This study is to investigate how adipocyte (fat cell) function and fat distribution differ between individuals with normal-weight type 2 diabetes (NWD), those with overweight type 2 diabetes (OWD), and normal-weight controls without diabetes (NWC). The study will assess whether adipocyte-directed therapies, specifically pioglitazone and tirzepatide, can improve insulin resistance, adipocyte function, and fat distribution in individuals with NWD. By analyzing the biological mechanisms underlying adipocyte dysfunction, the study aims to provide insights into novel treatment strategies for improving metabolic health in normal-weight individuals with type 2 diabetes.
The investigators aim to learn how adipocyte dysfunction and disordered fat distribution contribute to the development of type 2 diabetes in normal-weight individuals. The investigators hope to determine whether adipocyte-directed therapies, such as pioglitazone and tirzepatide, can improve insulin sensitivity, fat distribution, and metabolic health in this population. This study is important because most diabetes research focuses on overweight or obese individuals, and very little is known about how diabetes affects those with normal body weight. Understanding the unique biology of normal-weight diabetes could lead to more personalized and effective treatment strategies, filling a gap in diabetes care for a group that can be overlooked in clinical research.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
104
Steady state Plasma Glucose test
Will collect 5 blood draws during the test to measure insulin secretion
Needle biopsy to gather a sample of abdominal subcutaneous fat
Whole body DXA scan
Abdominal MRI
Spectroscopy of the abdominal region
16 weeks started at 2.5mg/week and increased to 5mg/week dose
16 weeks at a 45mg/day dose
Stanford University
Palo Alto, California, United States
RECRUITINGStanford University, Clinical and Translational Research Unit (CTRU)
Stanford, California, United States
NOT_YET_RECRUITINGInsulin resistance in normal weight women with diabetes compared to those with no diabetes
Insulin resistance will be measured by a Steady State Plasma Glucose test (SSPG). Results will be measured by glucose levels at steady state in mg/dL.
Time frame: Baseline measures comparison between the groups
Adipocyte function in women with normal weight diabetes as compared with those without diabetes
Adipocyte function will be measured as percent small adipocytes and peak diameter adipocytes from the fat biopsies.
Time frame: Baseline comparisons
Fat storage in women with normal weight diabetes compared to those without diabetes
Fat storage will be measured by MRI. Quantification of subcutaneous and visceral abdominal fat will be obtained by MRI using a fat-water imaging sequence (parameters: IDEAL-IQ: 3D GRE, 160x160 matrix, 6 echoes, 4 degree flip angle, minimum TR = 7.3 ms, 28 slices, 10 mm slice thickness.
Time frame: Baseline comparisons between the groups
Effect of adipose-directed therapy pioglitazone on HbA1c in both men and women with normal weight diabetes
Hemoglobin A1C measures will be compared baseline to end of 16 weeks of intervention with pioglitazone.
Time frame: 16 weeks
Effect of pioglitazone in insulin resistance in both men and women.
SSPG test results will be compared from baseline to end of pioglitazone intervention. Results will be measured by glucose levels at steady state in mg/dL.
Time frame: 16 weeks
Fat storage in men with normal weight diabetes (NWD) compared to those without diabetes (NWC).
Fat storage will be measured by MRI. Quantification of subcutaneous and visceral abdominal fat will be obtained by MRI using a fat-water imaging sequence (parameters: IDEAL-IQ: 3D GRE, 160x160 matrix, 6 echoes, 4 degree flip angle, minimum TR = 7.3 ms, 28 slices, 10 mm slice thickness.
Time frame: Baseline comparisons between the groups
Adipocyte function in men with normal weight diabetes as compared with those without diabetes
Adipocyte function as measured by percent small adipocytes and peak diameter adipocytes from the fat biopsies.
Time frame: Baseline comparisons
Insulin resistance in normal weight men with diabetes compared to those with no diabetes
Insulin resistance will be measured by a Steady State Plasma Glucose test (SSPG). Results will be measured by glucose levels at steady state in mg/dL.
Time frame: Baseline measures comparison between the groups
Insulin secretion in men and women with normal weight diabetes compared to those without diabetes
A five-point, three-hour OGTT will be done after overnight fast for calculation of insulin secretion using c-peptide deconvolution, and disposition index calculated by dividing this value by SSPG.
Time frame: Baseline measured compared between the groups
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.