Wenhui Zhao

HbA1c and Coronary Heart Disease Risk Among Diabetic Patients

OBJECTIVE Clinical trials to date have not provided definitive evidence regarding the effects of glucose lowering with coronary heart disease (CHD) risk among diabetic patients. RESEARCH DESIGN AND METHODS We prospectively investigated the association of HbA1c at baseline and during follow-up with CHD risk among 17,510 African American and 12,592 white patients with type 2 diabetes. RESULTS During a mean follow-up of 6.0 years, 7,258 incident CHD cases were identified. The multivariable-adjusted hazard ratios of CHD associated with different levels of HbA1c at baseline (<6.0 [reference group], 6.0–6.9, 7.0–7.9, 8.0–8.9, 9.0–9.9, 10.0–10.9, and ≥11.0%) were 1.00, 1.07 (95% CI 0.97–1.18), 1.16 (1.04–1.31), 1.15 (1.01–1.32), 1.26 (1.09–1.45), 1.27 (1.09–1.48), and 1.24 (1.10–1.40) (P trend = 0.002) for African Americans and 1.00, 1.04 (0.94–1.14), 1.15 (1.03–1.28), 1.29 (1.13–1.46), 1.41 (1.22–1.62), 1.34 (1.14–1.57), and 1.44 (1.26–1.65) (P trend <0.001) for white patients, respectively. The graded association of HbA1c during follow-up with CHD risk was observed among both African American and white diabetic patients (all P trend <0.001). Each one percentage increase of HbA1c was associated with a greater increase in CHD risk in white versus African American diabetic patients. When stratified by sex, age, smoking status, use of glucose-lowering agents, and income, this graded association of HbA1c with CHD was still present. CONCLUSIONS The current study in a low-income population suggests a graded positive association between HbA1c at baseline and during follow-up with the risk of CHD among both African American and white diabetic patients with low socioeconomic status.

Aggressive Blood Pressure Control Increases Coronary Heart Disease Risk Among Diabetic Patients

OBJECTIVE Blood pressure control can reduce the risk of coronary heart disease (CHD) among diabetic patients; however, it is not known whether the lowest risk of CHD is among diabetic patients with the lowest blood pressure level. RESEARCH DESIGN AND METHODS We performed a prospective cohort study (2000–2009) on diabetic patients including 17,536 African Americans and 12,618 whites. Cox proportional hazards regression models were used to estimate the association of blood pressure with CHD risk. RESULTS During a mean follow-up of 6.0 years, 7,260 CHD incident cases were identified. The multivariable-adjusted hazard ratios of CHD associated with different levels of systolic/diastolic blood pressure at baseline (<110/65, 110–119/65–69, 120–129/70–80, and 130–139/80–90 mmHg [reference group]; 140–159/90–100; and ≥160/100 mmHg) were 1.73, 1.16, 1.04, 1.00, 1.06, and 1.11 (P trend <0.001), respectively, for African American diabetic patients, and 1.60, 1.27, 1.08, 1.00, 0.95, and 0.99 (P trend<0.001) for white diabetic patients, respectively. A U-shaped association of isolated systolic and diastolic blood pressure at baseline as well as blood pressure during follow-up with CHD risk was observed among both African American and white diabetic patients (all Ptrend <0.001). The U-shaped association was present in the younger age-group (30–49 years), and this U-shaped association changed to an inverse association in the older age-group (≥60 years). CONCLUSIONS Our study suggests that there is a U-shaped or inverse association between blood pressure and the risk of CHD, and aggressive blood pressure control (blood pressure <120/70 mmHg) is associated with an increased risk of CHD among both African American and white patients with diabetes.

Blood Pressure and Stroke Risk Among Diabetic Patients

CONTEXT Blood pressure (BP) control can reduce the risk of stroke among diabetic patients; however, it is not known whether the lowest risk of stroke is among diabetic patients with the lowest BP level. OBJECTIVE Our objective was to investigate the race-specific association of different levels of BP with stroke risk among diabetic patients in the Louisiana State University Hospital-based longitudinal study. DESIGN, SETTING, AND PARTICIPANTS We prospectively investigated the race-specific association of different levels of BP at baseline and during an average of 6.7 years of follow-up with incident stroke risk among 17,536 African American and 12,618 white diabetic patients within the Louisiana State University Hospital System. MAIN OUTCOME MEASURE We evaluated incident stroke until May 31, 2012. RESULTS During follow-up, 2949 incident cases of stroke were identified. The multivariable-adjusted hazard ratios of stroke associated with different levels of systolic/diastolic BP at baseline (<110/65, 110-119/65-69, 120-129/70-80 [reference group], 130-139/80-90, 140-159/90-100, and ≥160/100 mm Hg) were 1.88 (95% confidence interval = 1.38-2.56), 1.05 (0.80-1.42), 1.00, 1.05 (0.86-1.27), 1.12 (0.94-1.34), and 1.47 (1.24-1.75) for African American diabetic patients and 1.42 (1.06-1.91), 1.22 (0.95-1.57), 1.00, 0.88 (0.72-1.06), 1.02 (0.86-1.21), and 1.28 (1.07-1.54) for white diabetic patients, respectively. A U-shaped association of isolated systolic or diastolic BP at baseline and during follow-up with stroke risk was observed among both African American and white diabetic patients. The U-shaped association was confirmed in both patients who were and were not taking antihypertensive drugs. CONCLUSIONS The current study suggests a U-shaped association between BP and the risk of stroke. Aggressive BP control (<110/65 mm Hg) and high BP (≥160/100 mm Hg) are associated with an increased risk of stroke among both African American and white patients with type 2 diabetes.

Kidney function and the risk of cardiovascular disease in patients with type 2 diabetes

The association of estimated glomerular filtration rate (GFR) with cardiovascular disease risk among patients with type 2 diabetes is unclear. Here we prospectively investigated the race-specific association of estimated GFR with the risk of coronary heart disease and stroke among 11,940 Caucasian and 16,451 African-American patients. During mean follow-up of 6.1-6.8 years, 6647 coronary heart disease and 2750 stroke incident cases were identified. Age- and sex-adjusted hazard ratios of coronary heart disease associated with baseline estimated GFR (90 or more, 75-89, 60-74, 30-59, and 15-29 ml/min per 1.73 m2) were 1.00, 1.04, 1.13, 1.37, and 2.07 (significant trend) for African Americans, and 1.00, 1.09, 1.10, 1.31, and 2.18 (significant trend) for Caucasians, respectively. A significantly increased stroke risk was observed among both African-American and Caucasian participants with an estimated GFR under 60 ml/min per 1.73 m2. When using the updated mean values of estimated GFR, these significant associations became stronger. Participants with mildly decreased estimated GFR (60-89 ml/min per 1.73 m2) during follow-up were also at a significantly higher risk of coronary heart disease and stroke. Thus, even mildly reduced estimated GFR at baseline (under 75 ml/min per 1.73 m2) and during follow-up (under 90 ml/min per 1.73 m2) increased the risk of incident coronary heart disease and stroke among both African-American and Caucasian type 2 diabetes patients.

Body Mass Index and the Risk of All-Cause Mortality Among Patients With Type 2 Diabetes Mellitus

Background— Several prospective studies have evaluated the association between body mass index (BMI) and death risk among patients with diabetes mellitus; however, the results have been inconsistent. Methods and Results— We performed a prospective cohort study of 19 478 black and 15 354 white patients with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of BMI stratification with all-cause mortality. During a mean follow-up of 8.7 years, 4042 deaths were identified. The multivariable-adjusted (age, sex, smoking, income, and type of insurance) hazard ratios for all-cause mortality associated with BMI levels (18.5–22.9, 23–24.9, 25–29.9, 30–34.9 [reference group], 35–39.9, and ≥40 kg/m2) at baseline were 2.12 (95% confidence interval [CI], 1.80–2.49), 1.74 (95% CI, 1.46–2.07), 1.23 (95% CI, 1.08–1.41), 1.00, 1.19 (95% CI, 1.03–1.39), and 1.23 (95% CI, 1.05–1.43) for blacks and 1.70 (95% CI, 1.42–2.04), 1.51 (95% CI, 1.27–1.80), 1.07 (95% CI, 0.94–1.21), 1.00, 1.07 (95% CI, 0.93–1.23), and 1.20 (95% CI, 1.05–1.38) for whites, respectively. When stratified by age, smoking status, patient type, or the use of antidiabetic drugs, a U-shaped association was still present. When BMI was included in the Cox model as a time-dependent variable, the U-shaped association of BMI with all-cause mortality risk did not change. Conclusions— The present study indicated a U-shaped association of BMI with all-cause mortality risk among black and white patients with type 2 diabetes mellitus. A significantly increased risk of all-cause mortality was observed among blacks with BMI <30 kg/m2 and ≥35 kg/m2 and among whites with BMI <25 kg/m2 and ≥40 kg/m2 compared with patients with BMI of 30 to 34.9 kg/m2.

HbA1c and Lower-Extremity Amputation Risk in Low-Income Patients With Diabetes

OBJECTIVE Diabetes confers a very high risk of lower-extremity amputation (LEA); however, few studies have assessed whether blood glucose control can reduce LEA risk among patients with diabetes, especially in practice settings where low-income patients predominate. RESEARCH DESIGN AND METHODS We performed a prospective cohort study (2000–2009) on patients with diabetes that included 19,808 African Americans and 15,560 whites. The cohort was followed though 31 May 2012. Cox proportional hazards regression models were used to estimate the association of HbA1c with LEA risk. RESULTS During a mean follow-up of 6.83 years, 578 LEA incident cases were identified. The multivariable-adjusted hazard ratios of LEA associated with different levels of HbA1c at baseline (<6.0% [reference group], 6.0–6.9, 7.0–7.9, 8.0–8.9, 9.0–9.9, and ≥10.0%) were 1.00, 1.73 (95% CI 1.07–2.80), 1.65 (0.99–2.77), 1.96 (1.14–3.36), 3.02 (1.81–5.04), and 3.30 (2.10–5.20) (P trend <0.001) for African American patients with diabetes and 1.00, 1.16 (0.66–2.02), 2.28 (1.35–3.85), 2.38 (1.36–4.18), 2.99 (1.71–5.22), and 3.25 (1.98–5.33) (P trend <0.001) for white patients with diabetes, respectively. The graded positive association of HbA1c during follow-up with LEA risk was observed among both African American and white patients with diabetes (all P trend <0.001). With stratification by sex, age, smoking status, blood pressure, LDL cholesterol, BMI, use of glucose-lowering agents, and income, this graded association of HbA1c with LEA was still present. CONCLUSIONS The current study conducted in a low-income population suggests a graded association between HbA1c and the risk of LEA among both African American and white patients with type 2 diabetes.

HbA1c and Heart Failure Risk Among Diabetic Patients

CONTEXT Diabetes is an independent risk factor for heart failure (HF); however, it is not known whether tight glycemic control can reduce the occurrence of HF among diabetic patients. OBJECTIVE The aim of the study was to investigate the race-specific association of different levels of glycosylated hemoglobin (HbA1c) with the risk of HF among patients with diabetes. DESIGN, SETTING, AND PARTICIPANTS We prospectively investigated the race-specific association of different levels of HbA1c at baseline and during an average of 6.5 years of follow-up with incident HF risk among 17 181 African American and 12 446 white diabetic patients within the Louisiana State University Hospital System. MAIN OUTCOME MEASURE We measured incident HF until May 31, 2012. RESULTS During follow-up, 5089 HF incident cases were identified. The multivariable-adjusted hazard ratios of HF associated with different levels of HbA1c at baseline (<6.0% [reference group], 6.0-6.9%, 7.0-7.9%, 8.0-8.9%, 9.0-9.9%, and ≥10.0%,) were 1.00, 1.02 (95% confidence interval, 0.91-1.15), 1.21 (1.05-1.38), 1.29 (1.12-1.50), 1.37 (1.17-1.61), and 1.49 (1.31-1.69) (P trend < .001) for African American diabetic patients, and 1.00, 1.09 (0.96-1.22), 1.09 (0.95-1.26), 1.43 (1.22-1.67), 1.49 (1.25-1.77), and 1.61 (1.38-1.87) (P trend < .001) for white diabetic patients, respectively. This graded positive association was also present in diabetic patients with and without glucose-lowering agent treatment; in diabetic patients with different age, gender, and smoking status; and in incident HF defined as systolic HF (ejection fraction ≤ 40%) and HF with a preserved ejection fraction (ejection fraction > 40%). CONCLUSIONS The current study suggests a graded positive association of HbA1c with the risk of HF among both African American and white patients with diabetes.

Body Mass Index and Stroke Risk Among Patients With Type 2 Diabetes Mellitus

Background and Purpose— Previous studies have evaluated the association of body mass index (BMI) with the risk of all-cause and cardiovascular disease mortality among diabetic patients, and results were controversial. No studies have focused on the association between BMI and stroke risk among diabetic patients. We aimed to examine the association of BMI with stroke risk among diabetic patients. Methods— We performed a prospective cohort study with 29 554 patients with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of BMI with stroke risk. Results— During a mean follow-up period of 8.3 years, 2883 participants developed stroke (2821 ischemic and 109 hemorrhagic). The multivariable-adjusted (age, sex, race, smoking, income, and type of insurance) hazard ratios associated with different levels of BMI at baseline (18.5–24.9 [reference group], 25–29.9, 30–34.9, 35–39.9, and ≥40 kg/m2) were 1.00, 0.86, 0.83, 0.76, and 0.70 (Ptrend<0.001) for total stroke, 1.00, 0.87, 0.85, 0.78, and 0.72 (Ptrend <0.001) for ischemic stroke, and 1.00, 0.76, 0.72, 0.54, and 0.53 (Ptrend=0.034) for hemorrhagic stroke, respectively. When we used an updated mean or the last visit value of BMI, the inverse association of BMI with stroke risk did not change. This inverse association was consistent among patients of different races, sex, ages, HbA1c levels, never and current smoking, and patients with and without using glucose-lowering, cholesterol-lowering, or antihypertensive agents. Conclusions— The present study demonstrates an inverse association between BMI and stroke risk among patients with type 2 diabetes mellitus.

HDL Cholesterol and Cancer Risk Among Patients With Type 2 Diabetes

OBJECTIVE To investigate the relationship between HDL cholesterol (HDL-C) and cancer risk among type 2 diabetic patients. RESEARCH DESIGN AND METHODS We performed a retrospective cohort study of 14,169 men and 23,176 women with type 2 diabetes. Cox proportional hazards regression models were used to estimate the association of various levels of HDL cholesterol (HDL-C) with cancer risk. RESULTS During a mean follow-up period of 6.4 years, 3,711 type 2 diabetic patients had a cancer diagnosis. A significant inverse association between HDL-C and the risk of cancer was found among men and women. The multivariable-adjusted hazard ratios (HRs) of cancer at various levels of HDL-C at baseline (<30, 30–39.9, 40–49.9, 50–59.9, 60–69.9, 70–79.9, and ≥80 mg/dL) were 1.00, 0.87, 0.95, 1.01, 0.61, 0.45, and 0.37, respectively, in men (Ptrend = 0.027) and 1.00, 0.98, 0.88, 0.85, 0.84, 0.86, and 0.84, respectively, in women (Ptrend = 0.025). When stratified by race, BMI, smoking status, or medication use, the inverse association was still present. With an updated mean of HDL-C used in the analysis, the inverse association of HDL-C with cancer risk did not change. The inverse association substantially attenuated after excluding patients who died of or were diagnosed with cancer during the first 2 years of follow-up. CONCLUSIONS The study suggests an inverse association of HDL-C with cancer risk among men and women with type 2 diabetes, whereas the effect of HDL-C was partially mediated by reverse causation.

Body Mass Index and the Risk of All-Cause Mortality Among Patients with Type 2 Diabetes

Background— Several prospective studies have evaluated the association between body mass index (BMI) and death risk among patients with diabetes mellitus; however, the results have been inconsistent. Methods and Results— We performed a prospective cohort study of 19 478 black and 15 354 white patients with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of BMI stratification with all-cause mortality. During a mean follow-up of 8.7 years, 4042 deaths were identified. The multivariable-adjusted (age, sex, smoking, income, and type of insurance) hazard ratios for all-cause mortality associated with BMI levels (18.5–22.9, 23–24.9, 25–29.9, 30–34.9 [reference group], 35–39.9, and ≥40 kg/m2) at baseline were 2.12 (95% confidence interval [CI], 1.80–2.49), 1.74 (95% CI, 1.46–2.07), 1.23 (95% CI, 1.08–1.41), 1.00, 1.19 (95% CI, 1.03–1.39), and 1.23 (95% CI, 1.05–1.43) for blacks and 1.70 (95% CI, 1.42–2.04), 1.51 (95% CI, 1.27–1.80), 1.07 (95% CI, 0.94–1.21), 1.00, 1.07 (95% CI, 0.93–1.23), and 1.20 (95% CI, 1.05–1.38) for whites, respectively. When stratified by age, smoking status, patient type, or the use of antidiabetic drugs, a U-shaped association was still present. When BMI was included in the Cox model as a time-dependent variable, the U-shaped association of BMI with all-cause mortality risk did not change. Conclusions— The present study indicated a U-shaped association of BMI with all-cause mortality risk among black and white patients with type 2 diabetes mellitus. A significantly increased risk of all-cause mortality was observed among blacks with BMI <30 kg/m2 and ≥35 kg/m2 and among whites with BMI <25 kg/m2 and ≥40 kg/m2 compared with patients with BMI of 30 to 34.9 kg/m2.