GH and insulin sensitivity

[tommyguns2]

I'm a bit embarrassed to admit this, but although I've been taking GH for years now, my knowledge on this subject is poor, and I'm thinking that I really need to consider this going forward for a couple of reasons: (1) my age, as I'm no longer a spring chicken, and (2) while in the past my GH dosing has been small, in the 2IU ED range, I'm thinking about running it higher in the future, for example 5 IU ED or more.

I've searched a couple of threads, and I hear people talk about metformin or berberine as a supplement to take with GH, and the threads quickly get clogged up with experienced people talking about what brand is best, side effects, etc, that I'm not able to digest what I should be doing going forward.

Can someone give me a primer on why exogenous GH can cause insulin sensitivity issues, and what metformin or berberine (or something else) does to mitigate those effects? Also, if I wanted to run 5IU ED GH going forward what is a simple strategy of supplementation to go with that that will be smart. I want to KISS (keep it simple stupid)

 

[Bigtex]

I'm a bit embarrassed to admit this, but although I've been taking GH for years now, my knowledge on this subject is poor, and I'm thinking that I really need to consider this going forward for a couple of reasons: (1) my age, as I'm no longer a spring chicken, and (2) while in the past my GH dosing has been small, in the 2IU ED range, I'm thinking about running it higher in the future, for example 5 IU ED or more.

I've searched a couple of threads, and I hear people talk about metformin or berberine as a supplement to take with GH, and the threads quickly get clogged up with experienced people talking about what brand is best, side effects, etc, that I'm not able to digest what I should be doing going forward.

Can someone give me a primer on why exogenous GH can cause insulin sensitivity issues, and what metformin or berberine (or something else) does to mitigate those effects? Also, if I wanted to run 5IU ED GH going forward what is a simple strategy of supplementation to go with that that will be smart. I want to KISS (keep it simple stupid)

1. GH Antagonizes Insulin's Action:
   • Growth hormone (GH) opposes or antagonizes the effects of insulin on peripheral tissues. Peripheral tissues include skeletal muscle, liver, and adipose tissue (fat).
2. Effects on Skeletal Muscle, Liver, and Adipose Tissue:
   • GH's antagonistic action on insulin in skeletal muscle, liver, and adipose tissue has specific consequences.
   • In skeletal muscle and liver, GH increases glucose production. This means that these tissues produce and release more glucose into the bloodstream.
   • In adipose tissue, GH decreases glucose uptake. This means that fat cells take up less glucose from the bloodstream.
3. Compensation by Increased Insulin Production:
   • Due to the increased circulating glucose resulting from GH administration, the body compensates by producing more insulin. Insulin is a hormone that helps regulate blood sugar levels by facilitating the uptake of glucose into cells.
4. GH-Induced Lipolysis and Circulating Free Fatty Acids (FFA):
   • GH stimulates lipolysis in visceral adipose tissue, leading to the breakdown of fats and release of free fatty acids (FFA) into the bloodstream.
   • Increased circulating FFA can interfere with insulin signaling pathways. Chronic exposure to high FFA levels may have direct toxic effects on beta-cells, which are cells in the pancreas that produce insulin.
5. IGF-1 and Insulin-Mimetic Actions:
   • Insulin-like Growth Factor-1 (IGF-1) is a hormone that is stimulated by GH and shares some insulin-like actions.
   • Increased circulating IGF-1 after GH administration may have beneficial effects on glucose homeostasis and insulin resistance, particularly in the skeletal muscle and liver.

In summary, GH has complex effects on glucose metabolism. While it antagonizes insulin in certain tissues, it also stimulates processes that can lead to increased glucose levels. The interplay between GH, insulin, and IGF-1 is intricate and involves multiple tissues and signaling pathways. The ultimate impact on glucose homeostasis depends on the balance between these various actions.

Here is a very technical explanation of the mechanisms behind this:

Growth Hormone Induces Cellular Insulin Resistance by Uncoupling Phosphatidylinositol 3-Kinase and Its Downstream Signals in 3T3-L1 Adipocytes

Growth hormone (GH) is well known to induce in vivo insulin resistance. However, the molecular mechanism of GH-induced cellular insulin resistance is largely un

diabetesjournals.org

Metformin simply reverses the negative actions with GH

1. AMP-activated protein kinase (AMPK) activation: Metformin activates an enzyme called AMPK in the liver and muscles. AMPK plays a crucial role in regulating cellular energy balance. When AMPK is activated, it inhibits certain processes in the liver that produce glucose and promotes glucose uptake in peripheral tissues, such as muscles.
2. Decreased hepatic glucose production: Metformin suppresses glucose production in the liver. The liver normally produces glucose through a process called gluconeogenesis. Metformin inhibits this process, leading to a reduction in the amount of glucose released into the bloodstream by the liver.
3. Improved insulin signaling: Metformin may enhance insulin receptor signaling, making cells more responsive to insulin. This improved insulin sensitivity helps cells take up glucose more effectively, reducing the need for higher insulin levels.
4. Increased peripheral glucose uptake: Metformin promotes the uptake of glucose by peripheral tissues, such as muscles, where it can be utilized for energy. This is partly achieved through the activation of AMPK, which enhances glucose uptake and utilization.
5. Changes in gut microbiota: Some studies suggest that Metformin may influence the composition of gut microbiota, and these changes could contribute to its metabolic effects. The gut microbiota plays a role in various aspects of metabolism, and alterations in its composition may impact insulin sensitivity.

 

[Wilson6]

One of my female competitor clients (masters BB) just started metformin (script), her HbA1c was 6.0 and she stays about 10% BF year around, so its not fat or excess CHO. Since she started taking the metformin she's lost weight and gone flat. Went for a Bod Pod and over 7 weeks dropped 4.5 lean and gained the same amount of fat. She was horrified. The MET is the only thing that has changed. She stopped the MET and is starting to fill back out, going to run Semaglutide instead and see if that is enough to bring her glucose down. I did some reading on MET, increased AMPK will downregulate mTORC1 and also upregulates myostatin. Both negative regulators of muscle protein synthesis. It has also been show clinically that MET will decrease lean mass over time. It is a great first line treatment in overweight sedentary folks, but lean fit, I'm not so sure esp with the GLP-1 drugs available now. Be curious if anyone else has noticed anything.

 

[tommyguns2]

It's my understanding that metformin requires a prescription (making it more complicated than going to the drugstore and likely more expensive) and that berberine is an OTC supplement. Is that correct?

If I go to >=5IUs GH ED, without any regard to potential insulin sensitivity effects, am I at a realistic risk of type II diabetes? Or is that concern a little overblown.

As GH has gotten more economical, I'm hearing more people running it at 5-10IUs ED, and while that seems great on staying lean, muscle fullness, etc., are all these people rolling the dice with diabetes?

 

[genetic freak]

I don't think you would be at risk for type II diabetes unless your diet also sucked. It is not like your glucose is elevated all day. How long is your glucose elevated for after taking GH? It depends. Did you take it with a meal? Pre-bed? Pre-cardio? Pre-workout? Did you inject sub-q or IM? etc... All of these things will impact how long your glucose will stay elevated.

Taking berberine does help with insulin sensitivity whether you are taking GH or not. I always suggest taking it unless you are in the last few weeks of contest prep and it starts making you go hypo.

 

[Bigtex]

Here is a statement from another study:

Many of the early studies using high GH doses (≥0.01 mg/kg/day) reported that fasting glucose and insulin levels increased after short-term GH treatment for less than 6 months, but were usually restored to baseline levels after 1 or 2 years of GH treatment.

So with a 2iu injection once a day, you may have a slightly elevated fasted glucose reading for a few months, but it will probably go back to baseline after a few months.

They go on to say:

With long-term GH replacement in high doses decreased insulin sensitivity and aggravated insulin resistance, which can be explained by the anti-insulin effects of GH. Despite increased insulin resistance, hemoglobin A1c (HbA1c) levels remained unchanged in both short-term and long-term treatment.

I think it would be wise to monitor your fasted serum glucose levels or just take 500mg of metformin and not worry about it. IMHO, metformin is an amazing drug. The good thing about metformin is metformin rarely produces hypoglycemia because it does not change how much insulin is secreted by the pancreas and does not cause high insulin levels. I do carb cycling and alternate between high carbs on training days, medium carbs on day off and low carbs on the weekends and have never felt hypoglycemic, I also cut calories on the weekend from 5200 to 2300. Never done berberine but can tell you that metformin is less expensive.

No prescription needed here Tommy

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Effects of growth hormone on glucose metabolism and insulin resistance in human

Growth hormone (GH) is important for promotion of somatic growth and the regulation of substrate metabolism. Metabolic action of GH occurs in multiple tissues including the liver, muscle, fat and pancreas either directly or indirectly through insulin-like ...

www.ncbi.nlm.nih.gov