Insulin secretion and action affect glucose variability in the early stages of glucose intolerance

Abstract

Since it is unknown whether glucose variability (GV) is increased and whether this is related to worsening of insulin secretion and action in prediabetes, we have assessed insulin secretion and sensitivity, and daily GV in early stages of dysglycemia. Twenty subjects with normal glucose tolerance (NGT; age 45.0±9.5years; BMI 31.1±6.4kg/m2), 25 with NGT and 1hrOGTT>8.6mmol/L (1hrOGTT; 45.7±8.5years; 32.4±7.0kg/m2), and 59 with isolated impaired glucose tolerance (iIGT; 47.7±11.2years; 31.3±6.1kg/m2) underwent OGTT and MMTT. CGM was performed with blinded FreeStyle Libre Pro for 24h under standard conditions. Parameters of beta-cell function, insulin sensitivity and GV were calculated. Overall insulin secretion and action as well as GV progressively worsened across glucose tolerance categories. On a matrix analysis, GV parameters were inversely related to ISSI-2; r=-0.37 to -0.52; p<0.0001; and IGI; r=-0.28 to -0.48; p<0.0001 for CV, SD, J-index, LI, HBGI and MAGE. Insulin secretion (IGI) and b-cell function (ISSI-2) emerged as independent contributors to GV in early stage of dysglycemia accounting for about 16%-38% of its variability. Our results show that daily GV worsens already with mild impairment of glucose tolerance. The increase in GV is inversely related to insulin secretion and action.