Recruiting nowPhase 4Interventional
What this study is about
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.
A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.
Basic eligibility
Age30 Years to 70 Years
SexAll
Healthy volunteersAccepted
ConditionDiabetes Mellitus, Type 2, Diabetes, Type 2 Diabetes, Pre Diabetes
Full registry criteria
Inclusion Criteria: Normal-Weight Diabetes (NWD) Group: 1. Age: 30 to 70 years old. 2. Diagnosis of Type 2 Diabetes (T2D): Based on a previous diagnosis or confirmed by laboratory testing at screening (A1c \> 5.7% or fasting glucose \> 100 mg/dL). 3. HbA1c Range: Between 5.7% and 8%, with a stable medication or lifestyle regimen for at least 3 months. 4. BMI: Between 19 and 24.9 kg/m². 5. Diabetes Medications: All diabetes medications are allowed, except insulin and pioglitazone. GLP-1 receptor agonists are permitted if the dose has been stable for 3 months. 6. Stable Body Weight: Body weight must have been stable (no more than 2 kg change) over the last 3 months. Normal-Weight Control (NWC) Group: 1. Age: 30 to 70 years old. 2. No Diagnosis of Diabetes: Fasting plasma glucose \< 100 mg/dL and A1c \< 5.7%, with no history of glucose-lowering medications. 3. BMI: Between 19 and 24.9 kg/m². 4. Stable Body Weight: No more than 2 kg change over the past 3 months. - Exclusion Criteria: 1. Pregnancy or Lactation: Women who are pregnant, planning to become pregnant, or breastfeeding are excluded due to potential risks to the fetus or infant. 2. Prior Use of Pioglitazone: Participants who have previously used pioglitazone are excluded to avoid confounding effects of prior drug exposure. 3. Unstable Body Weight: Individuals with a body weight change of more than 2 kg in the last 3 months are excluded to ensure stable metabolic conditions. 4. Liver or Kidney Disease: Participants with significant liver disease (ALT \> 3x upper limit of normal) or renal disease (creatinine \> 1.5 mg/dL) are excluded due to potential safety risks. 5. Congestive Heart Failure or Fluid Overload History: These conditions are exclusionary due to the risk of fluid retention with pioglitazone. 6. Uncontrolled Hypertension: Blood pressure \> 160/90 mmHg excludes participants due to increased cardiovascular risk. 7. Active Cancer: Individuals with a diagnosis of cancer in the past 3 years (except for skin cancer) are excluded. 8. Chronic Inflammatory Diseases: Excluded due to potential effects on metabolic measurements. 9. Use of Weight Loss Medications: Those currently taking weight loss medications are excluded to prevent confounding effects on body weight and metabolic function. 10. Bariatric Surgery or Liposuction History: Participants who have had weight-loss surgeries or liposuction are excluded due to alterations in fat tissue and metabolic profiles. 11. Insulin Use: Participants using insulin are excluded to focus on non-insulin-dependent diabetes. 12. Active Psychiatric Disease or Eating Disorders: Individuals with these conditions are excluded due to potential impacts on study compliance and data integrity. 13. Substance Abuse: Participants with a history of substance abuse are excluded for similar reasons. \-
Treatments and study arms
Insulin resistance testing
Procedure
Steady state Plasma Glucose test
OGTT
Procedure
Will collect 5 blood draws during the test to measure insulin secretion
Fat biopsy
Procedure
Needle biopsy to gather a sample of abdominal subcutaneous fat
DXA scan
Radiation
Whole body DXA scan
MRI
Procedure
Abdominal MRI
1H-MRS
Procedure
Spectroscopy of the abdominal region
Tirzepatide
Drug
16 weeks started at 2.5mg/week and increased to 5mg/week dose
Pioglitazone
Drug
16 weeks at a 45mg/day dose
Primary outcomes
Insulin resistance in normal weight women with diabetes compared to those with no diabetesBaseline measures comparison between the groupsInsulin 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.
Adipocyte function in women with normal weight diabetes as compared with those without diabetesBaseline comparisonsAdipocyte function will be measured as percent small adipocytes and peak diameter adipocytes from the fat biopsies.
Fat storage in women with normal weight diabetes compared to those without diabetesBaseline comparisons between the groupsFat 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.
