Does anybody know how much Beta-Cell Loss occurrs before T2 Diabetes sets in? 60% loss? 80% loss?
So, oral meds are good in T2 Diabetes ‘mostly’ when there is a little bit of beta-cell function left.
So how much does beta-cell function have to go down to ( loss of 90 %? 100% loss?) before those oral meds that rely on on increasing the output of insulin from the pancreas dont work anymore?
You may know ‘just off the top of your head’ or may have a reference to an article?
Thanks.
Ralph Defronzo discussed this in his 2008 Banting Lecture (http://diabetes.diabetesjournals.org/content/58/4/773). He equates remaining beta cell function to a measure he calls insulin secretion/insulin resistance. He summarizes this in the figure below:
Keep in mind that there is a difference between loss of beta cells and loss of beta cell function. If you read the DeFronzo article he notes 8 major vectors of dysfunction contributing to diabetes. You can lose beta cell function without killing your beta cells, this is why in many cases oral medications work, at least for a while.
BSC, I have a question.
How does a person then have a normal fasting C-PEP test after having a high BG reading after diagonsis? If you have lost 90% of ones beta cell function do they regenerate in a T-2? Or is it just cutting the carbs and the remaining beta cells can then give one a normal C-PEP. I know that some Docs make you eat a candy bar and put you under stress when giving the C-PEP.
I am confused on this issue. Thanks
Good question. I’ve struggled with this and have concluded that the fasting c-peptide test is a useless waste of my money, but I still pay for it. Your pancreas produces insulin on demand, and the c-peptide is produced as a by product of the insulin production proportional to the amount of insulin produced. If you are fasting, you are “normally” producing a modest level of basal insulin to regulate your fasting levels. That modest level is perhaps 10% of what might be needed by your body to “cover” high blood sugars when you eat. You might be able to produce a “normal” amount of fasting insulin even though you have lost 90% of your beta cell function.
If you took a “stimulated” c-peptide test, you would ingest something like 50g of carbs and test your c-peptide. If you produce a “normal” amount of insulin, your c-peptide would test much higher. Most diabetics with impaired insulin production would show distorted “stimulated” c-peptide tests. Unfortunately, this test is apparently not used much. There are also no “standards.” A big guy, like you or me might need to make lots of insulin, but a petite woman would need only a fraction. Thus, the definition of “normal” is highly individualistic.
Thanks BSC.
My Dr doesn’t think to much of the test either for the very thing you cite, lack of study and differences in lab normal. He is more interested in treating the BG levels and getting them in the range of 70-100 fasting.
Your explanation gave me a little more insight into this curious question.
Tupe 2 diabetes is about insulin resistance not beta cell loss. A person with Type 2 diabetes prodces insulin. Alot more than an average person in some cases, but the bodies cells are resistane to the insulin or they do not use it correctly.
A person wth Type 1.5 may appear to be a Type 2 diabetic, initially, because the Beta cell loss is so gradual and they respond to oral medicines to stimulate production… But, they eventually get to a point where there is no production and they need insulin to survive.
Thanks BSC
This beats the slide/info I hace been looking at till now see Slide 5 from this presentation:
Management of Type 2 Diabetes: INSULIN (adapted from UKPDS Study)
http://www.slideworld.org/viewslides.aspx/Management-of-Type-2-Diab…
I am not convinced that loss of beta cell function is always a factor in the persistent hyperglycemia referred to as “Type 2 Diabetes”. In the case of obese individuals who are diagnosed early in the progression and who are able to lose significant amounts of weight and return to “normal”, or even near-hypoglycemic, blood glucose levels and A1cs, it is possible that lipokines (hormone-like substances released by fatty tissues) interfere with insulin signalling mechanisms (when to produce more insulin) and insulin absorption mechanisms. The reduction of fatty tissues reduces the serum levels of these lipokines and thereby, their influence on glucose metabolism.
Glad it was helpful. It does appear that slide 5 is just a qualitative slide. I can’t look at the original source (UKPDS), but it appears that they just “speculate” on the normal beta-cell function. I’ve struggled with understanding my diabetes, I wasn’t heavy, I appeared to be fairly insulin sensitive, I have not responded well to oral medications and my tests have showed low insulin production. I am GAD negative and everyone insists I am T2. The paper from DeFronzo really helps to explain that there are a number of factors (he claims 8, including IR as mentioned by tmana) involved with diabetes. Diabetes manifests differently for everyone.
While many (if not most) of T2 diabetics are insulin resistant, the mere fact that there has been a loss of blood sugar control says that insulin production is “insufficient.” But the insulin resistance explanation never fit me and I always had trouble understanding what was going on. DeFronzo in the article cited above helps to explain this. His “Ominous Octet” highlights the other factors that come into play, and the factors that you mention are involved with several of them.
So based on this then BSC the parasympathetic nervous system signals are then messed up too?
I don’t know Pauly. I would think problems with the parasympathetic nervous system might occur with autonomic neuropathy. I think when DeFronzo talks about neurotransmitter dysfunction, he is talking about messed up insulin signalling. That your hypothalmus which is supposed to send out regulating signals to your pancreas just does not work properly.
Best of luck to you with everyrthing!