Diabetes improvement and potential remission in a liver transplant recipient treated with tacrolimus

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 758-785-Diabetes Case Reports: Type 1, Type 2, MODY & Complications
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-770
Maria Pallayova*1, Violet Wilson2, Reggie John2 and Shahrad Taheri3
1University of Birmingham, 2Heart of England NHS Foundation Trust, 3Heart of England NHS Fdn Trust, Solihull W Midlands, United Kingdom
Background:Organ transplantation (Tx) and subsequent immunosuppressive therapy tend to induce or worsen pre-existing diabetes mellitus. Specifically, tacrolimus is known to cause hyperglycaemia, which is ascribed to suppression of glucose-induced insulin secretion.

Clinical Case: A 49-year-old Chinese woman was seen in 07/2006 for newly diagnosed diabetes mellitus and hepatitis B with secondary liver cirrhosis, complicated by portal hypertension and oesophageal varices. Her initial HbA1c (DCCT-aligned) was 12.8%. The patient already had bilateral non-proliferative diabetic retinopathy. Intensive insulin therapy was started (detemir+aspart; 36 IU/day), maintaining fasting blood glucose levels between 5-7 mmol/l. At the same time, the patient was under regular review by hepatologists. Additional medications included propranolol, spironolactone, and tenofovir.

At 3-month follow-up, the patient’s overall glucose control improved as reflected by HbA1c of 6.6% that further decreased to 5.8% (09/2007), 5.7% (03/2008), and 5.9% (09/2008), while on basal-bolus regimen. Since 01/2009, the glucose control had deteriorated with HbA1c of 7.6%, 7.3% (03/2010), 8.4% (09/2010), and 7.8% (01/2011), following a progression of hepatic dysfunction and diabetic retinopathy with proliferative changes.

In 03/2011, the patient successfully underwent liver Tx and was subsequently treated with prednisolone, tacrolimus, and mycophenolate mofetil. Her glucose control improved after prednisolone was discontinued.  In 07/2011, the HbA1c was 5.0%. The doses of basal and bolus insulin were gradually decreased due to recurring night-time and daytime hypoglycaemia. Since 01/2012, the patient has been completely off insulin while continuing her antiviral (telaprevir) and combined immunosuppressive therapy (tacrolimus+mycophenolate). The HbA1c levels continue to remain good on diet: 5.2% (01/2012), 5.8% (04/2012), 6.5% (07/2012), and 6.3% (10/2012; 12/2012). Since liver Tx, the patient‘s BMI decreased from 27 to 24 kg/m2 and her renal function is stable at an estimated GFR of around 60 ml/min/1.73m2.

Conclusion: This is the first case demonstrating the improvement and potential remission of insulin-requiring hepatogenous diabetes in a liver transplant recipient treated with tacrolimus. The findings suggest that normalized glucose production and insulin sensitivity after liver Tx may restore preserved beta-cell function and thus eliminate insulin requirements even in patients treated with tacrolimus.

Disclosure: MP: Recipient Award, Lilly USA, LLC. ST: Clinical Researcher, Lilly USA, LLC, Clinical Researcher, Novo Nordisk. Nothing to Disclose: VW, RJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: M. Pallayova is supported by the Slovakian Diabetes Association/Lilly Diabetes Clinical Research Initiative. S. Taheri is supported by the UK National Institute of Health Research Collaborations for Leadership in Applied Health Research and Care.