The Occurrence and Burden of Hypophosphatasia in an Ambulatory Care Endocrinology Practice.

OBJECTIVE: Hypophosphatasia (HPP) is an inherited disease resulting from loss-of-function mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase. The presentation and severity of the disease are highly variable, ranging from perinatal onset with high mortality rates to adult identification with low mortality rates and symptoms ranging from minimal to severe. Moderate forms of HPP typically manifest during middle age and are often undiagnosed. The objective of this study was to determine the occurrence and burden of HPP in an ambulatory care endocrinology practice. METHODS: Potential subjects were identified with a computerized text search of patient electronic medical records. Search terms included serum alkaline phosphatase (ALP) levels of ≤40 U/L. Records of patients with at least 2 low ALP levels were reviewed manually to identify potential patients with a history consistent with hypophosphatasia. RESULTS: In total, 315 patients with ALP levels ≤40 U/L were identified from an estimated 20 000 patient records. Fifty-six patients with a single low level were excluded from further review. The remaining 259 patients were reviewed, 10 of whom had histories consistent with HPP. None of the identified 10 patients was currently being treated or had previously been treated for HPP. Information about these patients was shared with their respective providers, along with the recommendation to proceed with further evaluation to confirm the diagnosis of HPP. CONCLUSION: Hypophosphatasia is an uncommon condition with variable presentation, often resulting in a missed diagnosis. Surveillance of practices by identifying patients with low ALP levels is a rational screening approach to identifying potential patients with HPP.

A pharmacist-run anabolic osteoporosis clinic: An abaloparatide descriptive report.

OBJECTIVES: To review the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. SETTING: This ambulatory-care health system endocrinology practice consists of 10 board-certified endocrinologists and 6 nurse practitioners and physician assistants. Approximately 1200 patients are seen weekly. The practice is affiliated with the Albany College of Pharmacy and Health Sciences and hosts 2 clinical pharmacy faculty members and a PGY-2 endocrinology pharmacy resident. A pharmacist-run teriparatide clinic was implemented in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. No description of a pharmacist-run abaloparatide clinic has yet been reported. PRACTICE DESCRIPTION: Patients are referred to a clinical pharmacist for initiation and education of anabolic osteoporosis therapy. The pharmacist is responsible for assessing for contraindications to anabolic therapy, securing managed care coverage of an anabolic agent, and providing medication counseling. This pharmacist is available as a resource to patients throughout their course of anabolic osteoporosis therapy. PRACTICE INNOVATION: This is the first description of a pharmacist-run abaloparatide clinic. EVALUATION: Not applicable. RESULTS: During its first year of availability, 52 patients were referred for abaloparatide therapy. Of these, 31 patients (59.6%) initiated treatment. The population predominately consisted of postmenopausal white women. Approximately two-thirds of patients had a history of an osteoporosis-related fracture, and half of patients had previously received antiresorptive therapy for osteoporosis. Mean baseline T-scores for the lumbar spine and femoral neck were -2.41 and -2.57, respectively. Twenty-one patients did not initiate abaloparatide therapy owing to cost (9), concerns of therapy (8), or contraindication to therapy (4). An additional 5 patients discontinued abaloparatide therapy owing to adverse effects. CONCLUSION: This paper reviews the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. The fact that only 60% of referred patients initiated therapy indicates that significant barriers (e.g., high patient cost and safety concerns) remain.

Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial.

BACKGROUND: Many antihyperglycaemic drugs, including insulin, are primarily cleared by the kidneys, restricting treatment options for patients with kidney disease. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys, and confers a lower risk of hypoglycaemia than does insulin. We assessed the efficacy and safety of dulaglutide in patients with type 2 diabetes and moderate-to-severe chronic kidney disease. METHODS: AWARD-7 was a multicentre, open-label trial done at 99 sites in nine countries. Eligible patients were adults with type 2 diabetes and moderate-to-severe chronic kidney disease (stages 3-4), with an HbA1c of 7·5-10·5%, and who were being treated with insulin or insulin plus an oral antihyperglycaemic drug and were taking a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Participants were randomly assigned (1:1:1) by use of a computer-generated random sequence with an interactive response system to once-weekly injectable dulaglutide 1·5 mg, once-weekly dulaglutide 0·75 mg, or daily insulin glargine as basal therapy, all in combination with insulin lispro, for 52 weeks. Insulin glargine and lispro doses were titrated as per an adjustment algorithm; dulaglutide doses were masked to participants and investigators. The primary outcome was HbA1c at 26 weeks, with a 0·4% non-inferiority margin. Secondary outcomes included estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The primary analysis population was all randomly assigned patients who received at least one dose of study treatment and had at least one post-randomisation HbA1c measurement. The safety population was all patients who received at least one dose of study treatment and had any post-dose data. This study is registered with ClinicalTrials.gov, number NCT01621178. FINDINGS: Between Aug 15, 2012, and Nov 30, 2015, 577 patients were randomly assigned, 193 to dulaglutide 1·5 mg, 190 to dulaglutide 0·75 mg, and 194 to insulin glargine. The effects on HbA1c change at 26 weeks of dulaglutide 1·5 mg and 0·75 mg were non-inferior to those of insulin glargine (least squares mean [LSM] -1·2% [SE 0·1] with dulaglutide 1·5 mg [183 patients]; -1·1% [0·1] with dulaglutide 0·75 mg [180 patients]; -1·1% [0·1] with insulin glargine [186 patients]; one-sided p≤0·0001 for both dulaglutide doses vs insulin glargine). The differences in HbA1c concentration at 26 weeks between dulaglutide and insulin glargine treatments were LSM difference -0·05% (95% CI -0·26 to 0·15, p<0·0001) with dulaglutide 1·5 mg and 0·02% (-0·18 to -0·22, p=0·0001) with dulaglutide 0·75 mg. HbA1c-lowering effects persisted to 52 weeks (LSM -1·1% [SE 0·1] with dulaglutide 1·5 mg; -1·1% [0·1] with dulaglutide 0·75 mg; -1·0% [0·1] with insulin glargine). At 52 weeks, eGFR was higher with dulaglutide 1·5 mg (Chronic Kidney Disease Epidemiology Collaboration equation by cystatin C geometric LSM 34·0 mL/min per 1·73 m2 [SE 0·7]; p=0·005 vs insulin glargine) and dulaglutide 0·75 mg (33·8 mL/min per 1·73 m2 [0·7]; p=0·009 vs insulin glargine) than with insulin glargine (31·3 mL/min per 1·73 m2 [0·7]). At 52 weeks, the effects of dulaglutide 1·5 mg and 0·75 mg on UACR reduction were not significantly different from that of insulin glargine (LSM -22·5% [95% CI -35·1 to -7·5] with dulaglutide 1·5 mg; -20·1% [-33·1 to -4·6] with dulaglutide 0·75 mg; -13·0% [-27·1 to 3·9] with insulin glargine). Proportions of patients with any serious adverse events were similar across groups (20% [38 of 192] with dulaglutide 1·5 mg, 24% [45 of 190] with dulaglutide 0·75 mg, and 27% [52 of 194] with insulin glargine). Dulaglutide was associated with higher rates of nausea (20% [38 of 192] with dulaglutide 1·5 mg and 14% [27 of 190] with 0·75 mg, vs 5% [nine of 194] with insulin glargine) and diarrhoea (17% [33 of 192] with dulaglutide 1·5 mg and 16% [30 of 190] with 0·75 mg, vs 7% [14 of 194] with insulin glargine) and lower rates of symptomatic hypoglycaemia (4·4 events per patient per year with dulaglutide 1·5 mg and 4·3 with dulaglutide 0·75 mg, vs 9·6 with insulin glargine). End-stage renal disease occurred in 38 participants: eight (4%) of 192 with dulaglutide 1·5 mg, 14 (7%) of 190 with dulaglutide 0·75 mg, and 16 (8%) of 194 with insulin glargine. INTERPRETATION: In patients with type 2 diabetes and moderate-to-severe chronic kidney disease, once-weekly dulaglutide produced glycaemic control similar to that achieved with insulin glargine, with reduced decline in eGFR. Dulaglutide seems to be safe to use to achieve glycaemic control in patients with moderate-to-severe chronic kidney disease. FUNDING: Eli Lilly and Company.

A real-world, observational study of weekly exenatide added to basal insulin in patients with type 2 diabetes mellitus (NCT02895672).

AIM: This is a pre-post observational study from an endocrinology ambulatory care practice which assessed the effectiveness and safety following the addition of a glucagon-like peptide-1 (GLP-1) agonist, weekly exenatide (Bydureon), to basal insulin therapy in patients with type 2 diabetes mellitus (T2DM). Liraglutide plus basal insulin served as a comparison group. MATERIALS AND METHODS: A data collection form was utilized to collect study-related information. The primary study outcome was change in HbA1c from baseline to 12 months after GLP-1 receptor agonist therapy was added to basal insulin therapy. Secondary outcomes were change in weight, percentage of patients achieving an HbA1c of <7% (53 mmol/mol) or ≤6.5% (48 mmol/mol) and changes in blood pressure and lipid parameters. Safety was assessed by a collection of reported adverse events. RESULTS: One-hundred and fifty patients met inclusion criteria (seventy-five per treatment arm). After 1 year of therapy, HbA1c decreased by 0.7% in the entire cohort (once-weekly exenatide: -0.7%; once-daily liraglutide: -0.8%; no significant between-group difference). More subjects in the weekly exenatide arm achieved an HbA1c < 7% (53 mmol/mol) (P = .03), but a comparable number achieved an HbA1c ≤ 6.5% (48 mmol/mol). Although significantly more patients achieved an HbA1c < 7% (53 mmol/mol) in the once-weekly exenatide arm, the baseline HbA1c was lower (7.9%) than the liraglutide arm (8.4%). No significant differences were observed between groups for other secondary outcomes. A similar number of subjects discontinued therapy, mainly due to gastrointestinal-ill effects, and hypoglycaemia incidence did not increase compared with the previous year. CONCLUSION: The addition of once-weekly exenatide to basal insulin was associated with appreciable reductions in HbA1c and weight without an increase in hypoglycaemia.

Effects of exenatide twice daily, exenatide once weekly or insulin in patients with type 2 diabetes and baseline HbA1c ≥10.0%: Two pooled analyses including 20 randomised controlled trials.

AIMS: Patients with advanced type 2 diabetes (T2D) and high glycated haemoglobin (HbA1c) values can be difficult to treat because of their severe metabolic disease. This pooled analysis examined the treatment effects of exenatide twice daily (BID), exenatide once weekly (QW) and insulin in patients with high baseline HbA1c (≥10.0%). METHODS: This post hoc analysis used pooled data from 12 and 8 randomised controlled trials of exenatide BID and exenatide QW, respectively. Patients with T2D who completed at least 24 weeks of treatment with exenatide BID, exenatide QW or insulin (insulin glargine, insulin detemir or insulin aspart) were categorised by baseline HbA1c. Patients with HbA1c ≥10.0% were included in the analysis. RESULTS: Both exenatide and insulin reduced HbA1c (mean ± SE reduction: -2.0% ± 0.2% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide BID studies, and -2.6% ± 0.1% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide QW studies; all P < .001). Body weight decreased with exenatide and increased with insulin. Systolic blood pressure decreased with exenatide QW. Insulin dose increased over the course of treatment. The most common adverse events with exenatide were gastrointestinal. Insulin was associated with some hypoglycaemia risk. Hypoglycaemia events occurred infrequently with exenatide when given without sulphonylureas. CONCLUSIONS: For patients with high HbA1c, treatment with exenatide or insulin both improved glycaemic control. Given the associated weight loss and low risk of hypoglycaemia, exenatide may be a suitable alternative to treatment with insulin in certain patients with T2D and high HbA1c.

Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes.

Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia. use of glucose-lowering therapies with complementary activities that address multiple facets of the disease may improve long-term outcomes for patients with t2d. two recent drug classes developed for use in t2d, glucagon-like peptide-1 receptor agonists (glp-1ras) and sodium glucose cotransporter 2 (sglt2) inhibitors, have been shown in clinical trials to have beneficial effects on glycemic control, body weight, cardiovascular risk factors, and (for liraglutide, semaglutide, and empagliflozin) cardiovascular outcomes, while having an acceptable safety profile. between them, these drug classes directly or indirectly affect many of the organs and tissues involved in the pathogenesis of t2d, and their beneficial effects on glycemic- and cardiovascular-related parameters are likely to be complementary and potentially additive. in the largest clinical trial of a glp-1ra and an sglt2 inhibitor in combination (duration-8), patients with t2d (n = 685) who received exenatide plus dapagliflozin added to their treatment regimen for 28 weeks had significantly greater reductions from baseline in glycated hemoglobin, body weight, and systolic blood pressure compared with patients who received either drug as monotherapy. this review summarizes the complementary aspects of these drug classes and presents the available data among patients receiving dual therapy with a glp-1ra and an sglt2 inhibitor.

No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol-Secreting Adenomas Treated with Mifepristone Before Surgery.

BACKGROUND: Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic-pituitary-adrenal (HPA) axis, eliminating the need for postoperative glucocorticoid replacement. CASE PRESENTATION: A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier's gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0-50 µg/24 hours). Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL), suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2-63.3 pg/mL), and low-normal dehydroepiandrosterone sulfate (50.5 µg/dL, male reference range 30.9-295.6 µg/dL). Because of his poor medical condition and uncontrolled diabetes, his Cushing's syndrome was treated with medical therapy before surgery. Mifepristone therapy was started and, within five months, his diabetes was controlled and insulin discontinued. The previously suppressed ACTH increased to above normal range accompanied by an increase in dehydroepiandrosterone sulfate levels, indicating recovery of the HPA axis and atrophic contralateral adrenal gland. The patient received one precautionary intraoperative dose of hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL) and cortisol levels (44.8 µg/dL) were significantly elevated, reflecting an appropriate HPA axis response to the stress of surgery, and two weeks postoperatively, ACTH was within normal range and a repeat dexamethasone suppression test was normal. Six months postoperatively, ACTH was within normal limits and cortisol was approaching normal. The patient has exhibited no postoperative signs or symptoms of adrenal insufficiency in 12 months. CONCLUSION: Preoperative mifepristone therapy was associated with apparent recovery of the HPA axis prior to unilateral adrenalectomy in a patient with unilateral adrenal adenomas. Postoperatively, the patient experienced no signs or symptoms of adrenal insufficiency and no glucocorticoid replacement was required.

SGLT-2 INHIBITOR THERAPY ADDED TO GLP-1 AGONIST THERAPY IN THE MANAGEMENT OF T2DM.

OBJECTIVE: To assess the real-world efficacy and safety of canagliflozin therapy added to type 2 diabetes mellitus (T2DM) patients who have received a minimum 1 year of glucagon-like peptide-1 (GLP-1) agonist therapy. METHODS: This pre-post observational study assessed the efficacy and safety of canagliflozin in a group of T2DM patients from a community endocrinology practice who received GLP-1 agonist therapy for a minimum of 12 months. The primary study outcome was change in mean glycated hemoglobin (HbA1c) level from baseline. Secondary endpoints included changes in average weight, and comparison of the percentage of patients obtaining an HbA1c <7%. RESULTS: A total of 75 patients met all the study criteria. Baseline patient characteristics were as follows: average age, 58 ± 9 years; mean duration of T2DM, 14 ± 6 years; 56% male; 92% Caucasian; baseline body mass index (BMI), 39.4 ± 9.4 kg/m(2); and mean baseline HbA1c, 7.94 ± 0.69%. HbA1c and weight were significantly reduced by 0.39% and 4.6 kg, respectively. Adverse effects were reported by 13 (17.3%) patients, including 4 (5.3%) who discontinued canagliflozin because of adverse reactions. CONCLUSION: Canagliflozin was generally well tolerated and significantly further reduced mean HbA1c levels and body weight in patients with T2DM when added to GLP-1 regimen.

A clinical perspective of canagliflozin in the management of type 2 diabetes mellitus.

OBJECTIVE: To assess the real-world efficacy and safety of the first sodium-glucose cotransporter-2 inhibitor, canagliflozin, in the treatment of patients with type 2 diabetes mellitus (T2DM). METHODS: This observational study assessed the efficacy and tolerability of canagliflozin in T2DM patients. Primary study outcomes were changes in HbA1C and weight, and percentage of patients reporting adverse effects of therapy. RESULTS: The study criteria were met by 111 patient records. Baseline patient characteristics were: average age, 59 ± 9 years; mean duration of T2DM, 11.9 ± 7.3 years; 57.6% of patients were male; 92.8% were Caucasian; baseline BMI, 38.9 ± 11 kg/m(2); and mean baseline HbA1C, 7.53 (58.8 mmol/mol) ± 1.08%. HbA1C and weight were significantly reduced by 0.37% and 4.4 kg, respectively. Adverse effects were reported by 21 patients, and 17 (15.3%) discontinued canagliflozin because of adverse reactions. CONCLUSION: Canagliflozin was generally well tolerated and significantly reduced HbA1C levels and body weight in patients with T2DM when added to a regimen of other anti-hyperglycemic agents.

Weekly Exenatide Therapy: A Real-World Comparison of Incretin Therapies.

Background: Traditional diabetes therapies have been associated with weight gain, hypoglycemia, and/or high secondary failure rates. Glucagon-like peptide-1 (GLP-1) analog use is associated with a minimal risk of hypoglycemia, a persistent average weight loss of 2 to 3 kg, and sustained efficacy even after 3 years of use. Presently, 3 GLP-1 analogs are commercially available in the United States. Objective: To evaluate the real-world clinical utility of once weekly exenatide in type 2 diabetes mellitus (T2DM) patients who previously received once or twice daily GLP-1 therapy. Methods: In this pre-post observational study, electronic medical records (EMRs) were reviewed to identify patients meeting all study criteria. Data collected included baseline patient demographic information, duration of diabetes, disease states, medications, pertinent laboratory data, blood pressure, height, weight, and reported adverse drug events. Primary (changes in A1C and percentage of patients reporting adverse effects of therapy) and secondary (percentage of patients with A1C of <7% and changes in weight, blood pressure, and lipids) outcomes were evaluated using appropriate statistical analysis. Results: EMRs of 78 patients met all study criteria. Baseline patient demographic information included an average age of 61 ± 12 years, an average duration of T2DM of 14 ± 6 years, 59% of patients were male, and 93.6% were Caucasian. The baseline average body mass index was 39 ± 9.2, and mean A1C was 7.47 ± 1.45%. After a minimum of 3 months (average = 5.6 months) switchover, there were significant decreases in A1C (-0.35%; P = .0067) and weight (-1.6 kg; P = .0151). There were no significant changes in blood pressure or lipid levels. Two patients (2.5%) discontinued once weekly exenatide due to adverse reactions. Conclusion: Once weekly exenatide was generally well tolerated and significantly reduced A1C levels and body weight in patients with T2DM when switched from a shorter-acting GLP-1 analog.

Spontaneous resolution of primary hyperparathyroidism in parathyroid adenoma.

A 71 yo woman with primary hyperparathyroidism awaiting surgery because of significant hypercalcemia and hypercalciuria presented to the local emergency department with the chief complaints of discomfort in her neck, sore throat, and difficulty swallowing. She was found to be hypocalcemic with a calcium level of 8.1 mg/dL. She was seen by her endocrinologist three days later at which time serum calcium, iPTH, and serum phosphate levels were all within normal limits. Based on history and a series of ultrasounds the patient was diagnosed with spontaneous infarction of her parathyroid adenoma, which resulted in resolution of her primary hyperparathyroidism.

Efficacy of teriparatide in patients with resolved secondary hyperparathyroidism due to vitamin D deficiency.

OBJECTIVE: To determine the efficacy of at least 1 year of teriparatide therapy on bone mineral density (BMD), T-scores, and rates of occurrence of fractures in patients with a history of resolved secondary hyperparathyroidism due to vitamin D deficiency and to compare its efficacy with that in patients without a history of resolved secondary hyperparathyroidism. METHODS: In this retrospective study based on a search of electronic medical records, we collected the following data: patient demographics, doses of calcium and vitamin D supplementation, duration of teriparatide treatment, history and treatment of secondary hyperparathyroidism, BMD information, T-scores, and any history of fractures. Paired and unpaired t tests, the Fisher exact test, and the Wilcoxon rank sum test were used for statistical analysis. RESULTS: Ninety-five patients (7 with a history of resolved secondary hyperparathyroidism due to vitamin D deficiency and 88 without such a history) fulfilled the study inclusion criteria. Baseline characteristics (demographics, median calcium and vitamin D supplementation doses, mean BMD, mean T-scores, and fracture rates before teriparatide therapy) were similar between the 2 groups. In comparison with baseline data, after a mean of 21 months of teriparatide therapy: (1) hip BMD and T-scores did not change in either study group (with no significant differences between the 2 groups), (2) spine BMD and T-scores significantly improved in both study groups (with no significant differences between them), and (3) wrist T-scores significantly worsened in both study groups (with wrist BMD significantly lower in patients without a history of secondary hyperparathyroidism). No patients with a history of secondary hyperparathyroidism sustained a fracture while receiving teriparatide therapy versus 6 of 88 patients without a history of secondary hyperparathyroidism (P = .624). CONCLUSION: Patients with a history of resolved secondary hyperparathyroidism attributable to vitamin D deficiency responded to teriparatide therapy in a fashion similar to patients without such a history.

Accuracy and precision of four value-added blood glucose meters: the Abbott Optium, the DDI Prodigy, the HDI True Track, and the HypoGuard Assure Pro.

PURPOSE: This study compared the accuracy and precision of four value-added glucose meters. METHODS: Finger stick glucose measurements in diabetes patients were performed using the Abbott Diabetes Care (Alameda, CA) Optium, Diagnostic Devices, Inc. (Miami, FL) DDI Prodigy, Home Diagnostics, Inc. (Fort Lauderdale, FL) HDI True Track Smart System, and Arkray, USA (Minneapolis, MN) HypoGuard Assure Pro. Finger glucose measurements were compared with laboratory reference results. Accuracy was assessed by a Clarke error grid analysis (EGA), a Parkes EGA, and within 5%, 10%, 15%, and 20% of the laboratory value criteria (chi2 analysis). Meter precision was determined by calculating absolute mean differences in glucose values between duplicate samples (Kruskal-Wallis test). RESULTS: Finger sticks were obtained from 125 diabetes patients, of which 90.4% were Caucasian, 51.2% were female, 83.2% had type 2 diabetes, and average age of 59 years (SD 14 years). Mean venipuncture blood glucose was 151 mg/dL (SD +/-65 mg/dL; range, 58-474 mg/dL). Clinical accuracy by Clarke EGA was demonstrated in 94% of Optium, 82% of Prodigy, 61% of True Track, and 77% of the Assure Pro samples (P < 0.05 for Optium and True Track compared to all others). By Parkes EGA, the True Track was significantly less accurate than the other meters. Within 5% accuracy was achieved in 34%, 24%, 29%, and 13%, respectively (P < 0.05 for Optium, Prodigy, and Assure Pro compared to True Track). Within 10% accuracy was significantly greater for the Optium, Prodigy, and Assure Pro compared to True Track. Significantly more Optium results demonstrated within 15% and 20% accuracy compared to the other meter systems. The HDI True Track was significantly less precise than the other meter systems. CONCLUSIONS: The Abbott Optium was significantly more accurate than the other meter systems, whereas the HDI True Track was significantly less accurate and less precise compared to the other meter systems.

Safety and efficacy of exenatide in combination with insulin in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the 1-year efficacy and safety of treatment with exenatide in combination with insulin (a use not approved by the US Food and Drug Administration). METHODS: Electronic medical records of 3 private-practice endocrinologists were reviewed to identify patients with type 2 diabetes mellitus (T2DM) receiving insulin who subsequently began exenatide therapy. Patients' baseline hemoglobin A1c (A1C) levels, weights, lipid profiles, blood pressures, and medication utilization were compared with corresponding data obtained after a minimal duration of 12 months. RESULTS: We identified 134 patients with T2DM initiating exenatide therapy in combination with insulin between April 2005 and April 2006. One-year follow-up information was available for 124 patients. Exenatide use resulted in a significant 0.87% reduction in A1C (P<.001), despite a 45% discontinuation of premeal insulin use (P<.001), a 9-U reduction in mean premeal insulin doses (P = .0066), a reduction in the median number of daily insulin injections from 2 to 1 (P = .0053), and a 59% discontinuation rate of sulfonylurea use (P = .0088). Exenatide use was associated with a mean weight loss of 5.2 kg (P<.001), with 72% of evaluable patients losing weight. Forty-eight patients (36%) discontinued exenatide therapy during the first year, primarily attributable to gastrointestinal intolerance. Fourteen patients (10%) experienced hypoglycemia, most of which was mild. CONCLUSION: Exenatide in combination with insulin in patients with T2DM was associated with significant reductions in A1C and weight after 1 year of therapy. This was offset, however, by an exenatide discontinuation rate of 36%, primarily due to adverse gastrointestinal effects.

A glucose meter accuracy and precision comparison: the FreeStyle Flash Versus the Accu-Chek Advantage, Accu-Chek Compact Plus, Ascensia Contour, and the BD Logic.

BACKGROUND: This study compared the accuracy and precision of five blood glucose (BG) meters. METHODS: Diabetes patients undergoing venipuncture for glucose testing were randomized to one of two groups consisting of three meters: FreeStyle Flash (Abbott Diabetes Care, Alameda, CA), Accu-Chek Advantage (Roche Diagnostics Corp., Indianapolis, IN), and Accu-Chek Compact Plus (Roche Diagnostics) or FreeStyle Flash, Ascensia Contour (Bayer Healthcare, Diagnostic Division, Tarrytown, NY), and BD Logic (BD Diabetes Care, Franklin Lake, NJ). Within 5 min following venipuncture, duplicate finger BG measurements from three ipsilateral fingers were taken. Finger glucose measurements were compared with laboratory reference values. Accuracy was assessed by a Clarke error grid analysis (EGA) and within 10% of the laboratory value criteria. Meter precision was determined by calculating the absolute mean differences in glucose values between duplicate samples. RESULTS: Finger sticks were obtained from 202 patients. Mean venipuncture BG was 148 mg/dL (SD +/- mg/64 dL; range 25-439 mg/dL). Accuracy by Clarke EGA (Zone A results) was demonstrated in 69% of Advantage samples, 75% of Compact Plus, and 96% of the first group of Flash versus 88% of the Contour, 67% of the Logic, and 91% of the second Flash samples (P < 0.05 for both Flash and Contour). Meter accuracy using the 10% criteria was demonstrated in 30%, 38%, 70%, 46%, 48%, and 68% of the samples, respectively (P < 0.05 for both Flash groups compared to each of the other meters). There were no differences in meter precision. CONCLUSIONS: No statistically significant differences in accuracy were evident using the Clarke EGA criteria (pooled results of Zone A and B), though the more strict 20% accuracy criteria (Zone A results only) found the Flash and Contour to have significantly greater accuracy compared to the Advantage, Compact Plus, and the Logic. Using the 10% accuracy criteria found the Flash to have significantly greater accuracy than each of the other four meters. All five meters demonstrated similar precision.

Off-label use of exenatide for the management of insulin-resistant type 1 diabetes mellitus in an obese patient with human immunodeficiency virus infection.

Exenatide is an incretin mimetic indicated for the treatment of type 2 diabetes mellitus in combination with a sulfonylurea, a thiazolidinedione, metformin, or metformin plus a sulfonylurea or thiazolidinedione. Exenatide lowers postprandial blood glucose levels by stimulating glucose-dependent insulin secretion, inhibiting glucagon secretion, slowing gastric emptying, and increasing satiety. Therapy with exenatide often results in weight loss, which further assists in decreasing insulin resistance. This feature makes the drug an attractive therapeutic option for obese patients. We report the successful off-label use of exenatide in an obese, 40-year-old man with type 1 diabetes and human immunodeficiency virus (HIV) infection who had gastrointestinal intolerance to pramlintide. The patient had experienced a dramatic weight gain secondary to his antiretroviral drugs. This weight gain led to insulin resistance and the development of type 2 diabetes; thus he had characteristics of both types 1 and 2 diabetes, or double diabetes. Before the start of exenatide therapy, he weighed 123 kg, had a body mass index of 42.3 kg/m(2), and had a suboptimal hemoglobin A(1c) value of 8.7%. After 11 months of therapy, the patient lost 24 kg (19.5% of his body weight) and achieved a hemoglobin A(1c) value of 7.3%. His basal insulin requirement was reduced by 25%, and his use of short-acting insulin before breakfast and before dinner was discontinued. In addition, the patient's quality of life substantially improved, as he was able to return to work and exercise after being nearly incapacitated by his weight. To our knowledge, this is the first published case report of the use of exenatide in a patient with type 1 diabetes mellitus or human immunodeficiency virus infection. Given this experience, exenatide may prove to be a useful alternative in selected patients with type 1 diabetes.

Colesevelam hydrochloride-ezetimibe combination lipid-lowering therapy in patients with diabetes or metabolic syndrome and a history of statin intolerance.

OBJECTIVE: To determine the effectiveness and safety of colesevelam hydrochloride (HCl) and ezetimibe combination therapy in statin-intolerant patients with dyslipidemia and diabetes mellitus (DM) or metabolic syndrome (MS). METHODS: We identified potential study subjects through a computerized text search of patient electronic medical records using the terms colesevelam, WelChol, ezetimibe, and Zetia. Medical records were subsequently reviewed to identify all patients with DM or MS. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglyceride levels immediately before the initiation of therapy with colesevelam HCl (1.875 g twice a day) or ezetimibe (10 mg daily) were compared with those after a minimum of 3 months of single drug therapy and after a minimum of 3 months of combination therapy. Drug safety was evaluated by review of transaminase levels and reports of side effects or drug discontinuation. RESULTS: The computerized search initially identified 91 electronic medical records; 16 patients fulfilled all study criteria. Baseline patient demographics included a mean age of 62.5 (+/-11.8) years and a mean body mass index of 31.4 (+/-5.2) kg/m2; 50% of patients were female, 75% had type 2 DM, and 25% had MS. In comparison with baseline, colesevelam HCl-ezetimibe combination therapy was associated with significant reductions in mean levels of total cholesterol (27.5%), LDL-C (42.2%), and non-HDL-C (37.1%). In addition, 50% of patients achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C target of less than 100 mg/dL. Therapy was well tolerated, with no significant changes in mean transaminase levels, no reports of myalgia, and no discontinuation of therapy. CONCLUSION: Colesevelam HCl-ezetimibe combination therapy was associated with improved TC, LDL-C, and non-HDL-C lipid profiles and was well tolerated. Such therapy may be a reasonable consideration for statin-intolerant patients with DM or MS who have elevated cholesterol levels.

Precision and accuracy of two blood glucose meters: FreeStyle Flash versus One Touch Ultra.

PURPOSE: The precision and accuracy of two blood glucose meters were evaluated using finger and forearm blood samples. METHODS: Duplicate blood glucose measurements on the same forearm and finger as venipuncture were performed with the FreeStyle Flash and the One Touch Ultra. Accuracy was assessed by error-grid analysis and the number of values within 10% of the laboratory reference value. Precision was determined by calculating the absolute mean percent differences in glucose values between the first and second fingers and forearm test results. Forearm testing success was defined as an accurate glucose reading obtained with one lance. RESULTS: A total of 100 patients completed the study; 93% had diabetes and 53% were female. Patients' mean +/- S.D. age was 63 +/- 12 years, and glucose measurements ranged from 69 to 354 mg/dL. All finger-stick samples fell within error-grid zones A and B; 72% and 57% of FreeStyle Flash and One Touch Ultra values fell within 10% of the laboratory reference values, respectively (p = 0.027). Forearm samples were successfully obtained in 99 and 74 patients using the FreeStyle Flash and One Touch Ultra (p < 0.001), with 64 and 36 samples, respectively, falling within 10% of the laboratory reference values (p = 0.035). There was no difference in meter precision. CONCLUSION: The FreeStyle Flash and the One Touch Ultra are precise glucose meters; however, the FreeStyle Flash was associated with greater accuracy. Success rates of forearm glucose sampling were significantly greater when the FreeStyle Flash meter was used.