Liegang Liu

Sleep Duration and Risk of Type 2 Diabetes: A Meta-analysis of Prospective Studies

OBJECTIVE It remains unclear how many hours of sleep are associated with the lowest risk of type 2 diabetes. This meta-analysis was performed to assess the dose-response relationship between sleep duration and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS PubMed and Embase were searched up to 20 March 2014 for prospective observational studies that assessed the relationship of sleep duration and risk of type 2 diabetes. Both semiparametric and parametric methods were used. RESULTS Ten articles with 11 reports were eligible for inclusion in the meta-analysis. A total of 18,443 incident cases of type 2 diabetes were ascertained among 482,502 participants with follow-up periods ranging from 2.5 to 16 years. A U-shaped dose-response relationship was observed between sleep duration and risk of type 2 diabetes, with the lowest risk observed at a sleep duration category of 7–8 h per day. Compared with 7-h sleep duration per day, the pooled relative risks for type 2 diabetes were 1.09 (95% CI 1.04–1.15) for each 1-h shorter sleep duration among individuals who slept <7 h per day and 1.14 (1.03–1.26) for each 1-h increment of sleep duration among individuals with longer sleep duration. CONCLUSIONS Our dose-response meta-analysis of prospective studies shows a U-shaped relationship between sleep duration and risk of type 2 diabetes, with the lowest type 2 diabetes risk at 7–8 h per day of sleep duration. Both short and long sleep duration are associated with a significantly increased risk of type 2 diabetes, underscoring the importance of appropriate sleep duration in the delay or prevention of type 2 diabetes.

Interactions Between Zinc Transporter-8 Gene (SLC30A8) and Plasma Zinc Concentrations for Impaired Glucose Regulation and Type 2 Diabetes

Although both SLC30A8 rs13266634 single nucleotide polymorphism and plasma zinc concentrations have been associated with impaired glucose regulation (IGR) and type 2 diabetes (T2D), their interactions for IGR and T2D remain unclear. Therefore, to assess zinc-SLC30A8 interactions, we performed a case-control study in 1,796 participants: 218 newly diagnosed IGR patients, 785 newly diagnosed T2D patients, and 793 individuals with normal glucose tolerance. After adjustment for age, sex, BMI, family history of diabetes, and hypertension, the multivariable odds ratio (OR) of T2D associated with a 10 µg/dL higher plasma zinc level was 0.87 (95% CI 0.85–0.90). Meanwhile, the OR of SLC30A8 rs13266634 homozygous genotypes CC compared with TT was 1.53 (1.11–2.09) for T2D. Similar associations were found in IGR and IGR&T2D groups. Each 10 µg/dL increment of plasma zinc was associated with 22% (OR 0.78 [0.72–0.85]) lower odds of T2D in TT genotype carriers, 17% (0.83 [0.80–0.87]) lower odds in CT genotype carriers, and 7% (0.93 [0.90–0.97]) lower odds in CC genotype carriers (P for interaction = 0.01). Our study suggested that the C allele of rs13266634 was associated with higher odds of T2D, and higher plasma zinc was associated with lower odds. The inverse association of plasma zinc concentrations with T2D was modified by SLC30A8 rs13266634. Further studies are warranted to confirm our findings and clarify the mechanisms underlying the interaction between plasma zinc and the SLC30A8 gene in relation to T2D.

Acute and subchronic oral toxicities of Pu-erh black tea extract in Sprague–Dawley rats

ETHNOPHARMACOLOGICAL RELEVANCE Pu-erh black tea, which is obtained by first parching crude green tea leaves and then undergoes secondary fermentation with microorganisms, has been believed to be beneficial beverages for health for nearly 2000 years in China, Japan and Taiwan area. But its potential toxicity when administered at a high dose as concentrated extracts has not been completely investigated. THE AIM OF THE STUDY The present study was aimed at evaluating potential toxicity of Pu-erh black tea extracts (BTE) from acute and sub-chronic administration to male and female Sprague-Dawley (SD) rats. MATERIALS AND METHODS A single BTE dose of 10,000 mg/kg of body weight was administered by oral gavage for acute toxicity in SD rats. Four groups (10 males and 10 females per group) of dose levels of 1250, 2500, and 5,000 mg/kg/day of the test article, as well as controls (distilled water) were tested as the subchronic toxicity study. RESULTS No deaths and signs of toxicity occurred during the 14 days of the study. There were no test article related mortalities, body weight gain, feed consumption, clinical observation, organ weight changes, gross finding, clinical or histopathological alterations during the 91-day administration. CONCLUSIONS The LD(50) of BTE can be defined as more than 10,000 mg/kg, and a dose of 5,000 mg/kg/day was identified as the no-observed-adverse-effect-level (NOAEL) in this study.

Pu-erh black tea extract supplementation attenuates the oxidative DNA damage and oxidative stress in Sprague-Dawley rats with renal dysfunction induced by subchronic 3-methyl-2-quinoxalin benzenevinylketo-1,4-dioxide exposure.

3-Methyl-2-quinoxalin benzenevinylketo-1,4-dioxide (Quinocetone, QCT), has been used to treat dysentery and promote growth in animal feeding. However, available data show that QCT has potential nephrotoxicity. The present study was designed to investigate the protective effects of Pu-erh black tea extract (PBTE) which is a traditional remedy in China with antioxidant properties against oxidative DNA damage and oxidative stress in a rat model of QCT-induced renal dysfunction. Increased serum creatinine, blood urea nitrogen, pathological lesions, urinary 8-hydroxy 2-deoxyguanosine (8-OHdG) and renal DNA damage were observed in the QCT-fed rats. These were accompanied by intracellular reactive oxygen species accumulation, enhanced lipid peroxidation, and inhibited antioxidant system, i.e., glutathione glutathione S-transferase, glutathione peroxidase and glutathione reductase. Oral administration of PBTE effectively suppressed QCT-induced renal dysfunction, as evidenced by reduced serum creatinine, urinary 8-OHdG and DNA damage in isolated renal cells, amelioration of oxidative stress and modulation of antioxidative system. In conclusion, PBTE administration ameliorated QCT-induced nephrotoxicity by maintaining DNAs double-helix architecture and mitigating oxidative stress.

Evaluation of oral subchronic toxicity of Pu-erh green tea (camellia sinensis var. assamica) extract in Sprague Dawley rats

ETHNOPHARMACOLOGICAL RELEVANCE Pu-erh green tea, originally produced in the Yunnan province of P.R. China for about 1700 years, is believed to be beneficial to health in Asian countries. The potential toxicity of Pu-erh green tea when administered at high doses via concentrated extract, however, has not been completely investigated. THE AIM OF THE STUDY The present study was aimed to evaluate the potential toxicity of Pu-erh green tea extract (PGTE) of sub-chronic administration to Sprague Dawley (SD) rats. MATERIALS AND METHODS Growing SD rats were administrated orally by gavage with PGTE at doses of 0, 1250, 2500, and 5000 mg/kg/day for 91 consecutive days. Clinical observations, including survival, hematology, serum biochemistry, urinalysis and histopathological examination were measured to monitor treatment-related adverse effects in rats. RESULTS The results showed that oral administration of high dose of PGTE led to body weight gain suppression, liver and calcium deposition dysfunctions. CONCLUSIONS In conclusion, the no-observed-adverse-effect level for Pu-erh green tea extract derived from the results of the present study was 2500 mg/kg/day for both genders.

Roles of ROS mediated oxidative stress and DNA damage in 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide-induced immunotoxicity of Sprague–Dawley rats

3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) has been broadly used to treat dysentery and promote animal growth in food producing animals. However, its potential toxicity could not been neglected as parts of safety assessment according to the acceptable guidelines for QCT administration. In this study, the immunotoxicity of QCT was investigated in male Sprague-Dawley (SD) rats following a 28-day oral exposure at doses of 0, 50, 800, and 2400 mg/kg/day. The food consumption, body weight gain and relative spleen weight were significantly decreased by QCT in a dose-dependent manner. Treatment of rats with QCT also notably suppressed the T-cell proliferation and natural killer (NK) cell activity, accompanied by intracellular reactive oxygen species (ROS) accumulation, antioxidant system inhibition and DNA damage enhancement. Thus, the primary finding of this study is that QCT exposure (2400 mg/kg/day) could cause immunotoxicity in SD rats due to ROS mediated oxidative stress and DNA damage.

Evaluation of reproductive and developmental toxicities of Pu-erh black tea (Camellia sinensis var. assamica) extract in Sprague Dawley rats

ETHNOPHARMACOLOGICAL RELEVANCE Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in PR China. But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated. AIM OF THE STUDY The present study was aimed at evaluating potential reproductive and developmental toxicities of Pu-erh black tea extract (BTE) in Sprague Dawley rats. MATERIALS AND METHODS Growing rats were given BTE by gavage at levels of 0, 200, 700 and 2500mg/kg/day as the F0 generation in reproductive toxicity study. Additionally, BTE was administered to mate female rats from gestation day 0.5 through 19.5 at the doses of 0, 200, 700 and 2500mg/kg/day to evaluate the developmental toxicity. RESULTS In the reproductive toxicity study, only 2500mg/kg/day BTE reduced the body weight gain and altered the relative organ weights including testes, prostata and ovary both for F0 parents and F1 offspring compared to the controls. High dose of BTE (2500mg/kg/day) administration caused developmental disturbances in embryo-to-foetus period including resorbed embryos, decreased embryo size and skeletal anomalies. CONCLUSION In conclusion, the no-observed-adverse-effect level of BTE is 700mg/kg/day both for reproductive toxicity and developmental toxicities.