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.

Waist circumference is a better predictor of risk for frailty than BMI in the community-dwelling elderly in Beijing.

AIM: Obesity is found to be associated with frailty. Body mass index (BMI) and waist circumference (WC) are the commonly used measures for obesity, the former is more closely related to general obesity and body weight; the latter can more accurately reflect abdominal obesity and is more closely associated with metabolic disorders. In this study, we intend to study the relationship between frailty, BMI and WC among older people. METHODS: Data were derived from the Beijing Longitudinal Study on Aging II Cohort, which included 6320 people 65 years or older from three urban districts in Beijing. A Frailty Index derived from 33 items was developed according to Rockwood's cumulative deficits method. A Frailty Index ≥ 0.25 was used as the cut-off criteria. BMI was classified as underweight, normal, overweight, or obese (< 18.5, 18.5-< 24.0, 24.0-27.9, ≥ 28.0 kg/m2, respectively). High WC was defined as WC ≥ 85 cm in men and ≥ 80 cm in women. RESULTS: People with a larger BMI (≥ 28.0 kg/m2, 22.6%) or a larger WC (18.5%) were more likely to be frail. People with normal BMI and overweight people do not suffer from higher prevalence for frailty. In comparison with individuals with normal BMI (18.5-< 24.0 kg/m2) and normal WC (< 85 cm in men, <80 cm in women), the risk of frailty was higher among individuals who have normal BMI and large WC (odds ratio 1.68; 95% CI 1.33-2.12), have overweight and large WC (odds ratio 1.58; 95% CI 1.23-1.96), or have obesity and large WC (odds ratio 2.28; 95% CI 1.79-2.89). In people with normal WC, only those who are underweight have a higher risk for frailty (odds ratio 1.65, 95% CI 1.08-2.52). In comparison with BMI, the relation of WC with the risk for frailty was much closer. CONCLUSIONS: Abdominal obesity is more closely associated with incidence of frailty than general obesity in the elderly. Older adults with large waist circumference are more likely to be frail. Frailty in the elderly might be more closely related to metabolic disorders. WC might be a better measurement to detect frailty than BMI, given its relationship with metabolic disorders.

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.

Investigation of rhodamine derivative on behavioral impairment in a double neurotoxin lesion of substantia nigra and locus coeruleus dysfunctional mice.

Although multiple mechanisms have been studied, there is still a lack of effective treatment on non-motor symptoms in Parkinson's disease (PD) patients. Therapeutic effects of 5-(4-hydroxy-3-dimethoxybenzylidene)-thiazolidinone (RD-1), one of rhodamine derivatives, on motor recovery have been previously demonstrated, but its effects on non-motor symptoms remain unclear. Herein, we explored the beneficial effects of RD-1 on PD-related non-motor symptoms and changes in synaptic plasticity in the mesencephalon. To investigate its therapeutic effects in the non-motor symptoms of Parkinsonian model, we employed male C57BL/6N mice and double injection with noradrenergic specific neurotoxin N-2-Chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride, followed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Next, we performed behavioral tests, histological analyses and immunoblotting. Our findings showed that RD-1 significantly alleviated locomotor abnormality, motor disturbance, anxiety/depression-like behavior and memory deficit. It rescued the levels of tyrosine hydroxylase in substantia nigra, and striatum. Moreover, RD-1 upregulated expression levels of α-synuclein, synapsin II, postsynaptic density 95 and vesicle-associated membrane protein 2. The restoration of synaptic function may underlie the neuroprotective effects of RD-1 in double lesioned mice, confirming its protective effect for dopaminergic neurodegeneration.

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.

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.

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.

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.

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.

Risk factors for cognitive impairment in older people with diabetes: a community-based study.

AIM: The aim of this study was to investigate the risk factors for cognitive impairment in older people with diabetes. METHODS: This cross-sectional study included 2626 community-dwelling participants with diabetes aged ⩾55 years, living in Beijing, China. The participants were screened for risk factors, including smoking, obesity, hypertension, stroke, coronary heart disease, dyslipidemia, depression, apolipoprotein E (APOE) genotype, and low physical activity. Cognitive function was assessed with the scholarship-adjusted Mini-Mental State Examination (MMSE): MMSE ⩽17 for iliterate participants; MMSE ⩽20 for primary school graduates (⩾6 years of education); and MMSE ⩽24 for junior school graduates or above (⩾9 years of education). RESULTS: The prevalence of cognitive impairment in older people with diabetes was 9.90%. Multiple logistic regression analysis demonstrated that stroke [odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.20-2.43], less than 0.5 h exercise per day (OR = 1.89, 95% CI = 1.37-2.61), and depression (OR = 1.64, 95% CI = 1.06-2.54), but not smoking, obesity, hypertension, dyslipidemia, and coronary heart disease, were independent risks for cognitive impairment in older people with diabetes. In addition, being married (OR = 0.66, 95% CI = 0.47-0.93) and urban living (OR = 0.33, 95% CI = 0.22-0.48) could decrease the risk of cognitive impairment. CONCLUSIONS: Stroke, depression, and less than 0.5 h exercise per day were independent risks for cognitive impairment in older people with diabetes, whereas being married and urban living were protective.

Hyperglycemia is associated with poor in-hospital outcome in elderly patients with acute ischemic stroke.

Fasting hyperglycemia is associated with poor neurologic outcome in acute ischemic stroke (AIS), but its relationship with in-hospital outcome in elderly patients remains largely unknown. To assess the association of in-hospital outcome with fasting plasma glucose (FPG) levels at admission in individuals with AIS.This retrospective propensity score-matched case-control study included patients aged over 60 years suffering from AIS and who were admitted to the emergency department from November 2013 to October 2016. Subjects were grouped into the poor-outcome and good-outcome groups based on mortality and intensive care unit (ICU) admission.The poor- and good-outcome groups comprised 74 and 1927 cases, respectively, before propensity score matching (PSM), and 74 and 296 cases, respectively, after PSM. Univariable logistic regression analysis showed that initial FPG after admission was associated with poor in-hospital outcome. Multivariable logistic regression analysis showed that initial FPG after admission was an independent predictor of poor in-hospital outcome (odds ratio = 1.11, 95% confidence interval: 1.037-1.188, P = .003).This study used PSM and strongly suggests that FPG is an independent predictive factor of poor in-hospital outcome in elderly patients with AIS. High initial FPG levels after admission may predict poor in-hospital outcome. Prospective studies are needed to confirm these findings.

Different risk factors for cognitive impairment among community-dwelling elderly, with impaired fasting glucose or diabetes.

AIM: The aim of this study was to investigate whether elderly people with impaired fasting glucose (IFG) or diabetes mellitus (DM) share the common risk factors for cognitive impairment as compared to normal blood glucose population. METHODS: This cross-sectional study assessed 10,039 community-dwelling participants aged ≥ 55 years in Beijing, China. According to the glycemic status, subjects were classified into three groups: normal fasting plasma glucose (NG, n=6399), impaired fasting glucose (IFG, n=873) and DM (n=2626). The Mini-Mental State Examination (MMSE) was applied to evaluate the cognitive function status of the study population. Potential demographic, clinical, and genetic risk factors for cognitive impairment were collected and compared across the three groups. Multivariate logistic regression model was performed to explore the risk factors associated with cognitive impairment. RESULTS: Education-modified MMSE scores in the participants with NG, IFG, and DM were 26.91±3.94, 26.67±4.00, and 26.58±4.11, respectively (P=0.0008). In the age- and sex-adjusted comparisons, the MMSE scores in subjects with DM and IFG were significantly lower than that in subjects with normal glucose (P=0.01 and P=0.02, respectively). The logistic regression analysis showed that risk factors only in the NG population were older age, female, apoEε4 carrier, normal or lower uric acid (UA) levels. Hypertension was an independent risk factor only in IFG group, and the history of stroke and depression were the risk factors associated with cognitive impairment only in the DM group. CONCLUSION: Subjects with DM or IFG had a lower performance on the MMSE test compared with subjects who had normal blood glucose. The elderly with diabetes and IFG have some different risk factors for cognitive impairment as compared to those with normal blood glucose.

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.

Serum uric acid and impaired cognitive function in community-dwelling elderly in Beijing.

The relationship between serum uric acid (sUA) and cognitive function is contradictory. This study assessed the association between sUA and cognitive impairment in 10,039 community-dwelling subjects aged ≥55years living in Beijing, China. Participants underwent determination of sUA and an evaluation of cognitive function using the scholarship-adjusted Mini-Mental State Examination (MMSE): MMSE ≤17 for illiterates; MMSE≤20 for primary school graduates (≥6years of education); and MMSE≤24 for junior school graduates or above (≥9years of education). Among the 10016 persons with valid MMSE scores, the prevalence of cognitive impairment was 9.14%. A multivariate logistic regression model including demographic, clinical and genetic parameters was performed to assess the relationship between sUA and cognitive impairment. Persons with cognitive impairment had lower sUA levels than those with normal cognitive function: (302.30±82.80 vs. 312.20±84.01µmol/L, p=0.001). After adjusting for age, sex, lifestyle, relevant diseases and the apolipoprotein E (APOE) ε4 allele, stepwise logistic regression showed that participants with higher levels of sUA had a lower risk of cognitive impairment (hazard ratio (HR): 0.78; 95% confidence interval (CI): 0.62-0.96; p=0.022). In this baseline cross-sectional population-based sample, high levels of sUA were associated with a decreased risk of cognitive impairment.