Effect of a Basal/Pre-Meal Insulin Strategy (Detemir/Aspart) on Insulin Secretion and Action in Type 2 Diabetes

• Status: Completed
• Trial end date: 2010-02-01
• Target enrollment: 0
• Participant gender: All

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.

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

Details

• Lead Sponsor: University of Florida
• Collaborators: Novo Nordisk A/S; VA Office of Research and Development
• Treatments: Insulin; Insulin Aspart; Insulin degludec, insulin aspart drug combination; Insulin Detemir; Insulin, Globin Zinc; Insulin, Long-Acting

Criteria

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).