Oral Diabetes Medications Research Articles

Continuation or discontinuation of pioglitazone when starting bedtime insulin in patients with poorly controlled type 2 diabetes in an inner-city population

ObjectiveWe studied the impact of continuing versus discontinuing pioglitazone on hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and weight when starting bedtime insulin in patients with poor glycemic control. MethodsWe retrospectively analyzed data from a 13-month randomized control trial on 77 patients with type 2 diabetes mellitus (DM), who despite maximum doses of three oral diabetes medications (metformin, sulfonylurea and pioglitazone) had HbA1C levels above 7.5%. Patients were randomized to either continuing or discontinuing pioglitazone in addition to starting and up-titrating bedtime insulin. HbA1C, FPG, and weight were assessed at baseline, 3months, 7months and 13months with the differences from baseline for the two groups compared at each of the three time points using the Wilcoxon rank sum test. ResultsWe found that HbA1c was significantly lower at the 7-month (p=0.01) and 13-month time points (p=0.036), and FPG was significantly lower at all three time points in the group continuing pioglitazone compared with those discontinuing pioglitazone. Continuing pioglitazone resulted in a greater increase in weight at the 3-month (p=0.002), 7-month (p=0.0001) and 13-month (p=0.00003) time points. Patients with the lowest HbA1c (<8.2%) at baseline were more likely to benefit from continuing pioglitazone than those with higher baseline HbA1c. Patients who started insulin and discontinued pioglitazone had similar HbA1c, FPG and weight at the three time points as at baseline, suggesting that pioglitazone and bedtime insulin has similar glycemic effect in this population. ConclusionsWe conclude that in patients with uncontrolled type 2 DM, continuing pioglitazone while concurrently starting bedtime insulin within a 13-month period led to a significant decrease in both HbA1c and FPG levels compared with those who did not receive pioglitazone; however weight increased during this period.

Associations between diabetes medication use and risk of second breast cancer events and mortality

Diabetes and certain diabetes medications have been shown to influence breast cancer (BC) risk. Less is known about their relation to BC outcomes. Our objective was to evaluate the effects of diabetes and diabetes medications on risk of second breast cancer events (SBCE) and mortality. This population-based cohort study was conducted among women diagnosed with early-stage (I-II) BC and enrolled in an integrated health plan. Exposures of interest were diabetes and medication classes including insulin, metformin, and sulfonylureas. Outcomes of interest were SBCE defined as recurrence or second primary BC, BC-specific mortality, and all-cause mortality. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for diabetes and medication use while accounting for potential confounders and competing risks. Among 4,216 women, 13% developed SBCE during a median follow-up of 6.3years. 610 women had diabetes of which 76% used oral diabetes medication and/or insulin. Findings suggested that diabetes increased the risk of recurrence (HR=1.57; 95% CI 1.09-2.25) but not overall SBCE (HR=1.29; 95% CI 0.94-1.76) or second primary BC (HR=0.74; 95% CI 0.39-1.41). Among women with diabetes, insulin use was associated with increased risks of recurrence (HR=1.94; 95% CI 1.08-3.48) and all-cause mortality (HR=2.33; 95% CI 1.70-3.20). Metformin use was associated with lower all-cause mortality (HR=0.55; 95% CI 0.38-0.79). Our findings show an association between diabetes and increased recurrence risk, and risk may be greater among insulin users. Metformin may reduce all-cause mortality among BC survivors. Given the growing breast cancer survivor population, further research in larger, more diverse populations is warranted.

PDB35 - Modeling the Long Term Economic Benefits of a Patient-Adjusted Mealtime Insulin Titration Algorithm among Patients with Type 2 diabetes in the united States

PDB34 CHANges IN THe sAfeTy PRofIle of oRAl DIABeTes MeDICATIoNs APPRoveD By THe fDA Al-Mutairi R., Seoane-Vazquez E. MCPHS University, Boston, MA, USA OBJECTIVES: The increase in the prevalence of type-2 diabetes has resulted in a substantial increase in the utilization of oral diabetes drugs in the US. This study assessed changes in the safety profile of the oral diabetes medications approved by the US Food and Drug Administration (FDA) as of December 31, 2014. METHODS: Regulatory information for oral diabetes medications as of December 31 was derived from the FDA webpage. Label information was extracted from the FDA webpage and paper copies of the PDR Book. Drugs were classified according to the WHO anatomical therapeutic chemical classification. Descriptive statistics and chi-square tests were used for the analysis. RESULTS: The FDA listed a total of 44 oral diabetes medications as of December 31, 2014, including 30 single active ingredients and 14 fixed-dose combinations. Three of the single active ingredients and 1 of the combinations were discontinued from the market as of December 31, 2014. In total, 15.9% of the drugs were approved before 1990, 22.7% in the 1990s, 36.4% in the 2000s, and 25.0% in 2010-2014. The main changes in safety profile of the drugs included in the study occurred in contraindications (changes in 50.0% of the drugs), limitations (38.6%), warning and precautions (36.4%), and black box warnings (20.5%). Additionally, changes also occurred in the indications approved by the FDA for 31.8% of the drugs. Changes in safety profile did not significantly varied according to the year of approval of a drug; however, drugs approved in the period 2010-2014 had a lower number of safety changes due to the limited time these drugs have been in the market. CONCLUSIONS: This study found substantial changes over time in the safety profile of oral diabetes drugs. Future research should evaluate the effect of changes in the safety profile of oral diabetes medication on patient outcomes.

Abstract 366: Pharmacy Quality Alliance Measure: Adherence to Non-Warfarin Oral Anticoagulant Medication

Background: The Pharmacy Quality Alliance (PQA) has endorsed adherence to non-warfarin anticoagulant agents as a new performance measure, but it has not yet been adopted by the Medicare Part D Star Ratings program. Medication adherence and other pharmacy measures are currently weighted at nearly half of a plan’s Star rating. Two, 3, 4 and 5 Star ratings are based on achievement of adherence threshold levels (e.g. 74%, 79%, 82%, and 85% for oral diabetes medications). Inclusion of the adherence to non-warfarin anticoagulant measure in the Star Ratings program would increase a plan’s incentives to improve patient adherence. Objective: To assess the adherence to medication of patients who used the target-specific oral anticoagulants (TSOAC) rivaroxaban, dabigatran, or apixaban in 2013 based on the PQA’s adherence to non-warfarin anticoagulant agent measure. Methods: Healthcare claims from the Humana database during the year of 2013 were analyzed. Adult patients with ≥2 dispensings of TSOAC agents in 2013, at least 180 days apart between two TSOAC dispensings in 2013 (a criterion to include chronic users), and with at least 60 days of supply were identified. Patients were observed from the first rivaroxaban, dabigatran, or apixaban dispensing in 2013 up to end of insurance coverage or 12/31/2013. Patients who filled prescriptions for warfarin or other injectable anticoagulants during the follow-up were excluded. The PQA measure was calculated as the percentage of patients who had a proportion of days covered (PDC) ≥80% during the follow-up. PQA measures were evaluated for a) the index TSOAC agent and b) allowing switches to other TSOAC agents (i.e., a patient still counted as using therapy after a switch). Comparisons of PQA measures were made between the rivaroxaban group and each of the other two groups using chi-squared tests. Results: A total of 9,948 TSOAC users (rivaroxaban: n=4,194, dabigatran: n=5,489, apixaban: n=265) were identified; mean age was between 75-77 years; 49.7%, 45.7%, and 43.4% were female, respectively. The mean follow-up period was 308, 329, and 247 days for rivaroxaban, dabigatran, and apixaban users, respectively. For rivaroxaban users, the proportion of patients with a PDC ≥0.8 (PQA measure) calculated using the index TSOAC agent at 75.4% was significantly higher compared to dabigatran users (67.6%; P&lt;.001) and trending higher compared to apixaban users (70.6%; P=0.076). When allowing switches to other TSOAC agents in the PQA measure, rivaroxaban users had a significantly higher PQA measure at 76.9% compared to both dabigatran (72.9%; P&lt;.001) and apixaban (71.3%; P=0.037) users. Conclusion: Based on the PQA’s adherence to non-warfarin anticoagulant agent measure, rivaroxaban users were found to have a higher adherence compared to dabigatran and apixaban users. Healthcare providers should consider the impact of anticoagulation selection on achieving quality metrics.

PDB34 - Changes in the safety Profile of oral Diabetes Medications approved by the fda

PDB34 - Changes in the safety Profile of oral Diabetes Medications approved by the fda

Adherence vs. persistence

For the past year, Towncrest Pharmacy has been working with a payer on a pilot project to assess how community pharmacists can affect their patients' clinical outcomes in terms of medication adherence and persistence. Before this project began, we had already been monitoring our patients' adherence to statins, renin angiotensin system antagonists, and oral diabetes medications based on CMS performance measures for pharmacists. Although we felt we had a good understanding of adherence and how it is calculated based on proportion of days covered (PDC), we were not as sure about persistence. To help us get a better handle on persistence, I did a literature review and came across a small study that provided further information.1

Metformin Effect on Chest Tube Drainage After Coronary Artery Bypass Graft Surgery

Increasing numbers of patients with diabetes mellitus are referred to cardiac surgery. Biguanides are still first-line treatment for type 2 diabetes in all over the world. According preoperative guidelines, oral diabetes medications should be held on the day of surgery because of increased risk of lactic acidosis, induced by Metformin in patients after heart surgery. However, not well described in medical literature mechanism of biguanides is its influence to coagulation. We observed patients, who were scheduled for an elective coronary artery bypass graft surgery (CABG). Eighteen were diabetics, fourteen were Metformin users, where medication was stopped 72 to 24 hours before surgery. Prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen measurement were performed at the baseline, 2 hours and 6 hours after weaning from CPB. Chest tube drainage was checked at 2, 6 and 24 hours after weaning from CPB at the ICU. Presence of fibrinolysis was checked with rotational thromboelastometry testing (Rotem, Tem Innovation, Germany). Statistical analysis showed weak negative correlation between chest tube output in 24 hours and Metformin use (r=-0.255, p=0.03). Patients with Metformin preoperatively had less chest tube drainage (457.1 ± 143.9ml) compared to patients without Metformin (622.2 ± 269.9ml). Here was no significant fibrinolysis in ROTEM tests registered (ML 3.5 ± 2.5%) and apTEM didn`t show improved maximal cloth firmness (MCF) nor shor- ter clothing time (CF).

Adherence to Oral Medications for Hypertension and Diabetes in Veterans with Comorbid Airflow Limitation.

Diabetes and hypertension are common among patients with airflow limitation and contribute to cardiovascular (CV) mortality, one of the leading causes of death among patients with airflow limitation. Our goal was to examine the association of severity of airflow limitation with adherence to medications for hypertension and diabetes. We identified 7,359 veterans with hypertension and/or diabetes in the Veterans Integrated Service Network-20. Entry date into the cohort was defined as the date of a patient's first pulmonary function testing (PFT). Diagnostic codes (ICD-9), PFT, and pharmacy data were available via the electronic medical record or via direct interrogation of PFT equipment. Our primary exposure was airflow limitation defined as FEV1 ≥ 80% predicted (normal), 80 > FEV1 ≥ 50% predicted (mild/moderate), 50 > FEV1 ≥ 30% predicted (severe), and FEV1 < 30% predicted (very severe). We assessed adherence using a validated method based on electronic pharmacy refill data and defined adherence as ≥ 80% medication possession for the period 6-12 months after enrollment. Medications of interest included β-blockers, calcium channel blockers, thiazides, and angiotensin-converting-enzyme inhibitors for patients with hypertension, and metformin and sulfonylureas for patients with diabetes. We used logistic regression models to assess the association between severity of airflow limitation and adherence, adjusted for demographics, health behaviors, and comorbidities. Overall adherence was poor (44.6-55.1%). Among patients with hypertension, when compared with subjects with normal FEV1, subjects with each category lower of FEV1 were less adherent to β-blockers, with an odds ratio (OR) of 0.87 (95% confidence interval [CI], 0.80-0.95); calcium channel blockers, with an OR of 0.83 (95% CI, 0.74-0.93); and angiotensin-converting-enzyme inhibitors with an OR of 0.91 (95% CI, 0.84-0.99). Airflow limitation was not associated with adherence to thiazides. Among patients with diabetes, we found no significant association of FEV1 with adherence, although a similar lower trend with increasing airflow limitation. In a sensitivity analysis limited to patients with chronic obstructive pulmonary disease, we found a nonstatistically significant trend for decreased adherence to β-blockers, calcium channel blockers, and angiotensin-converting-enzyme inhibitors in subjects with higher GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage. Severity of airflow limitation is associated with decreased adherence to β-blockers, calcium channel blockers, and angiotensin-converting-enzyme inhibitors. The decreased adherence to these medications may be related to adverse effects on symptoms in patients with lung disease, and may partially explain excess CV mortality in these patients.

Diabetic patients undergoing coronary artery bypass grafting: effects of haemoglobin A1c and peri-operative glucose levels

Background: Nearly half of patients undergoing coronary artery bypass grafting (CABG) have diabetes. There is mixed data as to whether pre-operative (haemoglobin A1c=HbA1c) and/or peri-operative diabetes management is associated with mortality and morbidity after CABG. We reviewed the characteristics and outcomes of diabetic patients undergoing CABG with a focus on HbA1c, peri-operative glucose levels and diabetic treatments. Methods: Diabetic patients undergoing CABG during July 2010-June 2010 were studied (n=306). Last pre-operative HbA1c levels, and peri-operative glucose levels (mean) and variability (standard deviation and coefficient of variation (CV)) from the day before operation to 3 days after were retrospectively recorded, as well as the pre-existing and peri-operative diabetes treatment modalities for analyses. Results: Mean HbA1c was 7.7+/-1.6%, and 11.1% (34), 56.2% (172), and 32.7% (100) of patients were managed pre-operatively with diet, oral diabetic medications and insulin respectively. For operative mortality, C-statistics (95% confidence interval) was only significant for HbA1c 0.855 (0.757-0.975) and glucose CV on the day of surgery 0.722 (0.567-0.877). HbA1c also detected post-operative renal failure c-statistic 0.617 (0.504-0.730), but not other complications or mortality during follow-up. In multivariate analysis, HbA1c was the only diabetes-related independent predictor of operative mortality hazards ratio 4.13 (1.04-16.4), and none of the diabetes-related variables predicted mortality during follow-up or other post-operative complications. Conclusion: Pre-operative HbA1c was the only diabetic variable to independently predict after operative mortality after CABG, suggesting medium-term pre-operative diabetes control being more important and prognostic of operative outcomes than peri-operative diabetes control.

Diabetic patients undergoing coronary artery bypass grafting: effects of haemoglobin A1c and peri-operative glucose levels

Background: Nearly half of patients undergoing coronary artery bypass grafting (CABG) have diabetes. There is mixed data as to whether pre-operative (haemoglobin A1c=HbA1c) and/or peri-operative diabetes management is associated with mortality and morbidity after CABG. We reviewed the characteristics and outcomes of diabetic patients undergoing CABG with a focus on HbA1c, peri-operative glucose levels and diabetic treatments. Methods: Diabetic patients undergoing CABG during July 2010-June 2010 were studied (n=306). Last pre-operative HbA1c levels, and peri-operative glucose levels (mean) and variability (standard deviation and coefficient of variation (CV)) from the day before operation to 3 days after were retrospectively recorded, as well as the pre-existing and peri-operative diabetes treatment modalities for analyses. Results: Mean HbA1c was 7.7+/-1.6%, and 11.1% (34), 56.2% (172), and 32.7% (100) of patients were managed pre-operatively with diet, oral diabetic medications and insulin respectively. For operative mortality, C-statistics (95% confidence interval) was only significant for HbA1c 0.855 (0.757-0.975) and glucose CV on the day of surgery 0.722 (0.567-0.877). HbA1c also detected post-operative renal failure c-statistic 0.617 (0.504-0.730), but not other complications or mortality during follow-up. In multivariate analysis, HbA1c was the only diabetes-related independent predictor of operative mortality hazards ratio 4.13 (1.04-16.4), and none of the diabetes-related variables predicted mortality during follow-up or other post-operative complications. Conclusion: Pre-operative HbA1c was the only diabetic variable to independently predict after operative mortality after CABG, suggesting medium-term pre-operative diabetes control being more important and prognostic of operative outcomes than peri-operative diabetes control.

Prescriber continuity and medication adherence for complex patients.

Medication adherence is a critical aspect of managing cardiometabolic conditions, including diabetes, hypertension, dyslipidemia, and heart failure. Patients who have multiple cardiometabolic conditions and multiple prescribers may be at increased risk for nonadherence. The purpose of this study was to examine the relationship between number of prescribers, number of conditions, and refill adherence to oral medications to treat cardiometabolic conditions. In this retrospective cohort study, 7933 veterans were identified with 1 to 4 cardiometabolic conditions. Refill adherence to oral medications for diabetes, hypertension, and dyslipidemia was measured using an administrative claims-based continuous multiple-interval gap (CMG) that estimates the percentage of days a patient did not possess medication. We dichotomized refill adherence for each condition as a CMG ≤20% for each year of analysis. Condition-specific logistic regression models estimated the relationship between refill adherence and number of cardiometabolic conditions and number of prescribers, controlling for demographic characteristics, other comorbidities, and a count of cardiometabolic drug classes used. Compared with patients with 1 prescriber, antihypertensive refill adherence was lower in patients seeing ≥4 prescribers (odds ratio [OR] = 0.69; 95% CI = 0.59-0.80), but the number of cardiometabolic conditions was not a significant predictor. Antidyslipidemia refill adherence was lower in patients seeing 3 prescribers (OR = 0.80; 95% CI = 0.70-0.92) or ≥4 prescribers (OR = 0.77; 95% CI = 0.64-0.91). Conversely, antidyslipidemia refill adherence improved with the number of cardiometabolic conditions, but differences were only statistically significant for ≥3 conditions (OR = 1.31; 95% CI = 1.09-1.57). In multivariate regression models, the number of conditions and number of prescribers were not significant predictors of refill adherence in the group of patients with diabetes. Effective management of care and medication regimens for complex patients remains an unresolved challenge, but these results suggest that medication refill adherence might be improved by minimizing the number of prescribers involved in a patient's care, at least for hypertension and dyslipidemia.

Use of an Electronic Medical Record (EMR) to Identify Glycemic Intensification Strategies in Type 2 Diabetes.

Current treatment guidelines for type 2 diabetes (T2D) recommend individualized intensification of therapy for glycated hemoglobin (A1C) ≥ 7% in most patients. The purpose of this investigation was to explore the ability of an electronic medical record (EMR) to identify glycemic intensification strategies among T2D patients receiving pharmacologic therapy. Patient records between 2005 and 2011 with documentation of A1C and active prescriptions for any diabetes medications were queried to identify potential candidates for intensification based on A1C ≥ 7% while on 1-2 oral diabetes medications (ODM). Patients with follow-up A1C values within 1 year of index A1C were grouped according to intensification with insulin, GLP-1 receptor agonists (GLP-1RA), a new class of ODM, or no intensification. Changes in A1C and continuation of intensification therapy were determined. A total of 4921 patients meeting inclusion criteria were intensified with insulin (n = 416), GLP-1RA (n = 68), ODM (n = 1408), or no additional therapy (n = 3029). Patients receiving insulin had higher baseline (9.3 ± 2.0 vs 8.3 ± 1.2 vs 8.3 ± 1.3 vs 7.6 ± 1.0%, P < .0001) and follow-up A1C (8.1 ± 1.6 vs 7.5 ± 1.2 vs 7.6 ± 1.3 vs 7.2 ± 1.1%, P < .0001) despite experiencing larger absolute A1C reductions (-1.2 ± 2.1 vs -0.8 ± 1.4 vs -0.7 ± 1.4 vs -0.3 ± 1.1%, P < .0001). Patients receiving GLP-1RA were more obese at baseline (BMI: 33.6 ± 7.1 vs 37.7 ± 6.1 vs 33.7 ± 6.8 vs 32.9 ± 7.1 kg/m(2), P < .0001) and follow-up (BMI: 33.9 ± 7.3 vs 36.6 ± 6.1 vs 33.8 ± 7.0 vs 32.4 ± 7.0 kg/m(2), P < .0001) despite experiencing more absolute weight reduction. Insulin was the most and GLP-1RA the least likely therapy to be continued. An EMR allows identification of prescribing practices and compliance with T2D treatment guidelines. Patients receiving intensification of glycemic medications had baseline A1C >8% suggesting that treatment recommendations are not being followed.

A randomized controlled trial to provide adherence information and motivational interviewing to improve diabetes and lipid control.

The purpose of this study was to assess whether providing medication adherence information with or without motivational interviewing improves diabetes and lipid control. Study participants were adult members of a health system in southeast Michigan, were using both oral diabetes and lipid-lowering medications, and had glycated hemoglobin (A1C) or low-density lipoprotein cholesterol (LDL-C) levels not at goal. Participants were randomly assigned to receive usual care (UC), n = 567; have medication adherence information (AI) provided to their physician, n = 569; or have AI and receive motivational interviewing (MI) though trained staff (AI + MI), n = 556. Primary outcomes were A1C and LDL-C levels at 18 months post randomization. Primary outcomes were not significantly different between patients in the AI or AI + MI study arms when compared with UC. Similarly, neither oral diabetes nor lipid-lowering medication adherence was significantly different between groups. Patient participation in the AI + MI arm was low and limit the interpretation of the study results, but post hoc analysis of the AI + MI study arm showed that the number of MI sessions received was positively associated with only oral diabetes medication adherence. Neither AI nor MI significantly improved diabetes and lipid control when compared with UC. Moreover, patient participation appeared to be a particular barrier for MI.

Dapagliflozin: Clinical practice compared with pre-registration trial data

Background: Dapagliflozin is the first sodium-glucose cotransporter 2 (SGLT2) inhibitor to be approved in Europe and represents a new class of agents developed as oral diabetes medications. Improved glycaemic control and weight loss have been demonstrated in clinical trials but effectiveness outside of the trial environment has not yet been reported. Method: A systematic clinical case note audit of type 2 diabetes patients initiated on dapagliflozin in a diabetes specialist outpatient centre of a London teaching hospital. Results: Of the 96 people included, 42% had a reduction in glycated haemoglobin (HbA1c) of >1%, 29% had no reduction; 15% had weight loss >5kg, 3% had weight loss >10kg and 24% had no weight reduction. Improvements in HbA1c, weight, and blood pressure were consistent with those reported in clinical trials. The rate of discontinuation of dapagliflozin due to side effects (22%) was higher than reported in trials (3-4%), but 52% of people tolerating dapagliflozin were able to stop or reduce one or more other diabetes medications. Conclusions: Dapagliflozin is effective at improving glycaemic control. It also reduces blood pressure, results in weight loss, and reduces the need for concomitant diabetes medications. However, it is not as well tolerated in real-world patients as in participants of clinical trials.

Diabetes care and outcomes for American Indians and Alaska natives in commercial integrated delivery systems: a SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) Study

ObjectiveTo compare cardiovascular disease risk factor testing rates and intermediate outcomes of care between American Indian/Alaska Native (AI/AN) patients with diabetes and non-Hispanic Caucasians enrolled in nine commercial integrated delivery...

Influence of insulin and glargine on outgrowth and number of circulating endothelial progenitor cells in type 2 diabetes patients: a partially double-blind, randomized, three-arm unicenter study.

BackgroundEndothelial progenitor cells (EPC) are bone marrow-derived cells which can undergo differentiation into endothelial cells and participate in endothelial repair and angiogenesis. Insulin facilitates this in vitro mediated by the IGF-1 receptor. Clinical trials showed that the number of circulating EPCs is influenced by glucose control and EPC are a predictor of cardiovascular death. To study direct effects of insulin treatment on EPCs in type 2 diabetes patients, add-on basal insulin treatment was compared to an escalation of oral medication aiming at similar glucose control between the groups.Methods55 patients with type 2 diabetes (61.6±5.9 years) on oral diabetes medication were randomized in a 2:2:1 ratio in 3 groups. Patients were treated additionally with insulin glargine (n=20), NPH insulin (n=22) or escalated with oral medication (n=13). Number of circulating EPC, EPC-outgrowth, intima media thickness, skin microvascular function and HbA1c were documented at baseline and/or after 4 weeks and 4 months.ResultsHbA1c at baseline was, 7.3+/−0.7% in the oral group, 7.3+/−0.9% and 7.5+/−0.7% in the glargine and NPH insulin respectively (p=0.713). HbA1c after 4 months decreased to 6.8+/−0.8%, 6.6+/−0.7% and 6.7+/−0.6%, in the oral, glargine and NPH insulin group respectively (p=0.61). FACS analysis showed no difference in number of circulating EPC between the groups after 4 weeks and 4 months. However, the outgrowth of EPCs as detected by colony forming assay was increased in the NPH insulin and glargine groups (29.2+/−6.4 and 29.4+/− 6.7 units respectively) compared to the group on oral medication (23.2+/−6.3, p=0.013) after 4 months of treatment. A significant decrease of IMT from 0.80mm (+/−0.14) at baseline to 0.76mm (+/−0.12) after 4 months could be observed in all patients only (p=0.03) with a trend towards a reduction of IMT after 4 months when all patients on insulin treatment were compared to the oral treatment group (p=0.06). Skin microvascular function revealed no differences between the groups (p=0.74).ConclusionThe study shows that a 4-month treatment with add-on insulin significantly increases the outgrowth of EPC in patients with type 2 diabetes mellitus.Trial registration(Clinical Trials Identifier: NCT00523393).

Young Nepalese Male With Jaundice

Introduction: Pancreatic acinar cell carcinoma is a rare malignancy accounting for less than 1% of all pancreatic tumors. Given its rarity, diagnosis is often difficult and delayed. There are no current standard treatment protocols and surgical resection is the only curative measure. This cancer is primarily seen in older males. However, we report a case of acinar cell carcinoma in a young male from Nepal who presented with jaundice. Case Report: A 30-year-old Nepalese male with no significant past medical history who presented with jaundice, generalized pruritus, dark urine, and a 34-pound weight loss in 1.5 months. He presented with elevated serum liver enzymes. An abdominal ultrasound was performed, which showed fatty liver, distended gallbladder containing large amounts of sludge, and dilated common bile duct with sludge. A subsequent MRCP confirmed a dilated distal common bile duct along with a filling defect, 2.0 cm from ampulla of Vater with no other significant abnormalities. His initial ERCP showed a stricture in the common bile duct, a sphincterotomy was performed, and a stent was placed. Cytology was nondiagnostic and only showed atypical glandular cells. A CT did not show any other lesions or gross abnormalities. Subsequent endoscopic ultrasound (EUS) showed a well-demarcated mass in the lower third of the common bile duct with no significant pathology in the pancreas. Another ERCP was performed, which showed a dilated common bile duct with distal stricture that was restented and nondiagnostic biopsies. The patient’s laboratory values showed a slightly elevated CA 19-9, normal CEA, negative ANA, and normal IgG4, making autoimmune pancreatitis unlikely. The patient underwent a pylorus-sparing pancreaticoduodenectomy (partial Whipple resection), abdominal lymphadenectomy, and cholecystectomy. Pathology showed a 3-cm high-grade acinar cell carcinoma in the pancreatic head. The final staging of the tumor was T3N1M0 with 2 out of 5 resected abdominal lymph nodes being positive for metastasis. All resection margins were negative. Tumor cells were positive for Cam 5.2, AE1/AE3 and anti-chymotrypsin, making it consistent with acinar cell carcinoma in addition to positive PAS (periodic acid-Schiff-diastase) staining of cytoplasmic granules. The patient was started on a course of radiation with 5 fluorouracil, 3 months after surgery, followed by chemotherapy with Gemzar. After 1 month post-adjuvant radiation and chemotherapy, the patient’s CA 19-9 decreased. At 12 months’ follow-up, the patient is doing well and is on oral medications for brittle diabetes. The patient’s follow-up PET scan was negative.

Preprocedure and Preoperative Management of Diabetes Mellitus

Appropriate management of diabetes mellitus before a procedure or operation is important for the prevention of hypo- and hyperglycemia in the periprocedural/perioperative period. This can significantly influence glucose levels after a procedure, which in turn affects outcomes. There is a paucity of prospective trials addressing algorithms to guide adjustment of oral diabetes medications and insulin prior to a procedure. Our institution has developed guidelines that allowed us to standardize the periprocedural process for glucose management across departments. This article describes our experience with guidelines, discusses salient features of medication management, and summarizes prospective trials and expert opinion to provide recommendations for clinicians to effectively manage glucose preprocedurally for their patients with diabetes.

Defining the role of medication adherence in poor glycemic control among a general adult population with diabetes.

AimsThis study assesses the attributable impact of adherence to oral glucose medications as a risk factor for poor glycemic control in population subgroups of a large general population, using an objective medication adherence measure.MethodsUsing electronic health records data, adherence to diabetes medications over a two-year period was calculated by prescription-based Medication Possession Ratios for adults with diabetes diagnosed before January 1, 2010. Glycemic control was determined by the HbA1c test closest to the last drug prescription during 2010–2012. Poor control was defined as HbA1c>75 mmol/mol (9.0%). Medication adherence was categorized as “good” (>80%), “moderate” (50–80%), or “poor” (<50%). Logistic regression models assessed the role medication adherence plays in the association between disease duration, age, and poor glycemic control. We calculated the change in the attributable fraction of glucose control if the non-adherent diabetic medication population would become adherent by age-groups.ResultsAmong 228,846 diabetes patients treated by oral antiglycemic medication, 46.4% had good, 28.8% had moderate, and 24.8% had poor adherence. Good adherence rates increased with increasing disease duration, while glycemic control became worse. There was a strong inverse association between adherence level and poor control (OR = 2.50; CI = 2.43–2.58), and adherence was a significant mediator between age and poor control.ConclusionsA large portion of the diabetes population is reported to have poor adherence to oral diabetes medications, which is strongly associated with poor glycemic control in all disease durations. While poor adherence does not mediate the poorer glycemic control seen in patients with longer-standing disease, it is a significant mediator of poor glycemic control among younger diabetes patients. A greater fraction of poorly controlled younger patients, compared to older patients, could be prevented if at least 80% adherence to their medications was achieved. Therefore, our results suggest that interventions to improve adherence should focus on this younger sub-group.

Stick it to me

Stick it to me