Metabolic Characteristics of Lean Diabetes in Rural and Semi-urban India and in the United States

This purpose of this study is to define the metabolic characteristics of individuals with Lean Diabetes. We aim to determine whether differences in body composition, including any differences in lipid (fat) deposition, exist compared to individuals with either known forms of diabetes (eg, type 1 and type 2), or individuals without diabetes. Diabetes affects the ability of the body to process glucose (sugar). Therefore, we also plan to investigate the ability of the hormone insulin to regulate changes in glucose in these individuals. Developing a greater understanding of the features of this condition could have tremendous therapeutic benefit for these individuals.

India has the world's highest prevalence of diabetes, expected to rise to 80 million by 2030. This includes many patients with Lean Diabetes, which is a form of diabetes identified clinically by early onset, high insulin requirements, absence of other pancreatic disease, and low body mass index (typically ≤17 kg/m2) at presentation. Despite its prevalence, Lean Diabetes remains a relatively unknown disease that stirs conflicting opinions regarding its classification, diagnostic criteria, and pathogenesis.

In this study, the investigators will study individuals meeting the criteria for Lean Diabetes, Type 1 diabetes, Type 2 diabetes, and two group of participants without diabetes using a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Endogenous glucose production (a measure of the body's production of sugar) will also be measured. Participants will also have a fat biopsy, and will be given a mixed meal challenge which is a test that detects hyperglycemia and glucose intolerance.

The overall goal of this study is to define the metabolic characteristics of individuals with Lean Diabetes and to determine which differences exist compared to individuals with other known forms of diabetes or individuals without diabetes.

Eligibility Criteria:
Inclusion Criteria:

* Age 19-45 yr
* Diabetes duration at least one year (for the diabetes groups)
* BMI range: 16-22.5 kg/m2 (individuals with lean and type 1 diabetes and non-diabetic controls); 22.5-27 kg/m2 in individuals with type 2 diabetes
* Negative GAD antibodies
* Present (\>1.0pmol/l) C-peptide response to Sustacal challenge
* Stable and moderate-to-poor glycemic control (HbA1c greater than 8%)
* Able and willing to provide informed consent.

Exclusion Criteria:

* Mentally disabled persons
* Major psychiatric disorder on medication (excluding successfully treated depression)
* HIV/AIDS
* History of any cancer
* Alcohol or substance abuse or toxin exposure which could be associated with neuropathy
* Cushing's syndrome
* Pregnancy or breast-feeding
* Untreated or uncontrolled hypertension
* Any Chronic illness requiring medication
* History of bleeding disorder or with a prolonged PT or PTT
* Renal disease
* Liver impairment
* Prisoners