In 1993, the landmark Diabetes Control and Complications Trial (DCCT) showed definitively that those patients with Type 1 diabetes who practiced intensive blood glucose control had a significantly smaller risk of developing the microvascular complications of diabetes — diabetic retinopathy (eye disease), diabetic nephropathy (kidney disease) and diabetic neuropathy (nerve disease). However, growing evidence over the past decade shows that risks are associated with intensive blood glucose control and thus it might not be for everyone. Here’s what the research shows.
Many different tools can help achieve good blood glucose control. Frequent blood glucose monitoring allows individuals to change their dose of insulin based on their blood glucose readings and thereby keep their blood glucose levels in the normal range. Testing hemoglobin A1C (also called glycated hemoglobin or HbA1c) allows patients and their doctors to assess the level of blood glucose control over the previous three months. Continuous glucose monitoring (CGM) devices continuously monitor glucose in the interstitial fluid, the fluid between cells.
More medications are available for treating diabetes than ever before. Different insulin and insulin analog products, for example, come with different activity profiles. They vary in terms of onset of action (how long before they start to work), peak activity (when their effects are strongest) and duration of action (how long they continue to work). These various activity profiles allow people with diabetes to provide the baseline level of insulin their bodies need all the time along with the extra insulin they need to cover meals. Insulin pumps allow users to change their insulin infusion rate based on blood glucose readings and add extra insulin between meals. Recently, closed-loop insulin pump systems have become available that automatically change their insulin infusion rate based on CGM values.
Treatment options for Type 2 diabetes have also blossomed. Some classes of medication, such as the sulfonylureas, meglitinides and incretin mimetics (also known as GLP-1 analogs), work primarily by stimulating the pancreas to secrete more insulin. Others, such as the biguanide medication metformin and the thiazolindinediones, work primarily by helping the body use insulin more effectively. Other medications work by other means such as stimulating the release of insulin in response to rising blood glucose levels, blocking the release of glucose from the liver, slowing down the breakdown of starches and sugars in the intestines and blocking glucose from being reabsorbed by the kidneys.
In the DCCT, 1,441 volunteers with Type 1 diabetes were randomly assigned to receive either standard therapy of one or two daily insulin injections or intensive therapy with at least three daily insulin injections or an insulin pump in conjunction with blood glucose self-monitoring. The patients were then followed for an average of six and a half years, during which time they were assessed for the development and progression of diabetic complications. Those who practiced intensive therapy had an average HbA1c of 6.9 percent, while those practicing conventional therapy had an HbA1c of 8.0 percent. The results were so robust that the naysayers couldn’t ignore them, and even the proponents of intensive control were astounded. Compared with conventional therapy, intensive control lowered the risk of developing diabetic retinopathy by 76 percent. Among those who already had mild retinopathy, intensive control slowed its progression by 54 percent and reduced the development of severe nonproliferative retinopathy by 47 percent. Intensive control reduced microalbuminuria (an early marker of diabetic nephropathy) by 39 percent and albuminuria (a later marker of kidney disease) by 54 percent. Furthermore, intensive therapy reduced the development of clinical diabetic neuropathy by 60 percent. The DCCT was followed by several large studies showing similar benefits in patients with Type 2 diabetes. Based on these results, the American Diabetes Association (ADA) recommended that people with diabetes strive for HbA1c levels of 7 percent.
On the other hand, no convincing evidence has emerged from any of these trials that intensive control prevents or delays cardiovascular mortality in patients with either Type 1 or Type 2 diabetes.
Despite these benefits, intensive blood glucose control with insulin or specific types of oral agents called sulfonylyureas (glipizide and glyburide) and meglitinides (rapaglinide and nateglinide) carry a significant risk of hypoglycemia, or low blood sugar. Hypoglycemia can be a nuisance, causing unpleasant symptoms like trembling and sweating, and interfering with work, relationships and life in general. Severe hypoglycemia can be life-threatening and is associated with a higher risk of cardiovascular disease.
Based on accumulating evidence about the potential downside of intensive blood glucose control, the ADA and the European Association for the Study of Diabetes issued a joint policy statement in 2012 recommending more flexibility in selecting blood glucose goals. The ADA currently recommends an HbA1c of less than 7 percent in many patients. It recommends stringent blood glucose goals (such as less than 6.5 percent) in people with a short duration of diabetes, a long life expectancy and no cardiovascular disease if they could be achieved without significant hypoglycemia. On the other hand, it suggests less stringent blood glucose goals (such as less than 8 percent) for those having difficulty maintaining target blood glucose levels or with a history of severe hypoglycemia, long-standing diabetes and a limited life expectancy.
In 2015, the Internatonal Hypoglycemia Study Group made a number of recommendations for physicians. Among these recommendations are to avoid sulfonylurea medications and glinides, which tend to cause hypoglycemia. When insulin is required, the group recommends using insulin analogs and considering the use of insulin pumps, continuous glucose monitoring and a combination of these two in certain patients. Finally, they recommend seeking “to achieve the lowest hemoglobin A1C level that does not cause severe hypoglycemia and preserves awareness of hypoglycemia with an acceptable number of less-than-severe episodes of hypoglycemia, provided that benefit for glycemic control can be anticipated.”
If you have trouble reaching your blood glucose goals or have too many episodes of hypoglycemia, talk with your doctor. He or she will review your diabetes management program and make adjustments as needed.
When blood glucose levels begin to fall below normal, this triggers the body’s “fight or flight” response, causing such symptoms as anxiety, trembling, sweating and heart palpitations. If hypoglycemia becomes more severe, the brain becomes starved for glucose and cannot function properly, causing such symptoms as confusion, behavioral changes and mood swings.
To prevent hypoglycemia, the most important thing you can do is to check your blood glucose levels regularly. People who have frequent hypoglycemia or who are unaware they are experiencing hypoglycemia may want to talk with their health-care provider about the possibility of getting a continuous glucose monitor (CGM). A CGM automatically checks your blood glucose level throughout the day and night and sounds an alarm if you experience hypoglycemia while sleeping.
Treating hypoglycemia: The National Institutes of Health (NIH) recommends treating hypoglycemia with 15 grams of carbohydrate: four glucose tablets or one tube of glucose gel; one-half cup of regular fruit juice (not low-calorie or reduced sugar); one-half can of soda (not low-calorie or reduced sugar); one tablespoon of sugar, honey or corn syrup; or two tablespoons of raisins. Wait 15 minutes and check your blood glucose again. If it is still low, eat or drink another 15 grams of carbohydrate. Keep repeating these steps until your blood glucose is back to normal.
If you experience severe hypoglycemia, you may not always be able to treat it yourself. Talk with your health-care provider about buying and using a glucagon emergency kit. Teach your family, friends and coworkers when and how to give you a glucagon injection, and tell them to call 911 right away. You should also wear a medical alert bracelet or pendant, which will tell other people that you have diabetes and to call for medical care right away.
Want to learn more about managing blood sugar? Read “What Is a Normal Blood Sugar Level?” “Managing Your Blood Glucose Ups and Downs”, and “Making Your Blood Glucose Monitor Work for You,” then see our blood sugar chart.
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