Uncovering the 'ORIGINS' of Diabetes

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.

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.)