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.

Estimating the benefits of obesity prevention on productivity: an Australian perspective.

BACKGROUND/OBJECTIVES: Obesity poses one of the biggest public health challenges globally. In addition to the high costs of obesity to the healthcare system, obesity also impacts work productivity. We aimed to estimate the benefits of preventing obesity in terms of years of life, productivity-adjusted life years (PALYs) and associated costs over 10 years. SUBJECTS/METHODS: Dynamic life table models were constructed to estimate years of life and PALYs saved if all new cases of obesity were prevented among Australians aged 20-69 years from 2021 to 2030. Life tables were sex specific and the population was classified into normal weight, overweight and obese. The model simulation was first undertaken assuming currently observed age-specific incidences of obesity, and then repeated assuming all new cases of obesity were reduced by 2 and 5%. The differences in outcomes (years of life, PALYs, and costs) between the two modelled outputs reflected the potential benefits that could be achieved through obesity prevention. All outcomes were discounted by 5% per annum. RESULTS: Over the next 10 years, 132 million years of life and 81 million PALYs would be lived by Australians aged 20-69 years, contributing AU$17.0 trillion to the Australian economy in terms of GDP. A 5% reduction in new cases of obesity led to a gain of 663 years of life and 1229 PALYs, equivalent to AU$262 million in GDP. CONCLUSIONS: Prevention of obesity is projected to result in substantial economic gains due to improved health and productivity. This further emphasises the need for public health prevention strategies to reduce this growing epidemic.

Carnosine Did Not Affect Vascular and Metabolic Outcomes in Patients with Prediabetes and Type 2 Diabetes: A 14-Week Randomized Controlled Trial.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with prediabetes and type 2 diabetes mellitus (T2DM). Carnosine has been suggested as a potential approach to reduce ASCVD risk factors. However, there is a paucity of human data. Hence, we performed a 14-week double-blind randomized placebo-controlled trial to determine whether carnosine compared with placebo improves vascular and metabolic outcomes in individuals with prediabetes and T2DM. In total, 49 patients with prediabetes and T2DM with good glycemic control were randomly assigned either to receive 2 g/day carnosine or matching placebo. We evaluated endothelial dysfunction, arterial stiffness, lipid parameters, blood pressure, heart rate, hepatic and renal outcomes before and after the intervention. Carnosine supplementation had no effect on heart rate, peripheral and central blood pressure, endothelial function (logarithm of reactive hyperemia (LnRHI)), arterial stiffness (carotid femoral pulse wave velocity (CF PWV)), lipid parameters, liver fibroscan indicators, liver transient elastography, liver function tests, and renal outcomes compared to placebo. In conclusion, carnosine supplementation did not improve cardiovascular and cardiometabolic risk factors in adults with prediabetes and T2DM with good glycemic control. Therefore, it is improbable that carnosine supplementation would be a viable approach to mitigating the ASCVD risk in these populations. The trial was registered at clinicaltrials.gov (NCT02917928).

The Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes.

In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were 'Alive without type 2 diabetes', 'Alive with type 2 diabetes' and 'Dead'. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.

Use of carnosine in the prevention of cardiometabolic risk factors in overweight and obese individuals: study protocol for a randomised, double-blind placebo-controlled trial.

INTRODUCTION: Carnosine, an over the counter food supplement, has been shown to improve glucose metabolism as well as cardiovascular risk factors in animal and human studies through its anti-inflammatory, antioxidative, antiglycating and chelating properties. The aim of this study is to establish if carnosine supplementation improves obesity, insulin sensitivity, insulin secretion, cardiovascular risk factors including arterial stiffness and endothelial function, and other risk factors related to diabetes and cardiovascular disease in the overweight and obese population. METHODS AND ANALYSIS: Fifty participants will be recruited to be enrolled in a double-blind randomised controlled trial. Eligible participants with a body mass index (BMI) between 25 and 40 kg/m2 will be randomly assigned to the intervention or placebo group. Following a medical review and oral glucose tolerance test to check eligibility, participants will then undergo testing. At baseline, participants will have anthropometric measurements (BMI, dual X-ray absorptiometry and peripheral quantitative CT scan), measurements of glucose metabolism (oral glucose tolerance test, intravenous glucose tolerance test and euglycaemic hyperinsulinaemic clamp), cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), a muscle and fat biopsy, physical activity measurement, liver fibroscan, cognitive function and questionnaires to assess dietary habits, sleep quality, depression, and quality of life. Following baseline assessments, participants will be randomised to either 2 g carnosine or placebo for 15 weeks. In the 15th week, all assessments will be repeated. The preplanned outcome metric is the change between baseline and follow-up measures. ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia. TRIAL REGISTRATION NUMBER: NCT02686996.

Productivity Benefits of Preventing Type 2 Diabetes in Australia: A 10-Year Analysis.

OBJECTIVE: Diabetes imposes a heavy burden on both health and productivity. In this study, we sought to estimate the potential productivity gains associated with the prevention of type 2 diabetes over the next 10 years in Australia. RESEARCH DESIGN AND METHODS: Dynamic life table models were constructed to estimate years of life lived and productivity-adjusted life-years (PALYs) lived by Australians aged 20-69 years over the period from 2020 to 2029. The models distinguished people with and without type 2 diabetes. PALYs were ascribed a financial value equivalent to gross domestic product (GDP) per full-time worker in Australia (∼200,000 Australian dollars [AUD]). The model simulation was first undertaken assuming currently expected trends in the incidence of type 2 diabetes and then repeated assuming hypothetically that the incidence was reduced. The difference between the modeled outputs reflected the impact of new cases of type 2 diabetes on productivity as well as the potential benefits of prevention. An annual 5% discount rate was applied to all outcomes. RESULTS: Over the next decade, 140 million years of life and 87 million PALYs will be lived by Australians of working age, contributing AUD 18.0 trillion to the country's GDP. A 10% reduction in the incidence of type 2 diabetes would result in a gain of 2,510 PALYs and AUD 532 million in GDP. CONCLUSIONS: This study illustrates the health and economic impact of type 2 diabetes and the gains that could be potentially achieved from the implementation of effective prevention strategies. However, cost-effectiveness evaluations of these prevention strategies are needed.

Carnosine and histidine-containing dipeptides improve dyslipidemia: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Cardiovascular disease is a major public health problem and represents a significant burden of disease globally. Lifestyle interventions have their limitations and an intervention that will effectively address cardiovascular risk factors to help reduce this growing burden of disease is required. OBJECTIVE: Carnosine and other histidine-containing dipeptides (HCDs) have exerted positive effects on cardiovascular risk factors and diseases in animal and human studies. The authors conducted a systematic review and meta-analysis examining the effects of HCDs on cardiovascular outcomes in line with the PRISMA guidelines. DATA SOURCES: The Medline, Medline in process, Embase, Cumulative Index of Nursing and Allied Health, and All EBM databases were searched from inception until January 25, 2019, for randomized controlled trials (RCTs) examining the effects of HCDs on cardiovascular outcomes, compared with placebo or controls. DATA EXTRACTION: Basic characteristics of the study and populations, interventions, and study results were extracted. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of evidence for each outcome. DATA ANALYSIS: A total of 21 studies were included. Of these, 18 were pooled for meta-analysis (n = 913). In low risk of bias studies, HCD-supplemented groups had lower total cholesterol (n = 6 RCTs; n = 401; weighted mean difference [WMD], -0.32 mmol/L [95%CI, -0.57 to -0.07], P = 0.01) and triglyceride levels (n = 6 RCTs; n = 401; WMD, -0.14 mmol/L [95%CI, -0.20 to -0.08], P < 0.001) compared with controls. In studies using carnosine, triglycerides levels were also lower in the intervention group vs controls (n = 5 RCTS; n = 309; P < 0.001). There were no significant differences in blood pressure, heart rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) or the total cholesterol to HDL-C ratio between groups. CONCLUSIONS: Carnosine and other HCDs may have a role in improving lipid profiles. Larger studies with sufficient follow-up are necessary to confirm these findings and explore the use of HCDs in the prevention of cardiovascular diseases. SYSTEMIC REVIEW REGISTRATION: PROSPERO registration no.: CRD42017075354.

Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: A systematic review and meta-analysis of randomized controlled trials.

Supplementation with histidine-containing dipeptides has been shown to improve obesity and glycaemic outcomes in animal and human studies. We conducted a systematic review and meta-analysis of randomized controlled trials to examine these effects. Electronic databases were searched investigating the effects of histidine-containing dipeptides supplementation on anthropometric and glycaemic outcomes. Meta-analyses were performed using random-effects models to calculate the weighted mean difference and 95% confidence interval. There were 30 studies for the systematic review and 23 studies pooled for meta-analysis. Histidine-containing dipeptide groups had a lower waist circumference (WMD [95% CI] = -3.53 cm [-5.65, -1.41], p = 0.001) and HbA1c level (WMD [95% CI] = -0.76% (8.5 mmol/mol) [-1.29% (14.3 mmol/mol), -0.24% (2.8 mmol/mol)], p = 0.004) at follow-up compared with controls. In sensitivity analyses of studies with low risk of bias, waist circumference, HbA1c, and fasting glucose levels (WMD [95% CI] = -0.63 mmol/L [-1.09, -0.18], p = 0.006) were significantly lower in intervention groups versus controls. There was also a trend toward lower fat mass (p = 0.09), insulin resistance (p = 0.07), and higher insulin secretion (p = 0.06) in intervention versus control groups. Supplementation with histidine-containing dipeptides may reduce central obesity and improve glycaemic outcomes. Further studies exploring histidine-containing dipeptide use in obesity and diabetes prevention and treatment are warranted.

Effects of supplementation with carnosine and other histidine-containing dipeptides on chronic disease risk factors and outcomes: protocol for a systematic review of randomised controlled trials.

INTRODUCTION: Ageing of populations globally, coupled with the obesity epidemic, has resulted in the rising prevalence of chronic diseases including diabetes, cardiovascular diseases, cancers and neurodegenerative disorders. Prevention of risk factors that contribute to these diseases is key in managing the global burden of chronic diseases. Recent studies suggest that carnosine, a dipeptide with anti-inflammatory, antioxidative and antiglycating properties may have a role in the prevention of chronic diseases; however, no previous reviews have examined the effects of carnosine and other histidine-containing peptides (HCDs) on chronic disease risk factors and outcomes. We aim to conduct a comprehensive systematic review to examine the effects of supplementation with carnosine and other HCDs on chronic disease risk factors and outcomes and to identify relevant knowledge gaps. METHODS AND ANALYSIS: Electronic databases including Medline, Cumulative Index of Nursing and Allied Health, Embase and all Evidence-Based Medicine will be systematically searched to identify randomised controlled trials (RCTs) and systematic reviews of RCTs, comparing supplementation with carnosine and/or other HCDs versus placebo, usual care or other pharmacological or non-pharmacological interventions. One reviewer will screen titles and abstracts for eligibility according to prespecified inclusion criteria, after which two independent reviewers will perform data extraction and quality appraisal. Meta-analyses, metaregression and subgroup analyses will be conducted where appropriate. ETHICS AND DISSEMINATION: Ethics approval is not required as this review does not involve primary data collection. This review will generate level-one evidence regarding the effects of carnosine supplementation on chronic disease risk factors and outcomes and will be disseminated through peer-reviewed publications and at conference meetings to inform future research on the efficacy of carnosine supplementation for the prevention of chronic diseases. PROSPERO REGISTRATION NUMBER: CRD42017075354.

Does supplementation with carnosine improve cardiometabolic health and cognitive function in patients with pre-diabetes and type 2 diabetes? study protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Carnosine, an over-the-counter food supplement, has a promising potential for the prevention and treatment of chronic diseases such as type 2 diabetes (T2DM), cardiovascular and neurodegenerative diseases through its anti-inflammatory, antiglycation, antioxidative and chelating effects. We have previously shown that supplementation with carnosine preserves insulin sensitivity and secretion in non-diabetic overweight and obese individuals. The effect of carnosine on cardiometabolic risk and related cognitive outcomes in patients with pre-diabetes and T2DM has thus far not been studied. We therefore aim to investigate whether supplementation with carnosine improves cardiometabolic health and cognitive function in patients with pre-diabetes and T2DM. METHODS AND ANALYSIS: We will employ a parallel design randomised controlled trial. Fifty participants with pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) and T2DM (with HbA1c level < 8%) aged between 18 to 70 years will be randomly assigned to the intervention or control group. At baseline, participants will undergo a medical review and series of tests including anthropometric measurements (body mass index, a dual X-ray absorptiometry and peripheral quantitative computed tomography scan), an oral glucose tolerance test, cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), cognitive function, physical activity measurement, heart rate variability and liver fibroscan as well as questionnaires to assess dietary habits, sleep quality, depression and quality of life. The intervention group will receive 2 g of carnosine daily in two divided doses while the control group will receive identical placebo capsules for 14 weeks. All baseline measurements will be repeated at the end of the intervention. The change in glycaemic, cardiovascular and cognitive parameters as well as other measures will be compared between the groups. ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia. The findings will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION: NCT02917928; Pre-results.

Shared Medical Appointments May Be Effective for Improving Clinical and Behavioral Outcomes in Type 2 Diabetes: A Narrative Review.

Type 2 diabetes mellitus (T2DM) is a complex chronic disease affecting over 400 million people worldwide. Managing T2DM and its associated complications in individual patient consultations poses substantial challenges to physicians due to limited time and resources and lack of access to multidisciplinary teams. Shared medical appointments (SMAs) are consecutive medical consultations provided by a physician in a group setting, where integrated medical care and patient education are delivered in a single session. SMAs allow physicians to deliver the same level of care to multiple patients at the same time, thereby maximizing available resources. However, the effectiveness and practicality of SMAs in the management of T2DM remains unknown. This narrative review summarizes current and emerging evidence regarding the effectiveness of SMAs in improving clinical outcomes in patients with T2DM, as well as whether SMAs are associated with reduced costs and improved diabetes-related behavioral and lifestyle changes. An extensive literature search was conducted on major electronic databases including PubMed and Google Scholar using keywords, including SMAs, group visits, and T2DM to identify all studies of SMAs in patients with T2DM. Studies in type 1 diabetes or mixed or unspecified populations were excluded, as well as studies where SMAs did not involve a physician since these do not meet the classical definition of a SMA. Nineteen studies were identified and are included in this review. Overall, current evidence suggests that SMAs delivered regularly over time may be effective in improving glycemic outcomes, diabetes knowledge, and some diabetes-related behaviors. However, the main limitation of existing studies was the paucity of comparisons with standard care which limits the ability to draw conclusions regarding whether SMAs are superior to standard care in T2DM management. Moreover, the small number of studies and substantial heterogeneity in study designs, populations, and interventions creates difficulties in establishing the practicality and efficiency of SMAs in the clinical care setting. We conclude that there remains a need for larger studies to identify populations who may or may not benefit from the SMA model of care and to clarify the potential benefits and barriers to implementing SMAs into routine diabetes care.