Glycated Hemoglobin and All-Cause and Cause-Specific Mortality in Singaporean Chinese Without Diagnosed Diabetes: The Singapore Chinese Health Study

OBJECTIVEGlycated hemoglobin (HbA_1c) is a robust biomarker of the preceding 2 to 3 months average blood glucose level. The aim of this study was to examine the association between HbA_1c and mortality in a cohort of Southeast Asians.RESULTSRelative to participants with an HbA_1c of 5.4–5.6% (36–38 mmol/mol), participants with HbA_1c ≥6.5% (≥48 mmol/mol) had an increased risk of all-cause, cardiovascular, and cancer mortality during an average of 10.1 years of follow-up; HRs (95% CIs) were 1.96 (1.56–2.46), 2.63 (1.77–3.90), and 1.51 (1.04–2.18), respectively. No level of HbA_1c was associated with increased risk of respiratory mortality. Levels <6.5% HbA_1c were not associated with mortality during follow-up. The results did not materially change after excluding observation of first 3 years post–blood draw.CONCLUSIONSHbA_1c levels consistent with undiagnosed type 2 diabetes (≥6.5%) are associated with an increased risk of all-cause and cause-specific mortality in Chinese men and women.     

Type A Behavior and Risk of All-Cause Mortality,CAD, and CAD-Related Mortality in a Type 1 Diabetic Population: 22 Years of Follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study

OBJECTIVE

To determine whether type A behavior predicts all-cause mortality and incident coronary artery disease (CAD) in a type 1 diabetic population.

RESEARCH DESIGN AND METHODS

Follow-up data (22 years) from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset type 1 diabetes were analyzed for the 506 participants who completed the Bortner Rating Scale (measuring type A behavior) and Beck Depression Inventory (BDI) at baseline (1986–1988). CAD comprised myocardial infarction as determined by hospital records/Q waves on electrocardiogram (ECG), CAD death (determined by a mortality classification committee), angiographic stenosis, ischemic ECG, and angina.

RESULTS

There were 128 deaths (25.3%) during follow-up. Univariate analysis showed an inverse relationship between Bortner scores and all-cause mortality (P = 0.01), which remained significant after allowing for age, sex, duration, HbA_1c, education, smoking, BMI, and physical activity (P = 0.03). However, the addition of BDI scores attenuated the relationship (P = 0.11) with a significant interaction (P = 0.03) such that any protective effect against mortality was limited among individuals with lower BDI scores (bottom three quintiles) (P = 0.07), whereas no effect was seen in those with higher BDI scores (P = 0.97). Bortner scores showed only a borderline association with incident CAD (P = 0.09).

CONCLUSIONS

Those with higher type A behavior have lower all-cause mortality in our type 1 diabetic population, an effect that interacts with depressive symptomatology such that it is only operative in those with low BDI scores. Further research should focus on understanding this interaction.The incidence of type 1 diabetes, which remains incurable, has continued to rise annually by ∼3% (1). Unfortunately, prevention is not currently feasible. Therefore, the exploration of type 1 diabetes complications, untimely mortality and the associated risk factors, must continue. Type A behavior has been described as an action-emotion complex, meaning that the behavior is elicited by the outside environment (2). People characterized as having type A behavior tend to focus toward achieving and accomplishing more in less time than others. Because of these tendencies, these people tend to be competitive, aggressive, time urgent, and work oriented and can become annoyed if things are not achieved in a time frame they find sufficient (2). Therefore, it seems that type A behaviors are not a set of personality characteristics that come about due to the environment; rather, the behavior is a result of predispositions within a person that are exhibited due to specific situations (2). In an earlier review, Matthews and Haynes (2) noted that although type A behavior was linked to increased coronary heart disease (CHD) risk in the general population, findings were consistently negative in high-risk populations. For example, the prospective Western Collaborative Group Study (WCGS) found that those with type A behavior experienced an increased rate of CHD compared with type B behavior (P = 0.001) (3). However, in their high-risk population who had already undergone a CHD event, type A behavior had a lower CHD-associated mortality rate in those surviving 24 h or more than those characterized as having type B behavior (P = 0.03) (4). Therefore, it appears that type A behavior may have different effects on health depending on underlying chronic disease status.Little is known about the psychosocial contribution to the increased coronary artery disease (CAD) risk seen in people with type 1 diabetes beyond depression (5,6), in particular, whether type 1 diabetes is an additional high-risk group in which the inverse association between type A behavior and CAD/mortality exists. Cross-sectional data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study have shown (using the Bortner Rating Scale) that participants with multiple complications, including CAD, retinopathy, neuropathy, and/or nephropathy, reported less type A behaviors than those without complications (P < 0.05) (5). The long length of follow-up now available in the EDC allowed a prospective analysis of the role of type A behavior in mortality and CAD, and we are unaware of other investigations of this relationship. We also investigated the association between type A behavior and CAD-related mortality in those already diagnosed with CAD and whether the established effect of depressive symptomatology on CAD incidence interacted with or explained any effect of type A behavior. Thus, the aims of the current study were to investigate the relationships between type A behavior and mortality, type A behavior and incident CAD, and type A behavior and mortality among those with CAD during 22 years of follow-up.     

Serum 25-Hydroxyvitamin D Values and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort Study

Objective

To determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and all-cause and cause-specific mortality.

All-Cause Mortality Risk Among a National Sample of Individuals With Diabetes

OBJECTIVE

Little is known about the relative contributions of modifiable risk factors to overall diabetes mortality. The purpose of the current study is to 1) assess the association between modifiable risk factors and all-cause mortality among a nationally representative sample of individuals with diabetes and 2) determine the population-attributable risk percent (PAR%) for these factors.

RESEARCH DESIGN AND METHODS

We analyzed data from a nationally representative sample of 1,507 adults over the age of 17 years with a self-reported diagnosis of diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) mortality study. Our main outcome measures were all-cause mortality and PAR%. We used the Cox proportional hazard analysis to determine hazard ratios (HRs) for known diabetes risks and calculated PAR%.

RESULTS

Among adults with diabetes, the HRs for all-cause mortality were significant for individuals who had an A1C ≥8% (HR 1.65, 95% CI 1.11–2.45) or reported no regular physical activity (1.58, 1.24–2.02) or current tobacco use (1.77, 1.15–2.73). The population-attributable risk was 15.3% for A1C value ≥8%, 16.4% for no regular physical activity, and 7.5% for current tobacco use.

CONCLUSIONS

Health systems may consider prioritizing care to include smoking cessation, increasing physical activity, and moderate glycemic control among patients with diabetes. This study suggests that focusing on these areas may result in significant reductions in mortality in individuals with diabetes.Optimal disease management for individuals with diabetes often involves significant lifestyle modifications (including diet, physical activity, and smoking cessation) in addition to complex medication regimens to control blood glucose, blood pressure, and serum lipid levels. These treatments have the potential to improve risk factors for morbidity and mortality among individuals with type 2 diabetes (1). Given the complexity of care for individuals with diabetes and the time limitations of health care providers (2), the relative association of each of these factors will be useful to inform policy and planning for appropriate diabetes care.The purpose of the current study was to determine the association of modifiable risk factors for all-cause mortality among a nationally representative sample of individuals with diabetes and to assess the population-attributable risk percent (PAR%) for death for risk factors including blood pressure, lipid and glycemic control, smoking, and physical activity. Previous studies using data from the National Health and Nutrition Examination Survey (NHANES) have not examined the relative contribution of lifestyle factors such as physical activity (3) or have relied on older data that did not include information on glycemic control (4). In addition, previous studies have presented relative risk estimates for these factors, which do not necessarily give an indication of the public health implications of the exposure of interest or its effect on the population (3,5). In contrast, PAR% calculations are suitable in addressing public health policy questions regarding appropriate interventions, population-based treatment strategies, and quality improvement efforts (6).     

HbA1c and the Risks for All-Cause and Cardiovascular Mortality in the General Japanese Population: NIPPON DATA90

OBJECTIVE

Associations between HbA_1c and cardiovascular diseases (CVD) have been reported mainly in Western countries. It is not clear whether HbA_1c measurements are useful for assessing CVD mortality risk in East Asian populations.

RESEARCH DESIGN AND METHODS

The risk for cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. A total of 7,120 participants (2,962 men and 4,158 women; mean age 52.3 years) free of previous CVD were followed for 15 years. Adjusted hazard ratios (HRs) and 95% CIs among categories of HbA_1c (<5.0%, 5.0–5.4%, 5.5–5.9%, 6.0–6.4%, and ≥6.5%) for participants without treatment for diabetes and HRs for participants with diabetes were calculated using a Cox proportional hazards model.

RESULTS

During the study, there were 1,104 deaths, including 304 from CVD, 61 from coronary heart disease, and 127 from stroke (78 from cerebral infarction, 25 from cerebral hemorrhage, and 24 from unclassified stroke). Relations to HbA_1c with all-cause mortality and CVD death were graded and continuous, and multivariate-adjusted HRs for CVD death in participants with HbA_1c 6.0–6.4% and ≥6.5% were 2.18 (95% CI 1.22–3.87) and 2.75 (1.43–5.28), respectively, compared with participants with HbA_1c <5.0%. Similar associations were observed between HbA_1c and death from coronary heart disease and death from cerebral infarction.

CONCLUSIONS

High HbA_1c levels were associated with increased risk for all-cause mortality and death from CVD, coronary heart disease, and cerebral infarction in general East Asian populations, as in Western populations.Since the association between HbA_1c and microangiopathy was established in patients with diabetes, HbA_1c has been used for not only the determination of glucose control among patients with diabetes but also the diagnosis of diabetes (1). Measurement of HbA_1c is also recommended for cardiovascular risk assessment in asymptomatic adults without a diagnosis of diabetes (2) because the association between HbA_1c and the risk for cardiovascular disease (CVD) in general populations has been reported, mainly from Western countries (3–10).There have been only a few studies regarding the associations between HbA_1c and CVD in Asian populations (11–13). Furthermore, these studies were from Japan, and HbA_1c measurements were expressed mainly using Japan Diabetes Society (JDS) values rather than National Glycohemoglobin Standardization Program (NGSP) values; thus, we cannot compare these results with those from Western countries. Recently, the JDS provided an equation for the conversion from HbA_1c (JDS) to HbA_1c (NGSP) units (14), which allows a comparison of the results from Japanese studies and previous studies from Western countries.CVD in East Asian people is characterized by a higher rate of stroke and lower rate of coronary heart disease compared with CVD in Western populations (15). In one previous study evaluating the association between HbA_1c and incidence of stroke in Japan, ischemic stroke, but not hemorrhagic stroke, was associated with HbA_1c in Asian populations (12). Other studies from Japan (11,13) showed a significant association between HbA_1c and CVD; however, the number of participants and CVD events were too small to calculate the risk by subtype of CVD, such as coronary heart disease, stroke, cerebral infarction, and cerebral hemorrhage.The current study was performed to examine the association between HbA_1c using NGSP values and the risks for death from all causes and from CVD (coronary heart disease, cerebral infarction, and cerebral hemorrhage) in a 15-year cohort study of representative Japanese men and women randomly selected from the overall Japanese population.     

Type 2 Diabetes Genetic Predisposition,Obesity, and All-Cause Mortality Risk in the U.S.: A Multiethnic Analysis

OBJECTIVE

Type 2 diabetes (T2D) is associated with increased mortality in ethnically diverse populations, although the extent to which this association is genetically determined is unknown. We sought to determine whether T2D-related genetic variants predicted all-cause mortality, even after accounting for BMI, in the Third National Health and Nutrition Examination Survey.

RESEARCH DESIGN AND METHODS

We modeled mortality risk using a genetic risk score (GRS) from a weighted sum of risk alleles at 38 T2D-related single nucleotide polymorphisms. In age-, sex-, and BMI-adjusted logistic regression models, accounting for the complex survey design, we tested the association with mortality in 6,501 participants. We repeated the analysis within ethnicities (2,528 non-Hispanic white [NHW], 1,979 non-Hispanic black [NHB], and 1,994 Mexican American [MA]) and within BMI categories (<25, 25–30, and ≥30 kg/m²). Significance was set at P < 0.05.

RESULTS

Over 17 years, 1,556 participants died. GRS was associated with mortality risk (OR 1.04 [95% CI 1.00–1.07] per T2D-associated risk allele, P = 0.05). Within ethnicities, GRS was positively associated with mortality risk in NHW and NHB, but not in MA (0.95 [0.90–1.01], P = 0.07). The negative trend in MA was largely driven by those with BMI <25 kg/m² (0.91 [0.82–1.00]). In NHW, the positive association was strongest among those with BMI ≥30 kg/m² (1.07 [1.02–1.12]).

CONCLUSIONS

In the U.S., a higher T2D genetic risk was associated with increased mortality risk, especially among obese NHW. The underlying genetic basis for mortality likely involves complex interactions with factors related to ethnicity, T2D, and body weight.     

Angiopoietin-Like Protein 2 and Risk of Type 2 Diabetes in a General Japanese Population: The Hisayama Study

OBJECTIVE

To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM).

RESEARCH DESIGN AND METHODS

A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: <2.15, 2.16–2.71, 2.72–3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM.

RESULTS

In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14–2.85; P = 0.01).

CONCLUSIONS

Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels.Angiopoietin-like proteins (ANGPTLs), which are structurally similar to angiopoietins, are characterized by a coiled-coil domain in the N-terminus and a fibrinogen-like domain in the C-terminus. Seven ANGPTLs have been identified to date (1–3); one of them, ANGPTL2, has been shown to be expressed abundantly in adipose tissues and to be a key mediator linking obesity to adipose tissue inflammation and systemic insulin resistance in mice (4,5). In humans, ANGPTL2 is also closely related to adiposity and inflammation (4). However, the association of serum ANGPTL2 levels with the risk of developing type 2 diabetes (T2DM) has not been investigated to date. The objective of this study was to examine this issue in a cohort of the general Japanese population, taking into account a comprehensive range of confounders.     

Coffee Consumption and Risk of Cardiovascular Diseases and All-Cause Mortality Among Men With Type 2 Diabetes

OBJECTIVE

Coffee consumption has been linked to detrimental acute metabolic and hemodynamic effects. We investigated coffee consumption in relation to risk of CVDs and mortality in diabetic men.

RESEARCH DESIGN AND METHODS

We conducted a prospective cohort study including 3,497 diabetic men without CVD at baseline.

RESULTS

After adjustment for age, smoking, and other cardiovascular risk factors, relative risks (RRs) were 0.88 (95% CI 0.50–1.57) for CVDs (P for trend = 0.29) and 0.80 (0.41–1.54) for all-cause mortality (P for trend = 0.45) for the consumption of ≥4 cups/day of caffeinated coffee compared with those for non–coffee drinkers. Stratification by smoking and duration of diabetes yielded similar results. RRs for caffeine intake for the highest compared with the lowest quintile were 1.02 (0.70–1.47; P for trend = 0.96) for CVDs and 0.96 (0.64–1.44; P for trend = 0.69) for mortality.

CONCLUSIONS

These data indicate that regular coffee consumption is not associated with increased risk for CVDs or mortality in diabetic men.Coffee drinking is widespread across the world and has been linked with both beneficial and harmful effects on biological markers of cardiovascular disease (CVD) (1). Recently, caffeine has been reported to have acute detrimental effects on glucose tolerance in diabetes (2). Whereas most prospective studies have suggested that coffee consumption is not associated with increased risk for CVD in general population (3,4), data among diabetes are sparse (5). Therefore, we prospectively examined the relationship between coffee and coronary heart disease (CHD), stroke, and mortality among men with type 2 diabetes in the Health Professionals Follow-up Study (HPFS).     

Cardiovascular and All-Cause Mortality Over a 23-Year Period Among Chinese With Newly Diagnosed Diabetes in the Da Qing IGT and Diabetes Study

OBJECTIVE

Despite its growing prevalence in China, the extent to which diabetes leads to excess cardiovascular disease (CVD) mortality and all-cause mortality is unclear.

RESEARCH DESIGN AND METHODS

We compared death rates and causes of death among 630 people with newly diagnosed diabetes (NDD) and 519 with normal glucose tolerance (NGT) who, in 1986, were identified as a result of screening 110,660 adults aged 25–74 years for diabetes in Da Qing, China.

RESULTS

During 23 years of follow-up, 338 (56.5%) participants with NDD and 100 (20.3%) with NGT died. CVD was the predominant cause of death in those with diabetes (47.5% in men and 49.7% in women), almost half of which was due to stroke (52.3% in men and 42.3% in women). The age-standardized incidence of all-cause death was three times as high in those with NDD as in those with NGT with incidences (per 1,000 person-years) of 36.9 (95% CI 31.5–42.3) vs. 13.3 (10.2–16.5) in men (P < 0.0001) and 27.1 (22.9–31.4) vs. 9.2 (7.8–10.6) in women (P < 0.0001). The incidence of CVD deaths in men and women with NDD (17.5 [13.8–21.2] vs. 13.5 [10.5–16.5]) did not differ significantly. Significantly higher death rates attributable to renal disease and infection were also found in the NDD group.

CONCLUSIONS

Diabetes is associated with a substantially increased risk of death in Chinese adults, especially from CVD, almost half of which is due to stroke.     

Development and Validation of a Predicting Model of All-Cause Mortality in Patients With Type 2 Diabetes

OBJECTIVE

To develop and validate a parsimonious model for predicting short-term all-cause mortality in patients with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS

Two cohorts of patients with T2DM were investigated. The Gargano Mortality Study (GMS, n = 679 patients) was the training set and the Foggia Mortality Study (FMS, n = 936 patients) represented the validation sample. GMS and FMS cohorts were prospectively followed up for 7.40 ±2.15 and 4.51 ±1.69 years, respectively, and all-cause mortality was registered. A new forward variable selection within a multivariate Cox regression was implemented. Starting from the empty model, each step selected the predictor that, once included into the multivariate Cox model, yielded the maximum continuous net reclassification improvement (cNRI). The selection procedure stopped when no further statistically significant cNRI increase was detected.

RESULTS

Nine variables (age, BMI, diastolic blood pressure, LDL cholesterol, triglycerides, HDL cholesterol, urine albumin-to-creatinine ratio, and antihypertensive and insulin therapy) were included in the final predictive model with a C statistic of 0.88 (95% CI 0.82–0.94) in the GMS and 0.82 (0.76–0.87) in the FMS. Finally, we used a recursive partition and amalgamation algorithm to identify patients at intermediate and high mortality risk (hazard ratio 7.0 and 24.4, respectively, as compared with those at low risk). A web-based risk calculator was also developed.

CONCLUSIONS

We developed and validated a parsimonious all-cause mortality equation in T2DM, providing also a user-friendly web-based risk calculator. Our model may help prioritize the use of available resources for targeting aggressive preventive and treatment strategies in a subset of very high-risk individuals.The mortality rate of diabetic patients is about twice as much as that of nondiabetic individuals of a similar age (1); this makes diabetes a leading risk factor for mortality, which accounts for 2.9 million global events yearly (2). This scenario is expected to further deteriorate, given that diabetes prevalence is increasing worldwide (3). Thus, predicting mortality in diabetic patients is definitively needed in order to target aggressive prevention strategies to very high-risk patients.Only a few models for predicting all-cause mortality in diabetic patients have been proposed thus far (4–6). Unfortunately, none of them have been validated in an external cohort. In addition, these models have used standard approaches that are not specifically suited for prediction model building. Instead, new attractive statistical methods based on the use of the reclassification measures (7–13) have become recently available when prediction model building is at issue; among these, the continuous net reclassification improvement (cNRI) has been mathematically proven to be a measure of effect size.The aim of our study was to develop a parsimonious model for predicting short-term all-cause mortality in patients with type 2 diabetes mellitus (T2DM) based on the use of a forward variable selection driven by the cNRI approach and to validate it in a second independent sample. For this purpose, two prospective studies on patients with T2DM, the Gargano Mortality Study (GMS) and the Foggia Mortality Study (FMS), were analyzed.     

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.     

The Association Between Cardiorespiratory Fitness and Risk of All-Cause Mortality Among Women With Impaired Fasting Glucose or Undiagnosed Diabetes Mellitus

OBJECTIVE: To evaluate the independent and joint associations among cardiorespiratory fitness (CRF), body mass index, and risk of mortality from any cause among women with impaired fasting glucose (IFG) or undiagnosed diabetes mellitus (DM).PATIENTS AND METHODS: Female patients (N=3044; mean age, 47.4 years) with IFG or undiagnosed DM completed a maximal exercise treadmill test (between January 26, 1971, and March 21, 2001). The women had no history of a cardiovascular disease event or diagnosed DM at baseline. Cardiorespiratory fitness was defined categorically as low (bottom 20%), moderate (middle 40%), or high (upper 40%) according to previously published Aerobics Center Longitudinal Study guidelines. Body mass index was calculated as the weight in kilograms divided by the height in meters squared (kg/m²).RESULTS: During a 16-year follow-up period, 171 deaths occurred. There was an inverse association between CRF and all-cause mortality risk. Women with moderate or high CRF were at lower risk of mortality (moderate CRF, 35% lower; high CRF, 36% lower; P_trend=.03) than those with low CRF. An exercise capacity lower than 7 metabolic equivalents was associated with a 1.5-fold higher risk of death than an exercise capacity of 9 metabolic equivalents or higher (P_trend=.05). The multivariate adjusted hazard ratios (HRs), including adjustments for CRF, were higher for heavier patients than for patients of normal weight (overweight patients: HR, 0.86; 95% confidence interval, 0.57-1.30; obese patients: HR, 1.19; 95% confidence interval, 0.70-2.03; P_trend=.84). Combined analyses showed that women who were overweight or obese and unfit (low CRF) were at more than twice the risk of death than women who were of normal weight and fit (moderate or high CRF).CONCLUSION: Cardiorespiratory fitness, not body mass index, is a significant predictor of all-cause mortality among women with IFG or undiagnosed DM. Assessing CRF levels provides important prognostic information independent of traditional risk factors.ACLS = Aerobics Center Longitudinal Study; BMI = body mass index; CI = confidence interval; CRF = cardiorespiratory fitness; CVD = cardiovascular disease; DM = diabetes mellitus; HR = hazard ratio; IFG = impaired fasting glucose; MET = metabolic equivalentImpaired fasting glucose (IFG) has been associated with an elevated risk of premature mortality.^1,2 Recently, greater attention has been directed toward IFG in efforts to reduce the development of diabetes mellitus (DM) and cardiovascular disease (CVD). In 2003, the American Diabetes Association recommended that the definition of IFG be expanded to include fasting glucose concentrations between 100 mg/dL and 125 mg/dL (to convert to mmol/L, multiply by 0.0555), as opposed to the previous concentrations of 110 mg/dL to 125 mg/dL.³ In 2002, 54 million people in the United States aged 20 years or older had IFG, representing 26% of the total US population; this number would be higher if the more stringent definition were used.⁴ In 2005, 20.8 million people (7% of the total US population) in the same age group had DM.⁴ Half of these cases of DM were expected to be undiagnosed and asymptomatic.⁵ The risk of premature CVD and death is 2 to 4 times higher for persons with DM than for those of equivalent age without DM.^6,7 Therefore, the detection and treatment of CVD risk factors may be particularly important for preventing CVD among persons with asymptomatic IFG and DM.A low cardiorespiratory fitness (CRF) level is a predictor of all-cause mortality among men with type 2 DM.⁸ Recent studies^9,10 have also reported a strong and independent association between CRF and mortality among men with DM in all body mass index (BMI) and body fatness groups.¹¹ However, most previous studies have focused on the association between CRF and mortality among either men only or men and women who are sedentary but apparently healthy.^8,9,12For editorial comment, see page 771There is a strong independent association between obesity and all-cause mortality among both men and women.^13-17 Most studies have found that this association is J-shaped or U-shaped. Like CRF studies, most obesity studies have focused on the association between obesity and mortality in women, men, or both men and women in the general population, regardless of any disease state.^13-16 Few studies have focused on persons with IFG and undiagnosed DM, especially women. To our knowledge, no previous study has concurrently evaluated the association between CRF, overweight or obesity status as reflected by BMI, and death among women with IFG. Therefore, the primary aim of this study was to evaluate the association between CRF and risk of all-cause mortality among women with IFG or undiagnosed DM.     

糖尿病前期及糖尿病病人营养及运动健康教育需求调查

目的 了解糖尿病前期病人及糖尿病病人对营养、运动健康教育需求,为病人实施个性化、全程、优质的健康教育模式提供理论依据.方法 自行设计调查问卷,对12 所医院626例糖尿病前期病人及糖尿病病人,进行健康教育需求调查,并分析年龄、医疗费用及文化程度对其健康教育需求的影响.结果 (1)病人最希望了解的糖尿病营养健康教育内容是饮食治疗的意义,其次是食物选择方法、营养素分配与餐次、食物交换份法、热量计算方法和食物血糖生成指数的概念(P=0.000).(2)病人最希望了解的运动健康教育内容是运动疗法的意义,其次是运动疗法的注意事项、运动处方的内容(P=0.000).(3)健康教育中有5项内容与文化程度相关(P＜0.05),高学历病人需求明显(P＜0.05).该5 项需求分别是:了解食物血糖生成指数的概念,了解食物选择方法,了解运动疗法的意义,了解运动处方的内容及了解运动疗法的注意事项.(4)营养健康教育需求中"了解食物选择方法"、运动健康教育需求中"了解运动疗法的意义"均与患病时间相关(P＜0.05),患病时间短的病人需求更明显(P＜0.05).结论(1)病人认为健康教育需求重要性排序是从易到难的,建议将容易理解的项目排在前面,而相对较难理解的排在后面;并对病人需要了解的重要术语及相关知识做出通俗的解释,如食物交换份法、食物血糖生成指数.(2)在教育前,护士充分评估病人的影响因素,重点评估文化程度、患病时间,以便有针对性地给予健康教育.     

Effect of Postmenopausal Status and Age at Menopause on Type 2 Diabetes and Prediabetes in Japanese Individuals: Toranomon Hospital Health Management Center Study 17 (TOPICS 17)

OBJECTIVE

Findings on the effect of menopause or age at menopause on the presence of hyperglycemia are controversial, and why women after menopause have a higher probability of having hyperglycemia than men in the same age range remains unknown.

RESEARCH DESIGN AND METHODS

We reviewed data on 29,189 men, 6,308 premenopausal women, and 4,570 postmenopausal women in Japan. Odds ratios (ORs) for diabetes or prediabetes indicated by American Diabetes Association criteria were calculated for men and for pre- and postmenopausal women.

RESULTS

Compared with premenopausal women, women after natural menopause had an age-adjusted OR of 1.40 (95% CI 1.03–1.89) for diabetes, and women after menopause by surgical or other causes had an age-adjusted OR of 1.59 (1.07–2.37). The age-adjusted OR in men was 4.02 (3.15–5.14). Compared with premenopausal nondiabetic women, postmenopausal nondiabetic women had a significantly elevated OR of 1.33 (1.20–1.48) for prediabetes; nondiabetic men had an OR of 1.93 (1.77–2.10) independently of age and demographic and metabolic factors. Even among women aged <50 years, postmenopausal status was significantly associated with an elevated OR (1.50 [1.18–1.91]) for dysglycemia (either diabetes or prediabetes). Postmenopausal women aged ≥50 years had a particularly elevated OR for dysglycemia, regardless of age at menopause.

CONCLUSIONS

The postmenopausal state was significantly associated with the presence of dysglycemia independently of normal aging, although the increased probability in postmenopausal women did not equal that in men. Among women, menopause and older age might additively influence the elevated probability of dysglycemia.Questions remain about why women after menopause have an increased risk of diabetes compared with men in the same age-group. The prevalence of diabetes was reported to be lower in women than in men aged ≤60 years, whereas women in their 60s and 70s were more likely to have diabetes than men of the same age (1,2), suggesting that the hormonal changes that characterize menopause might be associated with the risk of diabetes in women after menopause (3). Although the association of menopausal status and hyperglycemia has been investigated (4–12), findings about whether the postmenopausal state would influence hyperglycemia independently of normal aging remain controversial. Two cohort studies with a large number of female participants investigated the impact of the postmenopausal state on diabetes compared with the premenopausal state (13,14). A study of 22,426 Japanese women suggested that there is no significant association between the postmenopausal state and diabetes when adjustment is made for chronological age (14). However, the other cross-sectional study of Italian women showed a positive association between spontaneous menopause and diabetes independently of age and demographic factors (13). A review indicated that neither natural nor surgical menopause per se has a strong association with diabetes risk (15).Weight gain, which commonly occurs during the menopausal transition, seems to be attributable to aging rather than to the menopausal transition itself (3,16). However, menopause is associated with changes in body composition, such as increased total body fat or abdominal fat and a decrease in lean body mass, which in turn are linked to impairments in glucose metabolism and insulin sensitivity (3). The occurrence of dysglycemia may be a direct result of ovarian failure or, alternatively, an indirect result of the metabolic consequences of central fat redistribution with estrogen deficiency (17). A study of Korean women showed that the prevalence rate of individuals with metabolic syndrome is markedly high in those ≥50 years of age and reached a peak in women in their 60s (7). Nonetheless, whether menopause would be associated with hyperglycemia independently of age and these other closely related metabolic factors remains unknown. In a prospective study in Spain that included 475 women, the presence of type 2 diabetes, impaired glucose tolerance, impaired fasting glucose, and other cardiometabolic markers did not differ significantly between women who went from premenopause to postmenopause and those who did not experience menopause during a 6-year follow-up period (18). To date, the joint effect of older age and the postmenopausal state on the presence of dysglycemia has not been clarified. Additionally, a few studies investigated whether a significant association exists between menopause and hyperglycemia among women without diabetes (6,19), and the results were inconsistent.Controversy also exists about whether early age at menopause would increase diabetes risk. A recent study of postmenopausal women found early menopause to be associated with an increased risk of developing diabetes (20). In another study, on the other hand, age at menopause was not associated with diabetes in Chinese postmenopausal women (21). Cross-sectional studies in Italy (13) and China (11) did not show a significant association of age at menopause with diabetes. It should be noted that the definition of the diagnosis of diabetes differed among these studies (11,13,20,21).Therefore, in the present cross-sectional study of Japanese individuals, we aimed to investigate whether menopause among women is associated with dysglycemia independently of normal aging and the possible mechanism whereby women after menopause would have a higher probability of having dysglycemia compared with men of a similar age. We also aimed to clarify the effect of age at menopause on the presence of type 2 diabetes and prediabetes in Japanese women.     

Sex Differences in All-Cause and Cardiovascular Mortality,Hospitalization for Individuals With and Without Diabetes,and Patients With Diabetes Diagnosed Early and Late

OBJECTIVE

To compare risk of all-cause mortality, cardiovascular disease (CVD) mortality, acute myocardial infarction (AMI) mortality, stroke mortality, and hospitalizations for males and females with and without diabetes and those with diabetes diagnosed early and late.

RESEARCH DESIGN AND METHODS

We conducted a population-based retrospective cohort study including 73,783 individuals aged 25 years or older in Newfoundland and Labrador, Canada (15,152 with diabetes; 9,517 with late diagnoses).

RESULTS

Males and females with diabetes had an increased risk of all-cause mortality, CVD mortality, AMI mortality, and CVD hospitalizations compared with individuals without diabetes, and the risk was stronger in females than in males. For females, risks of all-cause mortality (hazard ratio [HR] 1.85 [95% CI 1.74–1.96]) and CVD hospitalizations (2.57 [2.24–2.94]) were significantly higher compared with their male counterparts (1.59 [1.51–1.69] and 1.92 [1.72–2.14]). Females with diabetes diagnosed late had an increased risk of CVD mortality (6.54 [4.80–8.91]) and CVD hospitalizations (5.22 [4.31–6.33]) compared with females without diabetes, and both were significantly higher compared with their male counterparts (3.44 [2.47–4.79]) and (3.33 [2.80–3.95]).

CONCLUSIONS

Females with diabetes have a greater risk of mortality than males with diabetes. CVD has a greater impact on females with diabetes than males, especially when diagnosed at a later stage. Different management strategies should be considered for males and females and those with early and late diagnoses of diabetes.Diabetes has become a health problem of increasing significance in the past two decades. The number of individuals with diabetes will reach 366 million in 2011 and will increase to 552 million by 2030 (1). In Canada, the age-standardized incidence and prevalence of diabetes have been increasing in recent years (2).A challenge with type 2 diabetes is the late diagnosis of the disease because many individuals who meet the criteria are often asymptomatic. Approximately 183 million people, or half of those who have diabetes, are unaware they have the disease (1). Furthermore, type 2 diabetes can be present for 9 to 12 years before being diagnosed and, as a result, complications are often present at the time of diagnosis (3). Insulin resistance and β-cell dysfunction are largely responsible for the development of diabetes and its related complications, and both are present very early in the natural history of diabetes (4). However, the potential does exist to prevent or at least delay the onset of type 2 diabetes because several randomized control trials have shown that both lifestyle and pharmacologic interventions in adults are effective (5–8). In addition to preventing diabetes, it is also possible to reduce diabetes-related complications through intensive blood glucose control. Results from the UK Prospective Diabetes Study (UKPDS) have shown that intensive blood glucose control reduces diabetes-related complications (6–9). Early detection of type 2 diabetes is critical because effective and active management is essential for those with newly diagnosed diabetes who have not developed complications.Cardiovascular disease (CVD) is the most common comorbidity associated with diabetes, and with 50% of those with diabetes dying of CVD it is the most common cause of death (1). Acute myocardial infarction (AMI) and stroke are other common comorbidities associated with diabetes. Individuals with diabetes have an increased risk of all-cause mortality and morbidity related to CVD, AMI, and stroke compared with individuals without diabetes (9–12). Although studies consistently have found that individuals with diabetes have a higher risk of mortality and hospitalizations compared with those without diabetes, results have been inconsistent when comparing males and females. Most studies have found that females with diabetes have a greater risk of mortality and hospitalizations than males with diabetes (9,10,12–17). Two previous meta-analyses found that diabetes is a stronger risk factor for CVD mortality in females than in males; however, studies that did not adjust for major CVD risk factors were included in these meta-analyses (18,19). A meta-analysis conducted by Kanaya et al. (20), which included studies that controlled for CVD risk factors, found that the risks associated with diabetes for coronary heart disease mortality, nonfatal myocardial infarction, and CVD were higher among females than males. However, the differences were not statistically significant.Newfoundland and Labrador has the highest age-standardized prevalence of diabetes in Canada (2), and the age-standardized mortality and hospitalization rates for CVD, AMI, and stroke are some of the highest in the country (21,22). A better understanding of mortality and hospitalizations associated with diabetes for males and females is important to support diabetes prevention and management. Therefore, the objectives of this study were to compare the risk of all-cause, CVD, AMI, and stroke mortality and hospitalizations for males and females with and without diabetes and those with early and late diagnoses of diabetes.     

Nonlinear Associations Between Cumulative Dietary Risk Factors and Cardiovascular Diseases,Cancer, and All-Cause Mortality: A Prospective Cohort Study From UK Biobank

ObjectiveTo develop a score from cumulative dietary risk factors and examine its nonlinear associations with cardiovascular disease (CVD) and cancer incidence and mortality, as well as all-cause mortality.Patients and MethodsThere were 422,702 participants from UK Biobank included in this prospective study. Cumulative dietary risk factors were represented using a score ranging from 0 (healthiest) to 9 (least healthy). This was derived from 9 food items based on current UK guidelines using baseline data. Associations between the cumulative score and health outcomes were investigated using nonlinear penalized cubic splines fitted in Cox proportional hazard models. Follow-up was conducted until June 2020 for mortality, and for incidence, up to June 2020 in England and March 2017 in Wales and Scotland.ResultsThe median follow-up period was 9.0 years for incidence outcomes and 9.3 years for mortality outcomes. Each 1-point increment in the cumulative dietary risk factors score was associated with higher risk for incidence and mortality of the outcomes studied. The highest risks were identified for mortality due to heart failure (8.0% higher), CVD, and ischemic heart disease (both 7.0% higher). In addition, a higher diet score accounted for 18.8% of all deaths, 4.47% of incident cases of CVD, 25.5% of CVD deaths, 7.7% of incident cancers, and 18.2% of all cancer deaths.ConclusionOur findings show that dietary risk factors contributed to a large proportion of CVD and cancer events, as well as deaths, among those who did not meet most dietary recommendations.     

Genetic Risk Score Associations With Cardiovascular Disease and Mortality in the Diabetes Heart Study

OBJECTIVE

Given the high rates of cardiovascular disease (CVD) and associated mortality in individuals with type 2 diabetes, identifying and understanding predictors of CVD events and mortality could help inform clinical management in this high-risk group. Recent large-scale genetic studies may provide additional tools in this regard.

RESEARCH DESIGN AND METHODS

Genetic risk scores (GRSs) were constructed in 1,175 self-identified European American (EA) individuals comprising the family-based Diabetes Heart Study based on 1) 13 single nucleotide polymorphisms (SNPs) and 2) 30 SNPs with previously documented associations with CVD in genome-wide association studies. Associations between each GRS and a self-reported history of CVD, coronary artery calcified plaque (CAC) determined by noncontrast computed tomography scan, all-cause mortality, and CVD mortality were examined using marginal models with generalized estimating equations and Cox proportional hazards models.

RESULTS

The weighted 13-SNP GRS was associated with prior CVD (odds ratio [OR] 1.51 [95% CI 1.22–1.86]; P = 0.0002), CAC (β-coefficient [β] 0.22 [0.02–0.43]; P = 0.04) and CVD mortality (hazard ratio [HR] 1.35 [1.10–1.81]; P = 0.04) when adjusting for the other known CVD risk factors: age, sex, type 2 diabetes affection status, BMI, current smoking status, hypertension, and dyslipidemia. The weighted 30-SNP GRS was also associated with prior CVD (OR 1.33 [1.08–1.65]; P = 0.008), CAC (β 0.29 [0.08–0.50]; P = 0.006), all-cause mortality (HR 1.28 [1.05–1.56]; P = 0.01), and CVD mortality (HR 1.46 [1.08–1.96]; P = 0.01).

CONCLUSIONS

These findings support the utility of two simple GRSs in examining genetic associations for adverse outcomes in EAs with type 2 diabetes.     

Diabetes and Risk of Hip Fracture in the Singapore Chinese Health Study

OBJECTIVE

Asian populations are documenting rapid increases in the rates of diabetes and hip fracture, but there are no prospective data linking both diseases in Asian studies. We investigated this association among a cohort of Chinese in Singapore.

RESEARCH DESIGN AND METHODS

A prospective cohort of 63,257 Chinese in the Singapore Chinese Health Study, established between 1993 and 1998, was followed up for a mean duration of 12 years. Diabetes status was ascertained by baseline interviews, and incidence of hip fracture post-enrollment was identified through a nationwide hospital discharge database.

RESULTS

The risk of hip fracture, after adjustment for other risk factors, was almost double among people with diabetes compared with people without diabetes (relative risk 1.98, 95% CI 1.71–2.29). When stratified by BMI, the increase in risk of hip fracture among people with diabetes relative to people without diabetes was similar in all four strata. There was a very strong dose-dependent relationship between duration of diabetes and risk of hip fracture (P for trend <0.0001). Compared with people without diabetes, the relative risk (95% CI) among subjects with diabetes for <5 years at recruitment was 1.40 (1.08–1.82), and this risk increased to 2.66 (2.04–3.47) among individuals with diabetes for ≥15 years.

CONCLUSIONS

Asians with diabetes, like their Western counterparts, experience an increased risk of hip fracture. Early assessment for osteoporosis and increased fracture risk, as well as prevention of falls, should be part of the management of diabetes.The incidence of diabetes and osteoporotic hip fractures, two major causes of morbidity and mortality, is increasing rapidly among Asian populations. It has been predicted that in 2030, the prevalence of diabetes in Asian countries will be more than double the rates in 2000 (1). Similarly, it has been forecasted that while the current rates of osteoporotic hip fractures in Asian populations are lower than the rates seen among the Western populations, 50% of all hip fractures in the world will be occurring in Asia by the year 2050 (2). A meta-analysis using prospective data from 11 cohort studies done in Western populations has shown that a baseline history of diabetes is associated with a relative risk (RR) of 1.8 (95% CI 1.3–2.4) for hip fracture (3). However, none of these studies included Asian populations, which are known to have distinct anthropometric measurements and differ in dietary and other habits relative to their Western counterparts (4). Therefore, it is important to investigate the association between diabetes and hip fracture risk in Asian populations, which are documenting a rapid and parallel increase in the rates of both diseases. Furthermore, it is also not clear if the association between diabetes and hip fracture risk may differ between men and women, or between lean and obese individuals.In the present study, we examined the association between baseline history and duration of diabetes, and risk of hip fracture within a prospective cohort of 63,257 Chinese men and women (the Singapore Chinese Health Study). Furthermore, we examined whether BMI has a modifying effect on diabetes–hip fracture association.