Diabetes, Malnutrition; Diabetes
Conditions
Keywords
Diabetes, Malnutrition
Brief summary
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.
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.
Interventions
DRUGPancreatic 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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Albert Einstein College of Medicine
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endogenous Glucose Production | 120 min to 240 min | Measurements of Endogenous glucose production in each group during the low phase of the pancreatic clamp study. |
| Rate of Glucose Disposal (RD). | 240 min to 360 min | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Secretion | 0 min to 120 min | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 20 |
| Type 2 Diabetes Mellitus Subjects N=13 subjects with BMI 22.5-27 kg/m2. Will undergo pancreatic clamp
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. | 13 |
| Type 1 Diabetes Mellitus Subjects N=15 subjects with BMI 16-22.5 kg/m2. Will undergo pancreatic clamp
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. | 15 |
| 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 | 16 |
| 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 | 9 |
| Total | 73 |
Baseline characteristics
| Characteristic | Lean Diabetes Subjects | Type 2 Diabetes Mellitus Subjects | Type 1 Diabetes Mellitus Subjects | Lean Nondiabetic Subjects | Obese Nondiabetic Subjects | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 41.5 years | 36.2 years | 28.0 years | 26.0 years | 41.0 years | 33.5 years |
| BMI | 18.3 kg/m^2 STANDARD_DEVIATION 0.2 | 26.0 kg/m^2 STANDARD_DEVIATION 0.3 | 20.5 kg/m^2 STANDARD_DEVIATION 0.4 | 19.1 kg/m^2 STANDARD_DEVIATION 0.6 | 25.4 kg/m^2 STANDARD_DEVIATION 0.35 | 22.1 kg/m^2 STANDARD_DEVIATION 0.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 13 Participants | 15 Participants | 16 Participants | 9 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 13 Participants | 15 Participants | 16 Participants | 9 Participants | 73 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 20 participants | 13 participants | 15 participants | 16 participants | 9 participants | 73 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 13 Participants | 15 Participants | 16 Participants | 9 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 20 | 0 / 15 | 0 / 16 | 0 / 9 |
| other Total, other adverse events | 0 / 13 | 0 / 20 | 0 / 15 | 0 / 16 | 0 / 9 |
| serious Total, serious adverse events | 0 / 13 | 0 / 20 | 0 / 15 | 0 / 16 | 0 / 9 |
Outcome results
Primary
Endogenous Glucose Production
Measurements of Endogenous glucose production in each group during the low phase of the pancreatic clamp study.
Time frame: 120 min to 240 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lean Diabetes Subjects | Endogenous Glucose Production | 0.5 mg/kg/min | Standard Error 0.1 |
| Type 2 Diabetes Mellitus Subjects | Endogenous Glucose Production | 0.84 mg/kg/min | Standard Error 0.1 |
| Type 1 Diabetes Mellitus Subjects | Endogenous Glucose Production | 0.6 mg/kg/min | Standard Error 0.1 |
| Lean Nondiabetic Subjects | Endogenous Glucose Production | 0.4 mg/kg/min | Standard Error 0.1 |
| Obese Nondiabetic Subjects | Endogenous Glucose Production | 0.7 mg/kg/min | Standard Error 0.1 |
Primary
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.
Time frame: 240 min to 360 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lean Diabetes Subjects | Rate of Glucose Disposal (RD). | 10.1 mg/kg/min | Standard Error 0.7 |
| Type 2 Diabetes Mellitus Subjects | Rate of Glucose Disposal (RD). | 4.2 mg/kg/min | Standard Error 0.5 |
| Type 1 Diabetes Mellitus Subjects | Rate of Glucose Disposal (RD). | 8.5 mg/kg/min | Standard Error 0.4 |
| Lean Nondiabetic Subjects | Rate of Glucose Disposal (RD). | 10.8 mg/kg/min | Standard Error 0.7 |
| Obese Nondiabetic Subjects | Rate of Glucose Disposal (RD). | 7.6 mg/kg/min | Standard Error 0.5 |
Secondary
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.
Time frame: 0 min to 120 min
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean Diabetes Subjects | Insulin Secretion | 383.0 mg/kg/min |
| Type 2 Diabetes Mellitus Subjects | Insulin Secretion | 839.5 mg/kg/min |
| Type 1 Diabetes Mellitus Subjects | Insulin Secretion | 0.09 mg/kg/min |
| Lean Nondiabetic Subjects | Insulin Secretion | 591.1 mg/kg/min |
| Obese Nondiabetic Subjects | Insulin Secretion | 1277.0 mg/kg/min |