Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial.

INTRODUCTION: Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism. METHODS: PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m2. RESULTS: At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m2 from baseline (P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m2. In participants with baseline eGFR < 60 mL/min/1.73 m2, 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m2 (P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide. CONCLUSION: In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT04701203.

Chronic hypoparathyroidism is caused by inadequate parathyroid hormone (PTH) levels. Hypoparathyroidism is managed with conventional therapy (active vitamin D and calcium), but over time the disease itself and conventional therapy can increase the risk of medical complications including kidney problems. This study looked at how a new treatment for chronic hypoparathyroidism, palopegteriparatide (approved in the European Union under the brand name YORVIPATH^®), affects kidney function in adults in the PaTHway clinical trial. Participants were randomly assigned to receive palopegteriparatide or a placebo injection once daily along with conventional therapy. For both groups, clinicians used a protocol to eliminate conventional therapy while maintaining normal blood calcium levels. After 26 weeks, participants on placebo switched to palopegteriparatide. Ninety-five percent of participants were still enrolled in the PaTHway trial after 52 weeks. Of those, 86% had normal blood calcium levels and 95% did not need conventional therapy (not taking vitamin D and not taking therapeutic doses of calcium [> 600 mg/day]). After 52 weeks of treatment with palopegteriparatide, significant improvements were seen in a measure of kidney function called estimated glomerular filtration rate (eGFR). Improvements in eGFR from the beginning of the trial to week 52 were considered clinically meaningful for over 57% of participants. In participants with impaired kidney function at the beginning of the trial, eGFR improvements were even greater, and 74% of participants had a clinically meaningful improvement. These results suggest that palopegteriparatide treatment may be beneficial for kidney function in adults with chronic hypoparathyroidism, especially those with impaired kidney function.

Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1-84) in hypoparathyroidism.

Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 µg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 yr; 81.8% were women, and 90.9% were White. By the end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-h urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402-855 mg/d and 0.8-0.2 µg/d, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2-5 fold from baseline to EOT. The HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1-84) once daily for 1 yr improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings. Clinical trial identifier: NCT03364738.

Advanced glycation end products are not associated with bone mineral density, trabecular bone score, and bone turnover markers in adults with and without type 1 diabetes: a cross-sectional study.

It is unclear if AGEs are involved in the bone fragility of type 1 diabetes (T1D). We evaluated whether skin AGEs by skin autofluorescence and serum AGEs (pentosidine, carboxymethyl-lysine [CML]) are independently associated with BMD by DXA (lumbar spine, hip, distal radius), trabecular bone score (TBS), serum bone turnover markers (BTMs: CTX; P1NP; osteocalcin), and sclerostin in participants with and without T1D. Linear regression models were used, with interaction terms to test effect modification by T1D status. In participants with T1D, correlations between skin and serum AGEs as well as between AGEs and 3-year HbA1C were evaluated using Spearman's correlations. Data are mean ± SD or median (interquartile range). We included individuals who participated in a cross-sectional study and had BMD and TBS assessment (106 T1D/65 controls, 53.2% women, age 43 ± 15 yr, BMI 26.6 ± 5.5 kg/m2). Participants with T1D had diabetes for 27.6 ± 12.3 yr, a mean 3-yr HbA1C of 7.5 ± 0.9% and skin AGEs of 2.15 ± 0.54 arbitrary units. A subgroup of 65 T1D/57 controls had BTMs and sclerostin measurements, and those with T1D also had serum pentosidine (16.8[8.2-32.0] ng/mL) and CML [48.0 ± 16.8] ng/mL) measured. Femoral neck BMD, TBS, and BTMs were lower, while sclerostin levels were similar in participants with T1D vs controls. T1D status did not modify the associations between AGEs and bone outcomes. Skin AGEs were significantly associated with total hip and femoral neck BMD, TBS, BTMs, and sclerostin before, but not after, adjustment for confounders. Serum AGEs were not associated with any bone outcome. There were no significant correlations between skin and serum AGEs or between AGEs and 3-yr HbA1C. In conclusion, skin and serum AGEs are not independently associated with BMD, TBS, BTMs, and sclerostin in participants with relatively well-controlled T1D and participants without diabetes.

Metabolic-associated fatty liver disease is characterized by a post-oral glucose load hyperinsulinemia in individuals with mild metabolic alterations.

Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remain unclear. We compared the glucose metabolism, insulin resistance, insulin secretion, and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a body mass index (BMI) between 25 and 40 kg/m2 and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5-6.9 mmol/L, or glycated hemoglobin 5.7-5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3 h 75 g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic ß-cell function. Fifty percent of participants had MAFLD. Median age (IQR) [57 (45-65) vs. 57 (44-63) yr] and sex (60% vs. 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group (P < 0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity, and first-phase pancreatic ß-cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI (P < 0.02). Among individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance while exhibiting lower first phase ß-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede T2D.NEW & NOTEWORTHY Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic ß-cell function in individuals with MAFLD. This may explain part of the increased risk of incident type 2 diabetes in this population. These data also highlight implications of hyperinsulinemia and impaired insulin clearance in the progression of MAFLD to type 2 diabetes.

Prevalence and determinants of hypertension in the adult Inuit population of Nunavik (northern Quebec, Canada).

OBJECTIVES: To assess the prevalence of arterial hypertension among Inuit adults living in Nunavik (northern Quebec, Canada) in 2017 and identify its sociodemographic and lifestyle determinants. METHODS: We used data obtained from 1177 Inuit adults aged ≥ 18 years who participated in the cross-sectional Qanuilirpitaa? Nunavik Inuit Health Survey during late summer-early fall of 2017. Resting blood pressure (BP) and anthropometric characteristics were measured during a clinical session, while sociodemographic characteristics and lifestyle habits were documented using validated questionnaires. Information on current medication was retrieved from medical files. Sex-stratified population-weighted log-binomial regressions were conducted to identify determinants of hypertension, adjusting for potential confounders. RESULTS: Hypertension (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mmHg or taking antihypertensive medication) was present in 23% of the adult population and was more frequent in men than women (29% vs. 18%). About a third of hypertensive individuals (34%) were taking antihypertensive medication. These estimates are prone to biases due to the relatively low participation rate (37%). As expected, the prevalence of hypertension increased with age, but values were surprisingly elevated in 18 to 29-year-old men and women (18% and 8%, respectively) compared with 20 to 39-year-old adults of the general Canadian population (3% in both sexes, according to data from the Canadian Health Measures Survey, 2012-2015). Hypertension was associated with obesity and alcohol consumption in both men and women, and with higher socioeconomic status among men. CONCLUSION: This survey revealed a high prevalence of hypertension among young Nunavimmiut adults in 2017 and the need to improve hypertension diagnosis and treatment in the region. Curbing obesity and alcohol consumption, two actionable determinants of hypertension, will require improving food security and addressing the consequences of historical trauma linked to colonization.

RéSUMé: OBJECTIF: Mesurer la prévalence de l'hypertension artérielle chez les adultes vivant au Nunavik (Nord du Québec, Canada) en 2017 et identifier les caractéristiques sociodémographiques et les habitudes de vie qui lui sont associées. MéTHODES: Les données ont été recueillies chez 1177 adultes ≥ 18 ans ayant participé à l'enquête de santé Qanuilirpitaa? auprès des Inuit du Nunavik à la fin de l'été et au début de l'automne 2017. Lors d'une visite en clinique, la tension artérielle au repos et les caractéristiques anthropométriques ont été mesurées, puis des informations concernant les caractéristiques sociodémographiques et les habitudes de vie ont été recueillies à l'aide de questionnaires validés. Une revue des dossiers médicaux a permis de documenter la prise de médicaments antihypertenseurs. Nous avons utilisé des modèles de régression log-binomiale, pondérés pour la population et ajustés pour les co-variables d'intérêt afin d'identifier les déterminants de l'hypertension chez chaque sexe. RéSULTATS: La prévalence globale de l'hypertension était de 23 % et était plus élevée chez les hommes que chez les femmes (29 % vs. 18 %). Le tiers des hypertendus (34 %) recevait une médication antihypertensive. Ces estimés pourraient être biaisés puisque le taux de participation à l'enquête était relativement faible (37 %). Tel qu'attendu, la prévalence d'hypertension était associée à l'âge, mais des valeurs étonnamment élevées ont été notées chez les jeunes hommes et femmes âgés de 18 à 29 ans (18 % et 8 %, respectivement), comparativement aux jeunes adultes âgés de 20 à 39 ans de la population générale canadienne (3 % chez les deux sexes, selon les données de l'Enquête canadienne sur les mesures de santé, 2012­2015). Des associations avec l'obésité et la consommation d'alcool ont été notées chez les deux sexes. On a de plus observé une association avec le statut socio-économique plus élevé chez les hommes seulement. CONCLUSION: Cette étude a révélé une prévalence élevée d'hypertension chez les jeunes Inuit d'âge adulte résidant au Nunavik et un besoin d'améliorer le diagnostic et le traitement de la maladie dans cette région. Elle a de plus permis d'identifier deux facteurs de risque modifiables de l'hypertension dans cette population, soit l'obésité et la consommation d'alcool. Agir sur ces déterminants au Nunavik requiert l'amélioration de la sécurité alimentaire et l'atténuation des conséquences liées aux traumatismes découlant de la colonisation.

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

Comparison of Intranasal and Injectable Glucagon Administration Among Pediatric Population Responders.

Aims: Ease of use and acceptability of nasal versus injectable glucagon (IG) among pediatric responders have been little investigated. This study compared the performance of administering nasal and IG in parents of youth with type 1 diabetes (T1D) and in school workers. Enablers and barriers associated with each glucagon and preferred glucagon administration learning modality were also evaluated. Methods: Three months after watching short pedagogical videos, 30 parents and 30 school workers performed simulated scenarios where they administered both glucagon. Completion time and successful execution of critical steps were collected. Interviews assessed preferred learning modalities, barriers, and enablers associated with each glucagon. Results: Both groups administered nasal glucagon faster than IG (median [interquartile range]: parents 19 [12-29] vs. 97 [71-117] s, P < 0.001; school workers 24 [16-33] vs. 129 [105-165] s, P < 0.001). A lower proportion of participants successfully executed all critical steps for injectable versus nasal glucagon (significant difference for school workers [53% vs. 90%; P = 0.007] but not for parents [68% vs. 83%; P = 0.227]). Nasal glucagon was preferred for ease of use and acceptability. Preferred learning modalities were a combination of videos and workshops, but videos alone could suffice for nasal glucagon. Conclusions: Nasal glucagon is faster to use, more likely to be successfully administered, and more acceptable than IG for parents of children with T1D and school workers. Nasal glucagon training with videos could improve school workers' involvement in severe hypoglycemia management. Clinical Trial number, URL to the registration: NCT05395000, https://clinicaltrials.gov/ct2/show/NCT05395000.

Added value of waist circumference to body mass index for predicting fracture risk in obesity: a prospective study from the CARTaGENE cohort.

Larger waist circumference is significantly associated with an increased risk of distal lower limb fractures in individuals aged 40-70 years with a body mass index within the normal or overweight category. Therefore, waist circumference provides additive information to body mass index for the identification of individuals at risk of obesity-related fractures. INTRODUCTION: Waist circumference (WC) is a stronger risk factor of metabolic disorders than body mass index (BMI), but whether it holds true for fracture risk prediction remains unclear. We aimed to evaluate relationships between WC and fracture incidence within BMI categories and evaluate whether BMI modifies these relationships. METHODS: Men and women aged 40-70 years from the CARTaGENE cohort were divided by BMI category at baseline: normal weight, overweight, and obesity. Incident fractures were identified over 7 years via linkage with healthcare administrative databases. Cox proportional hazard models estimated the relationships between WC and incident fractures at any site and by skeletal site within each BMI category. Results are reported as adjusted hazard ratios (95% confidence intervals) per 10 cm increase in WC. Effect modification was evaluated qualitatively by comparing relationships between BMI categories. RESULTS: Of the 18 236 individuals included, 754 sustained a fracture. Significant relationships were found between WC and distal lower limb fractures in the normal (1.25 [1.08, 1.45]) and overweight (1.28 [1.07, 1.52]) BMI categories, but not in the obesity category. In the overweight category, we found an increased risk of distal upper limb fractures with increasing WC (1.49 [1.04, 2.15]). No significant relationship was observed regarding WC and fracture risk at any site or major osteoporotic fractures. An effect modification of BMI on the relationships between WC and distal lower limb fractures was observed. CONCLUSION: WC provides both independent and additive information to BMI for the identification of individuals at risk of obesity-related fractures.

Relationships between Obesity and Incidence of Fractures in a Middle-Aged Population: A Study from the CARTaGENE Cohort.

The association between obesity and fracture risk is complex and may vary by definition of obesity, skeletal site, and sex. We aimed to evaluate the relationships between obesity, defined using body mass index (BMI) or waist circumference (WC), and fracture incidence at any site and by skeletal site (i.e., major osteoporotic fractures [MOFs], distal lower limb fractures [tibia, ankle, feet], and distal upper limb fractures [forearm/elbow, wrist]). The secondary aim was to assess the aforementioned relationships by sex. We used CARTaGENE, a large population-based cohort of individuals aged 40-70 years from Quebec, Canada, who were assessed in 2009-2010. Incident fractures were identified via linkage with healthcare administrative databases over a 7-year period. Cox proportional hazard models adjusted for several potential confounders were used to estimate the relationships, with exposures treated as continuous variables. Results are reported as adjusted hazard ratios (aHRs) and 95% confidence intervals. We identified 19 357 individuals (mean ± standard deviation: age 54 ± 8 years, BMI 27 ± 5 kg/m2, WC 94 ± 14 cm; 51.6% women). During follow-up, 497 women and 323 men sustained a fracture. There was a linear relationship between fracture incidence and WC, while cubic splines best fitted the relationship for BMI. Greater WC was associated with an increased risk of fracture at the distal lower limbs in the whole cohort and in the subgroup of women: aHR for each 10 cm increased in WC of 1.12 (1.03, 1.21) and 1.12 (1.01, 1.24), respectively. In men, WC was not significantly associated with any fracture outcome. Higher BMI was also significantly associated with distal lower limb fracture risk in the whole cohort (p = 0.018). No significant relationships were found between either WC or BMI and the risk of any fracture, MOFs, and distal upper limb fractures. In middle-aged individuals, obesity, and mainly abdominal obesity, was associated with distal lower limb fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

First-trimester diet quality in association with maternal subcutaneous and visceral adipose tissue thicknesses and glucose homeostasis during pregnancy.

We aimed to characterise the associations between first-trimester diet quality, adiposity, and glucose homeostasis measurements throughout pregnancy in a sample of 104 healthy pregnant women. Three Web-based 24-h recalls were completed, from which the Alternate Healthy Eating Index (AHEI) was calculated. At each trimester (12.5 ± 0.7, 22.8 ± 1.0, and 33.6 ± 1.3 weeks of gestation), fasting glucose and insulin were measured to compute an insulin resistance index (HOMA-IR). Subcutaneous and visceral adipose tissue thicknesses were estimated by ultrasound at the end of the first trimester. Inverse associations were observed between the first-trimester AHEI and first-trimester fasting insulin (r = 0.24; p < 0.05), and HOMA-IR (r = -0.22; p < 0.05), as well as third-trimester fasting insulin (r = -0.20; p < 0.05). A trend was also observed between first-trimester AHEI and first-trimester SAT thickness (r = -0.17; p < 0.1). Pre- and early-pregnancy adiposity measurements were identified as high predictors fasting insulin concentrations throughout pregnancy. Higher early-pregnancy diet quality is associated with more favourable metabolic measurements during pregnancy.

Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial.

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 µg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Impact of glycemic variability on cognitive impairment, disordered eating behaviors and self-management skills in patients with type 1 diabetes: study protocol for a cross-sectional online study, the Sugar Swing study.

BACKGROUND: People living with type 1 diabetes (PWT1D) are at increased risk for impairments in brain function, which may impact on daily life. Cognitive impairments in PWT1D might contribute to increasing eating disorders, reducing self-management skills, and deteriorating glycemic control. Glycemic variability may be a key determinant of disordered eating behaviors, as well as of cognitive impairments. The main objective of this study is to better understand the impact of glycemic variability in disordered eating behaviors and cognitive impairment, and its consequences on self-management skills in PWT1D. METHOD: We aim to recruit 150 PWT1D with 50% of men and women in this cross-sectional study. Participants will record their glycemic variability over a 10-day period using a continuous glucose monitoring system (CGMS) and track their dietary intakes using image-assisted food tracking mobile application (2 days). Over four online visits, eating behaviors, diabetes self-management's skills, anxiety disorders, depression disorder, diabetes literacy and numeracy skills, cognitive flexibility, attention deficit, level of interoception, and impulsivity behaviors will be assessed using self-reported questionnaires. Cognitive functions (i.e., attention, executive functions, impulsivity, inhibition and temporal discounting), will be measured. Finally, medical, biological and sociodemographic data will be collected. To further our understanding of the PWT1D experience and factors impacting glycemic self-management, 50 PWT1D will also participate in the qualitative phase of the protocol which consist of individual in-depth face-to-face (virtual) interviews, led by a trained investigator using a semi-structured interview. DISCUSSION: This study will contribute to highlighting the consequences of blood sugar fluctuations (i.e., "sugar swings"), in daily life, especially how they disrupt eating behaviors and brain functioning. A better understanding of the mechanisms involved could eventually allow for early detection and management of these problems. Our study will also seek to understand the patients' point of view, which will allow the design of appropriate and meaningful recommendations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05487534. Registered 4 August 2022.

Trimester-Specific Serum Fructosamine in Association with Abdominal Adiposity, Insulin Resistance, and Inflammation in Healthy Pregnant Individuals.

This study aimed to (1) characterize the variations in serum fructosamine across trimesters and according to pre-pregnancy BMI (ppBMI), and (2) examine associations between fructosamine and adiposity/metabolic markers (ppBMI, first-trimester adiposity, leptin, glucose homeostasis, and inflammation measurements) during pregnancy. Serum fructosamine, albumin, fasting glucose and insulin, leptin, adiponectin, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were measured at each trimester. In the first trimester, subcutaneous (SAT) and visceral (VAT) adipose tissue thicknesses were estimated by ultrasound. In the 101 healthy pregnant individuals included (age: 32.2 ± 3.5 y.o.; ppBMI: 25.5 ± 5.5 kg/m2), fructosamine concentrations decreased during pregnancy whereas albumin-corrected fructosamine concentrations increased (p < 0.0001 for both). Notably, fructosamine concentrations were inversely associated with ppBMI, first-trimester SAT, VAT, and leptin (r = −0.55, r = −0.61, r = −0.48, r = −0.47, respectively; p < 0.0001 for all), first-trimester fasting insulin and HOMA-IR (r = −0.46, r = −0.46; p < 0.0001 for both), and first-trimester IL-6 (r = −0.38, p < 0.01). However, once corrected for albumin, most of the correlations lost strength. Once adjusted for ppBMI, fructosamine concentrations were positively associated with third-trimester fasting glucose and CRP (r = 0.24, r = 0.27; p < 0.05 for both). In conclusion, serum fructosamine is inversely associated with adiposity before and during pregnancy, with markers of glucose homeostasis and inflammation, but the latter associations are partially influenced by albumin concentrations and ppBMI.

Perceptions of fracture and fall risk and of the benefits and barriers to exercise in adults with diabetes.

The increased risk of fractures and falls is under-appreciated by adults living with diabetes and by their healthcare providers. Strategies to overcome perceived exercise barriers and exercise programs optimized for bone health should be implemented. PURPOSE: The purpose of the study was to assess the perceptions of fracture and fall risk, and the perceived benefits of and barriers to exercise in adults ≥ 50 years old living with type 1 (T1D) and type 2 diabetes (T2D). METHODS: Participants were recruited through social media and from medical clinics and invited to complete a self-administered online survey, comprising 38 close-ended questions and 4 open-ended questions. RESULTS: A total of 446 participants completed the survey: 38% T1D, 59% T2D, and 3% with unreported diabetes type. Most participants did not believe that having diabetes increased their risk of fractures (81%) nor falls (68%), and more than 90% reported having not been informed about diabetes-related fracture risk by their physicians. Among exercise types, participation in moderate aerobic exercise was most common (54%), while only 31%, 32%, and 37% of participants engaged in strenuous aerobic, resistance, and balance/flexibility exercise, respectively. The most prevalent barrier to exercise for both T1D and T2D was a lack of motivation, reported by 54% of participants. Lack of time and fear of hypoglycemia were common exercise barriers reported by participants with T1D. Most participants owned a smart phone (69%), tablet (60%), or computer (56%), and 46% expressed an interest in partaking in virtually delivered exercise programs. CONCLUSIONS: Adults living with diabetes have limited awareness of increased fall and fracture risk. These risks are insufficiently highlighted by health care providers; strategies to overcome perceived exercise barriers and exercise programs optimized for bone health should be implemented.

Self-reported Severe and Nonsevere Hypoglycemia in Type 1 Diabetes: Population Surveillance Through the BETTER Patient Engagement Registry: Development and Baseline Characteristics.

OBJECTIVES: The BETTER (BEhaviors, Therapies, TEchnologies and hypoglycemic Risk in Type 1 diabetes) registry is a type 1 diabetes population surveillance system codeveloped with patient partners to address the burden of hypoglycemia and assess the impact of new therapies and technologies. The aim of this report was to describe the baseline characteristics of the BETTER registry cohort. METHODS: A cross-sectional baseline evaluation was performed of a Canadian clinical cohort established after distribution of an online questionnaire. Participants were recruited through clinics, public foundations, advertising and social media. As of February 2021, 1,430 persons ≥14 years of age and living with type 1 diabetes or latent-autoimmune diabetes (LADA) were enrolled. The trial was registered on ClinicalTrials.gov (NCT03720197). RESULTS: Participants were (mean ± standard deviation) 41.2±15.7 years old with a diabetes duration of 22.0±14.7 years, 62.0% female, 92.1% Caucasian and 7.8% self-reporting as LADA, with 40.9% using a continuous subcutaneous insulin infusion (CSII) system and 78.0% using a continuous glucose monitoring (CGM) system. The most recent glycated hemoglobin ≤7% was reported by 29.7% of participants. At least 1 episode of hypoglycemia <3.0 mmol/L (level 2-H) in the last month was reported by 78.4% of participants, with a median (interquartile range) of 5 (3, 10) episodes. The occurrence of severe hypoglycemia (level 3-H) in the last 12 months was reported by 13.3% of participants. Among these, the median number of episodes was 2 (1, 3). CONCLUSIONS: We have established the first surveillance registry for people living with type 1 diabetes in Canada relying on patient-reported outcomes and experiences. Hypoglycemia is a highly prevalent burden despite a relatively wide adoption of CSII and CGM use.

Bone Marrow Adiposity, Bone Mineral Density and Wnt/ß-catenin Pathway Inhibitors Levels in Hemodialysis Patients.

BACKGROUND: Marrow adipose tissue (MAT) is known to accumulate in patients with chronic kidney disease. This pilot study aimed to evaluate bone mineral density (BMD), MAT, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) using computed tomography (CT) scans and to explore correlations between bone parameters, circulating Wnt/ß-catenin pathway inhibitor levels, and adipose tissue parameters. METHODS: Single-center cross-sectional pilot study conducted in hemodialysis patients at the Centre Universitaire de Québec, Hôtel-Dieu de Québec hospital, Canada. CT-scan slices were acquired at the levels of the hip, L3 vertebra, and tibia. Volumetric and areal BMD, tibia cortical thickness, VAT and SAT area, and fat marrow index (FMI) were analyzed using the Mindways QCT Pro software. Blood levels of sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor 23, and α-Klotho were assessed. Spearman's rho test was used to evaluate correlations. RESULTS: Fifteen hemodialysis patients (median age, 75 [66-82] years; 80% male; dialysis vintage, 39.3 [27.4-71.0] months) were included. While inverse correlations were obtained between L3 FMI and BMD, positive correlations were found between proximal tibial FMI and vertebral and tibial BMD, as well as with tibial (proximal and distal) cortical thickness. VAT had a positive correlation with α-Klotho levels, whereas L3 FMI had a negative correlation with DKK1 levels. CONCLUSIONS: CT-scan allows simultaneous evaluation of bone and marrow adiposity in dialysis patients. Correlations between MAT and BMD vary depending on the bone site evaluated. DKK1 and α-Klotho levels correlate with adipose tissue accumulation in dialysis patients.

Dietary intakes in pregnant women with previous bariatric surgery.

PURPOSE: To (1) assess dietary intakes of pregnant women with previous bariatric surgery in comparison with Dietary Reference Intakes (DRIs); (2) compare their dietary intakes as well as their diet quality with a control group of pregnant women with no history of bariatric surgery. METHODS: Twenty-eight (28) pregnant women with previous surgery (sleeve gastrectomy, n = 7 and biliopancreatic diversion with duodenal switch, n = 21) were matched for pre-pregnancy body mass index with 28 pregnant women with no history of bariatric surgery. In at least one trimester, participants completed a minimum of 2 Web-based 24-h dietary recalls from which energy, macro- and micronutrient intakes as well as the Canadian Healthy Eating Index (C-HEI) were derived. RESULTS: No differences were observed for energy intake between groups. All women had protein intakes within the recommended range, but most women with previous surgery had carbohydrate (67%) and dietary fiber intakes (98%) below recommendations. In both groups, mean total fat, saturated fatty acids, free sugars and sodium intakes were above recommendations, as opposed to mean vitamin D, folic acid and iron dietary intakes below recommendations for most women. Compared with the control group, pregnant women with previous bariatric surgery had lower overall C-HEI scores. CONCLUSION: These results suggest that pregnant women with previous bariatric surgery would benefit from a nutritional follow-up throughout their pregnancy. LEVEL OF EVIDENCE: III: Evidence obtained from well-designed cohort or case-control analytic studies.

Prevalence of Vertebral Fractures in Adults With Type 1 Diabetes: DenSiFy Study (Diabetes Spine Fractures).

CONTEXT: Vertebral fracture (VF) prevalence up to 24% has been reported among young people with type 1 diabetes (T1D). If this high prevalence is confirmed, individuals with T1D could benefit from preventative VF screening. OBJECTIVE: We compared the prevalence of VFs between adults with T1D and nondiabetic controls. METHODS: This cross-sectional study included 127 adults with T1D, and 65 controls with a similar age, sex, and BMI distribution, from outpatient clinics of 2 tertiary care centers. Vertebral fracture assessment (VFA) by dual-energy x-ray absorptiometry (DXA) was used for prevalent VFs. The modified algorithm-based qualitative (mABQ) method was applied. Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by DXA. Serum bone turnover markers and sclerostin were measured in a subgroup of participants. RESULTS: Participants with T1D (70 women, 57 men) had a mean age of 42.8 ±â€…14.8 years, median diabetes duration of 25.8 (15.8-34.4) years, mean BMI of 26.6 ±â€…5.4 kg/m2 and mean HbA1c over the past 3 years of 7.5 ±â€…0.9%. Controls (35 women, 30 men) had mean age of 42.2 ±â€…15.9 years and mean BMI of 26.1 ±â€…5.1 kg/m2. VF prevalence was comparable between groups (2.4% vs 3.1%, P = 0.99). TBS, BMD at the total hip and femoral neck, and bone formation and resorption markers were lower while sclerostin levels were similar in participants with T1D vs controls. CONCLUSION: Our VFA results using the mABQ method do not confirm increased prevalence of VFs in men and women with relatively well-controlled T1D.