Visible-Light-Mediated Catalyst-Free [2+2] Cycloaddition Reaction for Dihydrocyclobuta[b]naphthalene-3,8-diones Synthesis under Mild Conditions.

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[b]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Waist-to-height ratio, an optimal anthropometric indicator for metabolic dysfunction associated fatty liver disease in the Western Chinese male population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been entitled as metabolic-dysfunction associated fatty liver disease (MAFLD). Therefore anthropometric indicators of adiposity may provide a non-invasive predictive and diagnostic tool for this disease. This study intended to validate and compare the MAFLD predictive and diagnostic capability of eight anthropometric indicators. METHODS: The study involved a population-based retrospective cross-sectional design. The Fangchenggang area male health and examination survey (FAMHES) was used to collect data of eight anthropometric indicators, involving body mass index (BMI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), body adiposity index (BAI), cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and abdominal volume index (AVI). Receiver operating characteristics (ROC) curves and the respective areas under the curves (AUCs) were utilized to compare the diagnostic capacity of each indicator for MAFLD and to determine the optimal cutoff points. Binary logistic regression analysis was applied to identify the odds ratios (OR) with 95% confidence intervals (95% CI) for all anthropometric indicators and MAFLD. The Spearman rank correlation coefficients of anthropometric indicators, sex hormones, and MAFLD were also calculated. RESULTS: All selected anthropometric indicators were significantly associated with MAFLD (P < 0.001), with an AUC above 0.79. LAP had the highest AUC [0.868 (95% CI, 0.853-0.883)], followed by WHtR [0.863 (95% CI, 0.848-0.879)] and AVI [0.859 (95% CI, 0.843-0.874)]. The cutoff values for WHtR, LAP and AVI were 0.49, 24.29, and 13.61, respectively. WHtR [OR 22.181 (95% CI, 16.216-30.340)] had the strongest association with MAFLD, regardless of potential confounders. Among all the anthropometric indicators, the strongest association was seen between LAP and sex hormones. CONCLUSION: All anthropometric indicators were associated with MAFLD. WHtR was identified as the strongest predictor of MAFLD in young Chinese males, followed by LAP and AVI. The strongest association was found between LAP and sex hormones.

Vascular and metabolic effects of metformin added to insulin therapy in patients with type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly-onset cardiovascular disease (CVD). Mounting studies have shown that metformin may reduce maximal carotidintima-media thickness (cIMT), improve insulin resistance and metabolic control in subjects with T1DM, and thus, may extend cardioprotective benefits. This systematic review and meta-analysis was performed to assess the efficacy and safety of metformin added to insulin therapy on reducing CVD risks and improving metabolism in T1DM. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared metformin and insulin combination (duration ≥3 months) to insulin treatment alone in T1DM. Data were expressed as weighted/standardized mean differences (MDs/SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, along with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the overall certainty of the evidence. RESULTS: Nineteen RCTs (n = 1540) met the eligibility criteria. Metformin treatment significantly reduced carotid artery intima-media thickness (MD -0.06 mm [95% CI -0.88, -0.28], P < .001). Though no significant difference was found in insulin sensitivity (SMD 2.21 [95% CI -1.88, 6.29], P = .29), the total daily insulin dosage (SMD -0.81 [95% CI -1.25, -0.36], P < .001) along with traditional CVD risk factors showed improvement by better glycaemic control, partial lipid profiles, diastolic blood pressure, and limited weight gain, with neutral effect on diabetic ketoacidosis, lactic acidosis, and hypoglycaemia. However, metformin therapy increased the incidence of gastrointestinal adverse events. CONCLUSIONS: Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.

Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Higher Sensitivity to Thyroid Hormones May Be Linked to Maintaining the Healthy Metabolic Condition in People with Obesity: New Insight from NHANES.

INTRODUCTION: Obesity contributes to the pathogenesis of diverse metabolic diseases, yet the mechanism underlying metabolically healthy obesity (MHO) remains elusive. Thyroid hormones and sensitivity to them have a major impact on metabolism. Our study aimed to investigate the association between MHO and thyroid hormone sensitivity. METHODS: Thyroid hormone indices, including the thyroid-stimulating hormone (TSH) index (TSHI), the Thyrotroph Thyroxine Sensitivity Index (TTSI), the Thyroid Feedback Quantile-Based Index (TFQI), and the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), were calculated based on a non-institutionalized US sample in the National Health and Nutrition Examination Survey (NHANES, 2007-2012). Participants were divided into four groups (metabolically healthy non-obesity [MHNO], metabolically unhealthy non-obesity [MUNO], MHO, and metabolically unhealthy obesity [MUO]) according to their body mass index and metabolic profiles. Linear regression, logistic regression, and restricted cubic splines were employed to analyze the association between thyroid hormone indices and metabolic phenotypes. RESULTS: A total of 4,857 participants (49.6% men; mean age, 42.6 years) were included, with 1,539 having obesity and 235 identified as MHO. Participants in the MHO group exhibited lower levels of TSH, TSHI, TTSI, TFQI, and PTFQI compared with the MHNO group (all p < 0.05), while the differences among MHNO, MUNO, and MUO groups were not statistically significant (all p > 0.05). Among participants with obesity, TSH, TSHI, TTSI, TFQI, and PTFQI were positively associated with metabolic abnormality (all p < 0.05). CONCLUSION: Participants with MHO exhibited higher thyroid hormone sensitivity among various obesity phenotypes, even when compared with those with MHNO. A positive association was observed between metabolic abnormality and thyroid hormone sensitivity, while the trend of TSH was observed to be consistent with sensitivity to thyroid hormone indices in discriminating metabolic abnormality. Hence, TSH has the potential to serve as a convenient index for detecting sensitivity to thyroid hormones and further metabolic conditions.

Image-guided Thermal Ablation as a Promising Approach to Both Nontoxic and Toxic Autonomously Functioning Thyroid Nodules.

RATIONALE AND OBJECTIVES: Although thermal ablation has been recommended as an alternative therapy option for autonomously functioning thyroid nodules (AFTN), current clinical evidence mainly focuses on toxic AFTN. This study aims to evaluate and compare the efficacy and safety of thermal ablation (percutaneous radiofrequency ablation or microwave ablation) in treating nontoxic and toxic AFTN. MATERIALS AND METHODS: AFTN patients who received a single session of thermal ablation with a follow-up period ≥12 months were recruited. Changes in nodule volume and thyroid function, and complications were evaluated. Technical efficacy was defined as the maintenance or restoration of euthyroidism with a volume reduction rate (VRR) ≥80% at the last follow-up. RESULTS: In total, 51 AFTN patients (age: 43.8±13.9 years, female: 88.2%) with a median follow-up period of 18.0 (12.0-24.0) months were included, where 31 were nontoxic (nontoxic group), and 20 were toxic (toxic group) before ablation. The median VRR was 96.3% (80.1%-98.5%) and 88.3% (78.3%-96.2%) in the nontoxic and toxic groups, respectively, and the respective euthyroidism rates were 93.5% (29/31, 2 evolved to toxic) and 75.0% (15/20, 5 remained toxic). The corresponding technical efficacy was 77.4% (24/31) and 55.0% (11/20, p=0.126). Except for one case of stress-induced cardiomyopathy in the toxic group, no permanent hypothyroidism or other major complications occurred in both groups. CONCLUSION: Image-guided thermal ablation is efficacious and safe in treating AFTN, both nontoxic and toxic. Recognition of nontoxic AFTN would be helpful for treatment, efficacy evaluation, and follow-up.

Erratum: Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway.

[This corrects the article DOI: 10.3892/etm.2015.2220.].

Comparison of six anthropometric measures in discriminating diabetes: A cross-sectional study from the National Health and Nutrition Examination Survey.

BACKGROUND: Traditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating the risk of diabetes. This study aimed to evaluate the performance of new anthropometric measures and a combination of anthropometric measures for identifying diabetes. METHODS: A total of 46 979 participants in the National Health and Nutrition Examination Survey program were included in this study. Anthropometric measures, including weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), conicity index (CI), and A Body Shape Index (ABSI), were calculated. Logistic regression analysis and restricted cubic splines were used to evaluate the association between the anthropometric indices and diabetes. The receiver operating characteristic (ROC) curve analysis was performed to compare the discrimination of different anthropometric measures. RESULTS: All anthropometric measures were positively and independently associated with the risk of diabetes. After adjusting for covariates, the per SD increment in WC, WtHR, and CI increased the risk of diabetes by 81%, 83%, and 81%, respectively. In the ROC analysis, CI showed superior discriminative ability for diabetes (area under the curve 0.714), and its optimum cutoff value was 1.31. Results of the combined use of BMI and other anthropometric measures showed that among participants with BMI <30 kg/m2 , an elevated level of another metric increased the risk of having diabetes (P < .001). Similarly, at low levels of weight, CI, and ABSI, an elevated BMI increased diabetes risk (P < .001). CONCLUSIONS: WtHR and CI had the best ability to identify diabetes when applied to the US noninstitutionalized population. Anthropometric measures containing WC information could improve the discrimination ability.

Peripheral Nerve Conduction And Sympathetic Skin Response Are Reliable Methods to Detect Diabetic Cardiac Autonomic Neuropathy.

Aim: This study aimed to investigate the role of nerve conduction studies (NCS) and sympathetic skin response (SSR) in evaluating diabetic cardiac autonomic neuropathy (DCAN). Methods: DCAN was diagnosed using the Ewing test combined with heart rate variability analysis. NCS and SSR were assessed by electrophysiological methods. The association between NCS/SSR and DCAN was assessed via multivariate regression and receiver-operating characteristic analyses. Results: The amplitude and conduction velocity of the motor/sensory nerve were found to be significantly lower in the DCAN+ group (all P < 0.05). A lower amplitude of peroneal nerve motor fiber was found to be associated with increased odds for DCAN (OR 2.77, P < 0.05). The SSR amplitude was lower while the SSR latency was longer in the DCAN+ group than in the DCAN- group. The receiver-operating characteristic analysis revealed that the optimal cutoff points of upper/lower limb amplitude of SSR to indicate DCAN were 1.40 mV (sensitivity, 61.9%; specificity, 66.3%, P < 0.001) and 0.85 mV (sensitivity, 66.7%; specificity, 68.5%, P < 0.001), respectively. The optimal cutoff points of upper/lower limb latency to indicate DCAN were 1.40 s (sensitivity, 61.9%; specificity, 62%, P < 0.05) and 1.81 s (sensitivity, 69.0%; specificity, 52.2%, P < 0.05), respectively. Conclusions: NCS and SSR are reliable methods to detect DCAN. Abnormality in the peroneal nerve (motor nerve) is crucial in predicting DCAN. SSR may help predict DCAN.

Body Roundness Index Is a Superior Obesity Index in Predicting Diabetes Risk Among Hypertensive Patients: A Prospective Cohort Study in China.

Objective: Individuals with both hypertension and diabetes have been confirmed to significantly increase the risk of cardiovascular disease morbidity and mortality compared with those with only hypertension or diabetes. This study aimed to evaluate the potential of different anthropometric indices for predicting diabetes risk among hypertensive patients. Methods: The study group consisted of 6,990 hypertensive adults without diabetes who were recruited in China. Demographic and clinical assessment, physical examinations, laboratory tests, and anthropometric measurements, including body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and novel indices (ABSI, AVI, BAI, BRI, CI, WWI, and WHHR), were performed at baseline and during the (median) 3-year follow-up. Cox regression analyses were conducted to estimate effects from these indices for the onset of diabetes. Receiver operator characteristic (ROC) analyses were conducted to assess the predictive capacities of the anthropometric indices and determine the optimal cut-points. Results: A total of 816 (11.7%) developed diabetes during our prospective study. Multivariate Cox regression analyses revealed weight, WC, WHR, WHtR, BAI, BRI, and WWI as the independent risk factor for diabetes among hypertensive patients, regardless of whether it was treated as a continuous or categorical variable (P < 0.05). Further Cox analyses combining BMI and different central obesity indices showed that elevated WC, WHR, WHtR, AVI, BRI, CI, regardless of the general obesity status, were found to be each independently associated with increased diabetes risk (P < 0.05). Dynamic increases of BRI < 5.24 to BRI ≥ 5.24 were associated with increased risk (HR = 1.29; 95% CI, 1.02, 1.64), and its reversal was associated with reduced risk (HR = 1.56; 95% CI, 1.23, 1.98) compared with the others (HR = 1.95; 95% CI, 1.63, 2.32). ROC analysis indicated that the areas under the ROC curves (AUC) of the anthropometric indices ranged from 0.531 to 0.63, with BRI (cut-off value = 4.62) and WHtR having the largest area. Conclusions: Based on this novel study, BRI was the most superior predictor and independent determinant for diabetes onset among the hypertensive population. Hypertensive patients with BRI > 4.62, regardless of general obesity status, were at high risk of diabetes. Thus, the prompt screening and diagnosis of diabetes should be carried out among these patients for timely integrated intervention.

Association of Anthropometric Indices With the Development of Diabetes Among Hypertensive Patients in China: A Cohort Study.

Background: Patients with comorbidity of hypertension and diabetes are associated with higher morbidity and mortality of cardiovascular disease than those with hypertension or diabetes alone. The present study aimed to identify anthropometric risk factors for diabetes among hypertensive patients who were included in a retrospective cohort study. Methods: Hypertensive adults without diabetes were recruited in China. Demographic, clinical, biochemical, and anthropometric indices were collected at baseline and during the follow-up. Anthropometric measures included BMI, waist circumference, waist-to-height ratio (WHtR), and waist-to-hip ratio, and several novel indices. To estimate the effect of baseline and dynamic changes of each anthropometric index on risk of new-onset diabetes (defined as self-reported physician-diagnosed diabetes and/or use of hypoglycemic medication, or new-onset FPG≥7.0 mmol/L during follow-up), Cox regression models were used. Results: A total of 3852 hypertensive patients were studied, of whom 1167 developed diabetes during follow-up. Multivariate Cox regression analyses showed that there was a graded increased risk of incident diabetes with successively increasing anthropometric indices mentioned above (all P<0.05). Regardless of the baseline general obesity status, elevated WHtR was both related to higher risk of diabetes; the HRs (95%CI) of baseline BMI<24 kg/m2 & WHtR≥0.5 group and BMI≥24 kg/m2 & WHtR≥0.5 group were 1.34 (1.05, 1.72), 1.85 (1.48, 2.31), respectively. Moreover, the dynamic changes of WHtR could sensitively reflect diabetes risk. Diabetes risk significantly increased when patients with baseline WHtR<0.5 progressed to WHtR≥0.5 during the follow-up (HR=1.63; 95%CI, 1.11, 2.40). There was also a decreasing trend towards the risk of incident diabetes when baseline abnormal WHtR reversed to normal at follow-up (HR=1.93; 95%CI, 1.36, 2.72) compared with those whose WHtR remained abnormal at follow-up (HR=2.04; 95%CI, 1.54, 2.71). Conclusions: Central obesity is an independent and modifiable risk factor for the development of diabetes among hypertensive patients. Measuring indices of central obesity in addition to BMI in clinics could provide incremental benefits in the discrimination of diabetes among Chinese hypertensive patients. Dynamic changes of WHtR could sensitively reflect changes in the risk of diabetes. Therefore, long-term monitoring of hypertensive patients using non-invasive anthropometric measures and timely lifestyle intervention could effectively reduce the development of diabetes.

Insulin resistance is independently associated with cardiovascular autonomic neuropathy in type 2 diabetes.

AIMS/INTRODUCTION: Diabetic cardiovascular autonomic neuropathy (DCAN) seriously threatens the prognosis and quality of life of patients with type 2 diabetes mellitus, associated with increased mortality. The present study aimed to investigate the relevant risk factors of DCAN. MATERIALS AND METHODS: The present study enrolled a total of 109 patients with type 2 diabetes mellitus. DCAN was defined as a score of at least 2 points in Ewing tests. The updated homeostasis model assessment of insulin resistance (HOMA2-IR) based on fasting C-peptide was calculated to reflect insulin resistance. Logistic regression analysis, interaction and stratified analyses were used to investigate the relationship between HOMA2-IR or other indicators and DCAN. Receiver operating characteristic analysis was carried out to estimate the discriminative value of the variables independently associated with DCAN and to determine the optimal cut-off point of these models to screen DCAN. RESULTS: The HOMA2-IR levels were significantly higher in patients with DCAN, and tended to be worsened with the progression of the DCAN. Logistic regression analysis showed an independent association between HOMA2-IR (odds ratio 39.30, 95% confidence interval 7.17-215.47) and DCAN. HOMA2-IR (area under the curve 0.878, 95% confidence interval 0.810-0.946; cut-off value 1.735) individually predicted DCAN significantly higher than the other independent risk factors individually used, whereas models combining HOMA2-IR and other risk factors did not significantly boost the diagnostic power. CONCLUSIONS: Insulin resistance is independently associated with DCAN. HOMA2-IR presents to be a highly accurate and parsimonious indicator for DCAN screening. Patients with HOMA2-IR >1.735 are at a high risk of DCAN; thus, priority diagnostic tests should be carried out for these patients for timely integrated intervention.

Evaluation of the Degree of Agreement of Four Methods for Diagnosing Diabetic Autonomic Neuropathy.

Background: There are many methods to diagnose diabetic autonomic neuropathy (DAN); however, often, the various methods do not provide consistent results. Even the two methods recommended by the American Diabetes Association (ADA) guidelines, Ewing's test and heart rate variability (HRV), sometimes give conflicting results. The purpose of this study was to evaluate the degree of agreement of the results of the Composite Autonomic Symptom Score 31 (COMPASS-31), skin sympathetic reaction (SSR) test, Ewing's test, and HRV in diagnosing DAN. Methods: Patients with type 2 diabetes were recruited and each received the COMPASS-31, SSR, Ewing's test, and HRV for the diagnosis of DAN. Patients were categorized as DAN(+) and DAN(-) by each of the tests. Kappa consistency tests were used to evaluate the agreement of diagnosing DAN between any two methods. Spearman's correlation test was used to evaluate the correlations of the severity of DAN between any two methods. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic value and the cutoff value of each method. Results: A total of 126 type 2 diabetic patients were included in the study. The percentages of DAN(+) results by HRV, Ewing's test, COMPASS-31, and SSR were 61, 40, 35, and 33%, respectively. COMPASS-31 and Ewing's test had the best agreement for diagnosing DAN (κ = 0.512, p < 0.001). COMPASS-31 and Ewing's test also had the best correlation with respect to the severity of DAN (r = 0.587, p < 0.001). Ewing's test and COMPASS-31 had relatively good diagnostic values (AUC = 0.703 and 0.630, respectively) in the ROC analyses. Conclusions: COMPASS-31 and Ewing's test exhibit good diagnostic consistency and severity correlation for the diagnosis of DAN. Either test is suitable for the diagnosis of DAN and treatment follow-up.

Integrative analyses of biomarkers and pathways for adipose tissue after bariatric surgery.

We explored potential biomarkers and molecular mechanisms regarding multiple benefits after bariatric surgery. Differentially expressed genes (DEGs) for subcutaneous adipose tissue (AT) after bariatric surgery were identified by analyzing two expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs and gene-TFs networks were interrogated to identify hub genes and associated pathways. Co-expressed DEGs included one that was up-regulated and 22 that were down-regulated genes. The enrichment analyses indicated that down-regulated DEGs were significantly involved in inflammatory responses. GSEA provided comprehensive evidence that most genes enriched in pro-inflammation pathways, while gene-sets after surgery enriched in metabolism. We identified nine hub genes in the PPI network, most of which were validated as highly expressed and hypomethylated in obesity by Attie Lab Diabetes and DiseaseMeth databases, respectively. DGIdb was also applied to predict potential therapeutic agents that might reverse abnormally high hub gene expression. Bariatric surgery induces a significant shift from an obese pro-inflammatory state to an anti-inflammatory state, with improvement in adipocyte metabolic function - representing key mechanisms whereby AT function improves after bariatric surgery. Our study deepens a mechanistic understanding of the benefits of bariatric surgery and provides potential biomarkers or treatment targets for further research.

Verapamil Attenuated Prediabetic Neuropathy in High-Fat Diet-Fed Mice through Inhibiting TXNIP-Mediated Apoptosis and Inflammation.

Diabetic neuropathy (DN) is a common and severe complication of diabetes mellitus. There is still a lack of an effective treatment to DN because of its complex pathogenesis. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of thioredoxin, has been shown to be associated with diabetic retinopathy and nephropathy. Herein, we aim to investigate the role of TXNIP in prediabetic neuropathy and therapeutic potential of verapamil which has been shown to inhibit TXNIP expression. The effects of mediating TXNIP on prediabetic neuropathy and its exact mechanism were performed using high-fat diet- (HFD-) induced diabetic mice and palmitate-treated neurons. Our results showed that TXNIP upregulation is associated with prediabetic neuropathy in HFD-fed mice. TXNIP knockdown improved DN in HFD-induced prediabetic mice. Mechanistically, increased TXNIP in dorsal root ganglion is transferred into the cytoplasm and shuttled to the mitochondria. In cytoplasm, TXNIP binding to TRX1 results in the increased oxidative stress and inflammation. In mitochondria, TXNIP binding to TRX2 induced mitochondria dysfunction and apoptosis. TXNIP isolated from TRX2 then shuttles to the cytoplasm and binds to NLRP3, resulting in further increased TXNIP-NLRP3 complex, which induced the release of IL-1ß and the development of inflammation. Thus, apoptosis and inflammation of dorsal root ganglion neuron eventually cause neural dysfunction. In addition, we also showed that verapamil, a known inhibitor of calcium channels, improved prediabetic neuropathy in the HFD-fed mice by inhibiting the upregulation of TXNIP. Our finding suggests that TXNIP might be a potential target for the treatment of neuropathy in prediabetic patients with dyslipidemia.

Effects of Long-Versus Short-Term Exposure to the Mediterranean Diet on Skin Microvascular Function and Quality of Life of Healthy Adults in Greece and the UK.

The beneficial effects of the Mediterranean diet (MD) adherence in reducing cardiovascular disease (CVD) risk and improving CVD-related physiological indices have been well-documented. However, the exact MD adherence duration needed for these effects to occur is under-researched. The aim of the present, two-arm, two-site study clinical trial was to assess the effects of long- vs. short-term MD adherence on the skin microvascular circulation, and quality of life. Two groups were recruited, one being long-term MD adherers (>5 years; from Greece; control group), and one of the non-adherers (from the UK), with the latter participating in a four-week MD intervention (intervention group). Our main outcome was skin microvascular function assessed by cutaneous vascular conductance (CVC). Secondary outcomes included quality of life, dietary intake, blood pressure and lipidemic profile. At the end of the intervention, both groups had high MD adherence. For the intervention group, significantly improved post-intervention CVC values were noted concerning the initial peak phase (2.0 ± 0.6 vs. 2.8 ± 0.8; p < 0.05). CVC values of the control group, were however higher at the plateau phase in comparison to the intervention group (intervention end; 3.8 ± 0.8 vs. 3.1 ± 1.2; p < 0.05). As per QoL, the physical domain was improved post-intervention (13.7 ± 1.2 vs. 15.9 ± 1.2; p < 0.05). No differences were observed in the lipidemic profile between groups, or between the baseline and final intervention phases. The findings indicate that although short-term MD adherence is effective in improving certain microvascular physiological properties and QoL domains, there is room for additional improvement, observed in long-term adherers. Our findings are important in the design of future, MD-based, lifestyle interventions, with the advisable durations differing between target groups.

Physiological effects of a short-term lifestyle intervention based on the Mediterranean diet: comparison between older and younger healthy, sedentary adults.

OBJECTIVE: The aim of this study was to determine whether short-term adherence to the Mediterranean diet (MD) was associated with improved physiological function. METHODS: This was a single-center, cohort pilot study with 24 healthy, sedentary younger (18-35 y of age) and older (55-75 y of age) adults. Participants were advised to follow the MD for 4 wk. Baseline and post-intervention measurements were taken of weight, height, waist and hip circumference, blood pressure, and heart rate, as well as microvascular physiological assessments using laser Doppler flowmetry (LDF) at rest, as well as transcutaneous oxygen pressure (TcpO2) during a sub-maximal exercise assessment. RESULTS: We identified statistically-significant improvements in axon-mediated microvascular vasodilation (2.24 ± 0.56 to 3.14 ± 0.84; P = 0.03) and endothelial-mediated nitric oxide synthesis (2.59 ± 0.67 to 3.32 ± 0.87; P = 0.022) in the younger group. Despite the intervention not including an exercise element, the rate of perceived exertion was reduced in both groups (P < 0.001), after following the MD for 1 mo. CONCLUSIONS: Improvements in physiological function were observed after a short-term dietary intervention based on the MD in a younger population. These were not statistically matched in an older group. Our findings suggest that different durations should be applied when designing dietary interventions in different age groups, with expectations in physiological improvement differing.

Correlation Between Different Stages of Diabetic Nephropathy and Neuropathy in Patients with T2DM: A Cross-Sectional Controlled Study.

INTRODUCTION: Early detection of diabetic peripheral neuropathy (DPN) is critical in patients with type 2 diabetes mellitus (T2DM) due to the lack of targeted therapy for DPN. We have investigated the relationship between different stages of diabetic nephropathy and DPN in an attempt to elucidate whether albuminuria can be used as an early warning signal of DPN progression. METHODS: A total of 217 T2DM patients who met the inclusion criteria were recruited from the Department of Endocrinology, Nanfang Hospital between January 2016 and June 2016. These patients were placed in groups based on urinary albumin excretion rate (UAER) and estimated glomerular filtration rate. Nerve conduction studies, the Semmes-Weinstein monofilament test (SWMT) and the vibration perception threshold (VPT) test were conducted. Multiple linear regression analysis, multivariate logistic regression and receiver-operating characteristic (ROC) analysis were performed to investigate the relationship between different stages of diabetic nephropathy and DPN in these patients. RESULTS: Significant differences were observed in the conduction velocity (CV) and amplitude of sensory/motor nerve potential among the T2DM patients at different stages of diabetic nephropathy (all p < 0.05). The UAER and duration of diabetes were found to be independent factors associated with the mean CV and amplitude of sensory/motor nerve potential (all p < 0.05). A disease duration of > 10 years (p = 0.025) and a higher total cholesterol value (p = 0.024) were found to be significantly associated with abnormal SWMT results. A UAER of > 300 mg/24 h (p = 0.007) and a diastolic blood pressure of > 100 mmHg (p = 0.042) were associated with a higher risk for abnormal VPT. A UAER of > 300 mg/24 h (p < 0.001) and a disease duration of > 10 years (p = 0.02) were observed to be significantly correlated with DPN. The ROC analysis showed that the optimal cutoff values of UAER and duration as indicators of DPN were 90.5 mg/24 h and 9.5 years, respectively (both p < 0.001). CONCLUSIONS: The results suggest that diabetic nephropathy is closely associated with the development of DPN in T2DM patients and that UAER and disease duration can be used as warning indicators of DPN progression. CHINESE CLINICAL TRIALS REGISTER NUMBER: ChiCTR-ROC-16007701.

Contrasting Effects of Short-Term Mediterranean and Vegan Diets on Microvascular Function and Cholesterol in Younger Adults: A Comparative Pilot Study.

The Mediterranean diet has been shown to improve cardiovascular health. Vegan diets have demonstrated similar benefits, albeit in fewer studies. In a comparative pilot study, we compared the effects of a short-term Mediterranean Diet (MD) and Vegan Diet (VD) on microvascular function and cholesterol levels in a healthy population. Twenty-four young (aged 18 to 35 years) healthy volunteers followed a four-week intervention (MD = 12; VD = 12) ad libitum. Pre and post-intervention anthropometrics, microvascular function (assessed via LDF and expressed as raw CVC and %CVC MAX), dietary-analysis data (Calories, Protein, Carbohydrates, Total Fat, Saturated Fat, Fibre), Mean Arterial Pressure (MAP), Blood Pressure, Total Cholesterol (TC), High Density Lipoprotein (HDL-C) and TC:HDL-C were compared. MD participants reduced Total Fat intake (p = 0.05). Saturated Fat decreased (MD: p = < 0.001; VD: p = 0.004) and Fibre increased (MD: p = 0.02; VD: p = < 0.001) in both groups. Dietary changes reflected improvements in plateau raw CVC in the MD group (p = 0.005), and a reduction in TC (p = 0.045) and weight loss (p = 0.047) in the VD group. The MD led to improvements in microvascular function; the VD led to reduced TC and weight loss. Although both diets might offer CVD risk-reduction benefits, evidence for the MD appeared to be stronger due to changes in vasodilatory ability and NO bioavailability.