TABLE 2.
Recent advancements in knowledge about C‐peptide in clinical diabetes
| Study | Diabetes type | C‐peptide levels (nmol/L) of clinical interest | Interpretation | |
|---|---|---|---|---|
| Jacobsen et al. 34 | T1D (stage 1) | Index 60* <1.0 | ➔ | Reduced risk (77%) of T1D among children with multiple pancreatic aAb |
| Evans‐Molina et al. 35 | T1D (stage 1) | N/A |
Compared with aAb negative youths, those with detectable pancreatic aAb have lower C‐peptide levels already ≥5 y before T1D onset Among progressors, fasting C‐peptide increases and early C‐peptide response to OGTT decreases as the onset of T1D approaches |
|
| Willemsen et al. 22 | T1D | N/A | C‐peptide measurement in dried blood spots is feasible to monitor beta‐cell function slopes at home | |
| Rickels et al. 43 | T1D | >0.40 (after MMTT) | ➔ | Higher time in range |
| Zenz et al. 44 | T1D | ≥0.05 (fasting) | ➔ | Higher glucagon and endogenous glucose production in response to hypoglycaemia |
| Gibb et al. 45 | T1D | >0.01 (random) | ➔ | Lower time below range |
| Marren et al. 46 | T1D (>5 y) | >0.02 (after MMTT) | ➔ | Lower rate of self‐reported hypoglycaemia |
| Gubitosi‐Klug et al. 47 | T1D | >0.03 (after MMTT) | ➔ | Lower risk of severe hypoglycaemia |
| Thivolet et al. 48 | T1D | >0.03 (after MMTT) | ➔ | No association with glucagon response to MMTT |
| Jeyam et al. 50 | T1D | >0.20 (random) | Lower insulin requirement, HbA1c, DKA and hypoglycaemia risk. The association with hypoglycaemia episodes was linear down to C‐peptide levels of 0.003 nmol/L | |
| Foteinopoulou et al. 118 | T1D | ≥0.20 (random) | ➔ | Consider further evaluations to eventually reclassify diabetes type |
| Buzzetti et al. 91 | LADA | <0.30 | ➔ | Identify people requiring insulin therapy |
| ≥0.30 and ≤0.70 | ➔ | Identify people who might benefit from a flexible therapeutic approach and from regular C‐peptide measurements over time | ||
| >0.70 | ➔ | Identify people who can be treated according to the T2D guidelines and who should repeat C‐peptide measurement if glycaemic control deteriorates | ||
| Wod et al. 89 | Adult‐onset newly diagnosed diabetes | 0.30 (fasting) | ➔ | Stratify people with adult‐onset diabetes for different risk metabolic profiles independently from GADA and age at onset |
| Sokooti et al. 97 | T2D | N/A | Fasting C‐peptide improves the FOS risk score for the estimation of T2D risk in the general population (the higher the C‐peptide, the higher the risk) Sensitivity analyses showed C‐peptide was an independent predictor only among people without hypertension | |
| Tuccinardi et al. 104 | T2D (insulin‐treated) | 0.36 (fasting) | ➔ | Cut‐off with 45% sensitivity and 81% specificity for identifying people with T2D on basal‐bolus treatment among people with T2D on insulin treatment |
| Landgraf et al. 113 | T2D | ≤0.40 (fasting) | ➔ | Worse HbA1c values and higher rate of hypoglycaemic episodes (including severe) after starting basal insulin, despite lower insulin dose (IU/kg), compared with people with higher C‐peptide values |
| Hope et al. 114 | T2D (insulin‐treated) | <0.20 (random) | ➔ | High hypoglycaemic risk, including risk of severe hypoglycaemias |
Note. This table summarizes the main findings of studies published within the last 5 y about the clinical implications of C‐peptide measurement for the management of autoimmune and type 2 diabetes.
Abbreviations: aAb, autoantibodies; DKA, diabetic ketoacidosis; FOS, Framingham offspring; GADA, glutamic acid decarboxylase antibodies; IU, international units; LADA, latent autoimmune diabetes in adults; MMTT, mixed‐meal tolerance test; N/A, not appropriate; OGTT, oral glucose tolerance test; T1D, type 1 diabetes; T2D, type 2 diabetes.
*Index 60 is a composite measure of fasting C‐peptide, 60 min glucose and 60 min C‐peptide ([0.3695 × (log10[fasting C‐peptide])] + [0.0165 × 60 min glucose] − [0.3644× 60 min C‐peptide]).