Heritability of leptin levels and the shared genetic effects on body mass index and leptin in adult Finnish twins

OBJECTIVES: Leptin is involved in the regulation of body weight, but the relative role of genetic and environmental influences on inter-individual variation in leptin levels is unknown. DESIGN AND SUBJECTS: To investigate the genetic and environmental contributions to the association of body mass index (BMI) with serum leptin levels, 58 monozygotic (MZ, 27M, 31F), and 74 like-sexed dizygotic (DZ, 32M, 42F) Finnish twin pairs aged 50--76 y were studied. MEASUREMENTS: Serum leptin levels, weight, height, hip and waist measurements. RESULTS: Women had higher mean leptin levels (16.8+/-9.5 ng/ml), and more overall variability in leptin levels than men (6.4+/-3.5 ng/ml; P<0.0001). Leptin levels correlated highly with BMI in men and women. Among women, the MZ and DZ pairwise correlations for leptin were 0.41 (P=0.009) and 0.07 (P=0.32), respectively. Among men the MZ and DZ pairwise correlations for leptin were 0.47 (P=0.006) and 0.23 (P=0.10). Univariate twin analysis indicated that, among women, 34% and, among men, 45% of the variance in leptin can be attributed to additive genetic effects, and the remainder to unique environmental effects. Significant non-additive genetic or shared familial effects could not be demonstrated. A bivariate twin analysis of leptin and BMI indicated that the correlation between additive genetic effects on leptin and BMI was 0.79 (95% CI 0.68--0.86) in women, and 0.68 (0.51--0.80) in men. The correlation between environmental effects on leptin and BMI was 0.77 (95% CI 0.66--0.85) in women, and 0.48 (0.26--0.66) in men. CONCLUSION: Leptin levels are moderately heritable in older adults, and a substantial proportion of genetic effects are in common on leptin levels and obesity in both women and men. International Journal of Obesity (2001) 25, 132-137     

Effects of body mass index, plasma glucose and cholesterol levels on isolated systolic hypertension

Despite the high cardiovascular risk of diabetic patients, there is a paucity of data on isolated systolic hypertension (ISH) in diabetic patients. In this cross-sectional study, we examined the risk of ISH and its associated factors in Chinese type 2 diabetic patients. Isolated systolic hypertension was defined as systolic blood pressure (SBP) > or =140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg. The mean value of two BP measurements taken 1 min apart was used. There were 1048 type 2 diabetic patients recruited from the Prince of Wales Hospital Diabetes Clinic. Another 1043 age- and sex-matched non-diabetic subjects were recruited from the community. The mean age of the 2091 subjects was 40.6 +/- 7.6 years (median: 40 years, range: 16-69 years). Diabetic patients had an increased risk of ISH compared to non-diabetic subjects (7.6% vs. 3.4%, p < 0.001) with an odd ratio of 2.38. On multivariate analysis, age, body mass index, total cholesterol and duration of diabetes in diabetic subjects while age and waist-hip ratio (WHR) in non-diabetic subjects were independently associated with ISH. In conclusion, Chinese type 2 diabetic patients had increased risk to develop ISH than non-diabetic subjects. Age, obesity, lipid and duration of diabetes were independent associated with ISH. These findings suggest that control of body weight and metabolic profile might have beneficial effects on ISH.     

Gender-specific differences in the association of adiponectin gene polymorphisms with body mass index

OBJECTIVE: Adiponectin gene polymorphisms are associated with obesity, metabolic syndrome and type 2 diabetes (T2D). The study evaluated possible associations of +45T/G and -11391G/A adiponectin gene polymorphisms with body mass index (BMI), waist circumferences (WC), and blood pressure in diabetic and non-diabetic Iranians. METHODS: This cross-sectional study involved two groups of subjects: 243 diabetic patients and 173 non-diabetic subjects recruited from Rafsanjan city in the south-east of Iran. RESULTS: No significant association was found between +45T/G and -11391G/A adiponectin gene polymorphisms and systolic or diastolic blood pressure. However, male carriers of the TT genotype of +45T/G had a significantly higher mean BMI than male GG homozygotes (p = 0.018). Also, male carriers of the GG genotype of -11391G/A had significantly higher mean BMI than male GA or AA homozygotes (p = 0.041). Female carriers of the GG genotype of -11391G/A had significantly higher mean WC than female GA or AA homozygotes (p = 0.038). CONCLUSIONS: We observed a significantly higher BMI in women, and GA or AA carriers of -11391G/A polymorphism. Also, there was a significantly lower WC in females and GG carriers of +45T/G. These results point to a gender-specific impact of the studied genotypes on BMI and WC.     

血浆瘦素与体重指数和脂肪分布的关系

目的探讨血浆瘦素水平与体重指数和脂肪分布的关系。方法对100例肥胖者(男性52例,女性48例)和71非肥胖者(男性38例,女性33例)用免疫放射法测定血浆瘦素水平,测量身高、体重,计算体重指数(BMI)。对其中19例肥胖者(男12例,女7例),15例非肥胖者(男6例,女9例)经CT扫描测量腹部内脏和皮下脂肪面积,分析瘦素与肥胖程度和脂肪分布的关系。结果血浆瘦素水平性别差异显著(P<0.001),女性是男性的2～3倍;瘦素与体重指数呈正相关(男r=0.6772,P<0.01;女r=0.7191,P<0.01)。经CT扫描测量皮下和内脏脂肪面积,瘦素水平与皮下脂肪面积的正相关(r=0.8238,P<0.01),与腹部内脏脂肪面积无明显相关性(r=0.2118,P>0.05)。结论肥胖者血浆瘦素升高,瘦素水平不仅与肥胖程度有关,还与脂肪分布有关。     

Role of the duodenum in regulation of plasma ghrelin levels and body mass index after subtotal gastrectomy

AIM： To investigate the role of the duodenum in the regulation of plasma ghrelin levels and body mass index （BMI）, and the correlation between them after subtotal gastrectomy. METHODS： Forty-two patients with T0-1N0-1M0 gastric cancer were divided into two groups after gastrectomy according to digestive reconstruction pattern, Billroth Ⅰ group （n = 23） and Billroth Ⅱ group （n = 19）. Ghrelin levels were determined with radioimmunoassay （RIA） before and on d 1, 7, 30 and 360 after gastrectomy, and BMI was also measured. RESULTS： The two groups had identical postoperative trends in ghrelin alterations during the early stage, both decreasing sharply to a nadir on d 1 （36.7% vs 35.7%）, then markedly increasing on d 7 （51.0% vs 51.1%）. On d 30, ghrelin levels in the Billroth Ⅰ group were slightly higher than those in the Billroth Ⅱ group. However, those of the Billroth Ⅰ group recovered to 93.6% on d 360, which approached, although lower than, the preoperative levels, and no statistically significant difference was observed. Those of the Billroth Ⅱ group recovered to only 81.6% and manifested significant discrepancy with preoperative levels （P = 0.033）. Compared with preoperative levels, ghrelin levels of the two groups decreased by 6.9% and 18.4% and BMI fellby 3.3% and 6.4%, respectively. The linear regression correlations were revealed in both groups between decrease of ghrelin level and BMI （R12 = 0.297, P = 0.007; R22 = 0.559, P 〈 0.001）.CONCLUSION： Anatomically and physiologically, the duodenum compensatively promotes ghrelin recovery and accordingly enhances BMI after gastrectomy. Regarding patients with insufficient ghrelin secretion, ghrelin is positively associated with BMI.     

Heritability of left ventricular mass in a large cohort of twins

INTRODUCTION: Left ventricular hypertrophy is recognized as one of the most important independent predictors of adverse cardiovascular outcome. The aetiology of LVH includes a number of well-recognized causes but there is considerable interest in the genetics of cardiac muscle hypertrophy. We used a large prospective twin database in order to establish the heritability of left ventricular mass (LVM). METHODS: Normotensive twins were prospectively recruited. Demographic data were collected. The LVM was determined using the Penn formulae derived from data collected from echocardiography. RESULTS: A total of 376 Caucasian twin pairs (182 monozygotic and 194 dizygotic) aged 25-79 years were recruited. All subjects were normotensive with no significant differences in blood pressure (mean blood pressure: monozygotic twins, 132/83 mmHg; dizygotic twins, 131/82 mmHg) or body mass index between the monozygotic and dizygotic twins. The mean LVM for monozygotic twins was 140.9 g, compared with 140.2 g for dizygotic twins. Heritability estimates suggest that the genetic variance of LVM is 0.59 (95% confidence interval, 0.5-0.67). No common shared environmental effects were identified under this model. CONCLUSION: Our data from the largest set of twin pairs studied to date show that LVM has a sizeable genetic basis that is probably polygenic. This result has important implications for the understanding of normal and abnormal cardiac morphology at the molecular level.     

儿童哮喘严重程度与体重指数、脂联素和瘦素的关系

目的本研究旨在探讨儿童哮喘严重程度与体重指数(body mass index,BMI)、脂联素和瘦素的关系,探索这些参数对哮喘严重程度的判断作用。方法纳入2017年6月至2019年6月期间就诊于本院的102例儿童哮喘患者。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测脂联素和瘦素。统计分析BMI、脂联素和瘦素与哮喘严重程度的相关性。结果102例儿童哮喘患者,其中对照组50例(BMI≤28 kg/m^2),观察组52例(BMI>28 kg/m^2),观察组重度哮喘患者比例明显多于对照组(28/52 vs.12/50,P<0.05),而轻度哮喘患者比例则明显少于对照组(12/52 vs.23/50,P<0.05)。哮喘不同严重程度与BMI、脂联素和瘦素之间存在显著相关性(r=0.85,P<0.001;r=-0.91,P<0.001;r=0.88,P<0.001),其中脂联素浓度随着哮喘严重程度增加呈下降趋势,而BMI和瘦素则呈升高趋势。BMI、瘦素、脂联素和血压是哮喘患者病情严重程度的独立危险因素(OR=1.122,95%CI:1.021~1.512,P=0.030;OR=1.056,95%CI:1.017~1.311,P=0.012;OR=0.821,95%CI:0.685~0.939,P=0.016;OR=1.023,95%CI:1.004~2.076,P=0.036)。结论儿童哮喘与BMI、脂联素和瘦素相关。BMI和瘦素升高、脂联素水平降低与儿童哮喘患者病情严重相关,对哮喘的病情有一定的预测价值。     

Heritability of variation of plasma cortisol levels

Heritability of the variation of the plasma concentrations of total and unbound cortisol, cortisol binding globulin (CBG), and dehydroepiandrosterone sulfate (DHEA-S) was investigated in 20 monozygotic (MZ) and 20 dizygotic (DZ) male twin pairs. Three plasma samples collected between 8 AM and 9:30 AM were pooled for the assays. Heritability was calculated from the intraclass correlation [2(rMZ - rDZ)]. The mean age, total and unbound cortisol, CBG, and DHEA-S were not significantly different between the MZ and DZ groups of twins. The heritability index for variability of the plasma content of steroids was 45.4% (p less than .05) for total cortisol, 50.6% (P less than .05) for unbound plasma cortisol, 57.8% (P less than .05) for DHEA-S, and 32.4% (P greater than .05) for CBG. The data were analyzed by factor analysis, and heritability estimates were corrected for factors including age, smoking, drinking, exercise, and degree of obesity. These factors did not account for the variation in hormone values in twin pairs. Factor analysis of the three quantitative measurements, cortisol, percent free cortisol, and DHEA-S, provides no evidence for shared factors. The correlation coefficients between age and CBG and total and unbound plasma cortisol concentrations were insignificant. The correlation coefficient between total plasma cortisol levels and CBG was 0.57, which indicates that CBG accounts for 32% of the variation of plasma cortisol concentrations. The results suggest that genetic factors have a decided influence on the variation of the concentration of cortisol of DHEA-S in normal adult men.     

Association of body mass index with serum calcium and phosphate levels

ObjectiveIt has been shown that several environmental and physiological factors can affect on the serum levels of calcium and phosphate. The objective of the present study was explored the relationship between serum calcium and phosphate levels with anthropometric and hematological markers.Methods908 subjects were recruited from the Mashhad stroke and heart atherosclerosis disorder (MASHHAD) program. Anthropometric parameters, liver/kidney function tests (e.g., Urea nitrogen, creatinine, urea and uric acid, creatinine, AST, ALT) were determined in all participants. Serum concentrations of calcium and phosphate were measured using Autoanalyzer BT3000P (Pars Azmoon kit, Tehran, Iran). SPSS software was used for statistical analyses.ResultsWe observed that obese subjects had a lower level of serum calcium (p˂0.05). Moreover, a relationship was detected between serum phosphate level and different menopausal status (p˂0.05). Serum calcium and phosphate did not change by increasing age in the population. Additionally, there was a correlation between lymphocyte count with serum phosphate level (p˂0.05). No statistically different were detected for the levels of calcium/phosphate with respect to smoking status, physical activity, lipid profile, liver and renal function markers.ConclusionWe found an association between serum calcium and BMI as well as with serum phosphate and menopausal status.     

Heritability of plasma sex hormones and hormone binding globulin in adult male twins

Plasma sex hormone concentrations have been used as biomarkers in epidemiological studies of many conditions including cancer, obesity, bone density, and coronary heart disease. The objective of this analysis was to estimate genetic and nongenetic influences on endogenous sex hormones (testosterone, estradiol, estrone, and SHBG) in a large sample of 532 adult white male twins (134 monozygotic and 132 dizygotic twin pairs) from the National Heart, Lung, and Blood Institute Twin Study. Participants were aged 59-70 yr at the time of plasma collection, and hormone concentrations were determined with RIA. Genetic models were fitted by the method of maximum likelihood. Testosterone and SHBG concentrations have substantial genetic variation, with additive genetic factors accounting for 57 and 68% of the total phenotypic variation, respectively. In contrast, variation in estrone (37% shared environmental and 63% individual specific environmental effects) and estradiol concentrations (25% genetic effect, 44% shared environmental effects, and 31% individual specific environmental effects) were largely influenced by nongenetic factors. Assessment of the relative contribution of genetic and nongenetic influences on hormone concentrations may help in the search for genes underlying variation and covariation in complex traits affected by plasma sex hormone concentrations.     

不同体质指数心力衰竭患者的血浆apelin水平及相关因素分析

目的 探讨充血性心力衰竭患者的体质指数与血浆apelin、腰臀比值、空腹血糖、糖化血红蛋白、血脂及超声心动图等指标间的相关性.方法 41例老年心力衰竭患者,按体质指数分为正常体质量组(对照组)16例、超体质量组(超重组)13例和肥胖组12例;再按心功能分为2组,心功能Ⅲ级22例,心功能Ⅳ级19例.测定各组的血浆apelin水平.同时检测体质指数、腰臀比值、C反应蛋白、空腹血糖、肌酸激酵、肌酸激酶同工酶、血脂、电解质及超声心动图等指标.结果 3组腰围、臀围、腰臀比值比较差异有统计学意义(P<0.05或P<0.01).3组间左心室舒张末内径、左心室收缩末内径、室间隔舒张末厚度、二尖瓣前向血流频谱舒张早期左心室充盈峰速度、心房收缩期左心室充盈峰速度、左心室射血分数差异无统计学意义.超重组与肥胖组二尖瓣前向血流频谱舒张早期左心室充盈峰速度比较,差异有统计学意义(P<0.01).肥胖组apelin水平为(0.48±0.15)mg/L,高于对照组[(0.18±0.15)mg/L]及超重组[(0.27±0.06)mg/L3,而超重组高于对照组(均P<0.01).心功能Ⅳ级患者的apelin水平高于心功能Ⅲ级的患者[(0.35±0.16)mg/L与(0.26±0.13)mg/L,P<0.05].apelin与体质指数、白细胞、肌酸激酶、血红蛋白、三酰甘油呈正相关,与心功能、左心室射血分数呈负相关.影响apelin的主要因素为体质指数(β=0.672,P<0.01)、年龄(β=0.244,P<0.01)、高密度脂蛋白胆固醇(β=-1.000,P<0.01).血浆apelin水平是心功能分级的相关因素.结论 血浆apelin水平与心力衰竭的发生相关,充血性心力衰竭患者心功能愈差,其水平愈高.apelin水平升高可能是肥胖心力衰竭患者预后较好的标志之一,可以作为衡量心力衰竭患者预后的指标.     

体质指数与血清尿酸水平的相关性研究

目的探讨体检者的体质指数(BMI)与血清尿酸水平的相关性。方法选取2018年首都医科大学附属北京朝阳医院年龄大于18岁的行健康体检者1 514名作为研究对象,按照BMI分为正常组、超重组和肥胖组,检测代谢指标并行组间比较,分析血清尿酸水平与BMI、三酰甘油等的相关性,利用logistic回归分析高尿酸血症(HUA)的危险因素。结果体检者的血清尿酸水平随BMI增加而升高,在不同BMI分组中的差异有统计学意义。血清尿酸水平与BMI、三酰甘油、空腹胰岛素、稳态模型评估的胰岛素抵抗指数(HOMA-IR)均呈显著正相关(均为P<0.05)。男性(OR=3.02)、超重和肥胖(OR=1.51和2.59)、三酰甘油升高(OR=1.62)、低密度脂蛋白胆固醇升高(OR=2.23)是HUA的危险因素(均为P<0.05)。结论血清尿酸水平与BMI、三酰甘油、空腹胰岛素、HOMA-IR呈正相关,而男性、超重和肥胖、三酰甘油升高、低密度脂蛋白胆固醇升高是HUA的危险因素。     

Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy

OBJECTIVE: To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM). Study design: Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children. RESULTS: BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-alpha and IL-6 were increased at diagnosis and normalized at 1 month. CONCLUSIONS: These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease.     

Dehydroepiandrosterone sulfate levels in women. Relationships with age, body mass index and insulin levels

Sex and age are the major determinants of serum levels of dehydroepiandrosterone sulfate (DHEA-S): they are about twice in men than in women and show a progressive reduction from the end of the puberty to aging in both sexes. It has been reported that DHEA-S levels are also negatively influenced by insulin. Moreover, DHEA-S levels reduction has been associated to increased risk for cardiovascular disease, which connotes hyperinsulinemic states, such as obesity. We have evaluated serum levels of DHEA-S and insulin as function of age and body mass index (BMI) in 376 adult women (age 18.1-89.6 yrs, median 42.2; BMI 15.7-57.8 kg/m2, median 32.7) by multiple regression and piecewise regression analysis. Insulin levels positively associated to BMI (p=0.000002) and DHEA-S levels negatively associated with age (p=0.000001). Considering the whole population, DHEA-S levels were related positively with BMI (p=0.0013) independently of age. DHEA-S were also directly related to insulin levels independently of age (p=0.042), but this association disappeared after correction for BMI. Piecewise regression analysis did not reveal a threshold level for the increase of BMI (p=0.0004). Interestingly, DHEA-S levels and BMI were positively associated before but not after menopause. Taking into account only obese population, (no.=143, age 18.7-67.3 yrs, mean 39.0, median 39.4) DHEA-S levels were again related negatively with age and positively with BMI, while were unrelated with waist to hip ratio (p=0.391). Our data show that increasing body mass and insulin secretion is not associated to DHEA-S reduction in women. This evidence suggests that DHEA-S is unlikely implicated in the pathogenesis of cardiovascular disease in obese women.     

Beyond body mass index

Body mass index (BMI) is the cornerstone of the current classification system for obesity and its advantages are widely exploited across disciplines ranging from international surveillance to individual patient assessment. However, like all anthropometric measurements, it is only a surrogate measure of body fatness. Obesity is defined as an excess accumulation of body fat, and it is the amount of this excess fat that correlates with ill‐health. We propose therefore that much greater attention should be paid to the development of databases and standards based on the direct measurement of body fat in populations, rather than on surrogate measures. In support of this argument we illustrate a wide range of conditions in which surrogate anthropometric measures (especially BMI) provide misleading information about body fat content. These include: infancy and childhood; ageing; racial differences; athletes; military and civil forces personnel; weight loss with and without exercise; physical training; and special clinical circumstances. We argue that BMI continues to serve well for many purposes, but that the time is now right to initiate a gradual evolution beyond BMI towards standards based on actual measurements of body fat mass.     

Relationship between body mass index and high cystatin levels among US adults

High cystatin C levels among patients without clinically recognized chronic kidney disease (CKD) may identify patients who are at preclinical stages of CKD. Higher body mass index (BMI) has been found to be associated with increased risk of CKD. However, the association between BMI and high cystatin C levels is not clear. The authors examined participants older than 20 years from the National Health and Nutrition Examination Survey 1999 to 2002 (N=2583, 50.2% women). BMI was categorized as <25 kg/m(2), 25-29.9 kg/m(2), and ≥30 kg/m(2) . Main outcome was high cystatin C (>1 mg/dL) among patients without clinically recognized CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2) or microalbuminuria). Higher BMI was positively associated with high cystatin C, independent of age, sex, race-ethnicity, education, smoking, alcohol intake, cholesterol, and C-reactive protein levels. Compared with patients with BMI <25 kg/m(2) (referent), the multivariable odds ratio (95% confidence interval) of high cystatin C was 2.53 (1.79-3.58) (P trend <.0001 among patients with BMI ≥30 kg/m(2)). The association between BMI and high cystatin C persisted in subgroup analyses by sex, race-ethnicity, and among those without diabetes or hypertension. Among US adults without clinically recognized CKD, higher BMI levels were independently associated with high cystatin C levels.