Circulating levels of microRNA-122 and hepatic fat change in response to weight-loss interventions: CENTRAL Trial

Purpose Little is known about the relations between changes in circulating microRNA-122 (miR-122) and liver fat in response to weight-loss interventions. We aimed to investigate the association between miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions. Methods The CENTRAL trial is an 18-month randomized, controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat diet or a Mediterranean/low-carbohydrate diet. After six months of dietary intervention, each diet group was further randomized into added physical activity groups or no added physical activity groups for the following 12 months of intervention. The current study included 220 participants at baseline and 134 participants with repeated measurements on serum miR-122 and hepatic fat content over 18 months. Results Serum miR-122 significantly increased from baseline to 18 months, while no difference was observed across the four intervention groups. We found a significant association between miR-122 and hepatic fat content at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content (P<0.001). Furthermore, we found that higher elevations in miR-122 were associated with less reductions in hepatic fat percentage during 18-month interventions (β=1.56, P=0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months (P interaction=0.02). Conclusions Our data indicate that participants with higher elevation in serum miR-122 may benefit less in reduction of hepatic fat content in response to diet and physical activity interventions.

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.

Rapid Weight Loss, Central Obesity Improvement and Blood Glucose Reduction Are Associated with a Stronger Adaptive Immune Response Following COVID-19 mRNA Vaccine

Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet’s safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R −0.558, p = 0.013 for IFNγ-1; R −0.581, p = 0.009 for IFNγ-2; R −0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

Serum metabolomic analysis of men on a low-carbohydrate diet for biochemically recurrent prostate cancer reveal the potential role of ketogenesis to slow tumor growth: A secondary analysis of the CAPS2 diet trial

Background: Systemic treatments for prostate cancer (PC) have significant side effects. Thus, newer alternatives with fewer side effects are urgently needed. Animal and human studies suggest the therapeutic potential of low carbohydrate diet (LCD) for PC. To test this possibility, Carbohydrate and Prostate Study 2 (CAPS2) trial was conducted in PC patients with biochemical recurrence (BCR) after local treatment to determine the effect of a 6-month LCD intervention vs. usual care control on PC growth as measured by PSA doubling time (PSADT). We previously reported the LCD intervention led to significant weight loss, higher HDL, and lower triglycerides and HbA1c with a suggested longer PSADT. However, the metabolic basis of these effects are unknown. Methods: To identify the potential metabolic basis of effects of LCD on PSADT, serum metabolomic analysis was performed using baseline, month 3, and month 6 banked sera to identify the metabolites significantly altered by LCD and that correlated with varying PSADT. Results: LCD increased the serum levels of ketone bodies, glycine and hydroxyisocaproic acid. Reciprocally, LCD reduced the serum levels of alanine, cytidine, asymmetric dimethylarginine (ADMA) and 2-oxobutanoate. As high ADMA level is shown to inhibit nitric oxide (NO) signaling and contribute to various cardiovascular diseases, the ADMA repression under LCD may contribute to the LCD-associated health benefit. Regression analysis of the PSADT revealed a correlation between longer PSADT with higher level of 2-hydroxybutyric acids, ketone bodies, citrate and malate. Longer PSADT was also associated with LCD reduced nicotinamide, fructose-1, 6-biphosphate (FBP) and 2-oxobutanoate. Conclusion: These results suggest a potential association of ketogenesis and TCA metabolites with slower PC growth and conversely glycolysis with faster PC growth. The link of high ketone bodies with longer PSADT supports future studies of ketogenic diets to slow PC growth.

Self-Monitoring Blood Glucose Method and Outcome: A Review

Self-monitoring of blood glucose (SMBG) is a valuable technique for diabetes mellitus treatment. Patients with diabetes frequently monitor their blood glucose levels in order to identify hypoglycemia and modify their insulin dosage as necessary. In many large-scale outcome studies, self-monitoring of blood glucose (SMBG) in the management of diabetes plays a vital role, contributing significantly to the outcomes. It is recommended that the patient keep track of their SMBG readings in a log book. For interpreting the SMBG findings, information regarding food intake, medication, and activity may be useful. An explanation of the practical components of the process is required to assess a patient's grasp of SMBG knowledge. For SMBG lancing treatments to be effective, the patient must have a thorough understanding of the stages involved. With many studies suggesting the benefits of SMBG other studies say that SMBG has little clinical effectiveness in improving glycemic control in patients with T2DM who are taking oral medications or eating a low-carbohydrate diet alone, and is thus unlikely to be cost-effective. However, if patients have the ability to modify their treatment dosage then it can be much more effective. In this review we will be looking at the SMBG techniques, outcomes and the relationship with glucose management.

A Low-Carbohydrate Diet Realizes Medication Withdrawal: A Possible Opportunity for Effective Glycemic Control

ObjectiveMultiple studies have confirmed that diet restrictions can effectively realize glycemic control and reduce metabolic risks in patients with type 2 diabetes mellitus (T2DM). In 2018, the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) stated that individuals can select a low-carbohydrate diet (LCD) according to their needs and preferences. Owing to the influence of Chinese traditional eating habits, only a small portion of patients in China have achieved their blood glucose goals. As a result, the Chinese government will incur huge expenditures.MethodThis study recruited 134 T2DM participants and randomly assigned them to the LCD group (n = 67) or the low-fat diet (LFD) group (n = 67). All of the patients had a fixed amount of exercise and were guided by clinicians. After a period of dietary washout, all of the patients received corresponding dietary education according to group. The follow-up time was 6 months. The indicators for anthropometry, glycemic control, and medication application parameters were collected and compared between the two groups.ResultsThere were 121 participants who finally entered the study. The proportions of calories from three major nutrients the participants consumed met the requirements of LCD and LFD. Compared with baseline, the pre-postdifferences of body weight, BMI, and several other indicators were significant except for dosages of insulin used in the LCD group and MES in the LFD group. After the intervention, body weight, body weight index (BMI), fasting blood glucose (FBG), postprandial 2-h blood glucose (PPG), and glycosylated hemoglobin (HbA1c) levels in the LCD group decreased significantly (p < 0.05) compared with the LFD group. The number of patients using lipid-lowering agents was significant higher in the LCD group and lower in the LFD group. However, there was no significant difference between the two groups for antihypertensive, hormone-replacement, and other agents.ConclusionsThe LCD diet can decrease body weight, glycemic levels, MES, and lipid-lowering agents more than the LFD diet, thus decreasing cost burden in Chinese patients with T2DM. Strict diet control and monitoring are the keys to managing diabetes.