stevie96

hi ,just finishing off what ansomone i have,just 2 iu's at night after training,but when it gets to about six oclock ive started feeling realy tiered before my 2 iu's so ive just done a blood sugar test(my mums diabetic)urine stick and its pretty high next to the top level,do any of you guys know maybe whats going on ,thanks

magick69

hgh is known to worsen insuline sensitivity; use supplements such as ala and green tea to counteract the side effects



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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 4 1453-1454
Copyright © 2003 by The Endocrine Society



EDITORIAL

Growth Hormone Replacement Therapy and Insulin Sensitivity
Johan Svensson and Bengt-Åke Bengtsson
Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden

Address all correspondence and requests for reprints to: Johan Svensson, M.D., Ph.D., Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Göteborg, Sweden. E-mail: Johan.Svensson@medic.gu.se.

In adults with hypopituitarism, several studies show that untreated GH deficiency is associated with insulin resistance (1, 2). Short-term (<6 months) GH replacement further decreases insulin sensitivity (3, 4). After this initial deterioration of insulin sensitivity, however, an improvement of insulin sensitivity is observed and insulin sensitivity returns toward baseline values. In studies by O’Neal et al. (3) and Fowelin et al. (4), insulin sensitivity returned toward baseline values after 3 and 6 months of GH replacement, respectively. In the study presented in this issue of JCEM by Bramnert et al., insulin sensitivity was measured after 1 wk and 6 months of GH replacement therapy using the hyperinsulinemic, euglycemic clamp technique (5). In this study, insulin sensitivity was still decreased after 6 months of GH replacement therapy as compared with baseline (5). There was, however, a tendency to an improvement in insulin sensitivity between 1 wk and 6 months of treatment. At 1 wk, mean insulin sensitivity was -52% of that at baseline, and at 6 months, mean sensitivity was -39% of that at baseline.

A generally accepted hypothesis for the return of insulin sensitivity toward baseline values after 3–12 months of GH replacement therapy is the beneficial effects by GH on body composition. GH replacement therapy has been shown to induce a sustained increase in lean mass and a sustained reduction in body fat (6). In addition, GH replacement therapy increases well-being and physical activity level (7). When these beneficial effects exceed the negative effects, insulin sensitivity returns toward baseline values. In the study by Bramnert et al. (5), the GH replacement therapy did not increase lean mass. This absence of an increase in lean mass provides one explanation why insulin sensitivity was still decreased after 6 months of treatment.

There are now several studies that have determined the long-term (1 yr) effect of GH replacement therapy on insulin sensitivity. Some studies report that insulin sensitivity is still lower than at baseline (8, 9), whereas other studies report unchanged insulin sensitivity as compared with baseline during long-term GH replacement therapy (10, 11). The results of one study, using the hyperinsulinemic, euglycemic clamp technique, suggest that the decreased baseline insulin sensitivity persists at least up to 2 yr of GH treatment (12). However, in a study by Hwu et al. (13), 1 yr of GH treatment normalized insulin sensitivity as measured by a modified insulin suppression test. In a study by Jørgensen et al. (14), insulin sensitivity (M-value) was similar in GH-deficient patients as in controls after 5 yr of GH replacement therapy. In a 5-yr GH treatment trial, the circulating hemoglobin A1c level was reduced after 5 yr of GH replacement in adults with adult onset GH deficiency (6). In a study by Svensson et al. (15), insulin sensitivity was unchanged during 7-yr GH replacement therapy (15). In this study, there was even a tendency that the GH replacement therapy provided protection from the age-related decline in insulin sensitivity that was observed in the matched control subjects (15).

There are few data regarding the incidence of diabetes mellitus type 2 in GH-deficient adults. Preliminary analyses based on data from KIMS (Pharmacia Metabolic Database) suggest that the incidence of diabetes mellitus type 2 in GH-treated hypopituitary patients with normal body mass index is similar to that in the background population (16). Long-term (1 yr) GH replacement therapy, therefore, seems to be a safe procedure in terms of insulin sensitivity and diabetes mellitus type 2. The problem is mainly how to avoid the transient decrease in insulin sensitivity during the first months of GH replacement therapy.

GH replacement therapy increases lipolysis, thereby increasing circulating free fatty acid (FFA) concentrations (3, 4). According to the glucose-FFA cycle postulated by Randle et al. (17), these increased FFA concentrations may decrease the uptake of glucose in skeletal muscle. Later studies using acipimox, a blocker of FFA release, have confirmed the inverse relationship between circulating FFA concentrations and insulin sensitivity in GH-deficient adults (18, 19, 20). In the study by Bramnert et al. (5), there was a close correlation between lipid oxidation and circulating FFA concentration, suggesting that the increased rate of lipid oxidation was a consequence of the lipolytic action of GH. Therefore, the increased lipolysis induced by GH replacement therapy seems to be a sword with two edges in terms of insulin sensitivity. The short-term effect, with increased lipid oxidation and increased circulating FFA levels, deteriorates insulin sensitivity. The long-term effect, with a reduction in body fat, is beneficial for insulin sensitivity.

The study by Bramnert et al. (5) showed an increase in the relative distribution of insulin resistant type IIB fibers in skeletal muscle after 6 months of GH replacement therapy (5). It is unclear whether this is a primary effect by GH or merely a consequence of the decreased insulin sensitivity. In a study by Christopher et al. (12), decreased glycogen synthase activity was found in skeletal muscle in GH-deficient adults after 2 yr of GH replacement therapy (12). It was hypothesized that increased FFA availability could be important for the decreased glycogen synthase activity (12).

The initial studies with GH replacement therapy in adults used high doses of GH (21, 22). The high doses of GH induced profound changes in body composition and were also accompanied by fluid-related side effects. Later studies have shown that if GH replacement therapy is started at a low dose that is gradually increased based on the clinical response (body composition, well-being, and serum IGF concentration), a similar efficacy is achieved with a minimum of side effects (23). Individualized GH replacement therapy will result in a more gradual reduction in body fat than treatment with a high, fixed dose of GH. A slow, gradual reduction in body fat will result in lower increases in lipid oxidation and circulating FFA levels, thereby minimizing the transient decrease in insulin sensitivity the first months of GH treatment. In the study by Bramnert et al. (5), a fixed dose of GH was given. Although this was not a high dose of GH, it could be hypothesized that the response in insulin sensitivity could have been more beneficial if the dose of GH had been gradually increased based on the clinical response.

In normal subjects, obesity (especially abdominal obesity), high age, and decreased insulin sensitivity of other causes, are risk factors for the development of diabetes mellitus type 2. There is no reason to believe otherwise than that these are major risk factors also in hypopituitary adults. This is also our clinical experience (15), which finds support in the preliminary data from KIMS (16). In hypopituitary patients with high risk of developing diabetes mellitus type 2, it is essential to avoid a further decrease in insulin sensitivity during the first months of GH replacement therapy. Therefore, hypopituitary patients with high risk to developing diabetes type 2 should be given a very low dose of GH at initiation of therapy, and the dose of GH should be slowly increased based on the clinical response. In this way, we believe that the initial decrease in insulin sensitivity during GH replacement therapy can be minimized in these patients.

In conclusion, during the first months of GH replacement therapy there is a transient decrease in insulin sensitivity. Increased lipid oxidation and increased FFA availability can at least partly explain this transient decrease in insulin sensitivity. Long-term (1 yr) GH replacement is a safe procedure in terms of insulin sensitivity, and in some studies an improvement of insulin sensitivity has even been observed. Individualized GH replacement therapy, starting with a low dose of GH that is gradually increased based on the clinical response, can probably minimize the transient decrease in insulin sensitivity during the first months of treatment.

stevie96

thanks for the info, have a stock of green tea.

D-TROPIN

had same prob but luckily i had some metformin but ala...cinnamon and chromium work great to counteract the insulin desensitization form gh

also i started to do my gh shot at nite...that way yo get 8-12 hours without carbs...

low gi carbs is a must for me personally whilst on gh as my sugar levels were getting higher

also did gh eod mon 10iu wed 10iu fri 10iu and found i felt less tired in general and my sugar levels reflectedf that in my bloods

hope that helps