Glucagon Stimulation C-peptide testing

HOSP # WARD Endocrinology ward
CONSULTANT   Dr. Heleen Vreede DOB/AGE 22 y Male

Abnormal Result

Patient presented with Diabetic Ketoacidosis and a glucose value of 27.4 mmol/L.

Presenting Complaint

Signs and symptoms typical of Diabetic Ketoacidosis

History

Patient was diagnosed with diabetes 7 years ago after presenting with diabetic ketoacidosis. Upon diagnosis he was given insulin in the hospital. Upon discharge he was given Metformin and Glimeperide (oral hypoglycemic medication – reason for oral agents unknown – likely because of his young age?). Defaulted Rx completely. Presented with DKA again. Restarted about 2 y ago on insulin.

The differential diagnosis at the current presentation is thus one of:

  1. Ketosis prone diabetes
  2. LADA (Latent auto-immune diabetes of the adult)
  3. Type1 – went into honeymoon phase after diagnosis and now relapsed

To differentiate – the clinicians prompted to do antibodies, insulin levels and a glucagon stimulation c-peptide dynamic test.

Examination

N/A

Laboratory Investigations

Date 05/02/2021 02/02/2021 28/08/2018 25/01/2018 05/06/2017 03/03/2017 03/03/2017 24/02/2017 16/09/2016 14/04/2015
Na          134 L                             137.000                   133 L
K          4,6                               4.890            4,5   UOLD2
Cl           93 L                                                        
Urea         13,4 H                             5.000                   1,9 L
Creat           91                               69.000             66      34 L
Glu Random                       27,4                        21.860                
HbA1c (NGSP)         12,7   >14  13,7   >14                12,8    13,7         
Total chol  5,04                                      δ- 4,98                       
Triglyceride  1,74                                       1,25                       
HDL chol  1,35                                       1,16                       
LDL chol (calc)  2,89                                       3,25                       
Total chol                                                          8,99         
U creat   4,1                                        1,9                       
U albumin 32.70                                         <3                       
U alb : creat   8.0 H                                      UTC                       
Test referred                                    Anti-IA2 Antibody  Positive;
Anti-GAD antibody Positive 		                            

Other Investigations

A glucagon-stimulated C-peptide level was drawn.

0 min 1.5 ug/L 0.5 nmol/L
1 min 2.0 ug/L 0.67 nmol/L
2 min 1.9 ug/L 0.63 nmol/L
3 min 1.9 ug/L 0.63 nmol/L

Final Diagnosis

LADA – latent autoimmune diabetes of the adult

Take Home Message

Serum c-peptide has traditionally been thought to be an inconvenient method as immediate lab analysis is required before degradation (when collected in serum gel or plain sample tubes). This is because c-peptide is a small linear peptide, which is susceptible to enzyme proteolytic cleavage. Gel tubes are therefore traditionally required to be transported to the lab on ice, promptly centrifuged and separated, then stored in frozen conditions unless lab analysis is possible at that center.

However, c-peptide sample collection for c-peptide determination in whole blood in EDTA prepared tubes is stable at room temperature for up to 24 h. Venous blood c-peptide levels can be measured in the random, fasting, or stimulated scenarios. Random samples are taken at any time during the day without consideration of recent food intake, whereas fasting samples are taken after an 8- to 10-h fast.

Stimulation methods include using

  • glucagon
  • intravenous/oral glucose
  • tolbutamide
  • sulfonylurea
  • glucose-like peptide 1
  • amino acids
  • a mixedmeal

In this case a glucagon stimulation yielded sufficient results to assist the clinicians in making the diagnosis, indeed a case of atypical diabetes presentation.