Abstract

Osteosarcopenia is defined as the concurrent occurrence of osteopenia/osteoporosis and sarcopenia. The aim of the current study was to perform a systematic review with meta-analysis to determine the global prevalence, risk factors and clinical outcomes of osteosarcopenia. This review was registered in PROSPERO (CRD42022351229). PubMed, Cochrane, Medline and Embase were searched from inception to February 2023 to retrieve eligible observational population-based studies. Pooled osteosarcopenia prevalence was calculated with 95% confidence interval (CI), and subgroup analyses were performed. The risk factor of osteosarcopenia and its association with clinical outcomes were expressed as odds ratio (OR) and hazard ratio (HR), respectively. Heterogeneity was estimated using the I2 test. Study quality was assessed using validated instruments matched to study designs. The search identified 55 158 studies, and 66 studies (64 404 participants, mean age from 46.6 to 93 years) were analysed in the final analysis, including 48 cross-sectional studies, 17 cohort studies and 1 case-control study. Overall, the pooled prevalence of osteosarcopenia was 18.5% (95% CI: 16.7-20.3, I2  = 98.7%), including 15.3% (95% CI: 13.2-17.4, I2  = 97.6%) in men and 19.4% (95% CI: 16.9-21.9, I2  = 98.5%) in women. The prevalence of osteosarcopenia diagnosed using sarcopenia plus osteopenia/osteoporosis was 20.7% (95% CI: 17.1-24.4, I2  = 98.55%), and the prevalence of using sarcopenia plus osteoporosis was 16.1% (95% CI: 13.3-18.9, I2  = 98.0%). The global osteosarcopenia prevalence varied in different regions with 22.9% in Oceania, 21.6% in Asia, 20.8% in South America, 15.7% in North America and 10.9% in Europe. A statistically significant difference was found in the subgroups of the study population between the hospital (24.7%) and community (12.9%) (P = 0.001). Frailty (OR = 4.72, 95% CI: 2.71-8.23, I2  = 61.1%), malnutrition (OR = 2.35, 95% CI: 1.62-3.40, I2  = 50.0%), female sex (OR = 5.07, 95% CI: 2.96-8.69, I2  = 73.0%) and higher age (OR = 1.10, 95% CI: 1.06-1.15, I2 ==86.0%) were significantly associated with a higher risk for osteosarcopenia. Meta-analysis of cohort studies showed that osteosarcopenia significantly increased the risk of fall (HR = 1.54, 95% CI: 1.20-1.97; I2  = 1.0%, three studies), fracture (HR = 2.13, 95% CI: 1.61-2.81; I2  = 67.8%, seven studies) and mortality (HR = 1.75, 95% CI: 1.34-2.28; I2  = 0.0%, five studies). Despite the heterogeneity arising from varied definitions and criteria, our findings highlight a significant global prevalence of osteosarcopenia and its negative impact on clinical health. Standardizing diagnostic criteria for osteosarcopenia would be advantageous in the future, and early detection and management should be emphasized in this patient population.

Abstract

OBJECTIVES Among the over 80 different autoimmune diseases, psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) are common representatives. Previous studies indicated a potential link with cancer risk, but suffered often from low statistical power. Thus, we aimed to synthesize the evidence and quantify the association to different female-specific cancer sites. METHODS The systematic review was performed according to PRISMA guidelines. A search string was developed for the databases PubMed, Web of Science, Cochrane Library and Embase. Results were screened independently by two investigators and the risk of bias was assessed using the ROBINS-E tool. Meta-analyses were performed using inverse variance weighted random-effects models. Statistical between-study heterogeneity was quantified by calculating Cochran's Q, τ2, and Higgins' I2 statistics. Sources of heterogeneity were analyzed and adjusted for within an intensive bias assessment in the form of meta-regression, outlier, influential, and subgroup analyses. A range of methods were used to test and adjust for publication bias. RESULTS Of 10,096 records that were originally identified by the search strategy, 45 were included in the meta-analyses. RA was inversely associated with both breast and uterine cancer occurrence, while PsO was associated with a higher breast cancer risk. Outlier-adjusted estimates confirmed these findings. Bias assessment revealed differences in geographic regions, particularly in RA patients, with higher estimates among Asian studies. An additional analysis revealed no association between psoriatic arthritis and breast cancer. CONCLUSIONS RA seems to reduce the risk of breast and uterine cancers, while PsO appears to increase breast cancer risk. Further large studies are required to investigate potential therapy-effects and detailed biological mechanisms.

Abstract

BACKGROUND & AIMS Continuous glucose monitoring (CGM) provides data on short-term glycemic variability (GV). GV is associated with adverse outcomes in individuals with diabetes. Whether GV is associated with cardiometabolic risk in individuals without diabetes is unclear. We systematically reviewed the literature to assess whether GV is associated with cardiometabolic risk markers or outcomes in individuals without diabetes. METHODS Searches were performed in PubMed/Medline, Embase and Cochrane from inception through April 2022. Two researchers were involved in study selection, data extraction and quality assessment. Studies evaluating GV using CGM for ≥24 h were included. Studies in populations with acute and/or critical illness were excluded. Both narrative synthesis and meta-analyzes were performed, depending on outcome. RESULTS Seventy-one studies were included; the majority were cross-sectional. Multiple measures of GV are higher in individuals with compared to without prediabetes and GV appears to be inversely associated with beta cell function. In contrast, GV is not clearly associated with insulin sensitivity, fatty liver disease, adiposity, blood lipids, blood pressure or oxidative stress. However, GV may be positively associated with the degree of atherosclerosis and cardiovascular events in individuals with coronary disease. CONCLUSION GV is elevated in prediabetes, potentially related to beta cell dysfunction, but less clearly associated with obesity or traditional risk factors. GV is associated with coronary atherosclerosis development and may predict cardiovascular events and type 2 diabetes. Prospective studies are warranted, investigating the predictive power of GV in relation to incident disease. GV may be an important risk measure also in individuals without diabetes.

Abstract

AIMS/HYPOTHESIS Continuous glucose monitoring (CGM) is increasingly used in the treatment of type 2 diabetes, but the effects on glycaemic control are unclear. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the effect of CGM on glycaemic control in adults with type 2 diabetes. METHODS We performed a systematic review using Embase, MEDLINE, Web of Science, Scopus and ClinicalTrials.gov from inception until 2 May 2023. We included RCTs investigating real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) compared with self-monitoring of blood glucose (SMBG) in adults with type 2 diabetes. Studies with an intervention duration <6 weeks or investigating professional CGM, a combination of CGM and additional glucose-lowering treatment strategies or GlucoWatch were not eligible. Change in HbA1c and the CGM metrics time in range (TIR), time below range (TBR), time above range (TAR) and glycaemic variability were extracted. We evaluated the risk of bias using the Cochrane risk-of-bias tool version 2. Data were synthesised by performing a meta-analysis. We also explored the effects of CGM on severe hypoglycaemia and micro- and macrovascular complications. RESULTS We found 12 RCTs comprising 1248 participants, with eight investigating rtCGM and four isCGM. Compared with SMBG, CGM use (rtCGM or isCGM) led to a mean difference (MD) in HbA1c of -3.43 mmol/mol (-0.31%; 95% CI -4.75, -2.11, p<0.00001, I2=15%; moderate certainty). This effect was comparable in studies that included individuals using insulin with or without oral agents (MD -3.27 mmol/mol [-0.30%]; 95% CI -6.22, -0.31, p=0.03, I2=55%), and individuals using oral agents only (MD -3.22 mmol/mol [-0.29%]; 95% CI -5.39, -1.05, p=0.004, I2=0%). Use of rtCGM showed a trend towards a larger effect (MD -3.95 mmol/mol [-0.36%]; 95% CI -5.46 to -2.44, p<0.00001, I2=0%) than use of isCGM (MD -1.79 mmol/mol [-0.16%]; 95% CI -5.28, 1.69, p=0.31, I2=64%). CGM was also associated with an increase in TIR (+6.36%; 95% CI +2.48, +10.24, p=0.001, I2=9%) and a decrease in TBR (-0.66%; 95% CI -1.21, -0.12, p=0.02, I2=45%), TAR (-5.86%; 95% CI -10.88, -0.84, p=0.02, I2=37%) and glycaemic variability (-1.47%; 95% CI -2.94, -0.01, p=0.05, I2=0%). Three studies reported one or more events of severe hypoglycaemia and macrovascular complications. In comparison with SMBG, CGM use led to a non-statistically significant difference in the incidence of severe hypoglycaemia (RR 0.66, 95% CI 0.15, 3.00, p=0.57, I2=0%) and macrovascular complications (RR 1.54, 95% CI 0.42, 5.72, p=0.52, I2=29%). No trials reported data on microvascular complications. CONCLUSIONS/INTERPRETATION CGM use compared with SMBG is associated with improvements in glycaemic control in adults with type 2 diabetes. However, all studies were open label. In addition, outcome data on incident severe hypoglycaemia and incident microvascular and macrovascular complications were scarce. REGISTRATION This systematic review was registered on PROSPERO (ID CRD42023418005).

Abstract

OBJECTIVE This post hoc analysis assessed continuous glucose monitoring (CGM)-based metrics and hypoglycemia duration with once-weekly insulin icodec versus once-daily basal insulin analogs in insulin-experienced individuals with long-standing type 2 diabetes from two 26-week phase 3a trials (ONWARDS 2 and ONWARDS 4). RESEARCH DESIGN AND METHODS Time in range (TIR) (3.9-10.0 mmol/L), time above range (TAR) (>10.0 mmol/L), and time below range (TBR) (<3.9 mmol/L and <3.0 mmol/L) were assessed during three CGM time periods (switch [weeks 0-4], end of treatment [weeks 22-26], and follow-up [weeks 27-31]) for icodec versus comparators (ONWARDS 2, insulin degludec [basal regimen]; ONWARDS 4, insulin glargine U100 [basal-bolus regimen]) using double-blind CGM data. CGM-derived hypoglycemic episode duration (<3.9 mmol/L) was assessed. RESULTS In both trials, there were no statistically significant differences in TIR, TAR, or TBR (<3.0 mmol/L) for icodec versus comparators across all time periods. In the end-of-treatment period, mean TIR was 63.1% (icodec) vs. 59.5% (degludec) in ONWARDS 2 and 66.9% (icodec) vs. 66.4% (glargine U100) in ONWARDS 4. Mean TBR <3.9 mmol/L and <3.0 mmol/L remained within recommended targets (<4% and <1%, respectively) across time periods and treatment arms. Hypoglycemic episode duration (<3.9 mmol/L) was comparable across time periods and treatment arms (median duration ≤40 min). CONCLUSIONS In insulin-experienced participants with long-standing type 2 diabetes, CGM-based TIR, TAR, and CGM-derived hypoglycemia duration (<3.9 mmol/L) were comparable for icodec and once-daily basal insulin analogs during all time periods. TBR remained within recommended targets.

Abstract

BACKGROUND Previous clinical studies showing that cinnamon spice lowers blood glucose concentrations had inconsistent results. OBJECTIVES To determine the effect of daily cinnamon spice supplementation in an amount commonly used for seasoning on glucose concentrations in adults with obesity and prediabetes. METHODS Following a 2-wk run-in period of maintaining a low polyphenol/fiber diet, 18 participants with obesity and prediabetes underwent a 10-wk randomized, controlled, double-blind, crossover trial (mean age 51.1 y; mean fasting plasma glucose 102.9 mg/dL). The participants were randomly assigned to take cinnamon (4 g/d) or placebo for 4-wk, followed by a 2-wk washout period, and then crossed over to the other intervention for an additional 4-wk. Glucose changes were measured with continuous glucose monitoring. Oral glucose tolerance testing immediately following ingestion of cinnamon or placebo was performed at 4-time points to assess their acute effects both at the baseline and end of each intervention phase. Digestive symptom logs were obtained daily. RESULTS There were 694 follow-up days with 66,624 glucose observations. When compared with placebo, 24-h glucose concentrations were significantly lower when cinnamon was administered [mixed-models; effect size (ES) = 0.96; 95 % confidence interval (CI): -2.9, -1.5; P < 0.001]. Similarly, the mean net-area-under-the-curve (netAUC) for glucose was significantly lower than for placebo when cinnamon was given (over 24 h; ES = -0.66; 95 % CI: 2501.7, 5412.1, P = 0.01). Cinnamon supplementation resulted in lower glucose peaks compared with placebo (Δpeak 9.56 ± 9.1 mg/dL compared with 11.73 ± 8.0 mg/dL; ES = -0.57; 95 % CI: 0.8, 3.7, P = 0.027). Glucose-dependent-insulinotropic-polypeptide concentrations increased during oral glucose tolerance testing + cinnamon testing (mixed-models; ES = 0.51; 95 % CI: 1.56, 100.1, P = 0.04), whereas triglyceride concentrations decreased (mixed-models; ES = 0.55; 95 % CI: -16.0, -1.6, P = 0.02). Treatment adherence was excellent in both groups (cinnamon: 97.6 ± 3.4 % compared with placebo: 97.9 ± 3.7 %; ES = -0.15; 95 % CI: -1.8, 0.2, P = 0.5). No differences were found in digestive symptoms (abdominal pain, borborygmi, bloating, excess flatus, and stools/day) between cinnamon and placebo groups. CONCLUSIONS Cinnamon, a widely available and low-cost supplement, may contribute to better glucose control when added to the diet in people who have obesity-related prediabetes. This trial was registered at clinicaltrials.gov as NCT04342624.

Abstract

OBJECTIVE  This study evaluated the effects of receiving glucose feedback from continuous glucose monitoring (CGM) by intermittent scanning (unblinded group), and CGM with masked feedback (blinded group) in the subsequent development of gestational diabetes mellitus (GDM). STUDY DESIGN  This was a prospective, single-center, pilot, randomized controlled trial including n = 206 pregnant women in the first trimester of pregnancy with no prior diagnosis of type 1 or type 2 diabetes. The participants were randomized into the unblinded group or blinded group and wore the CGM in the first trimester of pregnancy (9-13 weeks), the second trimester of pregnancy (18-23 weeks), and late-second to early-third trimester (24-31 weeks). The primary outcome was GDM rate as diagnosed by the 75-g oral glucose tolerance test (OGTT) at 24 to 28 weeks. RESULTS  Over 47 months, 206 pregnant women were enrolled at 9 to 13 weeks. The unblinded group had a higher prevalence of women who developed GDM (21.5 vs. 14.9%; p > 0.05), compared to the blinded group. In the unblinded group compared to the blinded group, plasma glucose values were higher at 1 hour (median 7.7 [interquartile range {IQR}: 6.3-9.2] vs. 7.5 [6.3-8.7]) and 2 hours (6.3 [5.8-7.7] vs. 6.2 [5.3-7.2]), but lower at 0 hour (4.2 [4.0-4.5] vs. 4.3 [4.1-4.6]; p > 0.05). All these differences were not statistically significant. CONCLUSION  Glucose feedback from CGM wear in the first to the third trimester of pregnancy without personalized patient education failed to alter GDM rate. KEY POINTS · Continuous glucose monitoring (CGM) is feasible for use in pregnant women.. · No significant difference in gestational diabetes rates with or without CGM feedback.. · Future clinical trials should incorporate CGM education and personalized guidance to enhance study outcomes..

Abstract

AIMS: Management of blood glucose fluctuation is essential for diabetes. Exercise is a key therapeutic strategy for diabetes patients, although little is known about determinants of glycemic response to exercise training. We aimed to investigate the effect of combined aerobic and resistance exercise training on blood glucose fluctuation in type 2 diabetes patients and explore the predictors of exercise-induced glycemic response. MATERIALS AND METHODS Fifty sedentary diabetes patients were randomly assigned to control or exercise group. Participants in the control group maintained sedentary lifestyle for 2 weeks, and those in the exercise group specifically performed combined exercise training for 1 week. All participants received dietary guidance based on a recommended diet chart. Glycemic fluctuation was measured by flash continuous glucose monitoring. Baseline fat and muscle distribution were accurately quantified through magnetic resonance imaging (MRI). RESULTS Combined exercise training decreased SD of sensor glucose (SDSG, exercise-pre vs exercise-post, mean 1.35 vs 1.10 mmol/L, p = .006) and coefficient of variation (CV, mean 20.25 vs 17.20%, p = .027). No significant change was observed in the control group. Stepwise multiple linear regression showed that baseline MRI-quantified fat and muscle distribution, including visceral fat area (β = -0.761, p = .001) and mid-thigh muscle area (β = 0.450, p = .027), were significantly independent predictors of SDSG change in the exercise group, as well as CV change. CONCLUSIONS Combined exercise training improved blood glucose fluctuation in diabetes patients. Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise, providing new insights into personalized exercise intervention for diabetes.

Abstract

OBJECTIVES To assess the feasibility and change in clinical outcomes associated with continuous glucose monitoring (CGM) use among a rural population in Malawi living with type 1 diabetes. DESIGN A 2:1 open randomised controlled feasibility trial. SETTING Two Partners In Health-supported Ministry of Health-run first-level district hospitals in Neno, Malawi. PARTICIPANTS 45 people living with type 1 diabetes (PLWT1D). INTERVENTIONS Participants were randomly assigned to Dexcom G6 CGM (n=30) use or usual care (UC) (n=15) consisting of Safe-Accu glucose monitors and strips. Both arms received diabetes education. OUTCOMES Primary outcomes included fidelity, appropriateness and severe adverse events. Secondary outcomes included change in haemoglobin A1c (HbA1c), acceptability, time in range (CGM arm only) SD of HbA1c and quality of life. RESULTS Participants tolerated CGM well but were unable to change their own sensors which resulted in increased clinic visits in the CGM arm. Despite the hot climate, skin rashes were uncommon but cut-out tape overpatches were needed to secure the sensors in place. Participants in the CGM arm had greater numbers of dose adjustments and lifestyle change suggestions than those in the UC arm. Participants in the CGM arm wore their CGM on average 63.8% of the time. Participants in the UC arm brought logbooks to clinic 75% of the time. There were three hospitalisations all in the CGM arm, but none were related to the intervention. CONCLUSIONS This is the first randomised controlled trial conducted on CGM in a rural region of a low-income country. CGM was feasible and appropriate among PLWT1D and providers, but inability of participants to change their own sensors is a challenge. TRIAL REGISTRATION NUMBER PACTR202102832069874.

Abstract

OBJECTIVES To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. DESIGN Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. SETTING Children aged 0-18 years from 26 European birth cohorts. PARTICIPANTS 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. MAIN OUTCOME MEASURE Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6-18 years. RESULTS Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. CONCLUSIONS Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.