Diabetes –PBL 2- HDAsem shadid

What is diabetes?Diabetes is a chronic, often debilitating and sometimes fatal disease, in which the body either cannot produce insulin or cannot properly use the insulin it produces.

Insulin is a hormone that controls the amount of glucose (sugar) in the blood. Diabetes leads to high blood sugar levels, which can damage organs, blood vessels and nerves.

• The pancreas is an organ that sits behind the stomach and releases hormones into the digestive system.

• In the healthy body, when blood sugar levels get too high, special cells in the pancreas (called beta cells) release insulin.

• Insulin is a hormone and it causes cells to take in sugar to use as energy or to store as fat. This causes blood sugar levels to go back down.

Types of diabetes• There are two main types of diabetes mellitus: type 1 (caused

by beta cell destruction, leading to absolute insulin deficiency) and type 2 (caused by insulin resistance and relative insulin deficiency).

• Table 3 lists the classification of diabetes mellitus according to aetiology.

Signs and symptoms

Complications of Diabetes   –• – Atherosclerosis – Condition characterized by hardening or loss of

elasticity of the arterial blood vessels leading to insufficient blood supply to organs.

• – Diabetic Microangiopathy – Condition characterized by thickening and weakening of walls of blood vessels in different areas including eyes, resulting in slowing down of the blood flow, leakage of proteins and bleeding from these blood vessels.

• – Diabetic Nephropathy – Characterized by disfunctioning of the filtering system in the kidneys and later resulting in kidney failure.

• – Diabetic Neuropathy – Characterized by damage to nerves all over the body and in later stages resulting in dysfunction to organs and organ systems.

• – Diabetic Retinopathy – Condition characterized by damage to the blood vessels in the retina

• – Diabetic Ketoacidosis – Condition characterized by large concentration of Ketoacidosis, which on later stages may lead to many fatal complications.

Family Health History and Diabetes• Type 1 Diabetes: In general, if you are a man with type 1 diabetes, the

odds of your child developing diabetes are 1 in 17.• If you are a woman with type 1 diabetes and your child was born

before you were 25, your child's risk is 1 in 25; if your child was born after you turned 25, your child's risk is 1 in 100.

• Type 2 Diabetes: • In general, if you have type 2 diabetes, the risk of your child getting

diabetes is 1 in 7 if you were diagnosed before age 50 and 1 in 13 if you were diagnosed after age 50. –

• child's risk is greater when the parent with type 2 diabetes is the mother. If both you and your partner have type 2 diabetes, your child's risk is about 1 in 2.

Insulin autoantibodies

• RIA: Anti-GAD, Anti-IA2, Anti-Insulin; Insulin Antibodies - These tests are also used in early diagnosis for type 1 diabetes, and for differential diagnosis between LADA and type 2 diabetes, as well as for differential diagnosis of gestational diabetes, risk prediction in immediate family members for type 1, and to monitor prognosis of the clinical progression of type 1 diabetes.

• Persons with LADA may test positive for autoantibodies (GAD, ICA, IA-2, ZnT8); autoantibodies are not present in persons with type 2 diabetes.

Glycated hemoglobinhemoglobin A1c, HbA1c, A1C, or Hb1c; sometimes also HbA1c or HGBA1C)

• is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods.

• Hemoglobin is found in red blood cells, which carry oxygen throughout your body.

• When your diabetes is not controlled (meaning that your blood sugar is too high), sugar builds up in your blood and combines with your hemoglobin, becoming "glycated."

• The average amount of sugar in your blood can be found by measuring your hemoglobin A1c level.

• If your glucose levels have been high over recent weeks, your hemoglobin A1c test will be higher.

What's a Normal Hemoglobin A1c Test?• For people without diabetes, the normal range for the hemoglobin

A1c test is between 4% and 5.6%.

• Hemoglobin A1c levels between 5.7% and 6.4% indicate increased risk of diabetes

• and levels of 6.5% or higher indicate diabetes.

• People with diabetes should have this test every 3 months .

• People with diseases affecting hemoglobin, such as anemia, may get abnormal results with this test. Other abnormalities that can affect the results of the hemoglobin A1c include supplements such as vitamins C and E and high cholesterol levels. Kidney disease and liver disease may also affect the result of the hemoglobin A1c test.

Autoimmune diabetes: the role of T cells, MHC molecules and autoantigens.

• HLA types are inherited, and some of them are connected with autoimmune disorders and other diseases. People with certain HLA antigens are more likely to develop certain autoimmune diseases, such as type I diabetes .

• human leukocyte antigen (HLA) system is the locus of genes that encode for proteins on the surface of cells that are responsible for regulation of the immune system in humans.

• The HLA genes are the human versions of the major histocompatibility complex (MHC) genes that are found in most vertebrates (and thus are the most studied of the MHC genes)

• Type 1 diabetes (IDDM) is a T cell mediated autoimmune disease which in part is determined genetically by its association with major histocompatibility complex (MHC) class II alleles.

• The major role of MHC molecules is the regulation of immune responses through the presentation of peptide epitopes of processed protein antigens to the immune system .

• The strongest gene, IDDM1, is located in the MHC Class II region on chromosome 6 . Certain variants of this gene increase the risk for decreased histocompatibility characteristic of type 1.

• Recently it has been demonstrated that MHC molecules associated with autoimmune diseases preferentially present peptides of other endogenous MHC proteins, that often mimic autoantigen-derived peptides.

• Hence, these MHC-derived peptides might represent potential targets for autoreactive T cells.

• It has consistently been shown that humoral autoimmunity to insulin predominantly occurs in early childhood. The cellular immune response to insulin is relatively low in the peripheral blood of patients with IDDM.

Environmental

• Environmental factors can influence expression of type 1.

• For identical twins, when one twin has type 1 diabetes, the other twin only has it 30%–50% of the time.

• Thus for 50%-70% of identical twins where one has the disease, the other will not, despite having exactly the same genome; this suggests environmental factors, in addition to genetic factors, can influence the disease's prevalence.

• Other indications of environmental influence include the presence of a 10-fold difference in occurrence among Caucasians living in different areas of Europe, and that people tend to acquire the rate of disease of their particular destination country.

Diabetic ketoacidosis• ketoacidosis is a potentially life-threatening complication in patients with

diabetes mellitus. It happens predominantly in those with type 1 diabetes .

• DKA results from a shortage of insulin; in response the body switches to burning fatty acids and producing acidic ketone bodies that cause most of the symptoms and complications.

• Management

• Potassium levels can fluctuate severely during the treatment of DKA, because insulin decreases potassium levels in the blood by redistributing it into cells.

• A large part of the shifted extracellular potassium would have been lost in urine because of osmotic diuresis.

• Hypokalemia (low blood potassium concentration) often follows treatment. This increases the risk of dangerous irregularities in the heart rate.

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