Approximately 70% of obese AA patients with new-onset diabetes presenting with DKA and SH have near-normoglycemia remission with intensive insulin treatment. In addition to improvements in insulin secretion and/or sensitivity as potential mechanisms of remission, we hypothesize that gut glucose absorption may be associated with remission. To estimate gut glucose absorption, we developed a novel mathematical model that simultaneously estimates SI and gut glucose half-life (GIGt1/2, inversely related to glucose absorption). This study aimed to compare insulin sensitivity estimates of the novel model to estimates from Dalla Man’s OGTT model and also assess GIGt1/2.
We included 42 AA patients who presented with new-onset DKA (n= 17) and SH (n=25). All subjects had a 75-gm 2-hour OGTT 1 week after insulin remission (REM) or at 3 months after continuous insulin therapy (no-REM). We estimated insulin sensitivity using our novel first-order absorption OGTT model (SInew) and GIGt1/2 and Dalla Man’s OGTT model (SI).
SInew was highly concordant with SI (R=0.61, P<0.001; Concordance=0.90). When separating subjects by DKA status, there were significant differences in the frequency of remission status (χ2=5.00, P=0.03). Subjects with DKA+REM (98±19 min) had a significantly longer GIGt1/2 compared to those with SH+no-REM (47±9 min, P=0.02). GIGt1/2 between DKA+no-REM (108±46 min) and SH+no-REM was also significantly different (P=0.045). SH+REM showed a statistical trend to be different from SH+no-REM (P=0.07). There were no significant differences identified between DKA+REM, DKA+no-REM and SH+REM.
The SInew from our novel OGTT model is highly concordant with SI from Dalla Man’s OGTT model. Our model additionally estimates GIGt1/2 and indicates slower gut glucose absorption is associated with remission. This new model shows that obese African American patients presenting with new-onset DKA or SH may benefit from interventions that target gut glucose absorption.
D. Stefanovski: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. R.C. Boston: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. Research Support; Self; National Institutes of Health.
National Institutes of Health (K12HD085850 to P.V.)