Superatomic icosahedral-CnB12-n (n = 0, 1, 2) Stuffed mononuclear and binuclear borafullerene and borospherene nanoclusters with spherical aromaticity.

Boron and boron-based nanoclusters exhibit unique structural and bonding patterns in chemistry. Extensive density functional theory calculations performed in this work predict the mononuclear walnut-like Ci C50B54 (1) (C2B10@C48B44), C1 C50B54 (2) (CB11@C49B43), and S10 C50B54 (3) (B12@C50B42) which contain one icosahedral-CnB12-n core (n = 0, 1, 2) at the center following the Wade's skeletal electron counting rules and the approximately electron sufficient binuclear peanut-like Cs C88B78 (4) ((C2B10)2@C84B58), Cs C88B78 (5) ((CB11)2@C86B56), Cs C88B78 (6) ((B12)2@C88B54), Cs B180 (7) ((B12)2@B156), Cs B182 (8) ((B12)2@B158), and Cs B184 (9) ((B12)2@B160) which encapsulate two interconnected CnB12-n icosahedrons inside. These novel core-shell borafullerene and borospherene nanoclusters appear to be the most stable species in thermodynamics in the corresponding cluster size ranges reported to date. Detailed bonding analyses indicate that the icosahedral B122-, CB11-, and C2B10 cores in these core-shell structures possess the superatomic electronic configuration of 1S21P61D101F8, rendering spherical aromaticity and extra stability to the systems. Such superatomic icosahedral-CnB12-n stuffed borafullerenes and borospherenes with spherical aromaticity may serve as embryos to form bulk boron allotropes and their carbon-boron binary counterparts in bottom-up approaches.

The role of FGF21 in the pathogenesis of cardiovascular disease.

ABSTRACT: The morbidity and mortality of cardiovascular diseases (CVDs) are increasing worldwide and seriously threaten human life and health. Fibroblast growth factor 21 (FGF21), a metabolic regulator, regulates glucose and lipid metabolism and may exert beneficial effects on the cardiovascular system. In recent years, FGF21 has been found to act directly on the cardiovascular system and may be used as an early biomarker of CVDs. The present review highlights the recent progress in understanding the relationship between FGF21 and CVDs including coronary heart disease, myocardial ischemia, cardiomyopathy, and heart failure and also explores the related mechanism of the cardioprotective effect of FGF21. FGF21 plays an important role in the prediction, treatment, and improvement of prognosis in CVDs. This cardioprotective effect of FGF21 may be achieved by preventing endothelial dysfunction and lipid accumulating, inhibiting cardiomyocyte apoptosis and regulating the associated oxidative stress, inflammation and autophagy. In conclusion, FGF21 is a promising target for the treatment of CVDs, however, its clinical application requires further clarification of the precise role of FGF21 in CVDs.

A Novel Antidiabetic Monomers Combination Alleviates Insulin Resistance Through Bacteria-Cometabolism-Inflammation Responses.

The present study sought to examine the therapeutic effect of a novel antidiabetic monomer combination (AMC) in treating type 2 diabetes mellitus (T2DM); while also elucidating the potential functional mechanism. Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to establish T2DM. The AMC group showed significant reduction in weight, fasting blood glucose (FBG), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and experienced reduced insulin resistance based on oral glucose tolerance testing (OGTT) and hyperinsulinemic-euglycemic clamp testing ("gold standard" for determining in vivo insulin sensitivity). Further, AMC restored the altered intestinal flora by increasing the abundance of the beneficial bacteria Akkermansia, and decreasing the number of harmful bacteria, including Bacteroides, Odoribacter, Prevotella 9, Alistipes, and Parabacteroides. Components of the host-microbial metabolome were also significantly changed in the AMC group compared to the HFD group, including hydroxyphenyllactic acid, palmitoleic acid, dodecanoic acid, linoleic acid, and erucic acid. Furthermore, AMC was found to inhibit inflammation and suppress signaling pathways related to insulin resistance. Lastly, spearman correlation analysis revealed relationships between altered microbial community and co-metabolite levels, co-metabolites and inflammatory cytokines. Hence, the potential mechanism responsible for AMC-mediated alleviation of insulin resistance was suggested to be involved in modulation of bacteria-cometabolism-inflammation responses.

Serum biomarkers combined with ultrasonography for early diagnosis of non-alcoholic fatty liver disease confirmed by magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is notably accurate for even minimal degree of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). But routine use of MRS is limited by its cost and availability. In this study, we developed a diagnostic model combining ultrasonography with biomarkers to identify mild NAFLD, with MRS as the reference standard. A total of 422 eligible subjects were enrolled. The serum levels of fibroblast growth factor 21 (FGF21), cytokeratin 18 M65ED, proteinase 3, neutrophil elastase, alpha-1 antitrypsin, and neutrophil elastase/alpha-1 antitrypsin were measured using ELISA assays. We found that among the six biomarkers, only serum FGF21 was independently associated with intrahepatic triglyceride content (IHTC, standardized ß = 0.185, P < 0.001) and was an independent risk factor for mild NAFLD. Thus, we established a Mild NAFLD Model based on FGF21, alanine transaminase, triglycerides, and body mass index. The area under the receiver-operating characteristic curve of the Mild NAFLD Model was 0.853 (95% confidence interval: 0.816-0.886). Furthermore, a two-step approach combining ultrasonography with the Mild NAFLD Model displayed a better sensitivity for diagnosing mild NAFLD compared with each method alone, with a sensitivity of 97.32% and a negative predictive value of 85.48%. This two-step approach combining ultrasonography and the Mild NAFLD Model derived from serum FGF21 improves the diagnosis of mild NAFLD and can be applied to the early diagnosis of NAFLD in clinical practice.

Prevalence and clinical characteristics of hypertension and metabolic syndrome in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.

BACKGROUND: To investigate the prevalence and clinical characteristics of hypertension (HTN) and metabolic syndrome (MetS) in newly diagnosed diabetes with ketosis-onset. METHODS: A cross-sectional study was adopted in 734 newly diagnosed diabetics including 83 type 1 diabetics with positive islet-associated autoantibodies, 279 ketosis-onset diabetics without islet-associated autoantibodies and 372 non-ketotic type 2 diabetics. The clinical characteristics of HTN and MetS were compared across the three groups, and the risk factors of them were appraised in each group. RESULTS: The prevalence of HTN and MetS were substantially higher in the ketosis-onset diabetics (34.4% for HTN and 58.8% for MetS) than in the type 1 diabetics (15.7% for HTN, P = 0.004; 25.3% for MetS, P < 0.001), but showed no remarkable difference compared with the type 2 diabetics (42.7% for HTN, P = 0.496; 72.3% for MetS, P = 0.079). Furthermore, the risk factors for both HTN and MetS in the ketosis-onset diabetics resembled those in the type 2 diabetics, but significantly different from those in the type 1 diabetics. CONCLUSIONS: The prevalence of HTN and MetS in the ketosis-onset diabetics were magnificently higher than in the type 1 diabetics but showed no difference in comparison to the type 2 diabetics. Likewise, the clinical features and risk factors of HTN and MetS in the ketosis-onset diabetes resembled those in the type 2 diabetes but differed from those in the type 1 diabetes. Our findings indicate that ketosis-onset diabetes should be classified into type 2 diabetes rather than idiopathic type 1 diabetes.

Association between SLC2A9 Genetic Variants and Risk of Hyperuricemia in a Uygur Population.

EN: Summary]This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population, the Uygurs in Xinjiang, China. According to our inclusion and exclusion criteria, Uygur adults from Xinjiang constituted the study population. There were 1053 Uygur adults with hyperuricemia and 1373 normal Uygur adults who served as controls. Five single nucleotide polymorphisms within SLC2A9 (rs938557, rs7679916, rs7349721, rs13101785, and rs13137343) were selected with the HapMap dataset and TaqMan assays. We found that, in normouricemia group, rs938557 was significantly correlated with uric acid (ß=11.39±3.74, P=0.0024) adjusting for age, gender and BMI; rs7679916 and rs13137343 were marginally associated with uric acid concentration (ß=5.77±3.09, P=0.0626; ß= 5.99±3.08, P=0.0520). In the hyperuricemia group, no SNP was found to possibly influence uric acid concentration. None of these SNPs showed significant association with hyperuricemia after controlling for age, gender and BMI. There were significant or marginal correlations between certain single nucleotide polymorphisms in the SLC2A9 region and uric acid concentration in Uygur normouricemia samples. In turn, some of these single nucleotide polymorphisms in SLC2A9 may increase the risk of hyperuricemia.

Circulating miR-29b positively correlates with non-alcoholic fatty liver disease in a Chinese population.

OBJECTIVE: Early screening of non-alcoholic fatty liver disease (NAFLD) is of great significance for the early detection and intervention in NAFLD. MicroRNAs (miRNAs) are important regulators of metabolic diseases including NAFLD. The aim of this study was to investigate the association of serum miR-29a-c with NAFLD in a Chinese population. METHODS: Participants were divided into four groups based on the presence or absence of NAFLD and/or type 2 diabetes mellitus (T2DM). Quantitative polymerase chain reaction analysis was performed to quantify serum level of miR-29a-c. The association of miR-29a-c with NAFLD was evaluated. RESULTS: Serum miR-29b, but not miR-29a or miR-29c, was positively associated with NAFLD (odds ratio [OR] 2.04 [1.16- 3.58], P = 0.013). Additionally, age, serum triglyceride and fasting plasma glucose (FPG) levels were independently associated with miR-29b (ß ± standard error [SE] = 0.004 ± 0.002, P = 0.019 for age; ß ± SE = 0.110 ± 0.054, P = 0.042 for triglyceride; and ß ± SE = 0.389 ± 0.161, P = 0.016 for FPG). MiR-29b level was positively correlated with intrahepatic lipid content (ß ± SE = 6.055 ± 2.630, P = 0.024) after adjusted for age, sex, and body mass index. CONCLUSIONS: Serum miR-29b was associated with intrahepatic lipid content and NAFLD in a Chinese population-based study.

Predicted secreted protein analysis reveals synaptogenic function of Clstn3 during WAT browning and BAT activation in mice.

Promoting white adipose tissue (WAT) browning and enhancing brown adipose tissue (BAT) activity are attractive therapeutic strategies for obesity and its metabolic complications. Targeting sympathetic innervation in WAT and BAT represents a promising therapeutic concept. However, there are few reports on extracellular microenvironment remodeling, especially changes in nerve terminal connections. Identifying the key molecules mediating the neuro-adipose synaptic junctions is a key point. In this study, we used bioinformatics methods to identify the differentially expressed predicted secreted genes (DEPSGs) during WAT browning and BAT activation. These DEPSGs largely reflect changes of cytokines, extracellular matrix remodeling, vascularization, and adipocyte-neuronal cross-talk. We then performed functional enrichment and cellular distribution specificity analyses. The upregulated and downregulated DEPDGs during WAT browning displayed a distinctive biological pattern and cellular distribution. We listed a cluster of adipocyte-enriched DEPSGs, which might participate in the cross-talk between mature adipocytes and other cells; then identified a synaptogenic adhesion molecule, Clstn3, as the top gene expressed enriched in both mature white and brown adipocytes. Using Q-PCR and immunohistochemistry, we found significantly increased Clstn3 expression level during WAT browning and BAT activation in mice subjected to cold exposure (4 °C). We further demonstrated that treatment with isoproterenol significantly increased Clstn3 and UCP1 expression in differentiated white and beige adipocytes in vitro. In conclusion, our study demonstrates that the secretion pattern was somewhat different between WAT browning and BAT activation. We reveal that Clstn3 may be a key gene mediating the neuro-adipose junction formation or remodeling in WAT browning and BAT activation process.

Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia.

There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (ß = 0.151, P = 0.035) and HOMA-IR (ß = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes.

AIDA Selectively Mediates Downregulation of Fat Synthesis Enzymes by ERAD to Retard Intestinal Fat Absorption and Prevent Obesity.

The efficiency of intestinal absorption of dietary fat constitutes a primary determinant accounting for individual vulnerability to obesity. However, how fat absorption is controlled and contributes to obesity remains unclear. Here, we show that inhibition of endoplasmic-reticulum-associated degradation (ERAD) increases the abundance of triacylglycerol synthesis enzymes and fat absorption in small intestine. The C2-domain protein AIDA acts as an essential factor for the E3-ligase HRD1 of ERAD to downregulate rate-limiting acyltransferases GPAT3, MOGAT2, and DGAT2. Aida-/- mice, when grown in a thermal-neutral condition or fed high-fat diet, display increased intestinal fatty acid re-esterification, circulating and tissue triacylglycerol, accompanied with severely increased adiposity without enhancement of adipogenesis. Intestine-specific knockout of Aida largely phenocopies its whole-body knockout, strongly indicating that increased intestinal TAG synthesis is a primary impetus to obesity. The AIDA-mediated ERAD system may thus represent an anti-thrifty mechanism impinging on the enzymes for intestinal fat absorption and systemic fat storage.

Inhibition of mitochondrial complex I improves glucose metabolism independently of AMPK activation.

Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes. Glucose output was measured in primary hepatocytes. Compound C and adenoviruses expressing dominant negative AMP-activated protein kinase (AMPK) α1/2 were exploited to inactivate AMPK pathway. Cellular NAD+ /NADH ratio was assayed to evaluate energy transforming and redox state. Rotenone ameliorated hyperglycaemia and insulin resistance in db/db mice. It induced glucose consumption and glycolysis and reduced hepatic glucose output. Rotenone also activated AMPK. Furthermore, it remained effective with AMPK inactivation. The enhanced glycolysis and repressed gluconeogenesis correlated with a reduction in cellular NAD+ /NADH ratio, which resulted from complex I suppression. Amobarbital, another representative complex I inhibitor, stimulated glucose consumption and decreased hepatic glucose output in vitro, too. Similar changes were observed while expression of NDUFA13, a subunit of complex I, was knocked down with gene silencing. These findings reveal mitochondrial complex I emerges as a key drug target for diabetes treatment. Inhibition of complex I improves glucose homoeostasis via non-AMPK pathway, which may relate to the suppression of the cellular NAD+ /NADH ratio.

Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population.

Recent evidence shows that uric acid is protective against some neurological diseases, but can be detrimental in many metabolic and cardiovascular disorders. In this study, we examined the association between serum uric acid levels and bone metabolism in Chinese males and postmenopausal females. A total of 943 males and 4256 postmenopausal females were recruited in Shanghai. The levels of serum uric acid and bone turnover markers (BTMs) were detected along with other biochemical traits. In addition, the fat distribution was calculated through MRI and image analysis software, and bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry. For postmenopausal females, the prevalence of osteoporosis was significantly lower in the hyperuricemia group compared with the normouricemic group (P=4.65E-06). In females, serum uric acid level was significantly associated with osteoporosis, with odds ratio (OR) and 95% confidence interval (95% CI) of 0.844 [0.763; 0.933] (P=0.0009) after adjusting for age, body mass index, HbA1c, lean mass, visceral and subcutaneous fat areas, albumin, 25-hydroxyvitamin D3 [25(OH)D3], and parathyroid hormone (PTH). In females, serum uric acid level was positively correlated with the BMD of the femoral neck (ß±SE: 0.0463±0.0161; P=0.0042), total hip (ß±SE: 0.0433±0.0149; P=0.0038) and L1-4 (ß±SE: 0.0628±0.0165; P=0.0001) after further adjusting for age, BMI, HbA1c, lean mass, VFA, SFA, albumin, 25(OH)D3 and PTH. Regarding BTMs, serum uric acid level was negatively correlated with N-terminal procollagen of type I collagen (PINP) in females (ß±SE: -0.1311±0.0508; P=0.0100). In summary, our results suggest that uric acid has a protective effect on bone metabolism independent of body composition in Chinese postmenopausal females.

Association of bone turnover markers with glucose metabolism in Chinese population.

The association between type 2 diabetes (T2DM) and bone metabolism has been discussed previously but is controversial. In this study we aimed to evaluate the association of bone turnover markers with glucose metabolism in Chinese population, in which 919 males and 4171 postmenopausal females in a region of Shanghai were recruited. Anthropometric and biochemical traits related to glucose and bone metabolism were analyzed. Participants were classified according to their glucose tolerance as normal glucose tolerance (NGT), impaired glucose regulation (IGR) or T2DM. Males and females were analyzed separately, and then associations between bone turnover markers (BTMs) and glucose metabolism were evaluated. The results showed that in females, the serum levels of N-terminal osteocalcin (N-MID), N-terminal procollagen of type I collagen (PINP) and ß-cross-linked C-telopeptide of type I collagen (ß-CTX) were significantly decreased in the T2DM group compared to the NGT group (P<0.01). When age, body mass index, serum lipids, fat percentage, visceral fat area, subcutaneous fat area, anti-diabetic medicines, PINP, N-MID and ß-CTX were included in one logistic model, N-MID (OR [95% CI]: 0.954 [0.932; 0.976]; P=0.0001) was significantly associated with T2DM in females. In females, N-MID was associated with insulin sensitivity and HOMA-ß. PINP was significantly associated with HOMA-ß, GUTT-ISI, Stumvoll first-phase insulin secretion index (STU-1) and Stumvoll second-phase insulin secretion index (STU-2), but ß-CTX was associated only with HOMA-ß (ß±SE: 0.1331±0.0311; P=1.95×10-5) and GUTT-ISI (ß±SE: 0.0727±0.0229; P=0.0015). In males, N-MID was significantly correlated with HOMA-ß (ß±SE: 0.3439±0.0633; P=7.75×10-8), GUTT-ISI (ß±SE: 0.1601±0.0531; P=0.0027) and STU-1 (ß±SE: 0.2529±0.1033; P=0.0146). Significant associations were also detected between ß-CTX and HOMA-ß (ß±SE: 0.2736±0.0812; P=0.0009). This study reveals that BTMs are highly associated with T2DM, insulin sensitivity and beta cell function in both Chinese males and postmenopausal females.

Waist circumference-dependent peripheral monocytes change after gliclazide treatment for Chinese type 2 diabetic patients.

Gliclazide used for the treatment of type 2 diabetes mellitus (T2DM) stimulates insulin secretion and influences peripheral blood monocytes. The roles of gliclazide in peripheral monocytes of newly diagnosed T2DM patients were investigated in this study. A total of 105 newly diagnosed T2DM patients with no history of antihyperglycemic medication were treated with gliclazide-modified release for 16 weeks. The total and differential leukocyte profiles of peripheral blood were measured at baseline and week 16. The peripheral blood monocyte count at week 16 was significantly lower than that at baseline (P=0.019). Peripheral monocytes level at baseline was positively correlated with waist circumference. After gliclazide treatment, the peripheral monocytes were decreased [(320.09±15.13)×106/L vs. (294.19±14.22)×106/L] in non-abdominal obesity group, but increased in abdominal obesity group [(344.36±17.24)×106/L vs. (351.87±16.93)×106/L]. Compared with non-abdominal obese patients, abdominal obese patients showed higher Δmonocytes (P=0.046) and Δacute insulin secretion (P=0.049), but lower ΔHbA1c (P=0.047). There was significantly positive correlation between Δmonocytes and Δacute insulin secretion (P=0.015), which disappeared after adjusting for age, waist circumference and dosage at baseline. In conclusion, waist circumference is correlated with peripheral monocyte change after gliclazide treatment in Chinese newly diagnosed T2DM patients. Peripheral monocytes are decreased in non-abdominal obesity group and increased in abdominal obesity group after gliclazide treatment.

Serum uric acid levels are associated with obesity but not cardio-cerebrovascular events in Chinese inpatients with type 2 diabetes.

We aim to explore the associations between serum uric acid (SUA) and obesity and cardio-cerebrovascular events (CCEs) in Chinese inpatients with type 2 diabetes mellitus (T2DM). 2 962 inpatients with T2DM were stratified into quartile based on SUA concentrations. There were significant increases in the prevalence of both obesity (32.6%, 41.9%, 50.1%, and 62.8%, respectively, p < 0.001 for trend) and severe obesity (0.4%, 0.6%, 0.8%, and 1.3%, respectively, p < 0.001 for trend) across the SUA quartiles. A fully adjusted multiple logistic regression analysis revealed that SUA quartiles were independently associated with the presence of obesity (p < 0.001). The prevalence of CCEs was significantly higher in the obese diabetics than in the nonobese diabetics (16.8% vs. 13.2%, p = 0.027). After controlling for multiple confounding factors, BMI levels were also significantly correlated with the presence of CCEs (p = 0.020). However, there was no significant association of SUA quartiles/SUA levels with the presence of CCEs in T2DM. This study suggested that SUA levels were independently associated with obesity but not with CCEs in patients with T2DM. In selected populations such as subjects with T2DM, the role of uric acid in cardiovascular complications might be attributable to other cardiovascular risk factors, such as obesity.

Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes.

KCNQ1 channel is a member of the voltage-gated potassium channel KQT-like subfamily. The KCNQ1 gene has recently been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). In the present study, we examined the effects of KCNQ1 variants on the therapeutic response to modified-release gliclazide (gliclazide MR) treatment in Chinese patients newly diagnosed with T2DM. A total of 100 newly diagnosed T2DM patients without a history of any anti-diabetic medications were treated with gliclazide MR for 16 weeks, but 91 patients completed the entire study. The anthropometric parameters were determined at baseline and at the final visit, while clinical laboratory tests were performed at baseline and on weeks 2, 4, 6, 12, 16. Two SNPs, rs2237892 and rs2237895, in the region of the KCNQ1 gene were genotyped in all the participants. All calculations and statistical analyses were conducted using SPSS. The rs2237892 TT homozygotes exhibited significantly higher 2-h glucose levels at baseline (P<0.05) and a lower cumulative attainment rate of the target 2-h glucose level (Plog-rank=0.020) than the C allele carriers. Patients with greater numbers of rs2237892 T alleles exhibited larger augmentations (Δ) in the 2-h glucose levels (P=0.027); and patients with the rs2237892 TT genotype exhibited a higher Δ homeostasis model assessment of ß-cell function (HOMA-ß) than CC and CT genotype carriers (P=0.021 and P=0.043, respectively). Moreover, the rs2237895 C allele was associated with a greater decrement in Δ glycated hemoglobin (HbA1c) (P=0.024); and patients with the CC genotype exhibited greater variance than those with the AA and AC genotypes (P=0.005 and 0.021, respectively). Compared with the C allele, the odds ratio for treatment success among carriers of the rs2237892 T allele was 2.533 (P=0.007); and the rs2237895 C allele was associated with a 2.360-fold decrease in HbA1c compared with the A allele (P=0.009). KCNQ1 polymorphisms are associated with gliclazide MR efficacy in Chinese patients with type 2 diabetes.

Waist Circumference-dependent Peripheral Monocytes Change after Gliclazide Treatment for Chinese Type 2 Diabetic Patients / 华中科技大学学报（医学）（英德文版）

Gliclazide used for the treatment of type 2 diabetes mellitus (T2DM) stimulates insulin secretion and influences peripheral blood monocytes.The roles of gliclazide in peripheral monocytes of newly diagnosed T2DM patients were investigated in this study.A total of 105 newly diagnosed T2DM patients with no history of antihyperglycemic medication were treated with gliclazide-modified release for 16 weeks.The total and differential leukocyte profiles of peripheral blood were measured at baseline and week 16.The peripheral blood monocyte count at week 16 was significantly lower than that at baseline (P=0.019).Peripheral monocytes level at baseline was positively correlated with waist circumference.After gliclazide treatment,the peripheral monocytes were decreased [(320.09±15.13)×106/L vs.(294.19±14.22)×106/L] in non-abdominal obesity group,but increased in abdominal obesity group [(344.36±17.24)×106/L vs.(351.87±16.93)×106/L].Compared with non-abdominal obese patients,abdominal obese patients showed higher Amonocytes (P=0.046) and Aacute insulin secretion (P=0.049),but lower AHbAlc (P=0.047).There was significantly positive correlation between Amonocytes and Aacute insulin secretion (P=0.015),which disappeared after adjusting for age,waist circumference and dosage at baseline.In conclusion,waist circumference is correlated with peripheral monocyte change after gliclazide treatment in Chinese newly diagnosed T2DM patients.Peripheral monocytes are decreased in non-abdominal obesity group and increased in abdominal obesity group after gliclazide treatment.

Urine uric acid excretion is associated with nonalcoholic fatty liver disease in patients with type 2 diabetes.

AIMS: Elevated serum uric acid is closely associated with nonalcoholic fatty liver disease (NAFLD). However, the association of urine uric acid excretion (UUAE) with NAFLD has not been investigated. Our aims were to explore the associations between UUAE and NAFLD and serum alanine aminotransferase (ALT) in type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study included 2042 Chinese inpatients with T2DM. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartile based on UUAE levels. NAFLD was determined by ultrasonography. Elevated ALT level was defined with an ALT value >65U/L. RESULTS: There was an obvious increase in both NAFLD prevalence (26.3%, 34.6%, 43.8%, and 56.2%, respectively, p<0.001 for trend) and ALT value [16 (12-24), 17 (13-27), 20 (14-30), and 24 (15-38) U/L, respectively, p<0.001 for trend] across the UUAE quartiles after controlling for confounders. Multiple logistic regression analyses revealed independent associations between UUAE and NAFLD (p=0.002) and elevated ALT level (p<0.001). Compared with the patients in the first quartile of UUAE, those in the second, third and fourth quartiles had 1.528-, 1.869-, and 1.906-fold risk of NAFLD, and 3.620-, 6.223-, and 10.506-fold risk of elevated ALT level in T2DM, respectively. CONCLUSIONS: Increased UUAE levels were significantly associated with the presence of NAFLD and increase of ALT in T2DM. UUAE may be a clinically significant measure in assessing the risk of NAFLD in T2DM.

The coexistence of carotid and lower extremity atherosclerosis further increases cardio-cerebrovascular risk in type 2 diabetes.

BACKGROUND: Both carotid and lower limb atherosclerosis are associated with increased cardiovascular and cerebrovascular risks. However, it is still unclear whether the concomitant presence of carotid and lower extremity atherosclerosis further increases the cardiovascular and cerebrovascular risks. Therefore, our aim is to investigate whether the coexistence of carotid and lower extremity atherosclerosis was associated with higher cardiovascular and cerebrovascular risks in patients with type 2 diabetes. METHODS: This cross-sectional study was performed in 2830 hospitalized patients with type 2 diabetes. Based on carotid and lower limb Doppler ultrasound results, the patients were divided into three groups including 711 subjects without atherosclerosis, 999 subjects with either carotid or lower limb atherosclerosis, and 1120 subjects with both carotid and lower limb atherosclerosis. And we compared the clinical characteristics and prevalence of both cardio-cerebrovascular events (CCBVEs) and self-reported cardio- cerebrovascular diseases (CCBVDs) among the three groups. RESULTS: After adjusting for age, sex, and duration of diabetes, there were significant increases in the prevalence of both CCBVEs (3.8 vs. 11.8 vs. 26.4 %, p < 0.001 for trend) and self-reported CCBVDs (6.9 vs. 19.9 vs. 36.5 %, p < 0.001 for trend) across the three groups (diabetics without atherosclerosis, diabetics with either carotid or lower limb atherosclerosis, and diabetics with both carotid and lower extremity atherosclerosis). A fully adjusted logistic regression analysis also revealed that compared with those without atherosclerosis, those with either carotid or lower limb atherosclerosis had higher risk of CCBVEs (OR 1.724, 95 % CI 1.001-2.966) and self-reported CCBVDs (OR 1.705, 95 % CI 1.115-2.605), and those with concomitant presence of carotid and lower extremity atherosclerosis had the highest risk of CCBVEs (OR 2.869, 95 % CI 1.660-4.960) and self-reported CCBVDs (2.147, 95 % CI 1.388-3.320)(p < 0.001 for trend in CCBVEs and p = 0.002 for trend in CCBVDs, respectively). CONCLUSIONS: Either carotid or lower limb atherosclerosis was obviously related to increased cardio-cerebrovascular risk in type 2 diabetes. The concomitant presence of carotid and lower extremity atherosclerosis further increased cardio-cerebrovascular risk in patients with type 2 diabetes. The combined application of carotid and lower extremity ultrasonography may help identify type 2 diabetics with higher cardio-cerebrovascular risk.