Altered Temporal Organization of Plasma Insulin Oscillations in Chronic Renal Failure

Chronic renal failure (CRF) is associated with mechanistically unexplained impaired insulin sensitivity. Erratic insulin secretory patterns typify other states of insulin resistance. We sought to investigate possible alterations of plasma insulin oscillations in CRF. We assessed high- and low-frequency insulin and glucose oscillations in 7 male CRF patients and 11 controls by multiparametric deconvolution analysis and cluster analysis, approximate entropy (ApEn) statistic, and cross-ApEn statistics. Insulin sensitivity was appraised by euglycemic hyperinsulinemic clamps. Despite impaired glucose disappearance rates in CRF, fasting and 24-h mean insulin and glucose concentrations did not differ between patients and controls. However, patients showed a 2.5-fold increase of insulin elimination half-life, reduced frequency of both rapid (6.1 +/- 0.4 vs. 7.1 +/- 0.2 h(-1), P < 0.001) and slow oscillations of insulin release (0.54 +/- 0.11 vs. 0.71 +/- 0.1 h(-1), P < 0.001), lack of acceleration and paradoxically more orderly slow insulin and glucose pulses after meals, and increased temporal coupling between insulin and glucose patterns (cross-ApEn: 0.58 +/- 0.13 vs. 1.37 +/- 0.23, P < 0.001). Postprandial glucose intolerance was inferable by prolonged and amplified blood glucose excursions despite exaggerated insulin bursts of almost 3-fold higher area. In summary, CRF is associated with a complex disruption of the temporal organization of insulin release, which differs from abnormalities observed to date in other states of insulin resistance.