青少年中肥胖和2型糖尿病对心脏结构和功能的影响

The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults

青少年中肥胖和2型糖尿病对心脏结构和功能的影响海南医学院第一附属医院内分泌科王新军

摘要

目的/假设  我们的目的是在青少年中评估肥胖和肥胖相关的2型糖尿病对心脏几何结构（重塑）和收缩及舒张功能的影响。

方法  本研究为一项横断面研究，参与者包括非肥胖对照组、肥胖组、肥胖合并2型糖尿病组，用超声心动图比较各组受试者心脏结构和功能。组间差异用ANOVA评价。心脏预后的独立因素测量指标用一般线性模型评估。

 结果  研究发现与非肥胖对照组相比，肥胖组及肥胖相关2型糖尿病组其心脏几何结构存在异常（16%和20% vs <1%， P<0.05）。这两组其收缩功能也增加。从非肥胖组到肥胖组再到肥胖糖尿病组，舒张功能逐渐下降，肥胖糖尿病组舒张功能最低（P<0.05）。回归分析显示，各组间、BMI z值（BMIz）、组×BMIz交互作用和收缩压z值（BPz）是心脏结构的显著决定因素，而各组间、BMIz、收缩压BPz、年龄和空腹血糖是舒张功能的显著决定因素（P值均<0.05）。

 结论/解释  肥胖组和肥胖相关的2型糖尿病组显示出与心脏重塑一致的心脏几何结构的改变。与非肥胖组相比，这两组也显示出舒张功能的改变，在2型肥胖糖尿病组下降最大。已有研究显示舒张功能异常的成人进展为心力衰竭的风险增加。所以，我们的研究提示，与肥胖组和非肥胖组相比，肥胖相关的2型糖尿病的青少年或许进展为早期心力衰竭的风险增加。

关键词  心脏几何结构  舒张功能  肥胖  舒张功能  2型糖尿病

缩略词

A      左室充盈后期

Aa     环状血流后期

ANCOVA  协方差分析

BMIz      BMI z 值

BPz       BP z 值

CDC-NCS  疾病控制和预防中心-国家健康统计中心

E      左室充盈早期

Ea     左室充盈后期

LV     左心室

RWT   室壁相对厚度

VCF   环状纤维缩短速度

患肥胖或肥胖相关2型糖尿病的成人发展为早期冠心病的风险增加。众所周知，不论患者有无冠心病和高血压，肥胖和2型糖尿病可导致心脏结构和功能异常。特别是，这些进程导致心脏几何结构的异常（重塑）和舒张功能异常。实际上，一些研究显示，左室舒张功能代表糖尿病心肌病变最早的临床前表现，且可以进展到症状性心力衰竭。

基于在成人中的这些发现，我们假设，患有肥胖和肥胖相关2型糖尿病的青少年也会显示心脏几何学和舒张功能的早期改变，提示他们发展为早期心力衰竭的风险增加。我们还假设，肥胖相关2型糖尿病的患者与仅有肥胖的患者相比，其心脏结构和功能较差。

方法

研究人群

作为观察肥胖和2型糖尿病对青年心脏和血管功能作用的横断面研究一部分，我们评估了青少年人群。共募集的三组研究人群：（1）合并糖尿病的肥胖者；（2）肥胖对照者（即无2型糖尿病的肥胖者）；（3）非肥胖对照者（既无肥胖也无2型糖尿病）。参与者的年龄在10到24岁之间。妊娠女性和先天性心脏病患者剔除本研究。肥胖者其BMI≥95th百分位数，非肥胖者其BMI<85 th百分位数，定义是基于疾病控制和预防中心-国家健康统计中心生长表。2型糖尿病的诊断根据ADA标准。参与者至少有空腹血浆葡萄糖升高≥7.0mmol/L、有糖尿病症状且随机血糖≥11.1mmol/L或口服糖耐量试验2h血糖≥11.1mmol/L。所有2型糖尿病患者均无其他特殊糖尿病的证据，且在基线状态不需胰岛素治疗。总共有147个参与者胰岛细胞抗体阴性（谷氨酸脱羧酶、胰岛细胞抗原512、胰岛素抗体）。10人物胰岛细胞抗体数据，但符合ADA诊断2型糖尿病的标准。

研究人群是从辛辛那提儿童医院、社区医师办公室、卫生局、大学校园招募的。没有胰岛细胞抗体数据的糖尿病患者是从社区医师招募的。进入本研究前，根据赫尔辛基宣言，按照辛辛那提儿童医学中心伦理委员会指南签署知情同意书，≥18岁者本人签署，<18岁者其父母或监护人签署。

数据/实验室资料收集

至少10 h过夜空腹后，参与者到辛辛那提儿童医学中心的临床研究中心进行人口学资料登记、实验室和人体测量学指标检测、血压测量。BMIz值用CDC-NCHS生长参考数据计算得出。腰围测量用金属研究卷尺测量两次取均值，精确到0.5cm，具体操作参考美国国家心肺和血液健康研究所的标准研究操作规程。双能X线吸收仪（Hologic 4500A, Bedford, MA, USA）用于测量瘦肉量和计算体脂百分比。 体脂百分比用总体脂量除以总体重在乘以100计算。糖化血红蛋白用高效液相方法测量。2型糖尿病病程是指从诊断到研究的时间。

超声心动图
心脏用GE Vivid 5或 7（Milwaukee, WI, USA）或Philips Sonos 5500 （Andover, MA, USA）超声系统进行无创性评估。对每个参与者进行完整的二维脉冲多普勒、组织多普勒和彩色多普勒超声心动图检查。所有参与者在左侧卧位测量心脏长轴和短轴及四个房室内径。由一个对研究分组不知情的超声医师对每个参与者测量3个心动周期。数据由一个对分组不知情的医师用心脏分析系统（Digisonics, Houston, TX, USA）离线测量。

超声心动图测量

心脏结构和几何学    左心室重量指数（心肌肥厚的指标）和相对心室壁厚度（RWT）（测量左心室壁厚度相对于左心室腔大小）根据文献用左室舒张末内径、舒张末后壁厚度计算。左心室中来那个指数用左心室重量除以身高的2.7以消除年龄、性别和种族的影响。左心室重量指数和RWT阈值水平用于评估左心室几何学。对于左心室重量指数，成人阈值设定为>51g/m2.7，因为在成人这与心脏发病率相关。对于RWT，通常成人的阈值设定为> 0.43。心脏几何学测量结果分为四类：正常几何学、向心性重塑（正常左心室重量指数，RWT增加）、离心性肥大（左心室重量指数增加，RWT正常）、向心性肥大（左心室重量指数增加，RWT增加）。这些左心室几何学分类与心血管死亡率相关，向心性肥大是最严重的，常常是左心室心力衰竭的前兆。

心脏功能    左心室收缩功能按照文献所述进行评估。收缩功能的测量包括缩短率、收缩末压和周径纤维缩短速度差异。缩短率是衡量左心室收缩能力的指标，室壁压是衡量心脏负荷后指标，是由收缩末压力计算得来。周径纤维缩短速度差异是一种测量收缩性的指标，是在一定的室壁压下，每个参与者由测量的周径纤维速度和预测的周径纤维速度的差别。

More than one measure was also used to evaluate

diastolic function. First, Doppler interrogation of transmitral blood flow velocities was used to measure peak early

(E) and late (A) LV filling. The ratio of both was used to

calculate E/A. Tissue Doppler analyses of the myocardial

wall velocities at both the septal and lateral annuli was also

performed to obtain peak early (Ea) and late (Aa) velocities

of mitral annular flow. The ratios of these measures at the

septal and lateral annuli were averaged to calculate Ea/Aa

average. Finally, the ratio of mitral to myocardial early

filling was measured to calculate E/Ea average, a measure

of LV end-diastolic pressure [19]. These particular non-

invasive measures of diastolic function correlate well with

invasive measures of diastolic function (time constant of

relaxation [tau]) and LVend-diastolic pressure [20].

应用多个测量值评估舒张功能。首先，多普勒血流反流速度用于衡量早期峰值（E）和晚期（A）左室充盈。二者的比例用来计算E/A比值。组织多普勒分析心肌壁速度也用来获得演出获得早期峰值（Ea）和晚期（Aa）的速度。最后，二尖瓣和心肌早期充盈比值用于计算E/ Ea比值，即衡量左心室舒张末压的一个指标。这些非侵入性舒张功能的测量与侵入性舒张功能的测量相关性良好。

Statistical analysis

All analyses were performed with Statistical Analysis

Software (SAS, version 9.1.3) [21]. Average values for

demographic, anthropometric, blood pressure and labora-

tory values were obtained for each group. Non-normally

distributed variables were log transformed to the loge for

comparison. ANOVA was performed to compare means

among groups using Bonferroni correction methods for

multiple comparisons. Differences in LV geometry among

2 groups were assessed by χ analysis.

统计分析
所有分析均采用计算机软件统计分析（SAS，version 9.1.3）。分别计算每组人口学、人体测量学、血压和实验室测量值。非正态分布变量经log转化后进行比较。ANOVA用于比较多组间各组的平均值。两组间左心室几何学差异用χ2分析。

Bivariate correlations were calculated between LV mass index (component of

cardiac geometry), systolic (shortening fraction) and dia-

stolic outcomes (E/A, Ea/Aa average, E/Ea average) and

potential demographic and physiologic predictors. HbA1c,

glucose and duration of disease were only considered for

participants with type 2 diabetes. Significant variables from

the correlation analyses were then used to construct

analysis of covariance (ANCOVA) models using proc

GLM for each outcome variable. The full model potentially

included: demographic (group, age, race, sex), anthropo-

metric (BMIz, waist circumference, lean mass from dual-

energy x-ray absorptiometry [DXA]), and haemodynamic

(systolic and diastolic BPz scores) variables.

计算左心室重量指数（心脏几何学组分）、收缩指标（缩短分数）和舒张指标（E / A、Ea/Aa平均值、E/Ea平均值）、潜在的人口学和生理预测因素之间的二元相关性。糖化血红蛋白、血糖和疾病病程仅在2型糖尿病患者中考虑。相关性分析中的显著性变量用于构建协方差分析（ANCOVA）模型。完整的模型可能包括：人口学（组别、年龄、种族、性别）、人体测量学（BMIz、腰围、瘦体质量）和血流动力学变量（收缩压和舒张压BPz值）。

RWT and LV mass indices were only included in the models constructed

for diastolic variables. Group was forced into the model as

a class variable to ensure group differences would be

considered when determining significant predictors. The

significance level of each covariate was assessed with the

most significant term added in a stepwise manner. Any non-

significant term was removed after each step. This process

continued until all remaining covariates were significant.

Interaction terms between the group and the independent

predictors were included in the models and tested for

significance. Any non-significant interaction term was also

removed from the final models.

RWT和左心室重量指数仅包括在构建舒张变量的模型中。组别作为一个分类变量强制进入模型中，以确保分析显著预测因子时的组别差异。每个协变量的显著性水平用最显著因素多元增加的方法评估。任何非显著性因素在每步后剔除。这个过程继续进行直到所有的剩余协变量均是显著的。在组别和独立预测因素间的具有交互作用的因素进入模型并检测显著性。任何非显著性交互作用因素也从最后模型中剔除。

Results

The study population consisted of 612 adolescents. Table 1

lists the mean and standard deviations for anthropometric,

blood pressure and laboratory data for all participants

stratified by group (lean, obese, obese diabetic). The groups

did not differ by age or sex distribution (p<0.05). As

dictated by study design, lean individuals had a lower BMI

than obese and obese diabetic participants. Cardiovascular

risk profile (weight, waist circumference and systolic blood

pressure) worsened across groups from lean to obese to

obese diabetic (p<0.05). As expected, participants with

type 2 diabetes had a significantly higher fasting glucose

and HbA1c compared with lean and obese groups. Average

duration of disease in diabetic participants was 3.2±

2.5 years.

 

结果

研究人群包括612名青少年。表1列出了所有参与者各组（非肥胖、肥胖、肥胖糖尿病）的人体测量学、血压和实验室数据的平均值和标准差。各组间没有年龄和性别分布的差异。如研究设计的那样，非肥胖个体比肥胖和肥胖糖尿病个体具有较低的BMI。心血管风险因素（体重、腰围和收缩压）有非肥胖组到肥胖组再到肥胖糖尿病组逐渐加重（P<0.05）。和预期的那样，与非肥胖组及肥胖组相比，2型糖尿病人群空腹血糖和糖化血红蛋白较高。糖尿病参与者其糖尿病病程是3.2 ± 2.5年。

表1  各组研究人群的人体测量学和人体成分

数值以平均值±SD表示

a非肥胖和肥胖组<肥胖糖尿病组，p<0.05

b非肥胖组<肥胖组<肥胖糖尿病组，p<0.05

c非肥胖组<肥胖组和肥胖糖尿病组，p<0.05

变量     非肥胖组   肥胖组    肥胖糖尿病组

年龄

年龄范围

女性

人种（白色）

人种（黑色）

人种（其他/混合人种）

身高

体重

体重指数

瘦体重

腰围

收缩压

舒张压

空腹血糖

糖化血红蛋白

糖尿病病程

The absolute number of participants with abnormal BP

levels was lower in the lean (13.4% prehypertensive,

<0.01% with stage 1 or stage 2 hypertension) and obese

groups (30.5% prehypertensive, 5.8% with stage 1 or stage

2 hypertension), with the obese diabetic group having

higher prevalence of hypertension (46% prehypertensive,

16.6% with stage 1 or 2 hypertension).

参与者血压异常的绝对数在非肥胖组（13.4%高血压前期，<0.01% 1级或2级高血压）和肥胖组（30.5%高血压前期，5.8% 1级或2级高血压）较低，在肥胖糖尿病组高血压发病率较高（46%高血压前期，16.6% 1级或2级高血压）。

 

The presence of dyslipidaemia was also assessed.

Dyslipidaemia was defined by LDL >3.4 mmol/l, TG

>14.5 mmol/l or HDL <1.0 mmol/l [22–24]. In the lean

group 5.2% of participants were found to have evidence of

dyslipidaemia, which was significantly lower than those in

the obese and (24.2%) and obese diabetic group (26.2%).

Review of medication history revealed that three partic-

ipants in the obese group were taking metformin, while in

the obese diabetic group 86 were taking metformin and one

was taking long-acting insulin glargine (A21Gly,B31Arg,

B32Arg human insulin). BP medication history revealed

two obese participants and 27 diabetic participants were

taking anti-hypertensive medications.

本研究亦评估了血脂异常的发病率。血脂异常的定义是LDL >3.4 mmol/l, TG>14.5 mmol/l 或HDL <1.0 mmol/l。在非肥胖组，5.2%的参与者有血脂异常，显著低于肥胖组（24.2%）和肥胖糖尿病组(26.2%)。回顾分析病史显示肥胖组中有三人服用二甲双胍，而在肥胖糖尿病组中，有86人服用二甲双胍，一人注射长效甘精胰岛素。另外，有2名肥胖参与者及27名糖尿病患者正在服用抗高血压药物。

Measures of cardiac structure and geometry by group are listed in Table 2. Compared with the lean controls, LV massindex was increased but similar in both the obese and obese

diabetic groups (p<0.05). Further analysis of the components of LV mass index demonstrated that increased LV mass index was a result of increased LV end-diastolic dimension and septal and posterior wall thickness in the heart. RWT was also higher in the obese and obese diabetic

participants compared with lean participants, but averageRWT did not exceed threshold levels that would contribute to abnormal geometry. The presence of any type of abnormal geometry was similar for the obese and obese diabetic group (16% vs 20%), both higher than for the lean

group, who had abnormal geometry less than 1% of the time (p<0.05). The most prevalent abnormal geometry type in both the obese and obese diabetic groups was eccentric

hypertrophy (increased LV mass index, normal RWT).

 

各组间心脏结构和几何学测量值列于表2。与非肥胖组相比，左心室重量指数在肥胖组和肥胖糖尿病组升高。进一步分析左心室重量指数成分显示左心室重量指数增加是左心室舒张末内径和心脏室间隔和后壁厚度增加的结果。与非肥胖参与者相比，RWT在肥胖组和肥胖糖尿病组也升高，但平均RWT没有超过引起几何学异常的阈值水平。存在任何类型几何学异常的发生率在肥胖组和肥胖糖尿病组相似(16% vs 20%)，但均高于非肥胖组，在非肥胖组，几何学异常的发生率低于1%(p<0.05)。在肥胖组和肥胖糖尿病组最常见的几何学异常是离心性肥大（左心室重量指数增加，RWT正常）。

 

LV systolic function measures are shown in Table 2. The

shortening fraction was higher in both obese and obese

diabetic participants compared with lean controls but it was

not different from one another, indicating a similar increase in

LV performance. Wall stress was lower in the obese and obese

Diabetic groups compared with the lean group.Therewereno

significant differences in VCF difference (contractility)

among the three groups.

左心室收缩功能测量结果见表2。与非肥胖糖尿病对照组相比，肥胖组和肥胖糖尿病组参与者缩短分数较高，但这两组患者无明显差异。与非肥胖糖尿病对照组相比，肥胖组和肥胖糖尿病组参与者室壁压较低。VCF差异（收缩）在三组间无明显差异。

Diastolic function differed among the three groups

(see Fig. 1). Compared with the lean group, diastolic

function was decreased in the obese group and further

decreased in the obese diabetic group. Specifically, obese

participants had a higher mitral E/Ea average (increased

LV filling pressure) and lower mitral Ea/Aa average

(decreased diastolic function) compared with lean partici-

pants.TheobesediabeticgrouphadthehighestE/Eaaverage

and lowest Ea/Aa average. In this group, E/A ratio was also

lower compared with obese and lean controls (decreased

diastolic function) (Table 2). Five individuals in the obese

diabetic group had E/Ea mean >10, suggesting abnormal

diastolic filling pressure [25, 26].Therewerenoleanor

obese non-diabetic patients who met this criterion.

三组间舒张功能差异见表图1。与非肥胖组相比，肥胖组舒张功能降低，在肥胖糖尿病组进一步降低。特别是，与非肥胖组相比，肥胖参与者二尖瓣E/Aa平均值较高（左心室充盈压增加），二尖瓣Ea/Aa平均值较低（舒张功能降低）。肥胖糖尿病组具有最高的E/Ea平均值和最低的Ea/Aa平均值。与肥胖组和非肥胖组相比，这一组E/A比值也比较低（舒张功能降低）。肥胖糖尿病组有5人E/Ea平均值>10，提示舒张充盈压异常。没有非肥胖或肥胖非糖尿病患者达到此标准。

表2  各组人群中的超声心动图测量值

 

变量    非肥胖组  肥胖组   肥胖糖尿病组

心脏结构

左心室重量指数

左心室舒张末内径

左心室后壁厚度-舒张期

舒张末室间隔厚度

RWT

几何学

正常

向心性重塑

离心性肥大

向心性肥大

收缩功能

缩短分数

室壁压

收缩压

左心室收缩末内径

左心室后壁厚度-收缩期

VCF差异

 

舒张功能

左房直径

左房体积

峰Ea

峰Ab

二尖瓣E/A比值

二尖瓣Ea/Aa-avg

二尖瓣E/Ea-avg

二尖瓣E/Ea-avg>10

数值以平均值±SD表示

a非肥胖组vs肥胖组和肥胖糖尿病组，p<0.05

b非肥胖组vs肥胖组vs肥胖糖尿病组，p<0.05

c非肥胖组和肥胖组vs肥胖糖尿病组，p<0.05

avg，平均值

 

图1  各组间舒张功能（平均值和标准差）。白柱：非肥胖组；灰柱：肥胖组；黑柱：2型糖尿病组。非肥胖组<肥胖组<肥胖2型糖尿病组，* p<0.05。非肥胖组和肥胖组<肥胖2型糖尿病组，┼p<0.05。avg，平均值

 

 

Table 3 demonstrates significant correlation coefficients

for the LV mass index, shortening fraction and diastolic

function outcomes. Age, adiposity (BMIz, waist circumfer-

ence and per cent body fat), lean mass, and BPz were

significantly associated with LV mass index. Only adiposity

and systolic BPz were significantly associated with the

shortening fraction. Waist circumference, systolic BPz and

LV mass index were significantly correlated with all three

measures of diastolic function. Type 2 diabetes measures

(fasting glucose, HbA1c and duration of diabetes) were

significantly associated with LV mass index, Ea/Aa average

and E/Ea average.

表3显示左心室重量指数、缩短分数和舒张功能之间存在显著相关性。年龄、肥胖（BMIz、腰围和体脂百分比）、瘦肉量和BPz与左心室重量指数显著相关。仅有肥胖和收缩BPz与缩短分数显著相关。腰围、收缩BPz和左心室重量指数与舒张功能的三个指标均显著相关。2型糖尿病的指标（空腹血糖、糖化血红蛋白和糖尿病病程）与左心室重量指数、Ea/Aa均值和E/Ea均值显著相关。

 

 

 

 

 

变量  左心室重量指数  缩短分数  E/A  Ea/Aa均值  E/Ea均值

年龄

BMIz

体脂百分比

瘦肉量

腰围

收缩BPz

舒张BPz

左心室重量指数

空腹血糖

糖化血红蛋白

糖尿病病程

 

 

表3 左心室重量指数和收缩变量及舒张变量的关系（r值）

除标记为NS（无显著性）外，均有显著性r值（P<0.01）

空腹血糖、糖化血红蛋白和2型糖尿病病程仅在肥胖糖尿病组考虑

Avg：均值

The ANCOVA models are presented in Table 4. A model

for shortening fraction was constructed but omitted from

the manuscript as the amount of variation explained by the

model was too low to be considered meaningful. Group

was a significant predictor of E/Ea, indicating that the mean

values of E/Ea differed among the three groups, after

adjusting for other factors in the model. For LV mass index,

there was a significant BMIz by group interaction in the

obese diabetic group, indicating the regression slope in this

group was significantly higher than in the lean group.

ANCOVA模型结果见表4。缩短分数也进行了分析但本文已省略，因为通过这个模型解释变异量其意义过低。在校正模型中其他因素后，组别是E/Ea的一个显著预测因素，表明E/Ea的平均值在三组是有差异的。而左心室重量指数在肥胖糖尿病组与BMIz显著相关，表明在这组的回归斜率明显高于非肥胖组。

 

Cardiovascular risk factors were also important in explain-

ing the variance in cardiac structure and function. Higher

systolic BPz and waist circumference were associated with

higher LV mass index and poorer diastolic function.

Additionally, higher fasting glucose was associated with

poorer diastolic function but did not contribute to

increased LV mass index (for all model and variable

estimates p<0.05). Figure 2 is presented to visually

demonstrate the differences in LV mass index and BMIz

for study design groups described in Table 4.Theslopeof

the regression line is different among all three groups with

the obese diabetic group having the steepest slope. This

suggests that there is an additional burden on the heart in

the obese diabetic group beyond what is expected from

obesity alone.

心血管危险因素对于解释心脏结构和功能的变量也有重要意义。高收缩BPz和腰围与高左心室重量指数和较差的舒张功能相关。此外，高空腹血糖与舒张功能较差相关，但对左心室重量指数没有贡献（在所有模型中，变量估计p<0.05）。图2显示左心室重量指数和BMIz在各设计组的差异。回归线的斜率在所有这三组中是不同的，肥胖糖尿病组斜率最大。这就提示，肥胖糖尿病组比仅有肥胖相比，对心脏有额外负担。

 

表4  ANCOVA中左心室重量指数和舒张变量的回归系数

变量   组别  左心室重量指数  E/A  Ea/Aa均值  E/Ea均值

解释

组别   非肥胖组

       肥胖组

       肥胖糖尿病组

BMIz

组别±BMIz交互作用  非肥胖

                      肥胖

                      肥胖糖尿病

瘦肉量

收缩BPz

血糖

腰围

年龄

 

所有变量估计值p<0.05

组别强制进入模型。如果不显著以+表示。

左心室重量指数

BMIz

图2  左心室重量指数和BMIz的回归分析结果。白色方框/长灰线：非肥胖组；白色圆圈/短灰线：肥胖组；灰色方框/连续线：肥胖2型糖尿病。

 

Discussion

This study documents that adolescents and young adults

with obesity and obesity-related type 2 diabetes have a

higher frequency of abnormal cardiac geometry, increased

systolic function and decreased diastolic function compared

with age-matched lean controls. These data also demon-

strate that obese adolescents with type 2 diabetes have a

further decline in diastolic function compared with non-

diabeticobeseadolescents.Inadults,diastolicdysfunctionisa

significant risk factor for future development of congestive

heart failure [8, 27]; therefore, our data suggest that obese

adolescents with type 2 diabetes may be at higher risk of

progressing to premature heart failure compared with their

non-diabetic obese and lean counterparts.

讨论

本研究显示，与年龄匹配的非肥胖对照组相比，在肥胖和肥胖相关2型糖尿病的青少年中心脏几何学异常具有较高的发生率，收缩功能增加和舒张功能降低。这些数据也显示，与没有糖尿病的肥胖青少年相比，合并2型糖尿病的肥胖青少年舒张功能进一步降低。在成人，舒张功能是一个发展为充血性心力衰竭的一个显著危险因素；所以，我们的数据提示，与非糖尿病的肥胖者及非肥胖的对照人群相比，合并2型糖尿病的肥胖青少年可能处于进展为早发心力衰竭的高度风险中。

 

 

Adults with obesity and obesity-related type 2 diabetes

demonstrate increased LV mass index and increased RWT

leading to a predominant cardiac geometry of concentric

hypertrophy [5, 6, 28–31]. To date, no study has compared

cardiac geometry in lean, obese and obese diabetic

adolescents. Our data demonstrate that, compared with lean

controls, adolescents and young adults with obesity and

obesity-related type 2 diabetes have an increased LV mass

index, contributing to a higher frequency of eccentric

hypertrophy (increased LV mass and normal RWT).

肥胖和肥胖相关2型糖尿病的成人显示，左心室重量指数增加和RWT增加可导致向心性肥大为主的心脏几何学改变。到目前为止，尚无研究比较非肥胖、肥胖、肥胖糖尿病青少年中心脏几何学的变化。我们的数据显示，与非肥胖对照组相比，肥胖和肥胖相关2型糖尿病的青少年其左心室重量指数增加，导致离心性心肌肥大（左心室重量增加，RWT正常）发生率增加。

Although RWT was higher in obese and obese diabetic

participants compared with lean controls, their RWT values

did not exceed threshold levels to contribute to abnormal

geometry (RWT >0.43). These findings suggest that an

increase in RWT may be a late phenomenon and is likely to

be a result of sustained increased haemodynamic load on

the heart. As a result, adolescents with obesity and obesity-

related type 2 diabetes may be at risk of progressing to

concentric hypertrophy, the cardiac geometry commonly

found in obese adults and adults with type 2 diabetes. This

possibility has been suggested in work published by Ippisch

et al., in which concentric hypertrophy was the predominant

cardiac geometric pattern in adolescents with morbid

obesity [13].

与非肥胖组相比，虽然肥胖和肥胖糖尿病参与者RWT较高，但是他们的RWT值并未超过导致心脏几何学异常的阈值水平(RWT >0.43)。这些发现提示，RWT增加可能是一个较晚出现的现象，似乎是持续血流动力学负荷增加对心脏作用的结果。所以，肥胖和肥胖相关2型糖尿病的青少年或许具有进展为向心性肥大的风险，向心性肥大常在肥胖的成人及2型糖尿病的成人中出现。这或许在Ippisch等发表的论文中已有提示，在这篇文章中，向心性肥大是严重肥胖青少年中主要的心脏几何学改变。

 

 

It is normal for systolic function to increase in adults

early in the course of obesity and diabetes. There appears to

be a compensatory increase in ejection fraction and

shortening fraction [3, 30, 32], which declines with the

duration of disease [3] and as it develops in severity [30]. In

adolescents there is a paucity of data regarding the effects

of obesity and obesity-related type 2 diabetes on systolic

function. Ippisch et al. studied morbidly obese adolescents

and described increased systolic function (as measured by

stroke volume and cardiac output), which was unchanged

with weight loss after bariatric surgery [13]. In type 1

diabetes a similar increase in systolic function has been

described [33].

在成人肥胖和糖尿病早期，收缩功能增加时正常的。这可能是对射血分数和缩短分数的代偿性增加，但随着糖尿病病程的延长及糖尿病加重而下降。在青少年，尚缺乏关于肥胖和肥胖相关2型糖尿病对收缩功能影响的数据。Ippisch等研究了重度肥胖青少年，显示收缩功能增加（检测每博量和心输出量），但在减肥手术体重减轻后未发生改变。在1型糖尿病，有文献显示其收缩功能也同样增加。

 

 

 

 

Our data show that young individuals with obesity and

obesity-related T2DM have increased systolic function as

measured by increased shortening fraction and lower wall

stress. The changes in wall stress appear to be a result of

increased systolic pressure, increased LV ventricular end-

systolic dimension and even higher posterior wall thickness

in obese and obese diabetic individuals. Similarly to adults,

this appears to be a compensatory increase in systolic

function. The significance of this increase in systolic

function early in the course of both type 1 and type 2

diabetes in adolescents is not clear. Longitudinal studies are

needed in this population to determine if systolic function

declines with the duration and severity of disease.

我们的数据表明，肥胖和肥胖相关2型糖尿病的年轻个体其收缩功能增加（缩短分数增加，室壁压降低）。肥胖和肥胖糖尿病个体室壁压的改变提示是收缩压增加、左心室舒张末内径增加和心室后壁厚度增加的结果。在青少年1型和2型糖尿病中，这种收缩功能增加的意义尚不清楚。需要在这些人群中进行横断面研究，以确定是否收缩功能随着疾病的病程和严重程度而下降。

 

 

Published reports document diastolic dysfunction in

obese adults, both with and without type 2 diabetes. Both

the duration of disease [3] and severity [30] of obesity and

obesity-related type 2 diabetes appear to influence the

extent of diastolic dysfunction. Changes are seen in as little

as 4–5 years [34]. In adults with type 2 diabetes, the

prevalence of diastolic dysfunction is between 30% and

50% [34, 35]. In adolescents, reports of the effects of

obesity and type 2 diabetes on diastolic function have

yielded discrepant results.

已有文献报告，在合并或不合并2型糖尿病的肥胖成人存在舒张功能失调。肥胖和肥胖相关的2型糖尿病的病程和严重程度影响舒张功能失调的程度。在疾病发生4-5年即可见到这种改变。在成年2型糖尿病，舒张功能失调的发生率在30%和50%之间。在青少年，肥胖和2型糖尿病对舒张功能的影响仍不一致。

 

 

 

 

 

 

 

 

 

 

Specifically, the Strong Heart

Study demonstrated no differences in diastolic function

(E/A ratio) between obese and lean controls [36]. In

contrast, Sharpe et al. demonstrated a decrease in E/A in

obese, compared with lean adolescents [37]. Only one

previous study has investigated the relationship between

type 2 diabetes and diastolic function in adolescents;

Whalley et al demonstrated a decreased E/A ratio and

increased E/Ea ratio early in the course of type 2 diabetes in

female adolescents compared with obese and lean controls

[38].

Strong Heart Study未见肥胖组和非肥胖对照之间舒张功能的差异。相反，Sharpe等的研究显示，与非肥胖青少年相比，肥胖者可见E/A值的下降。仅有一项研究观察了青少年2型糖尿病和舒张功能的关系。Whalley等的研究显示，与肥胖和非肥胖对照相比，在青少年女性2型糖尿病病程的早期，E/A比值和E/Ea比值增加。

 

Similarly to the above studies, we demonstrate decreased

diastolic function in obese adolescents compared with lean

controls, and an even further decrease in diastolic function

in obese adolescents with type 2 diabetes. We extend

previous observations in the literature by studying both

males and females. Additionally, from our general linear

models, we provide data that demonstrate that this decrease

in diastolic function in obese diabetic adolescents is

probably due to independent contributions made by

increased systolic blood pressure, adiposity and increased

fasting glucose. These findings suggest that factors unique

to type 2 diabetes (increased fasting glucose) may contrib-

ute to the difference in diastolic dysfunction between obese

and obese diabetic individuals.

与以上研究结果相似，我们的研究显示，与非肥胖对照相比，肥胖青少年的舒张功能下降，在合并2型糖尿病的肥胖青少年，舒张功能进一步下降。此外，从我们的普通线性模型中，数据显示肥胖糖尿病青少年舒张功能的下降或许是由于收缩压升高、肥胖和空腹血糖升高所致。这些发现提示，2型糖尿病特异的因素（空腹血糖增加）或许是肥胖和肥胖糖尿病个体之间差异的原因。

 

 

 

 

 

 

 

 

 

Limitations

This study has limitations. First, our cross sectional design

does not allow us to determine the time sequence for the

development of changes in cardiac structure and function as

individuals move from lean to obese to type 2 diabetes.

Second, unlike trends in longitudinal analysis, we

cannot show cause and effect. Third, although we can

assess the effect of duration of type 2 diabetes, we

cannot assess the duration of obesity in either the obese

or obese diabetic group. Finally, we did not study the

potential influence of sleep apnoea on cardiac structure

andfunctioninthisstudy.

缺陷

本研究也有一些缺陷。首先，我们的横断面研究设计使我们无法确定从非肥胖到肥胖再到糖尿病个体中，心脏结构和功能变化的时间顺序。其次，不像纵向研究分析那样，我们无法观察的因果关系。第三，虽然我们可以评估2型糖尿病病程的效应，但我们无法评估肥胖或肥胖糖尿病组肥胖病程的影响。最后，我们没有研究睡眠呼吸暂停对心脏结构和功能的影响。

 

Conclusions

We conclude that adolescents and young adults with obesity

and obesity-related type 2 diabetes have a higher likelihood

of abnormal geometry and increased systolic function

compared with lean individuals. Furthermore, obese indi-

viduals have diastolic dysfunction that declines further in

the presence of type 2 diabetes. Since diastolic dysfunction

is known to be associated with progression to heart failure

in adults [7, 8], our findings suggest that obese adolescents

both with and without type 2 diabetes are at risk for

premature heart failure. However, the risk may be greater in

obese adolescents with type 2 diabetes.

结论

我们推测，与非肥胖个体相比，肥胖和肥胖相关2型糖尿病的青少年心脏几何学异常和收缩功能增加的概率较高。而且，肥胖个体有舒张功能异常，在存在2型糖尿病时进一步下降。由于在成人舒张功能异常与进展为心力衰竭相关，我们的发现提示无论有无2型糖尿病，肥胖青少年均存在早发心力衰竭的风险。然而，在合并2型糖尿病的肥胖青少年，这种风险可能更大。

 

（编译  王新军  滨州医学院附属滨州市人民医院）