Post up your Natty IGF-1 Level

[Trenbolonetax]

In classic DT2 conditions glut4 translocation is decreased, but apparently GH's diabetogenic effects dont involve this mechanism. Had to refresh my memory a bit on this one.

And if we are on the subject of glut4, @Trenbolonetax did you workout on the day you pulled bloods? As exercise would further drop your insulin levels due to exercises positive effect on muscles glucose uptake which involves increased glut4 translocation ...

I did. I went for a 1 to 2 hour cycle early in the AM, about 8 hours pre pulling bloods. Bloods would've been pulled about 10 hours after GH administration. That totally impacts fasting insulin, for sure.

 

[Jin23]

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?

I'll pray this is it, lol.

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:

The dual incretin co-agonist tirzepatide increases both insulin secretion and glucose effectiveness in model experiments in mice - PubMed

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

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:

https://www.sciencedirect.com/science/article/pii/S1550413124001864\

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)


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.

I haven't really researched tirz at all. Tnx, I'll have a look at those studies later.

Wait, you were keto? I thought you said low carb ...

 

[Trenbolonetax]

I haven't really researched tirz at all. Tnx, I'll have a look at those studies later.

Wait, you were keto? I thought you said low carb ...

I would best characterize it as a modified ketogenic diet. I was predominantly <50g carbs during each weekday, while perhaps going out of ketosis on the weekend with a cheat or two.

I don't remember exactly, but I do recall that the weeks leading up to the blood test I was pretty strict. I know that during that week I was getting blood ketone readings always greater than 1mmol.

I just have trouble characterizing the diet as "strict keto" because I'll bounce in and out all the time typically deviating on the weekend.

Now, right now? No fucking way. I'm just eating like an absolute asshole and I would characterize my diet as SAD, lol.

 

[Trenbolonetax]

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?

I'll pray this is it, lol.

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:

The dual incretin co-agonist tirzepatide increases both insulin secretion and glucose effectiveness in model experiments in mice - PubMed

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

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:

https://www.sciencedirect.com/science/article/pii/S1550413124001864\

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)


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.

Replying to this comment with another study that may actually be the most interesting I've come across re: tirz

JCI - GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

www.jci.org

JCI - GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

www.jci.org

3rd row far right shows a substantial decline in fasting insulin with Tirz treated mice AND a decrease in fasting glucose. Same result for fed state. Super interesting.

EDIT: And realizing this is a natty IGF1 thread. Lol, sorry for the detour.

 

[Trenbolonetax]

Replying to this comment with another study that may actually be the most interesting I've come across re: tirz

JCI - GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

www.jci.org

JCI - GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice

www.jci.org

View attachment 305596

3rd row far right shows a substantial decline in fasting insulin with Tirz treated mice AND a decrease in fasting glucose. Same result for fed state. Super interesting.

EDIT: And realizing this is a natty IGF1 thread. Lol, sorry for the detour.

I'm sorry...last detour but I had to add to my previous. The previous graph is over a 14 day period so doesn't demonstrate insulin sensitivity independent of weight loss. However, this graph does show they accomplished that:

Obese insulin-resistant mice dosed once daily with vehicle, semaglutide, or tirzepatide for 14 days (n = 14–15 per group). (A) Daily body weight and food intake. Following 14 days of treatment, insulin sensitivity was assessed via a hyperinsulinemic-euglycemic clamp. (B) Average glucose infusion rates (GIR) throughout and during the final 30 minutes of the clamp. (C) Average GIR fold change when comparing TZP to that of weight-matched groups during the final 30 minutes of the clamp. (D) Endogenous glucose production (EGP). Insulin-stimulated glucose disposal in (E–G) skeletal muscle, (H and I) white adipose tissue (epididymal and inguinal adipose tissue [eWAT and iWAT]), and (J) brown adipose tissue (interscapular brown adipose tissue [iBAT]). Data are presented as mean ± SEM. *P < 0.05 compared with vehicle, #P < 0.05 compared with semaglutide, and §P < 0.05 compared with pair fed. Statistical analyses performed included 1-way ANOVA or Kruskal-Wallis test followed by Bonferroni multiple comparisons test, where appropriate.

One of the most effective approaches to achieving clinically meaningful improvements in glycemic control is weight loss (35). Therefore, to determine if the effect of tirzepatide on systemic insulin sensitivity is driven in a weight-dependent and/or -independent manner, we compared the insulin-sensitizing action of tirzepatide to a selective GLP-1RA (semaglutide), a mechanism that has been shown to ameliorate IR entirely due to weight loss (36). For these studies, we matched weight loss in obese IR mice by dosing tirzepatide (3 nmol/kg) at a 3-fold lower dose than semaglutide (10 nmol/kg). To further control for weight-driven improvements in insulin sensitivity, we pair fed (PF) a group of animals the same daily food intake as animals dosed with tirzepatide. Chronic administration of either agent reduced body weight and food intake in obese IR mice (Figure 3A). Following 14 days of treatment, there was no difference in weight loss in animals treated with tirzepatide versus those treated with semaglutide. Tirzepatide reduced fasting glucose levels lower than those seen in semaglutide-treated or PF animals (Supplemental Figure 1G). Tirzepatide, semaglutide, and PF reduced fasting insulin when compared with that in vehicle-treated animals (Supplemental Figure 1H). To compare the insulin-sensitizing effects of the 2 treatments, we conducted hyperinsulinemic-euglycemic clamp experiments following the 14 days of dosing. Strikingly, despite eliciting equivalent weight loss, administration of tirzepatide increased whole-body insulin sensitivity more than that achieved in the semaglutide treatment and PF groups (Figure 3B). Tirzepatide increased the GIR by 4.7-fold, while the semaglutide and PF groups increased the GIR by 3.5-fold and 3-fold, respectively, when compared with the vehicle-treated group. There was a 1.4-fold and 1.5-fold increase in the GIR in animals administered tirzepatide when compared with treatment with semaglutide or PF, respectively (Figure 3C). Importantly, comparing the insulin-sensitizing action of tirzepatide to that of the weight-matched groups (semaglutide and PF) indicated that the weight-independent effect of tirzepatide accounts for 30% of the total improvement in insulin sensitivity in obese IR mice. No effect on EGP was observed for any of the groups (Figure 3D). Tirzepatide augmented insulin-stimulated glucose disposal in skeletal muscle significantly more than semaglutide (Figure 3, E–G), while inducing insulin stimulated uptake more than PF in epididymal WAT and BAT (P = 0.09; Figure 3, H–J). These data further support the notion that tirzepatide is indeed a highly effective insulin sensitizer capable of improving IR in both a weight-dependent and -independent manner. Such improvements in whole-body insulin sensitivity associated with the tirzepatide treatment shed light on the improvement in glycemic control observed clinically with tirzepatide when compared with GLP-1R agonism (31).

 

[Jin23]

I would best characterize it as a modified ketogenic diet. I was predominantly <50g carbs during each weekday, while perhaps going out of ketosis on the weekend with a cheat or two.

I don't remember exactly, but I do recall that the weeks leading up to the blood test I was pretty strict. I know that during that week I was getting blood ketone readings always greater than 1mmol.

I just have trouble characterizing the diet as "strict keto" because I'll bounce in and out all the time typically deviating on the weekend.

Now, right now? No fucking way. I'm just eating like an absolute asshole and I would characterize my diet as SAD, lol.

Ok, you were in ketosis. That is the reason for your low insulin numbers. I interpret low carb mostly as anywhere from 50 to 200g's of carb a day, but definitely not being in ketosis so this fact escaped me.

 

[FunkOdyssey]

Ok, you were in ketosis. That is the reason for your low insulin numbers. I interpret low carb mostly as anywhere from 50 to 200g's of carb a day, but definitely not being in ketosis so this fact escaped me.

I think the key thing with the GLP-1 drugs is that they increase glucose-dependent insulin secretion, emphasis on glucose-dependent. If they increased insulin secretion in the fasted or keto state, everyone on these drugs would be passing out from hypoglycemia.

 

[Trenbolonetax]

Ok, you were in ketosis. That is the reason for your low insulin numbers. I interpret low carb mostly as anywhere from 50 to 200g's of carb a day, but definitely not being in ketosis so this fact escaped me.

I would best characterize it as cyclical ketogenic diet at that time. And for further context, I’m able to eat a bit more carbs than your average individual and stay in ketosis or only transiently leave.

What I would love to see is fasting insulin in this scenario but without tirzepatide.

I’m sure it would be higher, I just don’t know how much higher. Per the study I linked, maybe about 30% higher, but I would love to have that demonstrated on blood work.

Interesting stuff.

 

[Jin23]

I think the key thing with the GLP-1 drugs is that they increase glucose-dependent insulin secretion, emphasis on glucose-dependent. If they increased insulin secretion in the fasted or keto state, everyone on these drugs would be passing out from hypoglycemia.

Yes ofc. Were you trying to emphasize something specific with this in regards to my opinion/answer?

 

[Trenbolonetax]

So I guess I’ll tie this ALL BACK to IGF1, in an effort to not derail the thread completely, lol.

It appears that tirzepatide has a high propensity to lower IGF1, all else equal, due to its reduction in fasting and fed insulin, independent of weight loss.

 

[FunkOdyssey]

Yes ofc. Were you trying to emphasize something specific with this in regards to my opinion/answer?

Just drawing attention to the nuances of glp-1 increased insulin secretion, that it is context dependent. The idea that glp-1 drugs increase insulin levels at all times seems to be a common misconception.

 

[Jin23]

I would best characterize it as cyclical ketogenic diet at that time. And for further context, I’m able to eat a bit more carbs than your average individual and stay in ketosis or only transiently leave.

What I would love to see is fasting insulin in this scenario but without tirzepatide.

I’m sure it would be higher, I just don’t know how much higher. Per the study I linked, maybe about 30% higher, but I would love to have that demonstrated on blood work.

Interesting stuff.

I don't have the time or the brain energy to dig in to that study now. However, you were in a fat adapted state, healthy mitochondria, glucose sensitized state and it was 10h after you pinned and you bicycled for 1 to 2h that day and you were in kcal deficit. I'm not surprised by your low normal insulin levels at all, cardarine/tirzepatide aside.

 

[Jin23]

So I guess I’ll tie this ALL BACK to IGF1, in an effort to not derail the thread completely, lol.

It appears that tirzepatide has a high propensity to lower IGF1, all else equal, due to its reduction in fasting and fed insulin, independent of weight loss.

Solid save.

 

[zmurphy]

So I guess I’ll tie this ALL BACK to IGF1, in an effort to not derail the thread completely, lol.

It appears that tirzepatide has a high propensity to lower IGF1, all else equal, due to its reduction in fasting and fed insulin, independent of weight loss.

Not to throw a wrench in the works but my 500+ IGF-1 (2.7iu GH) was on 15mg of TZ, with an insulin over 20. Not sure what conclusions to draw from that. I'm Starting Berberine 500mg with each meal and will retest in 30 days.

 

[Trenbolonetax]

Not to throw a wrench in the works but my 500+ IGF-1 (2.7iu GH) was on 15mg of TZ, with an insulin over 20. Not sure what conclusions to draw from that. I'm Starting Berberine 500mg with each meal and will retest in 30 days.

You probably eat pretty high carb if I had to guess? Also you were probably running AAS? There’s a million things that could be different about our experiences

 

[FunkOdyssey]

Not to throw a wrench in the works but my 500+ IGF-1 (2.7iu GH) was on 15mg of TZ, with an insulin over 20. Not sure what conclusions to draw from that. I'm Starting Berberine 500mg with each meal and will retest in 30 days.

Don't sleep on water-extracted cinnamon. Huge insulin sensitivity gains, without the digestive distress of metformin and berberine:

https://www.amazon.com/gp/aw/d/B06XXFSM3P

 

[AlexDavis43]

Not to throw a wrench in the works but my 500+ IGF-1 (2.7iu GH) was on 15mg of TZ, with an insulin over 20. Not sure what conclusions to draw from that. I'm Starting Berberine 500mg with each meal and will retest in 30 days.

You probably eat pretty high carb if I had to guess? Also you were probably running AAS? There’s a million things that could be different about our experiences

500+ ng/mL IGF-1 on 2.7 IU hGH is one of the highest multipliers and absolute values I've seen on Meso.

 

[Ateam2023]

500 igf1 number seems ? On 2.7 ius? Well Godammmn

 

[Trenbolonetax]

500+ ng/mL IGF-1 on 2.7 IU hGH is one of the highest multipliers and absolute values I've seen on Meso.

Yeah it is pretty wild. I’d venture to guessthe driving factor isn’t the 2.7iu of GH but rather the insulin piece.

 

[zmurphy]

You probably eat pretty high carb if I had to guess? Also you were probably running AAS? There’s a million things that could be different about our experiences

TRT for now, 125mg Test Cyp only. And yea, I've been eating like an asshole. Dangerous close to SAD if I'm honest. Gonna clean it up for 30 days, run Berberine and see what differences come of it.