Potassium-Based Sodium Substitutes Impact the Sodium and Potassium Content of Foods.

OBJECTIVE: Potassium-based sodium substitutes (PBSS) can be used to replace sodium during food processing. How potassium and sodium content is associated with PBSS is not known. The objectives of the study were to describe the prevalence of PBSS by sodium content claim category and describe how PBSS are associated with sodium and potassium concentrations by sodium level. DESIGN AND METHODS: This cross-sectional analysis used the July 2018 version of the United States Department of Agriculture's Branded Food Products Database. Products were divided into sodium content claim category and were analyzed for the presence of PBSS. Products with nonmissing values for sodium and potassium were grouped by sodium level and analyzed for the prevalence of PBSS to explore potassium and sodium concentration. Column proportion z-test with the Bonferroni correction was used to explore the occurrence of PBSS by sodium content claim category. Mann-Whitney U-test was used to assess differences in potassium and sodium concentrations across sodium levels and within levels by the presence/absence of PBSS. RESULTS: The prevalence of PBSS in the categories "without a sodium content claim" (2.4%), "lightly salted" (0.5%), and "unsalted" claims (0.6%) were statistically significantly lower than prevalence of PBSS in the "sodium free" (9.5%), "low sodium" (10.3%), and "reduced sodium" claim categories (23.3%; all P < .01). Among the group of products with serving sizes more than 30 g containing PBSS, there was a 357 mg per serving higher median sodium concentration and a 160 mg per serving higher median potassium concentration compared to the group without PBSS (both P < .01). CONCLUSION: In the "reduced sodium" claim category, a higher prevalence of PBSS was found compared to other sodium claim categories. The presence of PBSS was associated with higher potassium and sodium concentrations in foods.

Pancreas and Islet Transplantation: Comparative Outcome Analysis of a Single-centre Cohort Over 20-years.

OBJECTIVE: To provide the largest single-center analysis of islet (ITx) and pancreas (PTx) transplantation. SUMMARY BACKGROUND DATA: Studies describing long-term outcomes with ITx and PTx are scarce. METHODS: We included adults undergoing ITx (n=266) and PTx (n=146) at the University of Alberta from January 1999 to October 2019. Outcomes include patient and graft survival, insulin independence, glycemic control, procedure-related complications, and hospital readmissions. Data are presented as medians (interquartile ranges, IQR) and absolute numbers (percentages, %) and compared using Mann-Whitney and χ2 tests. Kaplan-Meier estimates, Cox proportional hazard models and mixed main effects models were implemented. RESULTS: Crude mortality was 9.4% and 14.4% after ITx and PTx, respectively ( P= 0.141). Sex-adjusted and age-adjusted hazard-ratio for mortality was 2.08 (95% CI, 1.04-4.17, P= 0.038) for PTx versus ITx. Insulin independence occurred in 78.6% and 92.5% in ITx and PTx recipients, respectively ( P= 0.0003), while the total duration of insulin independence was 2.1 (IQR 0.8-4.6) and 6.7 (IQR 2.9-12.4) year for ITx and PTx, respectively ( P= 2.2×10 -22 ). Graft failure ensued in 34.2% and 19.9% after ITx and PTx, respectively ( P =0.002). Glycemic control improved for up to 20-years post-transplant, particularly for PTx recipients (group, P= 7.4×10 -7 , time, P =4.8×10 -6 , group*time, P= 1.2×10 -7 ). Procedure-related complications and hospital readmissions were higher after PTx ( P =2.5×10 -32 and P= 6.4×10 -112 , respectively). CONCLUSIONS: PTx shows higher sex-adjusted and age-adjusted mortality, procedure-related complications and readmissions compared with ITx. Conversely, insulin independence, graft survival and glycemic control are better with PTx. This study provides data to balance risks and benefits with ITx and PTx, which could improve shared decision-making.

Cystic Fibrosis-Related Diabetes: Clinical approach and knowledge gaps.

Cystic Fibrosis-Related Diabetes (CFRD) is a unique type of diabetes mellitus that shares some features with both type 1 and type 2 diabetes. Yet, its distinguishing feature of acute pulmonary complications associated with hyperglycemia and the catabolic metabolism associated with a relative insulin deficiency poses challenges to the application of traditional definitions and treatments for diabetes mellitus. People with CF (pwCF) undergo rigorous annual screening starting at age 10, a process that is challenging for patients and limited by sensitivity, specificity, and reproducibility. As pwCF continue to live longer, over 50% are expected to develop CFRD over their lifetime, including up to 20% of adolescents. Increasing numbers of people with CFRD will make this disease increasingly relevant to diabetes practitioners. Evidence-guided practice in CFRD care is limited by small and short studies. Our current understanding of CFRD may change significantly with the recent introduction of CF Transmembrane Regulator (CFTR) modulator medications. This review will explore current challenges in the diagnosis and management of CFRD, specifically highlighting knowledge gaps in the pathophysiology of CFRD, optimal screening methods, priorities for research and provide guidance with regards to screening, diagnosis, and treatment.

The impact of protein source on serum potassium and phosphate levels in adults living with advanced kidney disease.

BACKGROUND AND AIMS: Plant proteins may be restricted on low potassium/phosphorus diets. The primary objective was to investigate the impact of protein source on serum potassium and phosphate levels in adults with stage 4-5 chronic kidney disease (CKD), including hemodialysis (HD). METHODS AND RESULTS: Using a cross-sectional design, 24-h recalls or food frequency questionnaires were used to assess dietary intake. Serum values were obtained from medical records. Quartiles (Q1-4) of plant:animal protein serving ratios was considered to investigate outcomes, with Q1 having high animal and low plant serving intake and those in Q4 having high plant and low animal servings. 216 participants were enrolled, 135 on HD and 81 stage 4/5 CKD. For both HD and CKD, there was no difference in either serum potassium or phosphate levels between those in Q4 consuming high plant:animal vs Q1 low plant:animal (for HD: potassium 4.6 mmol/L vs 4.6 mmol/L; phosphate 1.8 mmol/L vs 1.6 mmol/L, respectively; for CKD: potassium 4.7 mmol/L vs 4.6 mmol/L; phosphate 1.4 mmol/L vs 1.4 mmol/L; all p > 0.05). Those in Q4 consuming high plant:animal consumed 7.5 g (62%) more fibre than those in Q1 (low plant:animal). For diet quality, Q4 (high plant:animal) had a 12.8 point (24%) higher healthy eating index score than Q1 (low plant:animal). There was no relationship between plant:animal and serum albumin or hospital admissions (all p > 0.05). CONCLUSIONS: Consumption of higher proportions of plant protein was not associated with higher serum potassium or phosphate levels but was associated with higher fibre and diet quality.

Phosphorus Additives and Their Impact on Phosphorus Content in Foods-An Analysis of the USDAs Branded Foods Product Database.

OBJECTIVES: The frequency of phosphate additives reported in the United States Department of Agriculture Branded Foods Product Database and how these additives impact phosphate content is unknown. METHODS: All products included in the Branded Foods Product Database reporting phosphorus content were reviewed for presence of phosphate salts and/or lecithin additives. RESULTS: Phosphorus content information was available for 3,466 (1.45%) food items, of these 1791 (51.6%) contained additives. Median phosphorus content was lowest in products with lecithin only compared to products without phosphorus additives (86 [54-200] vs. 145 [77-351] mg per 100 g, P < .01), which was not different from products with phosphate salts (176 [101-276] mg per 100 g, P = .22) or products with both phosphate salts and lecithin (161 [99-285] mg per 100 g, P = 1.00). The impact of a phosphorus salt on phosphorus content (mg per 100) was explored among ultra-processed products grouped by similar phosphorus contents. The phosphorus content of in in nondairy alternatives, dairy, plant proteins, and grains were significantly higher when the product contained a phosphate salt compared to products without a phosphate salt. For all products phosphorus and potassium content were correlated, but the relationship was stronger for when a potassium phosphate additive was present compared to absent (rho = 0.81 vs. 0.53, P < .05). Similar patterns were seen for sodium, calcium, and iron with stronger correlations with phosphate content for products with additives than those without (calcium phosphate: rho = 0.47 vs. 0.32; iron phosphate: rho = 0.47 vs. 0.33; sodium phosphate: rho = 0.45 vs. 0.07. All P < .05). The relationship between phosphate and sodium for products without phosphate additives was weak. CONCLUSIONS: Lecithin may not be associated with increased phosphorus content. Calcium, potassium, sodium, and iron phosphorus salts appear to be associated with increases in the composite mineral and phosphorus content, with the strongest correlation between potassium and phosphorus content.

Estimation of Early Graft Function Using the BETA-2 Score Following Clinical Islet Transplantation.

Little is known about how early islet graft function evolves in the clinical setting. The BETA-2 score is a validated index of islet function that can be calculated from a single blood sample and lends itself to frequent monitoring of graft function. In this study, we characterized early graft function by calculating weekly BETA-2 score in recipients who achieved insulin independence after single transplant (group 1, n = 8) compared to recipients who required a second transplant before achieving insulin independence (group 2, n = 7). We also determined whether graft function 1-week post-transplant was associated with insulin independence in individuals who received initial transplant between 2000-2017 (n = 125). Our results show that graft function increased rapidly reaching a plateau 4-6 weeks post-transplant. The BETA-2 score was higher in group 1 compared to group 2 as early as 1-week post-transplant (15 + 3 vs. 9 + 2, p = 0.001). In an unselected cohort, BETA-2 at 1-week post-transplant was associated with graft survival as defined by insulin independence during median follow up of 12 months (range 2-119 months) with greater survival among those with BETA-2 score >10 (p < 0.001, log-rank test). These findings suggest that primary graft function is established within 4-6 weeks post-transplant and graft function at 1-week post-transplant predicts long-term transplant outcomes.

Comparison of diet quality tools to assess nutritional adequacy for adults living with kidney disease.

There is no specific diet quality tool recommended for adults living with chronic kidney disease (CKD). Identifying how diet quality tools assess nutritional adequacy and correlate with potassium and phosphorus (nutrients of interest in CKD) is warranted. Our aim was to compare Mediterranean Diet Scores (MDS), Healthy Eating Index (HEI), and Healthy Food Diversity (HFD) to determine their correlation with nutrient intake in adults living with diabetes and CKD. Using data from a longitudinal study of 50 participants with diabetes and CKD, diet quality was assessed at baseline and 1 or more times at annual visits up to 5 years (complete diet records n = 178). Diet quality was investigated for correlation with nutrient intake. Compared with HEI and HFD, MDS was poorly correlated with nutrient intake (all r values <0.40). HFD and HEI were moderately correlated with potassium (r = 0.66, P < 0.01 and r = 0.57, P < 0.01, respectively). HEI was weakly correlated with phosphorus (r = 0.365, P < 0.01). MDS recommends moderation of dairy and meat, this may have specific benefits for CKD as these are both sources of phosphorus, as such high MDS were associated with lower phosphorus intake. This study suggests that development of a renal specific diet quality assessment tool may be useful; however, further studies are needed.

Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes.

Allogeneic islet transplant offers a minimally invasive option for ß cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and HbA1c  ≤ 6.5% or reduced by ≥ 1 percentage point at 1 year posttransplant. Median HbA1c declined from 8.1% before to 6.0% at 1 year and 6.3% at 2 and 3 years following transplant (P < .001 for all vs baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality of life. The procedure was safe and kidney allograft function remained stable after 3 years. These results add to evidence establishing allogeneic islet transplant as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post-renal transplant setting.

Low Mediterranean Diet scores are associated with reduced kidney function and health related quality of life but not other markers of cardiovascular risk in adults with diabetes and chronic kidney disease.

BACKGROUND AND AIMS: How Mediterranean-style diets impact cardiovascular and health outcomes in patients with diabetes and chronic kidney disease (CKD) is not well known. Our aim was to investigate the association between diet quality, using Mediterranean Diet Scores (MDS) and health outcomes. METHODS AND RESULTS: This is a post-hoc analysis of an RCT and longitudinal study investigating patients with diabetes and CKD. MDS was calculated annually. Scores were analyzed for correlation with lipids, HbA1c, serum potassium, health-related quality of life (HRQOL) and depression. 178 diet records from 50 patients who attended two or more visits were included. Mean MDS was moderate (4.1 ± 1.6) and stable over time. Stage 1-2 vs 3-5 CKD had lower raw MDS (3.8 ± 1.5 vs 4.6 ± 1.5, p < 0.001). Having hyperkalemia was associated with a lower raw MDS scores (3.6 ± 1.6 vs 4.2 ± 1.5, p = 0.03) but not energy adjusted MDS. MDS was not associated with HbA1c or lipids. High vs low MDS was associated with improved HRQOL (mental health 84.4 ± 14.3 vs 80.3 ± 17.1, p < 0.05; general health 62.6 ± 21.0 vs 56.3 ± 19.8, p < 0.001) and fewer depressive symptoms (9.1 ± 7.4 vs 11.7 ± 10.6, p = 0.01). CONCLUSIONS: Low MDS was associated with reduced kidney function and health related quality of life, but not other markers of cardiovascular risk. Further studies are needed to understand the nature and direction of the association between diet quality and disease outcomes in this population.

Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild-to-moderate renal impairment.

AIM: To investigate the impact of renal function on the safety and efficacy of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100). MATERIALS AND METHODS: A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged ≥18 years with a diagnosis of type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300 or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m2 . RESULTS: The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100 groups, for both renal function subgroups. There was a reduced risk of nocturnal (12:00-5:59 am) confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 in both renal function subgroups (eGFR <60 mL/min/1.73 m2 : relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR ≥60 mL/min/1.73 m2 : RR 0.75 [95% CI 0.67-0.85]). For confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours) the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI 0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups. CONCLUSIONS: Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced overall risk of confirmed (≤3.9 and <3.0 mmol/L [≤70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups.

Comparison of metabolic responses to the mixed meal tolerance test vs the oral glucose tolerance test after successful clinical islet transplantation.

Following islet transplantation, mixed meal tolerance tests (MMTs) are routinely utilized to assess graft function, but how the 90-minute MMTT glucose value relates to a 120-minute glucose concentration of ≥11.1 mmol/L used to diagnose diabetes following a standardized 75 g-OGTT, is not known. We examined this relationship further. Thirteen subjects with Type 1 diabetes and stable transplant grafts, not on exogenous insulin with HbA1c < 7% (53 mmol/mol), were studied on 17 occasions with paired OGTTs and MMTTs. Receiver operating characteristic (ROC) curves were constructed to derive the 90-minute MMTT glucose threshold associated with a 120-minute glucose concentration following a 75 g-OGTT (OGTT120 ) ≥11.1 mmol/L and their diagnostic accuracy. Studies with OGTT120 ≥11.1 mmol/L (n = 5) had diminished C-peptide: glucose, greater integrated glucose and diminished insulin: glucose area under the curve (AUC) ratios (0-120 minutes) and disposition indices; all P < .05, contrasting with MMTTs where no difference in the 90-minute glucose concentrations, C-peptide:glucose, integrated glucose, C-peptide and C-peptide: glucose AUCs (0-90 minutes) was seen; all P > .05. A 90-minute MMTT glucose concentration ≥8.0 mmol/L demonstrated a sensitivity and specificity of ≥80% for the diagnosis of OGTT120 ≥11.1 mmol/L; area under ROC curve (mean ± SEM) 73 ± 13%. A 90-minute MMTT glucose ≥8.0 mmol/L, identifies islet transplant recipients who may require closer monitoring for graft dysfunction.

Defining outcomes for ß-cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop.

ß-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of ß-cell replacement therapy. There was consensus that ß-cell replacement therapy could be considered as a treatment for ß-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c ) and the occurrence of severe hypoglycemia. Optimal ß-cell graft function is defined by near-normal glycemic control [HbA1c  ≤ 6.5% (48 mmol/mol)] without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good ß-cell graft function requires HbA1c  < 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal ß-cell graft function is defined by failure to achieve HbA1c  < 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed ß-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good functional outcomes are considered successful clinical outcomes.

Stem cells and beta cell replacement therapy: a prospective health technology assessment study.

BACKGROUND: Although current beta cell replacement therapy is effective in stabilizing glycemic control in highly selected patients with refractory type 1 diabetes, many hurdles are inherent to this and other donor-based transplantation methods. One solution could be moving to stem cell-derived transplant tissue. This study investigates a novel stem cell-derived graft and implant technology and explores the circumstances of its cost-effectiveness compared to intensive insulin therapy. METHODS: We used a manufacturing optimization model based on work by Simaria et al. to model cost of the stem cell-based transplant doses and integrated its results into a cost-effectiveness model of diabetes treatments. The disease model simulated marginal differences in clinical effects and costs between the new technology and our comparator intensive insulin therapy. The form of beta cell replacement therapy was as a series of retrievable subcutaneous implant devices which protect the enclosed pancreatic progenitors cells from the immune system. This approach was presumed to be as effective as state of the art islet transplantation, aside from immunosuppression drawbacks. We investigated two different cell culture methods and several production and delivery scenarios. RESULTS: We found the likely range of treatment costs for this form of graft tissue for beta cell replacement therapy. Additionally our results show this technology could be cost-effective compared to intensive insulin therapy, at a willingness-to-pay threshold of $100,000 per quality-adjusted life year. However, results also indicate that mass production has by far the best chance of providing affordable graft tissue, while overall there seems to be considerable room for cost reductions. CONCLUSIONS: Such a technology can improve treatment access and quality of life for patients through increased graft supply and protection. Stem cell-based implants can be a feasible way of treating a wide range of patients with type 1 diabetes.

The Use of a Pre-operative Carbohydrate Drink in Patients with Diabetes Mellitus: A Prospective, Non-inferiority, Cohort Study.

BACKGROUND: Pre-operative fasting leads to insulin resistance and increased metabolic stress in non-diabetic patients. Consumption of a carbohydrate drink may alleviate these deleterious effects. Patients with diabetes mellitus represent over 15% of the surgical population, yet concerns over hyperglycemia and aspiration have excluded patients with diabetes mellitus from studies assessing the utility of pre-operative carbohydrate drinks. OBJECTIVE: To assess for a clinically significant increase in pre-operative blood glucose concentration (defined as >2 mmol/L) in patients with diabetes consuming a pre-operative carbohydrate drink. METHODS: A prospective observational non-inferiority cohort study of 106 subjects with diabetes mellitus was undertaken to assess the effect of consuming a pre-operative carbohydrate drink in surgical patients. All patients with diabetes mellitus undergoing surgery (including but not limited to cardiac, neurologic, urologic, and general surgical procedures) were enrolled. Subjects were instructed to consume two carbohydrate-rich drinks, one before sleeping the evening prior to surgery and another on the day of surgery. RESULTS: In total, 43% of subjects were fully compliant with the pre-operative carbohydrate drink regimen. There were no significant differences between the fully compliant and non-compliant subjects with respect to baseline characteristics. Consumption of a pre-operative carbohydrate drink was determined to be non-inferior to fasting in terms of pre-operative blood glucose concentration (absolute difference 0.23 mmol/L, 95% CI: -1.00 to 1.45 mmol/L, p non-inferiority < 0.01). Neither group was found to be superior in terms of pre-operative blood glucose concentration, hyperglycemia, or length of stay. CONCLUSIONS: These findings function as a step toward ensuring pre-operative carbohydrate drinks are safe in patients with diabetes undergoing surgery.

Vitamin D Status and Bone Mineral Density is Influenced by Vitamin D Supplementation and Vitamin K1 Intake in Adults with Diabetes and Chronic Kidney Disease.

PURPOSE: Patients with diabetes (DM) and chronic kidney disease (CKD) are at increased risk for suboptimal bone health. The study objective was to investigate the relationships between vitamin D (vitD), vitamin K1 (vitK1), and calcium intake with bone mineral density (BMD) and vitamin D status in an ambulatory population with DM and CKD. METHODS: Adults (age 18-80 years; n = 62) with DM and CKD (stages 1-4) were recruited from the Northern Alberta Renal Program. Primary outcome variables included vitD, vitK1, and calcium intake; serum 25(OH)D, 1,25(OH)2D; and BMD as measured by dual X-ray absorptiometry. Statistical significance was determined at P < 0.05. RESULTS: Participants met the estimated average requirement or adequate intake for vitD, vitK1, and calcium intake in 73% (n = 45), 66% (n = 39), and 52% (n = 31), respectively, with a combined intake of micronutrient supplementation and diet. Participants had serum 25(OH)D concentrations ≥75 nmol/L (n = 41), normal BMDs (n = 48), and 66% (n = 41/62) were taking vitD supplements (>1000 IU/D). BMD was positively influenced by serum 25(OH)D. However, serum 25(OH) ≥100 nmol/L was associated with lower BMD (absolute and T-scores) for whole-body and spine (P ≤ 0.05). VitK1 intake (≥200 µg/day) was associated with higher whole-body and femoral-neck BMDs (absoluteand T-scores; P ≤ 0.05). CONCLUSION: VitD status and BMD in adults with DM and CKD was influenced by vitD supplementation and vitK1 intake.

Cost effectiveness and value of information analyses of islet cell transplantation in the management of 'unstable' type 1 diabetes mellitus.

BACKGROUND: Islet cell transplantation is a method to stabilize type 1 diabetes patients with hypoglycemia unawareness and unstable blood glucose levels by reducing insulin dependency and protecting against severe hypoglycemia through restoring endogenous insulin secretion. This study analyses the current cost-effectiveness of this technology and estimates the value of further research to reduce uncertainty around cost-effectiveness. METHODS: We performed a cost-utility analysis using a Markov cohort model with a mean patient age of 49 to simulate costs and health outcomes over a life-time horizon. Our analysis used intensive insulin therapy (IIT) as comparator and took the provincial healthcare provider perspective. Cost and effectiveness data for up to four transplantations per patient came from the University of Alberta hospital. Costs are expressed in 2012 Canadian dollars and effectiveness in quality-adjusted life-years (QALYs) and life years. To characterize the uncertainty around expected outcomes, we carried out a probabilistic sensitivity analysis within the Bayesian decision-analytic framework. We performed a value-of-information analysis to identify priority areas for future research under various scenarios. We applied a structural sensitivity analysis to assess the dependence of outcomes on model characteristics. RESULTS: Compared to IIT, islet cell transplantation using non-generic (generic) immunosuppression had additional costs of $150,006 ($112,023) per additional QALY, an average gain of 3.3 life years, and a probability of being cost-effective of 0.5 % (28.3 %) at a willingness-to-pay threshold of $100,000 per QALY. At this threshold the non-generic technology has an expected value of perfect information (EVPI) of $260,744 for Alberta. This increases substantially in cost-reduction scenarios. The research areas with the highest partial EVPI are costs, followed by natural history, and effectiveness and safety. CONCLUSIONS: Current transplantation technology provides substantial improvements in health outcomes over conventional therapy for highly selected patients with 'unstable' type 1 diabetes. However, it is much more costly and so is not cost-effective. The value of further research into the cost-effectiveness is dependent upon treatment costs. Further, we suggest the value of information should not only be derived from current data alone when knowing that this data will most likely change in the future.

"Vitamin D supplementation and bone health in adults with diabetic nephropathy: the protocol for a randomized controlled trial".

BACKGROUND: Suboptimal vitamin D status is highly prevalent in Northern communities, particularly in those patients with chronic diseases such as diabetes and chronic renal disease. Emerging literature suggests that adherence to daily vitamin D supplementation may be an important factor influencing vitamin D status and overall bone health, but compliance with therapies for bone health is a major challenge. It is unknown what level of vitamin D supplementation will ameliorate or improve suboptimal vitamin D status in patients with diabetic nephropathy or contribute to improved bone health, particularly for those living in northern climates. METHODS/DESIGN: The study purpose was to examine two different strategies of vitamin D3 supplementation; daily dosing of 2000 IU per day verses monthly dosing of 40,000 IU per month on markers of vitamin D status, bone health and to examine whether adherence, quality of life and patient satisfaction with the supplementation strategy differs between the two vitamin D strategies in adults diagnosed with diabetic nephropathy. DISCUSSION: The need for RCTs assessing higher doses of vitamin D3 supplementation at varying frequencies of administration and its impact on bone health in adults with diabetes and chronic kidney disease are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT01476501.

Islet transplantation outcomes in type 1 diabetes and transplantation of HLA-DQ8/DR4: results of a single-centre retrospective cohort in Canada.

Background: In solid organ transplantation, HLA matching between donor and recipient is associated with superior outcomes. In islet transplantation, an intervention for Type 1 diabetes, HLA matching between donor and recipient is not performed as part of allocation. Susceptibility to Type 1 diabetes is associated with the presence of certain HLA types. This study was conducted to determine the impact of these susceptibility antigens on islet allograft survival. Methods: This is a single-centre retrospective cohort study. This cohort of transplant recipients (n = 268) received islets from 661 donor pancreases between March 11th, 1999 and August 29th, 2018 at the University of Alberta Hospital (Edmonton, AB, Canada). The frequency of the Type 1 diabetes susceptibility HLA antigens (HLA-A24, -B39, -DQ8, -DQ2 and-DQ2-DQA1∗05) in recipients and donors were determined. Recipient and donor HLA antigens were examined in relation to time to first C-peptide negative status/graft failure or last observation point. Taking into account multiple transplants per patient, we fitted a Gaussian frailty survival analysis model with baseline hazard function stratified by transplant number, adjusted for cumulative islet dose and other confounders. Findings: Across all transplants recipients of donors positive for HLA-DQ8 had significantly better graft survival (adjusted HRs 0.33 95% CI 0.17-0.66; p = 0.002). At first transplant only, donors positive for HLA-DQ2-DQA1∗05 had inferior graft survival (adjusted HR 1.96 95% CI 1.10-3.46); p = 0.02), although this was not significant in the frailty analysis taking multiple transplants into account (adjusted HR 1.46 95% CI 0.77-2.78; p = 0.25). Other HLA antigens were not associated with graft survival after adjustment for confounders. Interpretation: Our findings suggest islet transplantation from HLA-DQ8 donors is associated with superior graft outcomes. A donor positive for HLA-DQ2-DQA1∗05 at first transplant was associated with inferior graft survival but not when taking into account multiple transplants per recipient. The relevance of HLA-antigens on organ allocation needs further evaluation and inclusion in islet transplant registries and additional observational and interventional studies to evaluate the role of HLA-DQ8 in islet graft survival are required. Funding: None.

Successful treatment of brittle diabetes following total pancreatectomy by islet allotransplantation: a case report.

CONTEXT: Allotransplantation of islets can successfully treat subjects with type 1 diabetes complicated by severe hypoglycemia and erratic glycemic control. Insulin independence is often lost over time due to several factors, including recurrent autoimmunity. Brittle diabetes (frequent hypoglycemia and labile glycemic control) is common after pancreatectomy. This is ameliorated by auto-islet transplantation in pancreatectomized patients who have better glycemic control, even without insulin independence. CASE REPORT: We herein report a case where islet allotransplantation was carried out in a patient who had undergone total pancreatectomy. Following two islet infusions, he became insulin independent with excellent glycemic control and remains so currently, more than four years after his second islet infusion. Side effects from immunosuppressive therapy were minimal. DISCUSSION: Islet allotransplantation can be considered in selected individuals post-pancreatectomy. The absence of autoimmunity may be advantageous for long term graft function relative to islet allotransplantation in type 1 diabetic recipients.

Insulinogenic index and early phase insulin secretion predict increased risk of worsening glucose tolerance and of cystic fibrosis-related diabetes.

OBJECTIVE: Measures of stimulated insulin secretion are emerging as important predictors of diabetes mellitus in at-risk populations. We analyzed the utility of clinical estimates of insulin secretion in a prospective cohort at risk for cystic fibrosis-related diabetes (CFRD). METHODS: We divided the profiles of 189 people with CF (pwCF) followed longitudinally in the Montreal CF cohort (mean follow up 6.6 ± 1.2 years) according to quartiles of the insulinogenic index (IGI; (I30-I0)/(G30-G0)); area under the curve for insulin normalized for glucose (AUCins/glu), and HOMA-B at baseline to compare clinical characteristics and risk of CFRD according to quartiles for each measure. We also compared characteristics of 40 pwCF found to have de novo CFRD at baseline. RESULTS: At baseline, IGI and AUCins/glu were lower in subjects with de novo CFRD and those who later developed CFRD than those who never developed CFRD (p < 0.0001 for each). Subjects with the lowest quartiles of IGI, AUCins/glu, and AUCins/glu 0-30 had increased risk of developing CFRD by Kaplan-Meier analysis (p = 0.0244, p = 0.0024, and p = 0.0338, respectively). There was no significant difference in risk between quartiles of HOMA-B. Subjects in the lowest quartile of IGI showed a significant increase in 2-hour OGTT glucose and AUCglu between the initial and final study visits (p = 0.0027 and p = 0.0044, respectively). CONCLUSION: IGI is easily measured in a clinical setting and needs to be validated in prospective studies as a potential tool to improve risk stratification in CFRD with direct relevance to pathogenesis.