Is perinatal neuroendocrine programming involved in the developmental origins of metabolic disorders?

The discovery that small size at birth and during infancy are associated with a higher risk of diabetes and related metabolic disease in later life has pointed to the importance of developmental factors in these conditions. The birth size associations are thought to refl ect exposure to adverse environmental factors during early development but the mechanisms involved are still not fully understood. Animal and human work has pointed to the importance of changes in the setpoint of a number of key hormonal systems controlling growth and development. These include the IGF-1/GH axis, gonadal hormones and, in particular, the systems mediating the classical stress response. Several studies show that small size at birth is linked with increased activity of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in adult life. More recent human studies have shown associations between specif ic adverse experiences during pregnancy, such as famine or the consumption of adverse diets, and enhanced stress responses many decades later. The mediators of these neuroendocrine responses are biologically potent and are likely to have a direct infl uence on the risk of metabolic disease. These neuroendocrine changes may also have an evolutionary basis being part of broader process, termed phenotypic plasticity, by which adverse environmental cues experienced during development modify the structure and physiology of the adult towards a phenotype adapted for adversity. The changes are clearly advantageous if they lead to a phenotype which is well-adapted for the adult environment, but may lead to disease if there is subsequent overnutrition or other unexpected environmental conditions.     

Mechanisms of developmental programming of the metabolic syndrome and related disorders

There is consistent epidemiological evidence linking low birth weight, preterm birth and adverse fetal growth to an elevated risk of the metabolic syndrome (obesity, raised blood pressure, raised serum triglycerides, lowered serum high-density lipoprotein cholesterol and impaired glucose tolerance or insulin resistance) and related disorders. This "fetal or developmental origins/programming of disease" concept is now well accepted but the "programming" mechanisms remain poorly understood. We reviewed the major evidence, implications and limitations of current hypotheses in interpreting developmental programming and discuss future research directions. Major current hypotheses to interpret developmental programming include: (1) thrifty phenotype; (2) postnatal accelerated or catch-up growth; (3) glucocorticoid effects; (4) epigenetic changes; (5) oxidative stress; (6) prenatal hypoxia; (7) placental dysfunction; and (8) reduced stem cell number. Some hypothetical mechanisms (2, 4 and 8) could be driven by other upstream "driver" mechanisms. There is a lack of animal studies addressing multiple mechanisms simultaneously and a lack of strong evidence linking clinical outcomes to biomarkers of the proposed programming mechanisms in humans. There are needs for (1) experimental studies addressing multiple hypothetical mechanisms simultaneously; and (2) prospective pregnancy cohort studies linking biomarkers of the proposed mechanisms to clinical outcomes or surrogate biomarker endpoints. A better understanding of the programming mechanisms is a prerequisite for developing early life interventions to arrest the increasing epidemic of the metabolic syndrome, type 2 diabetes and other related disorders.     

Taste sensitivity,nutritional status and metabolic syndrome: Implication in weight loss dietary interventions

AIM: We investigated the relationship between taste sensitivity, nutritional status and metabolic syndrome and possible implications on weight loss dietary program. METHODS: Sensitivity for bitter, sweet, salty and sour tastes was assessed by the three-Alternative-Forced-Choice method in 41 overweight(OW), 52 obese(OB) patients and 56 normal-weight matched controls. OW and OB were assessed also for body composition(by impedence), resting energy expenditure(by indirect calorimetry) and presence of metabolic syndrome(MetS) and were prescribed a weight loss diet. Compliance to the weight loss dietary program was defined as adherence to control visits and weight loss ≥ 5% in 3 mo. RESULTS: Sex and age-adjusted multiple regression models revealed a significant association between body mass index(BMI) and both sour taste(P 0.05) and global taste acuity score(GTAS)(P 0.05), with lower sensitivity with increasing BMI. This trend in sensitivity for sour taste was also confirmed by the model refitted on the OW/OB group while the association with GTAS was marginally significant(P = 0.06). MetS+ subjects presented higher thresholds for salty taste when compared to MetS- patients while no significant difference was detected for the other tastes and GTAS. As assessed by multiple regression model, the association between salty taste and MetS appeared to be independent of sex, age and BMI. Patients continuing the program(n = 37) did not show any difference in baseline taste sensitivity when compared to drop-outs(n = 29). Similarly, no significant difference was detected between patients reporting and not reporting a weight loss ≥ 5% of the initial body weight. No significant dif-ference in taste sensitivity was detected even after dividing patients on the basis of nutritional(OW and OB) or metabolic status(MetS+ and MetS-). CONCLUSION: There is no cause-effect relationship between overweight and metabolic derangements. Taste thresholds assessment is not useful in predicting the outcome of a diet-induced weight loss program.     

Metabolic syndrome impact on nutritional deficiencies and metabolic status 1 year after sleeve gastrectomy

BackgroundA paucity of information is available on the comparative nutritional deficiencies considering the presence of metabolic syndrome (MetS) and nutritional changes after vertical sleeve gastrectomy (SG).ObjectivesTo compare the nutritional status in patients with and without MetS before and 1 year after SG and to investigate its association with metabolic status.SettingA tertiary referral center.MethodsRetrospective study, including all patients submitted to SG between January 2011 and July 2015. Patients were evaluated before and 12 months after surgery. MetS presence was classified using the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute 2009 definition. Univariate and multivariate analyses were applied to find associations between MetS, nutritional, anthropometric, and metabolic parameters.ResultsA total of 330 patients were included and MetS was present in 47%. Preoperatively, patients without MetS presented a higher percentage of folate deficiency (12% versus 2%, P < .001). Follow-up data were available for 202 patients. In the 1-year evaluation, MetS patients presented significantly lower body mass index and percent excess weight loss (70.96 ± 20.4 versus 79.55 ± 23.0, P < .001). These patients also presented lower homocysteine (11.76 ± 4.3 versus 13.66 ± 7.6, P = .027) and magnesium (19.41 ± 2.1 versus 20.22 ± 1.9, P = .004) levels but higher calcium (9.27 ± .3 versus 9.16 ± .4, P = .031) and vitamin B12 (396, P 312–504.5 versus 329, P 255–433, P = .002) levels comparing with those without MetS. Multiple linear regression evidenced that higher preoperative albumin and postoperative ferritin and homocysteine were predictors of a lower body mass index after surgery, and higher postoperative folate levels were associated with lower insulin-resistance.ConclusionsThe impact of SG on nutritional parameters is affected by MetS. If not treated, preoperative deficiencies can impair postoperative metabolic status and weight loss. MetS should be considered when evaluating bariatric surgery candidates, and preoperative supplementation and long-term nutritional follow-up are required to prevent further nutritional deficiencies.     

Developmental programming of the metabolic syndrome - critical windows for intervention

Metabolic disease results from a complex interaction of many factors,including genetic,physiological,behavioral and environmental influences.The recent rate at which these diseases have increased suggests that environmental and behavioral influences,rather than genetic causes,are fuelling the present epidemic.In this context,the developmental origins of health and disease hypothesis has highlighted the link between the periconceptual,fetal and early infant phases of life and the subsequent development of adult obesity and the metabolic syndrome.Although the mechanisms are yet to be fully elucidated,this programming was generally considered an irreversible change in developmental trajectory.Recent work in animal models suggests that developmental programming of metabolic disorders is potentially reversible by nutritional or targeted therapeutic interventions during the period of developmental plasticity.This review will discuss critical windows of developmental plasticity and possible avenues to ameliorate the development of postnatal metabolic disorders following an adverse early life environment.     

Adipose tissue and the physiologic underpinnings of metabolic disease

Adipose tissue dysfunction underlies the pathogenesis of metabolic disease. The metrics used to quantify adiposity and its association with metabolic disease, including body mass index, have limitations with important clinical implications. An understanding of the molecular and cellular mechanisms by which adipose tissue regulates systemic metabolism and contributes to metabolic disease will lead to next-generation adipose tissue–based therapy.     

Fetal programming of obesity and type 2 diabetes

The prevalence of obesity and type 2 diabetes mellitus has increased rapidly over the past few decades, and prevention efforts have not been successful. Fetal programming involves the earliest stage of obesity development, and provides a novel concept to complement other strategies for lifelong prevention of obesity and type 2 diabetes mellitus. The World Health Organization now advocates a life-course approach to prevent/control obesity, starting with pre-conceptional and antenatal maternal health. Maternal overnutrition, gestational diabetes mellitus and excessive gestational weight gain lead to fetal overgrowth, and “programs” the offspring with an increased risk of obesity and type 2 diabetes mellitus in childhood and adulthood. This review summarizes current data on fetal programming of obesity and type 2 diabetes mellitus including potential causative factors, mechanisms and interventions to reduce its impact.     

外科医师应重视对代谢相关脂肪性肝病的认识

非酒精性脂肪性肝病（NAFLD）影响着世界近1/4的人口。NAFLD病因复杂,个体异质性显著,因此,对于该术语的使用一直存在争议。近期,国际脂肪肝专家小组就NAFLD正式更名为代谢相关脂肪性肝病（MAFLD）达成共识,并制订了新的定义和诊断标准。既往MAFLD以内科治疗为主,外科医师对其关注度不够,但随着MAFLD发病...     

代谢综合征及其代谢因子与慢性肾损害相关性的临床研究

目的 探讨代谢综合征及其各组成因子与包括轻度肾损害在内的慢性肾损害的相关性&#65377; 方法 收集我院2003年1月至2003年12月心内科&#65380; 肾内科和内分泌科符合入选标准的住院患者966例进行回顾性分析&#65377;按有&#65380; 无慢性肾脏病(CKD)或轻度肾损害分组, 比较代谢综合征各因素与慢性肾脏损害的关系&#65377; 统计学处理包括单变量t检验&#65380;卡方检验和Logistic多因素回归分析&#65377;结果 (1)CKD组的年龄&#65380; 身体质量指数(BMI)&#65380; 总胆固醇(TC)&#65380; 甘油三酯(TG)&#65380; 高血糖&#65380; 高血压和尿酸水平, 冠心病&#65380; 脑卒中的患病率均高于无CKD组, 而高密度脂蛋白(HDL)水平明显低于无CKD组患者; (2)随着代谢综合征因子数量的增多, CKD发病率上升; (3)代谢综合征中各因子并存较各因子单独存在的CKD的危险性增加, 与高血糖并存的频率最高; (4)BMI增加也是CKD的重要危险因素; (5)高血糖患者发生轻度肾损害的风险最大(优势比OR=7.698)&#65377;结论 代谢综合征及其各组成因子是包括轻度肾损害在内的CKD的重要危险因素&#65377;随着代谢综合征因子的增多, CKD的危险也随之增加&#65377; 除了高血糖和高血压, BMI增加也是其中重要的影响因子&#65377;     

精准腹腔镜Roux-en-Y胃旁路术治疗肥胖与代谢病140例疗效分析

目的 探讨精准腹腔镜Roux-en-Y胃旁路手术（LRYGB）治疗肥胖与代谢性疾病的疗效和安全性.方法 回顾性分析暨南大学附属第一医院胃肠外科2011年6月至2013年4月期间行精准LRYGB的140例肥胖患者的临床及随访资料.结果 所有患者均顺利完成精准LRYGB手术,无中转开腹或死亡病例,手术时间（138.0±21.3） min;术后住院时间（5.2±1.2）d,未发现严重术后并发症.术后1、6、12和24月的多余体质量减少率分别为（26.4±8.6）％、（53.3±6.7）％、（75.3±7.9）％和（78.5±8.5）％.术后1年,肝肪肝、高脂血症、高血压和2型糖尿病等肥胖相关代谢性疾病的改善率分别为84.6％（33/39）、92.3％（12/13）、77.3％（17/22）和82.4％（14/17）.结论 对传统手术技术进行了改良与优化的精准LRYGB不会增加手术时间,安全可行;患者术后减重效果明显,能有效改善相关合并症.     

超级肥胖代谢手术操作技巧及并发症防治体会附35例临床结局

目的探讨超级肥胖代谢手术并发症的防治方法。 方法收集2011年3月至2017年11月接受代谢手术的超级肥胖患者35例临床资料,回顾性分析其手术并发症发生率。 结果35例患者中术后2例(5.71%)发生并发症,其中1例为胃切缘出血,再次手术修补,1例为Trocar疝,实施手术还纳。 结论超级肥胖的代谢手术通过宏观及微观把控,其手术并发症能在可控范围。     

Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease

PURPOSE: We determine the analytical accuracy and reliability of commonly used nutritional supplements for prostate disease by comparing the amounts of active ingredients of several brands of vitamin E, vitamin D, selenium, lycopene and saw palmetto. We also compared the amounts of active compound in different lots of the same brand to determine the consistency of the manufacturing process. MATERIALS AND METHODS: Samples purchased at pharmacies and specialty stores were sent for independent chemical analysis. The measured dose was compared to the stated dose on the product label. Analysis of variance was performed to test for significance in interlot reliability. RESULTS: Vitamin E (7 samples) and selenium (5) were within a range of -41% to +57% and -19% to +23% of the stated dosage, respectively. All vitamin D brands (4 samples) were within 15% of the stated dose. Saw palmetto (6 samples) were within a range -97% to +140% of the stated dosages with 3 containing less than 20% of the stated dosages. Lycopene brands were between -38% and +143% of stated dosages. Among the reliability assays 1 of 3 brands of vitamin E, 1 of 2 brands of selenium and 1 of 2 brands of saw palmetto demonstrated statistical differences in interlot dosage (p <0.0055, approximate 20% to 25% differences in dose). The 1 assayed form of vitamin D was reliable between lots. CONCLUSIONS: Commonly used nutritional supplements for prostate disease vary widely in measured dose. Saw palmetto demonstrated tremendous variability with some samples containing virtually no active ingredients. In contrast, the more regulated substances we measured, such as vitamins and minerals, demonstrated less variation.     

Impact of metabolic surgery on cost and long-term health outcome: a cost-effectiveness approach

BackgroundThe increase in obesity has become a major public health concern. Morbid obesity is associated with co-morbidities, reduced quality-of-life, and death. Metabolic surgery (MS) is the most effective treatment for obesity.ObjectivesThe aim of this study was to evaluate the costs and outcomes of MS compared with no surgery in patients with a body mass index ≥30 kg/m².SettingHealth care system, AustriaMethodsA total of 177 patients who underwent MS were documented retrospectively, based on the hospital records of 2 specialized centers in Austria, over a 1-year period. At baseline 26.0% of patients exhibited type 2 diabetes (T2D), 52.5% cardiovascular disease (CVD), 23.2% hyperlipidemia, and 23.7% depression. Following the observation period, a Markov chain simulation model was developed to analyze the long-term consequences of T2D, including diabetic complications, CVD, hyperlipidemia, depression, non-alcoholic steatohepatitis (NASH), myocardial infarction, and stroke, over a total of 20 years. Direct medical costs were expressed in 2017 euros from the payer’s perspective. Quality-adjusted life years (QALYs), life years (LYs), and costs were discounted.ResultsMS led to costs of €40,427 and 9.58 QALYs (15.58 LYs) per patient over 20 years. No MS was associated with €64,819 and 6.33 QALYs (13.92 LYs). Total cost-savings amounted to €24,392, which offset the cost of the procedure including re-operations. Over 20 years MS saved –6.7 patient-years per patient with T2D, –5.8 patient-years with CVD, –1.5 patient-years with hyperlipidemia, –1.8 patient-years with depression, and –3.8 patient-years with NASH.ConclusionMS is associated with substantial savings in long-term costs, expected health benefits, and reduced onset of complications. MS significantly increases quality of life.     

The metabolic and liver-related outcomes of bariatric surgery in adult patients with insulin-treated type 2 diabetes and nonalcoholic fatty liver disease at high risk of liver fibrosis

BackgroundNonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease, with a prevalence estimated to between 20% and 30% of the general population and approximately 70% of stage 2 obese people with type 2 diabetes (T2D) with normal liver enzymes.ObjectivesTo investigate the metabolic and liver-related outcomes of bariatric surgery among patients with insulin-treated T2D and NAFLD who are at high risk of liver fibrosis.SettingMore than 600 locations within the United Kingdom.MethodsThe study comprises a retrospective cohort comparison of patients with NAFLD and a fibrosis 4 (Fib-4) score > 1.45 who received a bariatric intervention versus comparable patients who received no bariatric intervention. Metabolic outcomes (glycated hemoglobin [HbA1C] level, weight, body mass index [BMI], and Fib-4 score) and composite liver-related outcomes (cirrhosis, portal hypertension, liver failure, and hepatoma) were compared between groups over a period of 5 years. The outcomes were adjusted for baseline and time-varying covariates.ResultsThe study sample included 4108 patients, 45 of whom underwent bariatric surgery. The mean age at baseline was 62.4 ± 12.4 years; 43.8% of patients were female; the mean weight was 89.5 ± 20.8 kg; the mean BMI was 31.7 ± 7.6 kg/m²; and the mean HbA1C level was 68.4 ± 16.7 mmol/mol. In addition, the median Fib-4 score was 2.3 (interquartile range, 1.7–4.2). During the 5 years during which follow-up outcomes were recorded, the weight and BMI reductions were significantly lowered compared with baseline in the bariatric surgery group. Similarly, the HbA1C levels were lower in the bariatric surgery group, with statistically significant differences observed in the first and second postintervention years (bariatric surgery versus non–bariatric surgery patient levels at 1 year, 63.1 mmol/mol versus 68.1 mmol/mol, respectively [P = .042], and at 2 years, 62.7 mmol/mol versus 68.1 mmol/mol, respectively [P = .028]). No significant difference was observed between groups in the proportion of patients with liver fibrosis or the likelihood of developing composite liver disease during the follow-up period (bariatric surgery group, 8.9%; non–bariatric surgery group, 4.7%; X² = 1.75; P = .18).ConclusionBariatric surgery amongst patients with insulin-treated T2D with NAFLD who were at high risk of liver fibrosis was associated with significant improvements in metabolic outcomes. No significant adverse effects were observed with regards to liver-related outcomes.     

合肥市成年体检人群慢性肾脏病患病率及相关危险因素调查

目的 调查合肥市成年体检人群慢性肾脏病（CKD）的患病情况及相关危险因素。 方法 回顾性分析2005年1月至2007年12月在安徽省立医院体检中心的所有年龄大于20周岁的人群体检资料,进行慢性肾脏病患病率和危险因素调查。 结果 在资料完整的33 451例成年体检者中,蛋白尿的患病率为2.74%（95% CI为2.57%~2.92%）;血尿的患病率为7.67%（95% CI为7.39%~7.96%）;肾小球滤过率下降的患病率为0.80%（95% CI为0.71%~0.90%）。该人群总CKD患病率为9.92%（95% CI为9.60%~10.25%）。 结论 合肥市体检人群中,CKD的患病率为9.92%;CKD的相关危险因素包括年龄、女性、糖尿病、高血压和高尿酸血症。     

新疆地区成年体检人群中慢性肾脏病患病率及相关危险因素调查

目的 调查新疆地区成年体检人群慢性肾脏病（CKD）的患病情况及相关危险因素。 方法 回顾性分析2009年1月至2010年4月在新疆医科大学第一附属医院体检中心所有年龄大于20周岁的人群体检资料,进行CKD患病率和危险因素调查分析。 结果 在资料完整的10 025例成年体检者中,蛋白尿的患病率为 4.86％（95％CI为4.44％～5.28％）;血尿的患病率为3.13％（95％CI为2.79％～3.47％）;肾小球滤过率下降的患病率为2.66％（95％CI为2.34％～2.98％）。该人群总CKD患病率为9.60％（95％CI为9.02％～10.18％）。多因素Logistic回归分析提示男性、高收缩压、肥胖、糖代谢异常、高三酰甘油血症与蛋白尿独立相关;女性、民族、高收缩压与血尿独立相关;性别、年龄增加10岁、肥胖、高脂血症、高尿酸血症与肾功能下降独立相关;与CKD总体独立相关的因素是性别、年龄增加10岁、高收缩压、糖代谢异常、高脂血症和高尿酸血症。 结论 新疆地区成年体检人群CKD的患病率为9.60％,提示健康体检人群CKD的患病率也很高,应引起重视。新疆地区CKD的疾病谱与国内及国外研究类似。     

Prevalence and determinants of the metabolic syndrome among subjects with advanced nondiabetes-related chronic kidney disease in Gran Canaria,Spain

Background The relationship between the metabolic syndrome and mild chronic kidney disease (CKD) has been extensively studied. This study was aimed to estimate the prevalence and factors associated with the metabolic syndrome among subjects with advanced stages of nondiabetes-related CKD. Methods Study population was composed of incident patients with advanced CKD not related to diabetes in a tertiary hospital from Gran Canaria (Spain) since February 2011 to December 2014. Participants fulfilled a survey questionnaire and underwent physical examination and biochemical evaluation. Results The sample was composed of 167 subjects (mean age 63.9?±?13.7 years; estimated glomerular filtration rate 21.9?±?6.6 mL/min/1.73 m²). The prevalence of the metabolic syndrome was 68.9% (65.2% in men and 73.3% in women). Highest rates were observed in groups with chronic interstitial nephropathy (80%), CKD of uncertain etiology (76.7%) and CKD related to vascular causes (76.2%). Subjects with metabolic syndrome were older, had higher values of C-reactive protein and more often reported to have first-degree relatives with diabetes and to be physically inactive. In multivariate analyses, age (OR: 1.034 [CI 95%: 1.004–1.065]; p = 0.024) and family history of diabetes (OR: 2.550 [1.159–5.608]; p = 0.020) were independently associated with the metabolic syndrome. Conclusions The prevalence of the metabolic syndrome among subjects with advanced nondiabetes-related CKD is high, and greater than that observed in general Canarian population of similar age groups. Age and family history of diabetes are the two factors more strongly associated with the metabolic syndrome in this population.     

肥胖代谢病合并甲状腺癌外科治疗中国专家共识（2021版）

肥胖症与甲状腺癌均为临床常见的内分泌与代谢疾病。肥胖与甲状腺癌的发生发展密切相关[1-2]。随着肥胖患病率的逐渐增加,接受减重手术的病人越来越多[3]。减重手术前甲状腺疾病筛查中经常会发现甲状腺结节,其中部分为甲状腺癌。临床上处理此类病人相对复杂。