Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: An Observational Cohort Study
Débora Dias de Lucena, João Roberto de Sá, José Osmar Medina Pestana, Érika Bevilaqua Rangel
Abstract
Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mn>46.2</mml:mn><mml:mo>±</mml:mo><mml:mn>1.3</mml:mn></mml:math> vs .<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mn>40.7</mml:mn><mml:mo>±</mml:mo><mml:mn>0.6</mml:mn></mml:math>years old, OR 1.04;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.001</mml:mn></mml:math>) and pretransplant hyperglycaemia and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mtext>BMI</mml:mtext><mml:mo>≥</mml:mo><mml:mn>25</mml:mn><mml:mtext> </mml:mtext><mml:mtext>kg</mml:mtext><mml:mo>/</mml:mo><mml:msup><mml:mrow><mml:mtext>m</mml:mtext></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math>(32.8% vs . 21.6%, OR 0.54;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.032</mml:mn></mml:math>and 57.4% vs . 27.7%, OR 3.5;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>P</mml:mi><mml:mo><</mml:mo><mml:mn>0.0001</mml:mn></mml:math>, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03;<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), acute rejection (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.021</mml:mn></mml:math>), calcium channel blockers (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.014</mml:mn></mml:math>), TG/HDL (triglyceride/high-density lipoprotein cholesterol)<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"><mml:mtext>ratio</mml:mtext><mml:mo>≥</mml:mo><mml:mn>3.5</mml:mn></mml:math>at 1 year (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M11"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.01</mml:mn></mml:math>) and at 3 years (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M12"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M13"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.035</mml:mn></mml:math>),<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M14"><mml:mtext>pretransplant</mml:mtext><mml:mtext> </mml:mtext><mml:mtext>BMI</mml:mtext><mml:mo>≥</mml:mo><mml:mn>25</mml:mn><mml:mtext> </mml:mtext><mml:mtext>kg</mml:mtext><mml:mo>/</mml:mo><mml:msup><mml:mrow><mml:mtext>m</mml:mtext></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math>(<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M15"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), posttransplant transient hyperglycaemia (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M16"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M17"><mml:mtext>TG</mml:mtext><mml:mo>/</mml:mo><mml:mtext>HDL</mml:mtext><mml:mtext> </mml:mtext><mml:mtext>ratio</mml:mtext><mml:mo>≥</mml:mo><mml:mn>3.5</mml:mn></mml:math>at 3-year posttransplant (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M18"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.003</mml:mn></mml:math>) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.