Undiagnosed diabetes presenting as hypertriglyceridemia-induced pancreatitis.

Sir,

A 45-year-old nonalcoholic obese [body mass index (BMI): 31 kg/m2) male was referred from a private hospital to our intensive care unit (ICU) with diagnosis of severe acute pancreatitis on the third day of his illness. At the time of admission in the ICU, he was conscious but irritable, pulse rate was 120/min with warm peripheries, blood pressure 135/65 mmHg, central venous pressure (CVP) 4–5 mmHg, respiratory rate 20–24/min, and urine output 40–50 mL/hr. The abdomen was distended and intra-abdominal pressure was 16 mmHg. At admission, the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were 7 and 2, respectively. His laboratory reports [Table 1] and ultrasonography of the abdomen (bulky pancreas with no sign of biliary sludge or stone) was suggestive of hypertriglyceridemia-induced pancreatitis. The patient was kept nil by mouth with free drainage of nasogastric tube. Parenteral nutrition was started along with insulin infusion to maintain blood sugar <150 mg/dL. Gemifibrogil 600 mg tablet was given twice daily with atorvastatin 20 mg once a day. Plasmapheresis was planned for hypertriglyceridemia but the consent for the procedure was not given by his relatives. By then, his triglyceride (TG) level reduced with clinical improvement and he was transferred to the ward. Repeat ultrasound after 10 days showed no peripancreatic collection and he was discharged home in a stable condition.

Table 1

Laboratory parameters of the patient during his illness

Hypertriglyceridemic pancreatitis (HTGP) is the third most common cause of pancreatitis after gall stone disease and alcohol, and accounts for approximately 5 to 10% of all acute episodes of pancreatitis.[123] However, mild to moderate hypertriglyceridemia occurs as an epiphenomenon in pancreatitis in which it is not the cause of the disease. A value greater than 1,000 mg/dL is considered as the trigger for acute pancreatitis. The mechanism of HTGP remains unclear; however, various theories have been postulated including increased formation of free fatty acid in the pancreas resulting in cytotoxic injury through inflammatory mediators and free radicals.[123] In a recent study, the role of the CFTR gene mutation has been associated with HTGP.[4]

Hypertriglyceridemia can be either primary or secondary. Secondary hypertriglyceridemia is associated with insulin deficiency, insulin resistance, or elevation of counter-regulatory hormones as seen in diabetes mellitus, obesity, pregnancy, alcohol, and with certain drugs like beta blockers, thiazides, and so on.[35] In uncontrolled diabetes, hypertriglyceridemia occurs due to the decreased activity of lipoprotein lipase enzyme (LPL) which hydrolyses the TGs into fatty acid that enters muscle cells to be utilized as a source of energy and in fat cells to get reconverted into TGs and get stored. In our patient there was no family history of primary hypertriglyceridemia. However, his initial blood sugar (452 mg/dL) and glycated hemoglobin (HbA1c) (11%) levels were suggestive of undiagnosed diabetes mellitus.

The clinical picture of HTGP is indistinguishable from other forms of pancreatitis. It is important to note that TG levels come down rapidly once the oral intake is stopped. Therefore if TG levels are not done early, it is possible to miss the diagnosis of hypertriglyceridemic pancreatitis and the patient might not receive specific therapy.

Treatment in the acute phase remains the same as with the other causes of pancreatitis. Insulin therapy is useful especially in poorly controlled diabetic patients, where it decreases the TG level by increasing the activity of lipoprotein lipase (LPL).[12] Heparin has also been used in some studies. Oral pharmacotherapy includes oral antihyperlipidemic agents.[125] Fibrates cause increase in LPL activity via PPAR alpha receptors (PPAR: paroxisome proliferator activated receptor). These drugs inhibit hepatic synthesis of TGs. Nicotinic acid (niacin) is a group B vitamin which, in high doses, lowers plasma lipids. Omega-3 fatty acids have also been used in the treatment of HTGP and they act by reducing hepatic TG synthesis and increasing LPL activity.[5] Also, there are case series suggesting the use of plasmapheresis for the rapid removal of chylomicrons.[2]

All patients of pancreatitis with predisposing factors for hypertriglyceridemia should be evaluated for raised TG levels in the early phase, so that specific treatment could be provided with better outcome.