Insulin Effects on Cardiac Function in Patients With Diabetes Mellitus
Condition: Diabetes Mellitus; Ventricular Dysfunction
MeSH terms: Ventricular Dysfunction; Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

Summary: 
      Our investigation studies the role of acute insulin administration on the diabetic heart, its
      corresponding effective blood-insulin level and the time-course applicability of insulin in a
      routine clinical setting.

      A case series of six male (48.1 ± 4.9 y/o) patients with controlled diabetes (HbA1c of 6.6 ±
      0.3%, disease duration of 14.4 ± 6.7 yr). Each subject was evaluated for glucose homeostatic,
      hemodynamic and echocardiographic systolic and diastolic parameters at baseline and following
      two successive insulin-load steps of a euglycemic hyperinsulinemic clamp study, each 2 h in
      duration. Results are presented as a mean ± SEM and analysed using the student's t-test.
    

Detailed description: 
      Patients:

      Six male diabetic (five type 2 and one type 1) patients, 30-65 year old, with an established
      diagnosis of diabetes mellitus for ≥2 years, who were free of significant valvular heart
      disease, atrial arrhythmia or cardiac pacing comprised the study population. Patients'
      characteristics are summarized in table 1.

      Each patient served as his or her own control. The study protocol was approved by the ethics
      committee at Rambam Medical Center, Haifa, Israel. Prior to the study, patients gave written
      informed consent after receiving a detailed explanation as to the purpose of the study, the
      technique, its side effects and the study protocol.

      Patients were studied within a clinical research facility at the Rambam Medical Center,
      Haifa, Israel. Baseline evaluation was conducted at 8:00 am after 12 h of fasting, followed
      by two hyperinsulinemic euglycemic clamp (EHC) steps (2 h each step); The following vital
      signs were monitored during the study protocol: manual heart rate, systolic blood pressure
      (SBP), diastolic blood pressure (DBP) and baseline 12-lead electrocardiogram (ECG) recording.
      Glucose consumption rates against changing insulin levels were measured by the EHC technique.
      Cardiac function parameters were measured in the last 10 min of each step by tissue Doppler
      echocardiography. Results are presented as a mean ± SEM.

      Clamp technique:

      Each patient underwent an EHC study according to the protocol described previously, and
      implemented in our institute. Baseline measurements of blood insulin and glucose levels were
      collected. Thereafter, two insulin loads were initiated. The blood glucose level was kept
      near euglycemia (90 ± 5 mg/dl) throughout 2 h period of each insulin load step. Intravenous
      (iv) insulin loads were administered by 1- and 10-mU/kg·min at steps 1 and 2 of insulin
      loading (Lispro Insulin, Eli Lilly, France), respectively. Dexstrose in water 50% (DW50) was
      infused at variable infusion rates, titrated to maintain euglycemia. Concomitant saline 0.45%
      was used to dilute the DW50 in order to prevent hypertonicity-induced irritation of the
      cannuled vein. During the baseline period, saline 0.45% infusion rates were 0.75 ml/min to
      keep the iv cannule open. Every patient was given a chance to urinate before step 2.

      Glucose and insulin homeostatic parameters of the study group were compared to those of
      healthy controls we studied earlier.

      Cardiac function assessment:

      Transthoracic echocardiography was performed by a qualified echocardiographer using a General
      Electric Vivid 3 machine (Tirat HaCarmel, Israel). Parameters were assessed as the mean of
      three consecutive heart beats.

      Systolic echocardiographic parameters:

      LV fractional shortening (LVFS) derived from end diastolic and end systolic LV dimensions; LV
      ejection fraction (LVEF) derived from end diastolic and end systolic LV volumes.

      Diastolic echocardiographic parameters:

        1. Mitral valve diastolic flow parameters by pulse wave Doppler: E wave, represents early
           diastolic filling; A wave, represents late diastolic filling concomitant with the atrial
           kick, E/A ratio and E wave deceleration time (DT).

        2. Tissue Doppler-derived velocities of the mitral annulus: E' represents early diastolic
           velocity synchronous to the mitral inflow E wave, measured close to the interventricular
           septum (E' medial) and lateral wall (E' lateral); E' mean, derived from E' lateral and
           E' medial. A' represents late diastolic velocity to the synchronous mitral inflow A
           wave, measured close to the septum (A' medial) and lateral wall (A' lateral). A' mean is
           derived from A' lat. and A' med. A' reflects mitral annulus movement during atrial
           contraction. The E to E' ratio represents diastolic LV compliance.

      Results are presented as mean ± SEM and analyzed using the student's t-test. Statistical
      significance considered when p value less than 0.05.
    

Intervention name(s): Insulin LISPRO intravenous loading
Intervention type(s): Drug
Intervention description(s): intravenous infusion of insulin Lispro.
Other intervention name(s): Humalog Insulin
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Lispro
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment