Nowadays, authors do not agree about the definition of little vessels alterations in the “pre-diabetic” stages (8). Some authors think that basal membrane thickening, initially small from biophysical semeiotic view-point, involves exclusively individuals particularly predisposed. Arterioles sclerosis, described by Butturini in digitals biopsies of obese subjects involved by “latent” diabetes (9), concerns more advanced stages of the disorder than those we consider, as demonstrates the temporary normalization of diagram, caused by apnea test as well as by venous-lympho-manual drainage. Therefore, Biophysical Semeiotics allows doctor to recognize the diabetic constitution in a “quantitative” manner.
As regards both glomical Arterio-Venous Anastomoses (AVA) and Endoarterial Blocking Devices (EBD), we can observe alterations similar to those described above, characterized by prolonged closure and shorter opening, which cause consequently insufficient blood-flow in local microvessels, at this moment at least, really counter-balanced successfully by microcirculatory activation, type III, incomplete. In a few words, arterioles and little arteries fluctuations are actually “intense”, but local capillaries and venules oscillation are “normal”.
In fact, the physiological temporal inhomogeneity is not present, and doctor can observe the above-illustrated microcirculatory activation, which represents the “zero stage” of the so-called pathological spatial inhomogeneity.
At this moment, arteriolar sphygmicity (= third upper urethral reflex oscillations) increases clearly with subsequent increasing of interstitial and venular capillaries dynamics, where fractal dimension appears reduced, indicating the activation of Functional Microcirculatory Reserve (FMR) already at rest.
At this point, it seems very interesting that the second and third diagram evaluation, performed after exactly 5 sec. interval (preconditioning), results physiological, indicating the mainly functional nature of described alterations (Fig. 4).
The interstitium (= “in toto” urethral reflex, which is carried out slowly), since initials stages of DM, is > 1 cm. – pathological sign – outlining the enlargement of this perivasal space (NN £ 1 cm.), partially due to increasing of capillaries and arterioles permeability. In initial phases, manual lymphatic drainage as well as apnea test (= sympathetic hypertonus) normalize temporarily these modified parameters values of IGT tissue-microvascular diagram, proving the primary role on vasomotion, played by the interstitium.
The modification of venous-vasomotor reflex – evaluated clinically as latency time of finger-pulp gastric aspecific or caecal reflex during “3 posture test” (in healthy lt appears always identical: 8 sec.) – occurs mainly precociously, when light, but present, organic, structural lesions occur or worsen.
An easy, but refined, method, useful in recognizing venous-arteriolar reflex (VAR) is the following: “intense” digital pressure upon a finger-pulp of an individual, lying down in supine position and psycho-physically relaxed, brings about physiologically disappearing of upper urethral reflex (type II, group B, AVA) when the arm is in high position, i.e. perpendicular to the bed: FMR promptly activated and realized, as type II, group B, AVA closure clearly demonstrates.
These clinical microangiological data agree perfectly with the demonstration of remarkable structural alterations of type II, group B, AVA, according to Bucciante, in case of obesity in individuals with glucose utilization in normal ranges. There are some modifications especially of intermediate glomic segment, which bring about hyperstomy, while local capillaries basal membrane only occasionally is well outlined by PAS (8).
It seems, therefore, also from biophysical-semeiotic vie-point, that in “latent” DM the first alterations are localized in myoepithelioid segments of glomic AVA, rather than in capillaries and arterioles (8). Therefore, Biophysical Semeiotics corroborates, once again, Curri’s statements. More precisely, in our mind, the original semeiotics complete really Curri’s bioptic data, emphasizing the simultaneous modifications of EBD, we observed in a long well established experience, starting from the very initial phase, i.e. diabetic constitution.
Clearly, not completely differentiated cells, as myoblasts of both myoepthelioid media and EBD muscular cells, are apparently more sensitive to dysmetabolic noxae – and, we add, to mitochondrial disorders (CAEMH- a ), always present, representing the conditio sine qua non “also” of DM – than all other differentiated muscular cells, which notoriously contract for a shorter time and dilate more rapidly, showing the physiological, periodic break of their diastolic-systolic movements (temporal inhomogeneity).
A further and important fact, thus, is the demonstration in IGT with insulin hyper-secretion (in which pancreatic preconditioning appears to be pathological and lt. of pancreatic-gastric aspecific reflex is > 12 sec. – physiological value –, due to insulin hypersecretion) of initial asynergy of derivative structures, premise of histangic suffering: arterioles contraction happens when EBD are only partially “open” and AVA (strictly speaking) are maximally open, causing blood-reflux towards capillaries-venules, bringing about local endoluminal pressure increasing and consequently histangium damage (lower urethral reflex results “intense”).
In conclusion, as regards the pancreatic interstititum of “pre-diabetic” phase, it is larger than normal (> 1 cm.), due to amyloid storage, and likely to free-water prevalence, indicating impairment of interstitial matrix, although initial and light (e.g., manual lymphoid drainage provokes disappearing of such alteration), in agreement with data of other authors on precocious glucosaminoglycanes (GAG) modifications of fundamental connectival substance, and then of the differentiation ability of cells, mesenchymal in origin, especially as regards the fibroblasts activity, as well as myoblasts metabolism (8).
In this stage, there are likely altered relations between local cytokines, particularly TGF b 1, 2, 3 , with their well-known negative influences on the local microcirculation (10).