Posttransplant Diabetes Mellitus: Recent Developments in Pharmacological Management of Hyperglycemia.

CONTEXT: The management of solid-organ transplantation is rapidly evolving, and posttransplant diabetes mellitus (PTDM), which is increasingly common, is a barrier to transplant success, adversely impacting infection rates, allograft survival, cardiovascular disease, quality of life, and overall mortality. Currently, the management of PTDM relies primarily on intensified insulin therapy. However, emerging studies report that several noninsulin glucose-lowering agents are safe and effective in improving metabolic control and enhancing treatment adherence. More importantly, their use in PTDM can potentially transform the long-term management of these complex patients, as some glucose-lowering agents may provide benefits beyond glycemic control. For instance, glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors may offer cardiorenal protection, and pioglitazone may treat nonalcoholic fatty liver disease (NAFLD). This review will focus on the pharmacological management of PTDM and the emerging evidence for noninsulin glucose-lowering agents in this population. EVIDENCE ACQUISITION: Evidence from observational studies, randomized controlled trials, and meta-analyses. EVIDENCE SYNTHESIS: PTDM adversely affects the outcomes of infection, organ survival, cardiovascular events, and mortality. Insulin therapy has been the drug of choice but is associated with weight gain and hypoglycemia. In contrast, noninsulin agents appear safe and may provide additional benefits, such as cardiorenal protection with SGLT-2 inhibitors and GLP-1 RA, and cardiometabolic benefits with pioglitazone, in patients undergoing solid-organ transplantation. CONCLUSIONS: Optimal care of patients with PTDM requires close monitoring and the early involvement of the endocrinologist as part of a multidisciplinary team. Noninsulin glucose-lowering agents will likely play an increasing role as more long-term, controlled studies become available in this setting.

Feasibility and performance of continuous glucose monitoring in hyperglycemia after lung transplantation.

Background: Post-Transplant Diabetes Mellitus (PTDM) affects 20%-40% of lung transplant recipients within five years, impacting rejection, infection, cardiovascular events, and mortality. Continuous glucose monitoring (CGM) is used in diabetes but not well-studied in PTDM. Objective: This study assessed CGM performance in detecting hypoglycemia and hyperglycemia post-lung transplantation, compared to self-monitoring blood glucose. Methods: A prospective pilot study included 15 lung transplant patients (mean age 58.6 years; 53.3% men; 73.3% with pre-transplantation diabetes) managing hyperglycemia with insulin. Patients used a blinded CGM and self-monitored glucose for ten days. Data were categorized (% time in range, % high, % very high, % low, % very low) and compared using paired t-tests. Results: CGM showed superior hyperglycemia detection. Mean differences for "% very high", "% high", and "% high and % very high" were 7.12 (95% CI, 1.8-12.4), 11.1 (95% CI, 3.5-18.8), and 18.3 (95% CI: 7.37-29.24), respectively. No significant difference was found for "% low and % very low". All patients reported a positive CGM experience. Conclusion: CGM use post-lung transplantation seems feasible and offers advantages in detecting hyperglycemia and in optimizing glucose management. Study limitations include a small sample size, requiring larger studies to assess glycemic control, hypoglycemia detection, and transplant outcomes.

A nurse-led intervention in patients with newly diagnosed cancer and Type 2 diabetes: A pilot randomized controlled trial feasibility study.

BACKGROUND: Undiagnosed Type 2 diabetes (T2D) has been associated with advanced stage cancer at diagnosis, higher mortality, and lower long-term all-cause survival. This was a RCT pilot study to examine the feasibility of a nurse-led T2D intervention for adults with newly diagnosed cancer (≤3 months), and T2D, undiagnosed or untreated with medication, conducted at an outpatient oncology clinic affiliated with a large academic institution. METHODS: Participants needed to meet the eligibility criteria including a HbA1c level between 6.5% and 9.9%. Randomization was 1:1 to a 3-month intervention that consisted of nursing-led diabetes education and immediate initiation of metformin versus referral to primary care for usual care (control). RESULTS: Three hundred and seventy nine patients were screened using EHR, 55 agreed to participate, and 3 had eligible HbA1c levels and were randomized in the study. Primary reasons for study exclusion included life expectancy ≤2 years (16.9%), current use or inability to tolerate metformin (14.8%), and abnormal labs that contraindicated metformin use (13.9%). CONCLUSION: This study was not feasible due to recruitment inefficiencies, but acceptable to all who qualified.

Examining the relationship between metformin dose and cancer survival: A SEER-Medicare analysis.

Cancer is a major health problem in the U.S and type 2 diabetes mellitus (T2DM) is known to increase the risk for the development of many cancers. Metformin, a first-line therapy for treating T2DM, is increasingly being used for its anticancer effects; however, the literature is limited on the effect of metformin dose on overall survival in patients with stage IV cancer. Overall survival was defined as the time interval from the date of diagnosis to the last known follow-up or death from any cause. Subjects who were alive on December 31, 2016 were censored. In this cohort study we examined the relationship between metformin dose and overall survival in persons with both T2DM and stage IV lung, breast, colorectal, prostate, or pancreas cancers. We used a retrospective study design with Cox proportional hazards regression analysis of the 2007-2016 of the Surveillance Epidemiology and End Results-Medicare (SEER) dataset. Of the 7,725 patients, 2,981(38.5%) had been prescribed metformin. Patients who used metformin had significantly better overall survival in both unadjusted (Unadjusted HR, 0.73; 95% CI, 0.69-0.76; p < 0.001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; p < 0.001). The overall survival between patients who took metformin with average daily dose ≥ 1000mg or < 1000mg were not statistically significant (aHR, 1.00; 95% CI, 0.93-1.08; p = 0.90). Metformin use regardless of dose is associated with increased overall survival in older adults with stage IV cancer.

New onset of type 2 diabetes as a complication after cancer diagnosis: A systematic review.

BACKGROUND: Despite improved survival rates, cancer survivors are experiencing worse health outcomes with complications of treatment, such as type 2 diabetes mellitus (T2D), that may deteriorate survivorship. The purpose of this review was to provide a comprehensive review of T2D incidence following cancer diagnosis. METHODS: The study included: (1) cohort studies, (2) cancer diagnosis by a doctor, (3) incidence of T2D after diagnosis of cancer, and (4) adult patients over 18 years. Studies that focused on patients who had T2D as a preexisting condition at cancer diagnosis were excluded. RESULTS: Of a total of 16 studies, overall incidence of T2D ranged from 5.4% to 55.3%. The highest T2D incidence rate was observed in colorectal patients with cancer (53%). While results in prostate patients with cancer were mixed, patients who underwent androgen deprivation therapy (ADT) had a significantly higher incidence of new-onset T2D (12.8%, p = 0.01). Patients treated with chemotherapy within 1-5 years of initial diagnosis of colorectal cancer were at approximately 30% higher risk of T2D. One study found that 48% of T2D was preventable with optimal management during the process of patient care. CONCLUSION: Blood glucose management may allow physicians to intervene early and improve outcomes among patients with cancer.

Usefulness of Oximetry Paradoxus to Diagnose Cardiac Tamponade.

Although echocardiography is usually diagnostic of cardiac tamponade, it may not be readily available at the point-of-care. We sought to develop and validate a measurement of respirophasic variation in the amplitude of pulse oximetry plethysmographic waveforms as a diagnostic tool for cardiac tamponade. Pulse oximetry plethysmographic waveforms were recorded, and the ratio of maximum-to-minimum measured amplitude of these waveforms from one respiratory cycle was calculated by blinded observers. Ratios from 3 consecutive respiratory cycles were then averaged to derive an "oximetry paradoxus" ratio. Cardiac tamponade was independently confirmed or excluded according to a "blinded" objective interpretation of echocardiography or right heart catheterization. Seventy four subjects were enrolled (51% men; mean age 54 ± 15 years); 19 of whom had cardiac tamponade. Oximetry paradoxus area under the curve for diagnosis of cardiac tamponade was 0.90 (95% confidence interval, 0.84 to 0.97); its diagnostic performance was superior to sphygmomanometer-measured pulsus paradoxus (area under the curve difference = 0.16, p = 0.022). In a derivation cohort (n = 37; tamponade, 9 cases), 3 diagnostic oximetry paradoxus thresholds were identified and validated in an independent validation cohort (n = 37; tamponade, 10 cases): 1.2 (100% sensitivity, 44% specificity), 1.5 (80% sensitivity, 81% specificity), and 1.7 (80% sensitivity, 89% specificity). Furthermore, oximetry paradoxus was significantly reduced after draining pericardial fluid. In conclusion, we defined and validated oximetry paradoxus as a simple and ubiquitous point-of-care test to diagnose cardiac tamponade using respirophasic changes in pulse plethysmography waveforms. This test can aid in identifying patients with cardiac tamponade, thus expediting confirmatory testing and life-saving treatment.

Aorto-right atrial fistula: Late complication of tricuspid valve infective endocarditis.

Abnormal connections between the ascending aorta and the cardiac chambers are rare, especially in the context of right-sided infective endocarditis (IE). Transthoracic echocardiography (TTE) with color-flow Doppler, transesophageal echocardiography (TEE), or both may be required for diagnosis. We present the case of a woman admitted with right-sided heart failure (HF) symptoms. She had a previous history of tricuspid valve IE 30 years ago. TTE and TEE revealed an aorto-right atrium fistula located just under the non-coronary cusp into the right atrium at the level of the previously affected tricuspid valve. The Patient refused surgery and was discharged home on HF medications. She has been stable for the last 3 years. The peculiarity of this case is the late symptomatic presentation of the aorto-atrial fistula and the unusual association to tricuspid valve IE.