Influence of genetic predisposition to diabetes and obesity on mitochondrial function

Inbred mice with the mutation diabetes C57BL/KsJ db+/db+ and the mutation obese C57BL/6J ob/ob displayed a total liver mitochondrial capacity to oxidize glutamate or succinate which was approximately eight times greater than the capacity of the C57BL/6J +/+ control mice. This increase in oxidation capacity was estimated by multiplying the observed twofold increase in each of the following components: total liver weight, the mitochondrial protein content per gram of liver, and glutamate or succinate respiration activity per milligram of liver mitochondrial protein. No significant difference in liver mitochondrial function and capacity for oxidation was observed between db+/db+ and ob/ob mutants, which indicated that these results may be primarily mediated by the genetic factors responsible for obesity and hyperphagia in these mutants, and not by the genetic traits associated with diabetes. These findings may provide a biochemical foundation in support of the thrifty gene hypothesis.     

降血糖药物治疗对糖尿病动物模型及患者肠道菌群的影响

随着人们生活方式和饮食结构的改变,我国糖尿病的发病率呈逐年上升趋势。如何预防并有效治疗糖尿病成为医疗工作者们重要的研究课题。目前,药物治疗是糖尿病最常用、安全以及经济的治疗手段。近年来,肠道菌群成为人们研究的焦点,越来越多证据表明它与糖尿病的发生发展存在密切的联系。本文总结了双胍类、噻唑烷二酮胰岛素增敏剂类、α糖苷酶抑制剂类、二肽基肽酶-4抑制剂(DPP-4)和胰高血糖素样肽-1(GLP-1)类似物、促胰岛素分泌剂和中药及其制剂等降血糖药物对糖尿病动物模型及患者肠道菌群的影响,以期为糖尿病的预测、预防及治疗提供参考。     

Thermal biofeedback as an effective substitute for sympatholytic medication in moderate hypertension: A failure to replicate

Thirty-three moderate hypertensives were converted to a 2-drug regimen of metoprolol and diuretic and BPs stabilized at a well-controlled level. They then completed one of three conditions over an 8-week interval: (I) 16 sessions of TBF (hand and foot warming); (II) 16 sessions of frontal EMG-BF; (III) regular home monitoring of BP. Attempts were then made to withdraw the patients from the sympatholytic medication. Those successfully withdrawn were followed up for one year. There were no significant advantages for TBF over the other two conditions in the short term or with long-term follow-up. Only 27% of treated patients (including Condition III failures who were remedicated and treated with TBF) were successfully off of the sympatholytic at a one-year follow-up. The generally poor results on clinical outcome were confirmed by clinic BPs, home BPs by patients, and 24-hour ambulatory BPs.This research was supported by grant No. HL-27622 from NHLBI. The authors wish to thank Dr. Guy C. McCoy for his role in the initial conceptualization of the study, Dr. Jim Jaccard and Barbara Greene for their assistance in the analyses of the 24-hour ambulatory BP data, and Annabel Prins, Bruce Steffek, and Debra Belkin, who served as therapists for a portion of the study.     

Accounting for variability in sample size estimation with applications to nonadherence and estimation of variance and effect size

We consider sample size calculations for testing differences in means between two samples and allowing for different variances in the two groups. Typically, the power functions depend on the sample size and a set of parameters assumed known, and the sample size needed to obtain a prespecified power is calculated. Here, we account for two sources of variability: we allow the sample size in the power function to be a stochastic variable, and we consider estimating the parameters from preliminary data. An example of the first source of variability is nonadherence (noncompliance). We assume that the proportion of subjects who will adhere to their treatment regimen is not known before the study, but that the proportion is a stochastic variable with a known distribution. Under this assumption, we develop simple closed form sample size calculations based on asymptotic normality. The second source of variability is in parameter estimates that are estimated from prior data. For example, we account for variability in estimating the variance of the normal response from existing data which are assumed to have the same variance as the study for which we are calculating the sample size. We show that we can account for the variability of the variance estimate by simply using a slightly larger nominal power in the usual sample size calculation, which we call the calibrated power. We show that the calculation of the calibrated power depends only on the sample size of the existing data, and we give a table of calibrated power by sample size. Further, we consider the calculation of the sample size in the rarer situation where we account for the variability in estimating the standardized effect size from some existing data. This latter situation, as well as several of the previous ones, is motivated by sample size calculations for a Phase II trial of a malaria vaccine candidate.     

Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension

INTRODUCTIONThe streptozotocin [STZ]-induced diabetes and NO-deficient hypertension are widely used experimental modelsfor the investigation of heart failure [1-4]. Cardiac dys-function in both models is consequence of different sig-nal and metabolic dera…     

Effects of gender and depression on oral medication adherence in persons with type 2 diabetes mellitus

Background: In a range of chronic conditions including diabetes, it has been observed that depressive symptoms may be associated with nonadherence to medications.Objective: The objective of the study was to determine the main effects, and interactive effect, of depression and gender on patients adherence to oral diabetes medications.Methods: A cross-sectional design was employed, in which persons with type 2 diabetes mellitus completed a questionnaire regarding medication use behaviors, depressive symptoms (measured by the 8-item Patient Health Questionnaire [PHQ-8]), health beliefs, and demographics. A 2 x 2 factorial analysis of variance was used to determine the effects of gender and depression on medication adherence after adjusting for age, education, self efficacy, social support, and number of doses of diabetes medications.Results: Of the 391 respondents who completed the questionnaire, 73 (18.7%) were categorized as having depression (ie, PHQ-8 score >10). Overall, women (n = 196) had a mean (SD) score of 6.10 (6.19) on the PHQ-8, and men (n = 195) had a lower score of 4.62 (5.28) (t = 2.75; P < 0.01). There was a significant main effect of depression, but not gender, on patients' adherence to diabetes medications in that those who were categorized as depressed had significantly worse adherence to diabetes medications (F = 4.82; P = 0.03).Additionally, there was a significant “gender x depression” interaction effect on adherence (F = 5.93; P = 0.01). Men with depression had mean adherence scores that indicated more nonadherence than did men without depression (9.44 [3.45] vs 7.47 [2.50], respectively), but adherence varied little between women with depression and women without depression (7.83 [2.69] vs 7.55 [2.58], respectively).Conclusions: The association between depression and medication adherence appears to be stronger in men than in women. Clinicians should be cognizant of the potential effect of depression on self-care for diabetes, particularly in men with depressive symptoms.     

郴州市高血压患者中药物抵抗型高血压的筛查和城乡比较研究

目的：通过调查郴州市城区和乡村高血压患者用药现状,筛查出药物抵抗型高血压患者,以提高药物抵抗型高血压患者的治疗率和控制率,为高血压患者个体化降压治疗方案和健康教育方案的制定提供依据。方法：随机选择郴州市区及乡村地区各200名高血压患者,以问卷的形式进行调查。结果：郴州市区药物抵抗型高血压在高血压患者中所占比例及知晓比例分别为6%、9.5%,乡村地区所占比例及知晓比例分别为7%、4%。结论：郴州市药物抵抗型高血压在高血压患者中所占比例为6.5%,农村药物抵抗型高血压患者知晓比例较低;药物抵抗型高血压患者个体化降压治疗方案有待于改进。     

Calculating sample size for studies with expected all-or-none nonadherence and selection bias

Summary .  We develop sample size formulas for studies aiming to test mean differences between a treatment and control group when all-or-none nonadherence (noncompliance) and selection bias are expected. Recent work by Fay, Halloran, and Follmann (2007, Biometrics 63, 465–474) addressed the increased variances within groups defined by treatment assignment when nonadherence occurs, compared to the scenario of full adherence, under the assumption of no selection bias. In this article, we extend the authors' approach to allow selection bias in the form of systematic differences in means and variances among latent adherence subgroups. We illustrate the approach by performing sample size calculations to plan clinical trials with and without pilot adherence data. Sample size formulas and tests for normally distributed outcomes are also developed in a Web Appendix that account for uncertainty of estimates from external or internal pilot data.     

郴州市高血压患者中药物抵抗型高血压的筛查和城乡比较研究

目的:通过调查郴州市城区和乡村高血压患者用药现状,筛查出药物抵抗型高血压患者,以提高药物抵抗型高血压患者的治疗率和控制率,为高血压患者个体化降压治疗方案和健康教育方案的制定提供依据。方法:随机选择郴州市区及乡村地区各200名高血压患者,以问卷的形式进行调查。结果:郴州市区药物抵抗型高血压在高血压患者中所占比例及知晓比例分别为6%、9.5%,乡村地区所占比例及知晓比例分别为7%、4%。结论:郴州市药物抵抗型高血压在高血压患者中所占比例为6.5%,农村药物抵抗型高血压患者知晓比例较低;药物抵抗型高血压患者个体化降压治疗方案有待于改进。     

Influence of hypertension and of antihypertensive drugs on the arterial wall

This paper reviews some of the experimental data regarding the effects of hypertension and antihypertensive drugs on the arterial wall. Hypertension induces major changes in both the arterial media and intima. Experimental studies from our own and other laboratories have demonstrated that medial smooth muscle cells in several forms of hypertension in the rat undergo hypertrophy and nuclear polyploidy which contribute, along with connective tissue alterations, to a large increase in medial mass. Our studies in the deoxycorticosterone/salt-hypertensive rat indicate that such changes may be difficult to regress, despite prolonged control of the hypertension. In the arterial intima, major alterations in the endothelium are induced by hypertension in association with increase in arterial permeability. Marked enhancements of adherence of circulating white blood cells to the endothelium can also be demonstrated along with penetration of blood monocytes and their accumulation in the subendothelial space. Hypertension also appears to stimulate the migration and proliferation of smooth muscle cells in the intima, and evidence is beginning to accumulate that endogenous growth factors within the artery may be involved in this process. Essentially all of the intimal changes which we have observed as a result of arterial hypertension are also present with cholesterol feeding although intimal accumulation of lipid and formation of atherosclerotic plaques do not occur with hypertension alone. On the other hand, in hypercholesterolemic animals, hypertension appears to act as a promoter of atherogenesis. Several antihypertensive drugs may influence the atherosclerotic process. The experimental data regarding the effects of beta blockers and calcium antagonists in the cholesterol-fed rabbit are discussed. Though of considerable interest, the clinical relevance of the findings remains uncertain.