RESUMEN
OBJECTIVE: To assess the landscape of digital health resources in the United States, better understand the impact of the digital health on shared decision-making, and identify potential barriers and opportunities for progress in the care of persons with diabetes. METHODS: The study consisted of two phases: A qualitative phase in which one-on-one interviews were conducted virtually with 34 physicians (endocrinologists {Endos}: n = 15; primary care physicians {PCPs}: n = 19) between February 11, 2021 and February 18, 2021, and a quantitative phase in which two online, email-based surveys in the English language were conducted between April 16, 2021 and May 17, 2021: one with healthcare professionals (HCP) (n = 403: n = 200 Endos and n = 203 PCPs), and one with persons with diabetes (n = 517: patients with type 1 diabetes, n = 257; patients with type 2 diabetes, n = 260). RESULTS: Diabetes digital health tools were found to be helpful in shared decision-making, but leading barriers include cost, coverage, and lack of time by healthcare professionals. Among diabetes digital health tools, continuous glucose monitoring (CGM) systems were used most commonly and viewed as most effective in improving quality of life and facilitating shared decision-making. Strategies for increasing use of diabetes digital health resources included lower cost, integration into electronic health records, and increased simplicity of tools. CONCLUSION: This study revealed that both Endos and PCPs feel that diabetes digital health tools have an overall positive impact. Integration with telemedicine and simpler, lower cost tools with increased patient access can further facilitate shared decision-making and improved diabetes care and quality of life.
Asunto(s)
Diabetes Mellitus Tipo 2 , Médicos , Humanos , Estados Unidos , Diabetes Mellitus Tipo 2/terapia , Calidad de Vida , Automonitorización de la Glucosa Sanguínea , GlucemiaRESUMEN
Significant hyperglycemia is commonly observed immediately after solid organ and bone marrow transplant as well as with subsequent hospitalizations. Surgery and procedures are well known to cause pain and stress leading to secretion of cytokines and other hormones known to aggravate insulin action. Immunosuppression required for transplant and preexisting risk are also major factors. Glucose control improves outcomes for all hospitalized patients, including transplant patients, but is often more challenging to achieve because of frequent and sometimes unpredictable changes in immunosuppression doses, renal function, and nutrition. As a result, risk of hypoglycemia can be greater in this patient group when trying to achieve glucose control goals for hospitalized patients. Key to successful management of hyperglycemia is regular communication between the members of the care team as well as anticipating and rapidly implementing a new treatment paradigm in response to changes in immunosuppression, nutrition, renal function, or evidence of changing insulin resistance.
Asunto(s)
Hospitalización , Cuidados Posoperatorios , Trasplante , Glucemia/metabolismo , Diabetes Mellitus/etiología , Diabetes Mellitus/prevención & control , Humanos , Factores de Riesgo , Trasplante/efectos adversosRESUMEN
Introduction: Type 2 diabetes mellitus (T2DM) has affected many people worldwide. One population that is greatly affected by T2DM is the Asian Indian population. The relative effects of genetics and environment on the development of diabetes in adults are not completely understood. Objectives: We conducted an analysis to determine if location, through the environment and different diets, affects T2DM inheritance in Asian Indians. We hypothesised that the prevalence of T2DM depended on location. Materials and Methods: We analysed previously collected data on T2DM in the individual states of India and the U.S. and used this information to compare the prevalence of T2DM in Asian Indians living in these two countries. Results: A total of 1,117,465,226 individuals were surveyed in India. Of these, 108,295,674 individuals had T2DM. Similarly, of the 1,704,846 individuals in the US, 298,107 had T2DM. The prevalence of T2DM was 17.49% in Asian Indians living in the US compared to 9.69% for Indians living in India (P < 0.00001). In individuals with similar genetic backgrounds, environmental factors significantly influence the development of T2DM.
RESUMEN
AIMS: Patients with diabetic foot ulcers are instructed to be non-weight bearing on the affected limb to promote healing. Therefore, the aim of this study was to investigate the effect of different assistive devices on whole foot plantar loading, peak forefoot force, ankle range of motion, and locomotion speed during gait in patients with Type 2 Diabetes Mellitus. METHODS: Participants walked normally, with crutches, a walker, and a wheeled knee walker (WKW) in randomized order. Force sensitive insoles and 3D motion capture were used to record plantar normal force and ankle kinematics. Force sensitive pads were wrapped around handles of the crutches and walker to measure bodyweight offloaded onto the assistive device. An instrumented WKW was used to measure bodyweight offloaded onto the handlebars and knee cushion. RESULTS: Locomotion with the WKW produced the lowest whole foot plantar loading and peak forefoot force in the propulsive limb, while also producing the greatest ankle range of motion and locomotion speed amongst assistive devices. CONCLUSIONS: This pre-clinical study found that the WKW could be the preferred assistive device for total unilateral offloading of diabetic foot ulcers as it reduced propulsive limb whole foot and forefoot plantar loading while retaining ankle range of motion and locomotion speed.
Asunto(s)
Diabetes Mellitus Tipo 2 , Pie Diabético , Humanos , Tobillo , Diabetes Mellitus Tipo 2/complicaciones , Presión , Caminata , Rango del Movimiento Articular , Fenómenos Biomecánicos , Peso CorporalRESUMEN
BACKGROUND: Analysis of cytologically indeterminate thyroid nodules with Afirma Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) can reduce surgical rate and increase malignancy rate of surgically resected indeterminate nodules. METHODS: Retrospective cohort analysis of all adults with cytologically indeterminate thyroid nodules from January 2013 through December 2019. We compared surgical and malignancy rates of those without molecular testing to those with GEC or GSC, analyzed test performance between GEC and GSC, and identified variables associated with molecular testing. RESULTS: 468 indeterminate thyroid nodules were included. No molecular testing was performed in 273, 71 had GEC, and 124 had GSC testing. Surgical rate was 68% in the group without molecular testing, 59% in GEC, and 40% in GSC. Malignancy rate was 20% with no molecular testing, 22% in GEC, and 39% in GSC (P = 0.022). GEC benign call rate (BCR) was 46%; sensitivity, 100%; specificity, 61%; and positive predictive value (PPV), 28%. GSC BCR was 60%; sensitivity, 94%; specificity, 76%; and PPV, 41%. Those with no molecular testing had larger nodule size, preoperative growth of nodules, and constrictive symptoms and those who underwent surgery in the no molecular testing group had higher body mass index, constrictive symptoms, higher Thyroid Imaging Reporting and Data System and Bethesda classifications. Type of provider was also associated with the decision to undergo surgery. CONCLUSION: Implementation of GEC showed no effect on surgical or malignancy rate, but GSC resulted in significantly lower surgical and higher malignancy rates. This study provides insight into the factors that affect the real-world use of these molecular markers preoperatively in indeterminate thyroid nodules.
RESUMEN
INTRODUCTION: Management of post-transplant diabetes mellitus is challenging; there is a lack of prospective randomized controlled trials for safety and efficacy of antidiabetic medications in solid organ recipients. Glucagon-like peptide 1 receptor agonists (GLP-1RA) are a relatively new class of medications used to manage type 2 diabetes in the general population. They have several benefits besides glycemic control, including weight loss and improved cardiovascular risk. However, they have not been studied extensively in the post-transplant population for safety and efficacy. METHODS: We conducted a retrospective study of patients who had received kidney, liver, or heart transplant, had diabetes either pre- or post-transplant, and were treated with GLP-1RA. We identified seven kidney, seven liver, and five heart transplant recipients who had received GLP-1RA. We assessed changes in immunosuppressant levels, rejection episodes, changes in hemoglobin A1c (HbA1c), weight, and body mass index (BMI) while on the GLP-1RA. We also looked at changes in insulin dose, other diabetes medications, heart rate, blood pressure, and renal function. RESULTS: After a mean follow-up period of 12 months, there were no significant changes in tacrolimus (FK506) levels and renal function for the period of GLP-1RA use. At the end of 12 months, the mean drop in weight was 4.86 kg [95% CI - 7.79, - 1.93]. The BMI decreased by a mean of 1.63 kg/m2 at the end of 12 months [95% CI - 2.53, - 0.73]. HbA1c decreased from baseline by 1.08% [95% CI - 1.65, - 0.51], 0.96% [95% CI - 1.68, - 0.25], and 0.75% [95% CI - 1.55, 0.05] at 3, 6, and 12 months, respectively. CONCLUSIONS: Our data suggest that GLP-1RA do not affect tacrolimus levels or transplant outcomes in solid organ transplant (SOT) recipients in the short term. GLP-1RA also seem to be as effective in SOT recipients for glycemic control and weight loss as in the non-transplant population with diabetes.
RESUMEN
We previously reported that fish oil in combination with cyclooxygenase (COX) inhibitors exerts enhanced hypolipidemic and anti-inflammatory effects in mice. Here, we sought to determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in combination with naproxen (NX), a COX inhibitor, on dyslipidemia and gene expression in adipose tissue (AT) in humans. Obese dyslipidemic patients were randomly assigned to one of these interventions for 12 wk: 1) Standard nutrition counseling (control), 2) ω-3 PUFAs (2â¯g twice daily), 3) NX (220â¯mg twice daily), and 4) ω-3 PUFAs (2â¯g twice daily)â¯+â¯NX (220â¯mg twice daily). The serum triglycerides showed a trend towards a reduction and a significant reduction (P<0.05) in ω-3 and ω3â¯+â¯NX-treated subjects, respectively, compared to control. The mRNA expression of vascular cell adhesion molecule-1 (Vcam1), an inflammatory marker, increased significantly in AT of ω-3 PUFA-treated subjects but not in ω-3 PUFAs+NX-treated group. The plasma level of glycine-conjugated hyodeoxycholic acid, a secondary bile acid with hypolipidemic property, increased significantly in ω-3 PUFAs + NX-treated group. Our data suggest that combining NX with ω-3 PUFAs increases their effectiveness in reducing serum TG and favorably altering AT gene expression and plasma bile acid profile.
Asunto(s)
Inhibidores de la Ciclooxigenasa/uso terapéutico , Dislipidemias/tratamiento farmacológico , Ácidos Grasos Omega-3/uso terapéutico , Aceites de Pescado/uso terapéutico , Naproxeno/uso terapéutico , Obesidad/complicaciones , Tejido Adiposo/patología , Adulto , Biopsia , Dislipidemias/sangre , Dislipidemias/etiología , Femenino , Humanos , Inflamación/sangre , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad/sangre , Sobrepeso/sangre , Sobrepeso/complicaciones , Proyectos Piloto , Estudios Prospectivos , Triglicéridos/sangreRESUMEN
This study investigates spatiotemporal gait adjustments that occur while stepping over virtual obstacles during treadmill walking in people with/without diabetic peripheral neuropathy (DPN). Eleven adults with Type 2 diabetes mellitus, ten DPN, and 11 age-matched healthy adults (HTY) participated in this study. They stepped over forthcoming virtual obstacles during treadmill walking. Outcomes such as success rate, spatiotemporal gait characteristics during obstacle crossing, and correlations between these variables were evaluated. The results partially supported our hypotheses that when comparing with HTY and DM, people with DPN adopted a crossing strategy which decreased obstacle crossing success rate and maximal toe elevation, and increased stride time and stance time during virtual obstacle crossing. This might be due to the compromised somatosensory functions of their lower extremity which may increase the risk of falling. This study also found an inter-leg relationship which may be applied to future stepping or obstacle crossing training that incorporates both legs as a means for improving outcomes of the trailing leg during daily obstacle negotiation.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/fisiopatología , Marcha/fisiología , Conducta Espacial/fisiología , Adulto , Anciano , Fenómenos Biomecánicos , Estudios de Casos y Controles , Prueba de Esfuerzo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Equilibrio Postural/fisiología , Realidad Virtual , Caminata/fisiologíaRESUMEN
Ept1, Ept2, Ept6, and Ept9 are quantitative trait loci mapped in crosses between the ACI and Copenhagen (COP) rat strains as genetic determinants of responsiveness of the pituitary gland to estrogens. We have developed four congenic rat strains, each of which carries, on the genetic background of the ACI rat strain, alleles from the COP rat strain that span one of these quantitative trait loci. Relative to the female ACI rats, female ACI.COP-Ept1 rats exhibited reduced responsiveness to 17beta-estradiol (E2) in the pituitary gland, as evidenced by quantification of pituitary mass and circulating prolactin, and in the mammary gland, as evidenced by reduced susceptibility to E2-induced mammary cancer. The ACI.COP-Ept2 rat strain exhibited reduced responsiveness to E2 in the pituitary gland but did not differ from the ACI strain in regard to susceptibility to E2-induced mammary cancer. Interestingly, female Ept2 congenic rats exhibited increased responsiveness to E2 in the thymus, as evidenced by enhanced thymic atrophy. The ACI.COP-Ept6 rat strain exhibited increased responsiveness to E2 in the pituitary gland, which was associated with a qualitative phenotype suggestive of enhanced pituitary vascularization. The ACI.COP-Ept9 rat strain exhibited reduced responsiveness to E2 in the anterior pituitary gland, relative to the ACI rat strain. Neither Ept6 nor Ept9 impacted responsiveness to E2 in the mammary gland or thymus. These data indicate that each of these Ept genetic determinants of estrogen action is unique in regard to the tissues in which it exerts its effects and/or the direction of its effect on estrogen responsiveness.
Asunto(s)
Resistencia a Medicamentos/genética , Estrógenos/farmacología , Hipófisis/efectos de los fármacos , Sitios de Carácter Cuantitativo/fisiología , Animales , Animales Congénicos , Atrofia/genética , Femenino , Marcadores Genéticos/fisiología , Predisposición Genética a la Enfermedad , Incidencia , Neoplasias Mamarias Animales/epidemiología , Neoplasias Mamarias Animales/genética , Tamaño de los Órganos/efectos de los fármacos , Tamaño de los Órganos/genética , Especificidad de Órganos/efectos de los fármacos , Especificidad de Órganos/genética , Hipófisis/crecimiento & desarrollo , Hipófisis/metabolismo , Prolactina/sangre , Ratas , Timo/patologíaRESUMEN
BACKGROUND: Patients with diabetes have been reported to have greater dyslipidemia after kidney transplant (KTX). Because postKTX management of diabetes has changed markedly since those reports, we hypothesized that lipids can be controlled as well in diabetic as in nondiabetic recipients. METHODS: We compared lipid levels up to 2 years after KTX (n=192) between diabetic and nondiabetic recipients. The cohort was subdivided into nondiabetic (nonDM-K; n=123), type 2 (DM2-K; n=33), or type 1 diabetes after KTX (DM1-K; n=14), or type 1 after kidney-pancreas transplant (DM1-KP; n=22). RESULTS: Mean age and body mass index of DM2-K were greater than the others (P<0.01), and diabetes groups had a higher pretransplant A1C than nonDM-K (P<0.001). After KTX, lipid levels were not higher in diabetic than in nondiabetic recipients, and did not increase in any group. Total and low-density lipoprotein cholesterol levels decreased in DM1-K (P<0.001), high-density lipoprotein levels decreased in DM1-KP (P=0.02), and triglyceride levels were unchanged after KTX for all groups. A1C improved in DM1-K and DM1-KP (P<0.0001). There was less improvement in lipid levels with tacrolimus-sirolimus immunosuppression than with other steroid-containing regimens (P<0.05). CONCLUSIONS: Multiple mechanisms may contribute to better lipid levels in both groups as well as the lack of difference between diabetic and nondiabetic recipients compared with what has been reported previously: greater use of and more effective lipid-lowering agents, no significant weight gain, no difference in renal function between groups, and better control of glucose in the diabetic group. Thus, overall, lipids can be controlled as well in diabetic as in nondiabetic KTX recipients.
Asunto(s)
Colesterol/sangre , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/cirugía , Dislipidemias/tratamiento farmacológico , Dislipidemias/etiología , Trasplante de Riñón/efectos adversos , Lípidos/sangre , Complicaciones Posoperatorias/tratamiento farmacológico , Adulto , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Factores de Tiempo , Triglicéridos/sangreRESUMEN
Post-transplant diabetes mellitus (PTDM) is common after most types of solid organ transplantation, though the actual incidence is as yet unknown because of the use of different diagnostic criteria. PTDM is the result of individual risk factors as well as risk factors associated with the transplant itself, particularly immunosuppressants. Previously called New Onset Diabetes, in many cases inadequate screening for diabetes before transplant cannot assure that the diabetes is new after transplant. The most recent international consensus guidelines suggest diagnosis should be delayed until the patient is taking maintenance doses of immunosuppressants even if they require treatment in the immediate hospitalization. Criteria for diagnosis follow those of the American Diabetes Association and the World Health Organization, although hemoglobin A1C should not be used as the only screening test at least until one year after transplant because of its insensitivity for significant glucose intolerance in the transplant patient and setting. Management of PTDM is best done in a team setting, with an emphasis on glycemic control, dyslipidemia, and hypertension, and taking into consideration immunosuppressant regimens and potential drug side effects and interactions. While PTDM has been associated with changes in outcomes, these have and may continue to improve with improved diabetes care in and out of the hospital, and other changes in post-transplant care.
Asunto(s)
Diabetes Mellitus/etiología , Diabetes Mellitus/terapia , Trasplante de Órganos/efectos adversos , Diabetes Mellitus/diagnóstico , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapiaRESUMEN
AIMS: The aim of this study was to compare the changes in the total daily dose (TDD) of insulin of patients on U-500 insulin; before hospitalization, during hospitalization and six weeks after discharge. METHODS: A retrospective chart review of veterans with type 2 diabetes receiving U-500 insulin in the ambulatory setting and who were admitted between 2012 and 2015 was performed. During hospitalization, patients were transitioned to receive U-100 insulin (detemir or glargine for basal and aspart for bolus). Paired t-tests were conducted to compare TDD of insulin during hospitalization to prior to admission and at six week of follow-up. RESULTS: The average hemoglobin A1c at the time of hospital admission was 8.3±1.5% (n=20). The average TDD of insulin during hospitalization (124±67units) was significantly less than prior to admission (295±123units) and at six week follow-up (310±105units). The average glucose during hospitalization was 180±36mg/dL. Hypoglycemia was less than 0.5%. CONCLUSION: We showed that patients received significantly less total daily insulin while hospitalized compared to their insulin doses in the ambulatory setting, and we demonstrate that patients receiving U-500 insulin can be safely transitioned to U-100 insulin while hospitalized, with minimal hypoglycemia.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Insulina Regular Humana/administración & dosificación , Anciano , Diabetes Mellitus Tipo 2/sangre , Monitoreo de Drogas , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Hospitales de Veteranos , Humanos , Hiperglucemia/epidemiología , Hiperglucemia/fisiopatología , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemia/fisiopatología , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Incidencia , Insulina Regular Humana/efectos adversos , Insulina Regular Humana/uso terapéutico , Tiempo de Internación , Masculino , Registros Médicos , Persona de Mediana Edad , Nebraska/epidemiología , Estudios Retrospectivos , Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.
Asunto(s)
Costo de Enfermedad , Diabetes Mellitus/terapia , Medicina Basada en la Evidencia , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/terapia , Medicina de Precisión , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Animales , Terapia Combinada , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Órganos/mortalidad , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/epidemiología , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Estrés FisiológicoRESUMEN
The dramatic rise in the prevalence of obesity and diabetes is associated with increased morbidity, mortality, and public health care costs worldwide. The need for new, effective, and long-lasting drugs is urgent. Recent research has focused on the role of the inhibitors of sodium- glucose co-transporter 2 (SGLT-2). Clinical trials have shown that SGLT-2 inhibitors have glycemic efficacy and weight-lowering potential. Dual drug therapy is a recommended therapy for patients with new-onset type 2 diabetes who need significant glycemic control. Fixed-dose combination therapy represents a particularly attractive option as it may reduce pill burden and improve adherence. The combination of metformin and empagliflozin was approved by the US Food and Drug Administration in 2014 and represents a safe and effective means to combat glycemic control and weight gain. The purpose of this systematic review is to summarize the background of the SGLT-2 inhibitors, particularly empagliflozin, and focus on the safety and efficacy of the fixed-dose combination of empagliflozin and metformin.
RESUMEN
A rare cause for rapid adrenal enlargement is adrenal oncocytoma of uncertain malignant potential. A full biochemical evaluation is warranted to screen secreting adrenal adenomas as well as to evaluate adrenal cortical carcinoma. Careful pathologic evaluation is required as the diagnosis of AOC cannot be made by imaging.
RESUMEN
Maturity onset diabetes of the young (MODY) is a rare form of diabetes mellitus typically seen in young adults that results from pancreatic beta-cell dysfunction. MODY4 is a rare subtype caused by a PDX1 mutation. In this case, we present a nonobese 26-year-old male with polyuria and polydipsia. Lab work showed a blood glucose of 511 mg/dL, no ketones or antibodies (insulin, islet cell, and glutamic acid decarboxylase [GAD]), C-peptide of 1.6 ng/mL, and A1c 9.3%. Genetic analysis revealed a novel nonsense mutation in the PDX1 gene, consistent with MODY type 4. Given this patient's particular genetic mutation affecting the incretin pathway, sitagliptin was substituted for glyburide, which led to significant improvement in glycemic control. Our case report identifies a unique mutation in a rare form of MODY and outlines management of ensuing diabetes through targeting its inherent genetic mutation.
RESUMEN
New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5 ± 17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients.
RESUMEN
Although the contribution of the immunosuppressants tacrolimus (TAC) and sirolimus (SIR) to the development of posttransplant diabetes mellitus (PTDM) are being increasingly recognized, the mechanisms of immunosuppressant-induced hyperglycemia are unclear. SIR induces insulin resistance predominantly, but is associated with ß-cell dysfunction in rodents. TAC affects islet function but is associated with worsening insulin sensitivity in a few, and improvement in some, clinical studies. We sought to clarify the contributions of TAC and SIR to insulin resistance and islet function. Four groups of male and female Sprague-Dawley rats received TAC, SIR, TAC and SIR, or control for 2 weeks. All rats were administered an oral glucose challenge at the end of treatment. Half the groups were sacrificed 10 minutes after administration of regular insulin whereas the other half did not receive insulin before sacrifice. Liver, pancreas, fat, and muscle were harvested subsequently. Quantification of Western blots revealed that SIR and TAC plus SIR suppressed the phospho-Akt (pAkt)-to-Akt ratios in liver, muscle, and fat compared with control, regardless of sex. TAC alone did not impair the pAkt-to-Akt ratios in any of the tissues in male and female rats. ß-Cell mass was reduced significantly after TAC treatment in male rats. SIR did not affect ß-cell mass, regardless of sex. Our study demonstrated very clearly that SIR impairs insulin signaling, without any effect on ß-cell mass, and TAC does not impair insulin signaling but reduces ß-cell mass. Our efforts are key to understanding the mechanisms of immunosuppressant-induced hyperglycemia and to tailoring treatments for PTDM.
Asunto(s)
Insulina/sangre , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Tacrolimus/farmacología , Tejido Adiposo/efectos de los fármacos , Animales , Femenino , Hiperglucemia/inducido químicamente , Hiperglucemia/etiología , Inmunosupresores/farmacología , Hígado/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Páncreas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factores Sexuales , TrasplantesRESUMEN
BACKGROUND: Immunosuppressants are an important cause of posttransplantation diabetes mellitus. We have shown that tacrolimus and sirolimus induce hyperglycemia and hyperinsulinemia in normal rats. We hypothesized that metformin, given concurrently with tacrolimus and/or sirolimus, prevents disturbances in glucose and insulin metabolism. METHODS: Eight groups (n=6) of normal Sprague-Dawley rats were studied: four groups received tacrolimus, sirolimus, tacrolimus/sirolimus, or control for 14 days, and four more groups received similar treatments along with metformin. Daily glucoses were measured. All rats were administered an oral glucose challenge before sacrifice. Pancreata were analyzed by terminal deoxynucleotide tranferase-mediated dUTP nick-end labeling staining and immunohistochemistry. RESULTS: Tacrolimus, sirolimus, and tacrolimus/sirolimus impaired glucose tolerance compared to control. Sirolimus and tacrolimus/sirolimus also increased random blood glucose levels. Sirolimus alone resulted in hyperinsulinemia after oral glucose challenge compared to control. In the sirolimus/metformin and tacrolimus/sirolimus/metformin groups, mean daily random glucose was no longer increased, although the response to glucose challenge was still impaired. Metformin decreased pancreatic exocrine and trended to decrease endocrine apoptosis in tacrolimus/sirolimus group and reduced islet insulin content in sirolimus group. CONCLUSIONS: This is the first study to show that metformin can improve immunosuppressant-induced hyperglycemia, when administered concurrently, and reduces exocrine apoptosis (reducing the impact on potential islet progenitor cells).