Insulin Effects on Cardiac Function in Patients With Diabetes Mellitus

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* Diabetes mellitus duration of 2 years and over.

Exclusion Criteria:

* Previous cardiac disease: valvular, Pacing, Arrhythmias, Primary Cardiomyopathy.