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.

Partnered Recruitment: Engaging Individuals With Lived Experience in the Recruitment of Co-Design Participants.

BACKGROUND: Young adults with type 1 diabetes (T1D) face complex health challenges, including a heightened risk for distress. To counter this distress, there is a need to develop accessible, acceptable comprehensive care solutions that integrate diabetes and mental health care to enhance self-efficacy and counter mental health challenges in this population. OBJECTIVE: To describe the engagement of individuals with lived experience of T1D and mental health challenges in the development of a recruitment strategy to support the co-design of an innovative integrated care programme. RESULTS: Seven individuals with lived experience formed a Partner Advisory Council (PAC) to recruit young adults (18-29 years old) living with T1D, their friends or family and health researchers and professionals in co-design interviews (n = 19) and co-design events (n = 12). The PAC played a key role in developing a comprehensive recruitment strategy, overcoming traditional barriers and stigmas in the design of an integrated model of care. CONCLUSION: Assuming the presence of mental health challenges in young adults living with T1D during recruitment had far-reaching impacts on the development of a whole-person and integrated diabetes and mental health care solution. The efficient recruitment of this sample provided invaluable insights into the nuanced challenges experienced by young adults with T1D, the individual skills developed in response to their mental health challenges and the ways that this understanding can shape future programming to support mental health, quality of life and well-being. The ongoing involvement of the PAC as co-researchers underscores the enduring impact of patient engagement in developing integrated care solutions. PATIENT OR PUBLIC CONTRIBUTION: The co-design of the TECC-T1D3 model was enriched by the invaluable contributions of individuals with lived experience. This included the engagement of a diverse PAC in the recruitment of participants in co-design interviews and co-design events. PAC members actively participated in research decision-making with their insights informing a robust recruitment strategy. Beyond recruitment, PAC members continue to serve as co-researchers, shaping ongoing research and actively contributing to the TECC-T1D3 project. Six PAC members are co-authors on this manuscript.

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.

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.

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.

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes.

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).

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.

Real word challenges in integrating electronic medical record and administrative health data for regional quality improvement in diabetes: a retrospective cross-sectional analysis.

BACKGROUND: Linked electronic medical records and administrative data have the potential to support a learning health system and data-driven quality improvement. However, data completeness and accuracy must first be assessed before their application. We evaluated the processes, feasibility, and limitations of linking electronic medical records and administrative data for the purpose of quality improvement within five specialist diabetes clinics in Edmonton, Alberta, a province known for its robust health data infrastructure. METHODS: We conducted a retrospective cross-sectional analysis using electronic medical record and administrative data for individuals ≥ 18 years attending the clinics between March 2017 and December 2018. Descriptive statistics were produced for demographics, service use, diabetes type, and standard diabetes benchmarks. The systematic and iterative process of obtaining results is described. RESULTS: The process of integrating electronic medical record with administrative data for quality improvement was found to be non-linear and iterative and involved four phases: project planning, information generating, limitations analysis, and action. After limitations analysis, questions were grouped into those that were answerable with confidence, answerable with limitations, and not answerable with available data. Factors contributing to data limitations included inaccurate data entry, coding, collation, migration and synthesis, changes in laboratory reporting, and information not captured in existing databases. CONCLUSION: Electronic medical records and administrative databases can be powerful tools to establish clinical practice patterns, inform data-driven quality improvement at a regional level, and support a learning health system. However, there are substantial data limitations that must be addressed before these sources can be reliably leveraged.

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.

Experimental studies and simple numerical modeling of underwater electric discharges.

At present, underwater electric pulsed discharges are used in a wide range of modern applications. During the development of a system for generating underwater acoustic pressure pulses, a numerical model is an essential tool for guiding the design and interpreting the data. Developing a complex one-dimensional numerical code, like those presented in the literature, requires a substantial dedicated effort. Unfortunately, previous work trying to use simple and elegant theoretical models developed many decades ago reported a fundamental issue, apparently related to the input data. The present work performs a detailed analysis of the real meaning of the voltage measured across an underwater discharge and clarifies the correct way the power input to a simple two-phase model should be calculated. Based on accurate measurements, a phenomenological methodology to obtain the input data is demonstrated, with theoretical predictions obtained from the simple two-phase model being successfully compared with the experimental evidence obtained from both the present work as well as from other reliable data presented in the literature.

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.

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.

18F-Sodium Fluoride Imaging of Coronary Atherosclerosis in Ambulatory Patients With Diabetes Mellitus.

Objective- Although patients with diabetes mellitus (DM) are considered at high risk of cardiovascular events, there is growing evidence that this notion is incorrect. Atherosclerosis imaging may identify patients at risk. Approach and Results- We performed coronary atherosclerosis with 18F-sodium fluoride (NaF) positron emission tomography/computed tomography and gated chest computed tomography for coronary artery calcium in 88 consecutive ambulatory patients with DM on a stable medical regimen. NaF has been shown to localize avidly in culprit lesions of patients with acute coronary syndromes and may identify unstable plaques. NaF activity was measured as target (coronary arteries)-to-background (left ventricular pool) ratio (TBR). High TBR was defined as ≥1.5. The mean age of the cohort was 54±14 years, 55% had type 2 DM, 65% were men, the median HgbA1c (hemoglobin A1c) and LDL (low-density lipoprotein) cholesterol were 7.5% (interquartile range, 7.1-8.5) and 1.9 mmol/L (interquartile range, 1.5-2.6), respectively. Mean coronary artery calcium score was 374±773, and median TBR was 1.2. Coronary artery TBR ≥1.5 was detected in 13 (15%) patients. In univariable analyses, male sex ( P=0.0002), estimated glomerular filtration rate ( P=0.02), and total coronary artery calcium score ( P=0.04) were associated with TBR. In multivariable analyses, TBR >median was associated with male sex ( P=0.0001) and statin use ( P=0.042). Conclusions- In ambulatory patients with DM asymptomatic for cardiovascular disease, the prevalence of potentially vulnerable plaques detected with NaF was low, but in the absence of follow-up data at this stage, we cannot assess the import of this information. Future research will establish whether NaF imaging helps risk stratify patients with DM. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03530176.

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.