Something I've been reading a lot lately would be along the lines of "first phase insulin response is deficient/missing from the early stages of diabetes". This is true, but even in the peer review literature that term seems to be misused to equate with the acute spike in insulin levels to a high oral glucose load. However the first phase insulin response, hereinafter FPIR, is a non-physiologic phenomenon sometimes used to assess pancreatic function.
First-phase insulin secretion: does it exist in real life? Considerations on shape and function (decluttered of references, please see origina, some parts bullet-pointed, etc. for clarityl)
IN THE PAST THREE DECADES, the relevance of insulin secretion abnormalities in the pathogenesis of type 2 diabetes mellitus have been extensively debated, and a consensus has been reached that, to fulﬁll its pivotal role in regulating glucose metabolism, insulin secretion must not only be quantitatively appropriate, but also possess qualitative, dynamic features that optimize insulin action on target tissues. In particular, increasing emphasis has been placed on the importance of the so-called ﬁrst-phase insulin secretion to glucose homeostasis. The aim of this review is to address the following questions:
- Does a ﬁrst-phase insulin secretion really exist in in vivo physiology?
- What is the relationship between the ﬁrst-phase insulin response to a brisk intravenous glucose challenge and the early insulin response following glucose ingestion?
- What are the effects of such insulin responses on glucose metabolism?
This figure shows the difference between insulin responses to the "diagnostic" IV glucose and glucose in a meal.
The glucose level does not rise abruptly as in the IV administration (left) when glucose is ingested. Therefore the biphasic insulin response seen for the IV glucose is not seen in response to a meal. The caption to this figure points out that in addition to the glucose itself, the following things are involved when glucose is ingested: Fatty acids and other secretagogues [stimulators] in the meal, the cephalic response, and gastrointestinal hormones [e.g. incretins like GLP-1]
Now the authors of this paper do some computer modeling and such in coming around to the following:
An increasing body of evidence indicates that the early insulin response following glucose ingestion plays a critical role in the maintenance of postprandial glucose homeostasis. The early surge in insulin concentration is capable of limiting the initial glucose excursion mainly through the prompt inhibition of endogenous glucose production, with the insulin mediated curtailment of glucagon secretion being particularly relevant. This conﬁrms, under physiological conditions, the ﬁndings of the studies that assessed the metabolic relevance of the ﬁrst-phase insulin response to intravenous glucose. In the following discussion, we will provide a brief synopsis of the studies that assessed the beneﬁts associated with the early phase of insulin release as well as the problems that are associated with its impairment.
Basically it comes down an acute response of some sort, whether it's a spike or more of a ramping up ... and being able to sustain the secretion necessary to maintain glucose homeostasis (and more).
So let's put this together with the changes in insulin secretion and glucose levels in the progression of glucose intolerance through diabetes. (From this blog post on this study). You can click to enlarge but top to bottom are series of glucose, insulin and proinsulin responses to a standard OGTT, from left to right in normal, IGT, and four "stages" of T2 based on progressive fasting glucose levels. It is clear that even before diabetes, the acute insulin response is lacking which causes glucose levels to go higher prompting an increased but delayed insulin response. It is also clear that the beta cells are already having a problem efficiently meeting this need for insulin and secreting incomplete product that can't do the job.
Mostly I'm posting this because it is not always made clear that the FPIR is not physiologically relevant per se, but there seems to be a clear relationship between it's presence or absence in an intravenous glucose test and proper insulin secretion in response to a glucose load. Given the very short time frames involved, and how there would be fewer complicating factors in assessing glucose and insulin levels, I'm surprised we don't hear more about this as a diagnostic measure. I admittedly haven't looked much into this aspect of things.