Aspirin for Primary Prevention of Cardiovascular Disease in Diabetes: a Review of the Evidence.

PURPOSE OF REVIEW: People with diabetes are at a higher risk of atherosclerotic cardiovascular disease (ASCVD) compared with those without diabetes. Though aspirin has been shown to have an overall net clinical benefit when used for secondary prevention of ASCVD in people with and without diabetes, the evidence for primary prevention, especially in those with diabetes, remains inconsistent. In this article, we review the latest studies examining the risks and benefits of aspirin use for primary prevention of ASCVD in adults with diabetes, discuss key aspects in assessing the risk-benefit ratio of aspirin use for primary prevention of ASCVD, and summarize current guidelines from professional societies on aspirin use for primary prevention in adults with diabetes. RECENT FINDINGS: In the general population, past studies have shown no difference in the beneficial effect of aspirin for primary cardiovascular disease prevention by diabetes status. However, several randomized controlled studies and meta-analyses in adults with diabetes have shown lack of net clinical benefit of aspirin use for primary prevention of ASCVD. The recent ASCEND trial documented cardiovascular benefit of aspirin for primary prevention in adults with diabetes but suggested that the increased risk of bleeding may outweigh the cardiovascular benefit. The decision to initiate aspirin for primary prevention of ASCVD must be considered carefully on an individual basis to balance the cardiovascular benefit and bleeding risk in all patients, especially those with diabetes. A multifactorial approach that focuses on managing ASCVD risk factors such as hypertension, dyslipidemia, dysglycemia, and smoking is recommended in all patients. More research is needed to identify subgroups of people with diabetes who are more likely to benefit from aspirin use for primary prevention of ASCVD and develop better antithrombotic strategies that shift the risk-benefit balance toward an overall net clinical benefit.

Glycemic Outcomes of Islet Autotransplantation.

PURPOSE OF REVIEW: While there has been a growing utilization of total pancreatectomy with islet autotransplantation (TPIAT) for patients with medically refractory chronic pancreatitis over the past few decades, there remains a lack of consensus clinical guidelines to inform the counseling and management of patients undergoing TPIAT. In this article, we review the current clinical practice and published experience of several TPIAT centers, outline key aspects in managing patients undergoing TPIAT, and discuss the glycemic outcomes of this procedure. RECENT FINDINGS: Aiming for lower inpatient glucose targets immediately after surgery (usually 100-120 mg/dl), maintaining all patients on subcutaneous insulin for at least 3 months to "rest" islets before an attempt is made to wean insulin, and close outpatient endocrinology follow-up after TPIAT particularly in the first year is common and related to better outcomes. Although TPIAT procedures and glycemic outcomes may differ across surgical centers, overall, approximately one third of patients are insulin independent at 1 year after TPIAT. Higher islet yield and lower preoperative glucose levels are among the strongest predictors of short-term post-operative insulin independence. Beyond 1 year post-operatively, the clinical management and long-term glycemic outcomes of patients after TPIAT are more variable. A multidisciplinary approach is essential in optimizing the preoperative, inpatient, and post-operative management and counseling of patients about the expected glycemic outcomes after surgery. Consensus guidelines for the clinical management of diabetes after TPIAT and harmonization of data collection protocols among TPIAT centers are needed to address the current knowledge gaps in clinical care and research and to optimize glycemic outcomes after TPIAT.

An Unusual Case of the "Terrible Triad" in a Transgender Woman.

With the increasing use of sodium-glucose cotransporter-2 inhibitors for type 2 diabetes and heart failure, clinicians need to understand how to treat euglycemic diabetic ketoacidosis (DKA), which is a potential side effect of the medication. The disease triad of euglycemic ketoacidosis, acute pancreatitis, and hypertriglyceridemia (HTG) has complex pathogenesis, and often the trigger of the triad is unknown. Here, we present an unusual case of euglycemic DKA in a transitioning transgender woman on canagliflozin who was treated with 10% dextrose and insulin infusions and apheresis. What makes our case unique is an added layer of complexity with her use of estrogen supplements contributing to HTG and gallstone formation, which could have set off the disease triad.

Recurrence of Pheochromocytoma With Metastases After Resection of Primary Tumor.

Pheochromocytomas and paragangliomas are rare tumors that arise from the chromaffin cells of the adrenal medulla or sympathetic paravertebral ganglia, respectively. Long-term surveillance is recommended regardless of the thoroughness of surgical resection. Here, we present a patient who was diagnosed with pheochromocytoma who underwent right adrenalectomy and was lost to follow up. She presented 15 years later with recurrence and was found to have multiple metastases. Subsequent genetic testing was also negative.

The relationship of health literacy to diabetes status differs by sex in older adults.

OBJECTIVE: Lower health literacy is associated with higher rates of mortality and chronic disease. It remains unclear whether health literacy is associated with diabetes and/or hyperglycemia in older adults, and if this relationship differs by sex. RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of 2510 older adults in the Health, Aging and Body Composition (Health ABC) Study who had both a Rapid Estimate of Adult Literacy in Medicine (REALM) measurement and diabetes status available. Sex-stratified logistic regression models were used to analyze the relationship of health literacy categories (low, medium, and high) to diabetes status, adjusting for key covariates. Secondary analyses examined the relationship of health literacy to glycemic markers (A1C, fasting blood glucose). RESULTS: Among participants in the Health ABC cohort, 429 had diabetes. Mean age was 76years old and 45% were female. Men with diabetes more commonly had low health literacy levels than men without diabetes (10.1% versus 9.3%, p=0.02). Similar results were seen among women (14.7% versus 6.1%, p<0.01). In a model adjusting for age, race, income, education, BMI, smoking, and alcohol use, women with low versus high health literacy had a two-fold higher likelihood of diabetes (OR=2.2; 95% CI 1.1-4.3). No significant relationship was observed in men. Progressively lower categories of health literacy were associated with higher age-adjusted mean A1C and fasting blood glucose levels in women (both p for trend <0.01) but not men. CONCLUSIONS: In this large, ethnically diverse sample of community-dwelling older adults, lower health literacy level is related to a greater likelihood of diabetes and higher A1C and fasting blood glucose levels in women-but not in men-after adjusting for age, race, and other demographic and lifestyle factors. Future studies are needed to assess mechanisms underlying this relationship and if interventions to improve health literacy are effective in reducing the burden of diabetes, particularly in women.

Comparative Effectiveness for Glycemic Control in Older Adults with Diabetes.

PURPOSE OF REVIEW: To review and summarize the current data for comparative effectiveness of glycemic control in older adults. RECENT FINDINGS: In the last several years, professional societies have released guidelines for glycemic control in older adults, generally recommending individualized HbA1c goals. However, recent observational studies demonstrate that many older adults remain aggressively managed and are at increased risk of hypoglycemia. Large randomized trials of older adults with diabetes have failed to show cardiovascular benefit from intensive glycemic control and show only minimal microvascular benefit. Additionally, a few studies suggest that suboptimal glycemic control can increase the risk for geriatric syndromes. Emerging research suggests similar safety and efficacy of glucose-lowering therapies in older versus younger adults. SUMMARY: Overall, there is a paucity of data supporting the benefit of intensive glycemic control in older adults. More research is needed in this vulnerable population.

Glycemic Predictors of Insulin Independence After Total Pancreatectomy With Islet Autotransplantation.

CONTEXT: Total pancreatectomy with islet auto transplantation (TPIAT) is a treatment for medically refractory chronic pancreatitis that can prevent postsurgical diabetes in some patients. Predictors of insulin independence are needed for appropriate patient selection and counseling. OBJECTIVE: To explore glycemic predictors of insulin independence after TPIAT. DESIGN: A prospective cohort of patients. METHODS: We investigated 34 patients undergoing TPIAT from 2011-2016 at Johns Hopkins Hospital, all had a 75-g oral glucose tolerance test (OGTT) administered prior to their TPIAT. The primary outcome was insulin independence 1 year after TPIAT. RESULTS: Ten of 34 (29%) patients were insulin independent 1 year after TPIAT. All patients with impaired fasting glucose and/or impaired glucose tolerance preoperatively were insulin dependent at 1 year. In age-adjusted regression analyses, fasting glucose ≤ 90 mg/dL [odds ratio (OR) = 6.56; 1.11 to 38.91; P = 0.04], 1-hour OGTT glucose ≤ 143 mg/dL (OR = 6.65; 1.11 to 39.91; P = 0.04), and 2-hour OGTT glucose ≤ 106 mg/dL (OR = 11.74; 1.46 to 94.14; P = 0.02) were significant predictors of insulin independence. In receiver operating characteristic analyses, homeostatic model assessment of ß-cell function (HOMA-ß) was the most robust predictor of insulin independence [area under the curve (AUC) = 0.88; 0.73 to 1.00]. CONCLUSIONS: Normal preoperative glucose status and lower fasting and postchallenge OGTT glucose values are significant predictors of insulin independence after TPIAT. Higher islet function (HOMA-ß) was the strongest predictor. OGTT testing may be a useful tool to aid in patient counseling prior to TPIAT and should be further investigated.

Laparoscopic Total Pancreatectomy With Islet Autotransplantation and Intraoperative Islet Separation as a Treatment for Patients With Chronic Pancreatitis.

Importance: Pain management of patients with chronic pancreatitis (CP) can be challenging. Laparoscopy has been associated with markedly reduced postoperative pain but has not been widely applied to total pancreatectomy with islet autotransplantation (TPIAT). Objective: To examine the feasibility of using laparoscopic TPIAT (L-TPIAT) in the treatment of CP. Design, Setting, and Participants: Thirty-two patients with CP presented for TPIAT at a tertiary hospital from January 1, 2013, through December 31, 2015. Of the 22 patients who underwent L-TPIAT, 2 patients converted to an open procedure because of difficult anatomy and prior surgery. Pain and glycemic outcomes were recorded at follow-up visits every 3 to 6 months postoperatively. Main Outcomes and Measures: Operative outcomes included operative time, islet isolation time, warm ischemia time, islet equivalent (IE) counts, estimated blood loss, fluid resuscitation, and blood transfusions. Postoperative outcomes included length of stay, all-cause 30-day readmission rate, postoperative complications, mortality rate, subjective pain measurements, opioid use, random C-peptide levels, insulin requirements, and glycated hemoglobin level. Results: Of the 32 patients who presented for TPIAT, 20 underwent L-TPIAT (8 men and 12 women; mean [SD] age, 39 [13] years; age range, 21-58 years). Indication for surgery was CP attributable to genetic mutation (n = 9), idiopathic pancreatitis (n = 6), idiopathic pancreatitis with pancreas divisum (n = 3), and alcohol abuse (n = 2). Mean (SD) operative time was 493 (78) minutes, islet isolation time was 185 (37) minutes, and warm ischemia time was 51 (62) minutes. The mean (SD) IE count was 1325 (1093) IE/kg. The mean (SD) length of stay was 11 (5) days, and the all-cause 30-day readmission rate was 35% (7 of 20 patients). None of the patients experienced postoperative surgical site infection, hernia, or small-bowel obstruction, and none died. Eighteen patients (90%) had a decrease or complete resolution of pain, and 12 patients (60%) no longer required opioid therapy at a median follow-up period of 6 months. Postoperative random insulin C-peptide levels were detectable in 19 patients (95%) at a median follow-up of 10.4 months. At a median follow-up of 12.5 months, 5 patients (25%) were insulin independent, whereas 9 patients (45%) required 1 to 10 U/d, 5 patients (25%) required 11 to 20 U/d, and 1 patient (5%) required greater than 20 U/d of basal insulin. The mean (SD) glycated hemoglobin level was 7.4% (0.5%). Conclusions and Relevance: This study represents the first series of L-TPIAT, demonstrating its safety and feasibility. Our approach enables patients to experience shorter operative times and the benefits of laparoscopy, including reduced length of stay and quicker opioid independence.

What We Know About Diet, Genes, and Dyslipidemia: Is There Potential for Translation?

Cardiovascular disease, particularly coronary artery disease (CAD), is the leading cause of death in the United States. Dyslipidemia, including elevated low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and low high density lipoprotein cholesterol (HDL-C), is a well-established risk factor for CAD and is influenced by both genetic and lifestyle factors, including the diet and dietary fat in particular. Major strides in elucidating the genetic basis for dyslipidemia have been made in recent years, and the quest to clarify how genetic differences influence lipid response to dietary intervention continues. Some monogenic conditions such as famililal hypercholesterolemia and sitosterolemia already have customized dietary recommendations. Some promising associations have emerged for more polygenic dyslipidemia, but further studies are needed in large dietary intervention studies capturing increasing amounts of explainable genetic variation before recommendations can be made for clinical translation.