Uncovering the 'ORIGINS' of Diabetes

Study Overview
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Brief Summary
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This is a study to identify different subtypes of type 2 diabetes. The investigators will look for information at the molecular level, which may lead to personalized diagnosis and therapies.

Detailed Description
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Type 2 diabetes mellitus (T2DM) is approaching epidemic prevalence in the US adult population (over 1 in 10 of all US adults over 20). Diabetes is diagnosed based on fasting hyperglycemia, oral glucose intolerance or markers of hyperglycemia such as HbA1c. However, we now recognize that diabetes is a heterogeneous disorder. With the existing overly simplistic diagnostic criteria, treatment failure rates are high for virtually every agent currently in the drug arsenal - including insulin. In the late 1990's oncologists pioneered the use of high-throughput molecular technologies, such as transcriptome profiling and more recently metabolomics to identify discrete sub-classes of cancers that cannot be distinguished histologically or by a small number of biochemical markers. That effort rapidly accelerated the pace of scientific discovery and quickly led to the development of personalized cancer therapeutics. We believe that those cancer efforts provide a roadmap for biomarker discovery and personalized therapy in diabetes. molecular phenotyping (profiling the metabolome, transcriptome, and epigenome) with advanced bioinformatics analysis will identify discrete subtypes of diabetes - ushering in a new era of personalized diagnosis and therapy in diabetes.

Official Title
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Uncovering the 'ORIGINS' of Diabetes

Conditions
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Type 2 Diabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 HbA1C < 8.0% * You have not gained or lost more than 3 kg or 6.6 pounds in the last 8 weeks You have not lost more than 10% of your heaviest body weight in your lifetime BMI < 25 kg/m2 or > 30 kg/m2 Women: more than 1 year post-partum Have diabetes and are able to maintain accurate and reliable home glucose monitoring logs Exclusion Criteria: Treatment with more than 2 of the following: metformin (Fortamet, Glucophage, Glumetza, Riomet), sulfonylureas (Glucotrol, Diabeta, Glynase, Micronase), Glucagon-like peptide-1 analogs (Byetta) and/or Dipeptidyl peptidase IV inhibitors (Januvia, Onglyza) Treatment with long acting Glucagon-like peptide-1 agonists within the last 3 months (i.e. exenatide once weekly) Treatment with thiazolidinediones (TZDs) (i.e. Avandia, Actos, Rezulin) within the last 3 months Known, untreated thyroid disease or abnormal thyroid function blood test.* Known diagnosis of liver disease (except NASH) or elevated liver function blood test Known diagnosis of kidney disease or elevated kidney function blood test Uncontrolled high blood pressure (BP > 140 systolic or > 90 diastolic) Start of or changes in oral contraceptives or hormone replacement therapy within the last 3 months Use of drugs or alcohol (> 3 drinks per day) within the last 5 years. Uncontrolled psychiatric disease that would interfere with study participation. History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable) History of organ transplant History of heart attack within the last 6 months Current treatment with blood thinners or antiplatelet medications that cannot be safely stopped for testing procedures Current anemia History of HIV, active Hepatitis B or C, or Tuberculosis Presence of clinically significant abnormalities on electrocardiogram. Current smokers (smoking any nicotine or non-nicotine product within the past 3 months) Use of any medications known to influence glucose, fat and/or energy metabolism within the last 3 months (e.g., growth hormone therapy, glucocorticoids [steroids], etc.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-Diabetic Lean Athletes<br>Athletes with a Body Mass Index (BMI) less than or equal to 25 kg/m2. | |
| Non-Diabetic Lean No Diabetes History<br>Adults with a BMI < 25 kg/m2 and no family history of diabetes | |
| Non-Diabetic Lean Yes Diabetes History<br>Adults with a BMI < 25 kg/m2 and family history of diabetes | |
| Non-Diabetic Obese<br>Adults with BMI greater than or equal to 30 kg/m2. | |
| Non-Diabetic Obese Female PCOS<br>Female adults with BMI > 30 kg/m2 and Polycystic Ovarian Syndrome (PCOS). | |
| Diabetic No Medication<br>Have diabetes and currently receiving no medication or early treatment with one medication. Some participants receiving insulin may also be included in this study | |
| Diabetic GAD Ab+<br>Have diabetes with Latent Autoimmune Diabetes in Adults (LADA). | |
| Diabetic With NASH<br>Have diabetes with Nonalcoholic Steatohepatitis (NASH), which is chronic liver disease with fat in the liver, inflammation, and damage not associated with drinking alcohol. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perform 'deep' clinical and molecular phenotyping of 360 adults- Diabetic and Non-Diabetic | Phenotyping will include whole body composition (DEXA), substrate metabolism, classic diabetes phenotypes, and detailed molecular phenotyping of circulating mononuclear cells/ plasma, muscle and adipose tissue. | up to Day 9 |