The Carb-Sane Asylum

Sixteen Post Bumps for 2016 ...  No. 2 Update Notes & Summary This post discusses the section entitled  INCREASED PROINSULIN AS THE MAIN BETA CELL SECRETORY DEFECT in the following 2007 article:   PROINSULIN, PROAMYLIN AND THE BETA CELL ENDOPLASMIC RETICULUM: THE KEY FOR THE PATHOGENESIS OF DIFFERENT DIABETES PHENOTYPES .     This is but one of the papers that turned up as I was delving deeper into the progression of Type 2 diabetes and what it really involves.  It was this work that began the research and blogging journey into sorting out what insulin resistance is, if indeed it does exist as it is commonly "understood" from the standpoint of peripheral tissue glucose metabolism.   In the words of the authors of the paper: ... for three decades, the beta cell dysfunction has been shaded by the theoretical construction of peripheral insulin resistance . These researchers have access to roughly 170,000 records of everyone diagn...

Random Bump: There has been some discussion of diagnosing diabetes type going on in my comments of late and I thought this might be a good post to bump in response.  It's pretty specific, but contains links to some background blogging. I think it would be safe to say that I'm of the belief -- and the scientific evidence seems overwhelming in support -- that peripheral insulin resistance is either non-existent or plays a minor role in T2 diabetes.   Nonetheless, the concept of IR remains, but for the most part is diagnosed using a fasting HOMA-IR score based on fasting insulin and glucose levels.  This is considered a measure of hepatic IR, but even here appears to be a flawed measure.    The "swamped insulin receptor" model is flawed.  Not saying it doesn't perhaps play a role, but glucose uptake is not the first defect nor the main determinant of elevated circulating glucose.   The WHO even classified Type 2 Diabetes as such (1999): ...

Continuing with our discussion on diabetes ... In my last post on the topic , I introduced this paper:   β-Cell dysfunction vs insulin resistance in type 2 diabetes: the eternal “chicken and egg” question .  This got me to thinking again about early insulin treatment for Type 2.   In an ideal world a more thorough post on EIT for T2 would precede this one, but I've got a paper on this open in the browser and don't want to forget it.  There are, however, several studies out there employing insulin early in the diagnosis of diabetes that have had remarkable results and this is worth revisiting briefly here.  Three of these studies are summarized in the table below from this paper

A slight detour in my current endeavors to put forth some information regarding the etiology of diabetes, insulin resistance and β-cell function, before I get to the two major reviews that prompted this. To review, in my last post , discussing this paper , a seminal observation/conclusion can be summed up as follows:   Insulin is formed in stepwise fashion from a larger protein (preproinsulin) that has a terminal signaling chain cleaved forming proinsulin that is then folded, cross-linked and has one of the three main chains cleaved in the last step(s) resulting in a protein with two parallel chains, insulin.  I like this newer representation I found below because it provides the numbers in the amino acid sequence at which the cuts are made.  This is important to better understanding the papers I'm going to discuss here.