Hyperglycaemia (Diabetic)
Conditions
Brief summary
To investigate whether longer-term improvement of glycemic control in poorly controlled diabetes patients with a 12-week intensified insulin treatment regimen will lead to decreased polyol pathway activity.
Detailed description
Polyol pathway activity will decrease in diabetic individuals who undergo intensification of their insulin treatment regimens as reflected by lower baseline brain intracellular fructose levels and higher intracellular glutathione levels. Furthermore, following longer-term improved glycemic control, patients may also have down-regulation of the pathway as reflected by decreased production of intracellular fructose in response to hyperglycemic clamp.
Interventions
DRUGInsulin
Insulin regimens will be adjusted on a weekly basis as needed to achieve a target blood glucose level.
BEHAVIORALexercise
Exercise in accordance to the guidelines established by the American Diabetes Association.
DIETARY_SUPPLEMENTDietary counseling
Dietary counseling in accordance to the guidelines established by the American Diabetes Association.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 15 Type 2 DM subjects with HbA1C \> 7.5% * 15 Type 1 DM subjects with HbA1C \> 7.5% * Age 18-60 * BMI ≥18 kg/m2 * Weight ≤ 285 pounds
Exclusion criteria
* Creatinine \> 1.5 mg/dL, Hgb \< 10 mg/dL, ALT \> 2.5 X ULN, * untreated thyroid disease, * uncontrolled hypertension, * known neurological disorders, * untreated psychiatric disorders, * malignancy, * bleeding disorders, * current or recent steroid use in last 3 months, * illicit drug use; * for women: pregnancy, actively seeking pregnancy, or breastfeeding; inability to enter * MRI/MRS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c Levels | Baseline and 12 weeks | HbA1c levels measured by MRS scanning during a hyperglycaemic clamp. Result reported is the mean decrease in HbA1C. A decrease in HbA1c indicates improvement in brain glucose levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gluthathione | 0 weeks | baseline MRS scan to measure gluthathione |
| Plasma Glucose | 0 weeks | MRS scan to measure plasma glucose |
| Plasma Fructose | 0 weeks | MRS scan to measure plasma fructose |
| Plasma Insulin | 0 weeks | MRS scan to measure plasma insulin |
Other
| Measure | Time frame | Description |
|---|---|---|
| Optional Hyperglycemic Clamp | upon enrollment | Hyperglycemic clamp administered to measure glucose levels. Data represented is the number of participants the clamp was used on successfully. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Type 2 Diabetes Mellitus Subjects with type 2 diabetes on insulin.
Insulin: Insulin regimens will be adjusted on a weekly basis as needed to achieve a target blood glucose level.
exercise: Exercise in accordance to the guidelines established by the American Diabetes Association.
Dietary counseling: Dietary counseling in accordance to the guidelines established by the American Diabetes Association. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Type 2 Diabetes Mellitus |
|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 8.3 |
| BMI | 31.4 kilograms/meter square STANDARD_DEVIATION 6.1 |
| Duration of Diabetes | 10 years STANDARD_DEVIATION 8.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HbA1c | 84.1 mmol/mol STANDARD_DEVIATION 16.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
| Weight | 85 kilograms STANDARD_DEVIATION 21.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Change in HbA1c Levels
HbA1c levels measured by MRS scanning during a hyperglycaemic clamp. Result reported is the mean decrease in HbA1C. A decrease in HbA1c indicates improvement in brain glucose levels.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Type 2 Diabetes Mellitus | Change in HbA1c Levels | 24.3 mmol/mol | Standard Deviation 15.3 |
p-value: 0.006Regression, Linear
Secondary
Gluthathione
baseline MRS scan to measure gluthathione
Time frame: 0 weeks
Population: Data for this outcome not collected.
Secondary
Gluthathione
MRS scan to measure gluthathione
Time frame: 12 weeks
Population: Data for this outcome not collected.
Secondary
Plasma Fructose
MRS scan to measure plasma fructose
Time frame: 0 weeks
Population: Data for this outcome not collected.
Secondary
Plasma Fructose
MRS scan to measure plasma fructose
Time frame: 12 weeks
Population: Data for this outcome not collected.
Secondary
Plasma Glucose
MRS scan to measure plasma glucose
Time frame: 0 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Type 2 Diabetes Mellitus | Plasma Glucose | 1.07 mmol/l | Standard Deviation 0.23 |
Secondary
Plasma Glucose
MRS scan to measure plasma glucose
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Type 2 Diabetes Mellitus | Plasma Glucose | 0.88 mmol/l | Standard Deviation 0.35 |
p-value: 0.266Mixed Models Analysis
Secondary
Plasma Insulin
MRS scan to measure plasma insulin
Time frame: 0 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Type 2 Diabetes Mellitus | Plasma Insulin | 31 μU/ml | Standard Deviation 26 |
p-value: 0.2Mixed Models Analysis
Secondary
Plasma Insulin
MRS scan to measure plasma insulin
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Type 2 Diabetes Mellitus | Plasma Insulin | 38 μU/ml | Standard Deviation 29 |
p-value: 0.25Mixed Models Analysis
Other Pre-specified
Optional Hyperglycemic Clamp
Hyperglycemic clamp administered to measure glucose levels. Data represented is the number of participants the clamp was used on successfully.
Time frame: upon enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Type 2 Diabetes Mellitus | Optional Hyperglycemic Clamp | 8 participants |