Children with type 2 diabetes mellitus are at greater risk of macrovascular complications

Background:  Type 2 diabetes mellitus (DM) is a risk factor for macrovascular complications in adults. Recently young-onset type 2 DM has increased worldwide and the increase of macrovascular complications in the young is worrisome.
Methods:  Plasma values for plasminogen activator inhibitor-1 (PAI-1) as a marker for promotion, and adiponectin as a marker for inhibition of atherosclerosis, were compared in 33 patients with type 1 DM (16 boys, 17 girls; age 14.9 ± 3.7 years, mean ± standard deviation) with those of 43 patients with type 2 DM (15 boys, 28 girls; age 16.5 ± 3.5 years).
Results:  The PAI-1 level was significantly higher (19.3 ± 8.1 vs 32.9 ± 17.2 ng/ml; P < 0.001) and the adiponectin level was significantly lower (10.1 ± 3.8 vs 7.4 ± 3.7 µg/ml; P < 0.005) in the type 2 DM group. In obese patients, the PAI-1 level was significantly higher ( P < 0.005) and the adiponectin level was lower ( P = 0.15) in the type 2 DM group. Also, in the non-obese subjects, the PAI-1 level was significantly higher ( P < 0.05) and the adiponectin level was lower ( P = 0.11) in the type 2 DM group.
Conclusions:  Even in young patients, type 2 DM is a risk factor for macrovascular complications compared with type 1 DM.     

大于胎龄儿脐血脂联素水平测定及其临床意义

目的探讨大于胎龄儿(LGA)血脂联素水平变化及其对新生儿的影响。方法研究对象为LGA和适于胎龄儿(AGA)各30例。应用酶联免疫吸附法(ELISA)测定脐血和产妇血脂联素水平,用免疫比浊法测定三酰甘油(TG)、总胆固醇(TCH)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c)水平,并分析脐血脂联素水平与母血脂联素、新生儿性别、出生体质量、体质量指数(BMI)、胎盘重量和血脂水平的相关性。结果1.LGA脐血浆脂联素水平低于AGA,差异有非常显著性(P<0.01);LGA血TG、TCH、LDL-c、HDL-c水平与AGA比较差异均无显著性(Pa>0.05)。2.LGA血浆脂联素水平与新生儿出生体质量、BMI、胎盘重量、脐血TG水平均呈显著负相关(r=-0.848,-0.785,-0.835 Pa<0.001),与母血脂联素水平、新生儿身长、孕前和分娩时产妇体质量及其BMI、其他脐血脂成分无相关性(Pa>0.05)。3.LGA男婴和女婴脐血浆脂联素、血脂各成分水平比较差异均无显著性(Pa>0.05)。结论血脂联素水平变化与LGA的发生有关,测定脐血脂联素水平有助于判断LGA的发展趋势。     

Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood

We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT and in sex and age-matched controls. Three patients (17%), but none of the controls, met the criteria for the MetS (p = 0.25). In the patients, we found higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p = 0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was significantly correlated inversely with triglycerides (r = -0.64, p = 0.008), total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p = 0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a significantly thicker carotid intima layer among the patients than among matched controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in childhood, long-term survivors may be at risk of developing premature CVD.     

胰岛素抵抗与低水平脂联素协同促小鼠心室重塑

目的分析低水平脂联素(APN)与胰岛素抵抗(IR)在心室重塑中的效应。方法将野生C57小鼠随机分为对照组(control组)和胰岛素抵抗组(IR组),每组n=8,脂联素基因敲除小鼠随机分为基因敲除组(APNKO组)和基因敲除+胰岛素抵抗组(APNKO+IR组),每组n=8,给予高脂饲料诱导产生IR。喂养12周后测定空腹血糖(FPG)、空腹胰岛素(FINS)、三酰甘油(TG)和总胆固醇(TC)等糖脂代谢指标,并计算各组胰岛素抵抗指数(HOMA-IR)、心脏质量指数(HWI)和左心室质量指数(LVWI)。取左心室心肌做Masson染色,计算心肌胶原容积分数(CVF)与血管周围胶原面积(PVCA)的大小,检测各组心肌纤维化的程度;用Western blot检测心肌基质金属蛋白酶-9(MMP-9)和APN表达量。结果低水平APN和IR均能增加心脏质量、左心室质量、HWI和LVWI(P0.05)。低水平APN和IR对TG、TC、FPG、FINS及心室重塑相关指标有交互效应(P0.05),且均为正效应,对心肌APN也有交互效应(P0.05),但为负效应。结论低水平APN和IR在小鼠心室重塑过程中起协同促进作用。     

原发性高血压肾病患者血浆leptin和血清APN及尿mAlb检测的临床意义

目的:探讨了原发性高血压肾病患者血浆瘦素(leptin)和血清脂联素(APN)及尿微量白蛋白(mAlb)水平的变化及意义。方法:应用放射免疫分析、酶联免疫法和化学法对38例原发性高血压肾病患者血浆leptin和血清APN及尿mAlb进行检测,并与35名正常健康人作比较。结果:原发性高血压肾病患者血浆leptin和尿mAlb水平非常显著地高于正常人组(P<0.01)。而血清APN水平则显著地低于正常人组(P<0.01)。血清APN水平与leptin、尿mAlb水平呈显著的负相关(r=-0.4084、-0.5132,P<0.01)。结论:检测原发性高血压肾病患者血浆leptin和血清APN及尿mAlb水平的变化对了解病情、探讨其发病机理、预防和指导用药均有重要的临床价值。     

Low plasma level of adiponectin is associated with stavudine treatment and lipodystrophy in HIV-infected patients

This study tested the hypothesis that in patients with HIV-associated lipodystrophy, adiponectin levels were related to insulin resistance, TNF-alpha and IL-6 and treatment with nucleoside analogues. HIV seropositive men undergoing highly active antiretroviral treatment were enrolled into three predetermined clinical groups: lipodystrophy with central fat accumulation (n = 12); lipodystrophy without central fat accumulation (n = 15); no lipodystrophy (n = 15). HIV-negative healthy men served as controls (n = 12). Both lipodystrophic groups had a low percentage of limb fat compared to the two control groups. Patients with lipodystrophy with fat accumulation had increased truncal fat compared with controls. Levels of adiponectin did not correlate with either TNF-alpha or IL-6. Low levels of adiponectin were found in both lipodystrophic groups and were associated with current or previous treatment with stavudine. Furthermore, the adiponectin level correlated with the percentage of limb fat. Patients with lipodystrophy with fat accumulation were more insulin resistant, measured by HOMA-IR, compared with controls. However, HOMA-IR did no correlate to adiponectin or other cytokines. In conclusion, the finding of no difference between the two lipodystrophic groups with regard to adiponectin, indicates that low levels of adiponectin reflects fat atrophy, whereas the insulin resistance was best explained by increased truncal fat mass.     

Hypoadiponectinemia is Related to Sympathetic Activation and Severity of Obstructive Sleep Apnea

Study Objectives:

Hypoadiponectinemia is associated with cardiovascular morbidity and diabetes mellitus. We hypothesize that adiponectin may be downregulated in sleep apnea through various mechanisms, contributing to cardiometabolic risks. This study investigated the relationship between serum adiponectin and sleep disordered breathing and its potential determinants.

Design:

Cross-sectional study.

Subjects and setting:

Adult men without prevailing medical comorbidity from the sleep clinic in a teaching hospital.

Measurements & Results:

One hundred thirty-four men underwent polysomnography, with mean age of 43.9 (9.8) years, and median apnea-hypopnea index (AHI) of 17.1 (5.7, 46.6). Overnight urine samples for catecholamines and blood samples for analyses of insulin, glucose and adiponectin levels from fasting subjects were taken. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Magnetic resonance imaging was performed to quantify the amount of abdominal visceral fat. Serum adiponectin level, adjusted for age, body mass index, and visceral fat volume, was significantly lower in subjects with severe obstructive sleep apnea (AHI ≥ 30) compared with those with an AHI of less than 30: 4.0 (3.1, 5.4) versus 5.4 (3.6, 7.9) μg/mL, P = 0.039. After we adjusted for adiposity, adiponectin levels remained negatively correlated with AHI (P = 0.037), arousal index (P = 0.022), HOMA-IR/fasting insulin (P < 0.001), and urinary norepinephrine and normetanephrine (P < 0.008). In a multiple stepwise regression model, the independent determinants of adiponectin after adjustment for adiposity were HOMA-IR (P < 0.001) and urinary norepinephrine and normetanephrine (P = 0.037).

Conclusions:

Adiponectin was suppressed in subjects with severe obstructive sleep apnea, independent of obesity. Adiponectin levels were determined by insulin resistance and sympathetic activation, factors that may be totally or partially attributed to sleep disordered breathing.

Citation:

Lam JCM; Xu A; Tam S; Khong PL; Yao TJ; Lam DCL; Lai AYK; Lam B; Lam KSL; Ip MSM. Hypoadiponectinemia is related to sympathetic activation and severity of obstructive sleep apnea. SLEEP 2008;31(12):1721–1727.     

脂联素、核因子-kB在胰岛素抵抗大鼠表达

目的 观察炎症相关因子脂联素、核因子-kB（NF—kB）在胰岛素抵抗大鼠的表达。方法 20只Wistar大鼠随机分为空白对照组与胰岛素抵抗组，分别给予基础饮食和高糖高脂饮食8周，应用高血浆胰岛素-正常血糖钳夹技术证明胰岛素抵抗的存在。用全自动生化分析仪测定各组血脂、脂联素等，并应用免疫组化技术测定NF-kB在血管内皮细胞的表达。结果 ①应用钳夹技术证明，胰岛素抵抗组存在胰岛素抵抗，而空白对照组未出现胰岛素抵抗；②胰岛素抵抗组甘油三酯、胆固醇、低密度脂蛋白、高密度脂蛋白较空白对照组明显升高（P〈0．05），而保护性因子脂联素浓度则明显降低（P〈0．05）；③免疫组化显示，胰岛素抵抗组大鼠血管内皮细胞NF-kB阳性细胞百分率明显多于空白对照组（P〈0．05）；④脂联素浓度与NF—kB的表达呈明显负相关（r=-0．854，P〈0．05）；结论 胰岛素抵抗时，脂联素浓度降低，NF—kB过表达，二者呈明显负相关。     

Immunological characteristics and management considerations in obese patients with asthma

Obesity is associated with severe, poorly controlled asthma that does not respond as well to therapy as asthma in leaner asthmatics. Important insights gained from animal models of obesity and asthma suggests that different forms of obesity may lead to different manifestations of airway disease: obesity is associated with both innate increased airway reactivity and altered responses to aeroallergen and pollutant challenges. In humans, at least two broad groups of obese asthmatics have been recognized: one that is likely unique to obesity and another that is likely lean allergic asthma much complicated by obesity. This article will discuss what we have learned about the immunological and pathophysiological basis of asthma in obesity from animal and human studies, and how this might guide therapy.