The etiological fraction (EF) values indicated that HLA D/DR alleles were the best markers for IDDM, the observed EF for HLA-DR4 in diabetes was as high as 0.70.
We conclude that increased fasting proinsulin levels precede abnormalities of insulin secretion, and are an early indication of minor B-cell damage in these twins irrespective of their risk of developing diabetes.
We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr.
The results suggest that newborn children have high proinsulin and low C-peptide levels unrelated to heredity of diabetes and that the previously described elevated proinsulin level observed in older first degree relatives of diabetic subjects occurs later in life.
In diabetes, insulin secretion is either completely absent (insulin-dependent diabetes mellitus [IDDM]) or inappropriately regulated (non-insulin-dependent diabetes mellitus [NIDDM]).
Since after 5 years only one of the children has developed IDDM, it can be concluded autoimmune reactions towards endocrine pancreas and insulin may occur in many children without the development of manifest diabetes.
In the case of IDDM, one must convince clinical diabetologists, patients, and their families that immunoprevention of the disease will only be achieved if research on both prediction and immunotherapy proceeds hand in hand: prediction programs are difficult to run without proposing access to preventive therapy, and the search for therapy cannot be successful without access to prediabetics or patients with preclinical diabetes and they can only be identified in prediction clinics.
Loss of ganciclovir sensitivity by exclusion of thymidine kinase gene from transplanted proinsulin-producing fibroblasts as a gene therapy model for diabetes.
While it appeared that common genetic traits characterize diabetes regardless of the subtype (1a or 1b), certain features differentiate the two forms of IDDM.
The clinical presentation of MIDD which can be IDDM-like or NIDDM-like, its frequency of occurrence, possible pathogenic mechanisms and the contribution of other mitochondrial DNA mutations to the development of diabetes will be discussed.
However, one difficulty involved in gene therapy for diabetes is a control of insulin/proinsulin production by the cells transfected with insulin cDNA.
This finding provides a plausible explanation for the dominant protective effect of class III VNTRs, and suggests that diabetes susceptibility and resistance associated with IDDM2 may derive from the VNTR influence on INS transcription in the thymus.
A total of 1440 patients (IDDM and NIDDM) of North European extraction attending two hospital diabetes services were initially screened by questionnaire.