Hypertransaminasemia in childhood as a marker of genetic liver disorders

Background The widespread use of routine biochemical assays has led to increased incidental findings of hypertransaminasemia. We aimed to evaluate the prevalence of different causes of raised aminotransferase levels in children referred to a university department of pediatrics.Methods We investigated 425 consecutive children (age range, 1–18 years) with isolated hypertransaminasemia. All patients had raised aminotransferase levels on at least two occasions in the last month before observation. Cases due to major hepatotropic viruses were excluded.Results During the first 6 months of observation, 259 children showed normalized liver enzymes. Among the remaining 166 patients with hypertransaminasemia lasting for more than 6 months, 75 had obesity-related liver disease; 51, genetic disorders; 7, autoimmune hepatitis; 5, cholelithiasis; 3, choledochal cyst; and 3, celiac disease. Among the 51 children with genetic disorders, 18 had Wilson disease; 14, muscular dystrophy; 4, alpha-1-antitrypsin deficiency; 4, Alagille syndrome; 4, hereditary fructose intolerance; 3, glycogen storage disease (glycogenosis IX); 2, ornithine transcarbamylase deficiency; and 2, Shwachman’s syndrome. In 22 children, the hypertransaminasemia persisted for more than 6 months in the absence of a known cause.Conclusions Genetic disease accounted for 12% of cases of isolated hypertransaminasemia observed in a tertiary pediatric department. A high level of suspicion is desirable for an early diagnosis of these disorders, which may present with isolated hypertransaminasemia and absence of typical clinical signs.     

N6-甲基腺嘌呤调控线粒体功能及其在代谢性疾病中的研究进展

N6-甲基腺嘌呤(6mA)是存在于真核生物中的表观遗传修饰,通过对线粒体DNA、非编码基因和核糖体DNA等进行修饰,进而动态调控转录。目前研究发现,6mA通过调节线粒体DNA的转录等影响线粒体活性和功能,进而参与代谢性疾病的发生发展。本文探讨6mA调控线粒体功能的机制及其在肥胖、动脉粥样硬化、高血压和癌症等代谢性疾病中的作用,有望为代谢相关疾病的防治提供新思路。     

Glomerular charge selectivity and the influence of improved blood glucose control in Type 1 (insulin-dependent) diabetic patients with microalbuminuria

Summary We first compared glomerular charge selectivity index in two matched groups of Type 1 (insulin-dependent) diabetic patients with micro and normoalbuminuria respectively, and secondly, investigated prospectively in a randomized clinical trial, the influence of improved metabolic control on selectivity index in diabetic patients with microalbuminuria. In Study 1, 27 patients with microalbuminuria (albumin excretion >-15 g/min in at least two out of three overnight urine samples) were matched (age, diabetes duration, mean 1-year HbA_1c, gender) with normoalbuminuria patients (n=24), and in Study 2, 23 microalbuminuric patients were randomly allocated to either intensive (continuous subcutaneous insulin infusion) or conventional treatment. Glomerular charge selectivity index was measured as IgG/IgG₄ selectivity index, i.e. total IgG/IgG₄ clearance ratio in timed overnight urine samples. The microalbuminuric patients had a significantly reduced selectivity index compared to the normoalbuminuric patients: 1.20 (0.92–1.40) vs 1.68 (1.22–2.21), median and 95% confidence interval (p<0.01). In Study 2, the HbA_1c improved in the intensive-treatment group compared to the conventional-treatment group: at 2, 6 and 12 months the difference in mean percentage HbA_1c between the groups was 1.1, 1.2 and 1.4, respectively (p<0.01). A sharp 50% increment in IgG/IgG₄ selectivity index was seen in the intensive-treatment group during the first 6 months (p<0.05 compared to the conventional group). We conclude that adolescents and young adults in an early stage of diabetic nephropathy have reduced glomerular charge selectivity, which may be improved by reducing the mean blood glucose level.     

Effect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome

Objective

Metabolic syndrome (MetS) is associated with cardiovascular disease (CVD). Insulin resistance has been hypothesized as the underlying feature of MetS. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are widely used antihypertensives that may improve insulin sensitivity. The aim of the study is to evaluate the effect of ACEI/ARB on incident CVD events in older hypertensive patients with MetS.

Materials/Methods

We used the Cardiovascular Health Study, a prospective cohort study of individuals > 65 years of age to evaluate ACEI/ARB use and time to CVD events (including coronary and cerebrovascular events). The study included 777 subjects who had hypertension and ATP III-defined MetS, but free of CVD and diabetes at baseline. Cox regression models were used to evaluate the effect of ACEI/ARB as compared to other antihypertensives on the time to the first CVD events.

Results

ACEI/ARB use was associated with a decreased risk of CVD events (adjusted HR = 0.658, 95 % C.I. [0.436–0.993]) compared to other antihypertensives. When CVD endpoints were evaluated separately, use of ACEI/ARB was associated with lower rates of angioplasty and coronary events (HR of 0.129 and 0.530 respectively, with 95 % CI [0.017–0.952] and [0.321–0.875]).

Conclusions

ACEI/ARB use was associated with a lower risk of CVD events in older hypertensive patients with MetS, primarily due to a reduction in coronary events. The potential protective effect of ACEI/ARB on CVD events in older individuals with MetS will need further confirmation from prospective studies.     

代谢性酸中毒对慢性肾衰患者血清瘦素水平的影响

目的初步探讨慢性肾功能衰竭(CRF)患者血清瘦素浓度的变化与代谢性酸中毒之间的关系.方法采用放射免疫分析法测定血清瘦素水平,观察代谢性酸中毒纠正前后CRF患者血清瘦素浓度的变化.结果正常人血清瘦素浓度为10.0±7.μg/L.CRF代谢性酸中毒患者血清瘦素浓度于纠酸前、纠酸后即刻和纠酸后3天分别为14.5±9.27、15.3±11.9、19.3±14.6μg/L,纠酸前、纠酸后即刻血清瘦素水平与正常对照组无明显差别,纠酸后3天血清瘦素浓度较纠酸前及正常对照组明显升高(P＜0.01).两组血清瘦素浓度与体重指数(BMI)均呈明显正相关,且女性血清瘦素浓度均分别高于男性(P＜0.01).结论①本研究提示,代谢性酸中毒可能对体内瘦素分泌具有抑制作用,且CRF患者的高瘦素血症很可能在某种程度上被酸中毒所掩盖.②CRF代谢性酸中毒患者中,女性血清瘦素水平明显高于男性.     

Pregnancy after bariatric surgery: Consensus recommendations for periconception,antenatal and postnatal care

The objective of the study is to provide evidence‐based guidance on nutritional management and optimal care for pregnancy after bariatric surgery. A consensus meeting of international and multidisciplinary experts was held to identify relevant research questions in relation to pregnancy after bariatric surgery. A systematic search of available literature was performed, and the ADAPTE protocol for guideline development followed. All available evidence was graded and further discussed during group meetings to formulate recommendations. Where evidence of sufficient quality was lacking, the group made consensus recommendations based on expert clinical experience. The main outcome measures are timing of pregnancy, contraceptive choice, nutritional advice and supplementation, clinical follow‐up of pregnancy, and breastfeeding. We provide recommendations for periconception, antenatal, and postnatal care for women following surgery. These recommendations are summarized in a table and print‐friendly format. Women of reproductive age with a history of bariatric surgery should receive specialized care regarding their reproductive health. Many recommendations are not supported by high‐quality evidence and warrant further research. These areas are highlighted in the paper.     

重症急性高原病患者电解质代谢紊乱与多脏器功能障碍的关系

重症急性高原病患者电解质紊乱可引发机体的钠水潴留,血管活性物质及自由基的大量产生,从而加重各脏器的损害,导致多脏器功能障碍(MODS),甚至危及患者生命.在高原现场救治过程中应加强电解质的监测.     

Peripheral vascular disease in Type 2 diabetic Chinese patients: associations with metabolic indices, concomitant vascular disease and genetic factors.

AIMS: Conventional and genetic risk factors have been reported to play a role in the pathogenesis of vascular disease, but do not explain the lower burden of cardiac and peripheral vascular disease (PVD) in Chinese compared with Caucasians. The role of renin-angiotensin system (RAS) gene polymorphisms and conventional vascular risk factors has not been determined. METHODS: A total of 3097 Chinese diabetic subjects were screened for PVD, which was identified in 194 of the 2967 patients with Type 2 diabetes. Biochemical parameters and the genotype and allele frequencies of three RAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms were then compared between the PVD patients and 1046 age, gender and diabetes duration-matched patients without PVD. RESULTS: PVD identified in 6.5% was associated with significantly worse glycaemic control, lipid profile and renal function. Smoking was more common, as were the other macro- and microvascular diseases. The prevalence of hypertension was similar between the groups, yet diastolic blood pressure was slightly lower in the PVD group. The ACE D allele was significantly more frequent in patients with PVD compared with the matched diabetic controls (38.1 vs. 29.8%, P = 0.039). No differences in the AT1R or AGT polymorphisms were observed. CONCLUSIONS: PVD was associated with a worse metabolic profile and greater concomitant vascular disease than controls. The ACE I/D polymorphism was associated with PVD in these Type 2 diabetic patients.