An abbreviated hyperinsulinemic-euglycemic clamp results in similar myocardial glucose utilization in both diabetic and non-diabetic patients with ischemic cardiomyopathy

Abstract

Background: Positron emission tomography (PET) with insulin-stimulated (18)F-2-deoxyglucose (FDG) uptake is the gold standard for myocardial viability. However, insulin stimulation is infrequently performed due to time and inconvenience. We therefore assessed the clinical applicability of an abbreviated hyperinsulinemic-euglycemic clamp.

Methods and results: Dynamic FDG PET was performed in 50 patients with ischemic cardiomyopathy (ejection fraction: .30 +/- .10) using an abbreviated hyperinsulinemic-euglycemic clamp with separate Non-Diabetic (n = 26) and Diabetic (n = 24) protocols (American Society of Nuclear Cardiology guidelines), and supplemental potassium. In regions with normal resting perfusion ((13)N-ammonia uptake >or=80% maximal segment), there were no differences in either maximal (Non-Diabetic: .60 +/- .20 vs Diabetic: .60 +/- .17 micromol/min/g, P = .93) or mean rates of myocardial glucose uptake (MGU) (Non-Diabetic: .52 +/- .18 vs Diabetic: .52 +/- .14 micromol/min/g, P = .63) between the protocols. Multivariate analysis showed that diastolic blood pressure alone (maximal MGU, r (2) = .20, P = .001) or with NYHA Heart Failure Class (mean MGU, r (2) = .25, P = .003) could account for some of the variability in normal-region MGU. Potassium supplementation safely attenuated the decline in plasma levels.

Conclusions: This abbreviated hyperinsulinemic-euglycemic clamp produced similar MGU values in normal resting myocardium in non-diabetic and diabetic subjects, which are no different than published rates with a standard insulin clamp. Thus, this abbreviated approach is sufficient to overcome myocardial insulin resistance.

Figure 1

Representative polar maps of NH₃ uptake and MGU using FDG imaging. A 17-segment model of the LV and computational software (MyoPC®) was used to determine segmental uptake of ¹³N-ammonia. Segments with uptake ≥80% of the maximal segment were identified (i.e., segments 1–8 in this example) and considered to have normal perfusion. Myocardial glucose uptake (MGU, μmol/min/g) was quantified for these segments by the method of Patlak and Blasberg. The average MGU values in these segments as well as the maximal segment were determined for each subject.

Figure 2

MGU by Patlak analysis in a representative subject. The polar tomograms from FDG PET illustrate both regional uptake (upper left image) and kinetic modeling by Patlak analysis (upper right image). The lower graph confirms the linear relationship expected between the normalized myocardial activity and normalized blood-pool integral (Time). The net influx constant, K_i = K/R_c, which accounts for myocardial FDG uptake and phosphorylation, is determined from the slope (K) of the linear portion of this relationship, divided by a recovery coefficient (R_c) accounting for partial volume losses in the myocardium. Data points are labeled by frame number (1–20). S, Interventricular septum; P, posterior wall; L, lateral wall.

Figure 3

MGU values in normally perfused segments of patients with ischemic cardiomyopathy. The maximal (left graph; Non-Diabetic: .60 ± .20 μmol/min/g, Diabetic: .60 ± .17 μmol/min/g) and mean (right graph; Non-Diabetic: .52 ± .18 μmol/min/g, Diabetic: .50 ± .14 μmol/min/g) MGU values for each subject are plotted relative to the HEC protocol used during FDG imaging. For both analyses, there were no differences in the range, scatter, or average MGU values between those subjects that underwent the Non-Diabetic (white circles) or Diabetic (black circles) protocols.

Figure 4

Relationship of MGU values with diastolic blood pressure. By univariate analysis, the maximal (left graph) and mean (right graph) MGU values from normally perfused segments were most highly correlated with diastolic blood pressure, and diastolic blood pressure remained an independent predictor by multivariate analysis (Table 3). However, diastolic blood pressure was only able to account for ~20–22% of the variability in MGU values among patients with ischemic cardiomyopathy.

Figure 5

Changes in plasma potassium with an abbreviated HEC. Consistent with electrolyte shifts during insulin administration, the HEC protocols resulted in a fall in plasma potassium (left graph). After the first few subjects had dramatic falls in their plasma potassium without supplementation (>1 mmol/L), we modified our protocol to include potassium supplementation for the majority of subjects (those with baseline plasma potassium <5 mmol/L). As expected, this modification abated the decline in plasma potassium levels (right graph) without induction of hyperkalemia.