Optimizing Insulin Therapy in Diabetes - Episode 1
Serge Jabbour, MD: We all know the importance of glycemic control in type 2 diabetics. In fact, in 1998 a famous landmark study called UKPDS (The United Kingdom Prospective Diabetes Study) was published. In the study, they enrolled 4000 type 2 diabetics in the United Kingdom and they compared intense treatment, either using metformin or SU (sulfonylurea) or insulin, to conventional treatment, where patients were given only diet without any medications. They showed over 10 years’ time that if you treat patients intensively with a drug, getting the A1C level to 7% or less, you can reduce the rates of microvascular complications by 25% in general. That included nephropathy, retinopathy, and neuropathy.
Now when the study ended at 10 years, they kept following patients over time to see what happened. And when they followed patients for another 10 years, what they saw was very interesting. 20 years from the beginning, not only had they reduced the rates of microvascular complications, but also the rates of macrovascular complications, meaning heart disease and stroke. So, it may take a long time to see the effect on CV events, but we can see the effect on microvascular complications really quickly. Based on that study, other smaller studies done, and the DCCT in type-1 diabetics, the ADA set the A1C goal at 7% or less in most patients.
Based on guidelines, mostly ADA guidelines, they tell you that the A1C goal for most patients should be 7% or less. That’s based on the UKPDS and DCCT trials. Now, there are exceptions. Exceptions are if you see older patients, defined as an age above 60, with underlying CV events. In those patients, the A1C goal shifts up to around mid-7%. Of course, if you also see patients in their 80s, you might say, “Why be too strict? Let’s have it go up to 8%.” So, you can vary that A1C goal based on the age of the patients and the comorbid conditions they might have, mostly heart disease. Now, if you have younger patients without any CV events and if you pick the agents that don’t cause hypoglycemia, you can lower that A1C to less than 6.5% based on ACE guidelines. That’s why it depends. For every patient, you set a different goal.
Robert Hood, MD: Over 90% of people with type 2 diabetes are insulin resistant, but 100% of them have defects of beta cell function. Unfortunately, this is progressive over time. So, it’s really a matter of when you’re going to require insulin, not if. As your endogenous insulin supplies dwindle, eventually you’re going to need endogenous insulin to maintain adequate glycemic control.
Serge Jabbour, MD: When patients are on insulin and we keep increasing the dose but A1C doesn’t come down and sugars remain high, patients become extremely frustrated. Every time they call or they come in, we increase the dose, but they don’t see the outcome expected and they keep gaining weight because the more insulin you give, the more weight gain you might see in these patients. So, what I see all the time is frustration from patients. That’s why it’s important that when we reach a certain limit where our patients are on high-dose insulin and not responding, we should think, “What can we do to help our patients? What are the options available?” We should also think about compliance issues, because when we place patients on 4 injections a day of high-dose insulin, obviously compliance could become a big factor in why A1C is not coming down. That’s when we should think about other options for these patients.
Now, A1C is extremely important, but you should not forget the importance of other factors. Many patients, at least 60% to 80%, could also have metabolic syndrome where there are weight issues, hypertension, and lipid abnormalities. So, we should not forget about educating patients about the importance of diet, weight loss, and exercise, or about treating hypertension, making sure that blood pressure is at goal, treating lipids by adding a statin, and smoking cessation, because that’s also a big risk factor for heart disease.
Transcript edited for clarity.