Is it normal for a type 2 patient to have C-peptide levels that are dropping about 1 point per year? In June 2003, the fasting level was 5.6. Now, in March 2006, the fasting level is 2.7 ng/dl. Will it continue to drop at the same rate? My sister could be pretty low in two years. Could this rate of the drop in C-peptide actually mean that she has LADA? She had a GAD65 antibody test that was negative at the time before the drop off in the C-peptide level. She’s wondering if the GAD test could be positive by now. I know that some type 1 patients have negative antibody levels. Her weight has remained the same for the past five years even though she is on 22 units of Lantus and four to six units of Humalog at breakfast. She weighs 160 pounds. She exercises several times a week and is careful with her diet.

Good question. Individuals who are over the age of 30 who develop diabetes and have a family history of diabetes, need to have some way of sorting out whether they have type 1 or type 2 diabetes. The antibody tests, of which anti-GAD is one, are helpful in that regard. An increased anti-GAD antibody is helpful in characterizing someone as having late onset autoimmune diabetes of adulthood (LADA). In practical terms, it may not make a difference. For instance, people with LADA may respond initially to oral agents. Theoretically, they may not be treated successfully as long with oral agents as someone with type 2 diabetes, although that is variable. It has not been determined definitively that insulin therapy up front is superior or prolongs beta cell function, although that might be the most logical assumption.

It has also been noted that patients with type 2 diabetes lose some beta cell mass and function over time. In fact, the natural history of type 2 diabetes is associated with some loss of insulin secretion over time. Now, when you see these C-peptide changes over time, you are asking a logical question as to whether you can differentiate LADA versus type 2 diabetes. To answer that, you have to understand how insulin secretion is evaluated. In most cases where a research study is involved, there is a standardized challenge. This is usually oral glucose, but it could also be intravenous glucose or intravenous amino acid such as arginine. It could also be an oral meal in the form of a commercially prepared liquid supplement. However, it is important to note that each of these challenges to insulin secretion have been studied, whereas the C-peptide levels you are providing have not. It is not clear whether the stimulus was the same when the C-peptide was 5 or 2. What some of the studies, to date, have told us about C-peptide with LADA is that, at some point, the C-peptide response falls fairly rapidly and end up looking like people with type 1 diabetes. So, to make a long story short, I do not think the two C-peptide levels can really tell us what you want to infer from the results. Rather, she needs to continue to watch her diet, exercise, and work with her doctor to adjust her insulin.

JTL