Population-Level Impact and Cost-effectiveness of Continuous Glucose Monitoring and Intermittently Scanned Continuous Glucose Monitoring Technologies for Adults With Type 1 Diabetes in Canada: A Modeling Study.

OBJECTIVE: Maintaining healthy glucose levels is critical for the management of type 1 diabetes (T1D), but the most efficacious and cost-effective approach (capillary self-monitoring of blood glucose [SMBG] or continuous [CGM] or intermittently scanned [isCGM] glucose monitoring) is not clear. We modeled the population-level impact of these three glucose monitoring systems on diabetes-related complications, mortality, and cost-effectiveness in adults with T1D in Canada. RESEARCH DESIGN AND METHODS: We used a Markov cost-effectiveness model based on nine complication states for adults aged 18-64 years with T1D. We performed the cost-effectiveness analysis from a single-payer health care system perspective over a 20-year horizon, assuming a willingness-to-pay threshold of CAD 50,000 per quality-adjusted life-year (QALY). Primary outcomes were the number of complications and deaths and the incremental cost-effectiveness ratio (ICER) of CGM and isCGM relative to SMBG. RESULTS: An initial cohort of 180,000 with baseline HbA1c of 8.1% was used to represent all Canadians aged 18-64 years with T1D. Universal SMBG use was associated with ∼11,200 people (6.2%) living without complications and ∼89,400 (49.7%) deaths after 20 years. Universal CGM use was associated with an additional ∼7,400 (4.1%) people living complications free and ∼11,500 (6.4%) fewer deaths compared with SMBG, while universal isCGM use was associated with ∼3,400 (1.9%) more people living complications free and ∼4,600 (2.6%) fewer deaths. Relative to SMBG, CGM and isCGM had ICERs of CAD 35,017/QALY and 17,488/QALY, respectively. CONCLUSIONS: Universal use of CGM or isCGM in the Canadian T1D population is anticipated to reduce diabetes-related complications and mortality at an acceptable cost-effectiveness threshold.

Assessment of Risks and Benefits of Beta Cell Replacement Versus Automated Insulin Delivery Systems for Type 1 Diabetes.

PURPOSE OF REVIEW: Current approaches to insulin replacement in type 1 diabetes are unable to achieve optimal levels of glycemic control without substantial risk of hypoglycemia and substantial burden of self-management. Advances in biology and technology present beta cell replacement and automated insulin delivery as two alternative approaches. Here we discuss current and future prospects for the relative risks and benefits for biological and psychosocial outcomes from the perspective of researchers, clinicians, and persons living with diabetes. RECENT FINDINGS: Beta cell replacement using pancreas or islet transplant can achieve insulin independence but requires immunosuppression. Although insulin independence may not be sustained, time in range of 80-90%, minimal glycemic variability and abolition of hypoglycemia is routine after islet transplantation. Clinical trials of potentially unlimited supply of stem cell-derived beta cells are showing promise. Automated insulin delivery (AID) systems can achieve 70-75% time in range, with reduced glycemic variability. Impatient with the pace of commercially available AID, users have developed their own algorithms which appear to be at least equivalent to systems developed within conventional regulatory frameworks. The importance of psychosocial factors and the preferences and values of persons living with diabetes are emerging as key elements on which therapies should be evaluated beyond their impact of biological outcomes. Biology or technology to deliver glucose dependent insulin secretion is associated with substantial improvements in glycemia and prevention of hypoglycemia while relieving much of the substantial burden of diabetes. Automated insulin delivery, currently, represents a more accessible bridge to a biologic cure that we expect future cellular therapies to deliver.

Neuropathy and presence of emotional distress and depression in longstanding diabetes: Results from the Canadian study of longevity in type 1 diabetes.

AIM: To determine the association of neuropathy and other complications with emotional distress and depression among patients with longstanding type 1 diabetes (T1DM). METHODS: Canadians with ≥50years of T1DM completed a questionnaire including assessment of distress and depression by the Problem Areas in Diabetes Scale (PAID) and Geriatric Depression Scale (GDS), respectively. Complications were determined using the Michigan Neuropathy Screening Instrument (Questionnaire Component), fundoscopy reports, renal function tests, and self-reported peripheral-(PVD) and cardiovascular (CVD) disease. Associations were analyzed by Poisson regression. RESULTS: Among 323 participants, 137 (42.4%) had neuropathy, 113 (36.5%) nephropathy, 207 (69.5%) retinopathy, 95 (29.4%) CVD, and 31 (9.8%) PVD. The neuropathy subgroup had higher prevalence of distress (13 (9.5%) vs. 6 (3.3%), p=0.029) and depression (34 (24.9%) vs. 12 (6.5%), p<0.001). Adjusting for diabetes complications, neuropathy was associated with higher PAID (adjusted RR 1.44 (95% CI 1.14-1.82), p=0.003) and GDS scores (adjusted RR1.57 (1.18-2.11), p=0.002). Independent of potential confounders, neuropathy remained associated with higher PAID (adjusted RR 1.39 (1.10-1.76), p=0.006) and GDS scores (adjusted RR 1.37 (1.03-1.83), p=0.032). Associations with neuropathy were not fully explained by neuropathic pain. CONCLUSION: Compared to other complications, neuropathy had the greatest association with distress and depression in longstanding T1DM, independent of pain. Strategies beyond pain management are needed to improve quality of life in diabetic neuropathy.

Assessment of urinary microparticles in normotensive patients with type 1 diabetes.

AIMS/HYPOTHESIS: Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes. METHODS: In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry. RESULTS: Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/µmol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/µmol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/µmol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/µmol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia. CONCLUSION/INTERPRETATION: Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.

Cooling detection thresholds in the assessment of diabetic sensory polyneuropathy: comparison of CASE IV and Medoc instruments.

OBJECTIVE: Cooling detection threshold testing may be an important quantitative method for assessing polyneuropathy, in that it has traditionally been viewed as a measure of small-fiber involvement. The present study sought to determine the agreement between two common testing devices and to determine whether these are concordant in their association with predictor variables for diabetic sensory polyneuropathy. RESEARCH DESIGN AND METHODS: A total of 83 patients with diabetes (10 patients with type 1 diabetes and 73 patients with type 2 diabetes) and a wide spectrum of diabetic sensory polyneuropathy severity underwent concurrent cooling detection threshold testing using the Medoc and CASE IV instruments. Common predictor variables for diabetic sensory polyneuropathy were measured on the same day. RESULTS: Measurements of cooling detection thresholds by both instruments were highly correlated (Spearman's correlation coefficient 0.81, P < 0.001) and demonstrated a high degree of agreement by the method of Bland and Altman (95% distribution critical values for the difference in cooling detection thresholds, +7.5 and -5.6 degrees C). Cooling detection thresholds by both instruments were strongly correlated with clinical indicators of large-fiber neuropathy but not with the symptoms of small-fiber neuropathy (pain). CONCLUSIONS: These two instruments available for assessment of cooling detection thresholds are interchangeable for research in diabetic sensory polyneuropathy. However, this modality is equivalent to other modalities of quantitative sensory threshold testing in its association with indicators of large-fiber neuropathy and does not seem to provide an advantage for the prediction of small-fiber involvement.