Normal-weight Diabetes: Adipocyte-directed Therapy With Pioglitazone or Tirzepatide

Who can take part

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. \-

Registry changes

No changes recorded since the trial was added.