Serum uric acid levels and the risk of type 2 diabetes: a prospective study

Purpose

To evaluate the impact of serum uric acid levels on the future risk of developing type 2 diabetes independent of other factors.

Methods

We used prospective data from the Framingham Heart Study original (n = 4883) and offspring (n = 4292) cohorts to examine the association between serum uric acid levels and the incidence of diabetes. We used Cox proportional hazards models to estimate the relative risk of incident diabetes adjusting for age, sex, physical activity, alcohol consumption, smoking, hypertension, body mass index, and blood levels of glucose, cholesterol, creatinine, and triglycerides.

Results

We identified 641 incident cases of diabetes in the original cohort and 497 cases in the offspring cohort. The incidence rates of diabetes per 1000 person-years for serum uric acid levels <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9 and ≥8.0 mg/dL were 3.3, 6.1, 8.7, 11.5, and 15.9, respectively, in the original cohort; and 2.9, 5.0, 6.6, 8.7, and 10.9, respectively, in the offspring cohort (P-values for trends <.001). Multivariable relative risks per mg/dL increase in serum uric acid levels were 1.20 (95% confidence interval; 1.11-1.28) for the original cohort and 1.15 (95% confidence interval; 1.06-1.23) for the offspring cohort.

Conclusions

These prospective data from 2 generations of the Framingham Heart Study provide evidence that individuals with higher serum uric acid; including younger adults, are at a higher future risk of type 2 diabetes independent of other known risk factors. These data expand on cross-sectional associations between hyperuricemia and the metabolic syndrome, and extend the link to the future risk of type 2 diabetes.     

老年2型糖尿病患者易患因素的对照分析

目的 研究老年２型糖尿病患者的易患因素,为预防和干预提供依据。方法 随机选择老年２型糖尿病就诊断病例６５例、医院对照７１例和人群对照６７例,进行频数匹配病例对照研究。结果 糖尿病阳性家族史（ＯＲ＝５．４８）、腰臀大（ＯＲ＝２．３３）、主食摄入量大（ＯＲ＝２．８６）、经常性肉类摄入（ＯＲ＝２．６１）、高血压（ＯＲ＝４．８３）和女性妊娠次数多（ＯＲ＝４．４６）,以及休闲时体力活动（ＯＲ＝０．４３）与２型糖尿病有显著性关联。结论 具有糖尿病家族史、肥胖、饮食高能量摄入、高血压和女性妊娠次数多等可能是老年２型糖尿病的危险因素;休闲时体力活动具有保护作用。倡导健康的生活方式,有计划地实施人群干预策略,是老年２型糖尿病防治的重要措施。     

老年2型糖尿病微血管病变相关危险因素分析

目的本研究旨在探讨老年2型糖尿病微血管病变相关危险因素。方法收集520例符合条件的老年2型糖尿病患者的临床相关信息,根据有无糖尿病微血管病变分为糖尿病性微血管病变组和无糖尿病性微血管病变组,收集两组一般情况、相关血液学指标及并发症情况。结果在单因素分析中,性别、年龄、糖尿病病程、吸烟史、HbA1c、TG、LDL-C、高血压病有统计学差异(P<0.05)。将单因素分析中有统计学差异的相关指标,包括性别、年龄、糖尿病病程、吸烟史、HbA1c、TG、LDL-C、高血压病纳入多因素Logistic分析模型中,结果显示:糖尿病病程、HbA1c、TG、LDL-C有统计学意义(P<0.05)。即老年2型糖尿病微血管病变与糖尿病病程(OR=1.063,95%CI 1.030~1.096,P=0.000),HbA1c(OR=1.086,95%CI 1.037~1.124,P=0.013),TG(OR=1.152,95%CI 1.046~1.267,P=0.005),LDL-C(OR=1.218,95%CI 1.024~1.610,P=0.028)风险增加相关。结论糖尿病病程、HbA1c、TG、LDL-C为老年2型糖尿病微血管病变的独立危险因素以预测其发生发展。     

Relationship between urinary excretion of sodium and dopamine in type 1 diabetic patients with an without microalbuminuria

The relationship between urinary sodium and dopamine excretion was investigated in 40 normal males and in 48 normotensive, Type 1 diabetic males, 11 with microalbuminuria and 37 with normal albumin excretion. In all three groups a significant correlation was demonstrated and the regression lines were similar. Thus, no evidence was found that a defect in dopamine mobilization contributes to the early renal pathophysiological changes of Type 1 diabetes.     

盐敏感性高血压患者的肾脏排泄钠、钾特征的研究

为了探讨原发性高血压病病因并对其治疗及预防提供依据,本研究对55例原发性高血压病患者进行了区分盐敏感者的研究及三种状态下肾脏排泄钠、钾和血浆有关激素水平的实验室测查及统计分析,结果表明:盐敏感者为34例,中间型11例,10例盐耐受者.在盐负荷状态下,盐敏感者中大部分(71%)呈现肾排钠增强,且排钠量与收缩压的升高呈正相关(r=0.700,P<0.05);另一部分(29%)的盐敏感者排钠减低,但血压增高幅度大.盐负荷期肾排钾量盐敏感组高于耐受组.盐负荷期与基础状态时相比较,盐敏感组的血浆肾素活性、血管紧张素Ⅱ及醛固酮水平没有得到有效的抑制.提示:盐敏感性高血压患者存在着肾排钾、钠障碍及肾素-血管紧张素-醛固酮系统调节紊乱.     

Determining type 2 diabetes risk factors for the adults: A community based study from Turkey

Aims

This study aimed to determine risk factors for type 2 diabetes among adults who were not diagnosed with diabetes.

Development of diabetic retinopathy and its associated risk factors in type 2 diabetic patients in Osaka district, Japan: a long-term prospective study

Incidence rates of diabetic retinopathy and its associated risk factors were studied in a long-term prospective study involving 976 type 2 (non-insulin dependent) diabetic patients that showed no retinopathy at entry to the study. 322 of the patients (one-third of the subjects studied) developed diabetic retinopathy during the observation period (average length 8.3 years). The incidence rate per 1000 person-years was 39.8. The rate was significantly related to age at onset of diabetes, to fasting plasma glucose (FPG) level at entry, and to type of treatment. The incidence rate was also related to the duration of the disease. Glycemic control clearly played a role in the occurrence of retinopathy. Patients with FPG ≥ 200 mg/dl had the highest incidence rate, while patients with FPG < 140 mg/dl showed the lowest incidence rate throughout the observation period. Furthermore, a longer period between onset of diabetes and development of retinopathy was observed in patients with FPG < 140 mg/dl compared to patients with FPG ≥ 200 mg/dl. The findings suggest that strict glycemic control may be of particular value to reduce the incidence of retinopathy and to delay its appearance in type 2 diabetic patients.     

Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75)

Aims/hypothesis The relative importance of glucose and blood pressure control in type 2 diabetes remains uncertain. We assessed interactive effects of glycaemia and systolic blood pressure (SBP) exposure on the risk of diabetic complications over time.Subjects, materials and methods HbA_1c and SBP, measured annually for a median of 10.4 years in 4,320 newly diagnosed type 2 diabetic patients from the UK Prospective Diabetes Study (UKPDS), were categorised as updated mean values <6.0, 6.0–6.9, 7.0–7.9 or ≥8.0%, and <130, 130–139, 140–149 or ≥150 mmHg, respectively. Clinical outcomes were UKPDS predefined composite endpoints.Results The incidence of the ‘any diabetes-related endpoint’ in the lowest (HbA_1c <6.0%, SBP <130 mmHg) and highest (HbA_1c ≥8%, SBP ≥150 mmHg) category combinations was 15 and 82 per 1,000 person-years, respectively, and 24 and 120 per 1,000 person-years in a Poisson model adjusted to white Caucasian male sex, age 50 to 54 years and diabetes duration of 7.5 to 12.5 years. Updated mean HbA_1c and SBP effects were additive in an adjusted proportional hazards model with risk reductions of 21% per 1% HbA_1c decrement and 11% per 10 mmHg SBP decrement. Endpoint rates obtained in the 887 patients randomised in both the glycaemia and hypertension intervention trial arms were consistent with the observational data. Those allocated to both intensive glucose and tight blood pressure control policies had fewer events than those allocated to either policy alone or to neither (p for trend 0.024).Conclusions/interpretation Risk of complications in type 2 diabetes is associated independently and additively with hyperglycaemia and hypertension. Intensive treatment of both these risk factors is required to minimise the incidence of complications.     

新诊断2型糖尿病患者亚临床大血管病变及危险因素分析

目的:研究新诊断2型糖尿病患者的亚临床大血管病变患病情况及危险因素分析。方法 :采取社区筛查、门诊收集的方法,获取178例新诊断2型糖尿病患者,行颈动脉彩色超声筛查亚临床大血管病变,并采集个人史、既往史、身高、体重、腰围及糖化血红蛋白(HbA1c)、血脂等数据。结果:178例患者中合并亚临床大血管病变者(A组)67例,患病率为37.6%,无亚临床大血管病变者(B组)111例(62.4%)。A组患者年龄较大,高血压患病率较高,且2组间高血压病程、收缩压差异具有统计学意义(P<0.05)。2组患者性别比例、吸烟率相似,腰围、腰臀比、舒张压、HbA1c、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇无明显差异,A组体质量指数(BMI)、总胆固醇(TC)水平较B组升高(P<0.05)。Logistic回归分析显示,高血压病史、BMI、TC是亚临床大血管病变患病的危险因素(P<0.05)。结论:部分新诊断2型糖尿病患者已合并亚临床大血管病变,高血压病程、BMI、TC是其患病的危险因素。     

A longitudinal study of foot ulceration and its risk factors in community-based patients with type 2 diabetes: The Fremantle Diabetes Study

Aims

To determine the prevalence and associates of foot ulcer, and the subsequent incidence and predictors of first-ever hospitalisation for this complication, in well-characterised community-based patients with type 2 diabetes.

Methods

Baseline foot ulceration was ascertained in 1296 patients (mean age 64 years, 48.6% male, median diabetes duration 4.0 years) recruited to the longitudinal Fremantle Diabetes Study between 1993 and 1996. Incident hospitalisation for foot ulceration was monitored through validated data linkage until end-December 2010.

Results

At baseline, 16 participants (1.2%) had a foot ulcer which was independently associated with intermittent claudication, peripheral sensory neuropathy (PSN) and diabetes duration (P ≤ 0.01). The incidence of hospitalisation for this complication in those without prior/prevalent foot ulceration was 5.21 per 1000 patient-years. This rate and other published data suggest that 1 in 7–10 foot ulcers require hospitalisation. In a Cox proportional hazards model, intermittent claudication and PSN were significant independent predictors of time to admission with foot ulceration, in addition to retinopathy, cerebrovascular disease, HbA_1c, alcohol consumption, renal impairment, peripheral arterial disease and pulse pressure (P ≤ 0.038).

Conclusions

These data confirm PSN as an important risk factor for foot ulceration but, in contrast to some other studies, peripheral arterial disease was also a major independent contributor. Associations between hospitalisation for foot ulcer and both retinopathy and raised pulse pressure suggest a role for local microvascular dysfunction, while alcohol may have non-neuropathic toxic effects on skin/subcutaneous structures. The multifactorial nature of foot ulceration complicating type 2 diabetes may have implications for its management.     

2型糖尿病尿微量白蛋白与心血管病危险因素的研究

目的探讨2型糖尿病（T2DM）患者尿微量白蛋白与心血管病危险因素（血糖、血脂、血压、尿酸等）的关系。方法选择192例确诊为T2DM住院患者,分为微量白蛋白尿（MAU）组（n=60）和正常微量白蛋白尿（NAU）组（n=132）,检测患者体质指数（BMI）、血脂、血压、尿酸等相关危险因素,并进行对比分析;同时以尿微量白蛋白为因变量,各相关危险因素为自变量进行了多元线性回归分析,以明确影响2型糖尿病患者尿微量白蛋白增加的因素。结果 MAU组糖化血红蛋白水平（HbA1c）、入院时收缩压（SBP）、舒张压（DBP）水平、血肌酐（Cr）、尿酸（UA）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）水平及TC、LDL-C、UA、SBP和DBP的异常率明显高于NAU组,而高密度脂蛋白胆固醇（HDL-C）水平明显低于NAU组（P〈0.05～0.01）,多元线性回归分析发现MAU与BMI、SBP、DBP、TC、TG、LDL-C、HbA1c、UA和Cr呈正相关,而与HDL-C呈负相关（P〈0.05～0.01）。结论血脂、血压等多种危险因素的异常影响T2DM患者尿微量白蛋白水平。     

Dietary selenium intake and risk of hospitalization for type 2 diabetes in the Moli-sani study cohort

Background and aimsExperimental and non-experimental human studies have consistently shown a positive association between exposure to the trace element selenium, which occurs primarily through diet, and risk of type 2 diabetes mellitus. Plausible biological mechanisms include adverse effects of selenium and selenium-containing proteins on glucose metabolism. However, the levels of exposure above which risk increases are uncertain.Methods and resultsWe examined the association between selenium intake and first hospitalization for type 2 diabetes during a median follow-up period of 8.2 years among 21,335 diabetes-free participants in the Moli-sani cohort, Italy. Selenium intake was ascertained at baseline using a food frequency questionnaire, showing a median value of 59 μg/day. During follow-up, we identified 135 incident cases of hospitalization for diabetes, based on population-based hospital discharge data. We used a Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization for diabetes, adjusting for potential confounders. HRs (95% CIs) were 1.01 (0.60–1.70), 1.13 (0.66–1.96) and 1.75 (0.99–3.10) comparing the second, third, and fourth sex-specific quartiles with the first quartile, respectively. Risk was 64% greater in the fourth quartile as compared with the previous three. Spline regression analysis also indicated a steeper increase in risk occurring among men compared with women.ConclusionsIn a large population of Italian adults free of type 2 diabetes at cohort entry, high dietary selenium intake was associated with increased risk of hospitalization for diabetes.     

2型糖尿病及糖尿病肾病危险因素分析

目的 研究2型糖尿病（DM）及糖尿病肾病（DN）的易患因素，指导临床及早防治。方法 随机选择2型糖尿病病例201例，人群对照110例作病例对照研究。根据尿白蛋白排泄率（UAER）将DM患者分为四组互为对照比较。结果 与人群对照组相比，DM组在饮酒、喜食甜食、过多摄入动物脂肪、糖尿病家族史、女性病人巨大儿生产史、合并冠心病、高血压、脑血管意外、高脂血症、胰岛素敏感性指标方面有显著差异。DM四组间在年龄、病程、继发糖尿病眼病、糖尿病神经病变、合并高血压、冠心病、脑血管意外、胆囊结石、心电图异常、收缩压、舒张压有显著差异。UAER与糖尿病肾病、眼病、冠心病正相关。结论 饮酒、喜食甜食、过多摄入动物脂肪、糖尿病家族史、女性病人巨大儿生产史、合并冠心病、高血压、脑血管意外、高脂血症、胰岛素抵抗等可能是2型糖尿病的危险因素。血糖、血脂、血压的不良控制导致糖尿病肾病的进展，DN与其他血管并发症或合并症有较好的相关性。定期监测尿白蛋白排泄率对于及早发现防治糖尿病肾病和其它血管并发症具有重要意义。     

Urinary growth hormone excretion during puberty in type 1 (insulin-dependent) diabetes mellitus

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.     

Causes of death,incidence and risk factors of cardiovascular diseases in Thai type 2 diabetic patients: a 5 year follow-up study

There appear to be ethnic disparities in frequencies of diabetic complications in type 2 diabetic patients and such data from Asian countries are relatively few and limited. Thai type 2 diabetic patients who attended the diabetic clinic at Prince of Songkla University hospital during January–December 1997 and had no history of coronary heart disease (CHD) and stroke were studied to determine cause of death and to establish the incidence of and risk factors for cardiovascular disease (CVD). All patients were followed to death or to the end of year 2001. End-points included death from any cause, fatal and nonfatal CHD, fatal and nonfatal stroke and lower-extremity amputation. There were 229 patients who were followed for 4.2±0.7 (S.D.) years (range: 0.6–5.0) with total follow-up period 958.2 patient-years. Twenty-nine patients died during follow-up; the total mortality rate was 30.3 (95%CI 20.2–43.4)/1000 patient-years. Of these, 9(9.4/1000 patient-years; 95%CI 4.3–17.8) died from sepsis, 7(7.3/1000 patient-years; 95%CI 2.9–15.0) from CVD, 5(5.2/1000 patient-years; 95%CI 2.7–12.2) from end-stage renal disease, 3(3.1/1000 patient-years; 95%CI 0.6–9.2) from malignancy and 1(1.0/1000 patient-years; 95%CI 0.03–5.8) from peripheral vascular disease. The incidences of fatal and nonfatal CHD as well as fatal and nonfatal stroke were 21.4(95%CI 13.0–33.0)/1000 and 12.8(95%CI 6.6–22.4)/1000 patient-years, respectively whereas the incidence of lower-extremity amputation was 4.3(95%CI 1.2–10.9)/1000 patient-years. Age, the presence of proteinuria and serum HDL-C0.9 mmol/l were independent risk factors of CHD with the respective Hazard ratios 1.09(95%CI: 1.02–1.17; P=0.016), 4.41(95%CI: 1.18–16.45; P=0.027) and 3.91(95%CI: 1.20–12.80; P=0.024). In conclusion, sepsis and CVD were the major causes of death accounting for 50% of total mortality in Thai type 2 diabetic patients. Age, the presence of proteinuria and low HDL-C were independent risk factors for the development of CHD. The mortality from and the incidence of CHD in Thai type 2 diabetic patients are lower than those reported from Caucasian populations but the incidence of stroke appears to be higher. These findings need to be confirmed by a large-scale population-based study.     

Association and relative importance of multiple risk factor control on cardiovascular disease,end-stage renal disease and mortality in people with type 2 diabetes: A population-based retrospective cohort study

AimsTo evaluate the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality, when implementing a multifactorial optimal control approach in primary care in the United Kingdom (UK), in individuals with newly diagnosed type 2 diabetes.Materials and methodsA retrospective cohort of 53 942 patients were stratified into 1 of the 8 groups according to whether glycated haemoglobin (HbA1c), blood pressure (BP) and total cholesterol (TC) target values were achieved or not from baseline to the date of last follow-up. Those with single or combinations of risk factor control targets achieved, were compared to those who achieved no targets in any of the risk factor. Hazard ratios from the Cox proportional hazards models were estimated against patients who achieved no targets.ResultsOf 53 942 patients with newly diagnosed type 2 diabetes, 28%, 55%, and 68% were at target levels for HbA1c <48 mmol/mol (<6.5%), BP < 140/85 mm Hg, and TC < 5 mmol/L respectively, 36%, 40%, and 12% were at target levels for any one, two, or all three risk factors respectively. Being at HbA1c, BP, and TC targets was associated with an overall 47%, 25%, 42%, 55% and 42% reduction in the risk of ischemic heart disease, cerebrovascular disease, ESRD, cardiovascular-mortality, and all-cause-mortality respectively. Among all subgroups, the risk reduction of study outcome events was greater in the subgroups of patients with microalbuminuria, males, smokers, and patients with BMI ≥ 30 kg/m².ConclusionsOptimal levels of HbA1c, BP, and TC occurring together in patients with newly diagnosed type 2 diabetes are uncommon. Achieving multiple risk factor control targets could substantially reduce the risk of CVD, ESRD and mortality.     

Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study

Aims/hypothesis Prospective data directly investigating the role of endogenous sex hormones in diabetes risk have been scant, particularly in women. We aimed to examine comprehensively plasma sex hormones in connection with risk of developing type 2 diabetes in postmenopausal women. Methods We conducted a prospective, nested case–control study of plasma oestradiol, testosterone and dehydroepiandrosterone sulfate and risk of type 2 diabetes in a cohort of women health professionals with a mean age of 60.3 and 12.2 years since menopause. Among women not using hormone therapy and free of baseline cardiovascular disease, cancer and diabetes, 359 incident cases of type 2 diabetes were matched with 359 controls during an average follow-up of 10 years. Results Oestradiol and testosterone were each strongly and positively associated with risk of type 2 diabetes. After adjustment for BMI, family history, lifestyle and reproductive variables, the multivariable relative risks (95% CI) comparing the highest vs lowest quintile were 12.6 (2.83–56.3) for total oestradiol (p = 0.002 for trend), 13.1 (4.18–40.8) for free oestradiol (p < 0.001 for trend), 4.15 (1.21–14.2) for total testosterone (p = 0.019 for trend) and 14.8 (4.44–49.2) for free testosterone (p < 0.001 for trend). These associations remained robust after adjusting and accounting for other metabolic syndrome components and baseline HbA_1c levels. Conclusions/interpretation In postmenopausal women, higher plasma levels of oestradiol and testosterone were strongly and prospectively related to increased risk of developing type 2 diabetes. These prospective data indicate that endogenous levels of sex hormones may play important roles in the pathogenesis of type 2 diabetes. ClinicalTrials.gov ID no.: NCT00000479.     

Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database

Aims/hypothesis Risk estimates for stroke in patients with diabetes vary. We sought to obtain reliable risk estimates for stroke and the association with diabetes, comorbidity and lifestyle in a large cohort of type 2 diabetic patients in the UK.Materials and methods Using the General Practice Research Database, we identified all patients who had type 2 diabetes and were aged 35 to 89 years on 1 January 1992. We also identified five comparison subjects without diabetes and of the same age and sex. Hazard ratios (HRs) for stroke between January 1992 and October 1999 were calculated, and the association with age, sex, body mass index, smoking, hypertension, atrial fibrillation and duration of diabetes was investigated.Results The absolute rate of stroke was 11.91 per 1,000 person-years (95% CI 11.41–12.43) in people with diabetes (n = 41,799) and 5.55 per 1,000 person-years (95% CI 5.40–5.70) in the comparison group (n = 202,733). The age-adjusted HR for stroke in type 2 diabetic compared with non-diabetic subjects was 2.19 (95% CI 2.09–2.32) overall, 2.08 (95% CI 1.94–2.24) in men and 2.32 (95% CI 2.16–2.49) in women. The increase in risk attributable to diabetes was highest among young women (HR 8.18; 95% CI 4.31–15.51) and decreased with age. No investigated comorbidity or lifestyle characteristic emerged as a major contributor to risk of stroke.Conclusions/interpretation This study provides risk estimates for stroke for an unselected population from UK general practice. Patients with type 2 diabetes were at an increased risk of stroke, which decreased with age and was higher in women. Additional risk factors for stroke in type 2 diabetic patients included duration of diabetes, smoking, obesity, atrial fibrillation and hypertension.