DIURNAL CYCLING OF INSULIN SENSITIVITY IN TYPE 2 DIABETES: EVIDENCE FOR DEVIATION FROM PHYSIOLOGY AT AN EARLY STAGE
Aim of study was to establish the contribution of insulin resistance to the morning (AM) vs afternoon (PM) lower glucose tolerance of people with T2DM. Eleven T2DM subjects [diabetes duration 0.79 (0.23) years, BMI 28.3 (1.8) kg/m2, A1C 6.6 (0.26%) (48.9 (2.9) mmol/mol), treatment life-style modification only] and 11 matched non-diabetic people (controls, CONs) were monitored 05.00-08.00 h (AM and PM, random order) on one occasion (study 1, S1), and on a subsequent occasion underwent an isoglycemic clamp (AM and PM, both 05.00-08.00 h, insulin infusion 10 mU/m2/min) (study 2, S2). In S1, PG, insulin, C-peptide and glucagon were higher, and insulin clearance was lower in T2DMs AM vs PM, and vs CONs (p<0.05), whereas FFA, glycerol and β-hydroxybutyrate were lower AM vs PM. However, in S2 at identical hyperinsulinemia AM and PM (~150 pmol/L), in T2DM glucose Ra and glycerol Ra were both less suppressed AM vs PM (p<0.05). In contrast, in CONs glucose Ra was more suppressed AM vs PM. Leucine turnover was no different AM vs PM. Conclusions. In T2DM insulin sensitivity for glucose (liver) and lipid metabolism has diurnal cycles (nadir AM) opposite to those of non-diabetic subjects already at an early stage suggesting a marker of T2DM.