Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial.

BACKGROUND AND AIMS: Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. METHODS AND RESULTS: In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (-1.31 mmol/L; p = 0.02) and 120 min (-1.60 mmol/L, p = 0.02) and total glucose area under the curve (-3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. CONCLUSION: This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.

Carnosine as a potential therapeutic for the management of peripheral vascular disease.

AIMS: To evaluate the potential role of carnosine in the management of peripheral vascular disease. DATA SYNTHESIS: Peripheral vascular disease is growing in its burden and impact; however it is currently under researched, and there are a lack of strong, non-invasive therapeutic options for the clinicians. Carnosine is a dipeptide stored particularly in muscle and brain tissue, which exhibits a wide range of physiological activities, which may be beneficial as an adjunct treatment for peripheral vascular disease. Carnosine's strong anti-inflammatory, antioxidant and antiglycating actions may aid in the prevention of plaque formation, through protective actions on the vascular endothelium, and the inhibition of foam cells. Carnosine may also improve angiogenesis, exercise performance and vasodilatory response, while protecting from ischemic tissue injury. CONCLUSIONS: Carnosine may have a role as an adjunct treatment for peripheral vascular disease alongside typical exercise and surgical interventions, and may be used in high risk individuals to aid in the prevention of atherogenesis. CLINICAL RECOMMENDATION: This review identifies a beneficial role for carnosine supplementation in the management of patients with peripheral vascular disease, in conjunction with exercise and revascularization. Carnosine as a supplement is safe, and associated with a host of beneficial effects in peripheral vascular disease and its key risk factors.

Carnosine/histidine-containing dipeptide supplementation improves depression and quality of life: systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Mental ill-health is a common and growing issue, affecting 1 in 8 individuals or 970 million people worldwide in 2019. Histidine-containing dipeptides (HCDs) have been suggested to mitigate some aspects of mental ill-health, but a quantitative synthesis of the evidence is lacking. Therefore, a systematic review and meta-analysis of randomized controlled trials was conducted. OBJECTIVE: To summarize the evidence on the effects of HCDs on mental health outcomes. DATA SOURCE: A systematic literature search was performed using electronic databases (Medline via Ovid, Embase via Ovid, Scopus, Google Scholar, and Cochrane) from inception to October, 2022. DATA EXTRACTION: Two authors independently extracted data using a structured extraction format. DATA ANALYSIS: Data analysis was performed using STATA version 17. Random-effects models were used, and heterogeneity was assessed using the I2 test. Quality appraisal was performed using the Cochrane risk-of-bias 2.0 tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. CONCLUSION: 5507 studies were identified, with 20 studies fulfilling the inclusion criteria. Eighteen studies comprising 776 participants were included in the meta-analysis. HCD supplementation (anserine/carnosine, l-carnosine, ß-alanine) caused a significant reduction in depression scores measured with the Becks Depression Inventory (-0.79; 95% CI: -1.24, -0.35; moderate certainty on GRADE) when compared with placebo. An increase in quality-of-life scores measured with the 36-item Short-Form survey (SF-36) (0.65; 95% CI: 0.00, 1.30) and low certainty on GRADE in HCDs (anserine/carnosine, l-carnosine, ß-alanine) when compared with placebo were found. However, the rest of the outcomes did not show a significant change between HCD supplementation and placebo. Although the number of studies included in the meta-analysis was modest, a significant mean reduction was observed in depression score as well as an increase in quality-of-life score for the HCD group when compared with placebo. Most of the studies included had small sample sizes with short follow-up periods and moderate to high risk of bias, highlighting the need for further, well-designed studies to improve the evidence base. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017075354.

Histidine-containing dipeptide supplementation improves delayed recall: a systematic review and meta-analysis.

CONTEXT: Histidine-containing dipeptides (carnosine, anserine, beta-alanine and others) are found in human muscle tissue and other organs like the brain. Data in rodents and humans indicate that administration of exogenous carnosine improved cognitive performance. However, RCTs results vary. OBJECTIVES: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) of histidine-containing dipeptide (HCD) supplementation on cognitive performance in humans to assess its utility as a cognitive stabiliser. DATA SOURCES: OVID Medline, Medline, EBM Reviews, Embase, and Cumulative Index to Nursing and Allied Health Literature databases from 1/1/1965 to 1/6/2022 for all RCT of HCDs were searched. DATA EXTRACTION: 2653 abstracts were screened, identifying 94 full-text articles which were assessed for eligibility. Ten articles reporting the use of HCD supplementation were meta-analysed. DATA ANALYSIS: The random effects model has been applied using the DerSimonian-Laird method. HCD treatment significantly increased performance on Wechsler Memory Scale (WMS) -2 Delayed recall (Weighted mean difference (WMD) (95% CI (CI)) = 1.5 (0.6, 2.5), P < .01). Treatment with HCDs had no effect on Alzheimer's Disease Assessment Scale-Cognitive (WMD (95% CI) = -0.2 (-1.1, 0.7), P = .65, I2 = 0%), Mini-Mental State Examination (WMD (95% CI) = 0.7 (-0.2, 1.5), P = .14, I2 = 42%), The Wechsler Adult Intelligence Scale (WAIS) Digit span Backward (WMD (95% CI) = 0.1 (-0.3, 0.5), P = .51, I2 = 0%), WAIS digit span Forward (WMD (95% CI) = 0.0 (-0.3, 0.4), P = .85, I2 = 33%) and the WMS-1 Immediate recall (WMD (95% CI) = .7 (-.2, 1.5), P = .11, I2 = 0%). The effect on delayed recall remained in subgroup meta-analysis performed on studies of patients without mild cognitive impairment (MCI), and in those without MCI where average age in the study was above 65. CONCLUSION: HCD, supplementation improved scores on the Delayed recall examination, a neuropsychological test affected early in Alzheimer's disease. Further studies are needed in people with early cognitive impairment with longer follow-up duration and standardization of carnosine doses to delineate the true effect. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017075354.

The dietary inflammatory index, obesity, type 2 diabetes, and cardiovascular risk factors and diseases.

An unhealthy diet is a recognized risk factor in the pathophysiology of numerous chronic noncommunicable diseases (NCD), including obesity, type 2 diabetes (T2DM), and cardiovascular diseases (CVD). This is, at least in part, due to unhealthy diets causing chronic low-grade inflammation in the gut and systemically. To characterize the inflammatory potential of diet, we developed the Dietary Inflammatory Index (DII®). Following this development, around 500 papers have been published, which examined the association between the DII, energy-adjusted DII (E-DII™), and the children's DII (C-DII™) and many chronic NCDs including obesity and cardiometabolic diseases. Although a previous narrative review published in 2019 briefly summarized the evidence in this area, there was a significant increase in papers on this topic since 2020. Therefore, the purpose of this narrative review is to provide an in-depth updated review by including all papers until July 2021 on DII and its relationship with obesity, T2DM, and CVD. Furthermore, we aim to identify potential gaps in the literature and provide future directions for research. Most studies found that DII was associated with an increased risk of obesity, T2DM, and CVD with some relationships being sex-specific. However, we identified the paucity of papers describing associations between dietary inflammation and T2DM and its risk factors. Few studies used gold-standard measures of cardiometabolic risk factors. We also identified the lack of interventional studies designed to change the inflammatory potential of diets and study its effect on cardiometabolic risk factors and diseases. We recommend that such interventional studies are needed to assess if changes in DII, representing the inflammatory potential of diet, independently of changes in body composition can modulate cardiometabolic risk factors and diseases.

Influence of AMY1A copy number variations on obesity and other cardiometabolic risk factors: A review of the evidence.

The rising incidence of obesity and type 2 diabetes is contributing to the escalating burden of disease globally. These metabolic disorders are closely linked with diet and in particular with carbohydrate consumption; hence, it is important to understand the underlying mechanisms that influence carbohydrate metabolism. Amylase, the enzyme responsible for the digestion of starch, is coded by the genes AMY1A, AMY1B, and AMY1C (salivary amylase) and AMY2A and AMY2B (pancreatic amylase). Previous studies demonstrate wide variations in AMY1A copy numbers, which can be attributed to several genetic, nutritional, and geographical diversities seen in populations globally. Current literature suggests that AMY1A copy number variations are important in obesity and other cardiometabolic disorders through their effects on glucose and lipid homeostasis, inflammatory markers, and the gut microbiome. This review synthesizes the available evidence to improve understanding of the role of AMY1A in obesity and related cardiometabolic risk factors and disorders including insulin resistance and type 2 diabetes, cardiovascular risk and inflammation, and the gut microbiome.

Utility of the methylated SEPT9 test for the early detection of colorectal cancer: a systematic review and meta-analysis of diagnostic test accuracy.

Background: Circulating tumour DNA from colorectal cancer (CRC) is a biomarker for early detection of the disease and therefore potentially useful for screening. One such biomarker is the methylated SEPT9 (mSEPT9) gene, which occurs during CRC tumourigenesis. This systematic review and meta-analysis aims to establish the sensitivity, specificity and accuracy of mSEPT9 tests for the early diagnosis of CRC. Methods: A systematic search of the relevant literature was conducted using Medline and Embase databases. Data were extracted from the eligible studies and analysed to estimate pooled sensitivity, specificity and diagnostic test accuracy. Results: Based on 19 studies, the pooled estimates (and 95% CIs) for mSEPT9 to detect CRC were: sensitivity 69% (62-75); specificity 92% (89-95); positive likelihood ratio 9.1 (6.1-13.8); negative likelihood ratio 0.34 (0.27-0.42); diagnostic OR 27 (15-48) and area under the curve 0.89 (0.86-0.91). The test has a positive predictive value of 2.6% and negative predictive value of 99.9% in an average risk population (0.3% CRC prevalence), and 9.5% (positive predictive value) and 99.6% (negative predictive value) in a high-risk population (1.2% CRC prevalence). Conclusion: The mSEPT9 test has high specificity and moderate sensitivity for CRC and is therefore a potential alternative screening method for those declining faecal immunochemical test for occult blood (FIT) or other screening modalities. However, it is limited by its poor diagnostic performance for precancerous lesions (advanced adenomas and polyps) and its relatively high costs, and little is known about its acceptability to those declining to use the FIT.

A global analysis of urban design types and road transport injury: an image processing study.

BACKGROUND: Death and injury due to motor vehicle crashes is the world's fifth leading cause of mortality and morbidity. City and urban designs might play a role in mitigating the global burden of road transport injury to an extent that has not been captured by traditional safe system approaches. We aimed to determine the relationship between urban design and road trauma across the globe. METHODS: Applying a combined convolutional neural network and graph-based approach, 1692 cities capturing one third of the world's population were classified into types based on urban design characteristics represented in sample maps. Associations between identified city types, characteristics contained within sample maps, and the burden of road transport injury as measured by disability adjusted life-years were estimated through univariate and multivariate analyses, controlling for the influence of economic activity. FINDINGS: Between Mar 1, 2017, and Dec 24, 2018, nine global city types based on a final sample of 1632 cities were identified. Burden of road transport injury was an estimated two-times higher (risk ratio 2·05, 95% CI 1·84-2·27) for the poorest performing city type compared with the best performing city type, culminating in an estimated loss of 8·71 (8·08-9·25) million disability-adjusted life-years per year attributable to suboptimal urban design. City types that featured a greater proportion of railed public transport networks combined with dense road networks characterised by smaller blocks showed the lowest rates of road traffic injury. INTERPRETATION: This study highlights the important role that city and urban design plays in mitigating road transport injury burden at a global scale. It is recommended that road and transport safety efforts promote urban design that features characteristics inherent in identified high-performance city types including higher density road infrastructure and high rates of public transit. FUNDING: See acknowledgments.