Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults

International Journal of Obesity volume 27, pages 219–226 (2003)Cite this article

Abstract

PURPOSE: Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults.

METHODS: Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of β-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup.

RESULTS: For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; ΔBMI<−3 kg/m2) and low responders (LR; ΔBMI between −3 and −0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; ΔBMI−0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, ΔBMI correlated with ΔCISI, Δfat mass, and Δleptin. ΔFat mass also correlated with ΔIAUC and ΔCISI.

CONCLUSIONS: In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL . Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Surveys, 1960 to 1991. JAMA 1994; 272: 205–211.

    Article  CAS  PubMed  Google Scholar 

  2. Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP . The spread of the obesity epidemic in the United States, 1991–1998. JAMA 1999; 282: 1519–1522.

    Article  CAS  PubMed  Google Scholar 

  3. Luepker RV, Perry CL, McKinlay SM, Nader PR, Parcel GS, Stone EJ, Webber LS, Elder JP, Feldman HA, Johnson CC et al. Outcomes of a field trial to improve children's dietary patterns and physical activity. The Child and Adolescent Trial for Cardiovascular Health. CATCH collaborative group. JAMA 1996; 275: 768–776.

    Article  CAS  PubMed  Google Scholar 

  4. Skender ML, Goodrick GK, Del Junco DJ, Reeves RS, Darnell L, Gotto AM, Foreyt JP . Comparison of 2-year weight loss trends in behavioral treatments of obesity: diet, exercise, and combination interventions. J Am Diet Assoc 1996; 96: 342–346.

    Article  CAS  PubMed  Google Scholar 

  5. Bray GA, Gray DS . Treatment of obesity: an overview. Diabetes Metab Rev 1988; 4: 653–679.

    Article  CAS  PubMed  Google Scholar 

  6. Lillioja S, Nyomba BL, Saad MF, Ferraro R, Castillo C, Bennett PH, Bogardus C . Exaggerated early insulin release and insulin resistance in a diabetes-prone population: a metabolic comparison of Pima Indians and Caucasians. J Clin Endocrinol Metab 1991; 73: 866–876.

    Article  CAS  PubMed  Google Scholar 

  7. Haffner SM, D'Agostino R, Saad MF, Rewers M, Mykkanen L, Selby J, Howard G, Savage PJ, Hamman RF, Wagenknecht LE, Bergman RN . Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study. Diabetes 1996; 45: 742–748.

    Article  CAS  PubMed  Google Scholar 

  8. Marin P, Rebuffe-Scrive M, Smith U, Bjorntorp P . Glucose uptake in human adipose tissue. Metabolism 1987; 36: 1154–1160.

    Article  CAS  PubMed  Google Scholar 

  9. Ramsay TG . Fat cells. Endocrinol Metab Clin North Am 1996; 25: 847–870.

    Article  CAS  PubMed  Google Scholar 

  10. Taylor SI, Accili D, Imai Y . Insulin resistance or insulin deficiency. Which is the primary cause of NIDDM? Diabetes 1994; 43: 735–740.

    Article  CAS  PubMed  Google Scholar 

  11. Sigal RJ, El-Hashimy M, Martin BC, Soeldner JS, Krolewski AS, Warram JH . Acute postchallenge hyperinsulinemia predicts weight gain: a prospective study. Diabetes 1997; 46: 1025–1029.

    Article  CAS  PubMed  Google Scholar 

  12. Le Stunff C, Bougneres P . Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity. Diabetes 1994; 43: 696–702.

    Article  CAS  PubMed  Google Scholar 

  13. Brandes JS . Insulin induced overeating in the rat. Physiol Behav 1977; 18: 1095–1102.

    Article  CAS  PubMed  Google Scholar 

  14. Cohen P, Barzilai N, Barzilai D, Karnieli E . Correlation between insulin clearance and insulin responsiveness: studies in normal, obese, hyperthyroid, and Cushing's syndrome patients. Metabolism 1986; 35: 744–749.

    Article  CAS  PubMed  Google Scholar 

  15. Weiner MF . Rapid weight gain due to overinsulinization. Obes Bariatric Med 1980; 9: 118–119.

    Google Scholar 

  16. Woods WC, Decke E, Vasselli JR . Metabolic hormones and regulation of body weight. Physiol Rev 1974; 81: 26–43.

    CAS  Google Scholar 

  17. Odeleye OE, de Courten M, Pettitt DJ, Ravussin E . Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children. Diabetes 1997; 46: 1341–1345.

    Article  CAS  PubMed  Google Scholar 

  18. Zannolli R, Rebeggiani A, Chiarelli F, Morgese G . Hyperinsulinism as a marker in obese children. Am J Dis Child 1993; 147: 837–841.

    CAS  PubMed  Google Scholar 

  19. Tokunaga K, Fukushima M, Kemnitz JW, Bray GA . Effect of vagotomy on serum insulin in rats with paraventricular or ventromedial hypothalamic lesions. Endocrinology 1986; 119: 1708–1711.

    Article  CAS  PubMed  Google Scholar 

  20. Inoue S, Bray GA . The effects of subdiaphragmatic vagotomy in rats with ventromedial hypothalamic obesity. Endocrinology 1977; 100: 108–114.

    Article  CAS  PubMed  Google Scholar 

  21. Bray GA, York DA . Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol Rev 1979; 59: 719–809.

    Article  CAS  PubMed  Google Scholar 

  22. Bray GA . Syndromes of hypothalamic obesity in man. Pediatr Ann 1984; 13: 525–536.

    CAS  PubMed  Google Scholar 

  23. Sklar CA . Craniopharyngioma: endocrine sequelae of treatment. Pediatr Neurosurg 1994; 21 (Suppl 1): 120–123.

    Article  PubMed  Google Scholar 

  24. Lustig RH, Rose SR, Burghen GA, Velasquez-Mieyer P, Broome DC, Smith K, Li H, Hudson MM, Heideman RL, Kun LE . Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J Pediatr 1999; 135: 162–168.

    Article  CAS  PubMed  Google Scholar 

  25. Guven S, El-Bershawi A, Sonnenberg GE, Wilson CR, Hoffmann RG, Krakower GR, Kissebah AH . Plasma leptin and insulin levels in weight-reduced obese women with normal body mass index: relationships with body composition and insulin. Diabetes 1999; 48: 347–352.

    Article  CAS  PubMed  Google Scholar 

  26. Heller RF, Heller RF . Are you a carbohydrate craver? The carbohydrate addict's diet. Signet, New York, NY. 1991.

    Google Scholar 

  27. Reaven GM, Brand RJ, Chen YD, Mathur AK, Goldfine I . Insulin resistance and insulin secretion are determinants of oral glucose tolerance in normal individuals. Diabetes 1993; 42: 1324–1332.

    Article  CAS  PubMed  Google Scholar 

  28. ADA. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–1197.

  29. Kadish AH, Little RH, Sternberg JC . A new and rapid method for the determination of glucose by measurement of rate of oxygen consumption. Clin Chem 1968; 14: 116–119.

    CAS  Google Scholar 

  30. Toft I, Bonaa KH, Lindal S, Jenssen T . Insulin kinetics, insulin action, and muscle morphology in lean or slightly overweight persons with impaired glucose tolerance. Metabolism 1998; 47: 848–854.

    Article  CAS  PubMed  Google Scholar 

  31. Tallarida RJ, Murray RB . Manual of pharmacologic calculations with computer programs. Springer-Verlag: New York, 1986. pp 77–81.

    Book  Google Scholar 

  32. Sluiter WJ, Erkelens DW, Terpstra P, Reitsma WD, Doorenbos H . Glucose tolerance and insulin release, a mathematical approach. II. Approximation of the peripheral insulin resistance after oral glucose loading. Diabetes 1976; 25: 245–249.

    Article  CAS  PubMed  Google Scholar 

  33. Matsuda M, DeFronzo RA . Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462–1470.

    Article  CAS  PubMed  Google Scholar 

  34. Meistas MT, Margolis S, Kowarski AA . Hyperinsulinemia of obesity is due to decreased clearance of insulin. Am J Physiol 1983; 245: E155–E159.

    CAS  PubMed  Google Scholar 

  35. Williams C, Gowan R, Perey BJ . A double-blind placebo-controlled trial of ursodeoxycholic acid in the prevention of gallstones during weight loss after vertical banded gastroplasty. Obes Surg 1993; 3: 257–259.

    Article  CAS  PubMed  Google Scholar 

  36. Alemzadeh R, Langley G, Upchurch L, Smith P, Slonim AE . Beneficial effect of diazoxide in obese hyperinsulinemic adults. J Clin Endocrinol Metab 1998; 83: 1911–1915.

    CAS  PubMed  Google Scholar 

  37. Gordon DF, Woodmansee WW, Lewis SR, James RA, Wood WM, Ridgway EC . Cloning of the mouse somatostatin receptor subtype 5 gene: promoter structure and function. Endocrinology 1999; 140: 5598–5608.

    Article  CAS  PubMed  Google Scholar 

  38. Mitra SW, Mezey E, Hunyady B, Chamberlain L, Hayes E, Foor F, Wang Y, Schonbrunn A, Schaeffer JM . Colocalization of somatostatin receptor sst5 and insulin in rat pancreatic beta-cells. Endocrinology 1999; 140: 3790–3796.

    Article  CAS  PubMed  Google Scholar 

  39. Lunetta M, Di Mauro M, Le Moli R, Burrafato S . Long-term octreotide treatment reduced hyperinsulinemia, excess body weight and skin lesions in severe obesity with acanthosis nigricans. J Endocrinol Invest 1996; 19: 699–703.

    Article  CAS  PubMed  Google Scholar 

  40. Giustina A, Girelli A, Buffoli MG, Cimino A, Legati F, Valentini U, Giustina G . Low-dose octreotide is able to cause a maximal inhibition of the glycemic responses to a mixed meal in obese type 2 diabetic patients treated with insulin. Diabetes Res Clin Pract 1991; 14: 47–54.

    Article  CAS  PubMed  Google Scholar 

  41. Bertoli A, Magnaterra R, Borboni P, Marini MA, Barini A, Fusco A, Bollea MR . Dose-dependent effect of octreotide on insulin secretion after OGTT in obesity. Horm Res 1998; 49: 17–21.

    CAS  PubMed  Google Scholar 

  42. Simsolo RB, Ezzat S, Ong JM, Saghizadeh M, Kern PA . Effects of acromegaly treatment and growth hormone on adipose tissue lipoprotein lipase. J Clin Endocrinol Metab 1995; 80: 3233–3238.

    CAS  PubMed  Google Scholar 

  43. Lotter EC, Krinsky R, McKay JM, Treneer CM, Porter Jr D, Woods SC . Somatostatin decreases food intake of rats and baboons. J Comp Physiol Psychol 1981; 95: 278–287.

    Article  CAS  PubMed  Google Scholar 

  44. Levine AS, Morley JE . Peripherally administered somatostatin reduces feeding by a vagal mediated mechanism. Pharmacol Biochem Behav 1982; 16: 897–902.

    Article  CAS  PubMed  Google Scholar 

  45. Campbell RM, Scanes CG . Inhibition of growth hormone-stimulated lipolysis by somatostatin, insulin, and insulin-like growth factors (somatomedins) in vitro. Proc Soc Exp Biol Med 1988; 189: 362–366.

    Article  CAS  PubMed  Google Scholar 

  46. Jimenez J, Zuniga-Guajardo S, Zinman B, Angel A . Effects of weight loss in massive obesity on insulin and C-peptide dynamics: sequential changes in insulin production, clearance, and sensitivity. J Clin Endocrinol Metab 1987; 64: 661–668.

    Article  CAS  PubMed  Google Scholar 

  47. Hansen TB, Gram J, Bjerre P, Hagen C, Bollerslev J . Body composition in active acromegaly during treatment with octreotide: a double-blind, placebo-controlled cross-over study. Clin Endocrinol (Oxf) 1994; 41: 323–329.

    Article  CAS  Google Scholar 

  48. Adami GF, Gandolfo P, Scopinaro N . Binge eating in obesity. Int J Obes Relat Metab Disord 1996; 20: 793–794.

    CAS  PubMed  Google Scholar 

  49. Blum I, Nessiel L, Graff E, Harsat A, Gabbay U, Sulkes J, Raz O, Vered Y . Food preferences, body weight, and platelet-poor plasma serotonin and catecholamines. Am J Clin Nutr 1993; 57: 486–489.

    Article  CAS  PubMed  Google Scholar 

  50. Hsu LK, Betancourt S, Sullivan SP . Eating disturbances before and after vertical banded gastroplasty: a pilot study. Int J Eat Disord 1996; 19: 23–34.

    Article  CAS  PubMed  Google Scholar 

  51. Peiris AN, Mueller RA, Smith GA, Struve MF, Kissebah AH . Splanchnic insulin metabolism in obesity. Influence of body fat distribution. J Clin Invest 1986; 78: 1648–1657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The work was supported in part by University of Tennessee GCRC 5M01RR 00211, and by a research grant from Novartis Pharmaceuticals Corporation.

The nurses of the University of Tennessee GCRC for their assistance in the care of these subjects, the staff of the University of Tennessee Obesity Wellness Center for their technical assistance, and Drs Laurie Letvak and Kurt Sizer of Novartis Pharmaceuticals Corp. for their support.

Author information

Author notes

  1. K L Arheart

    Present address: Dept Epidemiology and Public Health, University of Miami, FL, 33136, USA

  2. C K Buffington

    Present address: U.S. Bariatric, Fort Lavderdale, FL, 33308, USA

  3. R H Lustig

    Present address: Department of Pediatrics, University of California, San Francisco, CA, 94143, USA

Authors and Affiliations

  1. Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA

    P A Velasquez-Mieyer, K A Spencer, B E Connelly & R H Lustig

  2. Department of Nursing, University of Tennessee Health Science Center, Memphis, TN, USA

    P A Cowan

  3. Department of Preventative Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

    K L Arheart

  4. Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA

    C K Buffington & G W Cowan

Authors
  1. P A Velasquez-Mieyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P A Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K L Arheart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C K Buffington
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K A Spencer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B E Connelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G W Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R H Lustig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P A Velasquez-Mieyer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Velasquez-Mieyer, P., Cowan, P., Arheart, K. et al. Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults. Int J Obes 27, 219–226 (2003). https://doi.org/10.1038/sj.ijo.802227

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.802227

Keywords

This article is cited by

Search

Advanced search

Quick links