Glucotypes reveal new patterns of glucose dysregulation
(A) Comparison of glycemic response, insulin secretion, and insulin sensitivity across different glucotypes (low, moderate, severe) (S5 Data). Each column is a participant. The glycemic response is shown in the horizontal panels as fasting blood sugar concentration and as blood glucose concentration 2 hours after oral glucose load in an OGTT. Dashed lines for fasting blood sugar and 2-hour glucose in OGTT correspond to the ADA thresholds for prediabetes and diabetes. Insulin secretion rate was calculated using deconvolution of C-peptide concentrations at 0, 30, and 120 minutes during OGTT (ISEC software , see Methods). The average derivative of the insulin secretion curve is shown as aggregate measure of insulin secretion rate over the whole OGTT time course. Insulin sensitivity is shown as glucose concentration from SSPG test, with higher values reflecting greater insulin resistance. (B, C, D, E, F) Insulin secretion rate (black solid line) and blood glucose concentration (dots and purple solid line) during OGTT for 5 individuals (S8 Data). Shaded areas in panels B-F aggregate data of distribution of insulin secretion rate for participants diagnosed with diabetes (pink), prediabetes (green), and nondiabetic (blue). Each panel represents an individual with a different physiology. (B) Insulin-sensitive individual with normal insulin secretion and a low blood glucose 2 hours postprandially; (C) Individual diagnosed with diabetes demonstrating high glycemic concentrations despite high insulin secretion; (D) Nondiabetic individual with normal fasting blood glucose but high 2-hour OGTT value in setting of insulin resistance and absolute but relative deficiency of insulin secretion; (E) Nondiabetic individual with insulin resistance with low insulin secretion, characterized by early glucose rise after load; (F) Nondiabetic individual with insulin resistance and high compensatory insulin secretion with relatively normal postprandial glucose following oral glucose load. ADA, American Diabetes Association; ISEC, Insulin SECretion; OGTT, oral glucose tolerance test; SSPG, steady-state plasma glucose.