High-normal free thyroxine level is related with decreased bone mineral density in nonobese male patients with type 2 diabetes over 50 years old.

Background: The prevalence of 'low bone mineral density (BMD)' in Type 2 diabetes (T2DM), especially stratified by body mass index, is seldom reported. The relation of the euthyroid range and low BMD in T2DM remains to be further elucidated. Objectives: We aim to investigate the thyroid hormones' impact on BMD among euthyroid patients with T2DM. Design and methods: A total of 1452 hospitalized T2DM patients with normal thyroid function (43.6% males aged over 50 and 56.4% postmenopausal females) were enrolled in this cross-sectional study. BMD was measured at lumbar spine by GE lunar dual-energy X-ray absorptiometry system, and 'low BMD' was defined as T-score <-1.0 SD. The prevalence of 'low BMD' was compared between obese and nonobese (body mass index < 25 kg/m2) groups for both sexes, and the relation of low BMD and free T4 quartiles was explored by multiple logistic regression. Results: The general prevalence of 'low BMD' was 12.3% for male patients aged over 50 (15.5% in the nonobese group and 8.0% in the obese group) and 49.8% for postmenopausal females (56.7% in the nonobese group and 48.9% in the obese group). After adjustment in multiple linear regression, free T4 level remained significantly related to decreased BMD in nonobese male subgroup. Multiple logistic regression revealed that BMD of the highest free T4 quartile (1.12-1.48 ng/dL) decreased significantly than other three quartiles after adjusting for confounding factors including age, body mass index, serum calcium and creatinine level, fasting glucose, alkaline phosphatase, glycosylated hemoglobin, total cholesterol, and smoking history (OR = 2.724, 95% CI = 1.085-6.840, p = 0.033). No significant relation was found in obese male or postmenopausal female groups. Conclusion: High-normal free T4 is a potential independent risk factor for 'low BMD' in nonobese male T2DM patients aged over 50. Close attention should be paid to thyroid function profile, even within normal range, in nonobese men with underlying higher fracture risks on diabetes status.

Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.

OBJECTIVE: Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees. DESIGN, PATIENTS AND MEASUREMENTS: The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis. RESULTS: Both patients were middle-aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin-angiotensin-aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves' disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C>T (Thr60Met). The novel c.2159G>T (p. Gly720Val) and c.2675T>C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs-Polyphen-2, SIFT, Mutation Taster and LRT. CONCLUSIONS: We identified two novel SLC12A3 genetic variant [c.2159G>T (p.Gly720Val) and c.2675T>C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.

The Different Effects of Skeletal Muscle and Fat Mass on Height Increment in Children and Adolescents Aged 6-11 Years: A Cohort Study From China.

Objective: This study aimed to investigate the contribution of body composition including skeletal muscle mass (SMM) and body fat mass (BFM) to longitudinal growth among children and adolescents aged 6-11 years old. Methods: This cohort study was conducted from the annual health examination between 2019 and 2020. Annual height gain and weight gain and changes in SMM and BFM were calculated and compared between sexes, different nutritional status, and growth curve shifting mode. Spearman analyses and multiple linear regression analysis were performed to identify the impact of SMM, BFM, or body mass index (BMI) on height gain. Results: Of the 584 subjects, the annual height gains of boys (4.76 cm in the 6-9-year group and 4.63 cm in the 10-11-year group) were significantly lower than those of girls (5.48 and 5.74 cm, respectively). Spearman analysis showed that SMM gain and height gain were positively and significantly correlated in each examination of all children (r = 0.535 for boys and 0.734 for girls, p < 0.001). Conversely, BFM and height gains were negatively (r = -0.5240 for boys and -0.232 for girls, p < 0.001) correlated. Multiple linear regression analysis identified SMM gain as an independent predictor (95% CI: 1.20,1.44) of height gain after adjusting for age, gender, BMI, BFM gain, and percentage of body fat (PBF). Conclusion: SMM gains, rather than BFM gains, were associated with height gains in children and adolescents aged 6-11 years. Monitoring SMM changes in routine healthcare might motivate children and adolescents to achieve dietary and exercise recommendations, thereby growing taller without gaining excessive weight.

Growth Hormone and Counterregulation in the Pathogenesis of Diabetes.

PURPOSE OF REVIEW: Canonical growth hormone (GH)-dependent signaling is essential for growth and counterregulatory responses to hypoglycemia, but also may contribute to glucose homeostasis (even in the absence of hypoglycemia) via its impact on metabolism of carbohydrates, lipids and proteins, body composition, and cardiovascular risk profile. The aim of this review is to summarize recent data implicating GH action in metabolic control, including both IGF-1-dependent and -independent pathways, and its potential role as target for T2D therapy. RECENT FINDINGS: Experimental blockade of the GHR can modulate glucose metabolism. Moreover, the soluble form of the GH receptor (GHR, or GHBP) was recently identified as a mediator of improvement in glycemic control in patients with T2D randomized to bariatric surgery vs. medical therapy. Reductions in GHR were accompanied by increases in plasma GH, but unchanged levels of both total and free IGF-1. Likewise, hepatic GHR expression is reduced following both RYGB and VSG in rodents. Emerging data indicate that GH signaling is important for regulation of long-term glucose metabolism in T2D. Future studies will be required to dissect tissue-specific GH signaling and sensitivity and their contributions to systemic glucose metabolism.

High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control.

To improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR's mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling.Trial Registration: Clinicaltrials.gov NCT01073020.

Metabolic Syndrome and Its Components Are Associated With Altered Amino Acid Profile in Chinese Han Population.

Objective: Recent studies have found that the levels of plasma amino acids, such as branched-chain amino acids and aromatic amino acids, were associated with visceral obesity, insulin resistance, future development of diabetes and cardiovascular diseases. However, few studies have involved a Chinese Han population. This study aimed to examine the association between amino acid profile and metabolic syndrome (MetS) and its components in the Chinese Han population. Methods: This is a cross-sectional study, which enrolled a cohort of 473 participants from a community. We employed the isotope internal standard method to determine the plasma concentrations of 28 amino acids using high-performance liquid chromatography-tandem mass spectrometry (LC/MS). Participants were divided into MetS (n = 72) and non-MetS groups (n = 401) to analyze the association between amino acids and MetS and its components. Results: The prevalence of MetS was 15.2% according to the criteria. Plasma concentrations of isoleucine (Ile), leucine (Leu), valine (Val), tyrosine (Tyr), tryptophan (Trp), phenylalanine (Phe), glutamic acid (Glu), aspartic acid (Asp), alanine (Ala), histidine (His), methionine (Met), asparagine (Asn), and proline (Pro) were significantly higher in the MetS group than those in the non-MetS group (P < 0.05), but taurine (Tau) was significantly lower (P < 0.05). When MetS components were increased, the concentrations of these 13 amino acids significantly increased (P < 0.05), but Tau concentration was significantly decreased (P < 0.05). We extracted the amino acid profile by principal component analysis (PCA), PC1 and PC2, which extracted from the 14 amino acids, were significantly associated with MetS (odds ratio, 95% confidence interval: 1.723, 1.325-2.085 and 1.325, 1.043-1.684, respectively). A total of 260 non-MetS participants were followed up effectively, and 42 participants developed new-onset MetS within 5 years. We found that the amino acid profile of PC1 was linked to the occurrence of future MetS. Decreased Tau was correlated with the future development of MetS. Conclusion: Participants with MetS exhibit an abnormal amino acid profile, and its components gradually increase when these amino acids are altered. Amino acid PCA profile can be employed for assessing and monitoring MetS risk. Finally, decreased Tau may be linked to the future development of MetS.

miR-145 improves metabolic inflammatory disease through multiple pathways.

Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes, yet the mechanisms are not completely understood. Here, we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control. miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics. LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels. Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice. Conversely, lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration, reduced body weight, and improved glucose metabolism in db/db mice. And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE-/- mice. Both OPG and KLF5 were targets of miR-145. miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5. miR-145 also suppressed NF-κB activation by targeting OPG and KLF5. Our findings provide an association of the environment with the progress of metabolic disorders. Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.

Long noncoding RNA small nucleolar RNA host gene 12 promotes papillary thyroid carcinoma cell growth and invasion by targeting miR-16-5p.

Emerging evidence has shown that long noncoding RNA (lncRNA) plays an important role in various types of malignant cancer. Small nucleolar RNA host gene 12 (SNHG12) was found to be upregulated and to act as an oncogene in several cancers. However, the function and regulatory mechanism of SNHG12 remain unclear in papillary thyroid carcinoma (PTC). In this study, SNHG12 was found to be increased in PTC tissues and cell lines using quantitative real-time PCR. Knockdown of SNHG12 significantly inhibited PTC cell proliferation, migration and invasion and induced apoptosis in vitro. Mechanistic investigations revealed that SNHG12 functions as a competing endogenous RNA (ceRNA) to sponge miR-16-5p, which was downregulated in PTC tissues. In addition, rescue assays further confirmed that SNHG12 contributed to the progression of PTC through regulating miR-16-5p expression. These results indicated that SNHG12 might contribute to tumor progression in PTC by acting as a ceRNA to sponge miR-16-5p.

Notch1a can widely mediate innate immune responses in zebrafish larvae infected with Vibrio parahaemolyticus.

The Notch signaling pathway is known to regulate innate immunity by influencing macrophage function and interacting with the Toll-like receptor (TLR) signaling pathway. However, the comprehensive role of the Notch signaling pathway in the innate immune response remains unknown. To assess the function of Notch1a in immunity, we examined the innate immune responses to Vibrio parahaemolyticus strain Vp13 of wild-type (WT) and notch1a-/- zebrafish larvae generated using the clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system. The median lethal dose (LD50) of V. parahaemolyticus was significantly lower in notch1a-/- larvae than in WT larvae 3 days post fertilization (dpf). Transcriptome data analysis revealed 359 significantly differentially expressed genes (DEGs), including 246 significantly down-regulated genes and 113 significantly up-regulated genes, in WT infected groups compared with WT control groups. In contrast, 986 significantly DEGs were found in notch1a-/- infected groups compared with notch1a-/- control groups, of which 82 genes were significantly down-regulated and 904 genes were significantly up-regulated. These DEGs belonged to the tumor necrosis factor (TNF), complement, nuclear factor kappa B (NF-κB), cathepsin, interleukin (IL), chemokine, serpin peptidase inhibitor, matrix metallopeptidase, innate immune cells, pattern recognition receptor (PRR), and other cytokine families. Our results indicate that Notch1a plays roles in inhibiting many immunity-related genes and could comprehensively mediate the innate immune response by regulating TLRs, nucleotide-binding-oligomerization-domain-like receptors (NLRs), lectins, complement, ILs, chemokines, TNF, cathepsin, and serpin. Further studies are required to understand the specific mechanism of Notch1a in innate immunity.

Differential transcriptome analysis of zebrafish (Danio rerio) larvae challenged by Vibrio parahaemolyticus.

Zebrafish embryo and larva represent a useful in vivo model for identification of host innate immune responses to bacterial infection. Vibrio parahaemolyticus is a typical zoonotic pathogen worldwide that causes acute gastroenteritis in humans and vibriosis in fishes. However, the mechanism of the innate immune response in the zebrafish larvae infected by V. parahaemolyticus has not been clear. We analysed the transcriptomic profile of 3 days post-fertilization (dpf) zebrafish larvae immersed in V. parahaemolyticus 13 (Vp13) strain suspension for 2 hr. A total of 602 differentially expressed genes (DEGs) were identified in the infection group, of which 175 (29.07%) genes were upregulated and 427 (70.93%) genes were downregulated. These altered genes encoded complement and coagulation cascades, chemokine, TNF signalling pathway, NF-κB signalling pathway and JAK-STAT signalling pathway. Some significant DEGs, such as mmp13, cxcr4a, ccl20, hsp70, gngt, serpina1l, il8, cofilin and il11, were subjected to quantitative gene expression analysis, and the results were consistent with those of the transcriptome profile. These results clearly demonstrated that exposure to V. parahaemolyticus for 2 hr could activate innate immune response in 3dpf larvae by altered expression of downstream signalling pathway genes of pattern recognition receptors (PRRs). Our results also provide a useful reference for future analysis of signal transduction pathways and pathogenesis mechanisms underlying the systemic innate immune response to the external bacteria of V. parahaemolyticus.

Allicin inhibits tubular epithelial-myofibroblast transdifferentiation under high glucose conditions in vitro.

Previous studies have suggested that tubular epithelial-mesenchymal transition (EMT) is an important event in renal tubulointerstitial fibrosis, which is a clinical characteristic of diabetic nephropathy. The present study aimed to investigate the effect of allicin, the major biological active component of garlic, on the EMT of a human renal proximal tubular epithelial cell line (HK-2) cultured under high glucose concentrations. HK-2 cells were exposed for 48 h to 5.5 or 25 mmol/l D-glucose, 25 mmol/l D-glucose plus allicin (2.5, 5, 10 or 20 µg/ml) or 25 mmol/l D-glucose plus 20 µmol/l PD98059, a selective inhibitor of the mitogen activated protein kinase/extracellular signal-regulated kinase (ERK) signaling pathway. The EMT of HK-2 cells was assessed by analyzing the protein expression of E-cadherin, α-smooth muscle actin (α-SMA), vimentin and collagen I via immunocytochemistry. In addition, reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression levels of transforming growth factor (TGF)-ß1 and phosphorylated (p)-ERK1/2. Marked morphological changes were observed in HK-2 cells cultured under high glucose conditions, and these changes were abrogated by simultaneous incubation with allicin and PD98059. The expression levels of α-SMA, vimentin and collagen I were significantly increased in HK-2 cells cultured under high glucose conditions, as compared with those cultured under normal glucose conditions (P<0.01). Conversely, the expression levels of E-cadherin were significantly decreased upon stimulation with high glucose (P<0.01). Furthermore, the expression levels of TGF-ß1 and p-ERK1/2 were significantly upregulated in HK-2 cells cultured under high glucose conditions, as compared with those cultured under normal glucose conditions (P<0.05). Allicin partially reversed the high-glucose-induced increase in α-SMA, vimentin and collagen I expression (P<0.01 at 20 µg/ml), increased the expression of E-cadherin, and significantly downregulated the high glucose-induced expression of TGF-ß1 and p-ERK1/2 in a dose-dependent manner (P<0.05). The results of the present study suggested that high glucose concentrations induced the EMT of HK-2 cells, and that allicin was able to inhibit the EMT, potentially via regulation of the ERK1/2-TGF-ß1 signaling pathway.

Biallelic editing of a lamprey genome using the CRISPR/Cas9 system.

Lampreys are extant representatives of agnathans. Descriptions of lamprey development, physiology and genome have provided critical insights into early evolution of vertebrate traits. However, efficient means for genetic manipulation in agnathan species have not been developed, hindering functional studies of genes in these important Evo-Devo models. Here, we report a CRISPR/Cas system optimized for lamprey genomes and use it to disrupt genomic loci in the Northeast Chinese lamprey (Lethenteron morii) with efficiencies ranging between 84~99%. The frequencies of indels observed in the target loci of golden (gol), kctd10, wee1, soxe2, and wnt7b, estimated from direct sequencing of genomic DNA samples of injected lamprey larvae, were 68/69, 47/56, 38/39, 36/37 and 36/42, respectively. These indels often occurred in both alleles. In the CRISPR/Cas9 treatment for gol or kctd10, 38.6% or 85.3% of the targeted larvae had the respective recessive null-like phenotypes, further confirming the disruption of both loci. The kctd10 gRNA, designed against an essential functional region of Kctd10, resulted in null-like phenotypes and in-frame mutations in alleles. We suggest that the CRISPR/Cas-based approach has the potential for efficient genetic perturbation in organisms less amenable to germ line transmission based approaches.

Zebrafish as a useful model for zoonotic Vibrio parahaemolyticus pathogenicity in fish and human.

Vibrio parahaemolyticus is an important aquatic zoonotic pathogen worldwide that causes vibriosis in many marine fish, and sepsis, gastroenteritis and wound infection in humans. However, the pathogenesis of different sources of V. parahaemolyticus is not fully understood. Here, we examined the pathogenicity and histopathology of fish (V. parahaemolyticus 1.2164) and human (V. parahaemolyticus 17) strains in a zebrafish (Danio rerio). We found that different infection routes resulted in different mortality in zebrafish. Moreover, death due to V. parahaemolyticus 1.2164 infection occurred quicker than that caused by V. parahaemolyticus 17 infection. Hematoxylin-eosin staining of liver, kidney and intestine sections showed histological lesions in all three organs after infection with either strain. V. parahaemolyticus 1.2164 caused more severe damage than V. parahaemolyticus 17. In particular, V. parahaemolyticus 1.2164 treatment induced more serious hydropic degeneration and venous sinus necrosis in the liver than V. parahaemolyticus 17 treatment. The expression levels of three proinflammatory cytokines, interleukin 1ß (il1ß), interferon phi 1 (ifnϕ1) and tumor necrosis factor α (tnfα), as determined by quantitative real-time PCR, were upregulated in all examined tissues of infected fish. Notably, the peak levels of tnfα were significantly higher than those of il1ß and ifnϕ1, suggesting, together with pathological results, that tnfα and il1ß play an important role in acute sepsis. High amounts of tnfα may be related to acute liver necrosis, while ifnϕ1 may respond to V. parahaemolyticus and play an antibacterial role for chronically infected adult zebrafish. Taken together, our results suggest that the zebrafish model of V. parahaemolyticus infection is useful for studying strain differences in V. parahaemolyticus pathogenesis.

Prevalence of macro- and microvascular complications in patients with type 2 diabetes and kidney disease with or without albuminuria in a single Chinese Diabetes Centre.

OBJECTIVE: To investigate the relationship between diabetic retinopathy, neuropathy and low ankle-brachial index in mild-to-moderate chronic kidney disease of type 2 diabetic patients. METHODS: We enrolled 875 type 2 diabetic patients who were divided into two phenotypes (with or without albuminuria) and stratified into three groups (stage 1 with estimated glomerular filtration rate ⩾ 90 mL/min/1.73 m(2), stage 2 with estimated glomerular filtration rate of 60-89, stage 3 with estimated glomerular filtration rate of 30-59). The prevalence of diabetic retinopathy, neuropathy and low ankle-brachial index was compared and the risk factors of renal impairment were determined. RESULTS: Among chronic kidney disease stages, the prevalence of diabetic retinopathy increased from 42.5%, 56.6% to 66.7% in albuminuric subjects and from 29.4%, 33.0% to 50.0% with no significant trend in normoalbuminuric subjects (p = 0.005, 0.007 and 0.399 compared with albuminuric subjects in each stage). There was a significantly increased prevalence of low ankle-brachial index (17.5%, 22.6% and 44.4%) in normoalbuminuric subjects but no significant trend in albuminuric subjects. Diabetic retinopathy (odds ratio = 2.474, 95% confidence interval = 1.009-6.068) was an independent risk factor of declining kidney function in albuminuric patients. CONCLUSION: The prevalence of diabetic retinopathy was graded according to the estimated glomerular filtration rate declining in albuminuric patients while the prevalence of low ankle-brachial index was gradually increased in normoalbuminuric patients, indicating the diverse underlying mechanisms of mild to moderate chronic kidney disease between these two phenotypes.

Predicting diabetic nephropathy by serum proteomic profiling in patients with type 2 diabetes.

PURPOSE: The purpose of this work is to examine the serum proteomic profiles associated with the subsequent development of diabetic nephropathy (DN) in patients with type 2 diabetes and to develop and validate a decision tree based on the profiles to predict the risk of DN in advance by albuminuria. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to obtain the proteomic profiles from baseline serum samples of 84 patients with type 2 diabetes with normal albuminuria, including 42 case subjects who developed DN after 4 years and 42 control subjects who remained normoalbuminuric over the same 4 years. From signatures of protein mass, a decision tree was established for predicting DN. RESULTS: At baseline, urinary albumin/creatinine ratio was similar between the case and control groups. The intensities of 5 peaks detected by CM10 chips appeared up-regulated, whereas 18 peaks were down-regulated more than twofold in the case group than compared with the control group in the training set. An optimum discriminatory decision tree for case subjects created with four nodes using four distinct masses was challenged with testing set. The positive predictive value was 77.8% (7/9), and the negative predictive value was 72.7% (8/11). CONCLUSIONS: We developed and validated a decision tree to predict DN in patients with type 2 diabetes.

High-normal urinary albumin-to-creatinine ratio is independently associated with metabolic syndrome in Chinese patients with type 2 diabetes mellitus: A cross-sectional community-based study.

AIMS/INTRODUCTION: Microalbuminuria is positively related to metabolic syndrome (MetS). Our aim was to investigate whether urinary albumin-to-creatinine ratio (UACR) within the normal range is independently associated with MetS in Chinese community-based patients with type 2 diabetes. MATERIALS AND METHODS: A total of 514 participants (206 males and 308 females; mean age 66 years) with UACR less than 3.5 mg/mmol were enrolled from two downtown areas of Shanghai. The participants were stratified into quartiles according to UACR levels. The prevalence of MetS was assessed and compared among the four groups by binary logistic regression. RESULTS: Compared with participants with UACRs in the first quartile, the other quartiles had a higher prevalence of MetS (65.9%, 74.4% and 81.3%, respectively, P = 0.001) after adjustment for sex and age. After adjusting for potential confounders, participants in the second to the fourth quartile group had a 1.36-, 1.84- and 2.73-fold risk of MetS, respectively, relative to those in the lowest quartile. Furthermore, UACR, whether as quartile groups or as a continuous variable, is an independent predictor of MetS after fully adjusting for other variables. CONCLUSIONS: These results suggest that UACR even within the normal range is independently associated with MetS in Chinese community-based patients with type 2 diabetes mellitus.

Serum uric acid levels are associated with hypertension and metabolic syndrome but not atherosclerosis in Chinese inpatients with type 2 diabetes.

OBJECTIVE: Serum uric acid (SUA) is associated with many cardiovascular risk factors such as hypertension (HTN) and metabolic syndrome (MetS). However, the association of SUA with atherosclerosis remains controversial. Our aim was to investigate the relationships of SUA with HTN, MetS and atherosclerosis in Chinese inpatients with type 2 diabetes. METHODS: This cross-sectional study was performed with a sample of 2388 hospitalized Chinese patients with type 2 diabetes. Both carotid and lower limb atherosclerotic lesions were assessed for intima-media thickness, plaque and stenosis by Doppler ultrasound. Atherosclerotic plaque and stenosis were defined as the presence of either carotid or lower limb plaques and stenoses, respectively. RESULTS: There were significant increases in the prevalence of both HTN and MetS across the SUA quartiles (HTN: 43.4, 49.6, 56.1 and 66.3% for the first, second, third and fourth quartiles, respectively, P < 0.001; MetS: 59.9, 68.8, 74.7 and 84.9% for the first, second, third and fourth quartiles, respectively, P < 0.001). A fully adjusted multiple logistic regression analysis revealed that SUA quartile was independently associated with the presence of HTN (P = 0.001) and MetS (P = 0.006). The prevalence of atherosclerotic plaque and stenosis was obviously higher in the patients with either HTN or MetS than in those without HTN or MetS. However, there was no significant association of SUA quartile with the presence of atherosclerotic lesions. CONCLUSIONS: SUA levels were closely associated with HTN and MetS, but not with atherosclerosis in type 2 diabetes. Our findings strongly suggest that, in select populations such as those with type 2 diabetes, the role of uric acid in atherosclerosis might be attributable to other cardiovascular risk factors, such as HTN and MetS.

Low ankle-brachial index is associated with early-stage chronic kidney disease in type 2 diabetic patients independent of albuminuria.

AIMS: The role of low ankle-brachial index (ABI) in early-stage chronic kidney disease (CKD) is not fully known. This study was designed to investigate the prevalence of low ABI in early-stage CKD defined as an estimated glomerular filtration rate (eGFR) between 60-89 ml/min/1.73 m2 of type 2 diabetic patients without albuminuria and to determine the association between the low ABI and mildly decreased eGFR. METHODS: The cross-sectional study enrolled 448 type 2 diabetic patients with normoalbuminuria. The patients were stratified into two groups according to the CKD-EPI eGFR level: the normal group with eGFR level ≥ 90 mL/min/1.73 m2 and the lower group with eGFR of 60-89. ABI was categorized as normal (1.0-1.39), low-normal (0.9-0.99), and low (<0.9). Both stepwise forward multiple linear regression and binary logistic regression analyses were performed to examine the association between ABI categories and eGFR levels and to assess the relation of low ABI and early-stage CKD. RESULTS: The prevalence of low ABI in early-stage CKD of type 2 diabetic patients without albuminuria was 39.5%. Low ABI was associated with an approximate 3-fold greater risk of early-stage CKD in bivariate logistic regression analysis, and remained significantly associated with a 2.2 fold risk (95% confidence interval: 1.188-4.077; P = 0.012) after adjusting traditional chronic kidney disease risk factors. CONCLUSIONS: There was a high prevalence of low ABI in early-stage CKD patients of type 2 diabetes with normoalbuminuria and a close relation between low ABI and early-stage CKD, suggesting that we should pay much more attention to the patients who have only mildly decreased eGFR and normoalbuminuria but have already had a low ABI in clinic work and consider the preventive therapy in early stage.

[The correlation between serum uric acid level and abdominal obesity or metabolic syndrome].

OBJECTIVE: To investigate the relationship between serum uric acid (UA) level and abdominal obesity or metabolic syndrome (MS). METHODS: A total of 875 subjects, with 350 males and 525 females, aged 40-65 years old, were enrolled in this study. The clinical and biochemical data were collected and MRI was used to assess the visceral and subcutaneous adipose tissues. The relationships between UA level and abdominal obesity or MS were analyzed, and the cut-off values of UA for abdominal obesity and MS were determined. RESULTS: Raised risks of abdominal obesity(OR = 4.35, 95%CI 1.91-9.90 in males; OR = 5.44, 95%CI 2.41-12.31 in females) and MS(OR = 4.47, 95%CI 2.08-9.62 in males; OR = 11.62, 95%CI 3.43-39.37 in females) were observed with the increase of UA level. The multiple logistic regression analysis showed that UA was an independent risk factor for hypertriglyceridemia(OR = 2.23, 95%CI 1.02-4.87 in males; OR = 3.04, 95%CI 1.49-6.23 in females) in all subjects and for abdominal obesity(OR = 3.23, 95%CI 1.32-7.91) and hypertension (OR = 2.35, 95%CI 1.37-4.05) in the females. Among the females, the regression line analyzed by simple correlation indicated that the UA level of 244.0 µmol/L was corresponded to the visceral adipose tissue area of 80 cm(2). The optimal cut-off point of UA for the diagnosis of MS was 258.8 µmol/L determined by the receiver operating characteristic curve. CONCLUSIONS: The level of UA is closely correlated with abdominal obesity and MS in the middle-aged Chinese. The elevated UA level is an independent risk factor for abdominal obesity and MS in the female.

Low-grade albuminuria is associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes.

BACKGROUND: Low-grade albuminuria is associated with cardiovascular risk factors and mortality. Our aim was to investigate the association between low-grade albuminuria and carotid atherosclerotic lesions in community-based patients with type 2 diabetes. METHODS: A cross-sectional study was performed in 475 community-based patients with type 2 diabetes (190 males and 285 females) with normal urinary albumin-to-creatinine ratios (UACR) (< 3.5 mg/mmol) from Shanghai, China. The subjects were stratified into tertiles based on UACR levels (the lowest tertile was UACR ≤ 1.19 mg/mmol, and the highest tertile was UACR ≥ 2 mg/mmol). Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on ultrasonography. The urinary albumin excretion rate was determined as the mean of the values obtained from three separate early morning urine samples. RESULTS: Compared with the subjects with UACR in the lowest tertile, the subjects with UACR in the middle and highest tertiles had greater CIMT values (0.88 ± 0.35 mm, 0.99 ± 0.43 mm and 1.04 ± 0.35 mm, respectively; all p < 0.05) and a higher prevalence of carotid atherosclerotic plaques (25.3%, 39.0% and 46.2%, respectively; all p < 0.05) after adjusting for sex and age. Fully adjusted multiple linear regression and logistic regression analyses revealed that UACR tertiles were significantly associated with elevated CIMT (p = 0.007) and that, compared with the subjects in the first tertile of UACR, those in the second and third tertiles had 1.878- and 2.028-fold risk of carotid plaques, respectively. However, there was no statistical association between UACR tertile and the prevalence of carotid stenosis. CONCLUSIONS: Higher UACR within the normal range was independently associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes. Low-grade albuminuria contributes to the risk of carotid atherosclerosis and may be used as an early marker for the detection of atherosclerosis in patients with type 2 diabetes.