We evaluated the relationship between measurements of beta cell function and insulin resistance assessed from OGTT and 2-step glucose clamp data with indices of glucose variability (GV) obtained with a continuous glucose monitor (CGM) in obese subjects with and without type 2 diabetes (T2D). 17 healthy obese (OB) (FPG 91 ± 4.9mg/dl and A1c 5.2 ± 0.4%) and 8 age- and weight-matched participants with T2D treated with diet and/or metformin (FPG 131.5 ± 42.8 mg/dl and A1c 6.8 ± 0.8%) wore CGM (Dexcom®) for up to 5 days. EasyGV® software was used to calculate indices of GV: standard deviation (SD), mean amplitude of glycemic excursions (MAGE), J-Index, continuous overlapping net glycemic action (CONGA), and Glycemic Risk Assessment in Diabetes Equation (GRADE). Indices of glucose metabolism were determined with a 2 hour OGTT and a two-step hyperglycemic-euglycemic clamp. Insulin levels during the hyperglycemic-step of clamp (116 ± 126 vs. 40 ± 23 mU/mL) were equal in both groups, while glucose infusion rate (GIR) (7.7 ± 3.1 vs. 3.9 ± 2.4 mg/kg/minutes) during euglycemia was as expected significantly lower in the T2D subjects compared to OB subjects. GV indices (SD, CONGA, J-Index, GRADE) were statistically lower in OB vs. T2D (P<0.05). Insulin Sensitivity Index (ISI0-120) and the insulin secretion-sensitivity index-2 (ISSI-2) were also lower in obese than in T2D subjects (P<0.001). CGM indices (mean, CONGA, J-index, and GRADE) correlated with incremental AUC of insulin during the OGTT, but not for glucose; as well as insulin levels during the hyperglycemic-step (r=0.740, P<0.01), and GIR during the euglycemic step of the clamp (r= -0.733, P<0.01). CGM measures of GV (CONGA, J-Index, and GRADE) were lower in obese compared to T2D subjects. These results suggest that GV indices are surrogate measurements of beta cell function and insulin action in obese subjects, and may help determine progression to T2D.

Disclosure

A. Elshafie: None. W. Lam: None. L. Parikh: None. E. Sanchez Rangel: None. C.P. Schmidt: None. J. Hwang: None. C.W. Yeckel: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc..

© 2018 by the American Diabetes Association.
2018
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