Prevention of Clinical Onset of Type 1 Diabetes in High Risk First Degree Relatives

Inclusion Criteria: * Sibling/offspring of a Type 1 diabetic patient * in good general condition * age 5-39 years * fasting plasma glucose \<126 mg/dL AND an OGTT that is non-diabetic by 1997 ADA criteria (33): 1. Normal glycemia: * fasting plasma glucose \< 110 mg/dL and * 2 hour plasma glucose \< 140 mg/dL 2. Impaired Fasting Glucose (IFG): * fasting plasma glucose 110-125 mg/dL and * 2 hour plasma glucose \< 140 mg/dL 3. Impaired Glucose Tolerance (IGT): * fasting plasma glucose \<110 mg/dL and * 2 hour plasma glucose 140-199 mg/dL * at least positive for IA-2-A * absence of a protective DQ genotype: A4-B2/X or X/Y or X/X where X = A2-B3.3, A1-B1.9, A1-B1.2, A4-B3.1, A2-B2 or A4.23-B3.1 Y = A1-B1.1, A1-B2, A1-B1.AZH, A3-B2, A3-B3.1, A3-B3.3, A3-B4, A4-B4, A4.23-B4, A4-B3.2, A3-B1.1, A4-B3.3, A4-B1.1 or A4.23-B2 (32) * cooperative and reliable subject (age ≥ 14 yrs) / parents (age \< 14 yrs) giving informed consent by signature; the patient/parents should be informed in sufficient detail on the content and procedure of the protocol, indicating potential risks of insulin therapy; early intervention with metabolically active insulin treatment should be identified as a clinical trial. Both parents should sign and agree with the protocol procedure. Exclusion Criteria: * diabetes by 1997 ADA criteria (33): * fasting plasma glucose ≥ 126 mg/dL, or * 2 hour plasma glucose ≥ 200 mg/dL * donation of blood during the study or within one month prior to screening * pregnancy or lactation in women * use of inadequate anticonception by female patients of childbearing potential * use of illicit drugs or overconsumption of alcohol (\> 3 beers/day) or history of drug or alcohol abuse * being legally incapacitated, having significant emotional problems at the time of the study, or having a history of psychiatric disorders * having received antidepressant medications during the last 6 months * treatment with immune modulating or diabetogenic medication (such as corticosteroids) * presently participating in another clinical study or having done so during the last 12 months * history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient