Brendan Peterson Objectives Review background information Determine special considerations for pharmacotherapy in T2DM kidney transplant patients Summarize evidencebased treatment recommendations ID: 908232
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Management of Type II Diabetes in Patients with Kidney Transplantation
Brendan Peterson
Slide2ObjectivesReview background informationDetermine special considerations for pharmacotherapy in T2DM kidney transplant patientsSummarize evidence-based treatment recommendations
Slide3Background
Slide4106,687 people are currently on the transplant waiting list in the US, with a new person being added every 9 minutesEach day 17 people die waiting for an organ transplantApproximately 39,000 transplants were performed in 2020
Slide5https://www.organdonor.gov/learn/organ-donation-statistics
Slide6Slide7Special Considerations
Slide8Slide9Diagnosis of PTDM 1) Fasting glucose >126 mg/dL (7 mmol/L) on more than one occasion. 2) Random glucose >200 mg/dL (11.1 mmol/L) with symptoms. 3) Two-hour glucose after a 75-g OGTT of >200 mg/dL (11.1 mmol/L).
The diagnosis of PTDM can be made using any of the following American Diabetes Association/World Health Organization criteria for the diagnosis of diabetes once the transplant recipient has been discharged from the hospital and tapered to their maintenance immunosuppression. However, HbA1c should not be used alone to screen for diagnosis of PTDM within the first year after transplant.
Slide10Hemoglobin A1C is a less reliable measure for identifying significant glucose intolerance in the first 12 months after transplant due to reduced red blood cell survival after transplant
Slide11Slide12Associated Genetic ComponentType 2 candidate gene SNPs associated with PTDM include TCF7L2, KCNJ11-Kir6.2, and some but not all variants of KCNQ1PTDM has also been associated with SNPs in multiple IL genes, particularly IL-2, IL-7R, IL-17R, IL-1B, IL-4, IL-17-RE, IL-17R, and IL-17RB SNPs in the transcription factor NFATc4 and adiponectin are also associated with PTDM Calcineurin inhibitors (cyclosporine and tacrolimus), bind to nuclear factor of activated T-cells (NFAT). NFAT, in turn, can down-regulate adiponectin transcription, so individuals with SNP in this candidate gene may be at greater risk for glucose intolerance related to CNI-containing regimens.
Slide13Immunosuppressive Therapy and HyperglycemiaCorticosteroids induce or worsen pre-existing insulin resistance, increase hepatic gluconeogenesis, and long-term, stimulate appetite and weight gainEffect is dose-dependentA recent prospective randomized trial of early withdrawal of corticosteroids vs remaining on low-dose chronic prednisone (5 mg/d) from 6 months to 5 years after kidney transplant showed that incidence of PTDM was minimally impacted (LOW DOSE REGIMENS HAVE LITTLE IMPACT ON BG)
Slide14Immunosuppressive Therapy and HyperglycemiaMycophenolate mofetil and azathioprine have not been shown to have a large impact on insulin action or glucose metabolism Tacrolimus was shown to increase the incidence of prediabetes after kidney transplant (33% at 12 mo)Data from the U.S. Renal Database suggest that sirolimus is independently associated with increased risk for diabetes after kidney transplantHypomagnesemia alone is known to impact insulin signaling, is commonly associated with CNI treatment, and is associated with increased risk for PTDM
Slide15https://link.springer.com/article/10.1007%2Fs13300-018-0374-8
Slide16Why Should We Treat PTDM?Solid thin line- no diabetesDashed line- PTDMBold line- diabetes prior to transplant
Slide17Slide18MetforminWhy do we use it?Great for addressing pre-existing insulin resistance and increased hepatic gluconeogenesis (offset the side effects from high dose glucocorticoids)
Slide19Slide20SGLT-2 Inhibitors
Slide21Glucagon-like Peptide-1 Receptor agonists No guidance however preliminary case studies suggest GLP-1 RAs do not significantly alter the absorption of tacrolimus or glucocorticoids in patients on stable doses
Slide22Slide23SummaryInternational Consensus meeting on posttransplant diabetes recommends a stepwise approach starting with insulin therapy then initiating oral therapy and other non-insulin injectablesMetformin is a recommended 1st line oral option in patients with an eGFR >30SGLT-2 inhibitors show promise but require more data to support their use in this populationGLP-1 RAs have preliminary data illustrating safe use with immunosuppressive agentsLinagliptin (tradjenta) is the favored DPP-4 inhibitor since it is excreted in the feces 80% unchangedRepaglinide is favored over sulfonylureas due to a lower risk of hypoglycemia and favorable safety data in this population
Slide24Slide25CitationsOrgan Donation Statistics. organdonor.gov. https://www.organdonor.gov/learn/organ-donation-statistics. Accessed September 14, 2021. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020 Oct;98(4S):S1-S115. doi: 10.1016Vijay Shivaswamy, Brian Boerner, Jennifer Larsen, Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes, Endocrine Reviews, Volume 37, Issue 1, 1 February 2016, Pages 37–61. doi: 10.1210Nicole R. Pinelli, Anita Patel, Francine D. Salinitri. Coadministration of Liraglutide With Tacrolimus in Kidney Transplant Recipients: A Case Series. Diabetes Care Oct 2013, 36 (10) e171-e172; DOI: 10.2337Sharif A,
Hecking
M, de Vries AP, et al. Proceedings from an international consensus meeting on
posttransplantation
diabetes mellitus: recommendations and future directions. Am J Transplant. 2014 Sep;14(9):1992-2000.
doi
: 10.1111