Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes

• Status: Not yet recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The majority of people with type 2 diabetes (T2D) are overweight, and while weight gain is a major contributor to diabetes, a minority of patients with T2D are not overweight or obese. The reasons why lean or normal body weight individuals develop T2D (lean-T2D) are not yet understood. T2D occurs when the body does not produce enough insulin, or becomes less sensitive to its effects. Insulin acts like a key to allow sugar into cells and if someone is overweight that key works less well. Recent research suggests that T2D in lean people should be considered a different disease from the diabetes associated with obesity and the main problem in lean-T2D patients may be a reduced capacity of insulin secretion. However, some researchers argue that many seemingly thin people carry more fat than muscle, making them trim on the outside, but fat on the inside, and they are in fact not truly lean. This implies that just like overweight diabetics, lean diabetics also have high resistance to insulin. The main aim of this research is to better understand the main driver of T2D in lean individuals, as this will determine how best to treat these individuals.

There are many different types of drugs for treating T2D. Liraglutide improves insulin secretion capacity of the pancreas. Pioglitazone reduces resistance to insulin action. The investigators will compare the actions of these diabetes drugs on the blood supply and the heart's energy levels in lean-T2D and obese-T2D patients. This will allow the investigators to determine the ideal treatment strategies for improving cardiovascular health in lean-T2D patients, and better understand the role of impaired insulin secretory capacity, insulin resistance and excess fat deposition specifically in this group.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Leeds
• Treatments: Liraglutide; Pioglitazone

Criteria

Inclusion Criteria:

Lean cohort

1. Men and women>18 years of age;

2. Normal body weight (18.5 ≤ BMI ≤25 kg/m2);

3. T2D patients can be on treatment with oral glucose lowering therapies, and if they are, they must have been on these treatments for at least 12 weeks prior to screening;

4. 6.5≤HBA1c≤10% at screening;

5. Agreement to maintain prior diet and exercise habits for the duration of the study.

Overweight cohort

1. Men and women>18 years of age;

2. Increased body weight (BMI >27 kg/m2);

3. T2D patients can be on treatment with oral glucose lowering therapies, and must have been on these treatments for at least 12 weeks prior to screening;

4. 6.5≤HBA1c≤10% at screening;

5. Agreement to maintain prior diet and exercise habits for the duration of the study.

Exclusion Criteria:

1. Any type of diabetes other than T2D;

2. Past history of significant CAD;

3. Known HF;

4. Significant renal impairment (eGFR<30ml/min/m2);

5. Participation in a clinical trial of an investigational medicinal product (CTIMP) in the preceding 12 weeks;

6. Known hypersensitivity to dobutamine or gadolinium or any other contra-indications to MRI;

7. Participants with obesity where their girth exceeds the scanner bore;

8. History of pancreatitis;

9. Any history of liver disease;

10. Patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2);

11. Prior or current use of thiazolidinediones (aka PPAR-γ agonists), fibrates, GLP-1RA or insulin;

12. Patients that are pregnant (female participants only);

13. Inflammatory bowel disease

14. Diabetic gastroparesis