Case 1: Consistently Low Glucose and low C-peptide

by : Dr V.Parameswaran, Diabetes and Endocrinology Services,Royal Hobart Hospital, Australia,June 2006

 General comments and Diagnosis:   Proinsulin is the precursor to Insulin. When insulin is released in vivo, proinsulin is enzymatically cleaved to produce equimolar amounts of insulin (A & B chain) and C-peptide (connecting peptide).  In insulin dependant diabetics where serum insulin levels are affected by insulin therapy, C-peptide measurements can provide some idea of residual endogenous insulin secretion by the pancreas. Residual insulin secretion in IDDM is referred to “honeymoon” period and is a result of regeneration of pancreatic B cells. In some cases, the “honeymoon” period can last from a few months to a few years thus requiring no insulin therapy during this time. C-peptide levels can also be used to diagnose those patients who self administer insulin when not required. In these cases, endogenous pancreatic suppression leads to subnormal or suppressed C-peptide levels.

 Comments on case 1: The negligible C-peptide levels in this patient, at the time of hypoglycaemia, exclude insulinoma. In insulinoma, C-peptide levels will be high or inappropriate to the glucose. The hypoglycaemia in this patient was due to exogenous insulin administration. The diagnosis is factitious hypoglycaemia. The patient eventually confirmed this although initially denying it.

Additional Comments:           Pituitary or adrenal failure, eg Addison’s, results in lower glucose levels and can lead to increased insulin sensitivity (eg ¯ insulin release). However, persistent hypo’s like in this patient despite withdrawal of insulin therapy for a week makes self administration of insulin likely.

Comments on other questions raised in the case:  (1) Laboratory artefact: This is not the case since low C-peptide levels were consistently obtained. Additionally, in our hands, antibody specificity variations have lead to higher measured immunoactive C-peptide rather than low levels. (2) Insulinoma and glucose, insulin and C-peptide levels:        The characteristic laboratory finding in Insulinoma is always ­ insulin and C-peptide and ¯ glucose levels. In most cases, these patterns are clear-cut but it is important to appreciate that in some cases the relative levels of insulin, C-peptide to glucose could be suttle. Therefore appropriateness of relative levels has to be considered eg insulin or C-peptide and glucose ratios.

 IDDM and NIDDM results patterns:          Generally, in IDDM, C-peptide and Insulin levels are low or ND and glucose is high. In NIDDM, all parameters are high.

 Clinical usefulness of C-peptide:      Please see general comments and diagnosis section. In addition, C-peptide is also useful in picking up those cases of surreptitious administration of oral hypoglycaemic agents. In these instances, both C-peptide and insulin levels measured will be high in the presence of low glucose.

 Diagnostic investigation for insulinoma:      The golden standard method that is safe and sensitive is the 72 hour fast. This is done under strict supervision in a hospital setting. Prolonged fasting will gradually drop glucose levels causing pancreatic secretion to switch off. In a patient with insulinoma, the switching off does not occur hence resulting in inappropriate C-peptide or insulin relative to the falling glucose levels. This is because insulinomas are autonomous.