Predictors of mortality in patients with type 2 diabetes with or without diabetic nephropathy: a follow-up study

OBJECTIVE: To evaluate the prognostic significance of cardiovascular risk factors including 24-h ambulatory blood pressure level and rhythm for all-cause mortality in type 2 diabetic patients. METHODS: In a prospective observational study, 104 patients with type 2 diabetes were followed: 51 patients with diabetic nephropathy and 53 patients with persistent normoalbuminuria. At baseline, 24-h ambulatory blood pressure, left ventricular hypertrophy, glomerular filtration rate and cardiac autonomic neuropathy were measured. Blood samples were taken and patients answered a World Health Organization questionnaire. Dipping was calculated as the average nocturnal reduction in systolic and diastolic blood pressure. RESULTS: Mean follow-up was 9.2 years (range 0.5-12.9). During follow-up, 54 of 104 patients died. Sixteen patients (15%) had higher blood pressure at night than during the day (reversed pattern); 14 of these patients died (88%), compared to 40 of 88 patients (45%) with reduced dipping or normal dipping; log rank P = 0.001. In a Cox regression analysis, predictors of all-cause mortality were: age, male sex, presence of left ventricular hypertrophy, glycated haemoglobin A1c (HbA1c), daytime systolic blood pressure, cardiac autonomic neuropathy, glomerular filtration rate and dipping (1% increase; hazard ratio 0.97, 95% confidence interval 0.94-0.998, P = 0.033). CONCLUSION: Type 2 diabetes patients with non-dipping of night blood pressure were at higher risk of death as compared to dippers, independent of known cardiovascular risk factors. Since non-dipping has a high prevalence in patients with diabetic nephropathy, 24-h ambulatory blood pressure should be used to assess a full risk profile and blood pressure-lowering therapy in these patients.     

糖尿病肾病患者糖尿病慢性并发症合并情况的分析

目的:分析不同阶段2型糖尿病肾病(DN)患者合并糖尿病慢性并发症的发生率. 方法:临床或肾活检确诊的2型DN患者774例,根据尿蛋白及血清肌酐水平分为白蛋白尿期、临床蛋白尿期及血清肌酐升高期,分析不同时期患者并发症的发生率及代谢指标差异. 结果:774例DN患者平均年龄(56.6±11.3)岁,糖尿病病程中位时间为96个月,肾病病程中位时间为12个月.白蛋白尿者210例,蛋白尿者246例,肾功能不全者318例.DN患者视网膜病变的发生率随病程进展逐渐上升,肾功能不全者较肾功能正常者升高显著;周围神经病变占49.5%,以浅感觉障碍为主,自主神经病变以胃肠功能紊乱、性功能障碍最多见,肾功能不全的患者大部分出现神经病变;各期DN患者心绞痛和心肌梗死的发生率无明显差异,肾功能不全者心肌缺血的发生率明显升高,达40.3%;DN患者随病程进展,心肌舒张功能逐渐下降;脑血管病变中以缺血性脑血管病变为主;糖尿病足的发生率较低(1.4%),间歇性跛行达7.5%;80.6%DN患者存在高血压,以肾功能不全者尤著;白蛋白尿组患者糖化血红蛋白达标率明显高于蛋白尿组及肾功能不全组,与蛋白尿组比较达统计学差异;白蛋白尿组患者的空腹及餐后血糖均较后两组患者控制更好;DN患者脂质代谢异常以三酰甘油和低密度脂蛋白升高为主. 结论:2型DN患者同时存在糖尿病其它大小血管并发症,肾功能损害严重者,并发症多且严重.视网膜病变不能作为DN早期诊断的必备条件;神经病变的发生率亦随病程进展呈明显上升趋势,并进一步促进疾病的进展;随着DN的进展,心肌缺血比例增加,心肌舒张功能下降,可能增加DN患者心血管的死亡率.我国DN患者代谢控制达标率低,因此,强调DN患者综合治疗是改善患者远期预后,减少并发症,提高患者生活质量的关键.     

Maternal history of type 2 diabetes is associated with diabetic nephropathy in type 1 diabetic patients

AIMS: Insulin resistance is a key feature of type 2 diabetes. It is also involved in the development and progression of microvascular complications. We analysed the relationship between parental history of diabetes, insulin resistance and diabetic nephropathy (DN) and assessed the specific maternal and paternal influences of history of type 2 diabetes on DN in type 1 diabetic offspring. METHODS: We recorded information regarding family history of type 2 diabetes and of cardiovascular disease in 160 consecutive, unrelated type 1 diabetic patients. Insulin resistance was assessed using a validated estimation of the glucose disposal rate (eGDR). RESULTS: Type 1 diabetic patients with a maternal history of type 2 diabetes were more likely to be insulin-resistant (P=0.043) and to have renal complications (P=0.0041) than those from the reference group (without parental history of diabetes), while patients with a paternal history were not different from those from the reference group, regarding eGDR and DN. Time to development of abnormal albuminuria was significantly affected by maternal history of type 2 diabetes (log-rank=12.66; P=0.0004) and by familial history of premature cardiovascular disease (log-rank=5.48; P=0.0234). In multivariate analysis, a maternal history of type 2 diabetes was independently associated with nephropathy after adjustment for sex, diabetes duration and familial history of premature cardiovascular disease. CONCLUSION: Maternal history of type 2 diabetes is independently associated with DN in type 1 diabetic patients. This might suggest the transmission of a maternal trait related to microvascular complications, raising the hypothesis of imprinted genes predisposing to diabetic renal disease.     

胰高血糖素与2型糖尿病及其肾病的关系

胰高血糖素是调控糖代谢平衡的重要激素之一,血清胰高血糖素的异常升高与2型糖尿病的起始和进展相关.糖尿病肾病是糖尿病常见的微血管并发症之一,胰高血糖素及其受体信号系统可能在它的发生、发展中发挥重要作用.其可能机制是通过cAMP、一氧化氮和前列腺素等诱导肾小球高滤过,通过增加DNA和蛋白质的合成诱导系膜细胞的增生、肥大,并可与肾素-血管紧张素系统(RAS)相互作用,最终引起肾小球损伤.胰高血糖素及其受体可作为治疗2型糖尿病及其肾脏并发症的靶点.     

Relation of reduction in urinary albumin excretion to ten-year cardiovascular mortality in patients with type 2 diabetes and systemic hypertension

Microalbuminuria is one of the strongest predictors of both adverse renal and cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus. Although measurement of urinary albumin excretion (UAE) is widely recommended, limited data are available to suggest that reducing UAE translates into a reduction in long-term cardiovascular mortality, particularly among patients without overt nephropathy, who constitute most patients with type 2 diabetes worldwide. We assessed whether changes in the UAE at 1 year were associated with cardiovascular mortality in 393 patients with hypertension and type 2 diabetes during a 10-year period. On univariate analysis, CVD history, age, diabetes duration, and change in UAE at 1 year were associated with cardiovascular mortality risk (hazard ratio 2.60 for those with CVD history, 95% confidence interval [CI] 1.47 to 4.62; hazard ratio 1.59 per 10 years of diabetes duration, 95% CI 1.12 to 2.25; and hazard ratio 1.49 per log UAE increase, 95% CI 1.13 to 1.96). In a stepwise Cox regression model that included baseline UAE and CVD history, the 10-year predicted mortality of those with a decrease in UAE of 2 logs at 1 year was 4.7% (95% CI 1.4% to 7.8%). For those with an increase in UAE of 2 logs at 1 year, it was 24.5% (95% CI 10.1% to 36.5%). In conclusion, these data support current guideline recommendations to screen for UAE in all patients with type 2 diabetes, even in the absence of nephropathy, and suggest that serial UAE measurements even after the initiation of antihypertensive therapy has prognostic value independent of traditional cardiovascular risk factors.     

肥胖与2型糖尿病肾病

肥胖不仅是糖尿病、冠心病、高血压的高危因素,还可能导致肾脏损害。糖尿病肾病是糖尿病常见的慢性微血管并发症,是造成终末期肾病的主要原因。已有研究证明肥胖的2型糖尿病患者具有明显的多种代谢异常,能促进糖尿病肾病的发生发展。本文就肥胖导致糖尿病患者肾脏的损伤机制及糖尿病肾病的相关药物治疗做一综述。     

Monitoring of patients with type 2 diabetes and nephropathy in a specialized diabetic nephropathy clinic seems to be beneficial

Background

The purpose of this study was to evaluate the outcome of DM2 patients with nephropathy when they are under surveillance of a joined clinic run by endocrinologists & nephrologists.

糖尿病患者尿液中期因子与糖尿病肾病的关系

目的探讨尿液中期因子（MK）与糖尿病肾病的关系。方法96例糖尿病患者,根据尿白蛋白排泄率分为正常白蛋白尿组（NUAlb组）,微量白蛋白尿组（MUAlb组）,大量白蛋白尿组（CUAlb组）,设对照组（NC组）。用酶联免疫吸附法测定尿液MK水平。结果CUAlb组尿液MK水平高于NC组、NUAlb组及MuAlb组（P〈0．01）,MUAlb组高于NC组及NUAlb组（P〈0．05）,NUAlb组与NC组差异无统计学意义（P〉O．05）。相关分析显示,尿液MK与尿白蛋白排泄率（r=0．40,P〈O．05）及病程（r=0．23,P〈0．05）呈正相关,与内生肌酐清除率（CCr）呈负相关（r=-0．20,P=〈0．05）。结论尿液MK可能参与临床糖尿病肾病的发生。     

低血糖对青年2型糖尿病患者心血管事件的影响

目的：探讨低血糖对青年2型糖尿病患者心血管事件的影响。方法：采用回顾性研究方法,2014年8月到2016年6月选择在我院内分泌科诊治的青年2型糖尿病患者360例,收集所有患者的病历资料与血压样本检测结果,记录低血糖发生情况与调查相关因素,随访心血管事件发生情况。结果：360例患者中发生低血糖20例,发生5.6%。根据2型糖尿病患者是否发生低血糖分为低血糖组(n=20)与对照组(n=340),两组的HDL-C、HbA1c、LDL-C、TG、TC值等对比无明显差异(P>0.05),不过低血糖组的SCr、CRP、CK值等都明显高于对照组(P<0.05)。通过采用Logistic回归分析发现,引起低血糖的主要因素为CRP、病程、CK以及年龄。所有患者随访6个月,低血糖组的不稳定性心绞痛、心力衰竭、靶血管血运重建、猝死等心血管事件发生率为40.0%,明显高于对照组的3.8%(P<0.05)。结论：青年2型糖尿病患者存在低血糖状况,主要发病因素包括年龄、病程、CRP、CK等,可导致心血管事件的增加,在临床上要积极进行预防性控制。     

Risk of progression of nephropathy in a population-based sample with type 2 diabetes

Aims

Progression through stages of nephropathy has not been well described in a large, well-characterized, population-based study. Our aims were to describe the progression of nephropathy and identify characteristics associated with progression in a U.S. population-based sample.

Methods

We identified 10,290 members of a managed care organization who had hypertension and type 2 diabetes, a urine albumin-to-creatinine ratio (UACR) measurement in 2001-2003, and at least 2 follow-up UACRs. Progression of nephropathy was defined as progression to a higher stage of nephropathy than was present at baseline.

Results

At baseline, 57% had normoalbuminuria, 31% had microalbuminuria, and 12% had macroalbuminuria. The incidence of nephropathy progression (per 1000 person-years) was 94.7, 35.1, and 6.5 for normo-, micro-, and macro-albuminuria, respectively. ACEi/ARB use ranged from 61-67%, except among patients with macroalbuminuria at follow-up. Age, diabetes duration, and A1C were significant predictors of progression.

Conclusions

Our study, one of the first to examine the progression of nephropathy in a U.S. population-based sample, showed that among adults with diabetes and hypertension, the burden of nephropathy and its progression may be greater than previously reported. Further, the use of ACEi/ARBs was not optimal.     

Coffee consumption and risk of cardiovascular events and all-cause mortality among women with type 2 diabetes

Aims/hypothesis  Coffee has been linked to both beneficial and harmful health effects, but data on its relationship with cardiovascular disease and mortality in patients with type 2 diabetes are sparse. Methods  This was a prospective cohort study including 7,170 women with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Coffee consumption was assessed in 1980 and then every 2–4 years using validated questionnaires. A total of 658 incident cardiovascular events (434 coronary heart disease and 224 stroke) and 734 deaths from all causes were documented between 1980 and 2004. Results  After adjustment for age, smoking and other cardiovascular risk factors, the relative risks were 0.76 (95% CI 0.50–1.14) for cardiovascular diseases (p trend = 0.09) and 0.80 (95% CI 0.55–1.14) for all-cause mortality (p trend = 0.05) for the consumption of ≥4 cups/day of caffeinated coffee compared with non-drinkers. Similarly, multivariable RRs were 0.96 (95% CI 0.66–1.38) for cardiovascular diseases (p trend = 0.84) and 0.76 (95% CI 0.54–1.07) for all-cause mortality (p trend = 0.08) for the consumption of ≥2 cups/day of decaffeinated coffee compared with non-drinkers. Higher decaffeinated coffee consumption was associated with lower concentrations of HbA_1c (6.2% for ≥2 cups/day versus 6.7% for <1 cup/month; p trend = 0.02). Conclusions  These data provide evidence that habitual coffee consumption is not associated with increased risk of cardiovascular diseases or premature mortality among diabetic women. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up

Aims/hypothesis To study whether urinary orosomucoid excretion rate (UOER) predicts mortality in normoalbuminuric patients with diabetes at 5 years of follow-up, and to investigate the relationship between orosomucoid in serum and urine.Methods A cohort of 578 patients with diabetes (430 type 2, 148 type 1) was followed prospectively for an average of 5 years. UOER was measured in timed overnight urine samples.Results Eighty-two patients with type 2 diabetes and 17 patients with type 1 diabetes died. Among patients with type 2 diabetes, 251 (58%) had normoalbuminuria; increased UOER independently predicted cardiovascular mortality (OR 4.94, 95% CI 1.60–15.22; p<0.006) in those with normoalbuminuria and in the entire cohort of patients with type 2 diabetes (odds ratio 3.63, 95% CI 1.50–8.81; p<0.005). Patients with increased UOER had a higher all-cause mortality than those with normal UOER (log-rank test, p<0.001 for type 2 patients; p<0.04 for type 1 patients). In patients with type 1 diabetes, there were five cardiovascular deaths and no significant predictive value of UOER. Patients with increased UOER had a subclinical increase in serum orosomucoid.Conclusion/interpretation Increased UOER was an independent, powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes and in the entire cohort of patients with type 2 diabetes. There were indications of UOER as being a valuable marker in type 1 diabetes that showed differences in survival between patients with normal versus increased UOER. Serum orosomucoid was associated with UOER; UOER may be a marker of low-grade inflammation in patients with diabetes.     

Prediction of cardiovascular and total mortality in Chinese type 2 diabetic patients by the WHO definition for the metabolic syndrome

AIM: The aim of this study is to investigate the prevalence of metabolic syndrome (MES) in type 2 diabetic patients and the predictive values of the World Health Organization (WHO) and National Cholesterol Education Programme (NCEP) definitions and the individual components of the MES on total and cardiovascular mortality. METHODS: A prospective analysis of a consecutive cohort of 5202 Chinese type 2 diabetic patients recruited between July 1994 and April 2001. RESULTS: The prevalence of the MES was 49.2-58.1% depending on the use of various criteria. There were 189 deaths (men: 100 and women: 89) in these 5205 patients during a median (interquartile range) follow-up period of 2.1 (0.3-3.6 years). Of these, 164 (87%) were classified as cardiovascular deaths. Using the NCEP criterion, patients with MES had a death rate similar to those without (3.51 vs. 3.85%). By contrast, based on the WHO criteria, patients with MES had a higher mortality rate than those without (4.3 vs. 2.4%, p = 0.002). Compared to patients with neither NCEP- nor WHO-defined MES, only the group with MES defined by the WHO, but not NCEP, criterion had significantly higher mortality rate (2.6 vs. 6.8%, p < 0.001). Using Cox regression analysis, only age, duration of diabetes and smoking were identified as independent factors for cardiovascular or total death. Among the various components of MES, hypertension, low BMI and albuminuria were the key predictors for these adverse events. CONCLUSIONS: In Chinese type 2 diabetic patients, the WHO criterion has a better discriminative power over the NCEP criterion for predicting death. Among the various components of the MES defined either by WHO or NCEP, hypertension, albuminuria and low BMI were the main predictors of cardiovascular and total mortality.     

非肥胖2型糖尿病患者血清内脂素与不同阶段糖尿病肾病的关联性研究

目的研究非肥胖2型糖尿病患者血清内脂素(visfatin)与尿微量白蛋白/肌酐(ACR)之间的相关性,探讨内脂素在不同阶段糖尿病肾病中的改变。方法收集体重指数(BMI)28 kg/m2的2型糖尿病患者90例,按照尿ACR分为单纯糖尿病组30例(T2DM组,尿ACR30μg/mg),微量蛋白尿组30例(DN1组,尿ACR30~300μg/mg),大量蛋白尿组30例(DN2组,尿ACR300μg/mg),健康体检人员组(对照组)30例,测定血清内脂素及血脂、血糖等生化指标。结果非肥胖2型糖尿病患者组血清内脂素水平显著高于对照组(P0.01),糖尿病肾病患者组血清内脂素水平显著高于单纯糖尿病组(P0.01),其中大量蛋白尿组血清内脂素水平显著高于微量蛋白尿组(P0.01)。血清内脂素与尿ACR水平呈正相关(r=0.558,P0.01)。结论非肥胖的2型糖尿病患者血清内脂素水平升高,与尿ACR密切相关,随着糖尿病肾病加重,内脂素也逐渐升高。内脂素有希望作为糖尿病肾病的治疗靶点。     

Diabetic nephropathy is associated with increased albumin and fibrinogen production in patients with type 2 diabetes

Aims/hypothesis Hyperfibrinogenaemia and albuminuria are cardiovascular risk factors, often coexisting in diabetic and non-diabetic people. Albuminuria in turn is associated with a compensatory albumin overproduction in non-diabetic patients. It is not known whether the presence of albuminuria in patients with type 2 diabetes mellitus is associated with greater albumin and fibrinogen production rates than in normoalbuminuric patients.Subjects, materials, and methods Using leucine isotope methods, we measured fractional and absolute synthesis rates (FSR, ASR) of albumin and fibrinogen in post-absorptive type 2 diabetic patients with either normal (n=11) or increased (n=10) urinary albumin excretion.Results In albuminuric patients, albumin FSR (16.2±1.5%/day) and ASR (20.5±1.9 g/day) were greater (p<0.02 and p<0.05, respectively) than in normoalbuminuric patients (FSR=11.5±1.1%/day; ASR=15.7±1.2 g/day). Fibrinogen FSR was similar between patients with normal and increased albumin excretion, but concentration, the circulating pool and ASR of fibrinogen were 40 to 50% greater (p<0.035) in patients with albuminuria. Albuminuria was positively correlated with albumin ASR, with fibrinogen concentration, the fibrinogen pool and ASR, whereas albumin synthesis was inversely correlated with calculated oncotic pressure.Conclusions/interpretation Synthesis of albumin and fibrinogen is upregulated in type 2 diabetic patients with increased urinary albumin excretion. Albuminuria is associated with enhanced fibrinogen and albumin synthesis.     

Low human paraoxonase predicts cardiovascular events in Japanese patients with type 2 diabetes

Human serum paraoxonase (PON1) is associated with HDL and inhibits oxidative modification of LDL. PON1 enzymatic activity has been shown to decrease in diabetic patients; however, the effect of PON1 status on long-term outcome has not been reported. In this study, we examined the association between baseline PON1 status and the development of cardiovascular disease (CVD) during 10 years of follow-up in 88 type 2 diabetic patients whose enzymatic activities, concentrations, and genetic polymorphisms of PON1 had been determined. A total of 20 CVD events were recorded during the follow-up period. Using Kaplan–Meier survival curves, we found a significantly increased incidence of CVD in patients with a lower concentration or paraoxonase activity of PON1 than each median value (log-rank 7.460; P < 0.01, and log-rank 4.187; P < 0.05, respectively). By Cox regression analysis, both concentration and paraoxonase activity were significantly associated with the development of CVD, even after correction for gender, age, and preexisting CVD (P < 0.05). Low concentration and enzymatic activity of PON1 may be an independent predictor of cardiovascular events in diabetic patients.