Intensive Glucose Control in Patients with Type 2 Diabetes - 15-Year Follow-up.

BACKGROUND: We previously reported that a median of 5.6 years of intensive as compared with standard glucose lowering in 1791 military veterans with type 2 diabetes resulted in a risk of major cardiovascular events that was significantly lower (by 17%) after a total of 10 years of combined intervention and observational follow-up. We now report the full 15-year follow-up. METHODS: We observationally followed enrolled participants (complete cohort) after the conclusion of the original clinical trial by using central databases to identify cardiovascular events, hospitalizations, and deaths. Participants were asked whether they would be willing to provide additional data by means of surveys and chart reviews (survey cohort). The prespecified primary outcome was a composite of major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, and death from cardiovascular causes. Death from any cause was a prespecified secondary outcome. RESULTS: There were 1655 participants in the complete cohort and 1391 in the survey cohort. During the trial (which originally enrolled 1791 participants), the separation of the glycated hemoglobin curves between the intensive-therapy group (892 participants) and the standard-therapy group (899 participants) averaged 1.5 percentage points, and this difference declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a period of 15 years of follow-up (active treatment plus post-trial observation), the risks of major cardiovascular events or death were not lower in the intensive-therapy group than in the standard-therapy group (hazard ratio for primary outcome, 0.91; 95% confidence interval [CI], 0.78 to 1.06; P = 0.23; hazard ratio for death, 1.02; 95% CI, 0.88 to 1.18). The risk of major cardiovascular disease outcomes was reduced, however, during an extended interval of separation of the glycated hemoglobin curves (hazard ratio, 0.83; 95% CI, 0.70 to 0.99), but this benefit did not continue after equalization of the glycated hemoglobin levels (hazard ratio, 1.26; 95% CI, 0.90 to 1.75). CONCLUSIONS: Participants with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had a lower risk of cardiovascular events than those who received standard therapy only during the prolonged period in which the glycated hemoglobin curves were separated. There was no evidence of a legacy effect or a mortality benefit with intensive glucose control. (Funded by the VA Cooperative Studies Program; VADT ClinicalTrials.gov number, NCT00032487.).

Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.

BACKGROUND: The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants. METHODS: After the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS: The difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.4%) and declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome than did the standard-therapy group (hazard ratio, 0.83; 95% confidence interval [CI], 0.70 to 0.99; P=0.04), with an absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years, but did not have reduced cardiovascular mortality (hazard ratio, 0.88; 95% CI, 0.64 to 1.20; P=0.42). No reduction in total mortality was evident (hazard ratio in the intensive-therapy group, 1.05; 95% CI, 0.89 to 1.25; P=0.54; median follow-up, 11.8 years). CONCLUSIONS: After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. (Funded by the VA Cooperative Studies Program and others; VADT ClinicalTrials.gov number, NCT00032487.).

Blood pressure and pulse pressure effects on renal outcomes in the Veterans Affairs Diabetes Trial (VADT).

OBJECTIVE: Blood pressure (BP) control for renal protection is essential for patients with type 2 diabetes. Our objective in this analysis of Veterans Affairs Diabetes Trial (VADT) data was to learn whether on-study systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) affected renal outcomes measured as albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: The VADT was a prospective, randomized study of 1,791 veterans with type 2 diabetes to determine whether intensive glucose control prevented major cardiovascular events. In this post hoc study, time-varying covariate survival analyses and hazard ratios (HR) were used to determine worsening of renal outcomes. RESULTS: Compared with SBP 105-129 mmHg, the risk of ACR worsening increased significantly for SBP 130-139 mmHg (HR 1.88 [95% CI 1.28-2.77]; P = 0.001) and for SBP ≥140 mmHg (2.51 [1.66-3.78]; P < 0.0001). Compared with a PP range of 40-49 mmHg, PP <40 was associated with significantly lowered risk of worsening ACR (0.36 [0.15-0.87]; P = 0.022) and PP ≥60 with significantly increased risk (2.38 [1.58-3.59]; P < 0.0001). Analyses of BP ranges associated with eGFR worsening showed significantly increased risk with rising baseline SBP and an interaction effect between SBP ≥140 mmHg and on-study A1C. These patients were 15% more likely than those with SBP <140 mmHg to experience eGFR worsening (1.15 [1.00-1.32]; P = 0.045) for each 1% (10.9 mmol/mol) A1C increase. CONCLUSIONS: SBP ≥130 mmHg and PP >60 mmHg were associated with worsening ACR. The results suggest that treatment of SBP to <130 mmHg may lessen ACR worsening. The interaction between SBP ≥140 mmHg and A1C suggests that the effect of glycemic control on reducing progression of renal disease may be greater in hypertensive patients.

Basic fibroblast growth factor predicts cardiovascular disease occurrence in participants from the veterans affairs diabetes trial.

AIM: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in adults with type 2 diabetes mellitus. The aim of the present study was to test whether plasma basic fibroblast growth factor (bFGF) levels predict future CVD occurrence in adults from the Veterans Affairs Diabetes Trial (VADT). METHODS: Nearly 400 veterans, 40 years of age or older having a mean baseline diabetes duration of 11.4 years were recruited from outpatient clinics at six geographically distributed sites in the VADT. Within the VADT, they were randomly assigned to intensive or standard glycemic treatment, with follow-up as much as seven and one-half years. CVD occurrence was examined at baseline in the patient population and during randomized treatment. Plasma bFGF was determined with a sensitive, specific two-site enzyme-linked immunoassay at the baseline study visit in all 399 subjects and repeated at the year 1 study visit in a randomly selected subset of 215 subjects. RESULTS: One hundred and five first cardiovascular events occurred in these 399 subjects. The best fit model of risk factors associated with the time to first CVD occurrence (in the study) over a seven and one-half year period had as significant predictors: prior cardiovascular event [hazard ratio (HR) 3.378; 95% confidence intervals (CI) 3.079-3.807; P < 0.0001), baseline plasma bFGF (HR 1.008; 95% CI 1.002-1.014; P = 0.01), age (HR 1.027; 95% CI 1.004-1.051; P = 0.019), baseline plasma triglycerides (HR 1.001; 95% CI 1.000-1.002; P = 0.02), and diabetes duration-treatment interaction (P = 0.03). Intensive glucose-lowering was associated with significantly decreased hazard ratios for CVD occurrence (0.38-0.63) in patients with known diabetes duration of 0-10 years, and non-significantly increased hazard ratios for CVD occurrence (0.82-1.78) in patients with longer diabetes duration. CONCLUSION: High level of plasma bFGF is a predictive biomarker of future CVD occurrence in this population of adult type 2 diabetes.

The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial.

BACKGROUND: The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult-to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population. METHODS: This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat. FINDINGS: Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P < .0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR > 1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77-3.320, P < .01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently. INTERPRETATION: In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration.

Observation on renal outcomes in the Veterans Affairs Diabetes Trial.

OBJECTIVE: The Veterans Affairs Diabetes Trial (VADT) was a randomized, prospective, controlled trial of 1,791 patients with type 2 diabetes to determine whether intensive glycemic control would reduce cardiovascular events compared with standard control. The effect of intensive glycemic control and selected baseline variables on renal outcomes is reported. RESEARCH DESIGN AND METHODS: Baseline mean age was 60.4 years, mean duration of diabetes was 11.5 years, HbA(1c) was 9.4%, and blood pressure was 132/76 mmHg. The renal exclusion was serum creatinine >1.6 mg/dL. Renal outcomes were sustained worsening of the urine albumin-to-creatinine ratio (ACR) and sustained worsening by one or more stages in the estimated glomerular filtration rate (eGFR). RESULTS: Intensive glycemic control did not independently reduce ACR progression but was associated with a significant attenuation in the progression of ACR in those who had baseline photocoagulation, cataract surgery, or both. The beneficial effect of intensive glycemic control increased with increasing BMI and with decreasing diastolic blood pressure (DBP). Intensive glycemic control was associated with less worsening of eGFR with increasing baseline ACR and insulin use. Baseline systolic blood pressure, triglycerides, and photocoagulation were associated with worsening of eGFR. CONCLUSIONS: Intensive glycemic control had no significant effect on the progression of renal disease in the whole cohort but was associated with some protection against increasing ACR in those with more advanced microvascular disease, lower baseline DBP, or higher baseline BMI and on worsening of eGFR in those with high baseline ACR.

Insulin metabolism in human adipocytes from subcutaneous and visceral depots.

Subjects with the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, hypertension, etc.) have a relative increase in abdominal fat tissue compared to normal individuals and obesity has also been shown to be associated with a decrease in insulin clearance. The majority of the clearance of insulin is due to the action of insulin-degrading enzyme (IDE) and IDE is present throughout all tissues. Since abdominal fat is increased in obesity we hypothesized that IDE may be altered in the different fat depots. Adipocytes were isolated from fat samples obtained from subjects during elective abdominal surgery. Fat samples were taken from subcutaneous (SQ) and visceral (VIS) sites. Insulin metabolism was compared in adipocytes isolated from SQ and VIS fat tissue. Adipocytes from the VIS site degraded more insulin that those from SQ fat tissue. Inhibitors of cathepsins B and D has no effect on the degradation of insulin, while bacitracin, an inhibitor of IDE, inhibited degradation by approx. 33% in both SQ and VIS adipocytes. These data show that insulin metabolism is relatively greater in VIS than in SQ fat tissue and potentially due to IDE.

Rates and determinants of coronary and abdominal aortic artery calcium progression in the Veterans Affairs Diabetes Trial (VADT).

OBJECTIVE: To determine the predictors of progression of calcified atherosclerosis and the effect of intensive glycemic control on this process in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: As part of the Risk Factors, Atherosclerosis, and Clinical Events in Diabetes (RACED) substudy of the Veterans Affairs Diabetes Trial (VADT), 197 and 189 individuals with type 2 diabetes received baseline and follow-up computed tomographic scans for measurement of coronary and abdominal artery calcium, respectively. Standard and novel risk factors were assessed at baseline, and progression of calcified atherosclerosis was determined by several methods. Progression was defined both as a categorical (square root increase of volumetric scores ≥ 2.5 mm(3)) and continuous variable. In addition, annualized percent change of volume scores was determined. RESULTS: After an average follow-up of 4.6 years, >75% of individuals demonstrated coronary (CAC) and abdominal artery calcification (AAC) progression. Progression increased with higher baseline calcium categories but was not influenced by standard risk factors. However, the albumin-to-creatinine ratio (ACR) (P = 0.02) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) (P = 0.01) predicted progression of CAC, and these results were not altered by adjustment for age and other traditional risk factors. Treatment assignment (intensive versus standard) within the VADT did not influence CAC or AAC progression, irrespective of baseline calcium category. CONCLUSIONS: In patients with long-standing type 2 diabetes, baseline CAC, Lp-PLA(2), and ACR predicted progression of CAC. Intensive glycemic control during the VADT did not reduce progression of calcified atherosclerosis.

Retinoblastoma protein co-purifies with proteasomal insulin-degrading enzyme: implications for cell proliferation control.

Previous investigations on proteasomal preparations containing insulin-degrading enzyme (IDE; EC 3.4.24.56) have invariably yielded a co-purifying protein with a molecular weight of about 110kDa. We have now found both in MCF-7 breast cancer and HepG2 hepatoma cells that this associated molecule is the retinoblastoma tumor suppressor protein (RB). Interestingly, the amount of RB in this protein complex seemed to be lower in HepG2 vs. MCF-7 cells, indicating a higher (cytoplasmic) protein turnover in the former vs. the latter cells. Moreover, immunofluorescence showed increased nuclear localization of RB in HepG2 vs. MCF-7 cells. Beyond these subtle differences between these distinct tumor cell types, our present study more generally suggests an interplay between RB and IDE within the proteasome that may have important growth-regulatory consequences.

Pioglitazone reduces inflammatory responses of human adipocytes to factors secreted by monocytes/macrophages.

Infiltration of monocyte-derived macrophages into adipose tissue may contribute to tissue and systemic inflammation and insulin resistance. We hypothesized that pioglitazone (Pio) could specifically reduce the inflammatory response of adipocytes to factors released by monocytes/macrophages. We show that macrophage factors (Mphi-factors) greatly increase expression levels of proinflammatory adipokines, chemokines, and adhesion molecules in human subcutaneous and visceral adipose tissue (SAT and VAT) as well as in adipocytes (up to several hundredfold of control). Compared with SAT, VAT showed enhanced basal and Mphi-factor-induced inflammatory responses. Mphi-factors also induced greater lipolysis in adipocytes, as assessed by concentrations of glycerol released from the cells (196 +/- 13 vs. 56 +/- 7 microM in control, P < 0.05). Pretreatment of adipose tissue or adipocytes with Pio reduced these responses to Mphi-factors (by 13-86%, P < 0.05) and prevented Mphi-factor suppression of adiponectin expression. Furthermore, Pio pretreatment of adipocytes and macrophages tended to further reduce inflammatory responses of adipocytes to Mphi-factors and monocyte adhesion to Mphi-factor-activated adipocytes. In support of these in vitro data, media conditioned by monocytes isolated from impaired glucose-tolerant subjects treated with Pio (compared with placebo) induced release of lower concentrations of proinflammatory adipokines and glycerol (100 +/- 7 vs. 150 +/- 15 microM, P < 0.05) from adipocytes. In summary, Pio decreases inflammatory responses in adipose tissue/cells induced by monocytes/macrophages by acting on either or both cell types. These beneficial effects of Pio may attenuate proinflammatory responses resulting from monocyte/macrophage infiltration into adipose tissue and suppress tissue inflammation resulting from the interaction between both cell types.

Blood glucose monitoring is associated with better glycemic control in type 2 diabetes: a database study.

BACKGROUND: The value of self-monitoring blood glucose (SMBG) in type 2 diabetes is controversial. OBJECTIVE: To determine SMBG testing rates are positively associated with glycemic control in veterans on oral hypoglycemic agents (OHA). DESIGN: Observational database study. SUBJECTS: Southwestern Healthcare Network veterans taking OHA in 2002 and followed through the end of 2004. MEASUREMENTS: OHA and glucose test strip (GTS) prescriptions were derived from pharmacy files. Subjects were categorized into five groups according to their end-of-study treatment status: group 1 (no medication changes), group 2 (increased doses of initial OHA), group 3 (started new OHA), group 4 (both OHA interventions), and group 5 (initiated insulin). We then used multiple linear regression analyses to examine the relationship between the SMBG testing rate and hemoglobin A1c (HbA1c) within each group. RESULTS: We evaluated 5,862 patients with a mean follow-up duration of 798 +/- 94 days. Overall, 44.2% received GTS. Ultimately, 47% of subjects ended up in group 1, 21% in group 2, 9% in group 3, 8% in group 4, and 16% in group 5. A univariate analysis showed no association between the SMBG testing rate and HbA1c. However, after stratifying by group and adjusting for initial OHA dose, we found that more frequent testing was associated with a significantly lower HbA1c in groups 1, 4, and 5. The effect ranged from -0.22% to -0.94% for every ten GTS/week. CONCLUSIONS: Higher SMBG testing rates were associated with lower HbA1c, but only when stratifying the analyses to control for treatment intensification.

Regulation of protein degradation by insulin-degrading enzyme: analysis by small interfering RNA-mediated gene silencing.

Proteins are vital to the overall structure of cells and to the function of cells in the form of enzymes. Thus the control of protein metabolism is among the most important aspects of cellular metabolism. Insulin's major effect on protein metabolism in the adult animal is inhibition of protein degradation. This is via inhibition of proteasome activity via an interaction with insulin-degrading enzyme (IDE). IDE is responsible for the majority of cellular insulin degradation. We hypothesized that a reduction in IDE would reduce insulin degradation and insulin's ability to inhibit protein degradation. HepG2 cells were transfected with siRNA against human IDE and insulin degradation and protein degradation measured. Both IDE mRNA and protein were reduced by >50% in the IDE siRNA transfected cells. Insulin degradation was reduced by approximately 50%. Cells were labeled with [3H]-leucine to investigate protein degradation. Short-lived protein degradation was unchanged in the cells with reduced IDE expression. Long-lived and very-long-lived protein degradation was reduced in the cells with reduced IDE expression (14.0+/-0.16 vs. 12.5+/-0.07%/4h (long-lived), 9.6+/-2.2% vs. 7.3+/-0.2%/3h (very-long-lived), control vs. IDE transfected, respectively, P<0.005). The inhibition of protein degradation by insulin was reduced 37-76% by a decreased expression of IDE in HepG2 cells. This shows that IDE is involved in cellular insulin metabolism and provides further evidence that insulin inhibits protein degradation via an interaction with IDE.

Adoption of a new technology in a Veterans Affairs national formulary system with local implementation: the insulin glargine example.

A study group gathered by the Pharmacy & Therapeutics Society reviewed data on the Department of Veterans Affairs (VA) health care system's implementation of a new technology (insulin glargine) for patients with diabetes. It examined local implementation of VA criteria for nonformulary use of insulin glargine in 21 VA treatment facilities that were surveyed about the issue. The examination found differences in the use of insulin glargine across the 21 treatment facilities and in the approach to implementing the criteria for nonformulary use of insulin glargine used at the individual VA treatment facility level. Differences were identified regarding the respective roles of endocrinologists and PCPs in prescribing insulins, including insulin glargine. The study group urges further short- and long-term research to better understand the utilization, cost, and health outcome implications of the implementation process for the nonformulary criteria. Lessons learned from such research could benefit other health care systems and formulary committees.

Baseline achievement of lipid goals and usage of lipid medications in patients with diabetes mellitus (from the Veterans Affairs Diabetes Trial).

The American Diabetes Association has established lipid goals for patients with diabetes. Although diabetic populations historically have poor low-density lipoprotein (LDL) cholesterol goal adherence, little is known about adherence to triglyceride and high-density lipoprotein (HDL) cholesterol goals. To determine the degree of lipid goal attainment among patients with diabetes, and to characterize the patterns of lipid medication use, we evaluated the baseline data from 1,742 enrollees of the national Veterans Affairs Diabetes Trial. Using current American Diabetes Association lipid guidelines, we calculated the proportion of participants achieving a LDL cholesterol level <100 mg/dl, triglyceride level <150 mg/dl, and HDL cholesterol level >40 mg/dl in men (>50 mg/dl in women). We also performed a descriptive analysis of the use of lipid medications in this population. The baseline LDL cholesterol level was 111 +/- 63 mg/dl, triglyceride level was 213 +/- 277 mg/dl, and HDL cholesterol was 36 +/- 10 mg/dl. At enrollment, 44% of veterans met the LDL cholesterol goal, 58% met the triglyceride goal, and 16% met the HDL cholesterol goal, but only 6% met all 3 goals. Of the 1,742 enrollees, 2/3 were receiving lipid therapy, with statins (58%) the most commonly used drug. Combination lipid therapy was used by 11% of enrollees. Although the enrollees of the Veterans Affairs Diabetes Trial demonstrated better adherence to the American Diabetes Association's LDL cholesterol goal than other diabetic populations recently studied, more aggressive and directed lipid medication use is needed to treat the overall lipid profile better.

Racial and ethnic disparities in the control of cardiovascular disease risk factors in Southwest American veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study.

BACKGROUND: Racial/ethnic disparities in cardiovascular disease complications have been observed in diabetic patients. We examined the association between race/ethnicity and cardiovascular disease risk factor control in a large cohort of insulin-treated veterans with type 2 diabetes. METHODS: We conducted a cross-sectional observational study at 3 Veterans Affairs Medical Centers in the American Southwest. Using electronic pharmacy databases, we randomly selected 338 veterans with insulin-treated type 2 diabetes. We collected medical record and patient survey data on diabetes control and management, cardiovascular disease risk factors, comorbidity, demographics, socioeconomic factors, psychological status, and health behaviors. We used analysis of variance and multivariate linear regression to determine the effect of race/ethnicity on glycemic control, insulin treatment intensity, lipid levels, and blood pressure control. RESULTS: The study cohort was comprised of 72 (21.3%) Hispanic subjects (H), 35 (10.4%) African Americans (AA), and 226 (67%) non-Hispanic whites (NHW). The mean (SD) hemoglobin A1c differed significantly by race/ethnicity: NHW 7.86 (1.4)%, H 8.16 (1.6)%, AA 8.84 (2.9)%, p = 0.05. The multivariate-adjusted A1c was significantly higher for AA (+0.93%, p = 0.002) compared to NHW. Insulin doses (unit/day) also differed significantly: NHW 70.6 (48.8), H 58.4 (32.6), and AA 53.1 (36.2), p < 0.01. Multivariate-adjusted insulin doses were significantly lower for AA (-17.8 units/day, p = 0.01) and H (-10.5 units/day, p = 0.04) compared to NHW. Decrements in insulin doses were even greater among minority patients with poorly controlled diabetes (A1c > or = 8%). The disparities in glycemic control and insulin treatment intensity could not be explained by differences in age, body mass index, oral hypoglycemic medications, socioeconomic barriers, attitudes about diabetes care, diabetes knowledge, depression, cognitive dysfunction, or social support. We found no significant racial/ethnic differences in lipid or blood pressure control. CONCLUSION: In our cohort, insulin-treated minority veterans, particularly AA, had poorer glycemic control and received lower doses of insulin than NHW. However, we found no differences for control of other cardiovascular disease risk factors. The diabetes treatment disparity could be due to provider behaviors and/or patient behaviors or preferences. Further research with larger sample sizes and more geographically diverse populations are needed to confirm our findings.

Control of cardiovascular risk factors in the Veterans Affairs Diabetes Trial in advanced type 2 diabetes.

OBJECTIVE: To present a status report on the Veterans Affairs Diabetes Trial (VADT), a multisite long-term study examining the effect of glucose control on cardiovascular (CV) complications in older patients with established, poorly controlled type 2 diabetes. METHODS: We review the rationale, objectives, and design of the VADT and summarize the baseline data and the results achieved thus far. RESULTS: The main objective of this 20-site, 1,792-patient study is to ascertain whether intensive glucose control can reduce major CV events in patients with difficult-to-control type 2 diabetes. The study design consists of a standard treatment arm and an intensive treatment arm, with a goal of 1.5% difference in hemoglobin A1c values between the two groups. The trial is now in its fifth year, with completion expected in December 2007. The planned glucose separation has been achieved and maintained to this point. Blood pressure and hemoglobin A1c levels have been reduced from baseline values, and established CV risk factors are within recommended ranges. CONCLUSION: The current results of the VADT show that excellent control of glucose and CV risk factors can be achieved and maintained in the population studied. The results of these interventions on CV outcomes will ultimately have important implications for the clinical care of older patients with advanced type 2 diabetes.

Reliability and validity of the DCP among hispanic veterans.

The Diabetes Care Profile (DCP) was designed to measure psychosocial factors related to diabetes and its treatment. This study sought to determine the reliability and validity of the DCP in Hispanic veterans with Type 2 diabetes. Hispanic (n=81) and non-Hispanic White (n=238) patients were recruited at three southwestern VA hospitals. Scale reliabilities calculated by Cronbach's coefficient alpha revealed reliabilities ranging from .54 to .97 in Hispanics and .63 to .95 in non-Hispanic Whites. Only one scale, Monitoring Barriers, differed significantly between the two patient groups. Mean values on the DCP scales were consistent within and across ethnicities lending support for construct validity of the DCP in Hispanics. Convergent validity was also supported for DCP scales within the Hispanic patients as evidenced by correlations in expected directions with external measures.

Hypoglycemia in stable, insulin-treated veterans with type 2 diabetes: a prospective study of 1662 episodes.

UNLABELLED: We evaluated the incidence, severity, and predisposing risk factors for hypoglycemic episodes in subjects with type 2 diabetes. METHODS: We conducted a prospective observational study of Southwest veterans with stable, insulin-treated type 2 diabetes who were randomly selected from pharmacy databases. Electronically recorded self-monitored blood glucose (SMBG) results were collected during 12 months of routine monitoring. We defined hypoglycemia as an SMBG reading < or =60 mg/dl. Subjects graded the severity of each hypoglycemic episode: 0=asymptomatic, 1=mild/moderate symptoms, 2=severe, with mental impairment or need for assistance. Subjects also reported any predisposing factors for each hypoglycemic episode. RESULTS: We enrolled 344 subjects, mean (S.D.) age of 65.5 (9.7) years, 96.5% were men, and 35.2% were minorities. During an average follow-up of 41.2 (8.6) weeks, 176 subjects (51.2%) documented at least one hypoglycemic reading for a total of 1662 episodes. These subjects had a median of six (interquartile range 2-14.9) hypoglycemic episodes. The mean hypoglycemic blood glucose reading was 49.7 (7.5) mg/dl and the mean symptom score was 0.84 (0.45). Nearly 80% of episodes were symptomatic, 3.4% were severe. Subjects identified a cause for 45.2% of episodes: 53.3% of these were attributed to missing a meal, 23.8% to exercise, and 1.6% followed a medication increase. CONCLUSIONS: A high proportion of stable, insulin-treated subjects developed hypoglycemic episodes, but severe hypoglycemia occurred infrequently. Medication increases were rarely identified as causing hypoglycemic episodes. Efforts to achieve tight glycemic control should recognize that patient behaviors commonly cause hypoglycemia.