Brian L. Levy

Adrenal insufficiency as a complication of the acquired immunodeficiency syndrome.

Excerpt Since the acquired immunodeficiency syndrome was recognized in 1980, various malignancies, infections, and immunologic defects have been found in the affected population. Recently, adrenal ...

Efficacy and Safety of Technosphere Inhaled Insulin Compared With Technosphere Powder Placebo in Insulin-Naive Type 2 Diabetes Suboptimally Controlled With Oral Agents

OBJECTIVE—This double-blind, placebo-controlled, randomized, multicenter, parallel-group study compared the efficacy, safety, and tolerability of Technosphere insulin with Technosphere powder as placebo in insulin-naive type 2 diabetic patients whose diabetes was suboptimally controlled with oral antidiabetic agents. RESEARCH DESIGN AND METHODS—Patients (n = 126) were randomly assigned to 12 weeks of therapy with Technosphere insulin or Technosphere powder after lifestyle education on nutrition, exercise, and instructions on inhaler use. The primary efficacy outcome was change in A1C from baseline to study end, and the secondary efficacy outcome was area under the curve for postprandial glucose levels during a meal test at treatment weeks 4, 8, and 12. RESULTS—A1C reduction from a mean baseline of 7.9% was greater with Technosphere insulin than with Technosphere powder (−0.72 vs. −0.30%; P = 0.003). Postprandial glucose excursions were reduced by 56% with Technosphere insulin compared with baseline, and maximal postprandial glucose levels were reduced by 43% compared with Technosphere powder. Incidences of hypoglycemia, hyperglycemia, cough, and other adverse events were low in both groups. Body weight was unchanged in both groups. CONCLUSIONS—Technosphere insulin was well tolerated and demonstrated significant improvement in glycemic control with clinically meaningful reductions in A1C levels and postprandial glucose concentrations after 12 weeks of treatment.

Outcome measures for artificial pancreas clinical trials: A consensus report

Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes.

Synergism between vasopressin and phorbol esters in stimulation of insulin secretion and phosphatidylcholine metabolism in RIN insulinoma cells

The tumor promoter, tetradecanoylphorbolacetate (TPA), causes a significant increase in both insulin secretion and the incorporation of 32Pi into phosphatidylcholine (PC) in RIN insulinoma cells. The peptide hormone, arginine vasopressin (AVP), also stimulates these functions, although to a lesser degree. When added together, the effects on secretion and PC metabolism are synergistic. At the same time, TPA inhibits the AVP-stimulated rise in phosphoinositide (PI) metabolism. Neither phloretin nor tamoxifen, reported to be inhibitors of protein kinase C activity, are able to block the effects of TPA on secretion, although both influence PC metabolism.

Sensitivity of the Predictive Hypoglycemia Minimizer System to the Algorithm Aggressiveness Factor

Background: The Predictive Hypoglycemia Minimizer System (“Hypo Minimizer”), consisting of a zone model predictive controller (the “controller”) and a safety supervision module (the “safety module”), aims to mitigate hypoglycemia by preemptively modulating insulin delivery based on continuous glucose monitor (CGM) measurements. The “aggressiveness factor,” a pivotal variable in the system, governs the speed and magnitude of the controller’s insulin dosing characteristics in response to changes in CGM levels. Methods: Twelve adults with type 1 diabetes were studied in closed-loop in a clinical research center for approximately 24 hours. This analysis focused primarily on the effect of the aggressiveness factor on the automated insulin-delivery characteristics of the controller, and secondarily on the glucose control results. Results: As aggressiveness increased from “conservative” to “medium” to “aggressive,” the controller recommended less insulin (–3.3% vs –14.4% vs –19.5% relative to basal) with a higher frequency (5.3% vs 14.4% vs 20.3%) during the critical times when the CGM was reading 90-120 mg/dl and decreasing. Blood glucose analyses indicated that the most aggressive setting resulted in the most desirable combination of the least time spent <70 mg/dl and the most time spent 70-180 mg/dl, particularly in the overnight period. Hyperglycemia, diabetic ketoacidosis, or severe hypoglycemia did not occur with any of the aggressiveness values. Conclusion: The Hypo Minimizer’s controller took preemptive action to prevent hypoglycemia based on predicted changes in CGM glucose levels. The most aggressive setting was quickest to take action to reduce insulin delivery below basal and achieved the best glucose metrics.

Use of Blood Glucose Meters Featuring Color Range Indicators Improves Glycemic Control in Patients With Diabetes in Comparison to Blood Glucose Meters Without Color (ACCENTS Study)

Background: The ability of patients to improve glycemic control depends partly on their ability to interpret and act on blood glucose results. We investigated whether switching people with diabetes to blood glucose meters (BGMs) featuring a color range indicator (CRI) could improve glycemic control compared to remaining on their current BGM without color. Methods: 163 adults with type 1 (T1D) or type 2 diabetes (T2D) and a hemoglobin A1c (A1c) of 7.5-11% were randomized to: One Touch Verio™ (Verio), OneTouch Verio Flex™ (Flex), or controls remaining on their current BGM. Diabetes nurses had standard conversations about diabetes management with all subjects at baseline. No changes in medication, insulin dosing, or SMBG frequency were recommended. Results: After 12 weeks, subjects who switched to Verio or Flex meters with CRI (n = 108) had a mean change in A1c 0.36% lower than controls (n = 55) (P = .017). A1c reductions were greatest in T1D subjects (n = 45), with a decrease of 0.50% (P = .004). T1D subjects using Verio meters (n = 25) contributed a 0.59% reduction compared to controls (P < .008), whereas T1D subjects using Flex meters (n = 20) had a clinical meaningful reduction in A1c of 0.40% without reaching statistical significance (P > .05). Verio and Flex users reported taking more action and easier understanding of diabetes management compared to previous BGMs. Conclusions: This study demonstrated that switching patients to BGMs featuring a CRI resulted in improvements in glycemic control compared to subjects using currently marketed BGMs that do not use a CRI. Registration: Clinicaltrials.gov NCT02929654 https://clinicaltrials.gov/ct2/show/NCT02929654

Seven-Year Clinical Surveillance Program Demonstrates Consistent MARD Accuracy Performance of a Blood Glucose Test Strip:

Background: MARD (mean absolute relative difference) is increasingly used to describe performance of glucose monitoring systems, providing a single-value quantitative measure of accuracy and allowing comparisons between different monitoring systems. This study reports MARDs for the OneTouch Verio® glucose meter clinical data set of 80 258 data points (671 individual batches) gathered as part of a 7.5-year self-surveillance program Methods: Test strips were routinely sampled from randomly selected manufacturer’s production batches and sent to one of 3 clinic sites for clinical accuracy assessment using fresh capillary blood from patients with diabetes, using both the meter system and standard laboratory reference instrument. Results: Evaluation of the distribution of strip batch MARD yielded a mean value of 5.05% (range: 3.68-6.43% at ±1.96 standard deviations from mean). The overall MARD for all clinic data points (N = 80 258) was also 5.05%, while a mean bias of 1.28 was recorded. MARD by glucose level was found to be consistent, yielding a maximum value of 4.81% at higher glucose (≥100 mg/dL) and a mean absolute difference (MAD) of 5.60 mg/dL at low glucose (<100 mg/dL). MARD by year of manufacture varied from 4.67-5.42% indicating consistent accuracy performance over the surveillance period. Conclusions: This 7.5-year surveillance program showed that this meter system exhibits consistently low MARD by batch, glucose level and year, indicating close agreement with established reference methods whilste exhibiting lower MARD values than continuous glucose monitoring (CGM) systems and providing users with confidence in the performance when transitioning to each new strip batch.