First would be the possibility of insulin degradation in your whole blood sample. If not using coagulants like edta, insulin can degrade a lot in 24h. It also sticks to epruvete surfaces, gets degraded by temperature, mechanical damage, etc.
How would I get / is there a way to get a "proper" blood test done to measure fasting insulin to try and avoid these confounding variables?
The other would be your biology. You might not be at such risk for GH mediated insulin insensitivity for what ever reason.
I'll pray this is it, lol.
The third is ofc cardarine plus tirzepatide and all other factors that were relevant on the day you did your blood test. Tirz should elevate insulin, it's mostly how glp's modulate bg management. They have other moa's like decreasing inflammation, lowering hepatic glucose release, etc. but mostly it's the increased insulin secretion (somebody correct me if I'm wrong) that takes care of things and on 16 iu's you'd need a heck of a lot of insulin ...
I'm still trying to wrap my head around GLP1s, especially tirz + reta due to the multiple mechanism of action.
There is an interesting rodent study:
Tirzepatide is a dual GIP and GLP-1 receptor co-agonist which is approved for glucose-lowering therapy in type 2 diabetes. Here, we explored its effects on beta cell function, insulin sensitivity and insulin-independent glucose elimination (glucose effectiveness) in normal mice. Anesthetized...
pubmed.ncbi.nlm.nih.gov
Tirzepatide is a dual GIP and GLP-1 receptor co-agonist which is approved for glucose-lowering therapy in type 2 diabetes. Here, we explored its effects on beta cell function, insulin sensitivity and insulin-independent glucose elimination (glucose effectiveness) in normal mice. Anesthetized female C57/BL/6 J mice were injected intravenously with saline or glucose (0.125, 0.35 or 0.75 g/kg) with or without simultaneous administration of synthetic tirzepatide (3 nmol/kg). Samples were taken at 0, 1, 5, 10, 20 and 50 min. Glucose elimination rate was estimated by the percentage reduction in glucose from min 5 to min 20 (KG). The 50 min areas under the curve (AUC) for insulin and glucose were determined. Beta cell function was assessed as AUCinsulin divided by AUCglucose. Insulin sensitivity (SI) and glucose effectiveness (SG) were determined by minimal model analysis of the insulin and glucose data. Tirzepatide glucose-dependently reduced glucose levels and increased insulin levels. The slope for the regression of AUCinsulin versus AUCglucose was increased 7-fold by tirzepatide from 0.014 ± 0.004 with glucose only to 0.099 ± 0.016 (P < 0.001). SI was not affected by tirzepatide, whereas SG was increased by 78% (P < 0.001). The increase in SG contributed to an increase in KG by 74 ± 4% after glucose alone and by 67 ± 8% after glucose+ tirzepatide, whereas contribution by SI times AUCinsulin insulin (i.e., disposition index) was 26 ± 4% and 33 ± 8%, respectively. In conclusion, tirzepatide stimulates both insulin secretion and glucose effectiveness, with stimulation of glucose effectiveness being the prominent process to reduce glucose.
This tickles me because what I gather from this study is that yes, insulin secretion is increased, however, it's not the main driver of glucose reduction via Tirz.
Then, we consider this study speaking of adipocyte nutrient metabolism via GIP receptor agonism:
However, cellular mechanisms by which GIPR agonism may contribute to these improved efficacy outcomes have not been fully defined. Using human adipocyte and mouse models, we investigated how long-acting GIPR agonists regulate fasted and fed adipocyte functions. In functional assays, GIPR agonism enhanced insulin signaling, augmented glucose uptake, and increased the conversion of glucose to glycerol in a cooperative manner with insulin; however, in the absence of insulin, GIPR agonists increased lipolysis. In diet-induced obese mice treated with a long-acting GIPR agonist, circulating triglyceride levels were reduced during oral lipid challenge, and lipoprotein-derived fatty acid uptake into adipose tissue was increased. Our findings support a model for long-acting GIPR agonists to modulate both fasted and fed adipose tissue function differentially by cooperating with insulin to augment glucose and lipid clearance in the fed state while enhancing lipid release when insulin levels are reduced in the fasted state.
and considering that I was using GH in a fasted state, with cardarine, which you elucidated on the synergy of using those two together below, plus the fact I was very very well fat adapted and relatively strict ketogenic diet, makes me believe it's really all of these factors acting together:
(Tirz modulating lipid metabolism (fasted state context) plus glucose clearance + my fasted state + cycling during peak GH release / acute insulin resistance period of GH + cardarine increasing fatty acid oxidation to directly counter GH increase in FFA)
Excluding genetics and lab errors, chances are that cardarine played a major role here. It does kinda directly counteract GH's diabetogenic effects as it increases fatty acid oxidation (GH increases FFA's) and enhances glut4 translocation, which GH decreases. It's also a GDA, lowering the need for insulin on muscle tissue glucose uptake. If this is the case, maybe there is some warrant to use this potentially carcinogenic drug after all.
All of this is to say, I was astonished my fasting insulin came back so low despite the cocktail of PEDs, VLCD, and cycling at perfect time to attenuate the acute insulin resistance of GH post administration.
Your input and perspective on this is very much appreciated.
