adjusted life year for diabetes mellitus per 100,000 inhabitants in 2004
  No data
  <100
  100–200
  200–300
  300–400
  400–500
  500–600
  600–700
  700–800
  800–900
  900–1,000
  1,000–1,500
  >1,500
Globally, as of 2010, an estimated 285 million people had diabetes, with type 2 making up about 90% of the cases.[3] Its incidence is increasing rapidly, and by 2030, this number is estimated to almost double.[33] Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030.[33] The increase in incidence in developing countries follows the trend of urbanization and lifestyle changes, perhaps most importantly a "Western-style" diet. This has suggested an environmental (i.e., dietary) effect, but there is little understanding of the mechanism(s) at present, though there is much speculation, some of it most compellingly presented.[33]

History

Diabetes was one of the first diseases described,[34] with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine".[35]The first described cases are believed to be of type 1 diabetes.[35] Indian physicians around the same time identified the disease and classified it asmadhumeha or "honey urine", noting the urine would attract ants.[35] The term "diabetes" or "to pass through" was first used in 230 BCE by the GreekAppollonius of Memphis.[35] The disease was considered as rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[35] This is possibly due the diet and life-style of the ancient people, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa). The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation of diabetes with other diseases and he discussed differential diagnosis from the snakebite which also provokes excessive thirst. His work remained unknown in the West until the middle of the 16th century when, in 1552, the first Latin edition was published in Venice.[36]
Type 1 and type 2 diabetes where identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400-500 CE with type 1 associated with youth and type 2 with being overweight.[35] The term "mellitus" or "from honey" was added by the Briton John Rolle in the late 1700s to separate the condition from diabetes insipidus, which is also associated with frequent urination.[35] Effective treatment was not developed until the early part of the 20th century, when Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922.[35] This was followed by the development of the long-acting insulin NPH in the 1940s.[35]

Etymology

The word diabetes (/ˌd.əˈbtz/ or /ˌd.əˈbtɨs/) comes from Latin diabētēs, which in turn comes from Ancient Greek διαβήτης (diabētēs) which literally means "a passer through; a siphon."[37] Ancient Greek physician Aretaeus of Cappadocia (fl. 1st century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease.[38][39] Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through,"[37] which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go".[38] The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.
The word mellitus (/mɨˈltəs/ or /ˈmɛlɨtəs/) comes from the classical Latin word mellītus, meaning "mellite"[40] (i.e. sweetened with honey;[40] honey-sweet[41]). The Latin word comes from mell-, which comes from mel, meaning "honey";[40][41] sweetness;[41] pleasant thing,[41] and the suffix -ītus,[40] whose meaning is the same as that of the English suffix "-ite".[42] It was Thomas Willis who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a diabetic had a sweet taste (glycosuria).[39] This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.

Society and culture

The 1989 "St. Vincent Declaration"[43][44] was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy, but also economically—expenses due to diabetes have been shown to be a major drain on health—and productivity-related resources for healthcare systems and governments.
Several countries established more and less successful national diabetes programmes to improve treatment of the disease.[45]
Diabetic patients with neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.[46]

Other animals

In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are also more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such asMiniature Poodles.[47] The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognised in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.[47]