Association of plasma osteoprotegerin levels with the severity of lower extremity arterial disease in patients with type 2 diabetes.

BACKGROUND: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. However, little is known about the association between plasma OPG levels and lower extremity arterial disease. We investigated whether plasma OPG levels were associated with the presence and severity of lower extremity arterial disease in patients with type 2 diabetes. METHODS: This was a study of 712 patients with type 2 diabetes aged 40 years or older. Plasma OPG was measured using ELISA. The lower extremity arterial disease was diagnosed by high-frequency color Doppler ultrasonic. RESULTS: Of 712 patients, 505 (70.9 %) had lower extremity arterial stenosis. OPG levels were significantly increased in patients with lower extremity arterial stenosis [1.89 (1.48-2.41) vs. 2.39 (1.82-3.33) ng/mL, p < 0.001]. Plasma OPG levels increased gradually with increasing severity of lower extremity arterial stenosis (p < 0.001 for trend), after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index (BMI), systolic blood pressure(SBP). The risk of lower extremity arterial disease was increased (OR = 1.17, 95 % CI 1.09 -1.28, p < 0.001) with each standard deviation (SD) higher level of OPG in patients with type 2 diabetes after adjustment for traditional CVD risk factors. CONCLUSIONS: Plasma OPG levels were significantly associated with the presence and severity of lower extremity arterial disease. Our results suggest that OPG is an important plasma biomarker of lower extremity arterial disease in type 2 diabetes.

Serum lipocalin-2, cathepsin S and chemerin levels and nonalcoholic fatty liver disease.

Several novel circulating adipokines are associated with insulin resistance and inflammation. Little information exists in NAFLD about three recently recognized adipokines lipocalin-2, cathepsin S and chemerin. To assess the relationship between serum lipocalin-2, cathepsin S and chemerin levels and the development of non-alcoholic fatty liver in Chinese subjects, we measured serum lipocalin-2, cathepsin S and chemerin levels in 903 Chinese subjects by ELISA. Among the study population, 436 patients are with B-mode ultrasound-proven NAFLD and 467 controls. Levels of lipocalin-2, but not cathepsin S and chemerin, were significantly elevated in NAFLD versus control [lipocalin-2, 89.67 ± 4.47 vs. 68.70 ± 3.65 ng/mL (p < 0.001)]. After stepwise linear regression analysis adjusting for potential cofounders, further revealed that serum lipocalcin-2 was an independent predictor of NAFLD in whole cohort (standardized ß = 0.114, t = 2.347, p = 0.02). Lipocalin-2 levels correlated with insulin resistance (homeostasis model assessment of insulin resistance) and inflammation (CRP) in whole cohorts and NAFLD, whereas cathepsin S and chemerin only correlated positively with insulin resistance and inflammation in whole cohorts. Our results indicated that circulating lipocalin-2, produced by adipocytes, are elevated and may contribute to the development of NAFLD. Serum lipocalin-2, which correlates with inflammation and insulin resistance, may have a direct pathogenic link to disease progression.

[Analysis of CYP21A2 gene mutations in two families with 21-hydroxylase deficiency].

OBJECTIVE: To analyze CYP21A2 gene mutation in two families with 21-hydroxylase deficiency (21-OHD) and to explore the correlation between genotype and clinical phenotype. METHODS: Two patients with 21-OHD and their families were investigated. CYP21A2 gene mutation was analyzed by PCR and direct sequencing. RESULTS: The probands from family 1 and 2 have been respectively diagnosed with simple virilizing and non-classical 21-OHD. Both showed increased baseline serum 17hydroxyprogesterone, testosterone and adrenocorticotropic hormone (ACTH), but had no evidence of salt loss. Computer tomography revealed bilateral adrenal hyperplasia in both patients. After 1 year treatment, both had conceived successfully. DNA sequencing revealed that the proband of family 1 had compound heterozygous mutations for IVS2 13 A>G and Ile172Asn. Her father was heterozygous for Ile172Asn, whilst her mother and brother were heterozygous for IVS213A/C>G. In family 2, the proband was heterozygous for Arg341Trp and Gln318X. Her father, sister and nephew were heterozygous for Arg341Trp, whilst her mother was heterozygous for Gln318X. her brother and niece were non-affected. Carriers of single heterozygous mutations in both families had no clinical sign. CONCLUSION: In both families, the disease has been caused by compound heterozygous mutations, for which there has been a good genotype-phenotype agreement. Screening of CYP21A2 gene can facilitate both diagnosis and genetic counseling.

Effects of Yijinjing combined with resistance training on body fat distribution and hepatic lipids in middle-aged and older people with prediabetes mellitus: A randomized controlled trial.

PURPOSE: This randomized controlled trial aimed to study the effects of Yijinjing plus Elastic Band Resistance exercise on intrahepatic lipid (IHL), body fat distribution, glucolipid metabolism and biomarkers of inflammation in middle-aged and older people with pre-diabetes mellitus (PDM). PARTICIPANTS AGESND METHODS: 34 PDM participants (mean age, 62.62 ± 4.71 years; body mass index [BMI], 25.98 ± 2.44 kg/m2) were randomly assigned to the exercise group (n = 17) or control group (n = 17). The exercise group performed moderate-intensity Yijinjing and Elastic Band Resistance training 5 times per week for 6 months. The control group maintained their previous lifestyle. We measured body composition (body weight and body fat distribution), IHL, plasma glucose, lipid and the homeostatic model assessment of insulin resistance (HOMA-IR), inflammatory cytokines at baseline and 6 months. RESULTS: Compared with baseline, exercise significantly reduced IHL (reduction of 1.91 % ± 2.61 % vs an increase of 0.38 % ± 1.85 % for controls; P = 0.007), BMI (reduction of 1.38 ± 0.88 kg/m2 vs an increase of 0.24 ± 1.02 kg/m2 for controls; P = 0.001), upper limb fat mass, thigh fat mass and whole body fat mass. Fasting glucose, HOMA-IR, plasma total cholesterol (TC), and triglyceride (TG) were decreased in the exercise group (P < 0.05). There were no effects of exercise on liver enzyme levels and inflammatory cytokines. The decrease in IHL was positively correlated with the decreases in BMI, body fat mass and HOMA-IR. CONCLUSION: Six months of Yijinjing and resistance exercise significantly reduced hepatic lipids and body fat mass in middle-aged and older people with PDM. These effects were accompanied by weight loss, improved glycolipid metabolism and insulin resistance.

Effect of Yi Jin Jing exercise plus Elastic Band Resistance exercise on overall bone mineral density in postmenopausal women.

OBJECTIVES: This work aimed to study the effects of Yi Jin Jing plus Elastic Band Resistance exercise on bone mineral density at all parts of the body and bone metabolism index levels in postmenopausal women. DESIGN: Randomized controlled trial. METHODS: Forty postmenopausal women were randomly assigned equally to the exercise or to the control group. The control group maintained their lifestyle behaviors unaltered, whereas the exercise group received  Yi Jin Jing plus Elastic Band Resistance exercise. The primary outcome was overall bone mineral density at each part, and the secondary one was bone metabolism indicator levels and bone mineral density on both sides. RESULTS: The results after six months showed increased bone mineral density at all parts of the body in the exercise group (spine, P = 0.002; thighs, lumbar, and whole body, P < 0.05) and decreased bone mineral density in the control group (trunk, pelvis, and spine, P < 0.01). In particular, the decrease and increase were greater on the non-preferred (left) side than on the right side. As for bone metabolism indexes, ß-Crosslaps levels reduced (P = 0.016) and a significant increase in 1,25-(OH)2-D3 (P < 0.001) can be observed in the exercise group. CONCLUSIONS: The results suggested that Yi Jin Jing plus Elastic Band Resistance exercise could delay the overall decrease of bone mineral density in postmenopausal women, especially on the non-preferred side. It also increased bone formation metabolite levels and inhibited bone resorption metabolite levels.

Effects and safety of Ginkgo biloba on blood metabolism in type 2 diabetes mellitus: a systematic review and meta-analysis.

Background: There has existed controversy regarding the use of Ginkgo biloba (GKB) for blood metabolism among type 2 diabetes mellitus(T2DM) patients, and we tried to analyze the effects and safety of GKB on T2DM patients. Methods: We conducted a literature search between January 2003 and December 2022 of seven online databases (PubMed, Scopus, Embase, Google Scholar, Web of Sciences, Cochrane Library, and China National Knowledge Infrastructure). A systematic literature review and meta-analysis were performed to compare the effects and safety of GKB among T2DM patients. Four groups of parameters were extracted and analyzed: hemorheology parameters, lipid profile, glycemic control markers, and adverse events. Results: In the end, 13 eligible articles with 11 indicators among 1573 patients were included. In the hemorheology parameters section, GKB showed significantly lower plasma viscosity (PV) (SMD=-0.91, 95%CI [-1.45, -0.36], P<0.01) and hematocrit (Hct) (SMD=-0.60, 95%CI [-0.97, -0.24], P<0.01) than the control group. GKB shoed higher velocity of the dorsalis pedis artery (VDPA) (SMD=0.51, 95%CI [0.26, 0.76], P<0.01) and ankle brachial index (ABI) (SMD=0.71, 95%CI [0.32, 1.10], P<0.01) than the control. In both the lipid profile and glycemic control markers sections, we did not find any difference between GKB and control groups, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hemoglobin A1c (HbA1c), and fasting serum glucose (FSG). In addition, we saw no difference in adverse events (AE). The sensitivity analysis and funnel plot showed that the results in this research were robust and had no publication bias. Conclusion: In conclusion, GKB might safely reduce the risk of peripheral arterial or even systemic cardiovascular disease. However, GKB did not directly improve lipid and blood glucose levels in T2DM patients. Systematic review registration: https://inplasy.com/, identifier INPLASY202350096.

Study on low-temperature cycle failure mechanism of a ternary lithium ion battery.

This study is focused on the changes in parameters such as discharge capacity, and the possible failure mechanism of a 25 Ah ternary lithium ion battery during cycling at -10 °C. A new battery and a battery after 500 cycles were disassembled. The morphology and structure of the cathode and anode electrodes were characterized. Transmission electron microscopy (TEM) and X-ray photoelectron absorption spectroscopy (XPS) were used to analyze the changes in the microstructure and chemical environment of the anode electrode interface. The results show that after 500 cycles at -10 °C, the capacity of the battery is only 18.3 Ah, and there is a large irreversible capacity loss. The battery samples after low-temperature cycling produced gas during storage at 25 °C. It is found that a large amount of lithium plating on the anode surface is an important factor for the reduction in battery capacity. The dissolution of transition metal elements in the cathode electrode and deposition on the anode electrode, and the catalytic decomposition of electrolyte at the anode interface are the main reasons for the gassing of the battery.

Effect of Yijinjing combined with elastic band exercise on muscle mass and function in middle-aged and elderly patients with prediabetes: A randomized controlled trial.

Introduction: This study investigated the effect of Yijinjing combined with elastic band exercise on muscle mass and muscle function in patients with prediabetes. Methods: This study was a randomized controlled trial designed in parallel (Chinese Clinical Trial Registry: ChiCTR2000039049). Participants with prediabetes (n = 47) were randomly divided into control (n = 21, 63.5 ± 4.7 years,16 females) and exercise (n = 26, 62.0 ± 5.0 years, 20 females) groups. The former maintained their original lifestyle, and the latter received Yijinjing combined with elastic band exercise five times a week for 6 months. All the outcome measures were assessed immediately at baseline, after 3- and 6-month intervention. Results: After 6-month of the exercise, the body weight, body mass index, leg fat mass, gynoid fat mass, and total body fat mass in exercise group were significantly decreased compared with those at baseline (p < 0.05). Compared with those at baseline, total lean mass decreased at 3 and 6 months in both groups. The total muscle mass loss in the exercise group was always less than that in control group at all time periods, but the difference was not statistically significant. Handgrip strength, gait speed, reaction time, leg power, eye-closed and single-legged standing, and sit-and-reach were significantly improved for the exercise group at 3 and 6 months (p < 0.05). Gait speed and reaction time between both groups at 3 and 6 months were significant different (p < 0.05), and leg power at 6 months (p < 0.05). Compared with baseline, the reaction time of control group at six months was significantly improved (p < 0.05), and no other significant changes were observed. Compared with those at baseline, fasting plasma glucose, 2-h post-meal plasma glucose, fasting insulin, total cholesterol, and insulin resistance index in exercise group gradually decreased, and growth hormone was gradually increased with significance at 6 months (p < 0.05). 25-hydroxyvitamin D gradually and significantly increased in both groups at 3 and 6 months (p < 0.05). But two groups' testosterone levels weren't significant change. Conclusion: Yijinjing combined with elastic band exercise can substantially reduce the body weight and body fat content of middle-aged and elderly patients with Prediabetes, improve muscle function and growth hormone secretion, and delay muscle mass reduction and diabetes development. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=62753], identifier [ChiCTR2000039049].

[Study on the mitochondrial DNA mutations in familial diabetes mellitus in Chinese population].

OBJECTIVE: To assess the prevalence of mutations or variants of the mitochondrial DNA (mtDNA) in familial diabetes mellitus in Chinese population, and to explore the relationship between mtDNA mutations or variants and diabetes. METHODS: Seven hundred and seventy randomly selected, unrelated probands of diabetes pedigrees and 309 controls over 60 years of age with normal glucose tolerance were recruited. PCR-RFLP and PCR-direct sequencing were applied to the screening of mtDNA mutations or variants, including the mutations at nucleotides 3243, 3256 in tRNALeu region, 12258 in tRNASer region, 14709 in tRNAGlu region, 8296, 8344, 8363 in tRNALys region, 3316, 3394, 3426 in ND1 region and 12026 in ND4 region. RESULTS: In the diabetic group, 13 (1.69%) had mt3243 A>G mutation, 9(1.17%) had tRNAGlu 14709 T>C variant, 17 (2.21%) carried mt3316 G>A variant, 18 (2.34%) had mt3394 T>C variant, and 28 (3.63%) harbored the 12026 A>G variant. In the control group, the 14709, 3316, 3394, 12026 variants were detected in 5(1.62%), 5(1.62%), 6(1.94%), and 9(2.91%) subjects respectively. The 3256, 8296, 8344, 8363, 3426 and 12258 point mutations were not detected both in the diabetic patients and the controls. In the diabetic group, we found two double mutations, one was A3243G and T3394C, the other was A3243G and A12026G. Except that the A3243G mutation was only observed in the diabetic group, the frequencies of the other variants mentioned above were not statistically different between the diabetic and control groups. Moreover, clinical characteristics such as age of onset, BMI, and insulin resistance index were not different between diabetic patients with and without the variants. CONCLUSION: The tRNA (LeuUUR) 3243 A>G mutation may be the major cause of diabetes, representing 1.69% of the familial diabetes mellitus in Chinese. The other variants may be polymorphisms in this population, and the mutations not detected in our studied population may not be common contributors to diabetes mellitus in Chinese.

[Prevalence and clinical characteristics of the mitochondrial tRNA(Leu(UUR)) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population].

OBJECTIVE: To study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China. METHODS: The mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members. RESULTS: Thirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents. CONCLUSION: The mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.

[The genetic and clinical characteristics of transcription factor 1 gene mutations in Chinese diabetes].

OBJECTIVE: To investigate the genetic and clinical features of mutations and sequence variations of the transcription factor 1 gene (TCF1, HNF-1A) in Chinese with familial early-onset and/or multiplex diabetes mellitus. METHODS: All ten exons of the TCF1 gene were screened, including exon and intron junctions, by direct sequencing method in 341 unrelated Chinese subjects, including 80 healthy controls and 261 probands of early-onset and/or multiplex diabetes pedigrees. RESULTS: Five mutations were found in all. Four of the 5 different TCF1 mutations were newly identified novel mutations(T82M, Q130H, G253G, P353fsdelACGGGCCTGGAGC), mean body mass index of mutation carriers was 21.9 kg/m (2), and insulin secretion was impaired in the mutation carriers. In this study, the maturity-onset diabetes of the young type III (MODY3) only accounted for 3% of Chinese early-onset diabetes. Moreover, eleven substitutions were identified in 261 probands. Of them, three variants IVS1-8 (G-->A), IVS1 -128 (T-->G ) and IVS2+21 (G-->A) were not observed in 80 healthy controls and one of them IVS1-8 (G-->A) was not reported previously and the two promoter variants co-segregated with diabetes. CONCLUSION: TCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.

[Prevalence and clinical characteristics of the A to G variant at position 12026 of the mitochondrial ND4 gene in familial diabetes mellitus in Chinese population].

OBJECTIVE: To assess the prevalence of the A to G variant at nucleotide 12026 (mt12026) of the mitochondrial NADH-dehydrogenase subunit 4 (ND4) gene in familial diabetes mellitus in Chinese population. METHODS: The authors screened 770 randomly selected, unrelated probands of diabetic pedigrees, and 309 controls with normal glucose tolerance for the variant by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and PCR-direct-sequencing. RESULTS: The mt12026 A --> G variant was detected in 28 diabetic patients (3.63%) and 9 controls (2.91%). The frequency of the variant mt12026 A --> G was not statistically different between diabetic patients and controls. Moreover, clinical characteristics such as age, body mass index (BMI), and insulin resistant index were not different between diabetic patients with and without the mt12026 mutation. CONCLUSION: The mt12026 A --> G variant is a mitochondrial gene polymorphism in Chinese population, and it is unlikely that the mutation is in itself the cause of diabetes.

Plasma osteoprotegerin levels are inversely associated with nonalcoholic fatty liver disease in patients with type 2 diabetes: A case-control study in China.

OBJECTIVE: Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor (TNF) receptor superfamily, is a decoy receptor for the receptor activator of nucleus factor-κB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). OPG has an effect on systemic insulin sensitivity and glucose homeostasis. The objective of this study was to evaluate the relationship between plasma osteoprotegerin (OPG) levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes. MATERIALS/METHODS: A case-control study was performed with 746 patients with type 2 diabetes. Of the study population, 367 patients had B-mode ultrasound-proven NAFLD and 379 were controls. The plasma OPG levels were measured using ELISA methods. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. RESULTS: The OPG levels were significantly decreased in patients with NAFLD (2.3±1.1µg/L vs. 2.8±1.3µg/L, p=3.75×10(5)) compared to controls. Pearson correlation analysis showed that the OPG levels were associated with age and systolic blood pressure (both p<0.05). The participants in the lowest OPG quartile had a significantly increased risk for NAFLD (OR=3.49, 95% CI 1.86-6.94) after adjusting for potential cofounders. CONCLUSIONS: The plasma OPG level is negatively associated with NAFLD independent of potential cofounders.

Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24.

This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogeneous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showing linkage to type 2 diabetes/IGH from the entire sample group analysis was located on chromosome 6q21-q23 (128.93 cM, 1-LOD [logarithm of odds] support interval between 124 and 142 cM, according to the Marshfield genetic map), with a maximum likelihood score of 6.23, a nonparametric linkage (all) score of 4.48, and empirical P value <0.001. With a subanalysis based on 101 affected sibpairs with age at diagnosis of type 2 diabetes/IGH <40 years, we detected significant evidence for linkage to chromosome 1q21-q24 (192.1 cM, 1-LOD support interval between 182 and 197 cM), with a maximum likelihood score of 8.91, a nonparametric linkage (all) score of 5.70, and empirical P value <0.001. No interaction was observed between these two regions. Our independent replication of the region on chromosome 1q that has been shown to be linked significantly to type 2 diabetes/IGH in Chinese supports the notion that gene(s) in this region may be universally important in the development of human type 2 diabetes.

Osteoinductive factor is a novel biomarker for the diagnosis of early diabetic nephropathy.

BACKGROUND: Microalbuminuria is the earliest clinical sign of diabetic nephropathy (DN). However, earlier markers as a diagnostic tool for DN was required for the invalid of microalbuminuria in some cases. Osteoinductive factor (OIF) was known to be an essential component of the normal vascular matrix. We aimed to research the relationship between DN and OIF, and discussed the availability of the serological markers for earlier stage of DN. METHOD: One hundred twenty Chinese subjects, who included patients with type 2 diabetes mellitus (T2DM), DN with microalbuminuria, and DN with macroalbuminuria, as well as healthy controls, were enrolled in this study. Serum OIF levels were examined by ELISA and other clinical biochemical parameters were tested based on standard methods. RESULTS: Our results indicated that, serum OIF levels were significantly increased in DN subjects compared with healthy and T2DM subjects (P<0.05 respectively). However, no significant changes in serum OIF levels were found between T2DM and healthy subjects. Furthermore, serum OIF had negative correlation with estimated glomerular filtration rate (eGFR) and positive correlation with blood urea nitrogen(BUN) and creatinine. ROC curve analysis showed that serum OIF level was a good sensitive and specificity marker for microalbuminuria and early renal damage with sensitivity of 86.7% and specificity of 95%, as well as for macroalbuminuria and damage progress with sensitivity of 90% and specificity of 95%. CONCLUSION: OIF may be an indicator of the earlier-stage DN in subjects with T2DM. Understanding the exact mechanism of up-regulated OIF in subjects with DN requires further study.

The functional Q84R polymorphism of TRIB3 gene is associated with diabetic nephropathy in Chinese type 2 diabetic patients.

Increased oxidative stress and circulating free fatty acids (FFA) has been suggested to involve in the pathogenesis of diabetic nephropathy. TRIB3 can inhibit FFA and reactive oxygen species (ROS) stimulated podocyte production of MCP-1. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Q84R polymorphism (rs2295490), alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 812 Chinese patients with type 2 diabetes. Among patients, 214 had diabetic nephropathy with microalbuminuria (n=156) or overt albuminuria (n=58), and 598 did not show either of these symptoms but had diabetes for ≥10 years and were not undergoing antihypertension treatment. After adjustment for confounders, TRIB3 single-nucleotide polymorphism rs2295490 was associated with DN (OR 1.318, 95% CI 1.075, 1.653, p=0.017); smoking was also an independent risk factor for diabetic nephropathy (1.42 [1.25-2.04], p<0.001). In addition, we identified possible synergistic effects; i.e., the high-risk group (smokers with the AG+GG genotype) showed 2.13 times higher risk (1.51-3.96, p<0.001) of diabetic nephropathy than the low-risk group (nonsmokers with the AA genotype) in a multiple logistic regression analysis controlled for the confounders, but no departure from additivity was found. Our results indicate that smoking and the TRIB3 G-allele is associated with an increased risk of diabetic nephropathy, which supports the hypothesis that oxidative stress contributes to the development of diabetic nephropathy.

Pyruvate kinase, muscle isoform 2 promotes proliferation and insulin secretion of pancreatic ß-cells via activating Wnt/CTNNB1 signaling.

Failure of pancreatic ß-cells is closely associated with type 2 diabetes mellitus (T2DM), an intractable disease affecting numerous patients. Pyruvate kinase, muscle isoform 2 (PKM2) is a potential modulator of insulin secretion in ß-cells. This study aims at revealing roles and possible mechanisms of PKM2 in pancreatic ß-cells. Mouse pancreatic ß-cell line NIT-1 was used for high glucose treatment and PKM2 overexpression by its specific expression vector. Cell proliferation by Thiazolyl blue assay, cell apoptosis by annexin V-fluorescein isothiocyanate/prodium iodide staining and insulin secretion assay by ELISA were performed in each group. The mRNA and protein levels of related factors were analyzed by real-time quantitative PCR and western blot. Results showed that Pkm2 was inhibited under high glucose conditions compared to the untreated cells (P < 0.01). Its overexpression significantly suppressed NIT-1 cell apoptosis (P < 0.01), and induced cell proliferation (P < 0.05) and insulin secretion (P < 0.05). Related factors showed consistent mRNA expression changes. Protein levels of ß-catenin (CTNNB1), insulin receptor substrate 1 (IRS1) and IRS2 were all promoted by PKM2 overexpression (P < 0.01), indicating the activated Wnt/CTNNB1 signaling. These results indicated the inductive roles of PKM2 in pancreatic ß-cell NIT-1, including promoting cell proliferation and insulin secretion, and inhibiting cell apoptosis, which might be achieved via activating the Wnt/CTNNB1 signaling and downstream factors. This study offers basic information on the role and mechanism of PKM2 in pancreatic ß-cells, and lays the foundation for using PKM2 as a potential therapeutic target in T2DM.

Mitochondrial DNA mutations in diabetes mellitus patients in Chinese Han population.

BACKGROUND AND OBJECTIVE: Mutations of mitochondrial DNA are associated with diabetes mellitus (DM). The present case-control study aimed to investigate the mutations of mitochondrial DNA in DM patients of Chinese Han ethnicity. METHODS AND RESULTS: A total of 770 DM patients and 309 healthy control individuals were enrolled. The mitochondrial DNA was extracted from blood cells and analyzed by the polymerase chain reaction-restriction fragment length polymorphism assay. In the diabetes group, there were 13 (1.69%) individuals carrying the mt3243 A → G mutation while none of the healthy control had this mutation. Though the 14709, 3316, 3394, and 12026 mutation variants were identified in 9, 17, 18 and 28 in DM patients respectively, there were no significant differences compared with control group. And the 3256, 8296, 8344, 8363, 3426 and 12258 mutations were not detected in either group. In the diabetes group, two double mutations were identified: A3243G+T3394C and A3243G+A12026G. CONCLUSION: Our data suggested that mitochondrial gene tRNA(Leu(UUR)) 3243 A → G mutation may be one risk of prevalence of DM and associated with worse clinical status in Chinese Han population.