Severe COVID-19 associated hyperglycaemia is caused by beta cell dysfunction: a prospective cohort study

Abstract Background Hyperglycaemia was shown to be among the features of severe acute COVID-19 infection both in the acute and convalescence period. Mechanisms contributing to its development and/or maintenance in a post-COVID phase are still unclear. Materials and Methods Survivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: indirect calorimetry and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI), respectively. Resting energy expenditure (REE) was calculated using the Weir and Harris-Benedict equation and substrate preference using the respiratory quotient (RQ) and nitrogen losses. Results Thirty-two patients (12 women) were available for the analyses at T0 and 26 at T6. Baseline examination was within 21±6.5 days after COVID-19 diagnosis. Patients were hypermetabolic at baseline (30.7 ± 4.3 kcal/kg lean mass/day, ~120% predicted values) but REE declined over the 6 months (ΔT6-T0 mean difference (95% CI): -5.4 (-6.8, -4.1) kcal/kg lean mass/day, p<0.0001). 20 patients at T0 and 13 patients at T6 had hyperglycemia. None of the patients had positive islet autoantibodies. Insulin sensitivity at T0 was comparable between hyperglycaemic (H) vs. normoglycaemic (N) patients (T0 ISIH=3.07 ± 1.18, ISIN=3.23 ± 1.72, p=0.66), whereas insulin response was lower in the H group only (DIH=3.19 ± 2.16 vs DIN=8.78 ± 6.37, p=0.005). Over the 6 months, IS improved in the H group (ΔT6-T0 mean difference for ISI (95% CI): 1.84 (0.45, 3.24), p=0.01)), whereas IGI and DI did not improve in either group. Conclusions Severe COVID-19 infection was associated with hypermetabolism that did not persist over the follow-up. Patients were insulin resistant in the acute phase, but only those with insufficient insulin response developed hyperglycaemia. Insufficient beta cell response was a possible mechanism leading to hyperglycaemia.