肥胖和高血压患者餐后甘油三酯代谢异常与胰岛素抵抗的关系

目的　探讨高血压病与肥胖患者餐后甘油三酯 (TG)代谢异常与胰岛素抵抗的关系。方法　 19例健康人 ,19例单纯肥胖患者 ,2 1例高血压非肥胖患者 ,2 3例高血压合并肥胖患者禁食 12h后 ,进行标准脂肪负荷试验 ,以TG 8h曲线下面积 (TG AUC)和TG峰反应 (TGPR)作为标准脂肪负荷后TG反应水平的指标。以胰岛素敏感性指数 (ISI)及胰岛素曲线下面积 (IS AUC)作为胰岛素敏感性的判定指标。结果　 (1)高血压合并肥胖、高血压非肥胖、单纯肥胖组TG AUC ,TGPR均显著高于正常组 [TG AUC分别为 :(2 4 5 1± 10 6 8)mmol/L、(17 5 8± 7 6 8)mmol/L、(15 2 6± 4 93)比 (8 74± 2 34)mmol/L ,P <0 0 5 ;TGPR分别为 :(5 2 1± 2 2 7)mmol/L、(3 4 6± 1 82 )mmol/L、(3 0 2± 1 0 1)比 (1 5 4±0 5 6 )mmol/L ,P <0 0 5 ],高血压合并肥胖组TG AUC ,TGPR显著高于高血压非肥胖和单纯肥胖组 (P<0 0 1) ,高血压非肥胖组与单纯肥胖组之间无显著性差异。 (2 )高血压合并肥胖、高血压非肥胖、单纯肥胖组ISI(绝对值 ) ,IS AUC均显著高于正常组 ,高血压合并肥胖组IS AUC ,ISI显著高于高血压非肥胖和单纯肥胖组 (P <0 0 1) ,高血压非肥胖组与单纯肥胖组之间无显著性差异。 (3)高血压合并肥胖、高血压非肥胖和肥胖组中具     

Maximal post-prandial triglyceride increase reflects post-prandial hypertriglyceridaemia and is associated with the insulin resistance syndrome.

AIMS: To assess the value of maximal post-prandial triglyceride increase after a high fat, low carbohydrate (CHO) test meal, as index of post-prandial hypertriglyceridaemia and its relation with insulin resistance. METHODS: Fifty non-diabetic subjects, 22 male and 28 female, aged 52.1+/-4.5 and 56.9+/-3.8 years, were studied. Glucose, insulin and triglycerides were measured fasting and 1, 2, 3 and 4 h after a meal consisting of 40 g fat, 19 g protein and 10 g CHO. Insulin resistance was calculated according to the HOMA model. RESULTS: The maximal triglyceride increment occurred during the 4th hour. Its absolute value (delta-TG) and the per cent increase over the fasting value (PTI), were considered appropriate for the evaluation of the post-prandial triglyceride response. Both delta-TG and PTI were strongly correlated with triglycerides incremental area in males and females, r = 0.797 and r = 0.700, P<0.01 and r = 0.805 and r = 0.774, P<0.001, respectively, and thus they can be used as indices of the post-prandial triglyceride response. No correlation was found between fasting triglyceride and triglyceride incremental area or delta-TG. Thus, post-prandial hypertriglyceridaemia can occur irrespectively of the fasting triglyceride concentrations. A weak correlation was found between PTI and insulin resistance in females, r = 0.384, P<0.05, but not in males, r = 0.224, P>0.05. However further analysis by quartiles of PTI showed similar insulin resistance levels in the first three quartiles and a significant increase in the 4th, both for males and females, 4th vs. 3rd quartile 7.4+/-3.6 vs. 2.2+/-0.7 and 6.4+/-2.4 vs. 2.2+/-0.6, respectively. The 4th quartile corresponds to a PTI > or =80%. CONCLUSIONS: PTI after the high fat, low CHO test meal used, consistently reflects post-prandial hypertriglyceridaemia, is easily measured and it is not predicted by fasting triglycerides. A PTI > or = 80% is associated with a significant increase of insulin resistance, and might therefore be considered the cut-off point for an abnormal post-prandial hypertriglyceridaemic response, at least in relation with insulin resistance. Such response could be added to the abnormalities of the insulin resistance syndrome, as an independent parameter.     

新诊断2型糖尿病病人脂代谢紊乱状态与胰岛素抵抗及胰岛素分泌缺陷

目的 观察新诊断的2型糖尿病病人脂代谢紊乱状态与胰岛素抵抗及胰岛素分泌缺陷的关系。方法 143例新诊断的2型糖尿病病人，根据美国ATP Ⅲ标准分为血脂正常组，高甘油三酯组、高胆固醇组、混合性高脂组，应用稳态模型评估法评价胰岛素敏感性及胰岛B细胞功能，探讨各种类型的脂代谢紊乱与胰岛素抵抗及胰岛素分泌缺陷的关系。结果 新诊断的2型糖尿病病人血脂紊乱发生率为56．6％，高甘油三酯组的HOMA-IR较正常组显著升高。各组HOMAp无显著差别。结论 新诊断的2型糖尿病病人脂代谢紊乱类型以高TC／LDL最常见，但高TG者的胰岛素抵抗程度更为严重。     

Association of plasma cholinesterase and triglyceride level in patients with newly diagnosed type 2 diabetes

<正>Objective To investigate the relationship of plasma cholinesterase(ChE) with triglyceride(TG) levels in newly diagnosed patients with type 2 diabetes(T2DM).Methods Clinical data and biochemical parameters of 321 patients with newly diagnosed T2DM admitted to the Department of Endocrinology of People’s Hospital of Shanghai Putuo from January 2018 to June 2020 were retrospectively collected.     

Hepatic insulin responsiveness in patients with endogenous hypertriglyceridaemia

Summary Plasma insulin response to oral glucose, insulin resistance, and insulin suppression of hepatic glucose production were studied in 11 normal subjects and 11 hypertriglyceridaemic patients. Patients with hypertriglyceridaemia had a significantly higher insulin response to oral glucose. Insulin resistance was also significantly greater in hypertriglyceridaemic subjects as determined by measuring the steady-state plasma glucose response during a continuous infusion of epinephrine, propranolol, glucose, and exogenous insulin. Insulin suppression of hepatic glucose production was calculated from the results of two studies in which glucose turnover rate was measured by a continuous infusion of³H-2-glucose. The first study was performed under conditions of basal insulin secretion, and the second carried out at steady state exogenous insulin levels of approximately 100 U/ml. The results indicated that basal hepatic glucose production was the same in both groups, and was suppressed to an equal degree by physiological levels of insulin. These data demonstrate that hepatic glucose production can be suppressed to an equal degree in normal and hypertriglyceridaemic subjects at comparable circulating insulin levels, at the same time that resistance to insulin-stimulated glucose uptake is observed in the hypertriglyceridaemic individuals.     

老年高血压患者的胰岛素抵抗

目的探讨高胰岛素血症、胰岛素抵抗、高血脂和肥胖与老年人高血压之间的关系。方法对无糖尿病和糖耐量减低史的老年原发性高血压患者５０例、老年健康对照组１７８例的空腹血糖、胰岛素、血脂、体重指数和胰岛素敏感性指数等进行对比。结果高血压组胰岛素为１８０±１９５ｍＵ／Ｌ，对照组为７７±５４ｍＵ／Ｌ（Ｐ＜０００１），高血压组有明显的高胰岛素血症，其胰岛素敏感性指数亦显著降低（Ｐ＜０００１），血清甘油三酯明显增高和ａｐｏＡ１明显下降（Ｐ＜００５），肥胖者占７０％。结论老年高血压患者同时存在糖代谢和脂蛋白代谢异常，胰岛素抵抗所产生的高胰岛素血症为其基本的代谢异常。     

原发性高血压伴微量蛋白尿患者胰岛素抵抗性研究

目的 :研究原发性高血压 (EH)并发微量蛋白尿患者的胰岛素抵抗 (IR)状态。方法 :根据尿白蛋白排泄率将EH患者分为两组 :微量蛋白尿阳性组 (4 0例 )和微量蛋白尿阴性组 (35例 ) ,计算体重指数 (BMI)、腰臀比值 (WHR) ,空腹采血测血糖 (FBG)、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和空腹胰岛素(FINR)水平。按HOMA模型计算胰岛素抵抗指数 (HOMA IR) ,HOMA IR =(FBG×FINR) / 2 2 .5 ,再取其自然对数。两组进行比较。结果 :患者年龄、性别比例、高血压病程、血压水平和FBG、血脂水平在两组间差异均无显著性意义 (P >0 .0 5 ) ,但BMI、WHR、FINR和HOMA IR在微量蛋白尿阳性组显著高于阴性组 (P <0 .0 5 )。结论 :EH微量蛋白尿阳性患者存在明显的IR ,高血压肾病的发生与EH患者的胰岛素敏感状态密切相关。BMI、WHR可作为IR的初筛指标     

Relationship between serum CTRP6 level and insulin resistance in patients with newly diagnosed type 2 diabetes mellitus

<正>Objective To explore the relationship between serum C1q and tumor necrosis factor related protein 6 (CTRP6)level and insulin resistance in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods A total of 167 patients with newly diagnosed T2DM in the outpatient department of our hospital were recruited from April2016 to March 2017 and 165 subjects with normal glucose tolerance were used as the control group.The concentrations of CTRP6,interleukin 6 (IL-6),monocyte che-     

Antibody response to insulin in children and adolescents with newly diagnosed Type 1 diabetes

Aims To compare levels of insulin antibodies in children and adolescents after initiation of insulin therapy using either insulin aspart (IAsp) or human insulin (HI) in combination with Neutral Protamine Hagedorn (NPH) insulin, and to investigate the relationships between insulin antibodies and HbA_1c and insulin dose. Methods IAsp‐specific antibodies (IAsp‐Ab) and antibodies cross‐reacting with HI and IAsp (HI‐cross‐Ab) were analysed by radioimmunoassay at diagnosis of diabetes and every 3–6 months for 30 months. Seventy‐two patients (HI = 30, IAsp = 42) with Type 1 diabetes, aged 2–17 years were included. Data on HbA_1c, insulin dose and serious adverse events (SAEs) were collected retrospectively. Results IAsp‐Ab levels remained low throughout the study. After 9 months, the level of HI‐cross‐Ab increased [mean (sd ) HI, 48.8% (21.53); IAsp, 40.2% (17.92)] and remained elevated. Repeated measurement analysis of HI‐cross‐Ab levels showed no significant difference between treatments (P = 0.16). HI‐cross‐Ab were significantly associated with total insulin dose (U/kg) (P = 0.001) and time (P < 0.0001), but not with HbA_1c (P = 0.24). Mean (± sd ) HbA_1c was similar at diagnosis (HI 9.5 ± 1.97%; IAsp 9.6 ± 1.62%); HbA_1c then decreased and stabilized to about 6.0% in both groups. Few SAEs were reported, the majority being hypoglycaemic episodes. Conclusions Treatment with IAsp and with HI was associated with an increase in HI‐cross‐Ab in insulin‐naive children, but this did not influence treatment efficacy or safety. These results support the safe use of IAsp in children and adolescents with Type 1 diabetes.     

胰岛素对初发2型糖尿病患者胰岛β细胞功能和胰岛素抵抗的影响

目的观察胰岛素对初发2型糖尿病患者胰岛β细胞功能和胰岛素抵抗的影响。方法将120例空腹血糖≥11．1mmol／L的初发2型糖尿病患者随机分为胰岛素组、格列齐特组、二甲双胍组和吡格列酮组，在饮食及运动治疗的基础上，给予不同的药物治疗3个月，比较各组治疗前后空腹血糖（FBG）、餐后2h血糖（PBG2h）、糖化血红蛋白（HbAlc）、胰岛素糖负荷后曲线下面积（AUCi）、C肽糖负荷后曲线下面积（AUCcp）、胰岛素分泌指数（Homa-β）和胰岛素抵抗指数（Homa-IR）的变化。结果12W治疗后，胰岛素组的胰岛素AUC0-30min、C肽AUC0-30min、Homa-β水平均高于3个口服降糖药组，差别具有统计学意义（P〈0．05）；且在治疗后胰岛素组的Homa—IR低于格列齐特组（P〈0．05），而与二甲双胍组和吡格列酮组无显著性差异。结论对初发2型糖尿病患者，早期胰岛素治疗比常规的口服降糖药可更好地改善胰岛β细胞功能和胰岛素抵抗。     

Accumulation of microvascular target organ damage in newly diagnosed hypertensive patients

Early identification of hypertensive target organ damage (TOD) emerges as important for global cardiovascular risk assessment. Retinal vascular alterations, capillary rarefaction, and microalbuminuria represent different forms of microvascular TOD. However, data regarding their concomitant presence in the early stages of hypertension, the association of the number of affected organs with cardiovascular risk, and aldosterone effect on multiple TOD are lacking. We studied naïve, never-treated patients with recent duration of hypertension and healthy volunteers. Innovative software was developed to estimate retinal vascular diameters and capillary density. Biochemical parameters including microalbuminuria and serum aldosterone were derived. Framingham Risk Score was used to determine cardiovascular risk. In total 103 subjects, 66 hypertensives and 37 normotensives, were included. Hypertensive patients exhibited a greater number of affected target organs compared with normotensives (P = .014), with retinopathy and capillary rarefaction (40.9%) representing the most common TOD among hypertensives. The number of affected organs was linearly correlated with increased Framingham score and serum aldosterone, analyzed with univariate (P < .001 and P = .002) and multivariate analysis (P = .025 and P = .004), respectively. Physicians dealing with hypertensive patients should be aware of the possibility of diffuse microvascular impairment and seek multiple TOD even in the early stages of hypertension.     

416名新诊断的中老年2型糖尿病患者胰岛素抵抗及胰岛素敏感性表征的分析

目的　比较新诊断的老年2型糖尿病(T2DM)患者与中年糖尿病患者胰岛素抵抗(IR)及胰岛素敏感性表征的异同点。　方法　将416 名 40 岁以上新诊断的 T2DM患者分为两组, 其中40~60岁(中年组)222例,60岁以上(老年组)194 例。分别测量血压(BP)、体质指数(BMI)、腰臀比(WHR)、检测糖化血红蛋白(HbA1c)、口服葡萄糖耐量试验、胰岛素分泌曲线、尿白蛋白及低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL C)等。按HOMA IR和HOMA βcell公式,计算糖负荷 30 min净增胰岛素/净增葡萄糖比值。　结果　初诊的老年T2DM患者与中年患者相比,其WHR、收缩压明显较高(P<0.05~0.01),而 BMI、葡萄糖刺激 2 h后的胰岛素分泌明显较低(P<0.05~0.01),同时空腹血浆TC、TG、LDL C、HDL C的水平也明显低于中年组(P均<0.01)。老年组有较高的胰岛素抵抗指数(P<0.05)和较低的β细胞分泌指数(P<0.01)及初期分泌指数(P<0.01)。　结论　与中年发病的糖尿病患者相比,老年糖尿病患者存在明显的 IR及胰岛素分泌缺陷,其 IR的主要表征为中心型肥胖、高血压、微量白蛋白尿。     

Evaluation of multidrug resistance in 46 newly diagnosed patients with acute leukemia

Abstract

Objectives

The aim of the present study was to assess the expression profile of multidrug resistance (MDR)-related proteins ABCB1, ABCC1 and LRP in 46 patients with acute leukemia (AL).

Methods

The levels of MDR gene mRNA expression and protein expression at diagnosis were analyzed by semi-quantitative PCR and flow cytometry, respectively.

Results

In the adult group, higher expression levels of abcc1 gene were associated with older age and lower levels of lactate dehydrogenase (LDH). In the pediatric group, abcc1 gene expression levels were associated with higher CD34 expression and a higher ABCB1 protein expression was correlated with high WBC counts.

Discussion/Conclusion

The present data indicate that abcb1 gene overexpression may be associated with a poor prognosis in adults with AL and that ABCB1 and abcc1 expression correlates with different prognostic factors in pediatric patients with AL. Our findings demonstrate that the method of choice to evaluate chemotherapy resistance-related proteins is a major variable.     

Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects

Summary Insulin-dependent diabetes mellitus (IDDM) is the result of a T-cell mediated autoimmune beta-cell destruction,which is accompanied by autoantibodies. We analysed the cellular and humoral immune response to insulin and insulin peptides in patients with recent-onset IDDM, IDDM patients treated with insulin, non-diabetic first degree relatives and unrelated control subjects. There were no differences in T-cell reactivity to whole insulin or insulin peptides in general between age-matched groups of IDDM patients, relatives or healthy control subjects. In contrast to investigations in NOD mice, no immunodominant or disease-specific insulin peptide could be identified. Surprisingly, a positive correlation of T-cell responses to insulin with age was noted (p < 0.005). This resulted in an inverse relation of insulin autoantibodies (IAA) and insulin reactive T-cells (p < 0.001) together with the well-described negative correlation of IAA with age. Interestingly, insulin-treated patients differed from age-matched recent-onset IDDM patients: first, simultaneous immune recognition of insulin with T-cells and IAA was only seen in patients treated for 6 months with insulin; second, insulin-treated patients rarely responded to whole insulin; third, they displayed less determinant spreading, and finally, recognition of multiple insulin peptides was not accompanied by crossreactivity to whole insulin. These distinct observations in insulin-treated IDDM patients, together with the inverse correlation between humoral and cellular responses to insulin, may result from activation or modulation of different T-cell subsets, and may be of relevance to insulin therapy trials, in which selective activation of non-destructive T-cell subsets may be a key to successful intervention. [Diabetologia (1997) 40: 564–572] Received: 11 November 1996 and in revised form: 14 January 1997     

The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia

Summary Using I¹³¹ VLDL selectively labelled in the B-apoprotein and I¹²⁵ LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72–83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21–28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls.