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Tumor‐induced angiogenesis is important for further progression of solid tumors. The initiation of tumor angiogenesis is dictated by a shift in the balance between proangiogenic and antiangiogenic gene expression programs. However, the potential mechanism controlling the expression of angiogenesis‐related genes in the tumor cells, especially the process mediated by RNA‐binding protein (RBP) remains unclear. SAMD4A is a conserved RBP across fly to mammals, and is believed to play an important role in controlling gene translation and stability. In this study, we identified the potential role of SAMD4A in modulating angiogenesis‐related gene expression and tumor progression in breast cancer. SAMD4A expression was repressed in breast cancer tissues and cells and low SAMD4A expression in human breast tumor samples was strongly associated with poor survival of patients. Overexpression of SAMD4A inhibited breast tumor angiogenesis and caner progression, whereas knockdown of SAMD4A demonstrated a reversed effect. Mechanistically, SAMD4A was found to specifically destabilize the proangiogenic gene transcripts, including C‐X‐C motif chemokine ligand 5 (CXCL5), endoglin (ENG), interleukin 1β (IL1β), and angiopoietin 1 (ANGPT1), by directly interacting with the stem‐loop structure in the 3′ untranslated region (3′UTR) of these mRNAs through its sterile alpha motif (SAM) domain, resulting in the imbalance of angiogenic genes expression. Collectively, our results suggest that SAMD4A is a novel breast tumor suppressor that inhibits tumor angiogenesis by specifically downregulating the expression of proangiogenic genes, which might be a potential antiangiogenic target for breast cancer therapy., Here, we identified the expression pattern of RNA‐binding protein SAMD4A in breast cancers and its potential role in modulating angiogenesis‐related gene expression. Mechanistically, SAMD4A could suppress breast tumor angiogenesis and metastasis by selectively destabilizing proangiogenic mRNAs by targeting the stem‐loop structure in 3′UTR.

Tumor angiogenesis is a crucial step in the further growth and metastasis of solid tumors. However, its regulatory mechanism remains unclear. Here, we showed that TARBP2, an RNA‐binding protein, played a role in promoting tumor‐induced angiogenesis both in vitro and in vivo through degrading the mRNAs of antiangiogenic factors, including thrombospondin1/2 (THBS1/2), tissue inhibitor of metalloproteinases 1 (TIMP1), and serpin family F member 1 (SERPINF1), by targeting their 3′untranslated regions (3′UTRs). Overexpression of TARBP2 promotes tumor cell–induced angiogenesis, while its knockdown inhibits tumor angiogenesis. Clinical cohort analysis revealed that high expression level of TARBP2 was associated with poor survival of lung cancer and breast cancer patients. Mechanistically, TARBP2 physically interacts with the stem‐loop structure located in the 3′UTR of antiangiogenic transcripts, leading to mRNA destabilization by the dsRNA‐binding domains 1/2 (dsRBDs1/2). Notably, the expression level of TARBP2 in human tumor tissue is negatively correlated with the expression of antiangiogenic factors, including THBS1/2, and brain‐specific angiogenesis inhibitor 1 (BAI1). Moreover, TARBP2 expression is strongly associated with tumor angiogenesis in a group of human lung cancer samples. Collectively, our results highlight that TARBP2 is a novel tumor angiogenesis regulator that could promote tumor angiogenesis by selectively downregulating antiangiogenic gene expression., We demonstrated that TARBP2 was able to promote tumor angiogenesis through selectively destabilizing the mRNAs of antiangiogenic factor genes via binding to the stem‐loop structure located in the 3′UTRs. Strikingly, our basic research findings have also been confirmed by analyzing the clinical samples and data from human breast and lung cancers. Thus, TARBP2 is likely to be a useful molecular target for antiangiogenic tumor therapy.

Tumor angiogenesis is an essential step in tumor growth and metastasis. The initiation of tumor angiogenesis is dictated by a shift in the balance between proangiogenic and antiangiogenic gene expression programs. Roquin2 is a zinc-finger RNA-binding protein with important roles in mediating the expression of inflammatory genes, such as TNF, IL6 and PTGS2, which are also important angiogenic factors. In this study, we demonstrate that Roquin2 functions as a potent tumor angiogenesis regulator that inhibits breast tumor-induced angiogenesis by selectively destabilizing mRNA of proangiogenic gene transcripts, including endoglin (ENG), endothelin-1 (EDN1), vascular endothelial growth factor B (VEGFB) and platelet derived growth factor C (PDGFC). Roquin2 recognizes and binds the stem-loop structure in the 3'untranslated region (3'UTR) of these mRNAs via its ROQ domain to destabilize mRNA. Moreover, we found that Roquin2 expression was reduced in breast cancer cells and tissues, and associated with poor prognosis in breast cancer patients. Overexpression of Roquin2 inhibited breast tumor-induced angiogenesis in vitro and in vivo, whereas silencing Roquin2 enhanced tumor angiogenesis. In vivo induction of Roquin2 by adenovirus significantly suppressed breast tumor growth, metastasis and angiogenesis. Taken together, our results identify that Roquin2 is a novel breast cancer suppressor that inhibits tumor angiogenesis by selectively downregulating the expression of proangiogenic genes.

Background Dysregulation of cell cycle progression is a common feature of human cancer cells; however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest in breast cancer. Methods Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and its association with patient survival. Quantitative real-time PCR and Western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assays, flow cytometry, and in vivo analyses were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA sequencing was applied to identify the differentially expressed genes regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1. Results We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse-free survival of patients with breast cancer. Roquin1 overexpression inhibited cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizes cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2), by targeting the stem–loop structure in the 3′ untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs. Conclusions Our findings demonstrated that Roquin1 is a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might be a potential molecular target for breast cancer treatment.

This systematic review and meta-analysis aimed to evaluate the accuracy of fine-needle aspiration (FNA) and core-needle biopsy (CNB) in diagnosing thyroid cancer. The PubMed, Embase, and Cochrane Library databases were retrieved up to May 2019, and the overall accuracy of FNA and CNB in diagnosing thyroid cancer was evaluated by meta-analysis. The sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. The summary receiver operating characteristic (ROC) curve was estimated, and the area under the ROC curve (AUC) was calculated. Ten eligible studies, involving 10,078 patients with 10,842 thyroid nodules, were included. The overall sensitivity and specificity of FNA and CNB for thyroid cancer were 0.72 [95 % confidence interval (CI): 0.69-0.74], 0.99 (95% CI: 0.98-0.99), and 0.83 (95% CI: 0.81-0.85), 0.99 (95% CI: 0.98-0.99), respectively. Other parameters used to assess efficacy included PLR 41.71 (2.15-808.27) and 51.56 (3.20-841.47), NLR 0.31 (0.22-0.42) and 0.22 (0.15-0.32), for FNA and CNB, respectively. Overall, the pooled summary ROC (AUC) value of FNA and CNB was 0.9025 and 0.7926, respectively. No significant difference was observed between the two AUCs of FNA and CNB (P = 0.164). FNA and CNB are still similar as first-line diagnostic tools. FNA remains a good first-line method for detecting thyroid malignancies.

Introduction We compared the effects of insulin lispro mix 25 (LM25) and insulin lispro mix 50 (LM50) on postprandial glucose excursion in patients with type 2 diabetes mellitus (T2DM). Methods In this randomized, open-label, investigator-initiated trial, 81 T2DM patients treated with premixed human insulin 70/30 (PHI70/30) for more than 90 days were randomly divided into two groups and received a crossover protocol of either LM25 or LM50 twice daily for 16 weeks. Continuous glucose monitoring (CGM) was performed for 72 h at baseline and at the end of each treatment phase to evaluate glycemic excursions in the subjects. Results The LM50 regimen resulted in significantly smaller postprandial glycemic excursions than the LM25 regimen after breakfast (1.3 ± 2.5 vs. 2.4 ± 2.6 mmol/L, P = 0.046) and dinner (1.5 ± 2.8 vs. 2.8 ± 2.4 mmol/L, P = 0.036). Glycosylated hemoglobin levels were similar for the patients on the three regimens. The percentage of patients who achieved their glycosylated hemoglobin target was significantly higher for the LM25 and LM50 regimens than for the PHI70/30 regimen, regardless of whether the target was set at 7.0% or 6.5%. The proportion of the patients who were hypoglycemic for a high percentage (> 10%) of the time was lower for the LM50 regimen than for the LM25 and PHI70/30 regimens. Conclusions LM50 may provide better glycemic excursion control after breakfast and dinner than LM25 in T2DM patients. Trial Registration http://www.chictr.org.cn # ChiCTR-TTRCC-12002516. Funding Lilly Suzhou Pharmaceutical Co., Ltd. (Shanghai Branch, China) and National Key Program of Clinical Science of China (WBYZ 2011-873).

Aims/Introduction To investigate the effect of telomere shortening and other predictive factors of non‐alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus patients in a 6‐year prospective cohort study. Materials and Methods A total of 70 type 2 diabetes mellitus (mean age 57.8 ± 6.7 years) patients without NAFLD were included in the study, and 64 of them were successfully followed up 6 years later, excluding four cases with significant alcohol consumption. NAFLD was diagnosed by the hepatorenal ratio obtained by a quantitative ultrasound method using NIH image analysis software. The 39 individuals that developed NAFLD were allocated to group A, and the 21 individuals that did not develop NAFLD were allocated to group B. Fluorescent real‐time quantitative polymerase chain reaction was used to measure telomere length. Results There was no significant difference between the two groups in baseline telomere length; however, at the end of the 6th year, telomere length had become shorter in group A compared with group B. There were significant differences between these two groups in baseline body mass index, waistline, systolic blood pressure, glycated hemoglobin and fasting C‐peptide level. In addition, the estimated indices of baseline insulin resistance increased in group A. Fasting insulin level, body mass index, systolic blood pressure at baseline and the shortening of telomere length were independent risk factors of NAFLD in type 2 diabetes mellitus patients. Conclusions Telomere length became shorter in type 2 diabetes mellitus patients who developed NAFLD over the course of 6 years. Type 2 diabetes mellitus patients who developed NAFLD had more serious insulin resistance compared with those who did not develop NAFLD a long time ago.

Aims Our aim is to explore the associations between mitochondrial DNA (mtDNA) content and basal plasma glucose, plasma glucose after oral glucose administration and oxidative stress in a Chinese population with different levels of glucose tolerance. We also aimed to investigate the effect of mtDNA content on basal and oral glucose-stimulated insulin secretion. Methods Five hundred and fifty-six Chinese subjects underwent a 75-g, 2-h oral glucose tolerance test. Subjects with diabetes (n = 159), pre-diabetes (n = 197) and normal glucose tolerance (n = 200) were screened. Blood lipid profile was assessed, and levels of the oxidative stress indicators superoxide dismutase, glutathione reductase (GR) and 8-oxo-2′-deoxyguanosine (8-oxo-dG) were measured. Levels of HbA1c, plasma glucose, insulin and C-peptide were also determined. Measurements were taken at 0, 30, 60 and 120 min after 75 g oral glucose tolerance test. Peripheral blood mtDNA content was assessed using a real-time polymerase chain reaction assay. Insulin sensitivity was evaluated by homeostatic model assessment of insulin resistance and Matsuda index (ISIM). Basal insulin secretion index (HOMA-β), early phase disposition index (DI30) and total phase disposition index (DI120) indicate insulin levels at different phases of insulin secretion. Results Peripheral blood mtDNA content was positively associated with DI30 and DI120 and was negatively associated with plasma glucose measured 30, 60 and 120 min after oral glucose administration. However, there was no correlation between mtDNA content and basal insulin secretion (HOMA-β), serum lipid or oxidative stress indicators (8-oxo-dG, superoxide dismutase, GR). HbA1c was negatively associated with GR (r = −0.136, p = 0.001). Multiple linear regression analysis showed that reduced peripheral blood mtDNA content increased the risk of impaired glucose-stimulated β cell function (DI30: β = 0.104, p = 0.019; DI120: β = 0.116, p = 0.009). Conclusions Decreased peripheral blood mtDNA content was more closely associated with glucose-stimulated insulin secretion than with basal secretion. Reduction in glucose-stimulated insulin secretion causes postprandial hyperglycaemia. The oxidative stress was probably largely influenced by hyperglycaemia; it was probably that the decreased mt DNA content led to hyperglycaemia, which caused elevated oxidative stress. © 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

Objective. The RNAFH study (effect of rosuvastatin on nonalcoholic fatty liver disease in metabolic syndrome patients without overt diabetes evaluated by 1H-MRS) is a prospective randomized, single-center, open-label trail designed to assess the effect of rosuvastatin on the intrahepatocellular lipid (IHCL) level of nonalcoholic fatty liver disease (NAFLD). Methods. 40 NAFLD patients meeting inclusion and exclusion criteria with metabolic syndrome (MS) but without overt diabetes mellitus will be included. Patients will be randomized to 52-week treatment with either rosuvastatin (10 mg/d) or blank control. The primary end point is IHCL evaluated by 1H-MRS, which was considered to be the most accurate noninvasive method for the evaluation of NAFLD. Secondary end points include homeostasis model assessment of insulin resistance (HOMA-IR) index on behalf of insulin resistance level and lipid parameters. Safety indicators will be monitored such as liver function, renal function, muscle stability, and glucose metabolism. The aims of the present study are noteworthy in respect that (1) IHCL is a quantitative indicator for evaluating the degree of fatty liver disease and 1H-MRS is a noninvasive technique to provide this specific index precisely, (2) meanwhile the HOMA-IR index and lipid parameters will be monitored, and (3) the safety of rosuvastatin treatment for 52 weeks will be evaluated including glucose metabolism, muscle stability, liver function, and renal function.

Aims/Introduction Uncoupling protein 2 (UCP2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver-associated signaling pathway by expression profiling analysis. Materials and Methods Four-week-old male UCP2−/− mice and UCP2+/+ mice were randomly assigned to four groups: UCP2−/− on a high-fat diet, UCP2−/− on a normal chow diet, UCP2+/+ on a high-fat diet and UCP2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array. Results The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β-cell function were improved in the UCP2−/− group on high-fat diet. Enhanced insulin sensitivity was observed in the UCP2−/− group. The differentially expressed genes were mapped to 23 pathways (P

Background The aim of the present study was to explore whether the triglyceride to high density lipoprotein cholesterol ratio [log (TG)/HDL-C] and peripheral blood leukocytes DNA telomere length could predict future islet beta cell function decreased in Chinese type 2 diabetes mellitus (T2DM) during a 6-year cohort. Methods Sixty T2DM patients (without insulin treatment at baseline) were included in the 6-year cohort study. Peripheral blood leukocytes DNA telomere length, HbA1c, blood lipid profile, fatty fat acid, glucose, insulin and C peptide (3 h after a mixed meal) were determined. Delta C peptide area under curve (Delta CP AUC) was used to reflect change in beta cell secretion function (Delta CP AUC = baseline CP AUC – CP AUC after 6 years). Subjects were divided into slow decrease of beta cell function group (Delta CP AUCslow group) and fast decrease group (Delta CP AUCfast group) according to median of Delta CP AUC. Baseline demographic characteristics, clinical variables between two groups were compared. Correlations between baseline data and Delta CP AUC were analyzed. Results Baseline log (TG)/HDL-C was positively correlated with Delta CP AUC (r = 0.306, P = 0.027); log (TG)/HDL-C in Delta CP AUCfast group was higher than that in Delta CP AUCslow group (0.103 ± 0.033 vs 0.083 ± 0.030, P = 0.027). There was no significant difference in DNA telomere length between the two groups. Change in DNA telomere length over 6 years was not significantly correlated with baseline blood lipid. Conclusions In Chinese T2DM patients, high baseline log (TG)/HDL-C ratio predicts fast progression of islet beta cell dysfunction. It may be a simple index to predict progression speed of islet beta cell dysfunction. 摘要 目的： 本研究通过基于中国2型糖尿病患者的一项6年的队列研究探讨血甘油三酯与高密度脂蛋白胆固醇的比值 [triglyceride to high density lipoprotein cholesterol ratio，Log (TG)/HDL-C]及外周血白细胞DNA端粒长度对胰岛beta细胞功能下降的预测作用。 方法： 60名未用胰岛素治疗的2型糖尿病患者进入6年的队列研究。测定外周血白细胞DNA端粒长度，HbA1c，混合餐后3小时的血脂谱、游离脂肪酸、血糖、胰岛素、C肽值。用Delta C肽曲线下面积（Delta CP AUC）表示6年前后beta细胞分泌功能的变化 ( Delta CP AUC = 基线CP AUC–6年后CP AUC)，根据Delta CP AUC二分位将受试者分为beta细胞功能下降较慢组（Delta CP AUCslow组）和下降较快组（Delta CP AUCfast组）。比较两组间基线人口学特征及临床变量间的差异。并分析基线数据与Delta CP AUC的相关性。 结果： 基线log (TG)/HDL-C与Delta CP AUC呈显著正相关（r = 0.306，P = 0.027）；Delta CP AUCfast组的基线log (TG)/HDL-C值高于Delta CP AUCslow组（0.103 ± 0.033 vs. 0.083 ± 0.030，P = 0.027）。两组间端粒长度不存在显著性差异。6年间端粒长度变化与基线时血脂状况不存在显著相关性。 结论： 在中国2型糖尿病患者中，基线时Log (TG)/HDL-C比值高预示胰岛beta细胞功能障碍进展较快。基线Log (TG)/HDL-C可能成为预测胰岛beta细胞功能障碍进展速度的一种简单方法。

Objective To retrospectively analyze the clinical characteristics of 261 cases of hospitalized patients with type 1 diabetes mellitus (T1DM) in Peking Union Medical College Hospital (PUMCH). Methods Clinical data of 261 cases of hospitalized patients diagnosed with T1DM in the Department of Endocrinology at PUMCH from January 2007 to December 2014 were analyzed retrospectively. All patients were divided into the T1DM antibodies positive group ( n =180) and negative group ( n =81) according to the results of immunohistochemistry, in which 123 newly diagnosed T1DM patients were divided into the adult onset group (>18 years, n =58) and non-adult onset group (≤18 years, n =65) according to the onset age of T1DM, respectively. The clinical characteristics from different groups were compared. Results In 261 patients, the average age was 26.6±15.4 years, the average disease duration was 49 (1–480) months, the positive rate of antibodies to glutamic acid decarboxylase antibody was 58.8% (153/260). The level of 2-hour postprandial C peptide and the positive rate of T1DM antibodies in the non-adult onset group were higher than those in the adult onset group (0.98 vs. 0.52 ng/ml, P =0.002 and 80.4% vs. 62.5%, P =0.048). The age of onset in the T1DM antibodies positive group was smaller than that in the T1DM antibodies negative group (19.7±11.4 vs. 24.7±15.6 years, P =0.04), while the incidence of ketosis in the T1DM antibodies positive group was higher than that in the T1DM antibodies negative group (48.3% vs. 34.2%, P =0.035). With the progress of the disease, the fasting C peptide level of the T1DM antibodies positive group decreased more rapidly. Compared with the single time hospitalized patients, multiple hospitalized patients had a lower incidence of diabetic retinopathy (8.2% vs. 22.4%, P =0.032), a lower hemoglobin A1 c level (8.04%±2.10% vs. 9.56%±2.64%, P vs. 10.9±4.2 mmol/L, P Conclusions Compared with the non-adult onset T1DM patients, the islet function of adult onset patients was even worse. In the T1DM antibodies positive patients, the islet β cell function decreased more rapidly, so the antibodies could not only clarify the diagnosis of T1DM and also predict prognosis of the islet β cell function. In the management of T1DM patients, regular hospital revisits contributed to get better glycemic control and reduced the occurrence of diabetic complications.

Background Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was a surrogate marker of IR; however, the relationship of TG/HDL-C with IR might vary by ethnicity. This study aims to investigate whether lipid ratios-TG/HDL-C, cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio, low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (LDL-C/HDL-C)) could be potential clinical markers of insulin resistance (IR) and β cell function and further to explore the optimal cut-offs in a Chinese population with different levels of glucose tolerance. Methods Four hundred seventy-nine subjects without a history of diabetes underwent a 75 g 2 h Oral Glucose Tolerance Test (OGTT). New-onset diabetes (n = 101), pre-diabetes (n = 186), and normal glucose tolerance (n = 192) were screened. IR was defined by HOMA-IR > 2.69. Based on indices (HOMA-β, early-phase disposition index [DI30], (ΔIns30/ΔGlu30)/HOMA-IR and total-phase index [DI120]) that indicated different phases of insulin secretion, the subjects were divided into two groups, and the lower group was defined as having inadequate β cell compensation. Logistic regression models and accurate estimates of the areas under receiver operating characteristic curves (AUROC) were obtained. Results In all of the subjects, TG/HDL, TC/HDL-C, LDL-C/HDL-C, and TG were significantly associated with IR. The AUROCs of TG/HDL-C and TG were 0.71 (95 % CI: 0.66–0.75) and 0.71 (95 % CI: 0.65–0.75), respectively. The optimal cut-offs of TG/HDL-C and TG for IR diagnosis were 1.11 and 1.33 mmol/L, respectively. The AUROCs of TC/HDL-C and LDL-C/HDL-C were 0.66 and 0.65, respectively, but they were not acceptable for IR diagnosis. TG/HDL-C,LDL-C/HDL-C and TG were significantly associated with HOMA-β, but AUROCs were less than 0.50; therefore, the lipid ratios could not be predictors of basal β cell dysfunction. None of the lipid ratios was associated with early-phase insulin secretion. Only TG/HDL-C and TG were significantly correlated with total-phase insulin secretion, but they also were not acceptable predictors of total-phase insulin secretion (0.60

Background Mitochondrial diabetes is a kind of rare diabetes caused by monogenic mutation in mitochondia. The study aimed to summarize the clinical phenotype profiles in mitochondrial diabetes withm.3243A>G mitochondrial DNA mutation and to investigate the mechanism in this kind of diabetes by analyzing the relationship among clinical phenotypes and peripheral leukocyte DNA telomere length. Methods Fifteen patients with maternally inherited diabetes in five families were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. One hundred patients with type 2 diabetes and one hundred healthy control subjects were recruited to participate in the study. Sanger sequencing was used to detect the m.3243A>G mitochondrial DNA mutation. The peak height G/A ratio in the sequence diagram was calculated. Real-time polymerase chain reaction (PCR) was used to measure telomere length. Results The patients with mitochondrial diabetes all had definite maternally inherited history, normal BMI (19.5 ± 2.36 kg/m2), early onset of diabetes (35.0 ± 14.6 years) and deafness. The peak height G/A ratio correlated significantly and negatively with the age at onset of diabetes (≦25 years, 61.6 ± 20.17 %; 25–45 years, 16.59 ± 8.64 %; >45 years, 6.37 ± 0.59 %; p = 0.000). Telomere length was significantly shorter among patients with mitochondrial diabetes and type 2 diabetes than in the control group (1.28 ± 0.54 vs. 1.14 ± 0.43 vs. 1.63 ± 0.61; p = 0.000). However, there was no significant difference between patients with mitochondrial diabetes and those with type 2 diabetes. There was no correlation between telomere length and the peak height G/A ratio. Conclusion Deafness with definite maternal inheritance and normal BMI, associated with elevated blood lactic acid and encephalomyopathy, for the most part, suggest the diagnosis of mitochondrial diabetes . The peak height G/A ratio could reflect the spectrum of age at onset of the disease. Telomere length was shorter in patients with mitochondrial diabetes and those with type 2 diabetes, which suggests that the shorter telomere length is likely involved in the pathogenesis of diabetes but is not specific for this kind of diabetes.

Objectives To explore influence of carbohydrates/fat proportions, dietary ingredients on telomere length shortening, oxidative stress and inflammation in a Chinese population with different glucose tolerance status. Methods Five hundred and fifty-six Chinese subjects without diabetes history underwent a 75 g, 2 h Oral Glucose Tolerance Test (OGTT). Subjects with diabetes (n = 159), pre-diabetes (n = 197), and normal glucose tolerance (n = 200) were screened. Dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood leukocyte telomere length (LTL) was assessed using a real-time PCR assay. Blood lipid profile, levels of the oxidative stress indicators superoxide dismutase (SOD), glutathione reductase (GR), 8-oxo-2′-deoxyguanosine (8-oxo-dG) and inflammation indicators tumor necrosis factor (TNF-ɑ), interleukine-6 (IL-6) were measured. Levels of HbA1c, plasma glucose, insulin, and C peptide were also determined. Measurements were taken at 0 min, 30 min, 60 min, and 120 min after 75 g OGTT. Insulin sensitivity was evaluated by HOMA-IR. Basal insulin secretion index (HOMA-β), early phase disposition index (DI30) and total phase disposition index (DI120) indicate insulin levels at different phases of insulin secretion. Results In patients with newly diagnosed diabetes, LTL adjusted by age was longer in HbA1c