Background: Recent evidence suggests a bidirectional relationship between COVID-infection and new-onset diabetes (NOD) presenting with DKA.

Methodology: This one-year prospective study comprised of 29 COVID-negative DKA (controls) and 52 COVID-positive-DKA patients (18 NOD, 15 T1DM ,T2DM) . NOD were previously normoglycemic and negative for GAD/IA-2/ZnT8 autoantibodies. After 75g- OGTT with estimation of glucose, C-peptide, FFA and insulin at 0,15, 30,45, 60,90 ,120, 150 and 180minutes, Insulin secretion rate (ISR) [C-peptide-deconvolution] , Hepatic insulin sensitivity [AUC-glucose × AUC-insulin during first 30-minutes of OGTT ], Peripheral insulin sensitivity [ dG/dt ÷ mean plasma insulin concentration; dG/dt rate of decline in plasma glucose concentration]were calculated alongwith Metabolomics and Adipose tissue gene expression. All tests were performed at admission and 4, 8, and 12-months of followup.

Results: At baseline, ISR in NOD was significantly reduced than controls (p=0.001) but similar to T1DM (p=0.15) . Nearly 83% (n=17) of NOD with DKA had near-complete recovery of ISR on follow-up compared to T1DM (all p<0.01) ,with non-remitters (n=3) having significantly worse admission Hba1c and IL-6 (all p<0.01) . NOD had significantly increased hepatic and peripheral insulin resistance compared to T1DM (all p<0.05) ,but similar to T2DM (all p>0.05) . Their Metabolomics revealed increased inflammatory phosphatidylcholines, that correlated with peripheral glucose uptake (p<0.01) ,while RNA sequencing showed significantly enhanced WNT5A , TLR4 (Toll-like Receptor-4) and RETN (resistin) than T1DM and T2DM (both p=0.001) .

Conclusion: Our study provides novel insights into COVID-associated NOD with DKA. Majority have near-complete recovery of insulin secretion while simultaneous multi-tissue insulin resistance and inflammatory adipose tissue profiles persist as drivers of hyperglycemia .

Disclosure

R.Dasgupta: None. S.Mondal: None. R.Garai: None. B.Chowdhury: None. A.Hazra: None. M.Lodh: None. A.Ganguly: None.

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