In the absence of established guidance on insulin therapy among patients with hypertriglyceridemic pancreatitis (HTGP), a 2018 comparative review identified 34 HTGP cases demonstrating the safe use of insulin management with close monitoring of serum blood glucose. Insulin therapy becomes a reasonable approach for HTGP, particularly in a clinical setting with no or limited availability of plasmapheresis. The case patients examined had a mean age of 39.6 years (range: 13-65 years) with no clear gender preponderance (male, n=18; female, n=16). Major patient-specific comorbidities included moderate-to-severe hypertriglyceridemia, hypertension, diabetes mellitus, dyslipidemia, alcohol abuse, and obesity. Three patients out of the 16 females were pregnant upon the diagnosis of HTGP. Based on this review of insulin treatment in patients with HTGP, intravenous (IV) insulin was usually given at a rate of 0.1 to 0.3 units/kg/hour, and the serum triglyceride levels were monitored every 12 hours. Initial symptomatic management also included bowel rest, IV fluids, and analgesics. The authors of this review emphasized continuous monitoring of blood glucose levels and prompt administration of adjuvant 5% dextrose infusion once blood glucose falls below 200 mg/dL. All but one of the 34 patients fully recovered with intensive IV insulin therapy. [1]
Another 2018 clinical review also stated a lack of established guidelines in managing HTGP. The authors observed various treatments including insulin, heparin, fibric acids, and omega 3 fatty acids have been utilized to successfully reduced serum triglycerides (TG). Acute HTGP was defined in this article as the first 14 days from symptom onset, where nearly 50% of mortality occurs. Insulin administration in acute HTGP stimulates lipoprotein lipase (LPL) activity, which in turn lowers serum TG levels. A dosing regimen cited within the review was continuous IV insulin at a rate of 0.1 to 0.4 unit/kg/hour, which was shown to be effective in patients with severe HTGP with and without type 2 diabetes mellitus. It was reported that IV insulin (3 to 9 units/h for four days) decreased serum TG levels from 7,700 to 246 mg/dL in a patient without affecting the normal blood glucose concentration. Additional data cited from case reports found IV insulin decreased serum TG levels by 40% over 24 hours. A greater TG reduction of 87% was achieved within the same period when insulin was given in fasting state. In one example (Table 3) comparing IV insulin, IV insulin with plasmapheresis, and subcutaneous (SC) insulin, the efficacy of both IV and SC insulin in reducing TG was 85% upon discharge, compared to 92.6% reduction when using IV insulin combined with plasmapheresis. However, patients with plasmapheresis had complications, including respiratory failure and acute kidney disease. The authors concluded that insulin monotherapy for HTGP was overall safe and effective. [2]
The Bi-TPAI trial is a yet unpublished study registered on Clinicaltrials.gov as a multicenter, parallel-group randomized, controlled, non-inferiority trial to investigate whether intensive insulin therapy is as effective as plasmapheresis in lowering TG in patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP). Per the trial protocol, the estimated enrollment is 220 patients with HTG-AP from 17 large tertiary hospitals located in China. Eligible patients will be randomized to receive either continuous IV infusion of regular human insulin at a rate of 0.1 units/kg*hour, maximum of up to 0.3 units/kg*h, with simultaneous infusion of IV dextrose 5% or higher or standard-volume plasmapheresis (1–1.5 plasma volume) every 24-hours until the TG level is <5.6 mmol/L for both interventions. Diabetic patients allocated to plasmapheresis group will also simultaneously receive minimal IV insulin drips to manage patients’ diabetes. The predefined primary endpoint is the time for TG level to reduce to 500 mg/dl, and the secondary endpoints are ICU and hospital lengths of stay, 28-day mortality, severity of HTG-AP, incidence of hypoglycemia, HTG-AP complications, and cost-effectiveness. This trial, however, has not been updated since its registration (back in 2017), and the recruitment status is still listed as unknown. [3], [4]