Lifetime glycaemic exposure predicts reduced coronary vasoreactivity in Type 1 diabetic subjects.

AIMS: Subjects with Type 1 diabetes have impaired coronary vasoreactivity but the independent role of glycaemic control on myocardial perfusion is less clear. We examined the effect of lifetime glycaemic exposure on coronary vasoreactivity in 43 otherwise healthy Type 1 diabetic subjects. METHODS: Myocardial blood flow was calculated basally and during pharmacologically induced hyperaemia in the fasting state and during euglycaemic hyperinsulinaemic clamp (at an insulin infusion rate of 1 mU/kg per min for 60 min) using positron emission tomography and (15)O-water. Glycaemic exposure was estimated as glycosylated haemoglobin A(1c) (HbA(1c)) months. RESULTS: Hyperaemic myocardial blood flow was inversely associated with log HbA(1c) months in the fasting state (r = -0.72, P < 0.01) and during clamp (r = -0.35, P < 0.05). These correlations remained significant after adjustment for lipid values, blood pressures, sex, smoking, body mass index (BMI) and age (r = -0.70, P < 0.05 and r = -0.35, P < 0.05, respectively). No significant correlation was detected between hyperaemic flow and HbA(1c) or plasma glucose values measured immediately preceding the PET study. CONCLUSIONS: The present study demonstrates that the lifetime glycaemic exposure appears to be a better predictor of reduced coronary vasoreactivity than recent glycaemic control in Type 1 diabetic subjects. Reduced coronary vasoreactivity in diabetic subjects with poor glycaemic control and/or long duration of diabetes may represent an early precursor of coronary artery disease.     

Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes

We measured serum concentrations of advanced glycation endproducts (AGEs) in patients with type 2 diabetes, to elucidate the mechanisms underlying the elevated serum concentrations of AGEs and to clarify the relationship between serum AGE concentrations and the development of microangiography and macroangiopathy. Serum AGEs were significantly higher in diabetic patients than in age-matched control subjects (p < 0.0001). In diabetic patients, serum AGEs were positively correlated with HbA1c (r = 0.47, p < 0.0001), urinary albumin excretion (UAE) (r = 0.42, p < 0.0001), diabetes duration (r = 0.31, p = 0.0030), and fasting plasma glucose (r = 0.34, p = 0.0010). Multiple regression analysis disclosed that only the HbA1c and UAE levels independently correlated with serum AGE levels. Serum AGEs in diabetic patients with progressive retinopathy and overt nephropathy were significantly higher than in those with less severe retinopathy and nephropathy. Serum AGEs were significantly higher in the diabetic patients with coronary heart disease (CHD) than in those without CHD. These results suggest that the HbA1c and UAE levels are independent risk factors for increased serum AGE concentrations in type 2 diabetic patients, and that higher serum AGE concentrations are associated with increased severity of diabetic retinopathy and nephropathy. Serum AGE concentrations may be a useful marker not only for the severity of diabetic microangiopathy but also for the development of CHD in patients with type 2 diabetes mellitus. Received: 8 May 2000 / Accepted in revised form: 5 September 2000     

糖尿病合并冠心病患者血浆组织蛋白酶S和血小板反应蛋白-1浓度与心力衰竭的关系

目的探讨糖尿病合并冠状动脉粥样硬化性心脏病(冠心病)患者血浆组织蛋白酶S(cathepsin S,CatS)和血小板反应蛋白-1(thrombospondin-1,TSP-1)浓度与心力衰竭的关系。方法将浦东新区人民医院2016年9月至2019年1月间收治的197例糖尿病患者根据临床情况及冠状动脉造影检查结果院体检健康者80名为对照组。测定各组低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(highdensity lipoprotein cholesterol,HDL-C)、糖化血红蛋白(hemoglobin A1c,HbA1c)、总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、空腹血糖(fasting plasma glucose,FPG)、餐后2 h血糖(2 h postprandial blood sugar,2 hPBG)浓度、射血分数(ejection fraction,EF)、左心室舒张末期容积(end-diastolic volume,EDV)、左心室收缩末容积(end systole vol⁃ume,ESV)及血浆CatS和TSP-1浓度,并对两组相关指标进行比较和相关性分析。结果与对照组相比,合并组及单纯组患者ESV、EDV、HbA1c、LDL-C、FPG、2 hPBG、TC、TG、DBP、SBP显著升高,EF、HDL-C则明显下降,差异有统计学意义(P<0.05)。合并组与单纯组比较,除LDL-C、FPG、SBP比较差异无统计学意义(P>0.05)外,合并组ESV、EDV、HbA1c、HDL-C、2 hPBG、TC、TG及DBP均较单纯组高,EF较单纯组低,差异均有统计学意义(P<0.05)。单纯组及合并组CatS和TSP-1浓度高于对照组,差异有统计学意义(P<0.05);合并组CatS和TSP-1浓度明显高于单纯组,差异有统计学意义(P<0.05)。相关分析结果:TSP-1与LDL-C(r=0.453,P<0.01)、HbA1c(r=0.629,P<0.01)、HDL-C(r=0.435,P<0.01)、EDV(r=0.364,P<0.01)、ESV(r=0.408,P<0.01)呈正相关;与EF(r=-0.317,P<0.01)呈负相关。CatS与LDL-C(r=0.426,P<0.01)、HbA1c(r=0.530,P<0.01)、HDL-C(r=0.345,P<0.01)、EDV(r=0.380,P<0.01)、ESV(r=0.395,P<0.01)呈正相关;与EF(r=-0.465,P<0.01)呈负相关。结论糖尿病合并冠心病及心力衰竭患者血浆CatS和TSP-1浓度较单纯糖尿病患者高,可通过检测血浆CatS和TSP-1浓度来预测患者的心功能情况。     

Impairment of left and right ventricular longitudinal strain in asymptomatic children with type 1 diabetes

AimThe relationship between type 1 diabetes (T1DM) and cardiac function in children is not well established. The purpose of this study was to investigate whether children and adolescents with T1DM present early asymptomatic abnormalities of left ventricular (LV) and right ventricular (RV) function. In addition, we evaluated the relationship of any such abnormalities with glycemic control and diabetes duration.MethodsThis was a prospective study. Standard echocardiography, tissue Doppler imaging, and two-dimensional strain analysis were performed prospectively in 52 children with T1DM. The results were compared with those from 52 healthy children matched for age and sex.ResultsThere were no significant differences between the two groups in LV ejection fraction or RV systolic function. There was a difference between the two study groups in transtricuspid flow: the E-wave and A-wave velocities were significantly higher in the diabetic group. Left ventricular global longitudinal strain (LV GLS) was significantly lower in children with T1DM (?20.01 ± 1.86% vs. ?22.99 ± 0.98%, respectively; P < .001), as was RV free-wall longitudinal strain (RV FWLS) (?29.13 ± 1.85% vs. ?30.22 ± 1.53%, respectively; P = .002). LV GLS was correlated with diabetes duration (r = 0.444, P < .001) and glycated hemoglobin (HbA1c) (r = 0.683, P < .001); however, no correlation was found between RV FWLS and HbA1c or diabetes duration.ConclusionsOur findings suggest that LV GLS and RV FWLS are impaired in children with T1DM and that the decrease in LV GLS is correlated with diabetes duration and HbA1c levels.     

Child and parental mental ability and glycaemic control in children with Type 1 diabetes.

AIMS: Many psycho-social factors can affect the glycaemic control of children with Type 1 diabetes, but the influence of the intelligence of the child and their parents has not been reported. METHODS: Seventy-eight children and adolescents with Type 1 diabetes and their mothers performed standardized tests to assess psychometric intelligence. The children were aged (median (range)) 12.0 (5-17) years with duration of diabetes 5.0 (1.0-13.0) years and required an insulin dose of (mean +/- SD) 1.0 +/- 0.3 U/kg per day. The children completed the Wide Range Achievement Test 3 reading test (WRAT3) and Raven's Standard Progressive Matrices (RSPM). A mean annual HbA1c was calculated for each subject (8.6 +/- 1.4%). The mothers performed the National Adult Reading Test (NART) and provided details of the occupation of the main wage-earner in the family from which social class (SC) was derived. RESULTS: The HbA1c of the child correlated with their age (r = 0.26, P = 0.02), SC (Kendall's rank correlation, tau = 0.17, P = 0.03) and with the NART error score of their mother (r = 0.28, P = 0.01), but no correlation was observed with the child's WRAT3 or RSPM score. Stepwise regression revealed that age and NART error score were the strongest independent determinants of glycaemic control (total adjusted r2 = 0.117). CONCLUSIONS: Parental intelligence appears to have a significant influence on the glycaemic control of a child with Type 1 diabetes, accounting for 7.6% of the reliable variance in HbA1c.     

A randomized control trial of the effect of negotiated telephone support on glycaemic control in young people with Type 1 diabetes.

AIM: To evaluate changes in self-efficacy for self-management in young people with Type 1 diabetes participating in a "Negotiated Telephone Support" (NTS) intervention developed using the principles of problem solving and social learning theory. METHODS: One-year RCT with 79 young people (male 39; mean age +/- sd 16.5 +/- 3.2 years, duration 6.7 +/- 4.4 years, HbA(1c) 8.6 +/- 1.5%) randomized into: Group 1 (control group), continued routine management, n = 28; Group 2, continued routine management with NTS, n = 25; Group 3, annual clinic with NTS, n = 26. Outcome measures: HbA(1c), self-efficacy, barriers to adherence, problem solving, and diabetes knowledge. RESULTS: There were no differences between the groups at baseline. Participants in Groups 2 and 3 received an average of 16 telephone calls/year (range 5-19), median duration 9 min (2-30), with a median interval of 3 weeks (1-24) between calls. Significant correlations were found between age and average length of call (r = 0.44, P < 0.01) and frequency of contact (r = 0.36, P < 0.05). Social and school topics were discussed frequently. After 1 year, while the participants in the two intervention groups showed significant improvements in self-efficacy (P = 0.035), there was no difference in glycaemic control in the three groups. Barriers to insulin use adherence were a significant predictor of HbA(1c) (P < 0.001) after controlling for baseline. CONCLUSIONS: NTS is an effective medium to deliver a simple theory-based psychological intervention to enhance self-efficacy for diabetes self-management. Reduced clinic attendance, combined with NTS, did not result in a deterioration of HbA(1c). Intensive personal support needs to be combined with intensive diabetes therapy to improve glycaemic control in this age group.     

What is the relative contribution of blood glucose levels at different time points of the day to HbA1c in Type 1 diabetes?

AIMS: To evaluate the relative contribution of blood glucose levels at different time points of the day to HbA(1c) in Type 1 diabetes. METHODS: Consecutive home blood glucose records (n = 146) from 71 Type 1 diabetic patients who were on an intensive diabetes therapy programme were examined. Each home blood glucose record included six daily blood glucose profiles over 2 months. The relationship between glycaemic values at each time point and HbA(1c) measured at the end of each record period was analysed. RESULTS: Significant linear correlations were found between HbA(1c) and glycaemia at each time point of the day (ranged from 0.413 to 0.593), the strongest being with predinner glycaemia (r = 0.593; P = 0.000). Total daily glycaemia, mean preprandial and mean postprandial glycaemia were also significant and linearly correlated with HbA(1c) (r = 0.701; r = 0.686; r = 0.620, respectively; P < 0.0001). Multiple linear regression analysis showed that predinner, prebreakfast and post-breakfast glycaemia correlated significantly and independently with HbA(1c). The model accounted for 47.8% of the variance in HbA(1c). CONCLUSIONS: Our study shows that among individual time points, prebreakfast and predinner are those with more influence on HbA(1c) in Type 1 diabetes and, to a lesser extent, post breakfast. It also confirms that preprandial glycaemia better predicts overall glycaemic control in Type 1 diabetes than postprandial glycaemia.     

利拉鲁肽对2型糖尿病合并阻塞性睡眠呼吸暂停低通气综合征患者睡眠呼吸紊乱及微血管病变的影响

目的探讨胰高糖素样肽-1(GLP-1)类似物对2型糖尿病(T2DM)合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者睡眠呼吸紊乱及微血管病变的影响。方法选取2017年1月至2018年12月河南省人民医院内分泌科及睡眠中心239例T2DM住院患者为研究对象,进行多导睡眠图(PSG)监测及糖尿病微血管病变筛查,纳入患糖尿病微血管病变的T2DM合并OSAHS患者93例,其中利拉鲁肽治疗患者50例作为治疗组,常规降糖治疗患者43例作为对照组,比较两组治疗6个月前后体质指数(BMI)、腰围、糖化血红蛋白(HbA1c)、血压、血脂、尿酸、呼吸暂停低通气指数(AHI)等指标的变化及糖尿病微血管病变改善情况。两组间比较采用t检验、非参数秩和检验或χ2检验,评价各指标与AHI变化值的相关性采用偏相关分析、协方差分析,利拉鲁肽与糖尿病微血管病变改善的相关性采用Logistic回归分析。结果治疗后利拉鲁肽治疗组较对照组BMI、腰围、HbA1c、收缩压、AHI下降更显著[分别为(-1.85±2.46)比(0.02±0.46)kg/m2、(-3.24±10.34)比(-0.07±0.88)cm、(-0.83±0.55)%比(-0.06±0.40)%、(-7.92±14.16)比(-0.56±16.16)mmHg(1 mmHg=0.133 kPa)、(-3.16±3.52)比(0.5±1.54)次/h,t=2.159~7.703,均P<0.05],糖尿病周围神经病变改善比例更高[26.0%(13/50)比9.3%(4/43),χ2=4.315,P<0.05]。治疗后AHI变化值与BMI变化值、腰围变化值、HbA1c变化值呈正相关(r=0.238、0.232、0.317,均P<0.05),与年龄呈负相关(r=-0.21,P<0.05)。调整年龄、糖尿病病程、BMI、腰围、收缩压、HbA1c等因素后,利拉鲁肽与AHI变化值水平有关(F=8.155,P=0.005)。调整年龄、糖尿病病程、BMI、腰围、HbA1c、收缩压、AHI等因素后,多因素Logistic回归分析显示利拉鲁肽对糖尿病周围神经病变有改善作用(OR=3.426,95%CI:1.024~11.46,P=0.046)。结论利拉鲁肽治疗可能有改善T2DM合并OSAHS患者睡眠呼吸紊乱及糖尿病周围神经病变的作用,对糖尿病肾脏病变、糖尿病视网膜病变无影响。     

Insufficient adaptation of hypoglycaemic threshold for cognitive impairment in tightly controlled type 1 diabetes

It is well known that hypoglycaemic thresholds for hormones and symptoms occur at lower plasma glucose levels in patients with strict glycaemic control. However, whether the threshold for cognitive impairment also shifts is still an unresolved question. We studied 19 type 1 diabetic patients, including 8 with hypoglycaemia unawareness, aged 37.0 +/- 7.4 y.r., with diabetes duration 15.2 +/- 10.7 yr, and HbA1c 7.6 +/- 1.1%. Hypoglycaemic thresholds for hormones, symptoms, awareness and cognitive function using the 4-choice reaction time test (4RT), were measured every 30 min during a 150 min stepped 4.4 to 2.2 mM hypoglycaemic hyperinsulinemic clamp. We found that 4RT- accuracy deteriorated earlier than 4RT-time (3.2 and 2.7 mM, respectively, p<0.01), and that both correlated poorly with HbA1C before and after adjustment for age and diabetes duration (r=0.11, and 0.18, respectively). On the opposite, adrenaline, autonomic and neuroglycopenic symptoms, and awareness significantly correlated with HbA1c values (r=0.56, 0.70, 0.61, and 0.63, after adjustment, respectively). Furthermore, after allocating the patients into two subgroups according to HbA1c values (<8% n=12, and >=8% n=7), we found that, as opposed to other thresholds, accuracy and 4RT-time were minimally and not significantly influenced by glycaemic control, therefore exhibiting the smaller glucose thresholds shifts (- 0.2 and - 0.5 mM for accuracy and time, respectively, vs. 0.6 -0.8 for other thresholds). In conclusion: 1) the hypoglycaemic thresholds for cognitive dysfunction shift with strict glycaemic control, but not significantly and less than other thresholds, 2) as opposed to other reports, accuracy deteriorates earlier than speed during the 4RT test, and 3) these "maladapted" reactions may contribute to the higher risk for severe hypoglycaemia in subjects with tight glycaemic control.     

Plasma IL-6 concentration is inversely related to insulin sensitivity, and acute-phase proteins associate with glucose and lipid metabolism in healthy subjects

AIM: It has been shown that atherosclerosis is an inflammatory disease. Recent data suggest that inflammation precedes type 2 diabetes. Hence, we wanted to study the interrelationship between IL-6, insulin sensitivity, lipids and numerous acute-phase proteins. METHODS: Twenty-one healthy individuals [16 males/5 females, age 27.9+/-1.8 years, body mass index (BMI) 24.1+/-0.8 kg/m(2)] participated in the study. Each patient went through a 4-h hyperinsulinaemic (40 mU/m(2)/min) euglycaemic clamp and 4-h saline infusion. Blood samples were taken before and at the end of the infusions. RESULTS: Plasma interleukin (IL)-6 concentration correlated inversely with insulin sensitivity (M-value) (r=-0.49, p<0.05). Moreover, the plasma levels of IL-6 associated with c-peptide (r=0.49, p<0.05), fat% (r=0.43, p<0.05) and diastolic blood pressure (r=0.46, p<0.05). alpha-1-acid glycoprotein was related to HbA1(c) (r=0.47, p<0.05), insulin (r=0.55, p<0.01), diastolic blood pressure (r=0.58, p<0.01), systolic blood pressure (r=0.58, p<0.01) and triglycerides (r=0.58, p<0.01). Haptoglobin was correlated with insulin (r=0.46, p<0.05), total cholesterol (r=0.61, p<0.01), BMI (r=0.58, p<0.01), fat% (r=0.63, p<0.01) and lipid oxidation during clamp (r=0.43, p<0.05). Diastolic blood pressure decreased during the clamp (from 78.3+/-1.9 to 72.1+/-2.0 mmHg, p=0.001). Insulin infusion did not affect the serum levels of most acute-phase proteins. CONCLUSIONS: Our study suggests that low grade inflammation, as reflected by IL-6, A1GP and haptoglobin contributes to the regulation of insulin sensitivity, lipid metabolism and blood pressure in normal human physiology.     

Time course of specific AGEs during optimised glycaemic control in type 2 diabetes

BACKGROUND: Several advanced glycation endproducts (AGEs) are formed in the hyperglycaemic state. Although serum AGEs correlate with average glycaemic control in patients with type 2 diabetes and predict the development of complications, it is not known how serum AGEs change during optimisation of diabetes therapy. METHODS: We evaluated the change in serum levels of total AGE and the AGEs CML (Nepsilon-carboxymethyllysine) and MGHI (methylglyoxal-derived hydroimidazolone), as well as markers of endothelial function in 28 subjects with type 2 diabetes, who were poorly controlled on oral agents,before and after the institution of insulin therapy. RESULTS: Mean subject age (+/- SEM) was 58 +/- 2 years,body mass index 27.7 +/- 0.8 kg/m2, and known duration of diabetes was 8.1 +/- 0.9 years. With insulin treatment fasting blood glucose levels dropped from 12.1 +/- 0.9 mmol/l to 6.9 +/- 0.3 and 8.1 +/- 0.4 mmol/l after three and six months, respectively (both p<0.001), while HbA1c decreased from 10.0 +/- 0.3 to 7.8 +/- 0.2% (p<0.001). Endothelial function improved as indicated by a small but significant decrease in soluble intercellular cell adhesion molecule (sICAM-1) (152 +/- 10 to 143 +/- 8 ng/ml, p<0.02)and sE-selectin (111 +/- 16 to 102 +/-12 ng/ml, p<0.02)levels. In contrast, we observed only a tendency towards a decrease in CML levels (110 +/-22 to 86 +/- 13 microg/mg protein, p=ns), but a small increase of MGHI (from 0.23 +/- 0.02 to 0.29 +/- 0.04 U/mg protein, p<0.02). At baseline, 16 patients were on metformin, which is known to reduce methylglyoxal levels and reduce generation of reactive oxygen species. They had similar levels of CML and MGHI to the 12 non-metformin users, although their HbA1c was lower (9.4 +/- 0.3 vs 10.7 +/- 0.6 %). During insulin, patients receiving concomitant metformin therapy showed a similar course of CML and MGHI to those not taking metformin. CONCLUSION: Although insulin therapy improved HbA1c and markers of endothelial function, the levels of serum AGEs did not follow the same time course. This suggests that these specific AGEs are influenced by other factors in addition to overall glycaemia, such as oxidative stress.     

社区2型糖尿病患者HbA1c水平与营养状况的关系研究

目的 探讨社区2型糖尿病患者HbA1c与营养状况的关系.方法 将219例社区2型糖尿病患者以HbA1c水平分为2组,HbA1c<6.5%组108例、HbA1c≥6.5%组111例.分别比较两组的血压、血糖、血脂和胰岛素抵抗指数水平,以及膳食结构和营养素摄入情况.结果 (1)社区2型糖尿病患者HbA1c<6.5%者占49.32%;(2)HbA1c与空腹血糖、餐后血糖、稳态模型评估的胰岛素抵抗指数(HOMA-IR)水平呈正相关(r分别为0.56、0.49、0.20,P<0.05或P<0.01),与高密度脂蛋白胆同醇呈负相关(r=-0.16,P<0.05);(3)营养素摄入量与HbA1c的关系表现为:能量、碳水化合物、蛋白质和总脂肪是影响HbA1c的独立相关因素(均P<0.05);(4)与≥6.5%组相比,HbA1c<6.5%组摄入较多水果.≥6.5%组纯能量类食物摄入过多,且蛋白质、总脂肪和饱和脂肪酸摄入量多于HbA1c<6.5%组(P<0.05);(5)拟合线性回归模型发现:摄入较多粗粮杂豆、水果分别使HbA1c均值降低0.36%(P<0.10)、0.46%(P<0.01);适量减少畜肉、油脂摄入量平均使HbA1c降低0.42%(P<0.05)、0.37%(P<0.10).结论 目前社区2型糖尿病患者HbA1c<6.5%者比例不高,HbA1c<6.5%者与HbA1c>≥6.5%者的营养状况差异明显,饮食对HbA1c的影响较大,因此应对2型糖尿病患者进行合理的饮食治疗,尽早实现糖尿病控制达标.     

Skin Advanced Glycation End Product Accumulation Is Poorly Reflected by Glycemic Control in Type 2 Diabetic Patients (ZODIAC-9)

Background

Glycemic memory can be reflected by tissue accumulation of advanced glycation end products (AGEs). In type 1 diabetes mellitus (T1DM) patients, hemoglobin A1c (HbA1c) levels over various time periods poorly predicted the accumulation of different AGEs in skin biopsies. Our aim was to investigate whether HbA1c assessments can predict the change in skin AGEs during time in type 2 diabetes mellitus (T2DM).

Methods

We included 452 T2DM patients participating in a shared-care setting, who are screened annually for HbA1c and diabetic complications. Baseline and follow-up levels of skin AGEs were assessed with a validated noninvasive autofluorescence (AF) method, which is based on the fluorescence characteristics of certain AGEs.

Results

Our study population had a mean age of 65 years and 54% were female. After a mean follow-up duration of 3.3 years, linear regression analyses showed weak relationships among different assessments of HbA1c (baseline, maximum, mean, and variance of HbA1c) and skin AF at follow-up. Baseline skin AF and age were predictors of skin AF at follow-up, but diabetes duration, smoking, and creatinine were of less or no predictive value for skin AF at follow-up.

Conclusions

In our T2DM population, integrated HbA1c assessments over years poorly predict the change in skin AGE level measured by skin AF. These findings agree with results in patients with T1DM. This suggests either the need for longer exposure to glucose disturbances to change tissue AGEs or other mechanisms, such as oxidative stress, leading to AGE accumulation.     

Glycaemic control, disease duration and beta-cell function in patients with Type 2 diabetes in a Swedish community. Skaraborg Hypertension and Diabetes Project.

AIMS: To examine determinants for glycaemic control in primary care patients with Type 2 diabetes. METHODS: In a community-based surveillance of primary care patients with Type 2 diabetes, 190 men and 186 women were consecutively identified and examined for cardiovascular risk factors. Insulin resistance and beta-cell function were estimated using homeostasis model assessment (HOMA). Good glycaemic control was defined as HbA(1c) < 6.5%. RESULTS: Following adjustment for age and gender, HbA(1c) > or = 6.5% was associated with duration of diabetes (10.6 vs. 6.4 years, P < 0.001), lower levels of serum insulin (6.3 vs. 8.0 mU/l, P = 0.012), higher serum triglyceride levels (2.0 vs. 1.7 mmol/l, P = 0.002) and impairment of beta-cell function (HOMA index 19.5 vs. 45.8, P < 0.001). The association between HbA(1c) levels and duration remained with adjustment for age, gender, waist-hip ratio (WHR) and serum triglycerides (odds ratio (OR) for HbA(1c) > or = 6.5% by 5 years diabetes duration = 1.7; 95% confidence interval (CI) 1.4--2.1) but was lost following additional adjustment for beta-cell function (OR for HbA(1c) > or = 6.5% = 1.3; 95% CI 0.96-1.7). In a separate linear regression with beta-cell function as the dependent variable there was a significant association with HbA1c after adjustments for differences in age, gender, WHR, serum triglyceride levels and diabetes duration (P < 0.001). CONCLUSIONS: Increasing HbA1c by time was associated with declining beta-cell function.     

Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects

Dipeptidyl peptidase (DPP-IV) rapidly metabolizes hormones such as glucagon-like peptide-1(7-36)amide. This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. Blood samples were collected from type 2 diabetic patients in three main categories: good glycaemic control (HbA(1c) <7%, upper limit of non-diabetic range), moderate glycaemic control (HbA(1c) 7-9%) and poor glycaemic control (HbA(1c) >9%). Age- and sex-matched non-diabetic subjects were used as controls. Circulating DPP-IV activity of healthy control subjects was 22.5+/-0.7 nmol/ml/min (n=70). In the combined groups of type 2 diabetic subjects, circulating DPP-IV activity was significantly decreased at 18.1+/-0.7 nmol/ml/min (p<0.001, n=54). DPP-IV activity was negatively correlated with both glucose (p<0.01) and HbA(1c) (p<0.01) in this population. Furthermore, DPP-IV activity was reduced 1.2-fold (p<0.01, n=25), 1.3-fold (p<0.001, n=19) and 1.3-fold (p<0.05, n=10) in good, moderate and poorly controlled diabetic groups, 18.7+/-1.0, 17.4+/-1.4 and 18.0+/-1.5 nmol/ml/min, respectively. Degradation of GLP-1 by in vitro incubation with pooled plasma samples from healthy and type 2 diabetic subjects revealed decreased degradation to the inactive metabolite, GLP-1(9-36), in the diabetic group. These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. DPP-IV enzyme activity appears to be depressed in response to poor glycaemic control.     

The association of serum total sialic acid/total protein ratio with diabetic parameters in young type 1 diabetic patients

Abstract Sialic acid is a terminal component of the non-reducing end of carbohydrate chains of glycoproteins and glycolipids. The purpose of this study was to estimate serum total sialic acid (TSA) concentrations and serum TSA/serum total protein (TP) ratios in young type 1 diabetic subjects and to investigate their association with diabetes-related parameters in that population. Twentyfour young type 1 diabetic patients and 20 healthy controls were enrolled in this study. Serum TSA and serum TSA/TP ratio were measured in both groups. Moreover, we looked for correlation among serum TSA, serum TSA/TP ratio and clinically relevant parameters such as urinary albumin excretion, blood pressure, diabetes duration, HbA1c, daily insulin dose, serum lipids and magnesium in type 1 diabetic patients. Serum TSA concentrations and serum TSA/TP ratio showed no statistical difference between patients and controls (p>0.05). While serum TSA concentrations only correlated with urinary albumin excretion (r=0.44, p=0.028), serum TSA/TP ratio correlated with diastolic blood pressure (r=0.48, p=0.015), diabetes duration (r=0.46, p=0.022) and urinary albumin excretion (r=0.53, p=0.007) in the diabetic subjects. We concluded that serum TSA/TP ratio might be a better indicator than serum TSA as an index of diabetic complications.     

Relationship between proinsulin-to-insulin ratio and advanced glycation endproducts in Japanese type 2 diabetic subjects

OBJECTIVE: Type 2 diabetes (T2DM) is characterized by increased proinsulin-to-insulin ratio (P/I ratio), increased glycation and oxidative stress, and beta-cell dysfunction. Previous reports implicated that increased P/I ratio, glycation and oxidative stress constitute markers of beta-cell dysfunction in T2DM. However, its clinical relevance remains to be elucidated. Therefore, in the present study we investigated the relationship between the P/I ratio, glycation and oxidative stress markers in patients with T2DM, using newly developed intact chemiluminescent immunoassay for proinsulin. METHODS: Fasting intact proinsulin, insulin, advanced glycation endproducts (AGEs), pentosidine, lipid peroxide and urine 8-isoprostane as well as other metabolic parameters were measured in 64 T2DM subjects. RESULTS: Using univariate analysis, P/I ratio showed significant positive correlations with plasma glucose (r=0.465), HbA1c (r=0.434) and AGEs (r=0.282), and significant negative correlations with insulin (r=-0.330) and HOMA-beta (r=-0.520) even after adjustment for age, sex, duration of diabetes, family history of diabetes, use of sulfonylureas, smoking and body mass index. Additionally, stepwise multiple regression analysis revealed that HOMA-beta, HbA1c and AGEs were independently and significantly correlated with P/I ratio. CONCLUSION: These findings suggest that not only hyperglycemia per se but also glycation is involved in beta-cell dysfunction in T2DM subjects.     

Tumour necrosis factor-alpha plasma level in patients with type 1 diabetes mellitus and its association with glycaemic control and cardiovascular risk factors

OBJECTIVES: Diabetic patients reveal a significant increase in their cardiovascular risk. Beside glycaemic control and management of established risk factors, determination of cytokines, like serum levels of tumour necrosis factor-alpha (TNF-alpha), might offer a tool to determine patients at high risk. The cytokine TNF-alpha reveals a complex relationship with diabetes. It is involved in beta-cell damage leading to type 1 diabetes, causes insulin resistance associated with obesity and is of influence in the formation of atherosclerotic vascular lesions. We were interested in the possible association of this cytokine with metabolic control and cardiovascular risk factors in patients with type 1 diabetes. DESIGN AND SUBJECTS: TNF-alpha plasma levels were determined in 44 outdoor patients (15 women, 29 men) with type 1 diabetes mellitus (mean duration 11.2 +/- 8.7 years) and in 24 healthy controls by use of a solid phase enzyme amplified sensitivity immunoassay (TNF-alpha ELISA, Biosource Fleurus, Belgium). None of our study participants suffered from inflammatory or other concurrent diseases. Relationships between variables were evaluated by non-parametric Spearman correlation coefficients. RESULTS: TNF-alpha plasma levels were significantly higher in diabetic patients (19.3 +/- 7.5 pg mL-1) than in non-diabetic subjects (11.1 +/- 5.8 pg mL-1; P < 0. 023), and revealed a significant positive correlation with glycated haemoglobin (HbA1c) (r = 0.43; P < 0.004) and fructosamine (r = 0. 31; P < 0.049) values, and a negative correlation with HDL cholesterol (r = -0.36; P < 0.018) and apoAI-levels (r = -0.37; P < 0.015). These relationships could be observed in patients with a duration of diabetes for more than 5 years, as well as in patients with a shorter duration of diabetes. In the male group, TNF-alpha plasma levels revealed a significant positive correlation with plasma levels of thiobarbituric acid reacting substances (r = 0.61; P < 0.001). Plasma levels of thiobarbituric acid reacting substances showed a positive correlation with the duration of diabetes (r = 0. 58; P < 0.008), as well as with the serum levels of the vascular adhesion molecules intercellular adhesion molecule (ICAM) (r = 0.34; P < 0.051) and vascular cell adhesion molecule (VCAM) (r = 0.30; P < 0.052). CONCLUSIONS: Our data indicate that TNF-alpha plasma levels are increased in type 1 diabetes mellitus and reveal a significant association with metabolic long-term control parameters, HbA1c and fructosamine for glycaemic control, and HDL cholesterol for triglyceride metabolism, as well with lipid peroxidation.     

Detection of left ventricular asynchrony and its relationship with the Tei index in patients with coronary artery ectasia

OBJECTIVE:

To evaluate left ventricular (LV) systolic asynchrony and its relationship with the Tei index using tissue Doppler imaging (TDI); and to evaluate the relationship of thrombolysis in myocardial infarction frame count (TFC) and Tei index with LV asynchrony in patients with coronary artery ectasia (CAE).

METHODS:

A total of 50 CAE patients and 40 control subjects were evaluated. Diagnosis of CAE was made angiographically and TFC was calculated. LV systolic and diastolic function was assessed by conventional echocardiography and TDI. Evaluation of intra-LV systolic asynchrony was performed using tissue synchronization imaging (TSI).

RESULTS:

In patients with CAE, the Tei index was significantly higher than in controls (0.63±0.12 versus 0.52±0.12; P<0.001). LV systolic asynchrony parameters of TSI including SD of the peak tissue velocity (Ts) of the 12 LV segments (Ts-SD-12), maximal difference in Ts between any two of the 12 LV segments (Ts-12), SD of the Ts of the six basal LV segments (Ts-SD-6), maximal difference in Ts between any of the six basal LV segments (Ts-6) were significantly lengthened in patients with subclinical hypothyroidism compared with controls (P<0.001, P<0.001, P<0.001 and P<0.001, respectively). In addition, a positive correlation was found between Ts-SD-12 and the Tei index in patients with CAE (r=0.841; P<0.001) and mean TFC was positively correlated with Ts-SD-12 and the Tei index (r=0.345; P=0.013 and r=0.291; P=0.021, respectively).

CONCLUSION:

Patients with CAE exhibit evidence of LV systolic asynchrony according to TSI. LV systolic asynchrony is related to the Tei index and mean TFC. Furthermore, the Tei index is an independent risk factor for LV systolic asynchrony.     

2型糖尿病伴冠心病患者平均血小板体积的影响因素研究

目的:研究血糖和血脂等对合并2型糖尿病(DM)冠心病患者平均血小板体积(MPV)的影响。方法:冠状动脉造影等确诊的无糖代谢异常冠心病患者(非DM组)115例,合并DM的冠心病患者(DM组)183例,测定外周血MPV等血小板参数和其他常规实验室指标,分析合并DM冠心病患者MPV的变化及血糖和血脂等对MPV的影响。结果:MPV于DM组显著高于非DM组[(10.30±0.88)vs.(10.04±1.03)fL,P<0.05];DM组患者各亚组间比较,肥胖亚组显著高于非肥胖亚组[(10.51±0.77)vs.(10.21±0.91)fL,P<0.05],既往DM亚组显著高于新诊断DM亚组[(10.41±0.88)vs.(10.14±0.85)fL,P<0.05],HbA1c高值(HbA1c≥7%)亚组显著高于HbA1c低值(HbA1c<7%)亚组[(10.47±0.76)vs.(10.16±0.94)fL,P<0.05];MPV分别与体质量指数(BMI)(r=0.149,P=0.044)、空腹血糖(FBG)(r=0.191,P=0.009)、HbA1c(r=0.189,P=0.01)、hs-CRP(r=0.146,P=0.048)和白细胞计数(WBC)(r=0.169,P=0.022)显著正相关,与HDL-C显著负相关(r=-0.143,P=0.053);多元回归分析显示,对MPV有独立影响的因素是HDL-C、HbA1c、hs-CRP和FBG(均P<0.05)。结论:DM冠心病患者MPV进一步升高,MPV的升高与HDL-C、HbA1c、hs-CRP和FBG有密切关系。