Declining ß-cell function is associated with the lack of long-range negative correlation in glucose dynamics and increased glycemic variability: A retrospective analysis in patients with type 2 diabetes*

Objective To determine whether characteristics of glucose dynamics are reflections of β-cell function or rather of inadequate diabetes control. Materials/methods We analyzed historical liquid meal tolerance test (LMTT) and continuous glucose monitoring (CGM) data, which had been obtained from 56 non-insulin treated type 2 diabetic outpatients during withdrawal of antidiabetic drugs. Computed CGM parameters included detrended fluctuation analysis (DFA)-based indices, autocorrelation function exponent, mean amplitude of glycemic excursions (MAGE), glucose SD, and measures of glycemic exposure. The LMTT-based disposition index (LMTT-DI) calculated from the ratio of the area-under-the-insulin-curve to the area-under-the-glucose-curve and Matsuda index was used to assess relationships among β-cell function, glucose profile complexity, autocorrelation function, and glycemic variability. Results The LMTT-DI was inverse linearly correlated with the short-range α1 and long-range scaling exponent α2 (r = -0.275 and -0.441, respectively, p < 0.01) such that lower glucose complexity was associated with better preserved insulin reserve, but it did not correlate with the autocorrelation decay exponent γ. By contrast, the LMTT-DI was strongly correlated with MAGE and SD (r = 0.625 and 0.646, both p < 0.001), demonstrating a curvilinear relationship between β-cell function and glycemic variability. On stepwise regression analyses, the LMTT-DI emerged as an independent contributor, explaining 20, 38, and 47% (all p < 0.001) of the variance in the long-range DFA scaling exponent, MAGE, and hemoglobin A1C, respectively, whereas insulin sensitivity failed to contribute independently. Conclusions Loss of complexity and increased variability in glucose profiles are associated with declining β-cell reserve and worsening glycemic control.