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.

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.

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.

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.

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.

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.

Longitudinal Assessment of Vitamin D Status across Trimesters of Pregnancy.

BACKGROUND: The evolution of vitamin D status across pregnancy trimesters and its association with prepregnancy body mass index (ppBMI; in kg/m2) remain unclear. OBJECTIVES: We aimed to 1) assess trimester-specific serum total 25-hydroxyvitamin D [25(OH)D] concentrations, 2) compare those concentrations between ppBMI categories, and 3) examine associations between 25(OH)D concentrations, ppBMI, and vitamin D intake. METHODS: As part of a prospective cohort study, 79 pregnant women with a mean age of 32.1 y and ppBMI of 25.7 kg/m2 were recruited in their first trimester (average 9.3 weeks of gestation). Each trimester, vitamin D intake was assessed by 3 Web-based 24-h recalls and a Web questionnaire on supplement use. Serum total 25(OH)D was measured by LC-tandem MS. Repeated-measures ANOVA was performed to assess the evolution of 25(OH)D concentrations across trimesters of pregnancy and comparisons of 25(OH)D concentrations between ppBMI categories were assessed by 1-factor ANOVAs. Stepwise regression analyses were used to identify determinants of 25(OH)D concentrations in the third trimester. RESULTS: Mean ± SD serum total 25(OH)D concentrations increased across trimesters, even after adjustments for ppBMI, seasonal variation, and vitamin D intake from supplements (67.5 ± 20.4, 86.5 ± 30.9, and 88.3 ± 29.0 nmol/L at mean ± SD 12.6 ± 0.8, 22.5 ± 0.8, and 33.0 ± 0.6 weeks of gestation, respectively; P < 0.0001). In the first and third trimesters, women with a ppBMI ≥30 had lower serum total 25(OH)D concentrations than women with a ppBMI <25 (P < 0.05); however, most had concentrations >40nmol/L by the second trimester. Vitamin D intake from supplements was the strongest determinant of third-trimester serum total 25(OH)D concentrations (r2 = 0.246, ß = 0.51; P < 0.0001). CONCLUSIONS: There was an increase in serum total 25(OH)D concentrations across trimesters, independent of ppBMI, seasonal variation, and vitamin D intake from supplements. Almost all women had serum total 25(OH)D concentrations over the 40- and 50-nmol/L thresholds, thus our study supports the prenatal use of a multivitamin across pregnancy.

Cholecalciferol Supplementation Does Not Prevent the Development of Metabolic Syndrome or Enhance the Beneficial Effects of Omega-3 Fatty Acids in Obese Mice.

BACKGROUND: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood. OBJECTIVES: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. METHODS: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. RESULTS: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa. CONCLUSIONS: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.

Dairy product intake modifies gut microbiota composition among hyperinsulinemic individuals.

PURPOSES: The objectives of this study were to investigate differences in gut microbiota (GM) composition after high dairy intake (HD) compared to adequate dairy intake (AD) and to correlate GM composition variations with the change in glycemic parameters in hyperinsulinemic subjects. METHODS: In this crossover study, 10 hyperinsulinemic adults were randomized to HD (≥ 4 servings/day) or AD (≤ 2 servings/day) for 6 weeks, separated by a 6-week washout period. Fasting insulin and glucose levels were measured after each intervention. Insulin resistance was calculated with the homeostasis model assessment of insulin resistance (HOMA-IR). GM was determined with 16S rRNA-based high-throughput sequencing at the end of each intervention. Paired t test, correlations and machine learning analyses were performed. RESULTS: Endpoint glycemic parameters were not different between HD and AD intake. After HD compared with AD intake, there was a decrease in the abundance of bacteria in Roseburia and Verrucomicrobia (p = 0.04 and p = 0.02, respectively) and a trend for an increase abundance in Faecalibacteria and Flavonifractor (p = 0.05 and p = 0.06, respectively). The changes in abundance of Coriobacteriia, Erysipelotrichia, and Flavonifractor were negatively correlated with the change in HOMA-IR between the AD and HD phases. Furthermore, a predictive GM signature, including Anaerotruncus, Flavonifractor, Ruminococcaceae, and Subdoligranulum, was related to HOMA-IR. CONCLUSION: Overall, these results suggest that HD modifies the abundance of specific butyrate-producing bacteria in Firmicutes and of bacteria in Verrucomicrobia in hyperinsulinemic individuals. In addition, the butyrate producing bacteria in Firmicutes phylum correlate negatively with insulin resistance.

Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and ß-cell function.

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes (n = 132), ucOCN correlated negatively with fasting glucose (r = -0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = -0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity (n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = -0.50, P = 0.046) and glycated hemoglobin (r = -0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp (P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and ß-cell dysfunction in humans.

Do pregnant women eat healthier than non-pregnant women of childbearing age?

We aimed to compare the dietary quality and intake of pregnant women, women planning to conceive and women of childbearing age. Fifty-five pregnant women were matched for age and pre-pregnancy body mass index with 55 women planning to conceive and 55 women of childbearing age. Three Web-based 24-h recalls were completed, from which the Canadian Healthy Eating Index was calculated. Pregnant women had greater overall diet quality scores (66.8 ± 10.7, 60.3 ± 14.1 and 61.4 ± 12.8, in pregnant vs. planning to conceive and childbearing age women, p = .009), explained by a higher intake in fruits, vegetables and grain products and lower intake of foods that are high in fat, sugar or salt. Energy intake was significantly higher in pregnant versus planning to conceive women only (2283 ± 518 vs. 2062 ± 430 kcal, p = .03). Diet quality was greater among pregnant women, but diet quality scores were low in all groups, indicating that healthier dietary behaviours should be encouraged for all childbearing age women.

Acute Effects of Single Doses of Bonito Fish Peptides and Vitamin D on Whole Blood Gene Expression Levels: A Randomized Controlled Trial.

Fish contains high quality proteins and essential nutrients including 25-hydroxyvitamin D (25(OH)D). Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and studies have shown an association between 25(OH)D deficiency, CVD and CVD risk factors, such as diabetes. This study investigated acute effects of a single dose of cholecalciferol (VitD3), bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. A randomized, crossover, placebo controlled trial was conducted in 22 adults. They ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3 g of BPH, a combination of both, or a placebo. A 180 min oral glucose tolerance test was performed. Differences in whole-genome expression levels after versus before each supplementation were computed for 18 subjects. We observed that 16, 1 and 5 transcripts were differentially expressed post- vs. pre-ingestion for VitD3, BPH or VitD3 + BPH treatments, respectively. VitD3-containing treatments affected the expression of the solute carrier family 25 member 20 (SLC25A20) gene involved in fatty acid oxidation, various transcription factors and genes related to glucose metabolism. These results suggest that VitD3 rapidly modulates genes related to CVD risk factors in blood while BPH seems to moderately modulate gene expression levels.

Disparities in the timing and measurement methods to assess vitamin D status during pregnancy: A Narrative Review.

Studies that examined associations between low circulating 25-hydroxyvitamin D (25(OH)D) and adverse pregnancy outcomes used various designs, assay methods and time points for measurement of 25(OH)D concentrations, which creates some confusion in the current literature. We aimed to investigate the variability in the timing and measurement methods used to evaluate vitamin D status during pregnancy. Analysis of 198 studies published between 1976 and 2017 showed an important variability in the choice of 1) threshold values for 25(OH)D insufficiency or deficiency, 2) 25(OH)D measurement methods, and 3) trimester in which 25(OH)D concentrations were measured. Blood samples were taken once during pregnancy in a large majority of studies, which may not be representative of vitamin D status throughout pregnancy. Most studies reported adjustment for confounding factors including season of blood sampling, but very few studies used the 25(OH)D gold standard assay, the LC-MS/MS. Prospective studies assessing maternal 25(OH)D concentrations 1) by standardized and validated methods, 2) at various time points during pregnancy, and 3) after considering potential confounding factors, are needed.

The increase in serum 25-hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and ß-cell function.

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (ß-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m(2) were divided based on weight loss at 1 year: < 5% (non-responders, n 56) and ≥ 5% (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9.5% of their weight when compared with non-responders who lost only 0.8% of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P = 0.0003) and disposition index (P = 0.02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8.9 (SD 12.5) v. 3.6 (SD 10.7) nmol/l, P = 0.05). However, it had not been associated with amelioration of insulin sensitivity and ß-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or ß-cell function.

Clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury: a systematic review.

OBJECTIVES: To assess the clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury. DATA SOURCES: We searched Medline, Embase, Cochrane Registry, BIOSIS, and Trip Database up to February 2012 and consulted bibliographies of narrative reviews and selected articles. STUDY SELECTION: We included cohort, case-control, cross-sectional studies and randomized trials enrolling at least five adults with blunt traumatic brain injury in whom at least one anterior pituitary axis was assessed. We excluded case series and studies in which other neurological conditions were indistinguishable from traumatic brain injury. DATA EXTRACTION: Two independent reviewers selected citations, extracted data, and assessed the risk of bias using a standardized form. DATA SYNTHESIS: We performed meta-analyses using random effect models and assessed heterogeneity using the I index. RESULTS: We included 66 studies (5,386 patients) evaluating prevalence, 14 evaluating clinical outcomes, and 27 evaluating predictors. Thirty studies were at low risk of bias. Anterior pituitary disorders were associated with a trend toward increased ICU mortality (risk ratio, 1.79; 95% CI, 0.99-3.21; four studies) and no difference in Glasgow Outcome Scale score (mean difference, -0.45; 95% CI, -1.10 to 0.20; three studies). Age (mean difference, 3.19; 95% CI, 0.31-6.08; 19 studies), traumatic brain injury severity (risk ratio, 2.15; 95% CI, 1.20-3.86 for patients with severe vs nonsevere traumatic brain injury; seven studies), and skull fractures (risk ratio, 1.73; 95% CI, 1.03-2.91; six studies) predicted anterior pituitary disorders. Over the long term, 31.6% (95% CI, 23.6-40.1%; 27 studies) of patients had at least one anterior pituitary disorder. We observed significant heterogeneity that was not solely explained by the risk of bias or traumatic brain injury severity. CONCLUSIONS: Approximately one third of traumatic brain injury patients have persistent anterior pituitary disorder. Older age, traumatic brain injury severity, and skull fractures predict anterior pituitary disorders, which in turn may be associated with higher ICU mortality. Further high-quality studies are warranted to better define the burden of anterior pituitary disorders and to identify high-risk patients.

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.

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.

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.