Psychological Distress and Incidence of Type 2 Diabetes in High-Risk and Low-Risk Populations: The Whitehall II Cohort Study

OBJECTIVE

We examined whether psychological distress predicts incident type 2 diabetes and if the association differs between populations at higher or lower risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS

This was a prospective cohort of 5,932 diabetes-free adults (4,189 men and 1,743 women, mean age 54.6 years) with three 5-year data cycles (1991–2009): a total of 13,207 person-observations. Participants were classified into four groups according to their prediabetes status and Framingham Offspring Type 2 Diabetes Risk Score: normoglycemia with a risk score of 0–9, normoglycemia with a risk score of 10–19, prediabetes with a risk score of 10–19, and prediabetes with a risk score of >19. Psychological distress was assessed by the General Health Questionnaire. Incident type 2 diabetes was ascertained by 2-h oral glucose tolerance test, doctor diagnosis, or use of antihyperglycemic medication at the 5-year follow-up for each data cycle. Adjustments were made for age, sex, ethnicity, socioeconomic status, antidepressant use, smoking, and physical activity.

RESULTS

Among participants with normoglycemia and among those with prediabetes combined with a low risk score, psychological distress did not predict type 2 diabetes. Diabetes incidence in these groups varied between 1.6 and 15.6%. Among participants with prediabetes and a high risk score, 40.9% of those with psychological distress compared with 28.5% of those without distress developed diabetes during the follow-up. The corresponding adjusted odds ratio for psychological distress was 2.07 (95% CI 1.19–3.62).

CONCLUSIONS

These data suggest that psychological distress is associated with an accelerated progression to manifest diabetes in a subpopulation with advanced prediabetes.Type 2 diabetes is preceded by a period of marked changes in glucose regulation. The prediabetic period can last over 10 years (1), providing a crucial window for effective prevention of type 2 diabetes. To date, the focus of preventive efforts has been on lifestyle and pharmacological interventions (1–3). However, there has been widespread interest in the role of psychological factors, such as depression and stress, in the onset of type 2 diabetes. Suggested plausible mechanisms are health risk behaviors and increased body weight, dysregulation of the hypothalamus-pituitary-adrenal axis, overactivation of the sympathetic nervous system, and increased chronic inflammation, all of which are known to adversely affect glucose metabolism (4,5).There is some evidence that depression is an independent risk factor for type 2 diabetes (6–8), but findings for “general” stress and work stress are less consistent (9–18). A major limitation of existing research on psychological factors and diabetes risk is reliance on the crude dichotomization of no diabetes versus diabetes. This categorization does not take into account the long prediabetic period preceding manifest disease and the possibility that those at an advanced stage on the continuum between health and disease might be differentially vulnerable to the effects of psychological factors (17). Some evidence to support this hypothesis was found in a study including 128 male Japanese workers with prediabetes who reported an increased risk of type 2 diabetes among those with high levels of baseline stress (19).Although it captures a range of comorbid psychological factors, such as depressive and anxiety symptoms, stress, and disturbed sleep, psychological distress has rarely been examined as a psychological risk factor for type 2 diabetes (11,18,20), and no study has examined whether the associations differ in populations at higher or lower risk of progressing to manifest diabetes. In this study, we examined whether psychological distress at baseline differentially predicted incident type 2 diabetes in analyses stratified by the type 2 diabetes risk level based on 1) the presence or absence of prediabetes and 2) the Framingham Offspring Type 2 Diabetes Risk Score (FRS) (21).     

Contributors to Mortality in High-Risk Diabetic Patients in the Diabetes Heart Study

OBJECTIVE

Not all individuals with type 2 diabetes and high coronary artery calcified plaque (CAC) experience the same risk for adverse outcomes. This study examined a subset of high-risk individuals based on CAC >1,000 mg (using a total mass score) and evaluated whether differences in a range of modifiable cardiovascular disease (CVD) risk factors provided further insights into risk for mortality.

RESEARCH DESIGN AND METHODS

We assessed contributors to all-cause mortality among 371 European American individuals with type 2 diabetes and CAC >1,000 from the Diabetes Heart Study (DHS) after 8.2 ± 3.0 years (mean ± SD) of follow-up. Differences in known CVD risk factors, including modifiable CVD risk factors, were compared between living (n = 218) and deceased (n = 153) participants. Cox proportional hazards regression models were used to quantify risk for all-cause mortality.

RESULTS

Deceased participants had a longer duration of type 2 diabetes (P = 0.02) and reduced use of cholesterol-lowering medications (P = 0.004). Adjusted analyses revealed that vascular calcified plaque scores were associated with increased risk for mortality (hazard ratio 1.31–1.63; 3.89 × 10⁻⁵ < P < 0.03). Higher HbA_1c, lipids, and C-reactive protein and reduced kidney function also were associated with a 1.1- to 1.5-fold increased risk for mortality (3.45 × 10⁻⁶ < P < 0.03) after adjusting for confounding factors.

CONCLUSIONS

Even in this high-risk group, vascular calcification and known CVD risk factors provide useful information for ongoing assessment. The use of cholesterol-lowering medication seemed to be protective for mortality.     

The Impact of Bariatric Surgery on Incident Microvascular Complications in Patients With Type 2 Diabetes: A Matched Controlled Population-Based Retrospective Cohort Study

OBJECTIVETo assess the impact of bariatric surgery (BS) on incident microvascular complications of diabetes-related foot disease (DFD), sight-threatening diabetic retinopathy (STDR), and chronic kidney disease (CKD) in patients with type 2 diabetes and obesity.RESEARCH DESIGN AND METHODSA retrospective matched, controlled population-based cohort study was conducted of adults with type 2 diabetes between 1 January 1990 and 31 January 2018 using IQVIA Medical Research Data (IMRD), a database of primary care electronic records. Each patient with type 2 diabetes who subsequently had BS (surgical group) was matched on the index date with up to two patients with type 2 diabetes who did not have BS (nonsurgical group) within the same general practice by age, sex, preindex BMI, and diabetes duration.RESULTSIncluded were 1,126 surgical and 2,219 nonsurgical participants. In the study population 2,261 (68%) were women. Mean (SD) age was 49.87 (9.3) years vs. 50.12 (9.3) years and BMI was 46.76 (7.96) kg/m² vs. 46.14 (7.49) kg/m² in the surgical versus nonsurgical group, respectively. In the surgical group, 22.1%, 22.7%, 52.2%, and 1.1% of patients had gastric band, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and duodenal switch, respectively. Over a median follow-up of 3.9 years (interquartile range 1.8–6.4), BS was associated with reduction in incident combined microvascular complications (adjusted hazard ratio 0.53, 95% CI 0.43–0.66, P < 0.001), DFD (0.61, 0.50–0.75, P < 0.001), STDR (0.66, 0.44–1.00, P = 0.048), and CKD (0.63, 0.51–0.78, P < 0.001). Analysis based on the type of surgery showed that all types of surgery were associated with a favorable impact on the incidence of composite microvascular complications, with the greatest reduction for RYGB.CONCLUSIONSBS was associated with a significant reduction in incident diabetes-related microvascular complications.     

Racial/Ethnic Differences in Dementia Risk Among Older Type 2 Diabetic Patients: The Diabetes and Aging Study

OBJECTIVE

Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory factors among older diabetic patients.

RESEARCH DESIGN AND METHODS

We identified 22,171 diabetic patients without preexisting dementia aged ≥60 years (14,546 non-Hispanic whites, 2,484 African Americans, 2,363 Latinos, 2,262 Asians, 516 Native Americans) from the Kaiser Permanente Northern California Diabetes Registry. We abstracted prevalent medical history (1 January 1996 to 31 December 1997) and dementia incidence (1 January 1998 to 31 December 2007) from medical records and calculated age-adjusted incidence densities. We fit Cox proportional hazards models adjusted for age, sex, education, diabetes duration, and markers of clinical control.

RESULTS

Dementia was diagnosed in 3,796 (17.1%) patients. Age-adjusted dementia incidence densities were highest among Native Americans (34/1,000 person-years) and African Americans (27/1,000 person-years) and lowest among Asians (19/1,000 person-years). In the fully adjusted model, hazard ratios (95% CIs) (relative to Asians) were 1.64 (1.30–2.06) for Native Americans, 1.44 (1.24–1.67) for African Americans, 1.30 (1.15–1.47) for non-Hispanic whites, and 1.19 (1.02–1.40) for Latinos. Adjustment for diabetes-related complications and neighborhood deprivation index did not change the results.

CONCLUSIONS

Among type 2 diabetic patients followed for 10 years, African Americans and Native Americans had a 40–60% greater risk of dementia compared with Asians, and risk was intermediate for non-Hispanic whites and Latinos. Adjustment for sociodemographics, diabetes-related complications, and markers of clinical control did not explain observed differences. Future studies should investigate why these differences exist and ways to reduce them.     

基于心脏-血管弹性匹配探讨Ⅱ型糖尿病患者心血管功能变化

目的 初步探讨糖尿病患者心功能与全身动脉功能间的匹配关系.方法 对Ⅱ型糖尿病患者依据左心室射血分数(EF)分组:选取EF正常组(DMN组)40例,EF减低组(DMA组)40例共80例,另选42例为正常对照组.测量和计算左室舒张末容积(LVEDV)、收缩末容积(LVESV)、左室壁相对厚度(RWT)和左室质量(LVMI),计算EF、心排量(CO)、心脏指数(CI),做功参数(SW)和心肌耗氧参数(RPP),计算体循环血管阻力指数(SVRI)、有效动脉弹性(Ea).采用多元线性逐步回归,筛选Ea的独立关联指标.结果 (1)DMN和DMA组甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)和空腹血糖(FPG)增高(P＜0.05、P＜0.01); RWT、LVMI在3组间差异有统计学意义(P＜0.01);DMA组LVEDV、LVESV、EF、CI、RPP及SW与DMN组和对照组比较差异有统计学意义(P＜0.01).(2)Ea和SVRI在3组间差异均有统计学意义(P＜0.05、P＜0.01).(3)Ea与RPP、SW、HDL-C和FPG及RWT和EF高度关联.结论 Ⅱ型糖尿病患心脏血管功能间存在耦联关系.心脏结构、功能状态和血生化指标独立影响外周动脉.     

Diabetic Retinopathy and Microalbuminuria Can Predict Macroalbuminuria and Renal Function Decline in Japanese Type 2 Diabetic Patients: Japan Diabetes Complications Study

OBJECTIVE

To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline.

RESEARCH DESIGN AND METHODS

We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR−)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR−)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years.

RESULTS

Annual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94–6.50; P = 0.07), 10.40 (4.91–22.03; P < 0.01), and 11.55 (5.24–25.45; P < 0.01) in NA(DR+), MA(DR−), and MA(DR+), respectively, in comparison with NA(DR−). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (−1.92 mL/min/1.73 m²/year) than in the other groups.

CONCLUSIONS

In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists.Diabetic retinopathy (DR) and nephropathy (DN) are two major chronic microvascular complications in long-standing type 1 and type 2 diabetic patients. However, it is still unclear whether these 2 complications are related to or affect each other or whether both of them progress simultaneously after their onset, although many epidemiological studies have shown the coexistence of DR and DN (1,2). In fact, we sometimes see proteinuric diabetic patients without DR or normoalbuminuric patients with proliferative DR, which is the most advanced stage of DR. For example, it was shown that only 36% had no DR, while 53% had nonproliferative, 9% moderate to severe, and 2% severe DR in 285 normoalbuminuric Caucasian type 1 diabetic patients (3). In addition, there was marked discordance between DR and DN, especially in normoalbuminuria or low-level microalbuminuria, while advanced renal histological severity has been related to advanced DR severity in Caucasian type 1 diabetic patients (4). On the other hand, diabetic patients treated by diabetologists sometime miss their visits to ophthalmologists; therefore, the relationships or detailed clinical courses of DR and DN can hardly be analyzed in most clinical sites.All over the world, DN is a major cause of end-stage renal disease, which requires renal replacement therapy such as hemodialysis or renal transplantation (5,6). In Japan, the number of patients requiring renal replacement therapy has increased threefold in the last 15 years. Therefore, it is absolutely necessary to stop the progression of DN and to find biomarkers or easily available factors that represent the exact clinical course or prognosis of DN. However, it is not exactly known what factors affect an increase of urinary albumin excretion (UAE) or glomerular filtration rate (GFR) decline, which are typical clinical changes in DN.Microalbuminuria is well known as a risk factor resulting in macroalbuminuria in type 1 and type 2 diabetic patients (7–9). In addition, some Caucasian type 2 diabetic patients with microalbuminuria showed rapid decline of GFR, although it was unclear whether these patients had more frequent DR compared with the patients without rapid GFR decline (10). On the other hand, DR was shown to be a risk factor of microalbuminuria and macroalbuminuria (2,11). In addition, proliferative DR was shown to be a predictor of macroalbuminuria in Caucasian type 1 diabetic patients (13), but this association has not been investigated in Asian populations. Although DR and glomerulosclerosis seemed to be parallel to progress using the investigation of serial renal biopsy specimens (14) when the blood glucose control was fair to poor, detailed interaction between two complications are still obscure in a large number of patients. Whether DR can predict renal functional decline in type 1 and type 2 diabetic patients remains to be clarified.The Japan Diabetes Complications Study (JDCS) is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification (15,16). We have reported the extremely low transition rate from normoalbuminuria and low microalbuminuria in this Japanese cohort (9), as well as incidence and progression rates of DR that were also lower than in Caucasian populations (15). In addition, we have also shown that the incidence and progression rate of DR were lower than those in Caucasian populations and that glycemic control, duration of diabetes, and systolic blood pressure (SBP) were related to DR in the JDCS cohort (17). Here, we elucidated the relationships between DN and DR, and the risk factors of the UAE increase and GFR decline according to the presence or absence of microalbuminuria or DR in the JDCS cohort.     

Type 2 Diabetes and Cognitive Decline in Middle-Aged Men and Women: The Doetinchem Cohort Study

OBJECTIVE

To test the hypothesis that type 2 diabetes is associated with greater decline in cognitive function in middle-aged individuals.

RESEARCH DESIGN AND METHODS

In the Dutch prospective Doetinchem Cohort Study, cognitive functioning was measured twice within a 5-year time interval in 2,613 men and women. Participants were aged 43–70 years at baseline (1995–2002), and no one had a history of stroke. Change in scores on global cognitive function as well as on specific cognitive function domains (memory, speed of cognitive processes, and cognitive flexibility) were compared for respondents with and without type 2 diabetes (verified by the general practitioner or random plasma glucose levels ≥11.1 mmol/l).

RESULTS

At the 5-year follow-up, the decline in global cognitive function in diabetic patients was 2.6 times greater than that in individuals without diabetes. For individuals aged ≥60 years, patients with incident and prevalent diabetes showed a 2.5 and 3.6 times greater decline, respectively, in cognitive flexibility than individuals without diabetes. For most cognitive domains, the magnitude of cognitive decline in patients with incident diabetes was intermediate between that of individuals without diabetes and that of patients with diabetes at baseline.

CONCLUSIONS

Middle-aged individuals with type 2 diabetes showed a greater decline in cognitive function than middle-aged individuals without diabetes.Type 2 diabetes has been associated with cognitive impairments (1) and higher risks of developing vascular dementia (2,3) and Alzheimer disease (1,3). Cognitive dysfunction in type 2 diabetic patients may result from the interaction among metabolic abnormalities intrinsic to diabetes (hyperglycemia and hyperinsulinemia), diabetes-specific complications (such as retinopathy, nephropathy, and neuropathy), and other diabetes-related disorders (such as ischemic heart disease, cerebrovascular disease, hypertension, low serum HDL cholesterol, central obesity, and depression) (4).Most studies on cognitive functioning in relation to diabetes have been cross-sectional or focused on elderly individuals (5,6). We found only four longitudinal studies in which changes in cognitive functioning were evaluated in middle-aged populations (7–10). Longitudinal studies are needed to provide insight into the development of cognitive impairment and decline over time in relation to the onset and duration of diabetes. None of the four studies evaluated changes in cognitive functioning in individuals with recently diagnosed diabetes. Yet, to study the relation between onset of diabetes and cognitive decline, it is essential to include this group and measure cognitive function longitudinally, before and after the onset of diabetes. In the present study, we tested the hypothesis that individuals with prevalent diabetes at baseline and those with incident diabetes during follow-up show a greater decline in cognitive functioning than individuals without diabetes.     

Sulfonylurea Use and Incident Cardiovascular Disease Among Patients With Type 2 Diabetes: Prospective Cohort Study Among Women

OBJECTIVE

Evidence is inconsistent for the association between sulfonylurea use and risk of cardiovascular disease among patients with diabetes. We aimed to prospectively evaluate this association using the Nurses’ Health Study (NHS), a well-established cohort of U.S. women with long-term follow-up.

RESEARCH DESIGN AND METHODS

We followed 4,902 women (mean age 68 years) with diabetes (mean duration 11 years), but without cardiovascular disease at baseline. The use of sulfonylureas and other medications was self-reported at baseline and during the follow-up period of up to 10 years. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% CI for the association between the sulfonylurea use and incident cardiovascular disease while accounting for potential confounders, including age, diabetes duration, diabetes-related complications, other antihyperglycemic medications, BMI, lifestyle factors, family history of cardiovascular diseases, and present chronic conditions. We also applied the propensity score stratification method to address the possibility of residual confounding.

RESULTS

We identified 339 incident cases of cardiovascular disease, including 191 cases of coronary heart disease (CHD) and 148 cases of stroke. A longer duration of sulfonylurea use was significantly associated with a higher risk of CHD (P for trend = 0.002); the RRs for CHD were 1.24 (95% CI 0.85–1.81) for patients who used sulfonylurea therapy for 1–5 years, 1.51 (0.94–2.42) for 6–10 years, and 2.15 (1.31–3.54) for >10 years, compared with nonusers. Compared with users of metformin monotherapy, the RR for CHD was 3.27 (1.31–8.17) for those who were treated with the combination of metformin and sulfonylurea. The analysis using propensity score stratification yielded similar results. We did not observe a significant association between sulfonylurea therapy and stroke risk.

CONCLUSIONS

Long-term use of sulfonylureas was associated with a significantly higher risk of developing CHD among women with diabetes.     

老年糖尿病足的危险因素分析

目的 :分析老年 2型糖尿病并发糖尿病足的危险因素。方法 :检测老年 2型糖尿病并发糖尿病足患者 2 3例及未并发糖尿病足患者 4 8例的糖化血红蛋白 (GHbA1c)、血胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇(HDL C)、收缩压 (SBP)、舒张压 (DBP)、踝动脉 -肱动脉血压比值 (ABI)等指标 ,同时检查糖尿病足患者是否合并其它糖尿病慢性并发症。结果 :糖尿病足组与非糖尿病足组比较 ,GHbA1c、TG、SBP、DBP增高 ,HDL C、ABI降低 ,两组比较有显著差异 (P <0 .0 5 )。糖尿病足组患者常伴有周围神经病变、视网膜病变、高血压等慢性并发症 ,尤其以周围神经病变多见。结论 :老年糖尿病患者并发糖尿病足与高血糖、高甘油三酯血症、高血压显著相关 ,周围神经病变、周围血管病变在糖尿病足发病中具有重要作用。严格控制血糖、血脂、血压对预防糖尿病足有重要意义     

Prognostic Value of Gated Myocardial Perfusion Imaging for Asymptomatic Patients With Type 2 Diabetes: The J-ACCESS 2 investigation

OBJECTIVE

Individuals with type 2 diabetes are at high risk for cardiovascular events. We evaluated the prognostic value of gated myocardial perfusion single-photon computed tomography (SPECT) for asymptomatic diabetic patients in a Japanese population.

RESEARCH DESIGN AND METHODS

Asymptomatic patients (n = 485) aged ≥50 years with either a maximal carotid artery intima-media thickness of ≥1.1 mm, or a urinary albumin ≥30 mg/g creatinine or who had at least two of the following, abdominal obesity, low HDL cholesterol, high triglyceride levels, and hypertension, were enrolled at 50 institutions. The patients were evaluated using gated SPECT with the stress-rest protocol and followed up for 3 years.

RESULTS

During the follow-up period, 62 (13%) events occurred, including 5 cardiac deaths and 57 cardiovascular events. Patients with summed stress scores (SSS) of ≥9 had a significantly higher incidence (of either death or cardiovascular events) than those with SSS scores of <9 (23 vs. 12%; P = 0.009). Multivariate Cox regression analysis showed that significant variables were SSS ≥9, a low estimated glomerular filtration rate, and being a current smoker. Univariate Cox regression analysis showed that ticlopidine and insulin use are potent medical modulators of cardiovascular events.

CONCLUSIONS

The incidences of cardiovascular events and death were significantly high in a select population of type 2 diabetic patients with SPECT abnormalities. A targeted treatment strategy is required for asymptomatic but potentially high-risk patients with type 2 diabetes.Coronary stenosis, myocardial ischemia, and baseline cardiac functions are important factors for the risk stratification of cardiac events and thus are used to predict patient prognosis. Among various clinical factors, diabetes promotes atherosclerosis, resulting in a major pathophysiological cause of cerebral and myocardial infarction (MI) (1). The risk for diabetic patients without prior MI is two- to fourfold higher than that for nondiabetic patients, and it is comparable with the risk for nondiabetic patients with prior MI (2,3). However, because atherosclerosis can progress even in asymptomatic diabetic patients, diagnosing ischemic heart diseases at an early subclinical stage is vital (4).The role of single-photon emission computed tomography (SPECT) in detecting myocardial ischemia and evaluating prognosis has been validated (1,5–7). A prognostic investigation using gated SPECT (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT [J-ACCESS]) in a Japanese population was started in 2001, and the patients were followed up for 3 years (3). That study revealed that diabetes is the most important predictor of cardiac events in the Japanese population, as has been shown in the Finnish population (2). Therefore, we designed the J-ACCESS 2 prospective cohort study of asymptomatic patients with type 2 diabetes (8). The 1st year interim report clarified the value of gated SPECT for individuals with type 2 diabetes (9). The present final report evaluates the prognostic value of gated SPECT and includes a more detailed stratification of ischemic cardiovascular events in diabetic patients.     

Measures of Arterial Stiffness in Youth With Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth study

OBJECTIVE

Arterial stiffness occurs early in the atherosclerotic process; however, few data are available concerning risk factors for arterial stiffness in youth with diabetes. We identified factors associated with arterial stiffness in youth with diabetes and assessed the effects of these factors on the relationship between arterial stiffness and diabetes type (type 1 vs. type 2).

RESEARCH DESIGN AND METHODS

A subset of patients from the SEARCH for Diabetes in Youth study with type 1 (n = 535) and type 2 diabetes (n = 60), aged 10–23 years (52% male; 82% non-Hispanic white; diabetes duration 65 ± 49 months) had arterial stiffness, anthropometrics, blood pressure, fasting lipids, and A1C measured. Arterial stiffness was measured by brachial distensibility (brachD), pulse wave velocity (PWV), and augmentation index adjusted to heart rate of 75 beats/min (AI75).

RESULTS

Youth with type 2 diabetes had worse brachD (5.2 ± 0.9 vs. 6.1 ± 1.2%/mmHg), PWV (6.4 ± 1.3 vs. 5.3 ± 0.8 m/s), and AI75 (6.4 ± 9.9 vs. 2.2 ± 10.2%) than those with type 1 diabetes (P < 0.01 for each). These differences were largely mediated through increased central adiposity and higher blood pressure in youth with type 2 diabetes. We also found a pattern of association of arterial stiffness measures with waist circumference and blood pressure, independent of diabetes type.

CONCLUSIONS

Youth with type 2 diabetes have worse arterial stiffness than similar youth with type 1 diabetes. Increased central adiposity and blood pressure are associated with measures of arterial stiffness, independent of diabetes type. Whether these findings indicate that youth with type 2 diabetes will be at higher risk for future complications requires longitudinal studies.Adults with type 1 or type 2 diabetes are at greater risk for developing cardiovascular disease (CVD) than the general population (1). Nevertheless, the process of atherosclerosis is known to begin in childhood (1,2). Whereas most pediatric diabetes studies have focused on youth with type 1 diabetes, data are now emerging to show that the burden of diabetes-related complications among adolescents with type 2 diabetes is at least as high as that for those with type 1 diabetes (3).Vascular dysfunction occurs early in the atherosclerotic process and is associated with obesity and insulin resistance (4). Multiple methods have been developed to evaluate vascular function noninvasively, including several measures of arterial stiffness, such as brachial distensibility, pulse wave velocity (PWV), and augmentation index (5). Because atherosclerosis develops in a nonuniform fashion (6), multiple measures are needed in any noninvasive study of early CVD in youth.The aim of this report was to identify factors associated with measures of arterial stiffness in youth with diabetes participating in the SEARCH for Diabetes in Youth (SEARCH) study and to assess the effect of these factors on the relationship between arterial stiffness and diabetes type (type 1 vs. type 2).     

2型糖尿病患者血清铁代谢相关指标检测意义

目的 探讨2型糖尿病患者血清铁调素(Hepcidin)、铁蛋白(SF)、转铁蛋白受体(sTfR)和血清铁(SI)的变化与临床意义。方法 130例2型糖尿病患者,分为两组,A组为微量蛋白尿组45例(mAlb30～300 mg/24 h),B组为正常蛋白尿组85例(mAlb＜30 mg/24 h),另选同期45例健康体检者为对照C组。各组均取空腹晨血5 ml离心取血清检测铁调素,SF,sTfR和SI含量。结果 A组患者血清铁调素和SF水平(42.27±32.12 ng/ml,211.6±107.2 ng/ml)均显著高于B组(26.12±18.36 ng/ml,179.1±109.7 ng/ml; P均＜0.05)和C组(9.47±1.65 ng/ml,84.41±47.10 ng/ml),(P均＜0.01); B组患者铁调素和SF水平显著高于C组(P均＜0.01)。各组之间SI水平(15.26 μmol/L,18.65 μmol/L,17.71 μmol/L)和sTfR水平(1.12 μg/L,1.05 μg/L,1.16 μg/L)差异均无统计学意义(t=0.469～1.176,P均＞0.05)。相关分析显示,2型糖尿病患者铁调素与SF呈显著正相关(r=0.329,P＜0.05),铁调素与sTfR,SI无显著相关性(r=0.169,P＞0.05; r=-0.149,P＞0.05)。结论 2型糖尿病患者体内存在以血清铁调素、SF增高为主的铁超负荷和铁代谢紊乱,并与尿微量清蛋白的排泄呈正相关。因此,检测血清铁调素和SF可作为糖尿病早期肾功能损伤的重要预测因子。     

Time in Range in Relation to All-Cause and Cardiovascular Mortality in Patients With Type 2 Diabetes: A Prospective Cohort Study

OBJECTIVEThere is growing evidence linking time in range (TIR), an emerging metric for assessing glycemic control, to diabetes-related outcomes. We aimed to investigate the association between TIR and mortality in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSA total of 6,225 adult patients with type 2 diabetes were included from January 2005 to December 2015 from a single center in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline, and the participants were stratified into four groups by TIR: >85%, 71–85%, 51–70%, and ≤50%. Cox proportional hazards regression models were used to estimate the association between different levels of TIR and the risks of all-cause and cardiovascular disease (CVD) mortality.RESULTSThe mean age of the participants was 61.7 years at baseline. During a median follow-up of 6.9 years, 838 deaths were identified, 287 of which were due to CVD. The multivariable-adjusted hazard ratios associated with different levels of TIR (>85% [reference group], 71–85%, 51–70%, and ≤50%) were 1.00, 1.23 (95% CI 0.98–1.55), 1.30 (95% CI 1.04–1.63), and 1.83 (95% CI 1.48–2.28) for all-cause mortality (P for trend <0.001) and 1.00, 1.35 (95% CI 0.90–2.04), 1.47 (95% CI 0.99–2.19), and 1.85 (95% CI 1.25–2.72) for CVD mortality (P for trend = 0.015), respectively.CONCLUSIONSThe current study indicated an association of lower TIR with an increased risk of all-cause and CVD mortality among patients with type 2 diabetes, supporting the validity of TIR as a surrogate marker of long-term adverse clinical outcomes.     

糖尿病健康教育图教育模式对2型糖尿病患者自护行为的影响

目的 探讨糖尿病健康教育图应用于2型糖尿病患者健康教育的效果.方法 参考美国糖尿病健康教育对话图将图画教育和小组讨论相结合的健康教育理念,收集大量与糖尿病健康教育相关的图片,制作出5幅90 cm×150 cm的图文并茂糖尿病健康教育图.采用随机单盲对照法,将120例2型糖尿病患者分为糖尿病健康教育图教育组(观察组)60例和传统教育组(对照组)60例.观察组应用糖尿病健康教育图进行教育,以图画作为教育的媒介,结合小组讨论进行教育;对照组定期参加医院的糖尿病讲座.分别于教育前、教育后3个月和6个月调查两组糖尿病自护行为得分情况.结果 经重复测量方差分析,教育前后除吸烟维度外,改良糖尿病自护行为量表其他5个维度得分差异均有统计学意义(P<0.001);除吸烟维度外,其他5个维度得分呈上升趋势,教育前与教育后3个月、教育前与教育后6个月、教育后3个月与教育后6个月差异均有统计学意义(P<0.05);除吸烟维度外,两组间改良糖尿病自护行为量表得分差异均有统计学意义(P(0.05).结论 糖尿病健康教育图教育模式能有效提高糖尿病患者自护能力,作为一种新的健康教育方式值得推广.     

2型糖尿病患者血糖波动与糖尿病视网膜病变的相关性研究

[目的]探讨2型糖尿病(T2DM)患者血糖波动与糖尿病视网膜病变(DR)的相关性.[方法]T2DM患者进行眼底照相或眼底荧光造影,根据DR程度分为无视网膜病变(NDR)组、糖尿病背景型视网膜病变(BDR)组、糖尿病增殖型视网膜病变(PDR)组,记录性别、年龄、病程,测量血压、体重指数、糖化血红蛋白、空腹及餐后2h胰岛素、空腹及餐后2h C肽及血脂指标.选取三组中上述基线指标具可比性的病例共106例(NDR组33例,BDR组38例,PDR组35例)纳入观察.采用动态血糖监测系统(CGMS)连续监测患者血糖72 h.[结果]各组间平均血糖水平(MBG)、血糖标准差(SDBG)、平均血糖波动幅度(MAGE)及血糖波动最大幅度(LAGE)相比较有统计学差异(P＜0.05).Spearman相关分析显示,DR与MBG、SDBG、MAGE及LAGE呈正相关(P＜0.05).校正MBG后,DR与SDBG、MAGE及LAGE的相关系数分别为0.297、0.396、0.284(P ＜0.01).[结论]血糖波动与DR的发生发展有关,应尽早干预.     

Impact of Sleep Duration on Obesity and the Glycemic Level in Patients With Type 2 Diabetes: The Fukuoka Diabetes Registry

OBJECTIVE

Few studies are currently available regarding the influence of sleep duration on glycemic control in diabetic patients. The objective of the current study was to examine the relationship between sleep duration, obesity, and the glycemic level in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

A total of 4,870 Japanese type 2 diabetic patients aged ≥20 years were divided into six groups according to their self-reported sleep duration: less than 4.5 h, 4.5–5.4 h, 5.5–6.4 h, 6.5–7.4 h, 7.5–8.4 h, and more than 8.5 h. The associations of sleep duration with obesity and the HbA_1c levels were examined in a cross-sectional manner.

RESULTS

The HbA_1c levels showed a quadratic association with sleep duration; namely, a shorter or longer sleep duration was associated with a higher level compared with a sleep duration of 6.5–7.4 h (P for quadratic trend <0.001). This association remained significant after adjusting for potential confounders, including the total energy intake and depressive symptoms. Furthermore, additional adjustments for obesity, which also showed a U-shaped relationship with sleep duration, did not attenuate the U-shaped sleep-HbA_1c association. A significant interaction between sleep duration and age or the use of insulin was observed for the HbA_1c levels.

CONCLUSIONS

Sleep duration was shown to have U-shaped associations with obesity and the HbA_1c levels in type 2 diabetic patients, independent of potential confounders, and therefore may be an important modifiable factor for the clinical management of patients with type 2 diabetes.An increasing prevalence of type 2 diabetes and its complications, including macro- and microvascular diseases, is a growing public health concern in both developing and developed countries (1). This is probably because of population growth, aging, and the increasing prevalence of obesity, which results from environmental factors such as urbanization, physical inactivity, and the increased consumption of food. More recently, it has been reported that the habitual sleep duration has decreased (2) as a result of the modern lifestyle and 24-h society, and epidemiological evidence has suggested that this is associated with adverse consequences such as obesity or weight gain (3,4), hypertension (5), cardiovascular diseases (6,7), and increased mortality (6). The negative impacts of prolonged sleep duration on these outcomes have also been described (3–7), thus suggesting that there is a U-shaped relationship between sleep duration and health disorders. A possible association between an inadequate sleep duration and the development of type 2 diabetes among nondiabetic subjects has been described as well (8–14), but epidemiological evidence concerning the relationship between sleep duration and glycemic control or obesity among diabetic patients is scarce (15–17). Furthermore, to the best of our knowledge, no study has so far examined this relationship among diabetic patients in Asia, despite the fact that racial differences have been suggested in the association between sleep and diabetes (12,18). In this context, the objective of the current study was to investigate the association of sleep duration with the HbA_1c levels, as well as with obesity, which is the major factor related to poor glycemic control, among Japanese type 2 diabetic patients.     

Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

OBJECTIVE

Macrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Eight hundred thirty-one men and women (aged 60–75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change.

RESULTS

Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, −0.12) and of subclinical markers with actual 4-year decline (standardized β, −0.12, 0.12, and −0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors.

CONCLUSIONS

Stroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted.Cognitive abilities are essential for independent living in later life, and some domains of cognitive functioning decline in mean level from relatively early adulthood (1). Age-related cognitive decline is accompanied by pathological changes in the brain, including cerebral microvascular changes, and although individual differences exist in the severity of age-related microvascular damage in the brain, this is difficult to investigate noninvasively. Systemic atherosclerotic changes in the body may serve as a marker of vascular-related changes in the brain (2) that, in turn, lead to cognitive deficits (3,4). However, the potential of large vessel changes distant from the brain itself to function as markers of cognitive decline remains unclear. We aimed to study a range of measures of clinical and subclinical macrovascular disease that focus on different areas of the vasculature or different underlying pathophysiological mechanisms to assess which of these might function as proxies of cognitive decline.Understanding the role of macrovascular disease in age-related cognitive impairment is particularly important in diabetes, given the higher prevalence of atherosclerotic large vessel disease as well as the accelerated cognitive decline and increased risk of cognitive impairment (5,6) associated with this condition, and the potentially modifiable nature of macrovascular disease (7). The prevalence of stroke, of transient ischemic attack (TIA) (8), and of coronary heart disease (9) are higher in diabetic populations than in nondiabetic populations, and average natriuretic peptide levels, a marker of cardiac stress, are increased (10). Markers of subclinical atherosclerosis also are altered, with increased average carotid intima-media thickness (cIMT) (11) and reduced mean ankle brachial index (ABI) (12). Despite this, investigation into the role of macrovascular disease in age-related cognitive impairment in people with diabetes is limited compared with investigation into this issue in the general (predominantly nondiabetic) population. We set out to determine the association of a variety of measures of subclinical macrovascular disease and cardiovascular event categories with cognitive decline in a sample of older people, all of whom had diabetes (the Edinburgh Type 2 Diabetes Study [ET2DS]). We did so using two cognitive outcomes, actual late-life cognitive change over a 4-year period and estimated lifetime cognitive change. These analyses are timely given the increasing prevalence of diabetes at younger ages (13) that, together with greater survival (14) and greater lifetime exposure to diabetes in current generations, is likely to contribute to increasing prevalence of cognitive impairment.     

血清胱抑素C与2型糖尿病并发症的相关性研究

目的：研究血清胱抑素C （cystatin C,CysC）与2型糖尿病（T2DM）并发症的相关性.方法：将536例住院T2DM患者根据是否合并糖尿病慢性并发症分为不合并糖尿病并发症的对照组、合并周围血管病变（peripheral arterial disease,PAD）组、合并肾脏病变（diabetic nephropathy,DN）组、合并视网膜病变（diabetic retinopathy,DR）组、合并周围神经病变（diabetic peripheral neuropathy,DPN）组,记录患者的年龄、病程、身高、体质量、腰围、臀围,并检测空腹血糖（FPG）、糖化血红蛋白（HbA1c）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、血清肌酐（Scr）、血清CysC、空腹胰岛素（FINS）、肾小球滤过率（GFR）等,计算体质量指数（BMI）、胰岛素抵抗指数（HOMA-IR）,比较各组间所测指标的差异性,并分析CysC与T2DM并发症的相关性.结果：PAD组、DN组、DR组及DPN组的血清CysC水平均高于对照组（P＜0.05）.结论：T2DM患者的血清CysC升高与合并糖尿病周围血管病变、肾脏病变、视网膜病变、周围神经病变等慢性并发症具有相关性.