Plasmapheresis in hypertriglyceridemia-induced acute pancreatitis.

The study involved hospitalizations with a diagnosis of hypertriglyceridemia-induced acute pancreatitis (HTGAP). This cohort was grouped into plasmapheresis and nonplasmapheresis groups using ICD-10 codes (6A550Z3 and 6A551Z3). Information was obtained on inpatient mortality, length of stay, total hospital charges, as well as the occurrence of comorbid systemic immune response syndrome, sepsis, septic shock, acute respiratory failure, acute respiratory distress syndrome, kidney failure, hypocalcemia, and need for transfusion of blood products. The study identified independent predictors of plasmapheresis. The plasmapheresis group had a higher proportion of patients with diabetes mellitus and obesity. Inpatient mortality was higher in the plasmapheresis group (0.86% vs 0.57%), and plasmapheresis was also associated with longer length of stay and higher total hospital charges. Overall, plasmapheresis was associated with higher proportions of inpatient complications. Patients with HTGAP had higher odds of undergoing plasmapheresis if they were in an urban location (adjusted odds ratio [aOR] 6.14, 95% confidence Interval [CI] 1.86-20.28, P = 0.003), larger hospital (aOR 3.37, 95% CI 2.14-5.29, P < 0.001), and teaching hospital (aOR 2.01, 95% CI 1.39-2.92, P < 0.001). Black patients were less likely to undergo plasmapheresis than white patients (aOR 0.42, 95% CI 0.23-0.78, P = 0.006). Patients with HTGAP who receive plasmapheresis may be at higher risk of numerous in-hospital complications, including death, compared to those who do not receive plasmapheresis. Black and older patients were less likely to undergo plasmapheresis.

Hypertriglyceridemia-associated acute pancreatitis: Response to continuous insulin infusion.

OBJECTIVE: To assess the response of serum triglycerides (TG) to continuous insulin infusion (CII) in adults with hypertriglyceridemia-associated acute pancreatitis (HTGP). METHODS: Retrospective analysis of TG response to standardized CII therapy in 77 adults admitted to intensive care with TG >1000 mg/dL and HTGP. RESULTS: Participants had initial TG 3869.0 [2713.5, 5443.5] mg/dL and were 39.3 ± 9.7 years old, 66.2% males, 58.4% Hispanic, BMI 30.2 [27.0, 34.8] kg/m2, 74.0% with diabetes mellitus (DM) and 50.6% with excess alcohol use. TG-goal, defined as ≤1,000 ± 100 mg/dL, was achieved in 95%. Among the 73 TG-goal achievers (responders), 53.4% reached TG-goal in <36 hours after CII initiation (rapid responders). When compared to slow responders taking≥36 hours, rapid responders had lower initial TG (2862.0 [1965.0, 4519.0] vs 4814.5 [3368.8, 6900.0] mg/dL), BMI (29.4 [25.9, 32.8] vs 31.9 [28.2, 38.3] kg/m2), DM prevalence (56.4 vs 94.1%), and reached TG-50% (half of respective initial TG) faster (12.0 [6.0, 17.0] vs 18.5 [13.0, 32.8] hours). Those with DM (n = 57) vs non-DM (n = 20) were obese (31.4 [28.0, 35.6] vs 27.8 [23.6, 30.3] kg/m2), took longer to reach TG-final (41.0 [25.0, 60.5] vs 14.5 [12.5, 25.5] hours) and used more daily insulin (1.7 [1.3, 2.1] vs 1.1 [0.5, 1.9] U/kg/day). Among those with DM, the rapid responders had higher daily use of insulin vs slow responders 1.9 [1.4, 2.3] vs 1.6 [1.1, 1.8] U/kg/day. All results significant. In multivariable analysis, predictors of faster TG response were absence of DM, lower BMI and initial TG. CONCLUSION: CII was effective in reaching TG-goal in 95% of patients with HTGP. Half achieved TG-goal within 36 hours. Presence of DM, higher BMI and initial TG slowed the time to reach TG-goal. These baseline parameters and rate of decline to TG-50% may be real-time indicators to initiate and adjust the CII for quicker response.

EXTERNAL VALIDATION OF A PREDICTIVE MODEL FOR ACUTE PANCREATITIS RISK IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA.

Objective: We previously developed a predictive model to assess the risk of developing acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG). In this study, we aimed to externally validate this model. Methods: The validation cohort included cross-sectional data between 2013 and 2017. Adult patients (≥18 years old) with triglyceride levels ≥1,000 mg/dL were identified. Based on our previous 4-factor predictive model (age, triglyceride [TG], excessive alcohol use, and gallstone disease), we estimated the probability of developing AP. Model performance was assessed using area under receiver operating characteristic curve (AUROC). Results: In comparison to the original cohort, patients in the validation cohort had more prevalent acute pancreatitis (16.2% versus 9.2%; P<.001) and gallstone disease (7.5% versus 2.1%; P<.001). Other characteristics were comparable and not statistically significant. The AUROCs were almost identical: 0.8337 versus 0.8336 in the validation and the original cohorts, respectively. In univariable analyses, the highest increase in odds of AP was associated with HTG, followed by gallstones, excessive alcohol use, and younger age. Conclusion: This study externally validates the 4-factor predictive model to estimate the risk of AP in adult patients with severe HTG (TG ≥1,000 mg/dL). Younger age was confirmed to place patients at high risk of AP. The clinical risk categories suggested in this study may be useful to guide treatment options. Abbreviations: AP = acute pancreatitis; ASCVD = atherosclerotic cardiovascular disease; AUROC = area under the receiver operating characteristic curve; FRAX = fracture risk assessment tool; HTG = hypertriglyceridemia; OR = odds ratio; TG = triglyceride level.

ACUTE PANCREATITIS IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA IN A MULTI-ETHNIC MINORITY POPULATION.

OBJECTIVE: To investigate the prevalence and predictors of hypertriglyceridemic acute pancreatitis (HTG-AP) in a multi-ethnic minority population. METHODS: A retrospective, cross-sectional study from 2003 to 2013 of 1,157 adults with a serum triglyceride (TG) level ≥1,000 mg/dL comparing baseline characteristics and risk factors between those with and without HTG-AP. RESULTS: Mean study population age was 49.2 ± 11.5 years; 75.6% were male, 31.6% African American, 38.4% Hispanic, 22.7% Caucasian, 5.7% Asian, and 1.6% Pacific Islander. Prevalence of HTG-AP was 9.2%. Patients with HTG-AP were significantly younger (41.3 years vs. 50.0 years; P<.001) than those without HTG-AP. Excessive alcohol intake (odds ratio [OR], 3.9; 95% confidence interval [CI], 2.5 to 6.0; P<.001), gallstone disease (OR, 3.9; 95% CI, 1.4 to 10.8; P = .008), and TG >2,000 mg/dL (OR, 4.8; 95% CI, 3.1 to 7.4; P<.001) remained significant independent risk factors. TG levels for patients with HTG-AP were higher (median TG, 2,394 mg/dL; interquartile range [IQR], 1,152 to 4,339 mg/dL vs. median TG, 1,406 mg/dL; IQR, 1,180.7 to 1,876.5 mg/dL). TG levels >2,000 mg/dL were associated with higher incidence of AP (22% vs. 5%). Patients with TG levels <2,000 mg/dL and no risk factors had prevalence of 2% compared to 33.6% with one risk factor and TG >2,000 mg/dL. Patients with HTG-AP had higher incidence of diabetic ketoacidosis at admission (7.5% vs. 2.5%; P = .004). CONCLUSION: TG level ≥2,000 mg/dL is associated with higher HTG-AP prevalence in ethnic minorities. Presence of excessive alcohol intake and/or gallstones further accentuates risk. ABBREVIATIONS: AP = acute pancreatitis; CT = computed tomography; DM = diabetes mellitus; HbA1c = hemoglobin A1c; HIV = human immunodeficiency virus; HTG = hyper-triglyceridemia; HTG-AP = hypertriglyceridemic acute pancreatitis; ROC = receiver operating characteristic; TG = triglyceride.

Mode of administration of dulaglutide: implications for treatment adherence.

BACKGROUND: Medication complexity/burden can be associated with nonadherence in patients with type 2 diabetes mellitus (T2DM). Patients' satisfaction with their treatment is an important consideration for physicians. Strategies like using longer acting efficacious agents with less frequent dosing may help adherence. OBJECTIVE: To explore the mode of administration of dulaglutide and its implications for treatment adherence in T2DM. METHODS: PubMed search using the term "Dulaglutide" through October 31, 2015 was conducted. Published articles, press releases, and abstracts presented at national/international meetings were considered. RESULTS/CONCLUSION: Dulaglutide is a once-weekly glucagon like peptide-1 analog with a low intraindividual variability. Phase III trials demonstrated significant improvements in glycemia and weight, with a low hypoglycemia risk similar to liraglutide/exenatide, but with substantially fewer injections. A significant improvement was observed in the total Diabetes Treatment Satisfaction Questionnaire score, Impact of Weight on Self-Perception, and perceived frequency of hyperglycemia with dulaglutide when compared with placebo, exenatide, liraglutide, or metformin. Treatment satisfaction scores showed an improvement with dulaglutide (34%-39%) when compared with exenatide (31%). A positive experience with a high initial (97.2%) and final (99.1%) injection success rate along with a significant reduction in patients' fear of self-injecting, as measured by the modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire and Medication Delivery Device Assessment Battery, was found. Its acceptance was high (>96%) among a variety of patients including patients who fear injections and injection-naïve users. Dulaglutide is available as a single-dose automatic self-injecting device, which has a low volume, does not need reconstitution, and avoids patient handling of the needle. Dose adjustment based on weight, sex, age, race, ethnicity, or injection-site is not necessary. In chronic diseases like diabetes where patients need lifelong medications, the efficacy, safety, and convenience of a once-weekly, easy-to-use, self-injecting device should encourage patient adherence to dulaglutide therapy.

Combination of Saxagliptin and Metformin Is Effective as Initial Therapy in New-Onset Type 2 Diabetes Mellitus With Severe Hyperglycemia.

CONTEXT: The efficacy/safety of combination oral agents in those with stable newly diagnosed type 2 diabetes (T2DM) with severe hyperglycemia is unknown. OBJECTIVE: The objective of the study was to assess glycemic and ß-cell outcomes of two oral regimens. DESIGN: This was an open-label, randomized controlled trial with patients enrolled from 2011 through 2014 and followed up for 12 weeks. SETTING: The study was conducted at a major public hospital in Chicago. PATIENTS: One hundred adults with newly diagnosed T2DM and severe hyperglycemia (300-450 mg/dL) participated in the study. INTERVENTION: One hundred patients were randomized to receive Kombiglyze XR (saxagliptin 5 mg/metformin 2000 mg) daily (K group) vs glipizide XL 10 mg daily (G group). MAIN OUTCOME MEASURES: The measure was to maintain fasting/premeal glucose of less than 300 mg/dL up to 6 weeks and less than 250 mg/dL after 6 weeks until study end, and to have no return acute care-site visits. Those not meeting criteria were discontinued. Other outcomes included continuous glucose monitoring (CGM) and ß-cell function estimates at start and study end. RESULTS: Baseline characteristics and primary outcome (K group 94%, G group 98%) were similar in both groups. The enrollment glucose (K group 343 mg/dL, G group 341 mg/dL) and glycated hemoglobin (K group 10.8%, G group 11%) declined by week 12 (K group 137 mg/dL, G group 129 mg/dL, and K group 6.8%, G group 6.9%), respectively. Homeostasis model assessment to assess basal insulin secretion and early insulin response improved severalfold (K group ×5.8, G group ×5.9, and K group ×9.5, G group ×13.1). In follow-up, the incidence of hypoglycemia was lower in the K group (self-monitored blood glucose: K group 8.0%, G group 24%; CGM: K group 20%, G group 46.5%) as were the number of episodes of hypoglycemia (self-monitored blood glucose: K group 4 in 12 weeks, G group 27 in 12 weeks; CGM: K group 0.28 per 24 h, G group 0.31 per 24 h). CONCLUSIONS: Kombiglyze XR and glipizide XL are efficacious in improving glycemia and ß-cell function in stable newly diagnosed T2DM with severe hyperglycemia. The K group had less hypoglycemia. These results suggest that certain oral medications could be appropriate alternatives in treating severe hyperglycemia.

Patient profiling in diabetes and role of canagliflozin.

BACKGROUND: Physicians attempt to achieve glycemic goals in patients with type 2 diabetes mellitus (T2DM) through various means, including glucose-lowering medications. There is interindividual variability in response to medications, which can be partially explained by the presence of genetic polymorphisms that affect drug metabolism. Pharmacogenomics studies the hereditary basis of interpatient variations in drug response and aims to identify subgroups of patients whose drug management could be tailored accordingly. The aim of this review is to explore patient profiling in the management of T2DM with a focus on the sodium glucose transporter inhibitor canagliflozin. METHODS: The PubMed database was searched using the terms "pharmacogenomics" and "diabetes" through May 31, 2014. Published articles and abstracts presented at national/international meetings were considered. RESULTS AND CONCLUSION: Genome-wide association studies have opened the door for patient profiling and research into genetic variants in multifactorial T2DM. Clinically, it may be possible to tailor the type of medication used based on the presence or absence of the various genetic variants. However, the polymorphisms studied may only explain some of the variability in response to T2DM drugs and needs further validation to ensure its authenticity. There are still unidentified factors which appear to play a role in the interindividual variability seen in clinical practice. The potential exists for pharmacogenomics to promote efficacious, safe, and cost-effective individualized diabetes management. Pharmacogenomics is still in its early stages, and the idea of defining patients genetically to predict individual responses to drugs and obtain safe and effective T2DM management is promising, in spite of existing barriers. Currently, clinical profiling of patients with T2DM and using an individualized approach with most drugs, including canagliflozin, based on comorbid conditions still remains the most accepted approach for the management of T2DM.

Tumor-induced osteomalacia with normal systemic fibroblast growth factor-23 level.

A 38-year-old man presenting with long bone/rib fractures was diagnosed with tumor-induced osteomalacia (TIO) caused by a giant cell tumor in the right foot with normal systemic fibroblast growth factor-23 (FGF23) levels. Multiple imaging modalities done initially and one year later were unable to localize the tumor. New-onset foot pain discovered a right foot mass with resolution of metabolic abnormalities post-surgery. Sampling from both femoral veins showed an elevated FGF23 value on the right side. This case is unique in that the patient had a normal systemic FGF23 level even with severe clinical manifestations of TIO.