Publications by authors named "Bruce A Perkins"

182 Publications

Allopurinol adherence, persistence and patterns of use in individuals with diabetes and gout: A retrospective, population-based cohort analysis.

Semin Arthritis Rheum 2021 Sep 16;51(6):1162-1169. Epub 2021 Sep 16.

Department of Medicine, University of Toronto, Toronto, ON, Canada; ICES, ON, Canada; Women's College Hospital, Women's College Research Institute, Toronto, ON, Canada.

Objective: There has been growing interest in the potential role for allopurinol to reduce cardiovascular events in people with diabetes. While adherence to allopurinol is poor in those with gout, our aim was to characterize persistence, patterns of use, and predictors of allopurinol use in a population-based cohort of individuals with diabetes and gout.

Methods: Individuals with diabetes older than 66 (thus eligible for prescription medication coverage) and newly prescribed allopurinol were followed for up to three years in a retrospective cohort study. Allopurinol use patterns were categorized as adherer (used continuously throughout follow-up), interrupter (non-persistent but subsequently resumed), or discontinuer (non-persistent with no subsequent resumption). Main outcomes were allopurinol non-persistence (no subsequent prescription accounting for a grace period), and indicators of gout severity throughout follow-up (prescriptions for prednisone or colchicine, outpatient gout visits, hospitalization/emergency department visits for gout). Outcome frequencies were determined, a multivariable Cox proportional hazards model evaluated associations between predictors and non-persistence, and zero-inflated negative binomial (ZINB) models evaluated associations between allopurinol use pattern and indicators of gout severity.

Results: 22,056 individuals were followed for a maximum of 3.0 years (17,410 with 3 years of follow-up). 9092 (41.2%) were non-persistent with allopurinol. Higher risks of non-persistence were associated with female sex (HR, 95% CI: 1.28, 1.23-1.33), dementia (1.23, 1.11-1.35), and an outpatient visit for gout in the prior year (1.19, 1.09-1.29). There were 12,964 (58.8%) allopurinol adherers, 4618 interrupters (20.9%), and 4474 (20.3%) discontinuers. Allopurinol interrupters and discontinuers had indicators of more severe gout over time compared to adherers, including greater odds of being prescribed prednisone.

Conclusion: Allopurinol non-persistence and interruptions were frequent in individuals with diabetes and gout and were associated with prescriptions for prednisone. Suboptimal allopurinol adherence may not only increase the risk of gout complications in this population but also potentially diabetes complications through greater prednisone use and its negative effects on glycemic control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2021.09.003DOI Listing
September 2021

Omega-3 Nutrition Therapy for the Treatment of Diabetic Sensorimotor Polyneuropathy.

Curr Diabetes Rev 2021 Sep 1. Epub 2021 Sep 1.

Ellen and Martin Prosserman Centre for Neuromuscular Disorders. Division of Neurology, University Health Network, University of Toronto, Toronto. Canada.

Despite advances in clinical and translational research, an effective therapeutic option for diabetic sensorimotor polyneuropathy (DSP) has remained elusive. The pathomechanisms of DSP are diverse and along with hyperglycemia, the roles of inflammatory mediators and lipotoxicity in development of microangiopathy have been well elucidated. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential fatty acids with a vital role in a number of physiological processes including neural health, membrane structure integrity, anti-inflammatory processes and lipid metabolism. Identification of n-3 PUFA derived specialised proresolving mediators (SPM) namely resolvins, neuroprotectin and maresins which also favour nerve regeneration have positioned n-3 PUFA as potential treatment options in DSP. Studies in n-3 PUFA treated animal models of DSP showed positive nerve benefits in functional, electrophysiological and pathological indices. Clinical trials in humans are limited, but recent proof-of-concept evidence suggests n-3 PUFA have a positive effect on small nerve fibre regeneration with an increase in the small nerve fiber measure of corneal nerve fibre length (CNFL). Further randomized control trials, with longer duration of treatment, higher n-3 PUFA doses and more rigorous neuropathy measures are needed to provide a definitive understanding of the benefits of n-3 PUFA supplementation in DSP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1573399817666210901121111DOI Listing
September 2021

SGLT2-Inhibition reverts urinary peptide changes associated with severe COVID-19: An in-silico proof-of-principle of proteomics-based drug repurposing.

Proteomics 2021 Sep 3:e2100160. Epub 2021 Sep 3.

Department of Nephrology and Kuratorium for Dialysis and Transplantation (KfH) Renal Unit, Hospital St. Georg, Leipzig, Germany.

Severe COVID-19 is reflected by significant changes in urine peptides. Based on this observation, a clinical test predicting COVID-19 severity, CoV50, was developed and registered as in vitro diagnostic in Germany. We have hypothesized that molecular changes displayed by CoV50, likely reflective of endothelial damage, may be reversed by specific drugs. Such an impact by a drug could indicate potential benefits in the context of COVID-19. To test this hypothesis, urinary peptide data from patients without COVID-19 prior to and after drug treatment were collected from the human urinary proteome database. The drugs chosen were selected based on availability of sufficient number of participants in the dataset (n > 20) and potential value of drug therapies in the treatment of COVID-19 based on reports in the literature. In these participants without COVID-19, spironolactone did not demonstrate a significant impact on CoV50 scoring. Empagliflozin treatment resulted in a significant change in CoV50 scoring, indicative of a potential therapeutic benefit. The study serves as a proof-of-principle for a drug repurposing approach based on human urinary peptide signatures. The results support the initiation of a randomized control trial testing a potential positive effect of empagliflozin for severe COVID-19, possibly via endothelial protective mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmic.202100160DOI Listing
September 2021

Type 1 diabetes glycemic management: Insulin therapy, glucose monitoring, and automation.

Science 2021 07;373(6554):522-527

Department of Endocrinology, UZ Gasthuisberg, Katholieke Universiteit Leuven (KULeuven), Leuven, Belgium.

Despite innovations in insulin therapy since its discovery, most patients living with type 1 diabetes do not achieve sufficient glycemic control to prevent complications, and they experience hypoglycemia, weight gain, and major self-care burden. Promising pharmacological advances in insulin therapy include the refinement of extremely rapid insulin analogs, alternate insulin-delivery routes, liver-selective insulins, add-on drugs that enhance insulin effect, and glucose-responsive insulin molecules. The greatest future impact will come from combining these pharmacological solutions with existing automated insulin delivery methods that integrate insulin pumps and glucose sensors. These systems will use algorithms enhanced by machine learning, supplemented by technologies that include activity monitors and sensors for other key metabolites such as ketones. The future challenges facing clinicians and researchers will be those of access and broad clinical implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abg4502DOI Listing
July 2021

Changes in plasma and urine metabolites associated with empagliflozin in patients with type 1 diabetes.

Diabetes Obes Metab 2021 Jul 12. Epub 2021 Jul 12.

Toronto General Hospital Research Institute, UHN, Toronto, Ontario, Canada.

Aim: To examine the impact of the sodium-glucose co-transporter-2 inhibitor, empagliflozin, on plasma and urine metabolites in participants with type 1 diabetes.

Material And Methods: Participants (n = 40, 50% male, mean age 24.3 years) with type 1 diabetes and without overt evidence of diabetic kidney disease had baseline assessments performed under clamped euglycaemia and hyperglycaemia, on two consecutive days. Participants then proceeded to an 8-week, open-label treatment period with empagliflozin 25 mg/day, followed by repeat assessments under clamped euglycaemia and hyperglycaemia. Plasma and urine metabolites were first grouped into metabolic pathways using MetaboAnalyst software. Principal component analysis was performed to create a representative value for each sufficiently represented metabolic group (false discovery rate ≤ 0.1) for further analysis.

Results: Of the plasma metabolite groups, tricarboxylic acid (TCA) cycle (P < .0001), biosynthesis of unsaturated fatty acids (P = .0045), butanoate (P < .0001), propanoate (P = .0053), and alanine, aspartate and glutamate (P < .0050) metabolites were increased after empagliflozin treatment under clamped euglycaemia. Of the urine metabolite groups, only butanoate metabolites (P = .0005) were significantly increased. Empagliflozin treatment also attenuated the increase in a number of urine metabolites observed with acute hyperglycaemia.

Conclusions: Empagliflozin was associated with increased lipid and TCA cycle metabolites in participants with type 1 diabetes, suggesting a shift in metabolic substrate use and improved mitochondrial function. These effects result in more efficient energy production and may contribute to end-organ protection by alleviating local hypoxia and oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14489DOI Listing
July 2021

Corneal Confocal Microscopy Predicts the Development of Diabetic Neuropathy: A Longitudinal Diagnostic Multinational Consortium Study.

Diabetes Care 2021 Sep 1;44(9):2107-2114. Epub 2021 Jul 1.

University of Manchester, Manchester, U.K.

Objective: Corneal nerve fiber length (CNFL) has been shown in research studies to identify diabetic peripheral neuropathy (DPN). In this longitudinal diagnostic study, we assessed the ability of CNFL to predict the development of DPN.

Research Design And Methods: From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 participants who were free of DPN at baseline and completed at least 4 years of follow-up for incident DPN. The predictive validity of CNFL for the development of DPN was determined using time-dependent receiver operating characteristic (ROC) curves.

Results: A total of 203 participants had type 1 and 58 had type 2 diabetes. Mean follow-up time was 5.8 years (interquartile range 4.2-7.0). New-onset DPN occurred in 60 participants (23%; 4.29 events per 100 person-years). Participants who developed DPN were older and had a higher prevalence of type 2 diabetes, higher BMI, and longer duration of diabetes. The baseline electrophysiology and corneal confocal microscopy parameters were in the normal range but were all significantly lower in participants who developed DPN. The time-dependent area under the ROC curve for CNFL ranged between 0.61 and 0.69 for years 1-5 and was 0.80 at year 6. The optimal diagnostic threshold for a baseline CNFL of 14.1 mm/mm was associated with 67% sensitivity, 71% specificity, and a hazard ratio of 2.95 (95% CI 1.70-5.11; < 0.001) for new-onset DPN.

Conclusions: CNFL showed good predictive validity for identifying patients at higher risk of developing DPN ∼6 years in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc21-0476DOI Listing
September 2021

Glycaemic control in transition-aged versus early adults with type 1 diabetes and the effect of a government-funded insulin pump programme.

Diabet Med 2021 Jun 2:e14618. Epub 2021 Jun 2.

Department of Medicine, University of Toronto, Toronto, ON, Canada.

Aim: To compare glycaemic control and adverse outcomes between transition-aged and early adults with type 1 diabetes, and the impact of continuous subcutaneous insulin infusion (CSII) therapy funded through a government Assisted Devices Program.

Methods: This retrospective cohort study using healthcare administrative databases from Ontario, Canada included adults aged 18-35 with type 1 diabetes between 1 April 2011 and 31 March 2014. Mean HbA was compared between transition-aged (18-24 years) and early adults (25-35 years), overall and stratified by whether or not they received government-funded CSII therapy (CSII vs. non-CSII). Secondary outcomes included rates of hospitalizations/emergency department visits for hyperglycaemia and hypoglycaemia over a 3-year follow-up. Comparisons were adjusted for relevant covariates.

Results: Among 7157 participants with type 1 diabetes, mean HbA was significantly higher for transition-aged compared to early adults (71 mmol/mol [8.68%] vs. 64 mmol/mol [8.04%], p < 0.0001). This difference was smaller among CSII compared to non-CSII users (p = 0.02 for interaction between age group and CSII use). The transition-age group were more likely to experience a hyperglycaemic event compared to early adults (adjusted risk ratio, aRR: 1.56, 95% confidence interval [CI]: 1.25-1.96), which was attenuated by CSII use (aRR: 1.13, 95% CI: 0.7-1.69).

Conclusions: Transition-aged adults with type 1 diabetes had a significantly higher mean HbA and risk of hyperglycaemic events compared to early adults. This difference was attenuated for CSII users, indicating that a government-funded CSII programme is associated with narrowing of the gap in glycaemic control and associated adverse outcomes for this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dme.14618DOI Listing
June 2021

Afternoon aerobic and resistance exercise have limited impact on 24-h CGM outcomes in adults with type 1 diabetes: A secondary analysis.

Diabetes Res Clin Pract 2021 Jul 28;177:108874. Epub 2021 May 28.

University of Alberta, Augustana Faculty, 4901- 46th Avenue, Camrose, AB T4V 2R3, Canada; Physical Activity and Diabetes Laboratory, Alberta Diabetes Institute, L-052, Li Ka Shing Centre for Health Research Innovation, 112 Street, Edmonton, AB T6G 2T9, Canada; Faculty of Kinesiology, Sport and Recreation, University of Alberta, 3-100 University Hall, Van Vliet Complex, Edmonton, AB T6G 2H9, Canada; Women and Children's Health Research Institute, ECHA 4-081, University of Alberta, 11405 87 Avenue NW, Edmonton, AB T6G 1C9, Canada. Electronic address:

Aims: This study examined post-exercise glycemic variability in individuals with type 1 diabetes after acute bouts of resistance (RE) and aerobic exercise (AE) compared to a no-exercise day (CON). We hypothesized that exercise days would have greater glucose variability (standard deviation - SD, coefficient of variation - CV), and less time in range (TIR), compared to CON.

Methods: A secondary analysis was conducted on previously collected data. Twelve active participants with type 1 diabetes performed three testing sessions in random order with at least 48 h in between: AE (45-min treadmill run at 60%VO), RE (three sets of eight repetitions, seven weight-lifting exercises), and CON (45-min no-exercise control). Interstitial glucose levels were monitored by blinded continuous glucose monitoring (CGM). Glycemic variability was evaluated for 0-6 h, overnight (00:00-06:00) and 24 h after exercise.

Results: Mean CGM glucose, TIR, and time above/below range were similar among conditions (P > 0.05). Lower SD (0.8 [0.5-1.1], 1.4 [0.9-2.4]mmol/L, p = 0.009) and CV (11.4 [8.6-15.3], 23.4 [13.7-31.6]%, p = 0.007) were found overnight after AE versus CON. Otherwise, AE and RE had limited impact on post-exercise glycemia.

Conclusions: Acute RE and AE bouts may have limited impact on post-exercise glycemic variability compared to rest in habitually active individuals with type 1 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2021.108874DOI Listing
July 2021

Vitamin D Levels and the Risk of Posttransplant Diabetes Mellitus After Kidney Transplantation.

Prog Transplant 2021 06 1;31(2):133-141. Epub 2021 Apr 1.

Division of Nephrology and the Kidney Transplant Program, 7989University Health Network, Toronto, Ontario, Canada.

Introduction: Given the burden of posttransplant diabetes mellitus and the high prevalence of low vitamin D levels in kidney transplant recipients, it is reasonable to consider vitamin D as a novel and potentially modifiable risk factor in this patient population.

Research Question: To determine the association between 25- hydroxyvitamin D (25(OH)D) level and posttransplant diabetes among kidney transplant recipients. Design: In a multi-center cohort study of 442 patients who received a kidney transplant between January 1, 2005 and December 31, 2010, serum samples within one-year before transplant were analyzed for 25(OH)D levels. The association between 25(OH)D and posttransplant diabetes were examined in Cox proportional hazard models.

Results: The median 25(OH)D level was 66 nmol/L. The cumulative probability of diabetes at 12-months by quartiles of 25(OH)D (< 42, 42 to 64.9, 65 to 94.9, and > 95 nmol/L) were 23.4%, 26.9%, 21.4%, and 15.6%, respectively. Compared to the highest 25(OH)D quartile, hazard ratios (95% CI) for the risk were 1.85 (1.03, 3.32), 2.01 (1.12, 3.60), 1.77 (0.96, 3.25) across the first to third quartiles, respectively. The associations were accentuated in a model restricted to patients on tacrolimus. When modeled as a continuous variable, 25(OH)D levels were significantly associated with a higher risk of diabetes (hazard ratio 1.06, 95% CI: 1.01, 1.13 per 10 nmol/L decrease).

Discussion: Serum 25(OH)D was an independent predictor of posttransplant diabetes in kidney transplant recipients. These results may inform the design of trials using vitamin D to reduce the risk in kidney transplant recipients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15269248211002796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182337PMC
June 2021

Allopurinol and Renal Outcomes in Adults With and Without Type 2 Diabetes: A Retrospective, Population-Based Cohort Study and Propensity Score Analysis.

Can J Diabetes 2021 Oct 20;45(7):641-649.e4. Epub 2021 Jan 20.

Department of Medicine, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.

Objectives: Elevated uric acid (UA) is common in diabetes and is implicated in the pathogenesis of chronic kidney disease (CKD). Lowering UA with allopurinol may delay CKD progression. We assessed the association between allopurinol and renal outcomes in older adults both with and without diabetes, and whether this differed by diabetes status.

Methods: We conducted a population-based, retrospective cohort study of older adults ≥66 years of age with a gout flare using administrative data from Ontario, Canada. The primary outcome was doubling of creatinine or kidney failure. Secondary outcomes were a composite of death or kidney failure, decline in estimated glomerular filtration rate by >30%, death and kidney failure. New allopurinol users were compared with nonusers using Cox proportional hazards models and inverse probability of treatment weighting (IPTW). An interaction between allopurinol use and presence or absence of diabetes was assessed.

Results: Among 5,937 older adults with a gout flare (1,911 with diabetes), 1,304 (22%) were newly treated with allopurinol. Median follow-up time was 1.11 (interquartile range, 0.33 to 3.21) years for allopurinol users and 3.38 (interquartile range, 1.42 to 4.43) years for nonusers. There was no association between allopurinol use and the primary outcome (IPTW-adjusted hazard ratio, 0.97; 95% confidence interval, 0.72 to 1.31), and this did not differ by diabetes status. Allopurinol use was not associated with any of the secondary outcomes.

Conclusions: Allopurinol use was not associated with renal outcomes in older adults with or without diabetes. This supports the interpretation of UA as a biomarker of CKD risk rather than a modifiable target for prevention or treatment of CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjd.2021.01.005DOI Listing
October 2021

Relationships between inflammation, hemodynamic function and RAAS in longstanding type 1 diabetes and diabetic kidney disease.

J Diabetes Complications 2021 05 2;35(5):107880. Epub 2021 Feb 2.

Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Banting and Best Diabetes Centre, Toronto, Canada. Electronic address:

The renin angiotensin aldosterone system (RAAS) is associated with renal disease and inflammation in a diabetes setting, however, little is known about the implicated mechanisms in individuals with long standing diabetes. Accordingly, our aim was to perform an observational study to quantify urinary excretion of inflammatory biomarkers in participants with long standing type 1 diabetes (T1D) (with and without diabetic kidney disease [DKD]) and controls, at baseline and in response to RAAS activation. GFR, ERPF, and 42 urine inflammatory biomarkers were measured in 74 participants with T1D for ≥50 years (21 with DKD and 44 without DKD [DKD resistors]) and 73 healthy controls. Additionally, inflammatory biomarkers were measured before and after an angiotensin II infusion (ANGII, 1 ng∙kg∙min). Significantly lower urinary excretion of cytokines (IL-18, IL-1RA, IL-8), chemokines (MCP1, RANTES) and growth factors (TGF-α, PDGFAA, PDGFBB, VEGF-A) was observed in participants with T1D at baseline compared to controls. Urinary IL-6 was higher in DKD than in DKD resistors in an exploratory analysis unadjusted for multiple comparisons. In T1D only, lower GFR correlated with greater excretion of proinflammatory biomarkers (IL-18, IP-10, & RANTES), growth factors (PDGF-AA & VEGFAA), and chemokines (eotaxin & MCP-1). ANGII increased 31 of 42 inflammatory biomarkers in T1D vs controls (p < 0.05), regardless of DKD resistor status. In conclusion, lower GFR and intra-renal RAAS activation were associated with increased inflammation even after longstanding T1D. The increased urinary IL-6 in patients with DKD requires further investigation to determine whether IL-6 is a candidate protective biomarker for prognostication or targeted therapy in DKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2021.107880DOI Listing
May 2021

Discoveries from the study of longstanding type 1 diabetes.

Diabetologia 2021 Jun 4;64(6):1189-1200. Epub 2021 Mar 4.

Division of Nephrology, Department of Medicine, University of Toronto, Toronto, ON, Canada.

Award programmes that acknowledge the remarkable accomplishments of long-term survivors with type 1 diabetes have naturally evolved into research programmes to determine the factors associated with survivorship and resistance to chronic complications. In this review, we present an overview of the methodological sources of selection bias inherent in survivorship research (selection of those with early-onset diabetes, incidence-prevalence bias and bias from losses to follow-up in cohort studies) and the breadth and depth of literature focusing on this special study population. We focus on the learnings from the study of longstanding type 1 diabetes on discoveries about the natural history of insulin production loss and microvascular complications, and mechanisms associated with them that may in future offer therapeutic targets. We detail descriptive findings about the prevalence of preserved insulin production and resistance to complications, and the putative mechanisms associated with such resistance. To date, findings imply that the following mechanisms exist: strategies to maintain or recover beta cells and their function; activation of specific glycolytic enzymes such as pyruvate kinase M2; modification of AGE production and processing; novel mechanisms for modification of renin-angiotensin-aldosterone system activation, in particular those that may normalise afferent rather than efferent renal arteriolar resistance; and activation and modification of processes such as retinol binding and DNA damage checkpoint proteins. Among the many clinical and public health insights, research into this special study population has identified putative mechanisms that may in future serve as therapeutic targets, knowledge that likely could not have been gained without studying long-term survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-021-05403-9DOI Listing
June 2021

Reducing the need for carbohydrate counting in type 1 diabetes using closed-loop automated insulin delivery (artificial pancreas) and empagliflozin: A randomized, controlled, non-inferiority, crossover pilot trial.

Diabetes Obes Metab 2021 06 28;23(6):1272-1281. Epub 2021 Feb 28.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Aim: To assess whether adding empagliflozin to closed-loop automated insulin delivery could reduce the need for carbohydrate counting in type 1 diabetes (T1D) without worsening glucose control.

Materials And Methods: In an open-label, crossover, non-inferiority trial, 30 adult participants with T1D underwent outpatient automated insulin delivery interventions with three random sequences of prandial insulin strategy days: carbohydrate counting, simple meal announcement (no carbohydrate counting) and no meal announcement. During each sequence of prandial insulin strategies, participants were randomly assigned empagliflozin (25 mg/day) or not, and crossed over to the comparator. Mean glucose for carbohydrate counting without empagliflozin (control) was compared with no meal announcement with empagliflozin (in the primary non-inferiority comparison) and simple meal announcement with empagliflozin (in the conditional primary non-inferiority comparison).

Results: Participants were aged 40 ± 15 years, had 27 ± 15 years diabetes duration and HbA1c of 7.6% ± 0.7% (59 ± 8 mmol/mol). The system with no meal announcement and empagliflozin was not non-inferior (and thus reasonably considered inferior) to the control arm (mean glucose 10.0 ± 1.6 vs. 8.5 ± 1.5 mmol/L; non-inferiority p = .94), while simple meal announcement and empagliflozin was non-inferior (8.5 ± 1.4 mmol/L; non-inferiority p = .003). Use of empagliflozin on the background of automated insulin delivery with carbohydrate counting was associated with lower mean glucose, corresponding to a 14% greater time in the target range. While no ketoacidosis was observed, mean fasting ketones levels were higher on empagliflozin (0.22 ± 0.18 vs. 0.13 ± 0.11 mmol/L; p < .001).

Conclusions: Empagliflozin added to automated insulin delivery has the potential to eliminate the need for carbohydrate counting and improves glycaemic control in conjunction with carbohydrate counting, but does not allow for the elimination of meal announcement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14335DOI Listing
June 2021

The Prevalence of Autoimmune Diseases in Longstanding Diabetes: Results from the Canadian Study of Longevity in Adults with Type 1 Diabetes.

Can J Diabetes 2021 Aug 27;45(6):512-518.e1. Epub 2020 Oct 27.

Division of Endocrinology and Metabolism, Department of Medicine, Sinai Health System, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: We aimed to determine the prevalence of autoimmune diseases (e.g. thyroid disease, celiac disease, etc) in Canadians with longstanding type 1 diabetes (T1D) and to explore sex-specific differences and the association with complications.

Methods: Cross-sectional data were analyzed in an exploratory secondary analysis from the Canadian Study of Longevity in Type 1 Diabetes, a nationwide registry of people with T1D of at least 50 years' duration. In total, 374 participants provided self-reported questionnaire data and physician-reported laboratory results. Student's t-test, the Wilcoxon rank-sum test, the χ test and logistic regression were used to identify associations with autoimmune diseases.

Results: The 374 participants had a median T1D duration of 53 years (interquartile range, 51 to 58) and a median age of onset of 11 years (6 to 16), and 57.1% were females. Females had a greater prevalence of autoimmune diseases (60.6% vs 34.4%, p<0.001). Thyroid disease was most prevalent (41%, 153/374), especially in females (51.6% vs 26.9%), and the prevalence of 1 or more autoimmune disease was 49.3% (184/374). Autoimmune disease was associated with lower odds of cardiovascular disease (CVD)-odds ratio [OR] 0.61, 95% confidence interval [CI] 0.37 to 1.00 for thyroid autoimmune disease and OR 0.34 (95% CI 0.12 to 0.93) for nonthyroid autoimmune disease, both compared to those without autoimmune disease (p=0.033). Autoimmune diseases were not associated with the presence of nephropathy, neuropathy or retinopathy.

Conclusions: Lifetime risk of autoimmune disease in longstanding T1D approaches 50%, is greater in females and is driven by thyroid disease. The probability of diabetes complications, such as CVD, was lower in those with autoimmune disease, which was driven mostly by nonthyroid autoimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjd.2020.10.010DOI Listing
August 2021

Baseline omega-3 level is associated with nerve regeneration following 12-months of omega-3 nutrition therapy in patients with type 1 diabetes.

J Diabetes Complications 2021 03 26;35(3):107798. Epub 2020 Nov 26.

Ellen and Martin Prosserman Centre for Neuromuscular Disorders, Division of Neurology, University Health Network, University of Toronto, Toronto, Canada.

Aim: Omega-3 (n-3) polyunsaturated fatty-acids are essential for the development and maintenance of nerve function, but the relationship of plasma n-3 to the presence of diabetic distal-symmetric-polyneuropathy (DSP) and the effect of n-3 therapy on plasma levels and small nerve fibre morphology in T1D are unknown.

Methods: Participants with T1D (n = 40, 53% female, aged (mean ± SD) 48 ± 14 years, BMI 28.1 ± 5.8 kg/m, diabetes duration 27 ± 18 years), 23 of whom had DSP, took seal-oil (10 mL/day; 750 mg eicosapentaenoic acid (EPA), 560 mg docosapentaenoic acid (DPAn-3), and 1020 mg docosahexaenoic acid (DHA)) for 12-months in a single-arm open-label study. The improvement in corneal nerve fibre length (CNFL) (primary outcome) was previously reported. In this secondary analysis, plasma n-3s were measured at baseline, 4, 8 and 12-months.

Results: At baseline, participants with DSP had lower DHA than those without (1.73 ± 0.89 vs. 2.27 ± 0.70%, p = 0.049). Twelve-months seal-oil therapy increased mean plasma EPA by 185%, DPA by 29%, DHA by 79% (p < 0.001) and CNFL by 29% (p = 0.001). Change in CNFL was positively associated with higher baseline total n-3 (Spearman's correlation coefficient r = 0.41, p = 0.013), DPA (r = 0.33, p = 0.047) and DHA (r = 0.42, p = 0.012).

Conclusion: In conclusion, low plasma DHA was associated with prevalent DSP, n-3 therapy increased blood n-3 levels and higher baseline n-3s were associated with greater nerve regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2020.107798DOI Listing
March 2021

Vasopressin associated with renal vascular resistance in adults with longstanding type 1 diabetes with and without diabetic kidney disease.

J Diabetes Complications 2021 03 26;35(3):107807. Epub 2020 Nov 26.

Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address:

Objective: Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors.

Methods: Participants with type 1 diabetes (n = 62, duration ≥50 years) were stratified into 42 DKD Resistors and 20 with DKD (eGFR ≤60 mL/min/1.73m or ≥30 mg/day urine albumin), and age/sex-matched controls (HC, n = 74) were included. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were calculated by inulin and p-aminohippurate clearance before and after angiotensin II (ang II) infusion. Renal vascular resistance (RVR) was calculated as mean arterial pressure/renal blood flow. Plasma copeptin, renin, aldosterone, neutrophil gelatinase-associated lipocalin (NGAL), and urea concentrations were measured, along with 24-h urine volume.

Results: DKD resistors had lower copeptin (95% CI: 4.0 [3.4-4.8] pmol/l) compared to DKD (5.8 [4.5-7.6] pmol/l, p = 0.02) and HC (4.8 [4.1-5.5] pmol/l, p = 0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: -0.32, p = 0.01) and higher renin concentration (r: 0.40, p = 0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (β ± SE: -6.9 ± 3.4, p = 0.04).

Conclusions: In longstanding type 1 diabetes, copeptin was associated with intrarenal renin-angiotensin-aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2020.107807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397596PMC
March 2021

High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes.

Sci Rep 2020 07 29;10(1):12709. Epub 2020 Jul 29.

Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK.

Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type 1 diabetes (T1DM) during onset of microalbuminuria (MA) from the First Joslin Kidney Study, a prospective case-control study of patients with T1DM with and without early decline in GFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline in GFR. We recruited patients with T1DM and normoalbuminuria (NA) (n = 30) or new onset MA with and without early GFR decline (n = 22 and 33, respectively) for this study. We determined urinary protein glycation, oxidation and nitration free adducts by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC-MS/MS) and deduced fractional excretion using reported plasma levels and urinary and plasma creatinine estimates. We found urinary excretion of pentosidine was increased ca. twofold in patients with MA, compared to normoalbuminuria (0.0442 vs 0.0103 nmol/mg creatinine, P < 0.0001), and increased ca. threefold in patients with early decline in GFR, compared to patients with stable GFR (0.0561 vs 0.0176 nmol/mg creatinine, P < 0.01). Urinary excretion of all other analytes was unchanged between the study groups. Remarkably, fractional excretions of 6 lysine and arginine-derived glycation free adducts were higher in patients with early decline in GFR, compared to those with stable GFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with early GFR decline is likely involved. We conclude that higher fractional excretions of glycation adducts are potential biomarkers for early GFR decline in T1DM and MA. Measurement of these analytes could provide the basis for identifying patients at risk of early decline in renal function to target and intensify renoprotective treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-69350-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391737PMC
July 2020

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

N Engl J Med 2020 06;382(26):2493-2503

From the Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston (A.D., A.B.G., S.E.R.); the Division of Geriatrics, Institute of Gerontology (A.T.G., C.W.), the Department of Biostatistics, School of Public Health (A.T.G., C.S.), Statistical Analysis of Biomedical and Educational Research (SABER) (C.S.), and the Department of Internal Medicine, Metabolism, Endocrinology, and Diabetes (R.P.-B.), University of Michigan, Ann Arbor; the Departments of Medicine, Physiology, and Pharmacology and Toxicology (D.Z.C.) and the Division of Endocrinology and Metabolism (B.A.P.), University of Toronto, the Division of Nephrology, University Health Network (D.Z.C.), LMC Diabetes and Endocrinology (R.A.), and Lunenfeld-Tanenbaum Research Institute, Sinai Health System (B.A.P.), Toronto, the Departments of Medicine, Cardiac Sciences, and Community Health Sciences, Faculties of Medicine and Kinesiology, University of Calgary, Calgary, AB (R.J.S.), BCDiabetes, Vancouver (T.G.E.), and the Division of Endocrinology, University of Alberta, Edmonton (P.S.) - all in Canada; the Departments of Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (A.P.); Steno Diabetes Center, and the Department of Clinical Medicine, University Copenhagen, Copenhagen (P.R.); the Division of Nephrology, Department of Medicine, University of California, Davis (M.A.), and the Department of Pediatrics and Stanford Diabetes Research Center, Stanford University, Palo Alto (D.M.M.) - both in California; the Departments of Medicine and Pediatrics (M.L.C., W.N.R.. M.M.) and Laboratory Medicine and Pathology (A.B.K.), University of Minnesota, Minneapolis; the Division of Endocrinology and Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine (J.P.C.), and JDRF (Juvenile Diabetes Research Foundation) (M.P.), New York; the Department of Medicine (I.H.B., I.B.H.) and the Nephrology Division (K.R.T.), University of Washington, and the Institute of Translational Health Sciences, Kidney Research Institute (K.R.T.), Seattle, and Providence Health Care, Spokane (K.R.T.) - both in Washington; the Department of Medicine, Emory University, Atlanta (J.S.H., G.E.U.); the Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis (J.B.M.); the Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago (M.E.M., A.W.); the Barbara Davis Center for Diabetes, University of Colorado, Aurora (S.P.); and the Department of Medicine, State University of New York Upstate Medical University, Syracuse (R.S.W.).

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 m 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 m in the allopurinol group and 67.3 ml per minute per 1.73 m 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 m (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 m per year with allopurinol and -2.5 ml per minute per 1.73 m per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m 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.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1916624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375708PMC
June 2020

Sounding the alarm on rising diabetes-related amputations.

Authors:
Bruce A Perkins

CMAJ 2019 09;191(35):E953-E954

Division of Endocrinology, Leadership Sinai Centre for Diabetes, and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ont.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1503/cmaj.191064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721862PMC
September 2019

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

Diabetes Care 2020 07 28;43(7):1553-1556. Epub 2020 Apr 28.

Division of Endocrinology, Markham-Stouffville Hospital, Markham, Ontario, Canada.

Objective: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.

Research Design And Methods: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA and continuous glucose monitoring over 12 months.

Results: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, = 1,298] vs. 4.7% [95% CI 3.4-5.9%, = 1,089], = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, < 0.0001). Fifty-one participants were randomized to a GFD ( = 27) or GCD ( = 24). No HbA differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; = 0.014) emerged with a GFD.

Conclusions: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc19-1944DOI Listing
July 2020

Rethinking Neuropathy in Type 1 Diabetes: Had We Lost Sight of What Matters Most?

Authors:
Bruce A Perkins

Diabetes Care 2020 04;43(4):695-697

Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, and Lunenfeld-Tanenbaum Research Institute Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dci19-0076DOI Listing
April 2020

Rapid Corneal Nerve Fiber Loss: A Marker of Diabetic Neuropathy Onset and Progression.

Diabetes Care 2020 08 5;43(8):1829-1835. Epub 2020 Mar 5.

Division of Endocrinology, Leadership Sinai Centre for Diabetes, University of Toronto, Toronto, Canada

Objective: Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables.

Research Design And Methods: We examined 590 participants with diabetes (399 with type 1 diabetes [T1D] and 191 with type 2 diabetes [T2D]) and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the 5th percentile of the control patients without diabetes.

Results: Control patients without diabetes were 37.9 ± 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was -0.1% (90% CI -5.9% to 5.0%). RCNFL was defined by values exceeding the 5th percentile of 6% loss. Participants with T1D were 39.9 ± 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was -0.8% (90% CI -14.0% to 9.9%). Participants with T2D were 60.4 ± 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was -0.2% (90% CI -14.1% to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type (64 T1D [16.0%], 37 T2D [19.4%], = 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA or its change over follow-up.

Conclusions: An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc19-0951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372054PMC
August 2020

Talking Points for Helping Your Type 1 Diabetes Patient Decide About Hybrid Closed Loop.

Can J Diabetes 2020 Jun 26;44(4):356-358. Epub 2019 Oct 26.

Diabetes Clinical Research Unit, Leadership Sinai Centre for Diabetes, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjd.2019.10.004DOI Listing
June 2020

Low-dose empagliflozin as adjunct-to-insulin therapy in type 1 diabetes: A valid modelling and simulation analysis to confirm efficacy.

Diabetes Obes Metab 2020 03 21;22(3):427-433. Epub 2020 Jan 21.

Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.

Aim: To confirm the observed reduction in HbA1c for the 2.5 mg dose in EASE-3 by modelling and simulation analyses.

Materials And Methods: Independent of data from EASE-3 that tested 2.5 mg, we simulated the effect of a 2.5 mg dose through patient-level, exposure-response modelling in the EASE-2 clinical study. A primary semi-mechanistic model evaluated efficacy considering clinical insulin dose adjustments made after treatment initiation that potentially limited HbA1c reductions. The model was informed by pharmacokinetic, insulin dose, mean daily glucose and HbA1c data, and was verified by comparing the simulations with the observed HbA1c change in EASE-3. One of two empagliflozin phase 3 trials in type 1 diabetes (EASE-3 but not EASE-2) included a lower 2.5 mg dose. A placebo-corrected HbA1c reduction of 0.28% was demonstrated without the increased risk of diabetic ketoacidosis observed at higher doses (10 mg and 25 mg). Since only one trial included the lower dose, we aimed to confirm the observed reduction in HbA1c for the 2.5 mg dose by modelling and simulation analyses.

Results: The simulated 26-week mean HbA1c change was -0.41% without insulin dose adjustment and -0.29% at 26 weeks with insulin dose adjustment. A simplified (descriptive) model excluding insulin dose and mean daily glucose confirmed the -0.29% HbA1c change that would have been observed had the EASE-2 population received a 2.5 mg dose for 26/52 weeks.

Conclusions: The HbA1c benefit of low-dose empagliflozin directly observed in the EASE-3 trial was confirmed by two modelling and simulation approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.13945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064984PMC
March 2020

Sex differences in neuropathy & neuropathic pain: A brief report from the Phase 2 Canadian Study of Longevity in Type 1 Diabetes.

J Diabetes Complications 2019 12 20;33(12):107397. Epub 2019 Jun 20.

Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address:

To evaluate previous results from a questionnaire-based study, we studied objective neuropathy measures to determine sex differences in the prevalence of neuropathy and neuropathic pain in longstanding type 1 diabetes. Despite better neuropathy measures in females compared to males, we confirmed a trend towards higher neuropathic pain in females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2019.06.002DOI Listing
December 2019

Analysis of Prevalence, Magnitude and Timing of the Dawn Phenomenon in Adults and Adolescents With Type 1 Diabetes: Descriptive Analysis of 2 Insulin Pump Trials.

Can J Diabetes 2020 Apr 14;44(3):229-235. Epub 2019 Aug 14.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objectives: To better understand the dawn phenomenon in type 1 diabetes, we sought to determine its prevalence, timing and magnitude in studies specifically designed to assess basal insulin requirements in patients using insulin pumps.

Methods: Thirty-three participants from 2 sensor-augmented insulin pump studies were analyzed. Twenty participants were obtained from a methodologically ideal semiautomated basal analysis trial in which basal rates were determined from repeated fasting tests (the derivation set) and 13 from an artificial pancreas trial in which duration of fasting was variable (the "confirmation" set). Prevalence was determined for the total cohort and for individual trials using the standard definition of an increase in insulin exceeding 20% and lasting ≥90 minutes. Among cases, time of onset and percent change in the magnitude of basal delivery were determined.

Results: Seventeen participants (52%) experienced the dawn phenomenon (11 of 20 [55%] in the derivation set and 6 of 13 [46%] in the confirmation set). Time of onset was 3 AM (interquartile range [IQR], 3 to 4:15 AM) in the derivation set and 3 AM (IQR, 3 to 4 AM) in the confirmation set. The magnitude of the dawn phenomenon was a 58.1% (IQR, 28.8% to 110.6%) increase in insulin requirements in the derivation set and 65.5% (IQR, 45.6% to 87.4%) in the confirmation set.

Conclusions: The dawn phenomenon occurs in approximately half of patients with type 1 diabetes; when present, it has predictable timing of onset (generally 3 AM) and a substantial, but highly variable, magnitude. These findings imply that optimization of glycemic control requires clinical emphasis on fasted overnight basal insulin assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjd.2019.08.003DOI Listing
April 2020

Sex-Related Differences in Blood Glucose Responses to Resistance Exercise in Adults With Type 1 Diabetes: A Secondary Data Analysis.

Can J Diabetes 2020 Apr 22;44(3):267-273.e1. Epub 2019 Aug 22.

Augustana Faculty, University of Alberta, Camrose, Alberta, Canada; Physical Activity and Diabetes Laboratory, Alberta Diabetes Institute, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada; Faculty of Kinesiology, Sport and Recreation, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Objectives: In adults with type 1 diabetes, resistance exercise (RE) is associated with more stable blood glucose (BG) levels than aerobic exercise, both during and after exercise. In individuals without diabetes, growth hormone and epinephrine responses to RE differ between the sexes. These hormones are known to affect BG levels in individuals with type 1 diabetes. In this study, we explored whether sex-related differences may exist in BG responses to RE in individuals with type 1 diabetes.

Methods: A secondary data analysis was conducted on pooled data from 2 studies with identical RE protocols for individuals with type 1 diabetes (13 males, age range 16 to 63 years; 10 females, age range 19 to 45 years). The RE session consisted of 7 resistance-based exercises performed at 5 pm. Plasma glucose samples were collected before, immediately after and 1 h after exercise. Interstitial glucose levels were recorded through blinded continuous glucose monitoring 24 h before, during and 24 h after exercise.

Results: There was a significant sex-by-time interaction (p<0.001) in plasma glucose responses to RE. Plasma glucose decreased significantly in males from 8.6±2.5 to 6.3±2.1 mmol/L (p<0.001) during exercise, whereas females experienced no significant change (7.2±1.3 to 7.3±1.3 mmol/L, p=0.999). In the 6 h after RE, males developed significantly more hypoglycemia, as measured by continuous glucose monitoring (p=0.048).

Conclusions: Males may have a greater risk of hypoglycemia with an acute bout of RE than females. Further research is needed to examine this phenomenon more closely, as sex-specific recommendations for preventing hypoglycemia around RE may be necessary in type 1 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjd.2019.08.006DOI Listing
April 2020

Randomized, controlled crossover study of IVIg for demyelinating polyneuropathy and diabetes.

Neurol Neuroimmunol Neuroinflamm 2019 09 10;6(5). Epub 2019 Jul 10.

From the Division of Neurology (A.B.), Department of Medicine, the Ottawa Hospital; Ottawa Hospital Research Institute (A.B.); Division of Neurology (C.B., H.D.K., V.B.), Department of Medicine, Ellen and Martin Prosserman Centre for Neuromuscular Diseases, University Health Network, University of Toronto; Division of Endocrinology and Metabolism (L.E.L., B.A.P.), Department of Medicine, Mount Sinai, Hospital and Lunenfeld Tanenbaum Research Institute, University of Toronto, Canada; and Institute for Research and Medical Consultations (V.B.), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Objective: To determine whether IV immunoglobulin (IVIg) is more effective than placebo at reducing disability in patients with diabetes and demyelinating polyneuropathy features.

Methods: This is a double-blinded, single-center, randomized, controlled crossover trial of IVIg treatment vs placebo. The primary outcome measure was the mean change in Overall Neuropathy Limitation Scale (ONLS) scores during the IVIg phasecompared with the placebo phase. Secondary outcomes include changes in the Rasch-built Overall Disability Scale, Medical Research Council sum scores, grip strength, electrophysiologic measurements, quality of life, and adverse effects.

Results: Twenty-five subjects were recruited between March 2015 and April 2017. The mean change in ONLS scores was -0.2 points during the IVIg phase and 0.0 points during the placebo phase ( = 0.23). Secondary outcomes did not show significant differences between IVIg and placebo.

Conclusions: IVIg did not reduce disability, improve strength, or quality of life in patients with demyelinating polyneuropathy features and diabetes after 3 months of treatment in comparison with placebo. Therefore, careful consideration of the primary diagnosis is required before immunomodulatory therapy.

Classification Of Evidence: This study provides Class I evidence that for patients with diabetes and demyelinating polyneuropathy features, IVIg did not significantly reduce disability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000000586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943235PMC
September 2019

Graves' Disease After Chronic Hypothyroidism in Type 1 Diabetes.

Can J Diabetes 2020 Mar 13;44(2):131-132. Epub 2019 Jun 13.

Leadership Sinai Centre for Diabetes, Division of Endocrinology and Metabolism, Sinai Health System, University of Toronto, Toronto, Ontario, Canada. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjd.2019.05.012DOI Listing
March 2020
-->