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/m(2)) 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/m(2) and ≥35 kg/m(2) and among whites with BMI <25 kg/m(2) and ≥40 kg/m(2) compared with patients with BMI of 30 to 34.9 kg/m(2).

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/m(2)) 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.

Sex differences in the risk of stroke and HbA(1c) among diabetic patients.

AIMS/HYPOTHESIS: Sex differences in macrovascular disease, especially in stroke, are observed across studies of epidemiology. We studied a large sample of patients with type 2 diabetes to better understand the relationship between glycaemic control and stroke risk. METHODS: We prospectively investigated the sex-specific association between different levels of HbA(1c) and incident stroke risk among 10,876 male and 19,278 female patients with type 2 diabetes. RESULTS: During a mean follow-up of 6.7 years, 2,949 incident cases of stroke were identified. The multivariable-adjusted HRs of stroke associated with different levels of HbA(1c) at baseline (HbA(1c) <6.0% [<42 mmol/mol], 6.0-6.9% [42-52 mmol/mol] [reference group], 7.0-7.9% [53-63 mmol/mol], 8.0-8.9% [64-74 mmol/mol], 9.0-9.9% [75-85 mmol/mol] and ≥10.0% [≥86 mmol/mol]) were 0.96 (95% CI 0.80, 1.14), 1.00, 1.04 (0.85, 1.28), 1.11 (0.89, 1.39), 1.10 (0.86, 1.41) and 1.22 (0.92, 1.35) (p for trend = 0.66) for men, and 1.03 (0.90, 1.18), 1.00, 1.09 (0.94, 1.26), 1.19 (1.00, 1.42), 1.32 (1.09, 1.59) and 1.42 (1.23, 1.65) (p for trend <0.001) for women, respectively. The graded association between HbA(1c) during follow-up and stroke risk was observed among women (p for trend = 0.066). When stratified by race, whether with or without glucose-lowering agents, this graded association of HbA(1c) with stroke was still present among women. When stratified by age, the adjusted HRs were significantly higher in women older than 55 years compared with younger women. CONCLUSIONS/INTERPRETATION: The current study suggests a graded association between HbA1c and the risk of stroke among women with type 2 diabetes. Poor control of blood sugar has a stronger effect in diabetic women older than 55 years.

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.

Molecular brightness analysis reveals phosphatidylinositol 4-Kinase IIß association with clathrin-coated vesicles in living cells.

Mammalian cells express two classes of phosphatidylinositol 4-kinase (PI4K), designated as Types II and III, that phosphorylate phosphatidylinositol to generate PI4P. A number of studies have indicated that these enzymes are important for Golgi trafficking and both early and late stages of endocytosis. In this study, we focus on PI4KIIß, a protein that is evenly distributed between membrane and soluble fractions, and is believed to participate in stimulus-dependent phosphoinositide signaling. Using molecular brightness analysis, we found that EGFP-tagged PI4KIIß exists as two distinct species in the cytoplasm: a soluble monomer and a high-order complex enriched with multiple copies of PI4KIIß. This observation was confirmed by an autocorrelation analysis that identified two species with distinct mobilities. We further demonstrate that the high-order complex enriched with PI4KIIß is sensitive to inhibition of palmitoylation, indicating that it is associated with membranes, very likely vesicles. Indeed, we show that the high-order PI4KIIß complex is sensitive to expression of dynamin 2 (K44A), a dominant-negative inhibitor of endocytosis. Using dual-color heterospecies partition analysis, we directly detected that PI4KIIß comoves with clathrin light chain on vesicles. This analysis allows us to isolate the comobile species in the presence of strong background contribution from the monomeric pool of PI4KIIß. Our results strongly suggest that PI4KIIß is involved in an early stage of endocytosis and is associated with clathrin-coated vesicles. Moreover, we establish molecular brightness as a powerful tool for characterizing cellular cytosolic vesicles that are otherwise difficult to characterize by other techniques.

Characterization of cytoplasmic Gag-gag interactions by dual-color z-scan fluorescence fluctuation spectroscopy.

Fluorescence fluctuation spectroscopy (FFS) quantifies the interactions of fluorescently-labeled proteins inside living cells by brightness analysis. However, the study of cytoplasmic proteins that interact with the plasma membrane is challenging with FFS. If the cytoplasmic section is thinner than the axial size of the observation volume, cytoplasmic and membrane-bound proteins are coexcited, which leads to brightness artifacts. This brightness bias, if not recognized, leads to erroneous interpretation of the data. We have overcome this challenge by introducing dual-color z-scan FFS and the addition of a distinctly colored reference protein. Here, we apply this technique to study the cytoplasmic interactions of the Gag proteins from human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1). The Gag protein plays a crucial role in the assembly of retroviruses and is found in both membrane and cytoplasm. Dual-color z-scans demonstrate that brightness artifacts are caused by a dim nonpunctate membrane-bound fraction of Gag. We perform an unbiased brightness characterization of cytoplasmic Gag by avoiding the membrane-bound fraction and reveal previously unknown differences in the behavior of the two retroviral Gag species. HIV-1 Gag exhibits concentration-dependent oligomerization in the cytoplasm, whereas HTLV-1 Gag lacks significant cytoplasmic Gag-Gag interactions.

Characterization of brightness and stoichiometry of bright particles by flow-fluorescence fluctuation spectroscopy.

Characterization of bright particles at low concentrations by fluorescence fluctuation spectroscopy (FFS) is challenging, because the event rate of particle detection is low and fluorescence background contributes significantly to the measured signal. It is straightforward to increase the event rate by flow, but the high background continues to be problematic for fluorescence correlation spectroscopy. Here, we characterize the use of photon-counting histogram analysis in the presence of flow. We demonstrate that a photon-counting histogram efficiently separates the particle signal from the background and faithfully determines the brightness and concentration of particles independent of flow speed, as long as undersampling is avoided. Brightness provides a measure of the number of fluorescently labeled proteins within a complex and has been used to determine stoichiometry of protein complexes in vivo and in vitro. We apply flow-FFS to determine the stoichiometry of the group specific antigen protein within viral-like particles of the human immunodeficiency virus type-1 from the brightness. Our results demonstrate that flow-FFS is a sensitive method for the characterization of complex macromolecular particles at low concentrations.

Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stochiometry.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) is an important human retrovirus that is a cause of adult T-cell leukemia/lymphoma. While an important human pathogen, the details regarding virus replication cycle, including the nature of HTLV-1 particles, remain largely unknown due to the difficulties in propagating the virus in tissue culture. In this study, we created a codon-optimized HTLV-1 Gag fused to an EYFP reporter as a model system to quantitatively analyze HTLV-1 particles released from producer cells. RESULTS: The codon-optimized Gag led to a dramatic and highly robust level of Gag expression as well as virus-like particle (VLP) production. The robust level of particle production overcomes previous technical difficulties with authentic particles and allowed for detailed analysis of particle architecture using two novel methodologies. We quantitatively measured the diameter and morphology of HTLV-1 VLPs in their native, hydrated state using cryo-transmission electron microscopy (cryo-TEM). Furthermore, we were able to determine HTLV-1 Gag stoichiometry as well as particle size with the novel biophysical technique of fluorescence fluctuation spectroscopy (FFS). The average HTLV-1 particle diameter determined by cryo-TEM and FFS was 71 ± 20 nm and 75 ± 4 nm, respectively. These values are significantly smaller than previous estimates made of HTLV-1 particles by negative staining TEM. Furthermore, cryo-TEM reveals that the majority of HTLV-1 VLPs lacks an ordered structure of the Gag lattice, suggesting that the HTLV-1 Gag shell is very likely to be organized differently compared to that observed with HIV-1 Gag in immature particles. This conclusion is supported by our observation that the average copy number of HTLV-1 Gag per particle is estimated to be 510 based on FFS, which is significantly lower than that found for HIV-1 immature virions. CONCLUSIONS: In summary, our studies represent the first quantitative biophysical analysis of HTLV-1-like particles and reveal novel insights into particle morphology and Gag stochiometry.

Preferences for self-management support: findings from a survey of diabetes patients in safety-net health systems.

OBJECTIVE: We sought to identify interest in different modes of self-management support among diabetes patients cared for in public hospitals, and to assess whether demographic or disease-specific factors were associated with patient preferences. We explored the possible role of a perceived communication need in influencing interest in self-management support. METHODS: Telephone survey of a random sample of 796 English and Spanish-speaking diabetes patients (response rate 47%) recruited from four urban US public hospital systems. In multivariate models, we measured the association of race/ethnicity, primary language, self-reported health literacy, self-efficacy, and diabetes-related factors on patients' interest in three self-management support strategies (telephone support, group medical visits, and Internet-based support). We explored the extent to which patients believed that better communication with providers would improve their diabetes control, and whether this perception altered the relationship between patient factors and self-management support acceptance. RESULTS: Sixty-nine percent of respondents reported interest in telephone support, 55% in group medical visits, and 42% in Internet. Compared to Non-Hispanic Whites, Spanish-speaking Hispanics were more interested in telephone support (OR 3.45, 95% CI 1.97-6.05) and group medical visits (OR 2.45, 95% CI 1.49-4.02), but less interested in Internet self-management support (OR 0.56, 95% CI 0.33-0.93). African-Americans were more interested than Whites in all three self-management support strategies. Patients with limited self-reported health literacy were more likely to be interested in telephone support than those not reporting literacy deficits. Forty percent reported that their diabetes would be better controlled if they communicated better with their health care provider. This perceived communication benefit was independently associated with interest in self-management support (p<0.001), but its inclusion in models did not alter the strengths of the main associations between patient characteristics and self-management support preferences. CONCLUSION: Many diabetes patients in safety-net settings report an interest in receiving self-management support, but preferences for modes of delivery of self-management support vary by race/ethnicity, language proficiency, and self-reported health literacy. PRACTICE IMPLICATIONS: Public health systems should consider offering a range of self-management support services to meet the needs of their diverse patient populations. More broad dissemination and implementation of self-management support may help address the unmet need for better provider communication among diabetes patients in these settings.

Diabetes mellitus medication assistance program: relationship of effectiveness to adherence.

This retrospective study examines the effect of a medication assistance program (MAP) on HbA1c levels in an uninsured, low-income, type 2 diabetes population. It also examines the degree to which improvement in HbA1c level varied with adherence to medication regimens among those patients using the MAP. The MAP was found to have a mean effect of -0.60% on HbA1c levels. However, MAP users differed in how strictly they adhered to medication regimens, as measured by number of refill opportunities taken. The MAP's effect on HbA1c varied monotonically with adherence level, with greater adherence leading to greater HbA1c improvement. Never refilling the prescription (complete nonadherence) led to no change in HbA1c, while complete adherence led to an estimated -0.88% improvement in HbA1c. Further study is needed to investigate factors related to non-adherence within medication assistance programs and the effect of such programs on other patient outcomes.

HbA1c and all-cause mortality risk among patients with type 2 diabetes.

BACKGROUND: Several prospective studies have evaluated the association between glycosylated hemoglobin (HbA1c) and death risk among diabetic patients. However, the results have been inconsistent. METHODS: We performed a prospective study which included 13,334 men and 21,927 women with type 2 diabetes. Cox proportional hazards regression models were used to estimate the association of different levels of HbA1c with all-cause mortality. RESULTS: During a mean follow up of 8.7 years, 4199 (2082 men and 2117 women) patients died. The multivariable-adjusted hazard ratios (HRs) of all-cause mortality associated with different levels of HbA1c at baseline (<6.0%, 6.0-6.9% [reference], 7.0-7.9, 8.0-8.9%, 9.0-9.9%, 10.0-10.9%, and ≥11.0%) were 1.06, 1.00, 1.10, 0.93, 1.26, 1.18 and 1.31 (Pnon-linear=0.008) for men, and 1.21, 1.00, 1.01, 1.08, 1.30, 1.30 and 1.74 (Pnon-linear<0.001) for women, respectively. The J-shaped association of HbA1c with all-cause mortality was confirmed among African American and white diabetic patients, patients who were more than 50 years old, never smoked or used insulin. When we used an updated mean value of HbA1c, the J-shaped association of HbA1c with the risk of all-cause mortality did not change. CONCLUSIONS: Our study demonstrated a J-shaped association between HbA1c and the risk of all-cause mortality among men and women with type 2 diabetes. Both high and low levels of HbA1c were associated with an increased risk of all-cause mortality.

Blood pressure and all-cause mortality among patients with type 2 diabetes.

BACKGROUND: The recommended goal for blood pressure (BP) control has recently been adjusted for people with diabetes, but the optimal BP control range for the diabetic population is still uncertain. METHODS: We performed a prospective cohort study of 35,261 patients with type 2 diabetes. Cox proportional hazard regression models were used to estimate the association of BP with all-cause mortality. RESULTS: During a mean follow-up period of 8.7 years, 4199 deaths were identified. The multivariable-adjusted hazard ratios of all-cause mortality associated with different levels of systolic/diastolic BP (<110/65, 110-119/65-69, 120-129/70-80, 130-139/80-90 [reference group], 140-159/90-100, and ≥160/100 mmHg) were 1.70 (95% confidence interval [CI] 1.42-2.04), 1.26 (95% CI 1.07-1.50), 0.99 (95% CI 0.86-1.12), 1.00, 0.92 (95% CI 0.82-1.03), and 1.10 (95% CI 0.98-1.23) using baseline BP measurements, and 2.62 (95% CI 2.00-3.44), 1.77 (95% CI 1.51-2.09), 1.22 (95% CI 1.09-1.36), 1.00, 0.90 (95% CI 0.82-1.00), and 0.98 (95% CI 0.86-1.12) using an updated mean value of BP during follow-up, respectively. The U-shaped associations were confirmed in both African American and white patients, in both men and women, in those who were or were not taking antihypertensive drugs, and in patients aged 30-49 years and 50-59 years. CONCLUSIONS: The current study found a U-shaped association between BP at baseline and during follow-up and the risk of all-cause mortality among patients with type 2 diabetes.

Body mass index and heart failure among patients with type 2 diabetes mellitus.

BACKGROUND: Epidemiological data on the association between body mass index (BMI) and heart failure (HF) risk among diabetic patients are rare. METHODS AND RESULTS: We performed a prospective cohort study of risk for HF among 31 155 patients with type 2 diabetes mellitus (11 468 men and 19 687 women). Cox proportional hazards regression models were used to estimate the association of different levels of BMI with HF risk. During a mean follow-up of 7.8 years, 5834 subjects developed HF (2379 men and 3455 women). The multivariable-adjusted (age, race, smoking, income, and type of insurance) hazard ratios of HF associated with BMI levels (18.5-22.9, 23-24.9, 25-29.9 [reference group], 30-34.9, 35-39.9, and ≥40 kg/m(2)) at baseline were 0.95, 1.00, 1.00, 1.16, 1.64, and 2.02 (Ptrend<0.001) for men and 1.16, 1.16, 1.00, 1.23, 1.55, and 2.01 (Pnonlinear<0.001) for women, respectively. When we used an updated mean value of BMI, the association of HF risk with BMI did not change. When stratified by age, race, smoking status, and use of antidiabetic drugs, the positive associations among men and the J-shaped associations among women were still present. CONCLUSIONS: Our study suggests a positive association between BMI and HF risk among men and a J-shaped association between BMI and HF risk among women with type 2 diabetes mellitus.

Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels.

BACKGROUND: Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms. METHODS: A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable. RESULTS: The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly (P < .02) lower with the metformin-GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl). CONCLUSION: Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease.

Brightness experiments.

This chapter presents an overview of quantitative fluorescence brightness experiments with special emphasis on single-color measurements of protein homo-interactions inside living cells. We discuss practical considerations in the choice of the fluorescent labels and the calibration measurements necessary for quantitative interpretation of brightness experiments. Methods to identify and avoid common pitfalls, such as bleaching and saturation, are addressed. We examine the interpretation of brightness data with moment analysis. In particular, we focus on how to avoid or correct for undersampling, as well as how to characterize and adjust for photon detector effects. We conclude by describing brightness titration experiments which determine the binding curve and stoichiometry of a protein from apparent brightness data.

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.

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.

BMI and coronary heart disease risk among low-income and underinsured diabetic patients.

OBJECTIVE: The association between obesity and coronary heart disease (CHD) risk remains debatable, and no studies have assessed this association among diabetic patients. The aim of our study was to investigate the association between BMI and CHD risk among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The sample included 30,434 diabetic patients (10,955 men and 19,479 women) 30-95 years of age without a history of CHD or stroke in the Louisiana State University Hospital-Based Longitudinal Study. RESULTS: During a mean follow-up period of 7.3 years, 7,414 subjects developed CHD. The multivariable-adjusted hazard ratios for CHD across levels of BMI at baseline (18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and ≥40 kg/m(2)) were 1.00, 1.14 (95% CI 1.00-1.29), 1.27 (1.12-1.45), 1.54 (1.34-1.78), and 1.42 (1.23-1.64) (Ptrend < 0.001) in men and 1.00, 0.95 (0.85-1.07), 0.95 (0.84-1.06), 1.06 (0.94-1.20), and 1.09 (1.00-1.22) (Ptrend < 0.001) in women, respectively. When we used an updated mean or last visit value of BMI, the positive association between BMI and CHD risk did not change in men. However, the positive association of BMI with CHD changed to a U-shaped association in women when we used the last visit value of BMI. CONCLUSIONS: Our study suggests that there is a positive association between BMI at baseline and during follow-up with the risk of CHD among patients with type 2 diabetes. We indicate a U-shaped association between BMI at the last visit and the risk of CHD among women with type 2 diabetes.

Blood pressure and heart failure risk among diabetic patients.

BACKGROUND: Blood pressure (BP) control has been shown to reduce the risk of heart failure (HF) among diabetic patients; however, it is not known whether the lowest clinical BP achieved ultimately results in the lowest risk of HF in diabetic patients. METHODS: We performed a prospective cohort study which included 17,181 African American and 12,446 white diabetic patients without established coronary heart disease and HF at diabetes diagnosis. Cox proportional hazards regression models were used to estimate the association of different levels of BP stratification with incident HF. RESULTS: During a mean follow up of 6.5 years, 5,089 incident HF cases were identified. The multivariable-adjusted hazard ratios of HF associated with different levels of systolic/diastolic BP (<110/65, 110-119/65-69, 120-129/70-80, 130-139/80-90 [reference group], 140-159/90-100, and ≥ 160/100 mmHg) were 1.79 (95% confidence interval [CI] 1.53-2.11), 1.34 (95% CI 1.16-1.53), 1.02 (95% CI 0.92-1.13), 1.00, 1.04 (95% CI 0.95-1.12), and 1.26 (95% CI 1.16-1.37) using baseline BP measurements, and 2.63 (95% CI 2.02-3.41), 1.84 (95% CI 1.59-2.13), 1.25 (95% CI 1.14-1.37), 1.00, 1.11 (95% CI 1.03-1.19), and 1.32 (95% CI 1.20-1.44) using an updated mean value of BP during follow-up, respectively. The U-shaped association was confirmed in both patients who were and were not taking antihypertensive drugs, and in incident systolic HF (ejection fraction ≤ 40%) and incident HF with a preserved ejection fraction (ejection fraction >40%). CONCLUSIONS: The current study suggests a U-shaped association between observed BP and the risk of HF among diabetic patients.

Brightness analysis.

Brightness analysis provides a powerful tool for the study of protein interactions both in solution and in living cells. We provide a brief survey of some widely used techniques for extracting brightness from fluorescent fluctuation spectroscopy experiments. While all the techniques are equivalent under ideal conditions, we touch upon their relative strengths and discuss in detail a specific scenario wherein the photon-counting histogram (PCH) separates the brightness of rare, bright particles from a dominant background. In a practical vein for ensuring quantitative and unbiased brightness data, we address a number of potential issues stemming from both theoretical assumptions and experimental realities. Two additional issues arising from geometry are examined in greater detail. An oil-immersion objective skews the geometry of the excitation volume as a function of penetration depth. The bias can be characterized and corrected or avoided through the use of a water-immersion objective. Brightness measurements in thin sample geometries, frequently encountered in cells, may be biased. We use z-scan FFS to characterize sample geometry and correct any resulting bias in the brightness.