Key Studies in Diabetes

There have been many studies in those with diabetes. Below we summarize some of the most well-known and important studies.

Diabetes Prevention Trials

Many studies have investigated ways to prevent both type 1 and type 2 diabetes.  Below we summarize some of the largest and most well-recognized trials to date.

Da Qing IGT and Diabetes Study

Chinese researchers randomized more than 100,000 people with prediabetes and found that regular exercise and a healthy diet can reduce the risk of diabetes. Individuals who modified their diet had a 31 percent lower risk of diabetes, while those who adopted an exercise regimen had a 36 percent lower risk over a period of 6 years. Individuals who embraced both lifestyle changes (diet and exercise) had a 42 percent lower risk.

Pan et al. Diabetes Care. 1997;20:537.

Diabetes Prevention Program (DPP)

A study of 3,234 middle-age adults with prediabetes found that intensive lifestyle counseling (which included dietary changes and 150 minutes of exercise per week for a weight loss goal of ≥7%) could reduce the onset of diabetes by 58 percent compared to usual care. Metformin treatment reduced the onset of diabetes by 31 percent. These benefits persisted throughout the study’s 15-year follow up period.

Knowler et al. N Engl J Med. 2002;346(6):393-403.

TRoglitazone In the Prevention Of Diabetes (TRIPOD)

In another study of 133 women with a history of gestational diabetes, researchers found that the diabetes drug troglitazone (a thiazolidinedione medication) can reduce the risk of diabetes in half. This drug was removed from the market due to liver toxicity, but similar benefits in reducing the risk of diabetes were seen with another diabetes drug in the same class called pioglitazone. A separate study (the DREAM trial) of 5,269 people showed similar benefits from another drug in this class called rosiglitazone, but this class of drugs also has multiple side effects that need to be considered.

Buchanan et al. Diabetes. 2002 Sep;51(9):2796-803.

DREAM investigators et al. Diabetes Care. 2008;31(5):1007-14

 

Type 1 Diabetes Prevention

Studies of people with type 1 diabetes to date have found no evidence that preemptive insulin injections can prevent or delay the onset of disease. Studies of other early treatments are ongoing.

Key messages:

  • Lifestyle changes and certain medications (such as metformin) can prevent the progression from prediabetes to type 2 diabetes.
  • Type 1 diabetes prevention is more difficult. Some studies suggest this condition may be at least partially prevented by starting treatment at the first sign of immune dysfunction, but this is still unclear and multiple studies are ongoing.

Prevention of Diabetes Complications Trials

Diabetes can lead to many complications, both macrovascular (heart attack and stroke) and microvascular (eye, kidney, and nerve damage).  Below we summarize many of the largest and most well-known trials which investigated prevention of these complications with optimal blood glucose control.

Diabetes Control and Complications Trial (DCCT)

A study of 1,441 people with type 1 diabetes found that nerve damage to the retina, known as diabetic retinopathy, could be dramatically reduced by maintaining healthy blood sugar levels over a 6.5-year period. Tight blood sugar control also reduced development of kidney disease and cardiovascular disease. However, patients with tight blood sugar control were more likely than others to have bouts of low blood sugar.

A long-term follow-up of these patients saw that these benefits lasted long after the trial ended. After 30 years of follow up, the group that had tightly controlled blood glucoses from the beginning of the study had a 32% reduction in major cardiovascular events (nonfatal myocardial infarction; stroke or cardiovascular death) suggesting that better control early in type 1 diabetes can prevent cardiovascular disease.

N Engl J Med. 1993; 329(14):977-86.

N Engl J Med. 2000;342(6):381-9.

UK Prospective Diabetes Study (UKPDS)

Another study of 3,867 patients with newly diagnosed type 2 diabetes found that more intensive therapy leading to tighter glucose control (A1C <7%) lowered the risk of diabetes complications, mainly related to eye and kidney disease, over a 10-year period. A follow up study following the same patients for another 10 years found lower risk of heart attack and death from any cause in the intensive group in the original study.

Lancet. 1998;352(9131):837-53.

Holman et al. N Engl J Med. 2008;359(15):1577-89.

Action to Control Cardiovascular Risk in Diabetes (ACCORD)

Researchers studied 10,251 people (mean age in the sixties) with diabetes at high risk of cardiovascular disease, and found that aiming to achieve an A1C level of less than 6 percent (as opposed to a less strict A1C goal between 7 to 7.9 percent) unexpectedly increased the risk of death from cardiovascular disease. This was the first major trial to suggest that very intensive glucose control might lead to potential harm in persons with diabetes at high risk for cardiovascular disease.

Gaede et al. N Engl J Med. 2008;358(6):580-91.

Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE)

A study of 11,140 older people with type 2 diabetes at high risk for cardiovascular disease which investigated the benefits of tight control.  While the intensive control group had lower rates of diabetic kidney disease, there was no benefit for cardiovascular outcomes, even in a follow up study.

ADVANCE collaborative group et al. N Engl J Med. 2008;358(24):2560-72.

Veterans Affair Diabetes Trial (VADT)

A study of 1,791 male military veterans with diabetes, also studying the effects of intensive control (average A1C of 6.9%) compared to less aggressive control (average A1C of 8.4%).  The initial trial showed low rates of diabetic kidney disease in the intensive group.  A follow-up study showed lower rates of first cardiovascular event in the intensive group, but no difference in survival.

Duckworth et al. N Engl J Med. 2009;360(2):129-39

Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial

NICE was a study of 6,104 patients with diabetes who had been admitted to an Intensive Care Unit and were expected to stay at least 3 days and investigated the effects of intensive glucose control (goal glucose 80-108 mg/dl vs. <180 mg/dl).  Surprisingly, they found that aggressive glucose control in the intensive care hospital setting led to more deaths than conventional approaches to blood sugar control.

NICE SUGAR study investigators et al. N Engl J Med. 2009;360(13):1283-97.

Key messages:

  • Early and intensive glucose control immediately after the diagnosis of type 2 diabetes leads to lower rates of eye and kidney damage and cardiovascular events with benefits that extend over many years.
  • The benefits of intensive glucose control on cardiovascular outcomes in those with diabetes and at high risk for cardiovascular disease is unclear.
  • Too aggressive glucose lowering during hospital stays may lead to more hypoglycemia and higher rates of death.

Poll of the Month

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