Type 2 Diabetes
Conditions
Keywords
Type 2 diabetes mellitus, Insulin therapy, Detemir (Levemir), Aspart (Novolog), Hepatic steatosis
Brief summary
The optimal insulin therapy in T2DM is controversial and its impact on nonalcoholic fatty liver disease (NAFLD) has not been systematically studied before, and in particular, never when using the new insulin formulations detemir (Levemir®) or aspart (Novolog®). This study is to determine the effect on hepatic steatosis and insulin secretion/action of lowering the fasting plasma glucose (FPG) to target with once daily basal insulin detemir alone or combining insulin detemir with premeal insulin aspart in patients with uncontrolled type 2 diabetes mellitus (T2DM). In the first 3 months the investigators will optimize metabolic control in all patients with intensive basal (bedtime) detemir insulin aiming at a normal fasting plasma glucose. After this treatment period, patients will be randomized in the second 3 months in a 2:1 ratio to insulin detemir or detemir plus aspart. The investigators propose that insulin will improve day-long glycemic control and A1c, reduce hepatic steatosis (NAFLD) (primary endpoint) and insulin secretion/sensitivity being well tolerated while causing minimal weight gain and hypoglycemia (secondary endpoints). The study will allow to assess if there is an additional benefit of adding pre-meal rapid-acting insulin aspart to basal insulin to these endpoints.
Detailed description
The control of hyperglycemia in T2DM ameliorates the metabolic abnormalities of T2DM but whether this improves hepatic steatosis has not been examined carefully with the use of improved insulin formulations (long-acting insulins detemir or glargine, alone or combined with pre-meal short-acting insulins). Most research studies have focused on glycemic control without a careful examination to the underlying mechanisms, with some of these studies reporting on improved hepatic and muscle insulin sensitivity. The investigators have found in the laboratory that intensified insulin therapy in T2DM is associated with enhanced glycogen synthase fractional velocity and non-oxidative glucose disposal, but with no improvement at the level of insulin-stimulated insulin receptor tyrosine phosphorylation, hexokinase II mRNA or enzyme function, phosphatidylinositol 3-kinase (PI 3-kinase) associated with IRS-1, or Akt phosphorylation. Our work did not examine hepatic steatosis or insulin secretion/action, nor was designed to distinguish between the relative contribution of reduced glucotoxicity on insulin sensitivity vs. beta-cell function from pre-meal regular vs. NPH insulin. It is possible that the beneficial effects of insulin therapy of reduced plasma glucose and FFA concentrations may be offset by excessive hyperinsulinemia and weight gain from the use of insulins with suboptimal pharmacokinetics compared to the newer insulin formulations. Insulin detemir is an insulin analogue approved in 2005 by the FDA. It is a long-acting insulin analogue that has shown to be more predictable in achieving therapeutic plasma insulin levels compared to NPH insulin. This is associated with several clinical benefits, such as better glycemic control, less hypoglycemia, modest weight gain and better quality of life for patients with type 2 diabetes. If gluco-lipotoxicity likely play an important role in the development of hepatic steatosis (NAFLD) in T2DM the investigators speculate that if reversed by a strategy of basal long-acting insulin (insulin detemir) alone, or combined with a rapid-acting analog (pre-meal insulin aspart) may be a good strategy for the treatment of T2DM.
Interventions
DRUGLong-acting bedtime insulin detemir (Levemir)
This group will receive Insulin detemir. Insulin detemir is given at bedtime aiming at a fasting plasma glucose between 80-100 mg/dl.
DRUGInsulin detemir and pre-meal insulin aspart.
This group will receive Insulin detemir plus aspart. The group will start with Insulin detemir at bedtime. Then in three months they will Insulin aspart before breakfast, lunch and dinner.
Sponsors
VA Office of Research and Development
Novo Nordisk A/S
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
To participate patients must: 1. Be able to communicate meaningfully with the Investigator and be legally competent to provide written informed consent. 2. Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period. 3. Age range of 18 to 70 years (inclusive). 4. Patients must have been on a stable dose of allowed chronic medications for two months prior to entering the double-blind treatment period. 5. All participants must have the following laboratory values: * Hemoglobin ≥ 12 g/dl in males or ≥ 11 g/dl in females * Serum creatinine ≤ 1.5 mg/dl * AST (SGOT) ≤ 2.5 times upper limit of normal * ALT (SGPT) ≤ 2.5 times upper limit of normal * Alkaline phosphatase ≤ 2.5 times upper limit of normal
Exclusion criteria
Patients will be excluded if any of the following criteria are present: 1. Individuals with type 1 diabetes or type 2 diabetes and a FPG ≥ 300 mg/dl. 2. Subjects on sulfonylureas, metformin and/or TZDs unless the dose has been stable for at least 2 months prior to study entry. 3. Patients on any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on stable doses of such agents for the past two months before entry into the study. Patients may be taking stable doses of estrogens or other hormonal replacement therapy if the patient has been on these agents for the prior two months. Patients taking systemic glucocorticoids will be excluded. 4. Past (within 1 year) or current history of alcohol abuse. 5. Patients will be excluded if there is a history of clinically significant heart disease (New York Heart Classification greater than grade II), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) or chronic renal failure (serum creatinine greater than 1.5 mg/dl).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Steatosis | 3 and 6 months | Hepatic steatosis measured by proton magnetic resonance spectroscopy (1H-MRS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Secretion | 3 and 6 months. | Derived from the hyperglycemic clamp (Plasma C-peptide change vs. pretreatment in first and second phase). |
| Intramyocellular (IMCL) by Magnetic Resonance Imaging and Spectroscopy (MRS). | 3 and 6 months. | Percent intramyocellular (IMCL) by magnetic resonance imaging and spectroscopy (MRS). |
| Plasma Lipid Concentration. | 3 and 6 months. | Fasting plasma lipid concentration on day of admission at 3 and 6 months. |
| Change in Anthropometric Measure (Body Weight). | 3 and 6 months. | Change in anthropometric measure (body weight) done on day of admission at 3 and 6 months. |
| Number of Hypoglycemic Events | 3 and 6 months | Defined as hypoglycemia \<40 mg/dl and/or requiring medical assistance during the trial. |
| Metabolic Control as Measured by the A1c | 3 and 6 months | — |
| Metabolic Control as Measured by the Postprandial Plasma Glucose During the Day-long Plasma Glucose Profile. | 3 and 6 months | — |
| Advanced Lipid Testing | 3 and 6 months | Change in lipoprotein particle number was determined using NMR. |
| Change in Anthropometric Measure (Body Mass Index [BMI]). | 3 and 6 months. | Change in anthropometric measure (body mass index \[BMI\]) done on day of admission at 3 and 6 months. |
| Percent Change From Baseline in Vascular Inflammatory Markers | 3 and 6 months | Inflammatory Markers include: Adiponectin, MMP-9, E-selectin, sICAM, and sVCAM |
| Metabolic Control as Measured by the Fasting Plasma Glucose Concentration | 3 and 6 months | — |
Countries
United States
Participant flow
Recruitment details
Clinical Research Unit
Pre-assignment details
All participants started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio to either Insulin detemir only arm or to Insulin detemir plus aspart.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Detemir Only Patients with uncontrolled T2DM are treated with insulin detemir for 6 months
Long-acting bedtime insulin detemir (Levemir) : Insulin detemir is given at bedtime aiming at a fasting plasma glucose between 80-100 mg/dl. | 8 |
| Insulin Detemir Plus Aspart After baseline evaluations (admission #1) insulin detemir will be given at bedtime and titrated to achieve a fasting plasma glucose between 80-100 mg/dl. After 3 months patients will be admitted to assess the metabolic effects of intervention. After this, insulin aspart will be added before breakfast, lunch and dinner titrated to normalize the postprandial plasma glucose. After another 3 months patients are readmitted and all study procedures repeated as during admissions #1 and #2.
Insulin detemir and pre-meal insulin aspart. : Insulin detemir at bedtime. Insulin aspart before breakfast, lunch and dinner. | 22 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized Period (Months 3 to 6) | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Insulin Detemir Plus Aspart | Insulin Detemir Only | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 8 Participants | 30 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 8 | 50 years STANDARD_DEVIATION 8 | 57 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 22 participants | 8 participants | 30 participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 19 Participants | 8 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 22 |
| serious Total, serious adverse events | 0 / 30 | 0 / 22 |
Outcome results
Primary
Hepatic Steatosis
Hepatic steatosis measured by proton magnetic resonance spectroscopy (1H-MRS).
Time frame: 3 and 6 months
Population: In six patients liver MRS was not possible due to claustrophobia, metal parts, or too large for MRI scanner. N=30 participants in the Insulin detemir x 3 months, N=8 participants in the Insulin Detemir alone and 22 in the Detemir Plus Aspart at 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Hepatic Steatosis | Month 3 | 6.7 percentage of liver fat | Standard Deviation 4.4 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Hepatic Steatosis | Month 6 | 8.4 percentage of liver fat | Standard Deviation 7.2 |
| Insulin Detemir Plus Aspart | Hepatic Steatosis | Month 3 | NA percentage of liver fat | — |
| Insulin Detemir Plus Aspart | Hepatic Steatosis | Month 6 | 5.9 percentage of liver fat | Standard Deviation 4.2 |
Comparison: Baseline versus 3 monthsp-value: 0.03ANOVA
Secondary
Advanced Lipid Testing
Change in lipoprotein particle number was determined using NMR.
Time frame: 3 and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Advanced Lipid Testing | VLDL particles (3 months) | -15 Change in number of particles (nmol/L) | Standard Deviation 39 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Advanced Lipid Testing | VLDL particles (6 months) | -5 Change in number of particles (nmol/L) | Standard Deviation 38 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Advanced Lipid Testing | LDL particles (3 months) | -100 Change in number of particles (nmol/L) | Standard Deviation 313 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Advanced Lipid Testing | LDL particles (6 months) | 128 Change in number of particles (nmol/L) | Standard Deviation 206 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Advanced Lipid Testing | HDL particles (3 months) | 0 Change in number of particles (nmol/L) | Standard Deviation 3 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Advanced Lipid Testing | HDL particles (6 months) | 2 Change in number of particles (nmol/L) | Standard Deviation 4 |
| Insulin Detemir Plus Aspart | Advanced Lipid Testing | HDL particles (3 months) | NA Change in number of particles (nmol/L) | — |
| Insulin Detemir Plus Aspart | Advanced Lipid Testing | VLDL particles (3 months) | NA Change in number of particles (nmol/L) | — |
| Insulin Detemir Plus Aspart | Advanced Lipid Testing | LDL particles (6 months) | 85 Change in number of particles (nmol/L) | Standard Deviation 209 |
| Insulin Detemir Plus Aspart | Advanced Lipid Testing | VLDL particles (6 months) | -2 Change in number of particles (nmol/L) | Standard Deviation 31 |
| Insulin Detemir Plus Aspart | Advanced Lipid Testing | HDL particles (6 months) | 1 Change in number of particles (nmol/L) | Standard Deviation 4 |
| Insulin Detemir Plus Aspart | Advanced Lipid Testing | LDL particles (3 months) | NA Change in number of particles (nmol/L) | — |
Secondary
Change in Anthropometric Measure (Body Mass Index [BMI]).
Change in anthropometric measure (body mass index \[BMI\]) done on day of admission at 3 and 6 months.
Time frame: 3 and 6 months.
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 for first 3 months and N=28 for 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Anthropometric Measure (Body Mass Index [BMI]). | 3-month body mass index | -0.4 Change from baseline (Kg/m2) | Standard Deviation 2.7 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Anthropometric Measure (Body Mass Index [BMI]). | 6-month body mass index | 0.3 Change from baseline (Kg/m2) | Standard Deviation 0.6 |
| Insulin Detemir Plus Aspart | Change in Anthropometric Measure (Body Mass Index [BMI]). | 3-month body mass index | NA Change from baseline (Kg/m2) | — |
| Insulin Detemir Plus Aspart | Change in Anthropometric Measure (Body Mass Index [BMI]). | 6-month body mass index | 0.2 Change from baseline (Kg/m2) | Standard Deviation 1.2 |
Secondary
Change in Anthropometric Measure (Body Weight).
Change in anthropometric measure (body weight) done on day of admission at 3 and 6 months.
Time frame: 3 and 6 months.
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 for first 3 months and N=28 for 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Anthropometric Measure (Body Weight). | 3-month total body weight | -0.8 Change from baseline (Kg) | Standard Deviation 7.3 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Anthropometric Measure (Body Weight). | 6-month total body weight | 0.8 Change from baseline (Kg) | Standard Deviation 1.9 |
| Insulin Detemir Plus Aspart | Change in Anthropometric Measure (Body Weight). | 3-month total body weight | NA Change from baseline (Kg) | — |
| Insulin Detemir Plus Aspart | Change in Anthropometric Measure (Body Weight). | 6-month total body weight | 0.3 Change from baseline (Kg) | Standard Deviation 3.5 |
Secondary
Change in Insulin Secretion
Derived from the hyperglycemic clamp (Plasma C-peptide change vs. pretreatment in first and second phase).
Time frame: 3 and 6 months.
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 at 3 months and N=28 at 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Insulin Secretion | 3-month C-peptide level increase in first phase | 0.5 ng/ml | Standard Deviation 1.3 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Insulin Secretion | 3-month C-peptide level increase in second phase | 1.6 ng/ml | Standard Deviation 2.5 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Insulin Secretion | 6-month C-peptide level increase in first phase | -0.1 ng/ml | Standard Deviation 0.9 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Change in Insulin Secretion | 6-month C-peptide level increase in second phase | 0.6 ng/ml | Standard Deviation 2 |
| Insulin Detemir Plus Aspart | Change in Insulin Secretion | 6-month C-peptide level increase in second phase | 0.2 ng/ml | Standard Deviation 2.3 |
| Insulin Detemir Plus Aspart | Change in Insulin Secretion | 3-month C-peptide level increase in first phase | NA ng/ml | — |
| Insulin Detemir Plus Aspart | Change in Insulin Secretion | 6-month C-peptide level increase in first phase | 0.2 ng/ml | Standard Deviation 1.4 |
| Insulin Detemir Plus Aspart | Change in Insulin Secretion | 3-month C-peptide level increase in second phase | NA ng/ml | — |
Secondary
Intramyocellular (IMCL) by Magnetic Resonance Imaging and Spectroscopy (MRS).
Percent intramyocellular (IMCL) by magnetic resonance imaging and spectroscopy (MRS).
Time frame: 3 and 6 months.
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 for first 3 months and N=28 for 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Intramyocellular (IMCL) by Magnetic Resonance Imaging and Spectroscopy (MRS). | 3-month intramyocellular triglycerides | 0.63 % of intramyocellular triglyceride | Standard Deviation 0.62 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Intramyocellular (IMCL) by Magnetic Resonance Imaging and Spectroscopy (MRS). | 6-month intramyocellular triglycerides | 1.05 % of intramyocellular triglyceride | Standard Deviation 0.18 |
| Insulin Detemir Plus Aspart | Intramyocellular (IMCL) by Magnetic Resonance Imaging and Spectroscopy (MRS). | 3-month intramyocellular triglycerides | NA % of intramyocellular triglyceride | — |
| Insulin Detemir Plus Aspart | Intramyocellular (IMCL) by Magnetic Resonance Imaging and Spectroscopy (MRS). | 6-month intramyocellular triglycerides | 0.49 % of intramyocellular triglyceride | Standard Deviation 0.47 |
Secondary
Metabolic Control as Measured by the A1c
Time frame: 3 and 6 months
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Metabolic Control as Measured by the A1c | 3-month - A1c | 7.4 percentage of A1c | Standard Deviation 1.4 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Metabolic Control as Measured by the A1c | 6-month - A1c | 6.9 percentage of A1c | Standard Deviation 0.5 |
| Insulin Detemir Plus Aspart | Metabolic Control as Measured by the A1c | 3-month - A1c | NA percentage of A1c | — |
| Insulin Detemir Plus Aspart | Metabolic Control as Measured by the A1c | 6-month - A1c | 6.7 percentage of A1c | Standard Deviation 0.7 |
Secondary
Metabolic Control as Measured by the Fasting Plasma Glucose Concentration
Time frame: 3 and 6 months
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 for first 3 months and N=28 for 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Metabolic Control as Measured by the Fasting Plasma Glucose Concentration | 3-month - Fasting plasma glucose | 105 mg/dL | Standard Deviation 38 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Metabolic Control as Measured by the Fasting Plasma Glucose Concentration | 6-month - Fasting plasma glucose | 89 mg/dL | Standard Deviation 18 |
| Insulin Detemir Plus Aspart | Metabolic Control as Measured by the Fasting Plasma Glucose Concentration | 3-month - Fasting plasma glucose | NA mg/dL | — |
| Insulin Detemir Plus Aspart | Metabolic Control as Measured by the Fasting Plasma Glucose Concentration | 6-month - Fasting plasma glucose | 116 mg/dL | Standard Deviation 27 |
Secondary
Metabolic Control as Measured by the Postprandial Plasma Glucose During the Day-long Plasma Glucose Profile.
Time frame: 3 and 6 months
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 for first 3 months and N=28 for 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Metabolic Control as Measured by the Postprandial Plasma Glucose During the Day-long Plasma Glucose Profile. | 3-month - Day-long plasma glucose profile | 168 mg/dL | Standard Deviation 44 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Metabolic Control as Measured by the Postprandial Plasma Glucose During the Day-long Plasma Glucose Profile. | 6-month - Day-long plasma glucose profile | 153 mg/dL | Standard Deviation 38 |
| Insulin Detemir Plus Aspart | Metabolic Control as Measured by the Postprandial Plasma Glucose During the Day-long Plasma Glucose Profile. | 3-month - Day-long plasma glucose profile | NA mg/dL | — |
| Insulin Detemir Plus Aspart | Metabolic Control as Measured by the Postprandial Plasma Glucose During the Day-long Plasma Glucose Profile. | 6-month - Day-long plasma glucose profile | 170 mg/dL | Standard Deviation 48 |
Secondary
Number of Hypoglycemic Events
Defined as hypoglycemia \<40 mg/dl and/or requiring medical assistance during the trial.
Time frame: 3 and 6 months
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 for first 3 months and N=28 for 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Number of Hypoglycemic Events | 3-month rate of severe hypoglycemia | 0 Number of events |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Number of Hypoglycemic Events | 6-month rate of severe hypoglycemia | 0 Number of events |
| Insulin Detemir Plus Aspart | Number of Hypoglycemic Events | 3-month rate of severe hypoglycemia | NA Number of events |
| Insulin Detemir Plus Aspart | Number of Hypoglycemic Events | 6-month rate of severe hypoglycemia | 0 Number of events |
Secondary
Percent Change From Baseline in Vascular Inflammatory Markers
Inflammatory Markers include: Adiponectin, MMP-9, E-selectin, sICAM, and sVCAM
Time frame: 3 and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | Adiponectin (3 months) | 18 Percentage of change | Standard Deviation 63 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | Adiponectin (6 months) | 65 Percentage of change | Standard Deviation 71 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | MMP-9 (3 months) | 32 Percentage of change | Standard Deviation 59 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | MMP-9 (6 months) | 30 Percentage of change | Standard Deviation 115 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | E-selectin (3 months) | -6 Percentage of change | Standard Deviation 25 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | E-selectin (6 months) | 34 Percentage of change | Standard Deviation 34 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | sICAM (3 months) | -4 Percentage of change | Standard Deviation 22 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | sICAM (6 months) | 2 Percentage of change | Standard Deviation 12 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | sVCAM (3 months) | 1 Percentage of change | Standard Deviation 8 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Percent Change From Baseline in Vascular Inflammatory Markers | sVCAM (6 months) | 14 Percentage of change | Standard Deviation 13 |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | sICAM (6 months) | -1 Percentage of change | Standard Deviation 15 |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | Adiponectin (3 months) | NA Percentage of change | — |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | E-selectin (6 months) | 19 Percentage of change | Standard Deviation 29 |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | Adiponectin (6 months) | 5 Percentage of change | Standard Deviation 30 |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | sVCAM (6 months) | 7 Percentage of change | Standard Deviation 11 |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | MMP-9 (3 months) | NA Percentage of change | — |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | sICAM (3 months) | NA Percentage of change | — |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | MMP-9 (6 months) | 49 Percentage of change | Standard Deviation 73 |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | sVCAM (3 months) | NA Percentage of change | — |
| Insulin Detemir Plus Aspart | Percent Change From Baseline in Vascular Inflammatory Markers | E-selectin (3 months) | NA Percentage of change | — |
Secondary
Plasma Lipid Concentration.
Fasting plasma lipid concentration on day of admission at 3 and 6 months.
Time frame: 3 and 6 months.
Population: All participants were started in the Insulin detemir only arm. At week 12 the participants were randomized in a 2:1 ratio between the two arms. N=30 for first 3 months and N=28 for 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 6-month triglycerides | 150 mg/dL | Standard Deviation 66 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 3-month triglycerides | 154 mg/dL | Standard Deviation 76 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 3-month total cholesterol | 136 mg/dL | Standard Deviation 36 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 3-month HDL-C | 33 mg/dL | Standard Deviation 8 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 6-month HDL-C | 31 mg/dL | Standard Deviation 5 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 6-month total cholesterol | 147 mg/dL | Standard Deviation 31 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 3-month LDL-cholesterol | 76 mg/dL | Standard Deviation 27 |
| Insulin Detemir x 3 Months (All Pts Had Liver MRS) | Plasma Lipid Concentration. | 6-month LDL-cholesterol | 86 mg/dL | Standard Deviation 29 |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 3-month LDL-cholesterol | NA mg/dL | — |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 6-month triglycerides | 144 mg/dL | Standard Deviation 62 |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 6-month HDL-C | 33 mg/dL | Standard Deviation 7 |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 3-month total cholesterol | NA mg/dL | — |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 6-month LDL-cholesterol | 80 mg/dL | Standard Deviation 28 |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 3-month triglycerides | NA mg/dL | — |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 3-month HDL-C | NA mg/dL | — |
| Insulin Detemir Plus Aspart | Plasma Lipid Concentration. | 6-month total cholesterol | 145 mg/dL | Standard Deviation 37 |