Veterans diabetes trial

In the year interim follow-up of primary CVD outcomes, patients who had been randomly assigned to intensive glucose control had fewer major CV events than those assigned to standard therapy, but no improvement was seen in the rate of overall survival.

However, this equalized to the standard treatment group in years showing no statistically significant difference. Other observations, including hospitalization, median number of hospitalizations and health-related quality of life, did not demonstrate any statistical differences between groups.

These results are relatively consistent with other recent glucose lowering trials that also examined post trial follow-up.

Also, there was also no evidence of legacy benefits among any of the studies. This highlights the importance of considering nonglycemic approaches to reducing CVD events and mortality in these patients.

However, in the year VADT follow-up data, when HbA 1c separation waned, no statistical significance persisted for any renal outcomes. In the year time point and year VADT follow-up data, there was no statistical significance for any cataract outcomes and borderline significance for the retinal event composite outcome. Present disclosure: All of the presenters, with the exclusion of those listed below, have reported no disclosures related to the VADT study.

Peter D. Reaven, PhD: the presenter reported that he participated in an advisory panel for Sanofi and that he provided research support for Astra Zeneca and Novo Nordisk. Toggle navigation. If you are a Veteran in crisis or concerned about one, connect with our caring, qualified responders for confidential help. Many of them are Veterans themselves. Get more resources at VeteransCrisisLine. Diabetes is a chronic disease in which the body cannot produce or properly use insulin.

Normally, insulin brings sugar out of the bloodstream and into cells. If the body cannot make insulin or does not respond to it, the sugar stays in the bloodstream. As a result of high blood sugar levels, damage eventually occurs to blood vessels and organs. More than 30 million Americans have diabetes, according to the Centers for Disease Control and Prevention, and 84 million more Americans are at risk to develop the disease.

Many Veterans have the disease, including some who developed it as a result of being exposed to herbicides while serving in Vietnam. Symptoms of diabetes include blurry vision, excessive thirst, fatigue, frequent urination, hunger, and weight loss. Persons with diabetes need to have their hemoglobin A1c levels checked every three to six months. A1c is a measure of average blood glucose during the previous two to three months.

It is one of the markers, along with blood pressure and cholesterol control, of good diabetes care. There are three major types of diabetes. Type 1 diabetes is usually diagnosed in childhood. In this type of diabetes, the body makes little or no insulin, so daily injections of insulin are needed. Type 2 diabetes usually occurs in adults. In this type of diabetes, the pancreas does not make enough insulin to keep blood glucose levels normal, often because the body does not respond well to insulin.

Between 90 and 95 percent of adults with diabetes have Type 2 diabetes. More are at risk due to overweight or obesity. The third type of diabetes is gestational diabetes, high blood glucose that develops during pregnancy in a woman who does not have diabetes. Diabetes affects nearly 25 percent of VA's patient population.

The disease is also the leading cause of blindness, end-stage renal disease, and amputation for VA patients. VA researchers are studying innovative strategies and technologies, including group visits, telemedicine, peer counseling, and internet-based education and case management, to enhance access to diabetes care and to improve outcomes for patients. In addition, VA researchers are working to develop better ways to prevent or treat diabetes, especially in special populations such as the elderly, amputees, minorities, spinal cord-injured patients, and those with kidney or heart disease.

For more on Diabetes, visit our Cardiovascular Disease topic page. If you are interested in learning about joining a VA-sponsored clinical trial, visit our research study information page. Two of VA's three Nobel laureates have done important work to benefit Veterans with diabetes.

The late Dr. Rosalyn S. Yalow received the Nobel Prize for Physiology or Medicine in for her work in developing the radioimmunoassay, an extremely sensitive way to measure insulin and other hormones in the blood. The technique made possible major advances in diabetes research and in diagnosing and treating hormonal problems related to growth, thyroid function, and fertility.

Andrew V. Schally also received the Nobel Prize in Physiology or Medicine in for his discovery that the hypothalamus links the nervous system to the endocrine system via the pituitary gland. He is currently doing research, along with teams of national and international researchers, on growth hormone-releasing hormone GHRH. Among other possibilities opened up by Schally's work with GHRH is the possibility of reducing or eliminating the need for diabetics to regularly inject insulin. In , an international research team including Schally devised a way to transplant healthy cells into the body without the usual risk of rejection.

The study involved a middle-aged man with diabetes, but it may be relevant to a range of other diseases as well. The researchers developed what amounts to an artificial pancreas the place where the body makes insulin , which the patient tolerated well without taking drugs to suppress the immune system. A study by Schally and his team evaluated newly developed GHRH agonists' ability to promote the growth and function of pancreatic islet cells, and found that these new agonists may provide an improved approach to treating diabetes.

Artificially produced agonists are substances like naturally occurring stimulatory substances produced in the body and therefore can act to stimulate an action in the body. Islet cells, also called Islets of Langerhans, sense blood sugar levels and release insulin to maintain normal levels. Schally is still vigorously pursuing cures for diabetes and other illnesses affecting Veterans and others at his laboratory in the Miami VA Healthcare System.

His reflections on his VA career, written in , can be found here. For seven and a half years, researchers involved in a VA cooperative study CSP followed nearly 1, patients who had type 2 diabetes.

They were interested in examining cardiovascular disease in patients with diabetes. The researchers attempted to determine if intensive glucose control in diabetic patients—using medication and other methods to reduce elevated blood sugar levels to levels that are considered normal in people without diabetes—would reduce heart attacks, strokes, and death from cardiovascular disease.

It had been previously shown that improvements in blood pressure and cholesterol levels can reduce cardiovascular disease in patients with diabetes, but no previous study had shown the beneficial effects of glucose control on cardiovascular disease. The research team also found that the two groups of patients had similar death rates, and that both groups had similar levels of complications such as diabetic neuropathy and retinopathy, with the exception that patients who used standard glucose control measures had higher levels of albumin in their urine.

Albumin in the urine is a possible indicator of kidney disease. Trial researchers concluded that both very high and very low blood sugar levels can be dangerous, and that big swings between high and low levels are also potentially harmful. As a follow up to VADT, VA researchers looked at whether the improvements in glucose control made by one of the groups in the trial led to long-term improved consequences. They collected information on the VADT cohort for more than nine years of additional study, using VA's electronic records system.

The team found that, after nearly 10 years of follow-up, patients who had been in the intensive-control group had a lower incidence of cardiovascular events after the trial was over, but their survival rates were no better than those of the other group. The two groups of Veterans also showed no differences in death from all causes. A long-term trend of reduced kidney events was found to be insignificant, suggesting that there was no carryover benefit from the earlier period.

Maintaining good glucose control was shown to reduce cardiovascular consequences for patients with diabetes at 10 years, the researchers noted. They suggested that in order to keep that benefit, patients must continue to sustain good blood sugar levels. Air pollution contributes significantly to diabetes around the world —Outdoor air pollution, even at levels that are considered safe, can lead to an increased risk of diabetes globally according to a study published in led by researchers from the VA St.

The records of 1. They were linked to data from the U. The research team looked at particulate matter —airborne microscopic pieces of dust, dirt, smoke, soot, and liquid droplets. Previous studies have found that such particles can enter the lungs and invade the bloodstream, contributing to conditions such as heart disease, stroke, cancer, and kidney disease. In diabetes, the team hypothesized that pollution would reduce insulin production and trigger inflammation, preventing the body from converting blood glucose into the energy the body needs to maintain health.

Overall, the team estimated that pollution contributed to 3. They also estimated that 8. Increasing natural log of baseline triglycerides marginally increased the risk of worsening eGFR 1. Several large trials have assessed the magnitude and independence of the effects of intensive glucose and blood pressure control on macro- and microvascular clinical outcomes in patients with long-standing type 2 diabetes. Although intensive glycemic control in the VADT did not show any significant differences in retinopathy, major nephropathy defined as doubling of serum creatinine or need for renal replacement therapy , or neuropathy compared with the STD group, it seemed to significantly reduce any worsening of albumin excretion 1.

Kidney dysfunction is common in older patients with type 2 diabetes and coronary artery disease 4 , microalbuminuria is an early finding in diabetic nephropathy, and the presence of albuminuria predicts increased risk of coronary artery disease and peripheral vascular disease 5 , 6.

Therefore, we thought it would be useful to see if any factors predicted the development of nephropathy in patients with diabetes and to see which patients might benefit most from intensification of therapy. However, significant interactions in reduction of albuminuria with intensive glycemic treatment were only seen in those with baseline eye disease, higher BMI, and lower DBP; significant interactions in reduction of eGFR with intensive glycemic treatment were only seen in those with higher baseline ACRs.

Several other studies have addressed the question of the impact of good glycemic control on renal disease in both type 1 and type 2 diabetes. In the Diabetes Control and Complications Trial involving 1, individuals with type 1 diabetes, those in the INT group had markedly reduced incidence and progression of albuminuria and a delayed protective benefit on glomerular filtration 7 , 8. Several smaller glycemic intervention studies in type 1 diabetes preceded the Diabetes Control and Complications Trial 9 — 12 , generally confirming the albuminuria benefit of glycemic control.

There also are several earlier studies in people with type 2 diabetes showing an albuminuria benefit of better glycemic control 13 — The epidemiologic link between the presence of retinopathy and nephropathy has long been known This was also seen in baseline analyses in the VADT, where increasing baseline severity of retinopathy was significantly correlated with lower eGFR and higher levels of albuminuria Our finding that intensive glycemic therapy was associated with the greatest effect in those with markers of advanced eye disease photocoagulation and cataract surgery supports the general idea that the intervention was most effective in those with advanced and generalized microvascular disease.

However, this relationship did not occur with the eGFR end point. History of photocoagulation was a risk for worsening eGFR, but there was no interaction with intensive glycemic treatment. There has been growing appreciation that obesity, per se, independent of diabetes, increases the risk for the initiation and progression of kidney disease and that weight loss can reduce proteinuria Griffin et al. Thus, obesity seems to put people at greater risk for nephropathy, and the interaction between intensive glycemic treatment and BMI is again consistent with the idea that people at greatest risk might be those that benefit the most from an intervention.

We report that intensive glycemic treatment was associated with albuminuria benefit only in those with lower diastolic pressure. However, the micro- and macroalbuminuria at the final visit was significantly lower in the intensive-therapy group, and there was no between-group difference in the frequency of end-stage renal disease or the need for dialysis.

We also confirmed that higher SBP was associated with worsening eGFR, but intensive glycemic control did not prevent worsening of renal function in these patients.

The finding that intensive glycemic control retarded the decline in eGFR only in those with substantial proteinuria has, to the best of our knowledge, not been previously observed. The reason for this is not clear, but it is in concert with the idea that treatment of any kind may have the greatest impact in those at highest risk. After adjusting for other factors, we did not find that the presence of previous cardiovascular events was associated with worsening of renal function at baseline or with intensive glycemic control.

In the UK Prospective Diabetes Study, patients with type 2 diabetes had elevated triglycerides, which were an independent risk factor for microalbuminuria. Elevated LDL cholesterol and triglycerides were an independent risk factor for macroalbuminuria. The level of triglycerides rises as diabetic nephropathy progresses to overt proteinuria Our results suggest that higher HDL cholesterol at baseline was associated with less worsening of GFR only in univariate analyses.

Higher triglyceride concentration was associated with increased worsening of eGFR, which continued despite intensification of glycemic control. On the basis of our observations in this carefully followed cohort of older patients with diabetes, it seems that intensification of glycemic control was associated with the most benefit in reducing the progression of nephropathy in a subset of patients with worse baseline disease, especially those with microvascular eye disease, greater body weight, lower diastolic blood pressure, and higher levels of albuminuria.

We were not able to show the benefit in attenuating progression of renal disease in patients with higher SBP, higher triglycerides, and previous cardiovascular events.

Although this retrospective analysis generates interesting hypotheses, they cannot be used as treatment recommendations and need additional testing. Extrapolation of our findings to younger nonobese patients with diabetes and women must be done with caution. Clinical trial reg. NCT, clinicaltrials. These companies had no role in the design of the study, in the accrual or analysis of data, or in the preparation of the manuscript.

No other potential conflicts of interest relevant to this article were reported. All authors of this article had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Sign In or Create an Account. Advanced Search. User Tools. Sign In. Skip Nav Destination Article Navigation. Close mobile search navigation Article navigation. Volume 34, Issue 9. Previous Article Next Article.

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