Type 1 Diabetes Mellitus
Prepared by: Daniela Cihakova MD, PhD|
Definition: Insulin dependent diabetes mellitus (type 1) is an inflammatory autoimmune disease of the pancreas, resulting in a lack of insulin.
Description: Insulin is produced in the pancreas by beta cells of the islets of Langerhans. The main source of energy for all cells and especially for brain cells is glucose. Insulin is necessary for glucose to get into cells and be used for energy production. After eating, the glucose level in blood rises, which leads to insulin being released from the pancreas. In a person with IMDM, beta cells of Langerhans are damaged by autoimmune inflammation, leading to an insufficiency of insulin. The glucose level in blood rises and cells do not have enough energy for metabolism.
- Excessive urination, urination at night, thirst, dehydration. The kidneys are not able to return glucose back to blood when glucose increases above certain level. As a result, glucose appears in urine, taking with it lots of water. This results in frequent and excessive urination, which in turn causes intense thirst and dehydration and mineral loss.
- Weight loss: Because of the insufficient level of insulin, glucose can not be used as a energy source. The body of a patient with IMDM therefore has to use fat and muscles, which results in weight loss.
Diagnosis: High glucose level. In the case of doubts in the beginning of the disease, the level of glucose is measured after 12 hours of fasting (Fasting Plasma Glucose Test). If this test is not conclusive, Oral Glucose Tolerance Test (OGTT) may be used.
C-peptide and insulin levels are low in IMDM.
Islet-cell and anti-insulin autoantibodies are positive only in the beginning of IDDM
- Type 2 diabetes (non-insulin-dependent diabetes mellitus) Insulin concentrations are mostly increased but peripheral tissues are resistant to insulin (insulin resistance). Beta cells are not able increase secretion of insulin to overcome this resistance. Type 2 diabetes usually develops after 40 years of age in overweight people, lately in obese adolescents.
- Gestational diabetes mellitus: as type II is characterized by insulin resistance, usually is mild, but show risk of later development of diabetes 2 type.
- MODY (maturity onset diabetes of the young) – single-gene disorder, early onset, strong family history, present as type 2 diabetes, which gene is involved change clinical outcome of disease.
- LADA (latent Autoimmune Diabetes of Adulthood) or type 1.5 diabetes - a slowly progressive form of type 1 diabetes mellitus. Patients are often diagnosed as type II diabetes, but have positive pancreatic islet antibodies, especially to glutamic acid decarboxylase (GAD). They do not immediately require insulin for treatment, are often not overweight, and have little or no resistance to insulin.
Incidence: People under the age of 40. The disease often starts in childhood and affects more Caucasians than African-Americans. The male-to-female ratio is 1:1.
Treatment: Insulin is used as a substitute for the lost beta cells function. However, it does not treat IMDM. It has to be used life-long, several times per day in subcutaneous injections before meals. The proper dosage of insulin and appropriate menu plans have to be determined by a doctor. It is very important that patients follow the recommended doses and menu plans and that they regularly monitor their level of glucose in blood (which should be kept at 80–140 mg/dl). Good management of IDDM also requires good patient (or parent) education about the roles of sport, diseases, and food in maintaining a stable glucose level. As regards food, the diabetic diet is not sugar-free but rather a balanced diet with a carefully controlled calories intake and regular timing. Regular follow up is absolutely essential to avoid long term complications.
Pathogenesis: Diabetes mellitus type 1 is an autoimmune disease. The autoimmune process begins many years before clinical detection and presentation. It is directly against beta cell of the islets of Langerhans. The destruction must be very heavy, more then 90 percent of beta cells must be destroyed for clinical symptoms to develop. The speed of the beta cell destruction is variable. What is a trigger for autoimmune destruction is not known. Some authors have speculated about several viruses and other environmental factors in genetically susceptible individuals. The following evidence exists that diabetes type 1 is an autoimmune disease:
- Positive family history
- HLA class II association. HLA DR4-DQ8 and or DR3-DQ2 are positively associated with diabetes type 1, while DR15-DQ6 (B*0602) is negatively associated.
- Association with other autoimmune diseases – pernicious anemia, Addison’s disease, autoimmune thyroid disease (see polyglandular syndromes).
- Lymphocytic infiltration around the islets of Langerhans.
- Immunosuppressive treatment is able to delayed onset of disease.
- Autoantibody presence in serum:
- ICA (Islet cell antibodies) - against the antigen present in the cytoplasm of the endocrine cells in pancreatic islets.
- IAA (Insulin autoantibodies)
- GAD – autoantibodies to glutamic acid decarboxylase
- IA-2A (Insulinoma associated 2 autoantibodies) - against the protein tyrosine phosphatase
- NOD (non-obese diabetic) mice - In NOD mice – diabetes is present in 80% of females and 10% of males. Without insulin most animaSl die within 4 weeks.
- BB Wistar rat – these mice have incidence of diabetes 10-30%
- Diabetes in mice can be induced by immunization with pancreatic extract in adjuvant.
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