Advances in Closed-Loop Insulin Delivery Systems in Patients with Type 1 Diabetes

Purpose of Review

To provide a current review of closed-loop insulin delivery or artificial pancreas (AP) as therapy for people with type 1 diabetes mellitus (T1D)

Recent Findings

The Medtronic Minimed 670G AP system has been in use in clinical practice since March 2017. Currently, Medtronic is conducting a large randomized clinical trial to evaluate its efficacy further in T1D. Simultaneously, the NIH has funded four research consortia to accelerate progress to approval of other AP and decision support systems. Several research groups are currently developing next-generation AP systems, with a number of companies moving toward releasing closed-loop systems in the future. AP systems are also being tested in select populations such as hypoglycemia-unaware T1D and pregnant T1D.

Summary

AP research is rapidly advancing. The clinical range of AP will be expanded in the next decade.

     

An Overview of Safety Issues on Use of Insulin Pumps and Continuous Glucose Monitoring Systems in the Hospital

Purpose of Review

Summarize safety issues related to patients using insulin pump therapy and continuous glucose monitoring systems (CGMS) in the outpatient setting when they are hospitalized and to review steps that can be taken to mitigate risk associated with use or discontinuation of these devices.

Recent Findings

Two recent consensus conferences were held on the topics of inpatient use of insulin pumps and CGMS devices. In addition to commonly known safety issues (e.g., device malfunction, infection), cybersecurity and the vulnerability of contemporary technology to hacking have emerged. CGMS capabilities offer the promise of advancing the goal for development of glucometry (centralized monitoring of real-time glucose data). Strategies to assuring safe use of insulin pumps and CGMS in the hospital include collaboration between the patient and staff, proper patient selection, and clear policies and procedures outlining safe use. Available data indicates few adverse events associated with these devices in the hospital.

Summary

Current data suggests, with proper patient selection and a clear process in place for glycemic management, that adverse events are rare, and consensus favors allowing use of the technology in the hospital. The topic of insulin pump and CGMS in the hospital would greatly benefit from more institutions reporting on their experiences and prospective clinical trials.

     

Gut Microbiome in Obesity,Metabolic Syndrome,and Diabetes

Purpose of Review

Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.

Recent findings

Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation.

Summary

While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.

     

VA and Medicare Utilization Among Dually Enrolled Veterans with Type 2 Diabetes: A Latent Class Analysis

BACKGROUND

Many Veterans treated within the VA Healthcare System (VA) are also enrolled in fee-for-service (FFS) Medicare and receive treatment outside the VA. Prior research has not accounted for the multiple ways that Veterans receive services across healthcare systems.

OBJECTIVE

We aimed to establish a typology of VA and Medicare utilization among dually enrolled Veterans with type 2 diabetes.

DESIGN

This was a retrospective cohort.

PARTICIPANTS

316,775 community-dwelling Veterans age ≥ 65 years with type 2 diabetes who were dually enrolled in the VA and FFS Medicare in 2008–2009.

METHODS

Using latent class analysis, we identified classes of Veterans based upon their probability of using VA and Medicare diabetes care services, including patient visits, laboratory tests, glucose test strips, and medications. We compared the amount of healthcare use between classes and identified factors associated with class membership using multinomial regression.

KEY RESULTS

We identified four distinct latent classes: class 1 (53.9 %) had high probabilities of VA use and low probabilities of Medicare use; classes 2 (17.2 %), 3 (21.8 %), and 4 (7.0 %) had high probabilities of VA and Medicare use, but differed in their Medicare services used. For example, Veterans in class 3 received test strips exclusively through Medicare, while Veterans in class 4 were reliant on Medicare for medications. Living ≥ 40 miles from a VA predicted membership in classes 3 (OR 1.1, CI 1.06–1.15) and 4 (OR 1.11, CI 1.04–1.18), while Medicaid eligibility predicted membership in class 4 (OR 4.30, CI 4.10–4.51).

CONCLUSIONS

Veterans with diabetes can be grouped into four distinct classes of dual health system use, representing a novel way to characterize how patients use multiple services across healthcare systems. This classification has applications for identifying patients facing differential risk from care fragmentation.

     

Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes

BACKGROUND

Type 2 diabetes patients often initiate treatment with a sulfonylurea and subsequently intensify their therapy with insulin. However, information on optimal treatment regimens for these patients is limited.

OBJECTIVE

To compare risk of cardiovascular disease (CVD) and hypoglycemia between sulfonylurea initiators who switch to or add insulin.

DESIGN

This was a retrospective cohort assembled using national Veterans Health Administration (VHA), Medicare, and National Death Index databases.

PARTICIPANTS

Veterans who initiated diabetes treatment with a sulfonylurea between 2001 and 2008 and intensified their regimen with insulin were followed through 2011.

MAIN MEASURES

The association between insulin versus sulfonylurea?+?insulin and time to CVD or hypoglycemia were evaluated using Cox proportional hazard models in a 1:1 propensity score-matched cohort. CVD included hospitalization for acute myocardial infarction or stroke, or cardiovascular mortality. Hypoglycemia included hospitalizations or emergency visits for hypoglycemia, or outpatient blood glucose measurements <60 mg/dL. Subgroups included age < 65 and ≥ 65 years and estimated glomerular filtration rate ≥ 60 and < 60 ml/min.

KEY FINDINGS

There were 1646 and 3728 sulfonylurea monotherapy initiators who switched to insulin monotherapy or added insulin, respectively. The 1596 propensity score-matched patients in each group had similar baseline characteristics at insulin initiation. The rate of CVD per 1000 person-years among insulin versus sulfonylurea?+?insulin users were 49.3 and 56.0, respectively [hazard ratio (HR) 0.85, 95 % confidence interval (CI) 0.64, 1.12]. Rates of first and recurrent hypoglycemia events per 1000 person-years were 74.0 and 100.0 among insulin users compared to 78.9 and 116.8 among sulfonylurea plus insulin users, yielding HR (95 % CI) of 0.94 (0.76, 1.16) and 0.87 (0.69, 1.10), respectively. Subgroup analysis results were consistent with the main findings.

CONCLUSIONS

Compared to sulfonylurea users who added insulin, those who switched to insulin alone had numerically lower CVD and hypoglycemia events, but these differences in risk were not statistically significant.

     

Predictors of Insulin Initiation in Patients with Type 2 Diabetes: An Analysis of the Look AHEAD Randomized Trial

Background

The decision to initiate insulin in patients with type 2 diabetes is a challenging escalation of care that requires an individualized approach. However, the sociodemographic and clinical factors affecting insulin initiation are not well understood.

Objective

We sought to identify patient factors that were independent predictors of insulin initiation among participants in the Look AHEAD (Action for Health in Diabetes) clinical trial.

Design

Retrospective analysis of a randomized clinical trial.

Participants

Beginning in 2001, Look AHEAD enrolled ambulatory U.S. adults with type 2 diabetes who were overweight or obese and had a primary healthcare provider. Participants were randomized (1:1) to an intensive lifestyle intervention, or diabetes support and education. This study examined 3913 participants across the two trial arms who were not using insulin at baseline.

Main Measures

We used Cox proportional hazards models to estimate the association between participant characteristics and time to insulin initiation. We performed time-varying adjustment for HbA1c measured eight times over the 10-year study period, as well as for multiple clinical and socioeconomic factors.

Key Results

A total of 1087 participants (27.8%) initiated insulin during a median follow-up of 8.0 years. Age was inversely associated with insulin initiation (adjusted hazard ratio [aHR] 0.88 per 10 years, P?=?0.025). The risk of insulin initiation was greater with a higher number of diabetes complications (P?<?0.001 for trend); chronic kidney disease and cardiovascular disease were independently associated with insulin initiation. There was a lower risk of insulin initiation in black (aHR 0.77, P?=?0.008) and Hispanic participants (aHR 0.66, P?<?0.001) relative to white participants. Socioeconomic factors were not associated with insulin initiation.

Conclusions

Patient age, race/ethnicity, and diabetes complications may influence insulin initiation in type 2 diabetes, independent of glycemic control. Future work is needed to understand the drivers of racial differences in antihyperglycemic treatment, and to identify patients who benefit most from insulin.

     

Applying Systems Engineering Principles in Improving Health Care Delivery

Background

In a highly publicized joint report, the National Academy of Engineering and the Institute of Medicine recently recommended the systematic application of systems engineering approaches for reforming our health care delivery system. For this to happen, medical professionals and managers need to understand and appreciate the power that systems engineering concepts and tools can bring to redesigning and improving health care environments and practices.

Objective

To present and discuss fundamental concepts and tools of systems engineering and important parallels between systems engineering, health services, and implementation research as it pertains to the care of complex patients.

Design

An exploratory, qualitative review of systems engineering concepts and overview of ongoing applications of these concepts in the areas of hemodialysis, radiation therapy, and patient flow modeling.

Results

In this paper, we describe systems engineering as the process of identifying the system of interest, choosing appropriate performance measures, selecting the best modeling tool, studying model properties and behavior under a variety of scenarios, and making design and operational decisions for implementation.

Conclusions

We discuss challenges and opportunities for bringing people with systems engineering skills into health care.

     

Substance Use and Adherence to Antiretroviral Therapy: What Is Known and What Is Unknown

Purpose of Review

People who use drugs face multiple challenges to achieve optimal HIV treatment outcomes. This review discusses the current knowledge in substance use and antiretroviral therapy adherence, highlighting recent findings and potential interventions.

Recent Findings

Studies continue to demonstrate the negative impacts of substance use and related disorders on antiretroviral therapy adherence, with the exception of cannabis. Evidence-based addiction treatment, in particular, opioid agonist therapy, appears to improve adherence levels. Most individual-level adherence specific interventions did not provide sustained effects, and no studies evaluating structural-level interventions were found.

Summary

Findings suggest the urgent need to scale-up opioid agonist therapy, as well as to simultaneously address multiple structural barriers to care to optimize HIV treatment outcomes among people who use drugs.

     

Assessing Psychological Insulin Resistance in Type 2 Diabetes: a Critical Comparison of Measures

Purpose of Review

This study aims to examine the operationalisation of ‘psychological insulin resistance’ (PIR) among people with type 2 diabetes and to identify and critique relevant measures.

Recent Findings

PIR has been operationalised as (1) the assessment of attitudes or beliefs about insulin therapy and (2) hypothetical or actual resistance, or unwillingness, to use to insulin. Five validated PIR questionnaires were identified. None was fully comprehensive of all aspects of PIR, and the rigour and reporting of questionnaire development and psychometric validation varied considerably between measures.

Summary

Assessment of PIR should focus on the identification of negative and positive attitudes towards insulin use. Actual or hypothetical insulin refusal may be better conceptualised as a potential consequence of PIR, as its assessment overlooks the attitudes that may prevent insulin use. This paper provides guidance on the selection of questionnaires for clinical or research purpose and the development of new, or improvement of existing, questionnaires.

     

Identifying new Risk Markers and Potential Targets for Coronary Artery Disease: The Value of the Lipidome and Metabolome

Purpose

This systematic review was performed to summarize published data on lipidomic and metabolomic risk markers of coronary artery disease.

Methods

Studies were identified from a literature search of PubMed.

Results

Published data shows that analysis of metabolites and lipids offers an opportunity to increase our knowledge of the biological processes related to development and progression of atherosclerotic coronary disease. It is evident that advanced analytical technologies are able to detect and identify a large number of molecules that may have important structural and functional roles over and above currently used biomarkers in the cardiovascular field. It is suggested in a number of reports that the novel biomarkers can be used to improve risk stratification and patient selection for different treatments. Also, monitoring treatment efficacy and safety as well as lifestyle changes should be facilitated by such novel markers.

Conclusion

Until now a plethora of biomarker candidates associated with cardiovascular event risk have been identified, but very few have passed through clinical and analytical validation and found their way into clinical use. Consequently, the appetite of physicians to use these novel tests in daily clinical routine has not yet been truly tested.

     

Treatment of acute hepatitis C: recommendations from an expert panel of the Italian Society of Infectious and Tropical Diseases

Aim

This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).

Methods

This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.

Results

Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.

Conclusions

Early treatment with DAA should be offered when available.

     

Delta wave notching time is associated with accessory pathway localization in patients with Wolff-Parkinson-White syndrome

Purpose

Our aim was to investigate the relation between delta wave notching time (DwNt) and accessory pathway location in patients with Wolff-Parkinson-White (WPW) syndrome.

Methods

The retrospective study included 149 WPW patients who underwent ablation therapy. DwNt was defined as the duration between the initial point of QRS and the notching in the delta wave. DwNt was divided by QRS duration to obtain the delta wave index (Dwi).

Results

Patients with left-sided accessory pathway (AP) had significantly higher DwNt (p?<?0.001) and Dwi (p?=?0.027) values. The R wave voltage in lead I (p?=?0.037) and S wave voltage in lead V1 (p?=?0.005) values were significantly higher in patients with right-sided AP compared to patients with left-sided AP. When 27 ms was taken as the DwNt cut-off value, higher durations determined the left-sided AP location with a sensitivity of 91% and a negative predictive value of 91.4%. Dwi cutoff values ≥?0.29 were accepted to indicate a left-sided AP location with a sensitivity of 91.2% and a NPV of 91.4%.

Conclusions

WPW patients with left-sided AP have longer DwNt values than patients with right-sided AP.

     

Do-it-yourself Artificial Pancreas – Technologiehype oder realer Nutzen?

Background

Most type 1 diabetes mellitus patients are not capable of achieving close to normal glucose levels and thus face a constant risk of severe hypoglycemia and diabetic ketoacidosis.

Objectives

Patients develop their own personal non-approved medical devices to compensate for gaps in the existing medical technology.

Materials and methods

Current studies are assessed and basic work and challenges are discussed.

Results

The authorization of such systems from patients themselves results in the development of medical devices suitable for use but approved only based on freely available algorithms. Legal framework conditions, lack of standards on the interoperability of medical devices and uncertainties about future technology trends are giving rise to ongoing controversies.

Conclusions

There is a need to validate these new approaches, agree upon success criteria and provide solid evidence of their effectiveness.

     

Emerging Technologies for the Management of Type 1 Diabetes in Pregnancy

Purpose of Review

The purpose of the study is to discuss emerging technologies available in the management of type 1 diabetes in pregnancy.

Recent Findings

The latest evidence suggests that continuous glucose monitoring (CGM) should be offered to all women on intensive insulin therapy in early pregnancy. Studies have additionally demonstrated the ability of CGM to help gain insight into specific glucose profiles as they relate to glycaemic targets and pregnancy outcomes. Despite new studies comparing insulin pump therapy to multiple daily injections, its effectiveness in improving glucose and pregnancy outcomes remains unclear. Sensor-integrated insulin delivery (also called artificial pancreas or closed-loop insulin delivery) in pregnancy has been demonstrated to improve time in target and performs well despite the changing insulin demands of pregnancy.

Summary

Emerging technologies show promise in the management of type 1 diabetes in pregnancy; however, research must continue to keep up as technology advances. Further research is needed to clarify the role technology can play in optimising glucose control before and during pregnancy as well as to understand which women are candidates for sensor-integrated insulin delivery.

     

Die Rolle der Selbsthilfegruppen in der Onkologie

Background

Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.

Objectives

The psychosocial support given by self-help associations in different phases is evaluated.

Materials and methods

Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.

Results

On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.

Conclusions

The removal of barriers and development of effective structures are overdue.

     

Alcohol Screening and Intervention Among United States Adults who Attend Ambulatory Healthcare

BACKGROUND

There is limited data on the extent to which indicated alcohol interventions are delivered in U.S. ambulatory care settings.

OBJECTIVE

To assess the receipt of alcohol-related services, including assessment of use, advice to reduce drinking, and information about alcohol treatment, during ambulatory care visits.

DESIGN

Secondary data analysis of the 2013 National Survey on Drug Use and Health, a cross-sectional, nationally representative survey of civilians in the non-institutionalized U.S. general population (response rate 71.7 %).

PARTICIPANTS

Adult ambulatory care users in the public use data file who did not obtain emergency or inpatient services (n?=?17,266).

MAIN MEASURES

Measurements included respondents’ alcohol consumption, heavy episodic drinking, alcohol use disorder, healthcare use, and receipt of alcohol-related interventions.

KEY RESULTS

Approximately 71.1 % of ambulatory care users received an alcohol assessment. Among past-month heavy episodic drinkers without an alcohol use disorder who reported receiving an alcohol assessment, 4.4 % were advised to cut back. Among individuals with alcohol abuse and alcohol dependence who reported receiving an alcohol assessment, 2.9 % and 7.0 %, respectively, were offered information about treatment.

CONCLUSIONS

Rates of alcohol screening and assessment were relatively high among adults who attended healthcare visits, but rates of intervention were low, even when individuals were assessed for use. Efforts are needed to expand delivery of interventions when patients are identified as positive for risky drinking, hazardous alcohol use, and alcohol use disorders during ambulatory care visits.