The Effects of Ketogenic Diet on Brain Gene Expressions in Type 2 Diabetes Background.

Type 2 diabetes mellitus (T2DM) is a major risk factor of a number of neurodegenerative diseases (NDDs). Ketogenic diet (KD) has significant beneficial effects on glycemic control and may act effectively against NDDs, but the mechanism remains unclear. In this study, we aimed to investigate the potential effects of KD on gene expressions in the brains of T2DM model mice. Male db/db mice at the age of 9 weeks were fed with KD or normal diet to the age of 6 months, and the whole brains were subjected to mRNA-seq analysis for differentially expressed genes. KD significantly lowered fasting glucose and body weights in db/db mice (P < 0.05), and the expression of 189 genes in the brain were significantly changed (P < 0.05, |log2| > 1). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the differentially expressed genes upon KD are involved in inflammatory responses and the functions of biosynthesis. In inflammatory responses, NF-κB signaling pathway, viral protein interaction with cytokine and cytokine receptor, and cytokine-cytokine receptor interaction pathways were enriched, and in biosynthesis pathways, genes functioning in lipid and amino acid metabolism, protein synthesis, and energy metabolism were enriched. Moreover, consistent with the gene set enrichment analysis results, proteasomal activity measured biochemically were enhanced in KD-fed T2DM mice. These data may facilitate the understanding of how KD can be protective to the brain in T2DM background. KD could be a new strategy for the prevention of NDDs in T2DM patients.

Network meta-analysis of three different forms of intermittent energy restrictions for overweight or obese adults.

This network meta-analysis aimed to compare the efficacy of three forms of intermittent energy restriction (IER), including alternate-day fasting (ADF), the 5:2 diet, and time-restricted feeding (TRF), in overweight or obese adults. A literature search was conducted in PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) to find relevant randomized controlled trials (RCTs) until August 10, 2022. The modified Cochrane risk of bias assessment tool was applied to assess the methodological quality of eligible studies. Random network meta-analysis was conducted using STATA 14.0. Sixteen RCTs were included, with 1228 patients. Overall, the methodological quality ranged from low to moderate. ADF was superior to CER and 5:2 diet in reducing waist circumference, whereas 5:2 diet was superior to CER in reducing BMI. Regarding fat mass and drop-out, all forms of IER were comparable. Sensitivity analyses indicated that the type of individuals had no influence on the pooled results; nevertheless, ADF significantly reduced weight compared to CER and achieved significant waist circumference reduction compared to CER, 5:2 diet, and TRF. ADF may be preferentially prescribed for overweight or obese adults. More large-scale and high-quality studies are required, however, to investigate the effect of TRF on overweight and obesity.

The Significance and Correlation Analysis of Serum Uric Acid and High Sensitivity CRP in the Energy-Limiting Balance Intervention in Obese Patients.

Objective: Our aim was to explore the effects of the energy-limiting balance intervention on serum uric acid (SUA) and high sensitivity C-reactive protein (hs-CRP) and analyze the correlation between the two. Methods: Retrospectively chosen study patients were 98 obese individuals who received diagnoses and care in Xuanwu Hospital Capital Medical University between January 2021 and September 2022. The patients were divided into the intervention group and the control group via random number table, with 49 patients in each group. The control group received standard food interventions, while the intervention group received minimal energy balance interventions. The clinical outcomes in both groups were compared. We also compared patients' pre- and post-intervention levels of SUA, hs-CRP, and markers of glucose and lipid metabolism were assessed. Analysis was done on the relationship between markers of glucose and lipid metabolism and SUA and hs-CRP levels. Results: Patients in the intervention and control groups had respective ineffective rates of 6.12% and 20.41%, effective rates of 51.02% and 57.14%, substantial effective rates of 42.86% and 22.45% and overall effective rates of 93.88% and 79.59%. The intervention group's overall effective rate was substantially greater than the control group's rate (P < .05). After the intervention, patients in the intervention group had markedly decreased SUA and hs-CRP levels than patients in the control group (P < .05). Prior to the intervention, there was no clinically meaningful discrepancy between the two groups in terms of fasting blood glucose, insulin, glycated hemoglobin (HbA1c) or 2 hours postprandial blood glucose (P > .05). Following the intervention there was a statistically significant discrepancy between the intervention group and the control group in terms of fasting blood glucose, insulin, HbA1c and 2 hours postprandial blood glucose (P < .05). According to a Pearson correlation study, high-density lipoprotein (HDL) was negatively correlated with the SUA levels and positively correlated with fasting blood sugar, insulin, triglycerides, total cholesterol and low-density lipoprotein (LDL). Before the intervention, there was no clinically meaningful variation in the intervention or control groups in triglycerides, total cholesterol, LDL or HDL (P > .05). Following the intervention, patients in the intervention group had markedly decreased triglycerides, total cholesterol and LDL levels than patients in the control group, while their HDL levels had substantially increased compared with the control group (P < .05). Fasting blood sugar, insulin, triglycerides and LDL all had a positive correlation with their SUA levels (P < .05). The amount hs-CRP was inversely correlated with HDL (P < .05) and positively correlated with fasting blood glucose, insulin, 2h postprandial blood glucose, HbA1c, triglycerides and LDL. Conclusion: An energy-limiting balance intervention can effectively reduce SUA and hs-CRP, regulate the metabolism of glucose and lipid and were closely related.

Effects of different weight loss dietary interventions on body mass index and glucose and lipid metabolism in obese patients.

To investigate the effects of different weight loss interventions on body mass index (BMI) and glucose and lipid metabolism in obese patients. Obese patients (n = 135) admitted to our hospital between December 2020 and August 2022 were divided into 3 groups, according to their diet patterns: calorie-restricted diet (CRD) group (n = 39), high-protein diet (HPD) group (n = 28), and 5 + 2 intermittent fasting (IF) group (n = 68). Body weight, body fat rate, BMI, hip circumference, and waist circumference were measured before and 60 days after implementation of the respective diet plan. Glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 2h postprandial blood glucose (2hPG), triglyceride (TG), total cholesterol, low-density lipoprotein, high-density lipoprotein, and adverse events were evaluated. Following the dietary intervention, the weight (P = .005 for CRD, P < .001 for HPD, and P = .001 for IF), body fat rate (P = .027 for CRD, P = .002 for HPD, and P = .011 for IF group), BMI (P = .017 for CRD, P < .001 for HPD, and P = .002 for IF group), hip circumference (P < .001 for CRD, P = .013 for HPD, and P = .032 for IF group), waist circumference (P = .005 for CRD, P < .001 for HPD, and P = .028 for IF group), HbA1c (P = .014 for CRD, P = .002 for HPD, and P = .029 for IF group), FBG (P = .017 for CRD, P < .001 for HPD, and P = .033 for IF group), and 2hPG (P = .009 for CRD, P = .001 for HPD, and P = .012 for IF group), were significantly decreased. TG (P = .007 for CRD, P < .001 for HPD, and P = .018 for IF group), TC (P = .029 for CRD, P = .013 for HPD, and P = .041 for IF group), LDL-C (P = .033 for CRD, P = .021 for HPD, and P = .042 for IF group), and LDL-C (P = .011 for CRD, P < .001 for HPD, and P = .027 for IF group) improved significantly in the 3 groups, when compared to that before treatment. The HPD had the best effect on reducing blood lipids, followed by the CRD; the effect of IF was slightly lesser. Short-term HPD, CRD, and IF can reduce the weight and body fat of overweight/obese individuals and improve blood lipid and blood sugar levels. The effect of HPD on weight loss, body fat, and blood lipid levels was greater than that of CRD or IF.

Association between body fat and sarcopenia in older adults with type 2 diabetes mellitus: A cross-sectional study.

Objectives: To investigate the association between body fat (BF%) and sarcopenia in older adults with type 2 diabetes mellitus (T2DM) and potential link with increased levels of inflammatory indicators and insulin resistance. Methods: A total of 543 older adults with T2DM were included in this cross-sectional study. Appendicular skeletal muscle (ASM), handgrip strength and gait speed were measured to diagnose sarcopenia according to the updated Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition data were tested using dual-energy X-ray absorptiometry (DEXA). Levels of serum high-sensitive C-reactive protein (hs-CRP), interleukin-6, fasting blood insulin (FINS), hemoglobin A1c (HbA1c), 25-hydroxyvitamin D3 [25(OH) D3] were also determined. Results: The prevalence of sarcopenia in all participants was 8.84%, of which 11.90% were male and 5.84% females. The Pearson's correlation analysis revealed that BF% was negatively correlated with gait speed in men and women (R =-0.195, P=0.001; R = -0.136, P =0.025, respectively). After adjusting for all potential confounders, sarcopenia was positive associated with BF% (male, OR: 1.38, 95% CI: 1.15-1.65, P< 0.001; female, OR: 1.30, 95% CI: 1.07-1.56, P=0.007), and negatively associated with body mass index (BMI) (male, OR: 0.57, 95% CI: 0.44-0.73, P<0.001; female, OR: 0.48, 95% CI: 0.33-0.70, P<0.001). No significant differences were found in hs-CRP, interleukin-6, and insulin resistance between older T2DM adults with and without sarcopenia. Conclusion: Higher BF% was linked to an increased risk of sarcopenia in older adults with T2DM, suggesting the importance of assessing BF% rather than BMI alone to manage sarcopenia.

A Study of the Relationship between Blood Glucose and Serum Insulin in Acute Cerebrovascular Disease.

Objective: The objective of this study was to examine the correlation between blood glucose and serum insulin with acute cerebrovascular disease. Methods: A total of 1548 patients with acute cerebrovascular illness and 364 patients with a normal physical examination who were admitted to our hospital (endocrinology department) between January 2017 and July 2020 were recruited. Patients with acute cerebrovascular illness were included in the experimental group, while healthy individuals after physical examinations were included in the control group. All patients' blood glucose and serum insulin levels were measured, and the association of blood glucose and serum insulin with acute cerebrovascular illness was investigated. Results: Acute cerebrovascular disease is associated with significantly higher blood glucose and serum insulin levels versus healthy status (P < 0.05). Blood glucose and serum insulin levels were observed to be significantly higher in the hemorrhagic stroke group than in the ischemic stroke or mild hemorrhagic group (P < 0.05). Severe ischemic strokes were associated with significantly higher blood glucose levels versus mild ischemic strokes (P < 0.05). There were no significant differences in serum insulin levels between the severe ischemic stroke group and the mild ischemic stroke group (P > 0.05). Conclusion: A rise in blood glucose and serum insulin levels is associated with the incidence and prognosis of acute cerebrovascular disease, and it is positively correlated with the severity of the acute cerebrovascular disease.

Free fatty acids are associated with muscle dysfunction in Chinese adults with type 2 diabetes.

PURPOSE: Muscle dysfunction is considered a sign of poor prognosis in patients with type 2 diabetes (T2D). Thus, early detection of muscle disorders is particularly important in the T2D population. Free fatty acids (FFAs) are clinical indicators of metabolic diseases and muscle function; hence, we aimed to investigate the association between FFAs and muscle function. METHODS: A total of 160 adult subjects with T2D were characterized and analyzed in this study. Muscle mass and function were measured by walking speed, grip strength and height-adjusted appendicular skeletal muscle mass (ASMM). Partial correlation was applied to explore the correlations between FFAs and muscle indicators. Receiver operating characteristic (ROC) curves were utilized to determine the diagnostic value of FFAs in muscle mass and function. RESULTS: The FFAs levels were negatively correlated with ASMM (r = -0.347, P = 1.0E-05), grip strength (r = -0.313, P = 7.1E-05) and walking speed (r = -0.167, P = 0.039). Notably, the relationships between FFAs levels and ASMM and walking speed remained significant even after adjusting for age, sex, body mass index (BMI), diabetes duration, and hemoglobin A1C (HbA1c). The combination of conventional indicators, including age, BMI, and HbA1c levels, provided a discrimination of low grip strength with an AUC of 0.648, and low walking speed with an AUC of 0.714. Importantly, when FFAs levels were added to the model, the value of the ROC curve was further improved, with an AUC of 0.785 for low grip strength and 0.755 for low walking speed. CONCLUSIONS: The current study demonstrated a negative correlation between FFAs and muscle indicators in adult patients with T2D after adjusting for HbA1c levels. FFAs may play an important role in the pathological processes of muscle dysfunction in adults with T2D.

Hemoglobin level and osteoporosis in Chinese elders with type 2 diabetes mellitus.

OBJECTIVES: Several studies demonstrated a positive relationship between hemoglobin level and bone mineral density (BMD). Thus, the association between hemoglobin concentration and osteoporosis in elders with type 2 diabetes mellitus (T2DM) was explored in this study. METHODS: Totally, 573 elders with T2DM were included in the study. BMD was measured by dual-energy X-ray absorptiometry. Hemoglobin levels were tested. The association between the hemoglobin level and osteoporosis was subjected to logistic regression analysis. RESULTS: For men, the hemoglobin levels were significantly lower in osteoporosis group than that in non-osteoporosis group (135.98 ± 16.20 vs. 142.84 ± 13.78 g/L, P = 0.002). Hemoglobin levels were positively related with BMD of total hip and femoral neck in men (r = 0.170, P = 0.004; r = 0.148, P = 0.012, respectively). After adjusting for age, body mass index (BMI), hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR) and 25-hydroxyvitamin D3 [25(OH) D3], the hemoglobin level was related with a 0.97-fold lower risk of osteoporosis (odds ratio (OR): 0.97; 95% confidence interval (CI): 0.95-0.99; P = 0.004) in men, but no such association was found in women. CONCLUSION: Higher levels of hemoglobin play a protective role against osteoporosis in older men with T2DM.

Associations between homocysteine, inflammatory cytokines and sarcopenia in Chinese older adults with type 2 diabetes.

BACKGROUND: Sarcopenia, an age-related disease, has been implicated as both a cause and consequence of type 2 diabetes mellitus (T2DM) and a symbol of poor prognosis in older adults with T2DM. Therefore, early detection and effective treatment of sarcopenia are particularly important in older adults with T2DM. We aimed to investigate the prevalence of sarcopenia in Chinese older T2DM patients and explore whether homocysteine and inflammatory indexes could serve as biomarkers and participate in the development process of sarcopenia. METHODS: T2DM patients aged over 60 years were consecutively recruited from the ward of department of Endocrinology, Xuanwu Hospital between April 2017 and April 2019. Sarcopenia was defined based on the standard of the Asian Working Group of Sarcopenia, including muscle mass, grip strength and gait speed. Logistic regression was used to explore the association between biochemical indicators and sarcopenia. Receiver operating characteristic (ROC) curves were applied to determine the diagnostic effect of these clinical indicators. RESULTS: Totally 582 older adults with T2DM were characterized and analyzed in the study. Approximately 8.9% of the older T2DM patients had sarcopenia. After adjusting for age, sex, body mass index (BMI) and hemoglobin A1c (HbA1c), increased concentrations of homocysteine [odds ratio (OR): 2.829; 95% confidence interval (CI), 1.064-7.525] and high-sensitive C-reactive protein (hs-CRP) (OR: 1.021; 95% CI, 1.001-1.042) were independent predictors of sarcopenia; but not interleukin-6. The combination of age, sex, BMI and HbA1c provided a discriminatory effect of sarcopenia with an area under the curve (AUC) of 0.856, when homocysteine was added to the model, the value of the ROC curve was further improved, with an AUC of 0.861. CONCLUSION: In the current study, we demonstrated a positive correlation of homocysteine, hs-CRP with sarcopenia in older adults with T2DM and the relationship remained significant even after adjustment for HbA1c. These biomarkers (homocysteine and hs-CRP) may play important roles in the pathological process of sarcopenia.

Low prealbumin levels are associated with sarcopenia in older men with type 2 diabetes mellitus: A cross-sectional study.

OBJECTIVES: The aim of this study was to evaluate the association between the serum levels of prealbumin and sarcopenia in older adults with type 2 diabetes mellitus. METHODS: This cross-sectional study included 582 older adults with type 2 diabetes mellitus. Sarcopenia was defined based on the recently updated Asian Working Group for Sarcopenia 2019 criteria. Appendicular skeletal muscle was measured by dual energy x-ray absorptiometry. Serum levels of prealbumin, hemoglobin, hemoglobin A1c, and 25-hydroxyvitamin D3 were also tested. Multivariate analyses were used to assess the association between prealbumin levels and sarcopenia, adjusted for potential confounders. RESULTS: The overall prevalence of sarcopenia was 9%, of which 12% for men and 6% for women. Male participants with sarcopenia had lower prealbumin levels than those without sarcopenia (213 ± 72 versus 260 ± 56 mg/L, P < 0.001). The proportion of men with low prealbumin level (<170 mg/L) was significantly higher in individuals with sarcopenia than in those without (31% versus 6%, respectively). In a logistic regression model, after adjusting for all potential covariates, low prealbumin (odds ratio, 4.15; 95% confidence interval, 1.13-15.25; P = 0.03) was significantly associated with sarcopenia in men, but the relationship between prealbumin and sarcopenia was not found in women. CONCLUSION: Low prealbumin levels were associated with an increased risk for sarcopenia in older men with T2DM.

Low free triiodothyronine levels are associated with risk of frailty in older adults with type 2 diabetes mellitus.

OBJECTIVES: With aging populations around the world, frailty is becoming more prevalent increasing the need to early identify those at risk of frailty. The association between thyroid hormone levels and frailty in subjects with type 2 diabetes mellitus (T2DM) remains unclear. The objective of the study was to evaluate the relationship between thyroid hormone concentrations and frailty in older adults with T2DM. METHODS: A total of 240 older adults with T2DM were divided into three groups according to the frailty phenotype criteria: robust group (n = 94), pre-frail (n = 110) and frail group (n = 36). Concentrations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH), 25-hydroxyvitamin D3 [25(OH) D3], highly sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were determined. Handgrip strength was measured using a Jamar hand dynamometer. Physical function was assessed by gait speed and the timed go and up (TUG) test. Logistic regression analysis was performed to evaluate the association between FT3 and frailty. RESULTS: The FT3 level was the lowest among frail people (2.56 ± 0.42 pg/mL), followed by pre-frail participants (2.73 ± 0.38 pg/mL), with the highest among the robust subjects (2.83 ± 0.43 pg/mL). FT3 level was positively correlated with handgrip strength and gait speed (R = 0.313, P < 0.001; R = 0.250, P < 0.001, respectively), while negatively correlated with TUG time (R = -0.276, P < 0.001). After adjusting for age, sex, TSH, 25(OH) D3 and estimate glomerular filtration rate (eGFR), logistic regression showed that low FT3 was significantly associated with an increased risk of frailty (odds ratio (OR): 4.53; 95% confidence interval (CI): 1.89-10.83; P = 0.001). CONCLUSION: Low levels of FT3 were associated with an increased risk of frailty in older adults with T2DM. Measuring FT3 might be useful for identifying those at high risk of frailty.

Association of serum prealbumin with risk of osteoporosis in older adults with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Poor nutritional status is associated with osteoporosis. Prealbumin is a more sensitive marker than albumin to assess nutritional status. Therefore, the relationship between serum levels of prealbumin and osteoporosis in older adults with type 2 diabetes mellitus (T2DM) was investigated. METHODS: A total of 370 older adults with T2DM were divided into two groups: older adults with osteoporosis (n = 249) and older adults without osteoporosis (n = 121). Bone mineral density (BMD) and appendicular skeletal muscle (ASM) were measured by dual-energy X-ray absorptiometry (DEXA). Serum levels of prealbumin, highly sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), 25-hydroxyvitamin D3 [25(OH) D3] were also tested. Logistic regression analysis was performed to assess the association between prealbumin and osteoporosis. RESULTS: The adults with osteoporosis had lower prealbumin levels than those without osteoporosis (235.40 ± 60.66 versus 261.34 ± 55.28 mg/l, p < 0.001). The proportion of adults with prealbumin levels below the normal range was significantly higher in individuals with osteoporosis compared with those without osteoporosis (16.53% versus 4.42%, respectively). After adjusting for age, sex, body mass index (BMI), anemia, handgrip strength and skeletal muscle index (SMI), logistic regression showed that participants with lower levels of prealbumin had a higher risk of osteoporosis [odds ratio (OR): 3.85; 95% confidence interval (CI): 1.54-6.34; p = 0.004]. CONCLUSION: Our findings suggested that low levels of prealbumin were associated with an increased risk of osteoporosis in older adults with T2DM. Further longitudinal studies should be conducted to determine if there is a causative association between prealbumin and osteoporosis.