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Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients

Abstract

OBJECTIVE: To evaluate the effects of low-dose growth hormone (GH) therapy combined with diet restriction on changes in body composition and the consequent change in insulin resistance in newly-diagnosed obese type 2 diabetic patients.

DESIGN: Double-blind and placebo-controlled trial of 25-kcal/kg IBW diet daily with GH (n = 9; rhGH, 0.15 IU/kg body weight/week) or placebo (n = 9) for 12 weeks.

SUBJECTS: Eighteen newly-diagnosed obese type 2 diabetic patients (age 42–56 y, body mass index 28.1±2.7 kg/m2).

MEASUREMENTS: Body composition and fat distribution parameters (by bioelectrical impedance analyzer and CT scans), serum IGF-1; serum glucose, insulin and free fatty acid (FFA) during oral glucose tolerance test (OGTT); HbA1c; serum lipid profiles; and glucose disposal rate (GDR) by euglycemic hyperinsulinemic clamp at baseline and after treatment.

RESULTS: The fraction of body weight lost as fat lost was significantly greater (0.98±0.39 vs 0.52±0.32 kg/kg, P<0.05) and visceral fat area was decreased more in the GH-treated group compared to the placebo-treated group (27.9 vs 21.6%, P<0.05). Lean body mass and muscle area were reduced in the placebo-treated group, whereas an increase in both was observed in the GH-treated group. GDR the was significantly increased in only the GH-treated group (4.67±1.05 vs 6.95±0.91 mg/kg/min, P<0.05). The GH-induced increase in GDR was positively correlated with the decrease in the ratio of visceral fat area/muscle area (r = 0.588, P = 0.001). Serum glucose levels and insulin- and FFA-area under the curve during OGTT and HbA1c were significantly decreased after GH treatment. LDL-cholesterol level was decreased in only the GH-treated group.

CONCLUSION: Low-dose GH treatment combined with dietary restriction resulted not only in a decrease of visceral fat but also in an increase of muscle mass with a consequent improvement of the insulin resistance observed in obese type 2 diabetic patients.

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References

  1. Skarfors ET, Selinus KI, Lithell HO . Risk factors for developing non-insulin dependent diabetes: a 10 years follow up on men in Uppsala Br Med J 1991 303: 755–760.

    Article  CAS  Google Scholar 

  2. Kisselbach AH, Peiris AN . Biology of regional body fat distribution: relationship to non-insulin-depedent diabetes mellitus Diabetes Metab Rev 1989 5: 83–109.

    Google Scholar 

  3. Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S . Contribution of intra-abdominal fat accumulation to the impairement of glucose and lipid metabolism in human obesity Metabolism 1987 36: 54–59.

    Article  CAS  Google Scholar 

  4. Defronzo RA . The triumvirate; β-cell, muscle, liver: a collusion responsible for NIDDM Diabetes 1988 37: 667–687.

    Article  CAS  Google Scholar 

  5. Daniel PM, Love ER, Pratt OE . Insulin-stimulated entry of glucose into muscle in vivo as a major factor in the regulation of blood glucose J Physiol (Lond) 1975 247: 273–278.

    Article  CAS  Google Scholar 

  6. Ferini-Strambi L, Franceschi M, Cattaneo AG, Smirne S, Calori G, Caviezel F . Sleep-related growth hormone secretion in human obesity: effect of dietary treatment Neuroendocrinology 1991 54: 412–4l5.

    Article  CAS  Google Scholar 

  7. Nam SY, Lee EJ, Kim KR, Lee HC, Nam MS, Cho JH, Huh KB . Long-term administration of acipimox potentiates growth hormone response to growth hormone-releasing hormone by decreasing serum free fatty acid in obesity Metabolism 1996 45: 594–597.

    Article  CAS  Google Scholar 

  8. Abate N . Insulin resistance and obesity: The role of fat distribution pattern Diabetes Care 1996 9: 292–294.

    Article  Google Scholar 

  9. Forbes GB . Weight loss during fasting: implication for the obese Am J Clin Nutr 1970 23: 1212–1217.

    Article  CAS  Google Scholar 

  10. Clemmons DR, Snyder DK, Williams R, Underwood LE . Growth hormone administration conserves lean body mass during dietary restriction in obese subjects J Clin Endocrinol Metab 1987 64: 878–883.

    Article  CAS  Google Scholar 

  11. Snyder DK, Underwood LE, Clemmons DR . Anabolic effects of growth hormone in obese diet-restricted subjects are dose dependent Am J Clin Nutr 1990 52: 431–437.

    Article  CAS  Google Scholar 

  12. Bratusch-Marrain PR, Smith D, Defronzo RA . The effect of growth hormone on glucose metabolism and insulin secretion in man J Clin Endocrinol Metab 1982 55: 973–982.

    Article  CAS  Google Scholar 

  13. Rizza RA, Mandarino LJ, Gerich JE . Effects of growth hormone on insulin action in man Diabetes 1982 31: 663–669.

    Article  CAS  Google Scholar 

  14. Hansen I, Tsalikian E, Beaufrere B, Gerich J, Haymond M, Rizza R . Insulin resistace in acromegaly: defects in both hepatic and extrahepatic insulin action Am J Physiol 1986 250: E269–E273.

    CAS  PubMed  Google Scholar 

  15. Foss MC, Saad MJA, Paccola GM, Paula FJ, Piccinato CE, Moreira AC . Peripheral glucose metabolism in acromegaly J Clin Endocrinol Metab 1991 72: 1048–1053.

    Article  CAS  Google Scholar 

  16. Kim KR, Nam SY, Song YD, Lim SK, Lee HC, Huh KB . Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults Horm Res 1999 51: 78–84.

    CAS  PubMed  Google Scholar 

  17. Byrd-Bredbenner C . Computer nutrient analysis software packages: consideration for selection Nutr Today 1988 23: 3–21.

    Article  Google Scholar 

  18. Ashwell M, Cole TJ, Dixon AK . Obesity: new insight into the anthropometric classification of fat distribution shown by computed tomography Br Med J 1985 290: 1692–1694.

    Article  CAS  Google Scholar 

  19. Defronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance Am J Physiol 1979 237: E2l4–E223.

    Google Scholar 

  20. Beauville M, Harant I, Crampes F, Riviere D, Tauber MT, Tauber JP, Garrigues M . Effect of long-term rhGH administration in GH-dependent adults on fat cell epinephrine response Am J Physiol 1992 263: E467–472.

    CAS  PubMed  Google Scholar 

  21. Yang S, Xu X, Bjorntorp P, Eden S . Additive effects of growth hormone and testosterone on lipolysis in adipocytes of hypophysectomized rats J Endocrinol 1995 147: 147–152.

    Article  CAS  Google Scholar 

  22. Rosenbaum M, Gertner JM, Leibel RL . Effects of systemic growth hormone (GH) administration on regional adipose tissue distribution and metabolism in GH-deficient children J Clin Endocrinol Metab 1989 69: 1274–1281.

    Article  CAS  Google Scholar 

  23. Cuneo RC, Salomon F, Wilmshurst P, Byrne C, Wiles CM, Hesp R, Sonksen PH . Cardiovascular effects of growth hormone treatment in growth hormone deficient adults: Stimulation of the renin-aldosterone system Clin Sci 1991 81: 587–592.

    Article  CAS  Google Scholar 

  24. Bengtsson BA, Eden S, Lonn L, Kvist H, Stokland A, Lindstedt G, Bosaeus I, Tolli J, Isaksson OGP . Treatment of adults with growth hormone (GH) deficiency with recombinant human GH J Clin Endocrinol Metab 1993 76: 809–817.

    Google Scholar 

  25. Despres JP, Lamarche B . Effects of diet and physical activity on adiposity and body fat distribution: implications for the prevention of cardiovascular disease Nutr Res Rev 1993 6: 137–159.

    Article  CAS  Google Scholar 

  26. Yamashita S, Nakamura T, Shimomra I, Nishida M, Yoshida S, Kotani K, Kameda-Takemuara K, Tokunaga K, Matsuzawa . Insulin resistance and body fat distribution Diabetes care 1996 19: 287–291.

    Article  CAS  Google Scholar 

  27. Ferranini E, Barrett EJ, Bevilacqua S, Defronzo R . Effects of fatty acids on glucose production and utilization in man J Clin Invest 1983 72: 1737–1747.

    Article  Google Scholar 

  28. Bevilacqua S, Bonadonna R, Buzzigoli G, Boni C, Ciociaro D, Maccari F, Giorico MA, Ferranini E . Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects Metabolism 1987 36: 502–506.

    Article  CAS  Google Scholar 

  29. Despres JP . Abdominal obesity as important component of _insulin-resistance syndrome Nutrition 1993 9: 452–459.

    CAS  PubMed  Google Scholar 

  30. Matsuzawa Y, Shimomura I, Nakamura T, Keno Y, Tokunaga K . Pathophysiology and pathogenesis of visceral fat obesity Ann NY Acad Sci 1993 676: 270–278.

    Article  CAS  Google Scholar 

  31. Tagliaferri M, Scacchi M, Pincelli AI, Berselli ME, Silvestri P, Montesano A, Ortolani S, Dubini A, Cavagnini F . Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women Int J Obes Relat Metab Disord 1998 22: 836–841.

    Article  CAS  Google Scholar 

  32. O'Neal DN, Kalfas A, Dunning PL, Christopher MJ, Sawyer SD, Ward GM, Alford FP . The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults: a minimal model analysis J Clin Endocrinol Metab 1994 79: 975–983.

    CAS  PubMed  Google Scholar 

  33. Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Bjorntorp P, Sjostrom L, Bengtosson B . Growth hormone treat_ment_of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure J Clin Endocrinol Metab 1997 82: 727–734.

    CAS  PubMed  Google Scholar 

  34. Chong PK, Jung RT, Scrimgeour CM, Rennie MJ, Paterson CR . Energy expenditure and body composition in growth hormone deficient adults on exogenous growth hormone Clin Endocrinol 1994 43: 872–877.

    Google Scholar 

  35. Snel YEM, Doerga ME, Brummer RJM, Zelissen PMJ, Zonderland ML, Koppeschaar HPF . Resting metabolic rate, body composition and related hormonal parameters in growth hormone-deficient adults before and after growth hormone replacement therapy Eur J Endocrinol 1995 133: 445–450.

    Article  CAS  Google Scholar 

  36. Drent ML, Wever LD, Ader HJ, Van der Veen EA . Growth hormone administration in addition to a very low caloric diet and an exercise program in obese subjects Eur J Endocrinol 1995 132: 565–572.

    Article  CAS  Google Scholar 

  37. Ayling CM, Moreland BH, Zanelli JM, Schulster D . Human growth hormone treatment of hypophysectomized rats increases the proportion of type-I fibers in skeletal muscle J Endocrinol 1989 23: 429–435.

    Article  Google Scholar 

  38. Lund S, Flyvbjerg A, Holman GD, Larsen FS, Pedersen O, Schmitz O . Comparative effects of IGF-1 and insulin on the glucose transporter system in rat muscle Am J Physiol 1994 67: E461–E466.

    Google Scholar 

  39. Rudling M, Norstedt G, Olivecrona H, Reihner E, Gustafsson JA, Angelin B . Importance of growth hormone for the induction of hepatic low density lipoprotein receptors Proc Natl Acad Sci USA 1992 89: 6983–6987.

    Article  CAS  Google Scholar 

  40. Angelin B, Rudling M . Growth hormone and hepatic lipoprotein metabolism Curr Opin Lipidol 1994 5: 160–165.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank the dieticians for providing their skilled dietary support. We would also like to thank LG Biotech (Seoul, Korea) for providing the placebo/rhGH (Eutropin) preparations

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Correspondence to SY Nam.

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Nam, S., Kim, K., Cha, B. et al. Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients. Int J Obes 25, 1101–1107 (2001). https://doi.org/10.1038/sj.ijo.0801636

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