Glucose control and vascular complications in veterans with type 2 diabetes.

BACKGROUND: The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain. METHODS: We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene. RESULTS: The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group. CONCLUSIONS: Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.)

A twin study of erectile dysfunction.

BACKGROUND: The extent of genetic influence on erectile dysfunction (ED) is unknown. This study determines the contribution of heredity to ED in a sample of middle-aged men. METHODS: A classical twin study was conducted in the Vietnam Era Twin Registry, a national sample of male-male pairs (mean birth year, 1949) who served on active duty during the Vietnam era (1965-1975). A 1999 male health survey was completed by 890 monozygotic (MZ) and 619 dizygotic (DZ) pairs. The prevalence and heritability of 2 self-report indicators of ED, difficulty in having an erection and in maintaining an erection, are estimated. RESULTS: The prevalence of difficulty in having an erection is 23.3% and in maintaining an erection is 26.7%. Twin correlations for dysfunction in having an erection are 0.35 (95% confidence interval [CI], 0.28-0.41) in MZ and 0.17 (95% CI, 0.09-0.27) in DZ pairs. For dysfunction in maintaining an erection, the twin correlations in MZ and DZ pairs are 0.39 (95% CI, 0.32-0.45) and 0.18 (95% CI, 0.09-0.27), respectively. The estimated heritability of liability for dysfunction in having an erection is 35% and in maintaining an erection is 42%. The heritable influence on ED remained significant after adjustment for ED risk factors. CONCLUSIONS: The present study demonstrates an ED-specific genetic component that is independent of genetic influences from numerous ED risk factors. The results suggest that future molecular genetic studies to identify ED-related polymorphisms are warranted.

The Vietnam Era Twin Registry.

The Vietnam Era Twin (VET) Registry is composed of 7369 middle-aged male-male twin pairs both of whom served in the military during the time of the Vietnam conflict (1965-1975). The Registry is a United States Department of Veterans Affairs resource that was originally constructed from military records; the Registry has been in existence for more than 15 years. It is one of the largest national twin registries in the US and currently has subjects living in all 50 states. Initially formed to address questions about the long-term health effects of service in Vietnam the Registry has evolved into a resource for genetic epidemiologic studies of mental and physical health conditions. The management and administration of the VET Registry is described with particular attention given to the processes involved with database maintenance and study coordination. Several waves of mail and telephone surveys have collected a wealth of health-related information on Registry twins. More recent data collection efforts have focused on specific sets of twin pairs and conducted detailed clinical or laboratory testing. New Registry initiatives for the future include the construction of a web site and the development of a DNA repository.

Persistence and change of PTSD symptomatology--a longitudinal co-twin control analysis of the Vietnam Era Twin Registry.

INTRODUCTION: Previous twin studies have demonstrated a strong association between the degree of combat exposure and PTSD, and the continued presence of PTSD, almost two decades after combat. Independent genetic effects have also been demonstrated for both combat exposure and PTSD vulnerability in Vietnam veterans. The current study, involving a subset of male-male twin pairs discordant for service in Southeast Asia (SEA), is a follow-up to an earlier study conducted in 1987. The purpose of this study is to examine the changes in the combat exposure-PTSD relationship over an additional decade of time. METHODS: The Mississippi Scale for Combat-Related or Civilian PTSD was administered by telephone in 1997 during a follow-up survey of the Vietnam Era Twin Registry. Only twins discordant for service in Southeast Asia who originally participated in the 1987 study were included. Results of this scale and the original 1987 PTSD symptom scale were separately standardized using z-score transformations and used as dependent variables in a random effects regression model with zygosity, time and combat exposure as independent variables. Main effects and interactions were estimated to address whether there were differential effects of combat on PTSD over time, and whether there was evidence of genetic covariation between combat exposure and PTSD in 1987 that persisted to 1997. RESULTS: Combat exposure was strongly associated with PTSD in both 1987 and 1997. Although still highly significant, the effect sharply diminished over time. There is little evidence for a shared genetic vulnerability between combat and PTSD in either 1987 or 1997. CONCLUSION: This analysis documents the continuing role of combat exposure (i. e., trauma severity) on the persistence and chronicity of PTSD. Nearly 25 years after the end of hostilities, PTSD symptoms continue to be elevated in those exposed to the highest levels of combat. There is no evidence that genetic influences on exposure to combat are shared with those inducing a genetic vulnerability to PTSD. Clinicians need to be aware of the persistent and long-term residual effects of trauma exposure.