CASE 17 A CASE OF DIABETIC KETOACIDOSIS IN AN ELDERLY MALE

Original Case by Satoshi Yamagata et al

An 81-year-old male had experienced vomiting, dizziness, and appetite loss for 2 weeks. There had not been recognition of diabetes prior to the onset of this illness. On admission, he showed impaired consciousness (Glasgow Coma Scale score, 12) with no neurologically abnormal findings or abdominal tenderness. However, he had a dry tongue and decreased skin turgor. His height was 158 cm, body weight 42.1 kg, and body mass index 16.7 kg/m2. His blood pressure was 138/78 mm Hg with an irregular pulse and heartbeat. His body temperature was 35.8°C. Electrocardiography revealed atrial fibrillation. He had no familial history of diabetes. There was no history of falling or bruising.

Q Which endocrine condition would you suspect here ?

Clinically I would suspect Thyrotoxicosis from this history. Points in favour are

  1. Low BMI
  2. Atrial fibrillation
  3. Loss of appetite- Apathetic thyrotoxicosis in elderly

Biochemical analysis revealed high levels of serum 3-hydroxybutyrate (6,296 μmol/L) and the presence of urine ketones and metabolic acidosis, which suggested DKA. His plasma glucose level and glycated hemoglobin level were 732 mg/dL (40.6 mmol/L) and 6.9% (56 nmol/mol), respectively. Urinary C-peptide excretion was <0.1 μg/day, and serum C-peptide level was <0.1 ng/mL after intravenous glucagon loading at onset.  Table 1

Q What is the interpretation of Glucagon stimulation test ?

C peptide 6 min after 1 mg of Glucagon, if the value is <1.8 ng/ml it is considered to be low.

Q What is your interpretation from the biochemical investigations ?

  1. The high blood sugar, low C peptide and presence of ketoacidosis go in favour of absolute insulin deficiency.
  2. Absence of GAD 65 and IA2 antibody go against the possibility of autoimmune etiology. However, presence of other antibodies cannot be ruled out.
  3. The low calcium and increase phosphorous are suspicious. I would consider going a vitamin D and PTH. Also the alkaline phosphatase is high
  4. Amylase is high. I would do a pancreatic imaging.
  5. The increase CPK gives a hint of Rhabdomyolysis
  6. As you can see from the chart, there is multiple organ involvement. A possibility of multi system involvement must be kept in mind

Q The high blood sugar with a low HbA1c suggests what ?

It suggests a possibility of Fulminant type 1 diabetes

Q What is Fulminant type 1 Diabetes ?

It is a severe form of diabetes in which rapid destruction of pancreatic beta cell occurs within no time leading to absolute insulin resistance.

Q What are the clinical characteristics of Fulminant Type 1 Diabetes ?

  1. Abrupt onset of action
  2. Negligible C peptide at onset
  3. Negative islet associated antibodies
  4. Ketoacidosis at onset
  5. Relatively short history of symptoms- <1 week
  6. Elevated pancreatic enzymes

It is described predominantly in Japan

Laboratory data on admission showed high concentrations of serum creatine kinase (CK) (31,084 U/L), myoglobin (122,335 ng/mL), and myoglobinuria, which indicated the onset of rhabdomyolysis. Blood urea nitrogen and serum creatinine (Cr) were both increased (101 mg/dL and 3.6 mg/dL, respectively), and the plasma osmolality level was high (370 mOsm/kg H2O). Glutamic acid decarboxylase and insulinoma-associated antigen 2 antibodies were undetectable.

Q Which are the important antibodies in Type 1 Diabetes ?

  1. Anti GAD65 antibody
  2. Anti Insulinoma associated antibody 2
  3. Anti Insulin autoantibody
  4. Anti Znt8

Thyroid hormones were within normal ranges: free triiodothyronine, 2.62 pg/mL; free thyroxine, 0.90 ng/dL; thyroid-stimulating hormone, 2.08 μIU/mL. The following serological markers for viruses were all negative: coxsackie A9, B2, B4, and B5; cytomegalo; mumps; herpes 6; Epstein-Barr; influenza; herpes simplex; echo 1, 3, and 7; varicella zoster; and rubella. A drug screen performed by Triage® DOA (Biosite Diagnostics Inc, San Diego, CA) was negative.

We treated the patient with 4,000 mL/24 hour saline and continuous venous insulin infusion on the first day (Fig. 1). Empiric broad-spectrum antibiotics were administered for a urinary tract infection. Blood glucose and pH levels normalized 1 day after treatment. However, he was treated with continuous hemodiafiltration on the second day because of anuria and elevated serum CK concentrations (78,225 U/L). Although his serum CK concentrations improved to within the normal range 1 week after treatment, daily urinary volume remained decreased (<50–100 mL/day).

HD was introduced on hospital day 10. After 16 HD sessions, his serum Cr concentrations transiently increased to 12.5 mg/dL and then decreased to 6 mg/dL. Daily urinary volumes gradually increased to >1,500 mL/day. Finally, HD was completed 46 days after starting continuous hemodiafiltration (CHDF). Two weeks after the final HD, his serum Cr concentrations had improved to 2.0 mg/dL

Q Is there a link between Rhabdomyolysis and DKA ?

Yes. Rhabdomyolysis may be associated with DKA.

Learning points from this case

  1. Fulminant Type 1 diabetes is an antibody negative type 1 diabetes which presents rapidly with diabetic ketoacidosis
  2. Rhabdomyolysis may be associated with diabetes ketoacidosis .
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