High residual C-peptide likely contributes to glycemic control in type 1 diabetes

BACKGROUND. Residual C-peptide is detected in many people for years following the diagnosis of type 1 diabetes; however, the physiologic significance of low levels of detectable C-peptide is not known. METHODS. We studied 63 adults with type 1 diabetes classified by peak mixed-meal tolerance test (MMTT) C-peptide as negative (<0.007 pmol/mL; n =15), low (0.017-0.200; n = 16), intermediate (>0.200-0.400; n = 15), or high (>0.400; n = 17). We compared the groups' glycemia from continuous glucose monitoring (CGM), 13 cell secretory responses from a glucose-potentiated arginine (GPA) test, insulin sensitivity from a hyperinsulinemic-euglycemic (EU) clamp, and glucose counterregulatory responses from a subsequent hypoglycemic (HYPO) clamp. RESULTS. Low and intermediate MMTT C-peptide groups did not exhibit fi cell secretory responses to hyperglycemia, whereas the high C-peptide group showed increases in both C-peptide and proinsulin (P <= 0.01). All groups with detectable MMTT C-peptide demonstrated acute C-peptide and proinsulin responses to arginine that were positively correlated with peak MMTT C-peptide (P < 0.0001 for both analytes). During the EU-HYPO clamp, C-peptide levels were proportionately suppressed in the low, intermediate, and high C-peptide compared with the negative group (P <= 0.0001), whereas glucagon increased from EU to HYPO only in the high C-peptide group compared with negative (P = 0.01). CGM demonstrated lower mean glucose and more time in range for the high C-peptide group. CONCLUSION. These results indicate that in adults with type 1 diabetes, beta cell responsiveness to hyperglycemia and alpha cell responsiveness to hypoglycemia are observed only at high levels of residual C-peptide that likely contribute to glycemic control.