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- Apr 9, 2021
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Insulin resistance is a direct GH effect (due to GH's liberating free fatty acids into systemic circulation). Insulin resistance follows within 1 - 2 hr post-administration. RhGH, during prolonged subcutaneous administration (in a state of positive energy balance), causes the actions of IGF-I and insulin to prevail 8 - 10 h post-injection.
Broadly, rhGH modulates insulin sensitivity in a complex manner influenced by numerous factors such as age, body composition, and duration of therapy.
Of course, short-term perturbations are of only minor relevance versus HbA1c levels that reflect chronic insulin resistance.
The strategies that I believe in are A) timing strategies attendant to the pharmacodynamic effects of rhGH and nadir blood glucose measures & B) the use of exogenous drugs along a dose- & time- dependent continuum:
GDAs (biguanides, e.g., Metformin; Berberine) < Incretins (GLP-1 agonists; SGLT-2 inhibitors; DPP-4 inhibitors; glimepirid, etc.) < LR3 IGF-I; IGF-I < exogenous insulin (Aspart & Lispro << Glargine).
Note that exogenous insulin worsens insulin sensitivity (as HOMA-IR reflects the products of blood glucose AND insulin) by several mechanisms, including diminished autophosphorylation of the IR & downstream elements (e.g., IRS1). Indeed, only some of the incretins, e.g., GLP-1 agonists; dual GIP & GLP-1 agonists (e.g., tirzepatide), qualify as true insulin sensitizing agents.
While low-dose insulin glargine (e.g., Lantus) may confer a protective effect on pancreatic β-cell function in prediabetes, the very thing that distinguishes healthy bodybuilders from prediabetics is that β-cell function is not "on its last legs" in the healthy. Rather, glucose disposal at the initiation of an rhGH course should be implemented to protect pancreatic β-cell function (that is worsened by exposure to high circulating blood glucose levels) on a continuum. The very last tool to be used in the arsenal is insulin glargine (for those that have become prediabetic).
Rather than serving primarily to reduce blood glucose concentrations, insulin should be viewed as an agent to increase IGF-I bioavailability (and to counter the decrement to GH response [the increase to IGF-I] that occurs after several months at a constant rhGH dose).
Broadly, rhGH modulates insulin sensitivity in a complex manner influenced by numerous factors such as age, body composition, and duration of therapy.
Of course, short-term perturbations are of only minor relevance versus HbA1c levels that reflect chronic insulin resistance.
The strategies that I believe in are A) timing strategies attendant to the pharmacodynamic effects of rhGH and nadir blood glucose measures & B) the use of exogenous drugs along a dose- & time- dependent continuum:
GDAs (biguanides, e.g., Metformin; Berberine) < Incretins (GLP-1 agonists; SGLT-2 inhibitors; DPP-4 inhibitors; glimepirid, etc.) < LR3 IGF-I; IGF-I < exogenous insulin (Aspart & Lispro << Glargine).
Note that exogenous insulin worsens insulin sensitivity (as HOMA-IR reflects the products of blood glucose AND insulin) by several mechanisms, including diminished autophosphorylation of the IR & downstream elements (e.g., IRS1). Indeed, only some of the incretins, e.g., GLP-1 agonists; dual GIP & GLP-1 agonists (e.g., tirzepatide), qualify as true insulin sensitizing agents.
While low-dose insulin glargine (e.g., Lantus) may confer a protective effect on pancreatic β-cell function in prediabetes, the very thing that distinguishes healthy bodybuilders from prediabetics is that β-cell function is not "on its last legs" in the healthy. Rather, glucose disposal at the initiation of an rhGH course should be implemented to protect pancreatic β-cell function (that is worsened by exposure to high circulating blood glucose levels) on a continuum. The very last tool to be used in the arsenal is insulin glargine (for those that have become prediabetic).
Rather than serving primarily to reduce blood glucose concentrations, insulin should be viewed as an agent to increase IGF-I bioavailability (and to counter the decrement to GH response [the increase to IGF-I] that occurs after several months at a constant rhGH dose).