Diabetes Distal Peripheral Neuropathy: Subtypes and Diagnostic and Screening Technologies

Diabetes distal symmetrical peripheral neuropathy (DSPN) is the most prevalent form of neuropathy in industrialized countries, substantially increasing risk for morbidity and pre-mature mortality. DSPN may manifest with small-fiber disease, large-fiber disease, or a combination of both. This review summarizes: (1) DSPN subtypes (small- and large-fiber disease) with attention to clinical signs and patient symptoms; and (2) technological diagnosis and screening for large- and small-fiber disease with inclusion of a comprehensive literature review of published studies from 2015-present ( N = 66). Review findings, informed by the most up-to-date research, advance critical understanding of DSPN large- and small-fiber screening technologies, including those designed for point-of-care use in primary care and endocrinology practices.

In Vitro Evaluation of Miniaturized Amperometric Enzyme Sensor Based on the Direct Electron Transfer Principle for Continuous Glucose Monitoring

Background: The bacterial derived flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenase (FADGDH) is the most promising enzyme for the third-generation principle-based enzyme sensor for continuous glucose monitoring (CGM). Due to the ability of the enzyme to transfer electrons directly to the electrode, recognized as direct electron transfer (DET)-type FADGDH, although no investigation has been reported about DET-type FADGDH employed on a miniaturized integrated electrode. Methods: The miniaturized integrated electrode was formed by sputtering gold (Au) onto a flexible film with 0.1 mm in thickness and divided into 3 parts. After an insulation layer was laminated, 3 openings for a working electrode, a counter electrode and a reference electrode were formed by dry etching. A reagent mix containing 1.2 × 10−4 Unit of DET-type FADGDH and carbon particles was deposited. The long-term stability of sensor was evaluated by continuous operation, and its performance was also evaluated in the presence of acetaminophen and the change in oxygen partial pressure (pO2) level. Results: The amperometric response of the sensor showed a linear response to glucose concentration up to 500 mg/dL without significant change of the response over an 11-day continuous measurement. Moreover, the effect of acetaminophen and pO2 on the response were negligible. Conclusions: These results indicate the superb potential of the DET-type FADGDH-based sensor with the combination of a miniaturized integrated electrode. Thus, the described miniaturized DET-type glucose sensor for CGM will be a promising tool for effective glycemic control. This will be further investigated using an in vivo study.

Optimal Data Collection Period for Continuous Glucose Monitoring to Assess Long-Term Glycemic Control: Revisited

Background and Objective: It is not clear how the short-term continuous glucose monitoring (CGM) sampling time could influence the bias in estimating long-term glycemic control. A large bias could, in the worst case, lead to incorrect classification of patients achieving glycemic targets, nonoptimal treatment, and false conclusions about the effect of new treatments. This study sought to investigate the relation between sampling time and bias in the estimates. Methods: We included a total of 329 type 1 patients (age 14-86 years) with long-term CGM (90 days) data from three studies. The analysis calculated the bias from estimating long-term glycemic control based on short-term sampling. Time in range (TIR), time above range (TAR), time below range (TBR), correlation, and glycemic target classification accuracy were assessed. Results: A sampling time of ten days is associated with a high bias of 10% to 47%, which can be reduced to 4.9% to 26.4% if a sampling time of 30 days is used ( P < .001). Correct classification of patients archiving glycemic targets can also be improved from 81.5% to 91.9 to 90% to 95.2%. Conclusions: Our results suggest that the proposed 10-14 day CGM sampling time may be associated with a high correlation with three-month CGM. However, these estimates are subject to large intersubject bias, which is clinically relevant. Clinicians and researchers should consider using assessments of longer durations of CGM data if possible, especially when assessing time in hypoglycemia or while testing a new treatment.

Cost-Utility of an Online Education Platform and Diabetes Personal Health Record: Analysis Over Ten Years

Background and Aims: My Diabetes My Way (MDMW) is Scotland’s interactive website and mobile app for people with diabetes and their caregivers. It contains multimedia resources for diabetes education and offers access to electronic personal health records. This study aims to assess the cost-utility of MDMW compared with routine diabetes care in people with type 2 diabetes who do not use insulin. Materials and Methods: Analysis used the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model 2. Clinical parameters of MDMW users (n = 2576) were compared with a matched cohort of individuals receiving routine care alone (n = 11 628). Matching criteria: age, diabetes duration, sex, and socioeconomic status. Impact on life expectancy, quality-adjusted life years (QALYs), and costs of treatment and complications were simulated over ten years, including a 10% sensitivity analysis. Results: MDMW cohort: 1670 (64.8%) men; average age 64.3 years; duration of diabetes 5.5 years. 906 (35.2%) women: average age 61.6 years; duration 4.7 years. The cumulative mean QALY (95% CI) gain: 0.054 (0.044-0.062) years. Mean difference in cost: –£118.72 (–£150.16 to –£54.16) over ten years. Increasing MDMW costs (10%): –£50.49 (–£82.24-£14.14). Decreasing MDMW costs (10%): –£186.95 (–£218.53 to –£122.51). Conclusions: MDMW is “dominant” over usual care (cost-saving and life improving) in supporting self-management in people with type 2 diabetes not treated with insulin. Wider use may result in significant cost savings through delay or reduction of long-term complications and improved QALYs in Scotland and other countries. MDMW may be among the most cost-effective interventions currently available to support diabetes.

The First Interchangeable Biosimilar Insulin: Insulin Glargine-yfgn

On March 23, 2020, all insulin products were reclassified as biologics instead of drugs under the Biological Price Competition and Innovation (BPCI) Act of 2009. This allows biosimilar insulin products to be manufactured when the patent expires for the reference biologic, sometimes called the originator or brand name product. A biosimilar product may not be substituted for the reference biologic at the pharmacy counter unless the biosimilar undergoes further switch trials to earn the designation as an interchangeable biosimilar. Insulin glargine-yfgn 100 units/mL is the first biosimilar insulin to attain interchangeable status with the reference insulin glargine. In the INSTRIDE 1 and INSTRIDE 2 trials, insulin glargine-yfgn has proven noninferiority regarding blood glucose reduction and adverse effect profile versus reference insulin glargine; even in the INSTRIDE 3 trial in which treatment of diabetes was switched between insulin glargine-yfgn and reference insulin glargine throughout the trial without statistically significant changes to glucose levels or adverse effects. Insulin glargine-yfgn may be substituted at the pharmacy counter without consultation with the prescriber, in accordance with state laws. In suit with other biosimilars, insulin glargine-yfgn’s list price is significantly lower than other insulin glargine products. This increases market competition leading to decreases in costs of other insulin glargine products. Many patients who could not previously afford insulin therapy may now have significantly improved access to treatment. Providers will need education to increase awareness of these new biosimilars and interchangeable biosimilar insulin products, cost benefits, and substitution allowances.

The Effectiveness of Telemedicine Solutions for the Management of Type 2 Diabetes: A Systematic Review, Meta-Analysis, and Meta-Regression

Background: Previous systematic reviews have aimed to clarify the effect of telemedicine on diabetes. However, such reviews often have a narrow focus, which calls for a more comprehensive systematic review within the field. Hence, the objective of the present systematic review, meta-analysis, and meta-regression is to evaluate the effectiveness of telemedicine solutions versus any comparator without the use of telemedicine on diabetes-related outcomes among adult patients with type 2 diabetes (T2D). Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We considered telemedicine randomized controlled trials (RCT) including adults (≥18 years) diagnosed with T2D. Change in glycated hemoglobin (HbA1c, %) was the primary outcome. PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) were searched on October 14, 2020. An overall treatment effect was estimated using a meta-analysis performed on the pool of included studies based on the mean difference (MD). The revised Cochrane risk-of-bias tool was applied and the certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: The final sample of papers included a total of 246, of which 168 had sufficient information to calculate the effect of HbA1c%. The results favored telemedicine, with an MD of −0.415% (95% confidence interval [CI] = −0.482% to −0.348%). The heterogeneity was great (I2 = 93.05%). A monitoring component gave rise to the higher effects of telemedicine. Conclusions: In conclusion, telemedicine may serve as a valuable supplement to usual care for patients with T2D. The inclusion of a telemonitoring component seems to increase the effect of telemedicine.

Clinical Practice Experiences Using a Professional Diabetes Management Ecosystem During COVID

Background: Challenges of patient care in diabetes were exacerbated by COVID, undermining the ability of patients to engage in-person with health care professionals (HCPs). To combat this, there has been accelerated adoption of telemedicine to support patient and provider connectivity. Methods: We collated survey information regarding telemedicine from 21 European clinical institutions. Health care professionals joined virtual meetings focusing on the OneTouch Reveal (OTR) ecosystem and its utility for conducting telemedicine. Selected HCPs provided clinical case studies to explain how the OTR ecosystem supported patient care. Results: Remote consultations increased by nearly 50% in 21 European clinics during the pandemic (Belgium [24%], Iberia [65%], Germany [34%], Italy [54%]). In all, 52% of people with diabetes using OTR app to connect remotely with HCPs had type 1 diabetes and 48% had type 2 diabetes. Remote connection methods included telephone (60%), email (19%), video chat (10%), text only (3%), or a mix of these methods (8%). Health care professionals usually reviewed patient data during consultations (45%) rather than before consultations (25%). Fifty-five percent of HCPs indicated digital ecosystems like OTR ecosystem would become their standard of care for diabetes management. In-depth conversations with HCPs provided a deeper understanding of how a digital ecosystem integrated into clinical practice and population management. In addition, five patient case studies using OTR ecosystem were provided by a selection of our HCPs. Conclusion: Diabetes management solutions, such as OTR ecosystem, supported telemedicine during the pandemic and will continue to play a valuable role in patient care beyond the pandemic.

Automated Bolus Calculators and Connected Insulin Pens: A Smart Combination for Multiple Daily Injection Insulin Therapy

Although automated bolus calculators (ABCs) have become a mainstay in insulin pump therapy, they have not achieved similar levels of adoption by persons with diabetes (PWD) using multiple daily injections of insulin (MDI). Only a small number of blood glucose meters (BGMs) have incorporated ABC functionality and the proliferation of unregulated ABC smartphone apps raised safety concerns and eventually led to Food and Drug Administration (FDA)–mandated regulatory oversight for these types of apps. With the recent introduction of smartphone-connected insulin pens, manufacturer-supported companion ABC apps may offer an ideal solution for PWD and health care professionals that reduces errors of mental math when calculating bolus insulin dosing, increases the quality of diabetes data reporting, and improves glycemic outcomes.

An Adaptive, Algorithm-based Text Message Intervention to Promote Health Behavior Adherence in Type 2 Diabetes: Treatment Development and Proof-of-Concept Trial

Background: Most individuals with type 2 diabetes (T2D) struggle to adhere to one or more health behaviors. Text message interventions (TMIs) have the potential to improve adherence but have had mixed effects on diet and activity in T2D. We developed an eight-week, adaptive, algorithm-driven TMI to promote physical activity, diet, self-care, and well-being. Then, in a single-arm trial, we assessed its feasibility, acceptability, and preliminary efficacy in 15 individuals with T2D and suboptimal adherence. Methods: Participants received daily text messages and were asked to rate the utility of each message (0=not helpful, 10=very helpful). These ratings were used by an algorithm to select subsequent messages based on each participant’s prior ratings. We assessed intervention feasibility by rates of message transmission/response and acceptability through ratings of message utility and burden. Finally, we examined pre-post changes in diabetes self-care, diet, physical activity, and psychological outcomes and calculated effect sizes (Cohen’s d). Results: All text messages were delivered, and participants provided ratings for 79% of messages, above our a priori thresholds for feasibility. Participants rated the individual messages and overall TMI as subjectively useful (utility: 8.1 [SD=2.1] and 7.8 [SD=2.0], respectively) and not burdensome (burden: 0.8 [SD=1.8]). The intervention led to significant, medium- to large-sized improvements in self-care ( d=0.77), diet ( d=0.99), and activity ( d=0.61) but minimal change in psychological outcomes. Conclusions: The TMI was feasible and well-accepted, and it led to promising improvements in adherence-related outcomes. These findings should be confirmed in a larger randomized controlled trial.