Genetics of Diabetes: What do we know and what can we do?
Genetics of Diabetes: What do we know and what can we do? Toni I. Pollin, MS, PhD Associate Professor of Medicine and Epidemiology & Public Health Div...
Genetics of Diabetes: What do we know and what can we do? Toni I. Pollin, MS, PhD Associate Professor of Medicine and Epidemiology & Public Health Division of Endocrinology, Diabetes & Nutrition University of Maryland School of Medicine
March 13, 2012
Overview
Why genetics? DNA Mutations Inheritance Genetics of diabetes subtypes Genetic testing/ services/ resources
Molecular medicine comes to the rescue Targeted therapy turns life around for child with neonatal diabetes On Monday, August 14, Lilly Jaffe, a six-year-old North Shore suburban girl who had been diagnosed with type 1 diabetes when she was one month old, checked into the Clinical Research Center at the University of Chicago Medical Center. On Friday, August 18, she checked out, starting to make her own insulin, well on her way to insulin independence and ready to get in a few days of beach time in Michigan before starting first grade.
Type 1 Diabetes (T1DM) Type 2 Diabetes (T2DM) Other specific types (known etiology) Gestational diabetes mellitus (GDM, ~4% of pregnancies)
Type 2
*ADA = American Diabetes Association WHO = World Health Organization
Type 1
Other specific types
Diabetes Genetics “The genetics of diabetes is a confused subject in which almost every possible mode of inheritance has been proposed. It is apparent, however, that no simple genetic hypothesis is compatible with the data gathered from large groups of diabetics. One reason . . . may be that diabetes is not homogeneous but rather consists of a number of different diseases in which carbohydrate intolerance is the common factor.” R. B. Tattersall (1974). Mild familial diabetes with dominant inheritance. QJM 170:339
% Risk
Type 1 Diabetes: Familial Aggregation 100 90 80 70 60 50 40 30 20 10 0 Gen. Pop. MZ Twin
DZ Twin
Sibling
Genetics of Type 1 (Autoimmune) Diabetes Insulin (Chr 11) 10%
HLA (Chr 6) 45%
(IDDM2)
’s w Co Other 45%
(IDDM 3 – 24)
(IDDM1) Genes
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Environmental Factors
Type 1 Diabetes
Non-HLA Genetics of T1DM 2009
Concannon et al (2009), NEJM 360 (16)
% Risk
Type 2 Diabetes: Familial Aggregation 100 90 80 70 60 50 40 30 20 10 0 Gen. Pop. MZ Twin
DZ Twin
Sibling
Genetics of Type 2 Diabetes J11 N 2 7L KC PP F C ARG T
Type 2 Diabetes
Genes
Obesity Medication
Physical Activity
Diet
Complications
Courtesy J.C. Florez 2010
Fajans et al, NEJM 2001
Maturity Onset Diabetes of the Young (MODY) Transcription Factor/ Glucokinase Diabetes
Definition:
Obesity not required Several different single gene forms
