Effect of metformin use on graft and patient survival in kidney transplant recipients with type 2 diabetes: a systematic review protocol.

INTRODUCTION: Metformin is a first-line antihyperglycaemic agent for type 2 diabetes (T2DM). In addition to glycaemic control, it offers benefits related to cardiovascular health, weight neutrality and metabolic syndrome. However, its benefits in kidney transplant recipients remain unclear as metformin use is controversial in this population due to a lack of evidence and there are recommendations against its use in patients with poor kidney function. Hence, we seek to describe a protocol for a systematic review, which will assess the impact of metformin use on graft survival and mortality in kidney transplant recipients. METHODS: This protocol was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science Core Collection for relevant studies conducted in kidney transplant recipients using metformin, which report outcomes related to graft and patient survival. All studies meeting these criteria in adults and published in English from inception to 2023 will be included in our review. We will employ the Cochrane Risk of Bias Tool 2 for randomised controlled trials and the Risk of Bias in Non-randomised Studies of Intervention for non-randomised studies. We will present our data and study characteristics in a table format and determine if a meta-analysis can be performed by clinical and methodological heterogeneity, using the I2 statistics. If a meta-analysis cannot be performed, we will provide a narrative synthesis of included studies using the Synthesis Without Meta-Analysis Reporting Guideline. ETHICS AND DISSEMINATION: Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of metformin use on graft and patient survival in kidney transplant recipients, evidence gathered through it will be disseminated using traditional approaches that include open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate academic bodies in charge of publishing guidelines related to T2DM and transplantation, as well as patient and research centred groups. PROSPERO REGISTRATION NUMBER: CRD42023421799.

Basal insulin initiation in adults with type 2 diabetes mellitus: A retrospective cohort study using administrative health data in Alberta, Canada.

BACKGROUND: Pharmacological treatment of type 2 diabetes mellitus (T2DM) follows a stepwise approach. Typically, metformin monotherapy is first-line treatment, followed by other non-insulin anti-hyperglycemic agents (NIAHAs) or progression to insulin if hemoglobin A1c (A1C) targets are not achieved. We aimed to describe real-world patterns of basal insulin initiation in people with T2DM and A1C not at target despite treatment with ≥2 NIAHAs. METHODS: A retrospective cohort study was conducted using administrative health data from Alberta, Canada among adults with T2DM, indexed on the first test with 7.0%

Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and Women Without Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

BACKGROUND: We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline. METHODS AND RESULTS: This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5-year follow-up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07-1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95-1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women. CONCLUSIONS: In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the "normal" range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.

Real-world Use and Outcomes of Sodium-glucose Cotransporter-2 Inhibitors in Adults With Diabetes and Heart Failure: A Population-level Cohort Study in Alberta, Canada.

OBJECTIVES: Since 2016, clinical guidelines have recommended sodium-glucose cotransporter-2 inhibitors (SGLT2is) for people with type 2 diabetes with heart failure. We examined SGLT2i dispensation, factors associated with dispensation, and heart failure hospitalization and all-cause mortality in people with diabetes and heart failure. METHODS: This retrospective, population-based cohort study, identified people with diabetes and heart failure between Jan 1, 2014 to Dec 31, 2017 in Alberta, Canada and followed them for a minimum of three years for SGLT2i dispensation and outcomes. Multivariate logistic regression assessed the factors associated with SGTL2i dispensation. Propensity scores were used with regression adjustment to estimate the effect of SGLT2i treatment on heart failure hospitalization. RESULTS: Among 22,025 individuals with diabetes and heart failure (43.4% women, mean age 74.7±11.8 years), only 10.2% were dispensed an SGLT2i. Male sex, age <65 years, a higher baseline A1C, no chronic kidney disease, presence of atherosclerotic cardiovascular disease, and urban residence were associated with SGLT2i dispensation. Lower heart failure hospitalization rates were observed in those with SGLT2i dispensation (548.1 per 100 person years) vs those without (813.5 per 1,000 person years; p<0.001) and lower all-cause mortality in those with an SGLT2i than those without (48.5 per 1,000 person years vs 206.1 per 1,000 person years; p<0.001). Regression adjustment found SGLT2i therapy was associated with a 23% reduction in hospitalization. CONCLUSIONS: SGLT2is were dispensed to only 10% of people with diabetes and established heart failure, underscoring a significant care gap. SGLT2i use was associated with a real-world reduction in heart failure hospitalization and all-cause death. This study highlights an important opportunity to optimize SGLT2i use.

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.

Impact of a modified screening approach during the COVID-19 pandemic on the diagnosis and outcomes of gestational diabetes mellitus: A population-level analysis of 90,518 pregnant women.

AIMS: To provide real-world evidence on the uptake of and outcomes associated with the modified gestational diabetes mellitus (GDM) screening approach offered during the COVID-19 pandemic compared with the standard screening approach. METHODS: All pregnancies between 01 January 2020 and 31 December 2021, in Alberta, Canada, were included in the study. We examined GDM screening and diagnosis rates, and large-for-gestational-age (LGA) outcomes. RESULTS: Annual GDM screening rates were > 95% during the study time period. Overall, 84.7%, and 11.6% of the 92,505 pregnancies underwent standard and modified screening for GDM, respectively. The use of modified screening was the highest among deliveries in August 2020 (49.8%) which corresponded to the early first wave of the pandemic. GDM diagnosis rate was lower in the modified screening (7.4%) than in the standard screening (12.3%, p < 0.001) group. The LGA rates in the modified screening with GDM and the standard screening with GDM groups were 24.8% and 12.6%, respectively (p < 0.001). Women in the modified screening with GDM group were at a higher risk of having an LGA infant (adjusted odds ratio: 3.46; 95% confidence interval: 2.93, 4.08) compared to the standard screening with no GDM group. CONCLUSIONS: The COVID-19 epidemic had no impact on screening for GDM. Women who underwent modified screening, based on HbA1c/random plasma glucose, had lower rates of GDM cases.

C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis.

BACKGROUND: Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent ß-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of ß-cell function and metabolic outcomes in new-onset type 1 diabetes. METHODS: 21 trials of disease-modifying interventions within 100 days of type 1 diabetes diagnosis comprising 1315 adults (ie, those 18 years and older) and 1396 children (ie, those younger than 18 years) were combined. Endpoints assessed were stimulated area under the curve C-peptide, HbA1c, insulin use, hypoglycaemic events, and composite scores (such as insulin dose adjusted A1c, total daily insulin, U/kg per day, and BETA-2 score). Positive studies were defined as those meeting their primary endpoint. Differences in outcomes between active and control groups were assessed using the Wilcoxon rank test. FINDINGS: 6 months after treatment, a 24·8% greater C-peptide preservation in positive studies was associated with a 0·55% lower HbA1c (p<0·0001), with differences being detectable as early as 3 months. Cross-sectional analysis, combining positive and negative studies, was consistent with this proportionality: a 55% improvement in C-peptide preservation was associated with 0·64% lower HbA1c (p<0·0001). Higher initial C-peptide levels and greater preservation were associated with greater improvement in HbA1c. For HbA1c, IDAAC, and BETA-2 score, sample size predictions indicated that 2-3 times as many participants per group would be required to show a difference at 6 months as compared with C-peptide. Detecting a reduction in hypoglycaemia was affected by reporting methods. INTERPRETATION: Interventions that preserve ß-cell function are effective at improving metabolic outcomes in new-onset type 1 diabetes, confirming their potential as adjuncts to insulin. We have shown that improvements in HbA1c are directly proportional to the degree of C-peptide preservation, quantifying this relationship, and supporting the use of C-peptides as a surrogate endpoint in clinical trials. FUNDING: JDRF and Diabetes UK.

Degree of Albuminuria is Associated With Increased Risk of Fragility Fractures Independent of Estimated GFR.

Introduction: Fragility fractures are common in persons with chronic kidney disease (CKD); however, the association between fragility fractures and albuminuria is not well-studied. The primary objective of this study is to determine the association of albuminuria with incident risk of fragility fractures. The secondary objective is to examine the risk of fragility fracture by estimated glomerular filtration rate (eGFR) and Kidney Disease Improving Global Outcomes (KDIGO) risk categories. Methods: Community dwelling adults residing in Alberta, Canada who had at least 1 creatinine and albuminuria measurement between April 1, 2008 and March 31, 2019 participated in the study (N = 2.72 million). Incident fragility fractures were identified using Canadian Chronic Disease Surveillance Systems Osteoporosis Working Group algorithms. Albuminuria was categorized as none/mild (albumin-to-creatinine ratio [ACR] <30 mg/g, protein-to-creatinine ratio [PCR] <150 mg/g, trace/negative dipstick); moderate (ACR 30-300 mg/g, PCR 150-500 mg/g, 1+ dipstick) or severe (ACR >300 mg/g, PCR >500 mg/g, ≥2+ dipstick). Multivariable analysis controlled for 42 variables. Results: Patients with severe albuminuria had an increased risk of hip fracture (odds ratio [OR] = 1.37; 95% confidence interval [CI] 1.28, 1.47]), vertebral fracture (OR = 1.31; 95% CI 1.21, 1.41) and any-type fracture (OR = 1.22; 95% CI 1.17, 1.28) compared with patients with none/mild albuminuria. Patients in the most severe KDIGO risk category had an increased risk of hip fracture (OR = 1.22; 95% CI 1.16, 1.29), vertebral fracture (OR = 1.18; 95% CI 1.09, 1.26) and any type of fracture (OR = 1.25; 95% CI 1.21, 1.30). Conclusion: This study demonstrates the important role of albuminuria as a risk factor for fragility fractures in CKD and may help inform risk stratification and prevention strategies in this high-risk population category.

Associations of Estradiol With Mortality and Health Outcomes in Patients Undergoing Hemodialysis: A Prospective Cohort Study.

Background: Both lower and higher estradiol (E2) levels have been associated with increased mortality among women with kidney failure. However, robust data are still lacking. Objective: We investigated the interaction of diabetes and age on linear and nonlinear associations between E2 levels, adverse outcomes, and health-related quality of life (HRQOL) in Canadian women undergoing hemodialysis (HD). Design: Population-based cohort study; data from Canadian Kidney Disease Cohort Study (CKDCS). Setting & patients: A total of 427 women undergoing HD enrolled in the CKDCS. Measurements: Baseline E2 (in pmol/L) and E2 tertiles (<38 pmol/L, 38-95 pmol/L, >95 pmol/L). Methods: Cox-proportional hazards used for all-cause and cardiovascular disease (CVD) mortality. Fine-Gray models used for incident CVD. Mixed models used for Health Utilities Index Mark 3 (HUI3), Kidney Disease Quality of Life Physical Component Scores (KDQOL12-PCS), and Mental Component Scores (KDQOL12-MCS). Results: Over a median follow-up of 3.6 (interquartile range [IQR]: 1.6-7.5) years, 250 (58.6%) participants died; 74 deaths (29.6%) were CV-related. Among 234 participants without prior CV events, 80 (34.2%) had an incident CVD event. There were no significant linear associations between E2 and all-cause mortality, CVD mortality, and incident CVD. However, E2 showed a significant concave association with all-cause mortality, but not with CVD mortality and incident CVD. Among patients aged ≥63 years, higher E2 levels were associated with lower HUI3 scores, mean difference (MD) = -0.062 per 1 - SD pmol/L, 95% confidence interval (CI) = -0.112 to -0.012, but the opposite was observed in younger patients (<63 years) in whom higher E2 levels were associated with higher HUI3 scores (MD = 0.032 per 1 - SD pmol/L, 95% CI = 0.008-0.055), Pinteraction = .045. No associations were observed among E2, KDQOL12-PCS (MD = -0.15 per 1 - SD pmol/L, 95% CI = -1.15 to 0.86), and KDQOL12-MCS (MD = -0.63 per 1 - SD pmol/L, 95% CI = -1.82 to 0.57). Limitations: Unmeasured confounding and small sample size. Conclusions: The association between E2 and all-cause mortality may be nonlinear, while no association was observed for CVD mortality, incident CVD, KDQOL12-PCS, and KDQOL12-MCS. Furthermore, the association between serum E2 and HUI3 was modified by age: Higher levels were associated with higher utility among women aged <63 years and the converse observed among older women.

Contexte: Les taux faibles comme les taux élevés d'estradiol (E2) ont été associés à une mortalité accrue chez les femmes souffrant d'insuffisance rénale. Les données fiables à ce sujet font cependant encore défaut. Objectif: Nous avons étudié l'incidence du diabète et de l'âge sur les associations linéaires et non linéaires entre les niveaux d'E2, les issues défavorables et la qualité de vie liée à la santé (QVLS) chez les Canadiennes suivant des traitements d'hémodialyse (HD). Conception: Étude de cohorte en population réalisée à partir des données de la Canadian Kidney Disease Cohort Study (CKDCS). Sujets et cadre de l'étude: 427 femmes sous HD inscrites à la CKDCS. Mesures: Le taux d'E2 initial (pmol/L) et les taux d'E2 tertiles (<38 pmol/L; 38-95 pmol/L; >95 pmol/L). Méthodologie: Des modèles à risques proportionnels de Cox ont été utilisés pour mesurer la mortalité toutes causes confondues et la mortalité liée aux maladies cardiovasculaires (MCV). Des modèles Fine-Gray ont été utilisés pour mesurer les MCV incidentes; et des modèles mixtes ont été utilisés pour calculer l'indice Health Utilities Index Mark 3 (HUI3) et les scores des composantes physique (KDQOL12-PCS [Physical Component Score]) et mentale (KDQOL12-MCS [Mental Component Score])) du questionnaire sur la qualité de vie (KDQOL). Résultats: Au cours d'un suivi médian de 3,6 ans (intervalle interquartile [IIQ]: 1,6 à 7,5 ans), 250 participantes (58,6 %) sont décédées; 74 décès (29,6 %) étaient liés à un événement CV. Parmi les 234 participantes sans événements cardiovasculaires antérieurs, 80 (34,2 %) ont vécu un événement incident de MCV. Aucune association linéaire significative n'a été observée entre le taux d'E2 et la mortalité toutes causes confondues, la mortalité par MCV ou les MCV incidentes. Le taux d'E2 a cependant montré une association concave significative avec la mortalité toutes causes confondues, mais pas avec la mortalité par MCV ni avec les MCV incidentes. Chez les patientes âgées de 63 ans et plus, des taux élevés d'E2 ont été associés à des scores HUI3 plus faibles (différence moyenne [DM] = -0,062 par 1-SD pmol/L; intervalle de confiance à 95 % [IC95]: -0,112 à 0,012); alors qu'on a observé le contraire chez les patientes plus jeunes (< 63 ans), où des taux élevés d'E2 étaient plutôt associés à des scores plus élevés d'HUI3 (DM = 0,032 par 1-SD pmol/L; IC95: 0,008 à 0,055; p=0,045). Aucune association n'a été observée entre le taux d'E2, le KDQOL12-PCS (DM = -0,15 par 1-SD pmol/L; IC 95: -1,15 à 0,86) et le KDQOL12-MCS (DM = -0,63 par 1-SD pmol/L; IC95: -1,82 à 0,57). Limites: Facteurs de confusion non mesurés; échantillon de petite taille. Conclusion: Il pourrait exister une association non linéaire entre le taux d'E2 et la mortalité toutes causes confondues. Aucune association n'a toutefois été observée entre le taux d'E2 et la mortalité par MCV, les MCV incidentes, le KDQOL12-PCS et le KDQOL12-MCS. En outre, l'association entre le taux sérique d'E2 et l'HUI3 a été modifiée par l'âge: des taux plus élevés d'E2 ont été associés à un indice de santé plus élevé (HUI) chez les femmes âgées de moins de 63 ans, alors que l'inverse a été observé chez les femmes plus âgées.

Quantifying beta cell function in the preclinical stages of type 1 diabetes.

Clinically symptomatic type 1 diabetes (stage 3 type 1 diabetes) is preceded by a pre-symptomatic phase, characterised by progressive loss of functional beta cell mass after the onset of islet autoimmunity, with (stage 2) or without (stage 1) measurable changes in glucose profile during an OGTT. Identifying metabolic tests that can longitudinally track changes in beta cell function is of pivotal importance to track disease progression and measure the effect of disease-modifying interventions. In this review we describe the metabolic changes that occur in the early pre-symptomatic stages of type 1 diabetes with respect to both insulin secretion and insulin sensitivity, as well as the measurable outcomes that can be derived from the available tests. We also discuss the use of metabolic modelling to identify insulin secretion and sensitivity, and the measurable changes during dynamic tests such as the OGTT. Finally, we review the role of risk indices and minimally invasive measures such as those derived from the use of continuous glucose monitoring.

A glycosylated hemoglobin A1c above 6% (42 mmol/mol) is associated with a high risk of developing Cystic Fibrosis-Related Diabetes and a lower probability of weight gain in both adults and children with Cystic Fibrosis.

OBJECTIVES: The classical glycosylated hemoglobin A1c threshold of 6.5% is an insensitive screening test for cystic fibrosis-related diabetes (CFRD). We sought to identify CF-specific A1C thresholds associated with 1) risk of progression to CFRD and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1). METHODS: We studied the cross sectional and longitudinal associations between A1c, BMI, and FEV1 in 2 cohorts of 223 children (followed for up to 8 years) and 289 adults (followed for a mean of 7.5 ± 4.3 years) with CF but without diabetes at baseline and undergoing regular assessments including Oral Glucose Tolerance Test (OGTT). RESULTS: For the onset of OGTT-defined CFRD optimal A1c threshold was 5.9% in adults (sensitivity: 67% and specificity: 71%) and 5.7% for children (sensitivity: 60% and specificity: 47%). Kaplan-Meier analysis of progression to CFRD according to baseline A1C showed increased the risk of developing CFRD for A1c ≥ 6.0% in adults (P = 0.002) and ≥ 5.5% in children (p = 0.012). Temporal changes in BMI and FEV1 according to baseline A1C in adults were assessed with a linear mixed-effect model, BMI significantly increased over time in subjects with a baseline A1c < 6%, but those with a A1C ≥ 6.0% gained significantly less weight over time (P = 0.05). There was no difference in FEV1 according to baseline A1c category. CONCLUSION: An A1C above 6% may be associated with a high risk of developing CFRD and a lower probability of weight gain in both adults and children with CF.

Technology-Supported Integrated Care Innovations to Support Diabetes and Mental Health Care: Scoping Review.

BACKGROUND: For individuals living with diabetes and its psychosocial comorbidities (eg, depression, anxiety, and distress), there remains limited access to interprofessional, integrated care that includes mental health support, education, and follow-up. Health technology, broadly defined as the application of organized knowledge or skill as software, devices, and systems to solve health problems and improve quality of life, is emerging as a means of addressing these gaps. There is thus a need to understand how such technologies are being used to support, educate, and help individuals living with co-occurring diabetes and mental health distress or disorder. OBJECTIVE: The purpose of this scoping review was to (1) describe the literature on technology-enabled integrated interventions for diabetes and mental health; (2) apply frameworks from the Mental Health Commission of Canada and World Health Organization to elucidate the components, type, processes, and users of technology-enabled integrated interventions for diabetes and mental health; and (3) map the level of integration of interventions for diabetes and mental health. METHODS: We searched 6 databases from inception to February 2022 for English-language, peer-reviewed studies of any design or type that used technology to actively support both diabetes and any mental health distress or disorder in succession or concurrently among people with diabetes (type 1 diabetes, type 2 diabetes, and gestational diabetes). Reviewers screened citations and extracted data including study characteristics and details about the technology and integration used. RESULTS: We included 24 studies described in 38 publications. These studies were conducted in a range of settings and sites of care including both web-based and in-person settings. Studies were mostly website-based (n=13) and used technology for wellness and prevention (n=16) and intervention and treatment (n=15). The primary users of these technologies were clients and health care providers. All the included intervention studies (n=20) used technology for clinical integration, but only 7 studies also used the technology for professional integration. CONCLUSIONS: The findings of this scoping review suggest that there is a growing body of literature on integrated care for diabetes and mental health enabled by technology. However, gaps still exist with how to best equip health care professionals with the knowledge and skills to offer integrated care. Future research is needed to continue to explore the purpose, level, and breadth of technology-enabled integration to facilitate an approach to overcome or address care fragmentation for diabetes and mental health and to understand how health technology can further drive the scale-up of innovative integrated interventions.

Stem Cell-Derived Islet Transplantation in Patients With Type 2 Diabetes: Can Diabetes Subtypes Guide Implementation?

Historically, only patients with brittle diabetes or severe recurrent hypoglycemia have been considered for islet transplantation (ITx). This population has been selected to optimize the risk-benefit profile, considering risks of long-term immunosuppression and limited organ supply. However, with the advent of stem cell (SC)-derived ITx and the potential for immunosuppression-free ITx, consideration of a broader recipient cohort may soon be justified. Simultaneously, the classical categorization of diabetes is being challenged by growing evidence in support of a clustering of disease subtypes that can be better categorized by the All New Diabetics in Scania (ANDIS) classification system. Using the ANDIS classification, 5 subtypes of diabetes have been described, each with unique causes and consequences. We evaluate consideration for ITx in the context of this broader patient population and the new classification of diabetes subtypes. In this review, we evaluate considerations for ITx based on novel diabetes subtypes, including their limitations, and we elaborate on unique transplant features that should now be considered to enable ITx in these "unconventional" patient cohorts. Based on evidence from those receiving whole pancreas transplant and our more than 20-year experience with ITx, we offer recommendations and potential research avenues to justify implementation of SC-derived ITx in broader populations of patients with all types of diabetes.

Canadian Cystic Fibrosis-related Diabetes Clinical Practice Survey: Analysis of Current Practices and Gaps in Clinical Care.

OBJECTIVES: Our aim in this study was to identify challenges and gaps in Canadian practices in screening, diagnosis, and treatment of cystic fibrosis-related diabetes (CFRD), with the goal of informing a Canadian-specific guideline for CFRD. METHODS: We conducted an online survey of health-care professionals (97 physicians and 44 allied health professionals) who care for people living with CF (pwCF) and/or CFRD (pwCFRD). RESULTS: Most pediatric centres followed <10 pwCFRD and adult centres followed >10 pwCFRD. Children with CFRD are usually followed at a separate diabetes clinic, whereas adults with CFRD may be followed by respirologists, nurse practitioners, or endocrinologists in a CF clinic or in a separate diabetes clinic. Less than 25% of pwCF had access to an endocrinologist with a special interest or expertise in CFRD. Many centres perform screening oral glucose tolerance testing with fasting and 2-hour time points. Respondents, especially those working with adults, also indicate use of additional tests for screening not currently recommended in CFRD guidelines. Pediatric practitioners tend to only use insulin to manage CFRD, whereas adult practitioners are more likely to use repaglinide as an alternative to insulin. CONCLUSIONS: Access to specialized CFRD care may be a challenge for pwCFRD in Canada. There appears to be wide heterogeneity of CFRD care organization, screening, and treatment among health-care providers caring for pwCF and/or pwCFRD across Canada. Practitioners working with adult pwCF are less likely to adhere to current clinical practice guidelines than practitioners working with children.

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.