Type 1 Diabetes is a diabetes type which progresses with almost absence of the insulin.  Although it starts in the earlier years of life, it may also appear in elder ages.  Majority of the patients have some destructive blood products that we call antibodies which kills β-beta cells producing insulin or deactivates insulin.  Information obtained from observations performed during last 20 years has shown that the disease may progress with normal blood sugar levels without presenting any finding during first years of life.  Predisposition to the disease may be detected by presence of antibodies in tests performed during this period.  However, studies conducted and patient researches has shown that there was not any antibody which breaks insulin down or kills β-beta cells in anyway in a group of patients whom insulin is never produced like Type-1 Diabetes and who have to survive insulin-dependent during lifetime.   These patients are classified as Type 1 Diabetes with all findings.  However, the underlying cause is not known.  Therefore, a necessity to examine Type 1 Diabetes under two different subgroups has arisen.  American Diabetes Association (ADA) has divided Type 1 Diabetes into two groups.

	Insulin Shots

Type 1A: It is completely autoimmune (in other words, the immune system fights with a destructive effect against β-beta cells in the pancreas and insulin itself).  Most of the patients progresses through severe insulin deficiency.

Type 1B: It is idiopathic (in other words, cause is unknown) type.  It is most common in Japan in the world.  No antibody exists.  It appears with severe insulin absence like Type 1A.  First findings may reveal itself with emergency coma (ketoacidosis coma) in some African-American pediatric patients and these children may be treated with oral diabetes drugs without insulin although they have Type 1 Diabetes.

We understand from the abovementioned descriptions and classifications that it is not possible to explain Type 1 Diabetes with all causes.  There are many different groups of classes.

Although cause for Type 1 Diabetes is autoimmune (due to antibody production against different tissues), these patients may be under risk for other autoimmune diseases.   Major autoimmune diseases  are in the following.

• Addison’s Disease:

Antibodies against 21-hydroxlase enzyme exist on the adrenal glands.  When Addison appears in a patient with Type 1 Diabetes, insulin requirements reduce.  Because, hypoglycemia (low blood sugar) appears in Addison’s.  Although most of the patients provide mild-intermediate symptoms until the diagnosis, they can not be diagnosed for many years.  While incidence of Addison’s is 1 per 10,000 individuals, this incidence raises up to 1 per 200 in patients with Type 1 Diabetes.

• Celiac Diseases:

It does not provide symptoms in general.  It has been shown that patients diagnosed with Celiac disease are at most 10% of total patients.  Antibodies against transglutaminase is a sensitive indicator for diagnosis.  Transglutimanse antibody is detected in 12% of the patients with Type 1 Diabetes.  Half of the patients with Type 1 Diabetes who has Transgultaminase antibody are diagnosed with Celiac Disease via intestinal biopsy.  Celiac disease is caused by a sensibility against a cereal called Gluten.  Diet programs of these patients for Type 1 Diabetes includes food without gluten.

• Autoimmune Thyroid Diseases:

Autoimmune thyroid diseases are common in patients with Type 1A Diabetes.   Thyroid antibodies are detected in one fourth of patients with Type 1 Diabetes, however, thyoriditis develops in minority of these.

• Pernicious Anemia:

Anemia appears because of antibodies against parietal cells of the stomach.  It accompanies to Type 1 Diabetes.  About 10% of the patients whose antibodies were detected in the blood presents Pernicious Anemia findings.

Genetic Substructure of Type 1 Diabetes

• Familial Predisposition

	Blood Sugar Measurement

While incidence of Type 1 Diabetes is 1/300, the incidence is 1/20 for individuals who have family members with Type 1 Diabetes.  In a study conducted in twins, Type 1 Diabetes possibility in children who have Type 1 Diabetes in their twins increase up to 50%.

• Tissue Groups

Type 1 Diabetes is closely related with HLA DR3-4 and DQ2-3 tissue groups.  However, very complex combinations may appear between thousands of different types.  A tissue grouping which may be used as a screening test have not been clarified yet.

• Insulin Gene

It has been shown in animal experiments that dominancy of thymus-originated insulin gene products may be protective for diabetes and this may be an indicator for low risk.

Type 1 Diabetes and Environmental Factors

Stimulation of antibody production by different environmental factors against different tissues is a case known.  For example, Celiac disease is a sample for such cases.  Gluten taken with cereals creates antibody against intestines in the body and the disease appears. Similar cases may appear for Type 1 Diabetes as well.

Viruses:

Viral infections may trigger autoimmunity.  If the individual has an autoimmune sensibility, diabetes may develop in such individual.  It is clearly known that rubeola transmitted from mother during delivery causes Type 1 Diabetes (especially Type 1 A Diabetes).  Congenital rubeola may cause many other autoimmune disease as well as Type 1 Diabetes.  Diabetes may appear after years for individuals who have tissue groups such as HLA DR3-4 which have high risk.  Besides rubeola, congenital infections causes by enterovirus may cause Type 1 A Diabetes.  It is believed that autoimmunity against β-beta cells appeared by enterovirus causes diabetes possibly by meeting the virus during intrauterine period.  It is believed that similarity of Glutamic Acid Decarboxylase enzyme with a protein in Coxackie A virus plays an important role in this autoimmunity.  Antibodies appeared against Coxackie A virus also destroys Glutamic Acid decarboxylase enzyme and Type 1 Diabetes appears.

Vaccinations:

	Childhood Diabetes: Type 1 Diabetes

It has been shown in experiments conducted on animals that BCG (Tuberculosis) vaccination prevents diabetes.  However, trials conducted on humans have presented that BCG vaccination has no effect on C-peptide reduction after appearance of diabetes.  Furthermore, it has been shown in multi-centered large studies that routine vaccinations or application of these in different times has no effect on progress or appearance of diabetes.

Diet:

It has been shown that nursing is protective for Type 1 Diabetes. It has been reported that cow milk may trigger antibody production.  However, in other studies, it is reported that there is not any connection between mother milk and Type 1 Diabetes.  DAISY study has shown that there is not any significant relationship between early passage to cow milk and Type 1 Diabetes.  Although these studies provide different and sometimes conflicting findings, it is not recommended for babies to cut from nursing and start cow milk.  It is considered that vitamins may also be protective for Type 1 Diabetes because of antioxidant effects.

Self Causes in Type 1 diabetes (Humoral Autoimmunity)

• Insulin

Antibodies against insulin appears very early in Type 1 Diabetes.  Antibodies are detected before start of insulin treatment.  However, sole presence of insulin antibodies is far away from a specific finding for Type 1 Diabetes.  These antibodies occur in patients who receive insulin treatment because of Type 2 Diabetes.

• Glutamic Acid Decarboxylase (GAD)

It is one of the most important antibodies for Type 1 Diabetes.  Antibodies which appears in a disease called Stiff Man Syndrome and reveals itself with antibodies developed against Purkinje cells also reacts against GAD enzyme.   However, Stiff Man Syndrome is a very rare case and this accompanies in very less of patients with Type 1 Diabetes.

Clinic Forms of Type 1 Diabetes

• Appearance During Childhood

Type 1 Diabetes frequently appears during childhood and patients become insulin dependent since earlier periods of life.  The underlying cause under this case which appears during early period is insulin and GAD antibodies.  It is known that mothers of many patients have Type 1 Diabetes.  It has been shown that these babies have these antibodies through transmission from mother during intrauterine period.  Although these antibodies which are transmitted via placenta from mother reduce gradually, they may be detected in blood of the baby during the first months of life.   These antibodies start to occur between 9^th month and 3^rd year in majority of the children with Type 1 Diabetes.

First antibodies occur against insulin in general.  Therefore, complete occurrence of Type 1 Diabetes with clinic findings is caused by deficiency in first phase insulin secretion.  Disruption of First Phase Insulin Secretion is directly proportional to severity and progression rate of the disease.

• Appearance During Adulthood – Latent Autoimmune Diabetes of Adults ( LADA)

Type 1 Diabetes may appear in any age.  The oldest patient diagnosed with Type 1 Diabetes in the literature is a 69 year old woman who was a mother of a child with Type 1 Diabetes.  Very strong GAD antibody level has been detected in this patient.  However, the disease has reminded latent for years.  First phase insulin secretion is under first percentile when she was diagnosed first.

Many studies conducted shows that 5 to 30% of patients monitored with diagnosis of Type 2 Diabetes have Type 1 Diabetes. If Type 1 Diabetes develops in an adult, it generally progresses slowly.  Patients with Type 1A Diabetes are about 10% of all patients with diabetes.  LADA patients are about 50% of all patients with Type 1 Diabetes.  Moreover, more than half of the patients with Type 1 Diabetes are adult Type 1 Diabetes (LADA) in Japan.

Most of the patients with LADA may be treated with diabetes drugs when they are diagnosed first.  However, these drugs loose their efficiencies after a short period and insulin treatment is started.  A small-scaled study performed in Japan has shown that early insulin treatment started when the disease is diagnosed preserves C-peptide levels for longer.