Type2 Diabetes
Conditions
Brief summary
Cross-sectional study to investigate subjects at different stages of type 2 diabetes development with expected stratification of pancreatic islet mass. Non-diabetic individuals were assigned as control. The primary outcome was the \[11C\]5-hydroxy-tryptophan uptake and retention in the pancreas as a surrogate marker for the endogenous islet mass.
Interventions
RADIATIONPositron emission tomography with the tracer [11C]5-hydroxy-tryptophan
Estimation of islet mass by PET using the tracer \[11C\]5-hydroxy-tryptophan
Sponsors
Per-Ola Carlsson
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Type 2 diabetes fulfilling criteria for the four different study groups, or healthy volunteers
Exclusion criteria
* Ongoing pregnancy * Renal failure (GFR\<60 ml/min) * Magnetic metal parts in the body * Ongoing treatment with selective serotonin receptor inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| [11C]5-hydroxy-tryptophan Uptake in the Pancreas | Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release | Uptake of tracer with correlation to functional measurement with glucose-potentiated arginine stimulation of insulin release |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pancreatic Perfusion | Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release | Uptake of radioactive water with correlation to functional measurement with glucose-potentiated arginine stimulation of insulin release |
| Pancreatic Volume | Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release | — |
| Pancreatic Fat Content | Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release | — |
| Hepatic Fat Content | Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Control Healthy control
Positron emission tomography with the tracer \[11C\]5-hydroxy-tryptophan: Estimation of islet mass by PET using the tracer \[11C\]5-hydroxy-tryptophan | 8 |
| Obese With Oral Antidiabetic Drugs BMI\>30, Type 2 diabetes treated with oral antidiabetic drugs
Positron emission tomography with the tracer \[11C\]5-hydroxy-tryptophan: Estimation of islet mass by PET using the tracer \[11C\]5-hydroxy-tryptophan | 7 |
| Obese, Treated With Oral Antidiabetic Drugs + Insulin BMI\>30, Type 2 diabetes treated with oral antidiabetic drugs + insulin
Positron emission tomography with the tracer \[11C\]5-hydroxy-tryptophan: Estimation of islet mass by PET using the tracer \[11C\]5-hydroxy-tryptophan | 9 |
| Normal Weight, Treated With Oral Antidiabetic Drugs BMI 20-26. Type 2 diabetes treated with oral antidiabetic drugs
Positron emission tomography with the tracer \[11C\]5-hydroxy-tryptophan: Estimation of islet mass by PET using the tracer \[11C\]5-hydroxy-tryptophan | 7 |
| Normal Weight, Treated With Oral Antidiabetic Drugs + Insulin BMI 20-26. Type 2 diabetes treated with oral antidiabetic drugs + insulin
Positron emission tomography with the tracer \[11C\]5-hydroxy-tryptophan: Estimation of islet mass by PET using the tracer \[11C\]5-hydroxy-tryptophan | 8 |
| Total | 39 |
Baseline characteristics
| Characteristic | Healthy Control | Obese With Oral Antidiabetic Drugs | Obese, Treated With Oral Antidiabetic Drugs + Insulin | Normal Weight, Treated With Oral Antidiabetic Drugs | Normal Weight, Treated With Oral Antidiabetic Drugs + Insulin | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 6.2 | 56.7 years STANDARD_DEVIATION 10.1 | 61.8 years STANDARD_DEVIATION 7.2 | 60.3 years STANDARD_DEVIATION 10.8 | 66.3 years STANDARD_DEVIATION 5.4 | 61.8 years STANDARD_DEVIATION 7.8 |
| Body mass index | 28.1 kg/m^2 STANDARD_DEVIATION 3.4 | 33.3 kg/m^2 STANDARD_DEVIATION 2.6 | 33.2 kg/m^2 STANDARD_DEVIATION 3.6 | 25.1 kg/m^2 STANDARD_DEVIATION 2.4 | 25.8 kg/m^2 STANDARD_DEVIATION 1.4 | 29.2 kg/m^2 STANDARD_DEVIATION 2.7 |
| Race and Ethnicity Not Collected | — | — | — | — | — | 0 Participants |
| Region of Enrollment Sweden | 8 participants | 7 participants | 9 participants | 7 participants | 8 participants | 39 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 7 Participants | 5 Participants | 4 Participants | 25 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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 7 | 0 / 9 | 0 / 7 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 9 | 0 / 7 | 0 / 8 |
Outcome results
Primary
[11C]5-hydroxy-tryptophan Uptake in the Pancreas
Uptake of tracer with correlation to functional measurement with glucose-potentiated arginine stimulation of insulin release
Time frame: Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release
Population: Two healthy controls and two individuals in the group Normal weight, treated with oral antidiabetic drugs + insulin were not included in the analysis because of not being able to participate in the PET scan, pancreatic anatomical abnormality or insufficient image quality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Control | [11C]5-hydroxy-tryptophan Uptake in the Pancreas | 0.17 % of injected dose | Standard Deviation 0.04 |
| Obese With Oral Antidiabetic Drugs | [11C]5-hydroxy-tryptophan Uptake in the Pancreas | 0.21 % of injected dose | Standard Deviation 0.1 |
| Obese, Treated With Oral Antidiabetic Drugs + Insulin | [11C]5-hydroxy-tryptophan Uptake in the Pancreas | 0.20 % of injected dose | Standard Deviation 0.07 |
| Normal Weight, Treated With Oral Antidiabetic Drugs | [11C]5-hydroxy-tryptophan Uptake in the Pancreas | 0.23 % of injected dose | Standard Deviation 0.11 |
| Normal Weight, Treated With Oral Antidiabetic Drugs + Insulin | [11C]5-hydroxy-tryptophan Uptake in the Pancreas | 0.15 % of injected dose | Standard Deviation 0.14 |
p-value: 0.5875ANOVA
Secondary
Hepatic Fat Content
Time frame: Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release
Population: Some of the study participants were not included in the analysis because of not being able to participate in the MRI scan or insufficient image quality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Control | Hepatic Fat Content | 5.30 % of liver volume | Standard Deviation 3.15 |
| Obese With Oral Antidiabetic Drugs | Hepatic Fat Content | 14.40 % of liver volume | Standard Deviation 7.18 |
| Obese, Treated With Oral Antidiabetic Drugs + Insulin | Hepatic Fat Content | 13.42 % of liver volume | Standard Deviation 7.14 |
| Normal Weight, Treated With Oral Antidiabetic Drugs | Hepatic Fat Content | 5.50 % of liver volume | Standard Deviation 2.98 |
| Normal Weight, Treated With Oral Antidiabetic Drugs + Insulin | Hepatic Fat Content | 9.01 % of liver volume | Standard Deviation 4.55 |
p-value: 0.0048ANOVA
Secondary
Pancreatic Fat Content
Time frame: Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release
Population: Some of the study participants were not included in the analysis because of not being able to participate in the MRI scan, pancreatic anatomical abnormality or insufficient image quality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Control | Pancreatic Fat Content | 11.33 % of pancreatic volume | Standard Deviation 7.62 |
| Obese With Oral Antidiabetic Drugs | Pancreatic Fat Content | 11.54 % of pancreatic volume | Standard Deviation 10.3 |
| Obese, Treated With Oral Antidiabetic Drugs + Insulin | Pancreatic Fat Content | 8.75 % of pancreatic volume | Standard Deviation 2.97 |
| Normal Weight, Treated With Oral Antidiabetic Drugs | Pancreatic Fat Content | 9.58 % of pancreatic volume | Standard Deviation 9.37 |
| Normal Weight, Treated With Oral Antidiabetic Drugs + Insulin | Pancreatic Fat Content | 9.72 % of pancreatic volume | Standard Deviation 7.97 |
p-value: 0.9472ANOVA
Secondary
Pancreatic Perfusion
Uptake of radioactive water with correlation to functional measurement with glucose-potentiated arginine stimulation of insulin release
Time frame: Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release
Population: Some individuals in the study population were not included in the analysis because of not being able to participate in the PET scan, pancreatic anatomical abnormality or insufficient image quality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Control | Pancreatic Perfusion | 84.37 ml/min | Standard Deviation 18.17 |
| Obese With Oral Antidiabetic Drugs | Pancreatic Perfusion | 134.90 ml/min | Standard Deviation 47.84 |
| Obese, Treated With Oral Antidiabetic Drugs + Insulin | Pancreatic Perfusion | 107.72 ml/min | Standard Deviation 32.91 |
| Normal Weight, Treated With Oral Antidiabetic Drugs | Pancreatic Perfusion | 72.20 ml/min | Standard Deviation 18.88 |
| Normal Weight, Treated With Oral Antidiabetic Drugs + Insulin | Pancreatic Perfusion | 59.82 ml/min | Standard Deviation 51.16 |
p-value: 0.0065ANOVA
Secondary
Pancreatic Volume
Time frame: Within two weeks after functional measurement with glucose potentiated arginine stimulation of insulin release
Population: Some participants were not included in the analysis because of not being able to participate in the imaging, pancreatic anatomical abnormality or insufficient image quality.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Control | Pancreatic Volume | 67.68 cm^3 | Standard Deviation 8.9 |
| Obese With Oral Antidiabetic Drugs | Pancreatic Volume | 88.54 cm^3 | Standard Deviation 23.99 |
| Obese, Treated With Oral Antidiabetic Drugs + Insulin | Pancreatic Volume | 98.96 cm^3 | Standard Deviation 23.85 |
| Normal Weight, Treated With Oral Antidiabetic Drugs | Pancreatic Volume | 64.1 cm^3 | Standard Deviation 13.46 |
| Normal Weight, Treated With Oral Antidiabetic Drugs + Insulin | Pancreatic Volume | 53.39 cm^3 | Standard Deviation 41.17 |
p-value: 0.0072ANOVA