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.

Psychosocial determinants of healthy sleep habits in adults with type 1 and type 2 diabetes.

Background: Many adults with type 1 (T1D) and type 2 diabetes (T2D) have inadequate sleep increasing their risk of hyperglycemia and developing complications. The objective was to identify psychosocial determinants of healthy sleep habits (HSH) among adults with T1D and T2D. Methods: The two HSH were: avoiding screen use in bed and having sleep regularity. Adults (≥18 years) with T1D and T2D were invited to complete an anonymous online survey. The questionnaires were based on the Reasoned Action Approach and formative qualitative research previously conducted in 56 adults with T1D and T2D. Habit was included as an additional variable for screen use in bed. Results: In total, 320 adults with diabetes (T1D: 39%; T2D: 61%) completed the questionnaires (screen use in bed: 174; sleep timing: 146). Close to 75% of participants reported screen use in bed and close to 90% reported sleep timing variability in the last month. Perceived behavioral control (PBC) to avoid screen use in bed (ß = -0.4486, p < 0.0001), habit of using screens in bed (ß = 0.4002; p < 0.0001), and age (ß = -0.0202; p = 0.0086) were determinants of screen use in bed, and this model explained 71% of the variance. PBC for sleep regularity (ß = -0.2909; p = 0.0004) and being female (ß = 0.5057; p = 0.0069) were determinants of sleep timing variability, and this model explained 28% of the variance. The most important beliefs associated with each HSH were identified to obtain information to design targeted interventions. Conclusions: Few adults with diabetes have HSH. Screen use in bed was strongly influenced by habit and the results suggest that both HSH are not easy to adopt among adults with diabetes. Younger adults with diabetes should be prioritized for screen use in bed, while females with diabetes should be prioritized for sleep timing variability. Adults with diabetes should have access to behavior change interventions to encourage them to adopt HSH.

Association between Beverage Consumption and Sleep Quality in Adolescents.

The objective of this study was to verify if the consumption of different beverages (such as water, 100% pure fruit juice, and sugar-sweetened beverages (SSBs)) is associated with adolescents' sleep quality. French-speaking adolescents were recruited in person and online throughout the province of Québec (Canada) from the end of March to early July 2023. Beverage consumption and sleep quality were measured using French versions of validated questionnaires specifically designed for adolescents. A total of 218 adolescents (14-17 years; 55.5% female) completed the online survey. Among caffeinated SSBs, energy drink (rs = -0.16; p = 0.0197) and sugar-sweetened coffee (rs = -0.33; p < 0.0001) intake was correlated with adolescents' sleep quality. Energy drink consumption (ß = -0.0048; p = 0.0005) and being male (ß = 0.6033; p < 0.0001) were associated with adolescents' sleep quality. There was an interaction between sugar-sweetened coffee intake and biological sex that was associated with adolescents' sleep quality (p = 0.0053). Sugar-sweetened coffee consumption was correlated with adolescent girls' abilities to go to bed (rs = -0.21; p = 0.0203) and fall asleep (rs = -0.28; p = 0.0020), while in boys, it was only significantly correlated with their abilities to go to bed (rs = -0.27; p = 0.0069). Public health interventions aimed at adolescent boys should primarily target lowering energy drink consumption, while those aimed at girls should prioritize sugar-sweetened coffee intake to possibly improve their sleep quality.

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.

Association between obesity and risk of fracture, bone mineral density and bone quality in adults: A systematic review and meta-analysis.

BACKGROUND: The association between obesity and fracture risk may be skeletal site- and sex-specific but results among studies are inconsistent. Whilst several studies reported higher bone mineral density (BMD) in patients with obesity, altered bone quality could be a major determinant of bone fragility in this population. OBJECTIVES: This systematic review and meta-analysis aimed to compare, in men, premenopausal women and postmenopausal women with obesity vs. individuals without obesity: 1) the incidence of fractures overall and by site; 2) BMD; and 3) bone quality parameters (circulating bone turnover markers and bone microarchitecture and strength by advanced imaging techniques). DATA SOURCES: PubMed (MEDLINE), EMBASE, Cochrane Library and Web of Science were searched from inception of databases until the 13th of January 2021. DATA SYNTHESIS: Each outcome was stratified by sex and menopausal status in women. The meta-analysis was performed using a random-effect model with inverse-variance method. The risks of hip and wrist fracture were reduced by 25% (n = 8: RR = 0.75, 95% CI: 0.62, 0.91, P = 0.003, I2 = 95%) and 15% (n = 2 studies: RR = 0.85, 95% CI: 0.81, 0.88), respectively, while ankle fracture risk was increased by 60% (n = 2 studies: RR = 1.60, 95% CI: 1.52, 1.68) in postmenopausal women with obesity compared with those without obesity. In men with obesity, hip fracture risk was decreased by 41% (n = 5 studies: RR = 0.59, 95% CI: 0.44, 0.79). Obesity was associated with increased BMD, better bone microarchitecture and strength, and generally lower or unchanged circulating bone resorption, formation and osteocyte markers. However, heterogeneity among studies was high for most outcomes, and overall quality of evidence was very low to low for all outcomes. CONCLUSIONS: This meta-analysis highlights areas for future research including the need for site-specific fracture studies, especially in men and premenopausal women, and studies comparing bone microarchitecture between individuals with and without obesity. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42020159189.

Association between changes in bioactive osteocalcin and glucose homeostasis after biliopancreatic diversion.

PURPOSE: Bone may regulate glucose homeostasis via uncarboxylated bioactive osteocalcin (ucOCN). This study explored whether changes in ucOCN and bone remodeling are associated with change in glucose homeostasis after biliopancreatic diversion (BPD). METHODS: In this secondary exploratory analysis of a 1-year prospective observational study, 16 participants (11 men/5 women; 69% with type 2 diabetes; mean BMI 49.4 kg/m2) were assessed before, 3 days, 3 months and 12 months after BPD. Changes in plasma ucOCN and bone markers (C-terminal telopeptide (CTX), total osteocalcin (OCN)) were correlated with changes in insulin resistance or sensitivity indices (HOMA-IR; adipose tissue insulin resistance index (ADIPO-IR) and insulin sensitivity index (SI) from the hyperinsulinemic-euglycemic clamp), insulin secretion rate (ISR) from the hyperglycemic clamp, and disposition index (DI: SI × ISR) using Spearman correlations before and after adjustment for weight loss. RESULTS: ucOCN was unchanged at 3 days but increased dramatically at 3 months (+257%) and 12 months (+498%). Change in ucOCN correlated significantly with change in CTX at 3 months (r = 0.62, p = 0.015) and 12 months (r = 0.64, p = 0.025) before adjustment for weight loss. It also correlated significantly with change in fasting insulin (r = -0.53, p = 0.035), HOMA-IR (r = -0.54, p = 0.033) and SI (r = 0.52, p = 0.041) at 3 days, and ADIPO-IR (r = -0.69, p = 0.003) and HbA1c (r = -0.69, p = 0.005) at 3 months. Change in OCN did not correlate with any glucose homeostasis indices. Results were similar after adjustment for weight loss. CONCLUSION: The increase in ucOCN may be associated with the improvement in insulin resistance after BPD, independently of weight loss. These findings need to be confirmed in larger, less heterogeneous populations.

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.

Increased Dairy Product Intake Modifies Plasma Glucose Concentrations and Glycated Hemoglobin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Dairy product intake is inversely associated with the risk of type 2 diabetes (T2D) in numerous cohort studies; yet, the beneficial effects of increased dairy product intake on T2D risk factors such as fasting plasma glucose, fasting insulin, insulin resistance with the homeostasis model assessment, and glycated hemoglobin (HbA1c) remain inconclusive in clinical trials. The objective of this study was to systematically review clinical trials observing the effects of elevated compared with minimal intake of dairy products on T2D risk factors in subjects without diabetes. Five databases [Medline, EMBASE, Central, CINAHL, AMED (Allied and Complementary Medicine)] were searched to identify randomized controlled trials that used elevated quantities of dairy products from ruminant sources in comparison with a lower intake in control groups. The review outcomes were fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HbA1c. Risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development, and Evaluation were addressed. From the 10,627 citations screened, 44 studies (3016 participants) were included, 38 of which were used in the meta-analyses. Fasting glucose was positively associated with elevated dairy intake [34 studies, n = 2678; mean difference (MD): 0.07 mmol/L; 95% CI: 0.01, 0.12 mmol/L; P = 0.01, I2 = 23%]. Fasting insulin (29 studies, n = 1902; MD: -2.97 pmol/L; 95% CI: -7.05, 1.10 pmol/L; P = 0.15, I2 = 21%) and HOMA-IR (13 studies, n = 840; standardized MD: -0.07; 95% CI: -0.26, 0.12; P = 0.49, I2 = 38%) were not associated with elevated dairy consumption. HbA1c was negatively associated with elevated dairy product intake in 4 studies (n = 512; MD: -0.09%; 95% CI: -0.09%, -0.03%; P = 0.005, I2 = 0%). Most studies had high risk of bias and the quality of evidence was very low or low. In conclusion, evidence suggests that elevated dairy product intake is associated with increased fasting plasma glucose concentrations together with reduced HbA1c in nondiabetic subjects. Hence, the clinical significance of these results remains uncertain. Additional well-designed, long-term studies are required.

Effects of Biliopancreatic Diversion on Bone Turnover Markers and Association with Hormonal Factors in Patients with Severe Obesity.

BACKGROUND: This study evaluated early and medium-term changes in bone turnover markers, and their associations with weight loss, total bone mineral density (BMD), and hormonal changes after biliopancreatic diversion (BPD). METHODS: Ancillary study from a one-year prospective cohort of 16 individuals assessed before, 3 days, 3 and 12 months after BPD. Bone turnover markers (C-terminal telopeptide (CTX), intact osteocalcin (OC), sclerostin, and osteoprotegerin (OPG)) and several hormones were measured at each visit. Total BMD by DXA was assessed at baseline, 3 and 12 months after BPD. Three participants were lost to follow-up. RESULTS: CTX increased significantly at 3 days (+ 66%), 3 months (+ 219%), and 12 months (+ 295%). OC decreased at 3 days (- 19%) then increased at 3 months (+ 69%) and 12 months (+ 164%). Change in sclerostin was only significant between 3 days and 3 months (+ 13%), while change in OPG was significant between baseline and 3 days (+ 48%) and baseline and 12 months (+ 45%). CTX increase correlated negatively with weight loss at 3 (r = - 0.63, p = 0.009) and 12 months (r = - 0.58, p = 0.039), and total BMD decrease (r = - 0.67, p = 0.033) at 12 months. Change in insulin and adiponectin correlated with changes in bone turnover markers independently of weight loss. CONCLUSION: BPD causes an earlier and greater increase in bone resorption over bone formation markers and a decrease in total BMD. Sclerostin did not increase as expected following extensive weight loss. Changes in insulin and adiponectin seem to play a role in the activation of bone remodeling after BPD.