Effect of a Basal/Pre-Meal Insulin Strategy (Detemir/Aspart) on Insulin Secretion and Action in Type 2 Diabetes
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Long-acting bedtime insulin detemir (Levemir); Insulin detemir and pre-meal insulin aspart.
Intervention description: This group will receive Insulin detemir. Insulin detemir is given at bedtime aiming at a fasting plasma glucose between 80-100 mg/dl.; 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.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Type 2 diabetes mellitus; Insulin therapy; Detemir (Levemir); Aspart (Novolog); Hepatic steatosis

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.
    

Eligibility 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).