Common Types of Juvenile Diabetes
Trends and Risk Factors for the Growth of Juvenile Type 2 Diabetes
Islet autoantibody assay and juvenile diabetes mellitus staging
HLA Class II Gene Polymorphisms and Juvenile Diabetes Typing
Obesity and Juvenile Diabetes Mellitus
Type 1A DM
Type 1B DM
Type 2 DM
MODY(maturity-onset diabetes of the young)1-5
Secondary and endocrine
Rare diabetic syndrome
Wolfram S
Prader-Willi S
Laurence-Moon-Biedle S
Leprechaunism S
Rabson-Mendenhall S
Mitochondrial diabetes (MCD)
A3243G mutation [Am J Hum Genet. 2003; 72:1005-1012 ]
T3271C transitional mutations [Pediatr Res. 2005; 58:258-262].
A1555G mutation [J Hum Genet. 2003;48:480-483 ]
Kearns Sayre syndrome (KSS) resulted from mtDNA deletions [Exp Clin Endocrinol Diabetes 2004; 112: 80-83 ]
Mitochondrial diabetes
mtDNA mutation
mtDNA deletion
Diabetes mellitus is one of the manifestations of many mitochondrial diseases (presenting with rare syndromes)
Juvenile diabetes mellitus typing confusion — Type 1b DM
The number of patients suitable for diagnosis of Type 1b DM or who can be classified as Type 1b DM continues to expand globally
The need to reclassify this group of patients into clinically relevant subtypes according to etiology
Fulminant type 1 DM, a recently discovered subtype of type 1 —- Type 1B?
Sudden onset with fulminant symptoms: significant hyperglycemia, severe DKA coma normal or near normal HbA1c
Negative islet autoantibodies (ICA, GADAb, IA-2Ab/ICA512, IAA)
Involvement of exocrine pancreas as well as pancreatic islets with elevated serum levels of pancreatic enzymes
Involvement of both genetic background-class II HLA genes-and viruses has been suggested.
Clinical features of fulminant type 1 diabetes
Hyperglycemic symptoms for an average of 4 days
High rate of prodromal symptoms —- flu-like and gastrointestinal symptoms
Near normal HbA1c despite severe hyperglycemia and DKA
Sometimes associated with pregnancy
Elevated pancreatic enzyme levels
Lack of C-peptide levels
Almost undetectable islet ß-cell autoantibodies
The presence of the above characteristics strongly indicates the diagnosis of fulminant type 1 diabetes.
Genomics of fulminant type 1 diabetes mellitus
In Japanese classical type 1 DM, DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 are the major HLA-DR-DQ susceptible haplotypes, and DRB1*1502-DQB1*0601 and DRB1*1501-DQB1*0602 are the protective genes.
Only DRB1*0405-DQB1*0401 pure haplotypes in Japanese may be associated with both burst type 1 and classical type 1DM
a different contribution of class II HLA in the mechanisms of beta cell damage between fulminant and “classic” type 1 diabetes
Ketosis-Prone Diabetes (KPD; type 1B ? )
KPD is a newly named heterogeneous syndrome.
The current classification of type 1B is not related to the long-term prognosis of the patient
Some require lifelong insulin therapy due to permanent severe ß-cell failure
others requiring only temporary insulin treatment due to partially preserved ß-cell function or reversible ß-cell defects
KPD
DKA is present in 25-40% of newly diagnosed children with juvenile diabetes in the United States
However, an increasing number of these patients have a family history of obesity and diabetes without autoimmune markers
Intensive treatment can restore ß-cell function and improve insulin sensitivity to the point where blood glucose approaches normal and insulin can be stopped for months or even years
It was first identified in African-American populations, but has been reported in other populations
This variant of type 2 diabetes referrs to as idiopathic type 1 diabetes, atypical diabetes, Flatbush diabetes, diabetes type 1.5 ,and more recently as ketosis-prone type 2 diabetes
In the West most juvenile diabetes is still diagnosed as type 1 DM, and only a minority of patients are diagnosed with type 2 DM
But this is changing, with a rapid increase in the prevalence of type 2 DM among white adolescents
Type 2 has long been the predominant type of DM among Asian adolescents
Austrian children under 15 years of age 1999-2001
529 cases of DM