Summary
In parallel with an increased focus on climate changes and carbon footprint, the interest in plant‐based diets and its potential health effects have increased over the past decade. The ...objective of this systematic review and meta‐analysis was to examine the effect of vegan diets (≥12 weeks) on cardiometabolic risk factors in people with overweight or type 2 diabetes. We identified 11 trials (796 participants). In comparison with control diets, vegan diets reduced body weight (−4.1 kg, 95% confidence interval (CI) −5.9 to −2.4, p < 0.001), body mass index (BMI) (−1.38 kg/m2, 95% CI −1.96 to −0.80, p < 0.001), glycated hemoglobin (HbA1c) (−0.18% points, 95% CI −0.29 to −0.07, p = 0.002), total cholesterol (−0.30 mmol/L, 95% CI −0.52 to −0.08, p = 0.007), and low‐density lipoprotein cholesterol (−0.24 mmol/L, 95% CI −0.40 to −0.07, p = 0.005). We identified no effect on blood pressure, high‐density lipoprotein cholesterol, and triglycerides. We found that adhering to vegan diets for at least 12 weeks may be effective in individuals with overweight or type 2 diabetes to induce a meaningful decrease in body weight and improve glycemia. Some of this effect may be contributed to differences in the macronutrient composition and energy intake in the vegan versus control diets. Therefore, more research is needed regarding vegan diets and cardiometabolic health.
Time-restricted eating (TRE) has been shown to improve body weight and glucose metabolism in people at high risk of type 2 diabetes. However, the safety of TRE in the treatment of type 2 diabetes is ...unclear. We investigated the safety of TRE interventions in people with type 2 diabetes by identifying published and ongoing studies. Moreover, we identified the commonly used antidiabetic drugs and discussed the safety of TRE in people with type 2 diabetes considering the use of these drugs. In addition, we addressed the research needed before TRE can be recommended in the treatment of type 2 diabetes. A literature search was conducted to identify published (MEDLINE PubMed) and ongoing studies (ClinicalTrials.gov) on TRE in people with type 2 diabetes. To assess the usage of antidiabetic drugs and to discuss pharmacodynamics and pharmacokinetics in a TRE context, the most used antidiabetic drugs were identified and analysed. Statistics regarding sale of pharmaceuticals were obtained from MEDSTAT.DK which are based on data from the national Register of Medicinal Product Statistics, and from published studies on medication use in different countries. Four published studies investigating TRE in people with type 2 diabetes were identified as well as 14 ongoing studies. The completed studies suggested that TRE is safe among people with type 2 diabetes. Common antidiabetic drugs between 2010 and 2019 were metformin, insulin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sulfonylureas, and sodium-glucose cotransporter-2 inhibitors. Existing studies suggest that TRE is not associated with major safety issues in people with type 2 diabetes as long as medication is monitored and adjusted. However, because of low generalisability of the few studies available, more studies are needed to make concrete recommendations regarding efficacy and safety of TRE in people with type 2 diabetes.
Individuals diagnosed with and treated for type 1 diabetes (T1D) have increased risk of micro- and macrovascular disease and excess mortality. Improving cardiovascular (CV) risk factors in ...individuals with T1D is known to reduce diabetes- related CV complications.
To examine time trends in CV risk factor levels and CV-protective treatment patterns. Additionally, examine incidence rates of diabetes-related CV complications in relation to exposure CV-protective treatment.
We analysed records from 41,630 individuals with T1D, registered anytime between 1996 and 2017 in a nationwide diabetes register. We obtained CV risk factor measurements (2010-2017), CV-protective drug profiles (1996-2017) and CV complication history (1977-2017) from additional nationwide health registers.
From 2010 to 2017 there were decreasing levels of HbA
, LDL-C, and blood pressure. Decreasing proportion of smokers, individuals with glycaemic dysregulation (HbA
≥ 58 mmol/mol), dyslipidaemia (LDL-C > 2.6 mmol/l), and hypertension (≥ 140/85 mmHg). Yet, one fifth of the T1D population by January 1st, 2017 was severely dysregulated (HbA
> 75 mmol/mol). A slight increase in levels of BMI and urinary albumin creatinine ratio and a slight decrease in estimated glomerular filtration rate (eGFR) levels was observed. By January 1st, 2017, one fourth of the T1D population had an eGFR < 60 ml/min/1.73 m
. The proportion of the T1D population redeeming lipid-lowering drugs (LLDs) increased from 5% in 2000 to 30% in 2010 followed by a plateau and then a decline. The proportion of the T1D population redeeming antihypertensive drugs (AHDs) increased from 28% in 1996 to 42% in 2010 followed by a tendency to decline. Use of LLDs was associated with lower incidence of micro- and macrovascular complications, while use of AHDs had higher incidence of CVD and CKD, when compared to non-use and discontinued use, respectively.
Improvements were seen in CV risk factor control among individuals with T1D in Denmark between 2010 and 2017. However, there is clearly a gap between current clinical guidelines and clinical practice for CV risk management in T1D. Action is needed to push further improvements in CV risk control to reduce CVD and the related excess mortality.
Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day ...cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types—a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.
Knowledge on how energy intake and macronutrients are distributed during the day and the role of daily eating patterns in body composition among adults with overweight/obesity and prediabetes is ...lacking. Therefore, we evaluated the diurnal dietary intake and studied the associations of daily eating patterns with body fat percentage. A total of 119 adults with prediabetes were included (mean (SD) HbA
41 (2.3) mmol/mol, BMI 31.5 (5.0) kg/m
, age 57.8 (9.3) years, 44% men). Information on dietary intake was obtained from self-reported food records for three consecutive days. All foods and beverages (except water) were registered with information on time of ingestion. Body fat was measured by dual-energy X-ray absorptiometry. A total of 60.5% of the participants reported a daily eating window of 12 or more hours/day, and almost half of the daily total energy intake was reported in the evening. In analyses adjusted for age, gender, and total daily energy intake, having the first daily energy intake one hour later was associated with slightly higher body fat percentage (0.64% per hour, 95% CI: 0.28; 1.01;
< 0.001), whereas higher meal frequency was associated with slightly lower body fat percentage (0.49% per extra daily meal, 95% CI: -0.81; -0.18;
= 0.002). Prospective studies are warranted to address the clinical implications of daily eating patterns on body fat and cardiometabolic health.
The oral glucose tolerance test (OGTT) is together with haemoglobin A
(HbA
) gold standard for diagnosing prediabetes and diabetes. The objective of this study was to assess the concordance between ...glucose values obtained from venous plasma versus interstitial fluid after oral glucose administration in 120 individuals with prediabetes and overweight/obesity.
120 adults with prediabetes defined by HbA
39-47 mmol/mol and overweight or obesity who participated in the randomised controlled PRE-D trial were included in the study. Venous plasma glucose concentrations were measured at 0, 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT) performed on three different occasions within a 26 weeks period. During the OGTT, the participants wore a CGM device (IPro2, Medtronic), which assessed glucose concentrations every five minutes.
A total of 306 OGTTs with simultaneous CGM measurements were obtained. Except in fasting, the CGM glucose values were below the OGTT values throughout the OGTT period with mean (SD) differences of 0.2 (0.7) mmol/L at time 0 min, -1.1 (1.3) at 30 min, -1.4 (1.8) at 60 min, and -0.5 (1.1) at 120 min). For measurements at 0 and 120 min, there was a proportional bias with an increasing mean difference between CGM and OGTT values with increasing mean of the two measurements.
Due to poor agreement between the OGTT and CGM with wide 95% limits of agreement and proportional bias at 0 and 120 min, the potential for assessing glucose tolerance in prediabetes using CGM is questionable.
Introduction:Increasing interest in real-world evidence has fueled the development of study designs incorporating real-world data (RWD). Using the Causal Roadmap, we specify three designs to evaluate ...the difference in risk of major adverse cardiovascular events (MACE) with oral semaglutide versus standard-of-care: (1) the actual sequence of non-inferiority and superiority randomized controlled trials (RCTs), (2) a single RCT, and (3) a hybrid randomized-external data study.Methods:The hybrid design considers integration of the PIONEER 6 RCT with RWD controls using the experiment-selector cross-validated targeted maximum likelihood estimator. We evaluate 95% confidence interval coverage, power, and average patient time during which participants would be precluded from receiving a glucagon-like peptide-1 receptor agonist (GLP1-RA) for each design using simulations. Finally, we estimate the effect of oral semaglutide on MACE for the hybrid PIONEER 6-RWD analysis.Results:In simulations, Designs 1 and 2 performed similarly. The tradeoff between decreased coverage and patient time without the possibility of a GLP1-RA for Designs 1 and 3 depended on the simulated bias. In real data analysis using Design 3, external controls were integrated in 84% of cross-validation folds, resulting in an estimated risk difference of –1.53%-points (95% CI –2.75%-points to –0.30%-points).Conclusions:The Causal Roadmap helps investigators to minimize potential bias in studies using RWD and to quantify tradeoffs between study designs. The simulation results help to interpret the level of evidence provided by the real data analysis in support of the superiority of oral semaglutide versus standard-of-care for cardiovascular risk reduction.
IntroductionBlood oxygen saturation is low compared with healthy controls (CONs) in the supine body position in individuals with type 1 diabetes (T1D) and has been associated with complications. ...Since most of daily life occurs in the upright position, it is of interest if this also applies in the standing body position. In addition, tissue oxygenation in other anatomical sites could show different patterns in T1D. Therefore, we investigated blood, arm and forehead oxygen levels in the supine and standing body positions in individuals with T1D (n=129) and CONs (n=55).Research design and methodsBlood oxygen saturation was measured with pulse oximetry. Arm and forehead mixed tissue oxygen levels were measured with near-infrared spectroscopy sensors applied on the skin.ResultsData are presented as least squares means±SEM and differences (95% CIs). Overall blood oxygen saturation was lower in T1D (CON: 97.6%±0.2%; T1D: 97.0%±0.1%; difference: −0.5% (95% CI −0.9% to −0.0%); p=0.034). In all participants, blood oxygen saturation increased after standing up (supine: 97.1%±0.1%; standing: 97.6%±0.2%; difference: +0.6% (95% CI 0.4% to 0.8%); p<0.001). However, the increase was smaller in T1D compared with CON (CON supine: 97.3%±0.2%; CON standing: 98.0%±0.2%; T1D supine: 96.9%±0.2%; T1D standing: 97.2%±0.1%; difference between groups in the change: −0.4% (95% CI −0.6% to −0.2%); p<0.001). Arm oxygen saturation decreased in both groups after standing and more in those with T1D. Forehead oxygen saturation decreased in both groups after standing and there were no differences between the changes when comparing the groups.ConclusionCompared with CON, individuals with T1D exhibit possible detrimental patterns of tissue oxygen adaptation to standing, with preserved adaptation of forehead oxygenation. Further studies are needed to explore the consequences of these differences.
In recent years, human papillomavirus (HPV) vaccination of boys has been added to childhood vaccination programmes in several countries but, so far, no systematic population-based assessment with ...long-term follow-up has been undertaken of the relative incidence of adverse outcomes following HPV vaccination in this group. We investigated if quadrivalent HPV (qHPV) vaccination of 10-17-year-old boys is associated with any unusual risk of autoimmune diseases, neurological diseases or venous thromboembolism.
We conducted a national cohort study of 568 410 boys born in Denmark 1988-2006 and followed for 4 million person-years during 2006-16, using nationwide registers to obtain individual-level information about received doses of the qHPV vaccine and hospital records for 39 autoimmune diseases, 12 neurological diseases and venous thromboembolism. For each outcome, we estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) according to qHPV vaccination status.
Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10-17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96; 95% CI: 0.71-1.28, n = 46 cases in qHPV-vaccinated boys) and neurological diseases (RR = 0.67; 0.41-1.10, n = 16), as well as for venous thromboembolism (RR = 0.88; 0.33-2.35, n = 4). After taking multiple testing into account, none of the 52 individual outcomes studied appeared to occur in excess among qHPV-vaccinated boys.
Although additional large-scale epidemiological studies are warranted, our findings provide population-based reassurance that qHPV vaccination of 10-17-year-old boys is unlikely to be associated with an elevated risk of autoimmune diseases, neurological diseases or venous thromboembolism.
The wireless motility capsule (WMC) technique is a noninvasive and radiation-free method for measuring regional and whole gut transit in response to ingestion of a granola bar (SmartBar) or an ...eggbeater meal. The WMC has the potential to measure gastrointestinal transit in metabolic research as part of a standardized mixed meal tolerance test.
To evaluate gastrointestinal transit with the WMC and postprandial plasma/serum concentrations of metabolites and gastrointestinal hormones as well as subjective appetite following ingestion of a SmartBar compared with a standardized mixed meal.
Fourteen healthy participants 3 men, median (IQR) age 53.8 (45.8; 64.50) y, body weight 63.9 (59.9; 69.7) kg, BMI 23.1 (21.8; 23.9) kg/m2 completed a 2-d crossover study. Following ingestion of either a SmartBar (260 kcal, 7 energy percent (E%) fat, 74E% carbohydrate, and 19E% protein) or a standardized mixed meal (498 kcal, 34E% fat, 49E% carbohydrate, and 17E% protein), participants swallowed the WMC. Blood samples were drawn in the fasted state and postprandially for analyses of gastrointestinal hormones and metabolites. The primary outcome was difference in gastric emptying time between the 2 test days. Wilcoxon signed rank tests were used to test differences between test days.
Median (IQR) gastric emptying time was 98.0 (70.0; 113.0) min longer (P = 0.001) and incremental area under the curve of triglyceride, glucose-dependent insulinotropic polypeptide, and peptide YY were 40 mmol/L × min, 45.7%, and 63.7% greater after the standardized mixed meal compared with the SmartBar (all P < 0.001).
The WMC can be used in combination with a standardized mixed meal for evaluation of gastrointestinal transit in healthy men and women. Gastric emptying time was prolonged in response to the standardized mixed meal whereas transit times of the small bowel, colon, and whole gut did not differ between the test meals.
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