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.

Study Overview

• Status: Completed
• Conditions: Diabetes; Malnutrition; Diabetes
• Intervention / Treatment: Drug: Pancreatic Clamp

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 100

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from the community and outpatient practices in India. Diabetes subjects must meet the following criteria: Age 19-45 years, diabetes duration at least one year, negative GAD antibodies, >1.0pmol/l C-peptide response to meal, stable and moderate glycemic control (HbA1c 8-11%), no pancreatic calcification, and not suffering from complications. Subjects will be otherwise in good health. Non diabetic subjects (ND): BMI 16-22.5kg/m2 (lean ND) and BMI 24.5-29.5 (obese ND), Age 19-45 years and in general good health, and no family diabetic history. Subjects will be recruited through various means of community outreach.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lean Diabetes Subjects; N=20 subjects with BMI 16-22.5 kg/m2, with a history of low birth weight and malnutrition documented on at least one occasion. Will undergo pancreatic clamp.	Drug: Pancreatic Clamp; We are not performing any interventions; we are only characterizing participants using tests. The hormones that we are administering are not a treatment but are typically used in context of routine care.; Other Names: Clamp
Type 2 Diabetes Mellitus Subjects; N=13 subjects with BMI 22.5-27 kg/m2. Will undergo pancreatic clamp	Drug: Pancreatic Clamp; We are not performing any interventions; we are only characterizing participants using tests. The hormones that we are administering are not a treatment but are typically used in context of routine care.; Other Names: Clamp
Type 1 Diabetes Mellitus Subjects; N=15 subjects with BMI 16-22.5 kg/m2. Will undergo pancreatic clamp	Drug: Pancreatic Clamp; We are not performing any interventions; we are only characterizing participants using tests. The hormones that we are administering are not a treatment but are typically used in context of routine care.; Other Names: Clamp
Lean Nondiabetic Subjects; N=16 nondiabetic with BMI 16-22.5 kg/m2 subjects 19-45 years of age and in general good health, taking no medications, with normal glucose tolerance and no family history of diabetes. These subjects will be similar in age, ethnicity and BMI with the lean DM group, and will be recruited through various means of community outreach, including notices in shops and newspapers. Will undergo pancreatic clamp
Obese Nondiabetic Subjects; N=9 nondiabetic with BMI 16-22.5 kg/m2 subjects 19-45 years of age and in general good health, taking no medications, with normal glucose tolerance and no family history of diabetes. These subjects will be similar in age, ethnicity and BMI with the Type 2 diabetes Mellitus group, and will be recruited through various means of community outreach, including notices in shops and newspapers. Will undergo pancreatic clamp

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endogenous Glucose Production	Measurements of Endogenous glucose production in each group during the low phase of the pancreatic clamp study.	120 min to 240 min
Rate of Glucose Disposal (RD).	Peripheral Insulin Sensitivity (RD) measured by the change in Glucose Rates of Disappearance in each group during the low phase of the pancreatic clamp study.	240 min to 360 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Secretion	Insulin secretion assessed during a 120min mixed-meal tolerance test (MMTT). Insulin secretion was calculated from the C-peptide deconvolution studies with measurements mg/kg/min using the trapezoidal method.	0 min to 120 min

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Meredith Hawkins, Albert Einstein College Of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2010
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Estimate): December 6, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Diabetes; Malnutrition
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Nutrition Disorders; Diabetes Mellitus; Malnutrition
• Other Study ID Numbers: 2013-2191; R01DK079974 (U.S. NIH Grant/Contract); R01DK069861 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No