Molecular and Clinical Profile of Diabetes Mellitus and Its Complications
Molecular and Clinical Profile of Diabetes Mellitus and Its Complications
Background:

 - Family and twin studies have suggested that genetic factors influence approximately 50
 percent of a person's susceptibility to type 2 diabetes. Recently, some of the genes involved
 in the development of type 2 diabetes have been identified, in large part by genome-wide
 association studies. Certain risk factors for type 2 diabetes, such as obesity and insulin
 resistance, are highly inheritable, as are diabetic complications such as diabetes-related
 eye and kidney disorders. However, few genes associated or linked with diabetes risk factors
 or complications have been conclusively identified, and more research is needed to study
 specific genetic factors associated with these aspects of diabetes.

 Objectives:

 - To identify and characterize genetic variants associated with type 2 diabetes, its risk
 factors, and its complications.

 Eligibility:

 - Individuals at least 18 years of age who are not pregnant or nursing mothers at the start
 of the study.

 Design:

 -  All participants will provide information about family history, ethnicity and ethnic
 background, occupation, behavioral risk factors, and other data as requested by the
 researchers.

 -  In addition to a general health history, participants will provide specific information
 about diabetes history, with particular emphasis on date of diagnosis, symptoms,
 initiation of insulin therapy, complications, and current medications.

 -  Testing procedures will be different for individuals with and without diabetes. Those
 without diabetes will have an oral glucose tolerance test, while those with diabetes
 will be examined for diabetic complications.

 -  Other tests during the study will include the following:

 -  Physical examination with measurements of height and weight, waist circumference, blood
 pressure, and other tests for individuals who have been diagnosed with diabetes

 -  Glucose tolerance test for those who have not been classified as having diabetes

 -  Retinal photographs

 -  Electrocardiograms

 -  Hepatic Ultrasound

 -  Blood and urine tests

 -  Depending on the results of the examination and laboratory findings, participants may be
 asked to return to the clinic for supplemental interviews, physical examinations, or
 blood tests, or to arrange referrals for medical evaluation and treatment.

 -  Participants who have diabetes will be asked to return for yearly follow-up visits.
 Participants who do not have diabetes at the initial examination will be asked to return
 for follow-up visits every 2 years.
Genetic factors play an important role in diabetes mellitus, its risk factors and
 complications, but most of the specific genetic determinants remain unidentified. The
 molecular pathways by which diabetes-susceptibility genes influence risk for diabetes and
 related conditions are also largely unknown. This project will seek to identify, and quantify
 the effects of, the genetic determinants of type 2 diabetes, its risk factors and
 complications in a multiethnic sample. Diabetes and glycemic status will be assessed from
 clinical interviews, an oral glucose tolerance test and glycated hemoglobin. Insulin
 sensitivity and insulin secretion will be assessed from indices derived from the oral glucose
 tolerance test. Other potential risk factors for type 2 diabetes (e.g., obesity) and its
 complications (e.g., retinopathy, nephropathy) will be measured. DNA will be collected and
 analyzed to identify genetic variants associated with or linked to diabetes or other traits.
 Studies of gene transcription, protein expression and metabolic profiling will be performed,
 and the resulting patterns will be analyzed for their relationships with diabetes, related
 traits and variants in diabetes susceptibility genes. Individuals will be studied
 longitudinally to determine if gene transcription, protein expression and metabolic profiles
 predict development of diabetes or its complications. These studies will help to determine
 the molecular pathways between genetic variants and susceptibility to type 2 diabetes and its
 complications.
-  INCLUSION CRITERIA:

 -  Women and Men

 -  Individuals of any race (recruitment will focus on American Indians and Mexican
 Americans)

 -  18 years and older

 EXCLUSION CRITERIA:

 -  Pregnant Women

 -  Children under 18 years old