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Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

Abstract

BACKGROUND:

Little is known about the effects of short-term caloric restriction (CR) and overfeeding (OF) on glucose homeostasis in healthy lean individuals. In addition, it remains unclear whether the effects of CR and OF are reversed by a complementary feeding period.

METHODS:

Ten healthy men participated in two cycles of controlled 7-day periods of CR and refeeding (RF; protocol A), and OF and CR (protocol B) at ±60% energy requirement. At baseline, insulin sensitivity (IS) was assessed by euglycemic clamp (M). Before and during each feeding cycle, fasting and oral glucose tolerance test-derived indices were used to estimate glucose tolerance, IS and glucose-stimulated insulin secretion.

RESULTS:

Clamp tests revealed normal IS at baseline (M-values 9.4±2.1 mg kg−1 min−1, coefficient of variation (CV)inter 22%). M-values were significantly correlated with indices of IS. In protocol A, CR-induced weight loss (−3.0±0.4 kg) was associated with an increase in fasting IS. Postprandial IS and glucose-stimulated insulin secretion remained unchanged, but glucose tolerance decreased. RF decreased fasting and postprandial IS at increased glucose-stimulated insulin secretion. In protocol B, OF significantly increased the body weight (+1.6±0.9 kg). Concomitantly, fasting and postprandial IS decreased at increased glucose-stimulated insulin secretion. Subsequent CR reversed these effects. Inter-individual variability in indices of glucose metabolism was high with coefficients of variation ranging from 9 to 59%.

CONCLUSION:

Significant changes in glucose metabolism are evident within 7-day periods of controlled OF and underfeeding. Although IS was impaired at the end of the CR–RF cycle, IS was normalized after the OF–CR cycle. At different feeding regimens, homeostatic responses of glucose metabolism were highly variable.

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References

  1. Kahn SE, Hull RL, Utzschneider KM . Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 444: 840–846.

    Article  CAS  Google Scholar 

  2. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R . Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54: 2506–2514.

    Article  CAS  Google Scholar 

  3. Doherty R . Obesity-related insulin resistance is reversible after weight loss. Nat Clin Pract Endocrinol Metab 2006; 2: 64–65.

    Article  Google Scholar 

  4. Assali AR, Ganor A, Beigel Y, Shafer Z, Hershcovici T, Fainaru M . Insulin resistance in obesity: body-weight or energy balance? J Endocrinol 2001; 171: 293–298.

    Article  CAS  Google Scholar 

  5. Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S . Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 2009; 136: 1552–1560.

    Article  CAS  Google Scholar 

  6. Karczewska-Kupczewska M, Straczkowski M, Adamska A, Nikolajuk A, Otziomek E, Gorska M et al. Insulin sensitivity, metabolic flexibility, and serum adiponectin concentration in women with anorexia nervosa. Metabolism 2010; 59: 473–477.

    Article  CAS  Google Scholar 

  7. Mansell PI, Macdonald IA . The effect of starvation on insulin-induced glucose disposal and thermogenesis in humans. Metabolism 1990; 39: 502–510.

    Article  CAS  Google Scholar 

  8. Webber J, Taylor J, Greathead H, Dawson J, Buttery PJ, Macdonald IA . Effects of fasting on fatty acid kinetics and on the cardiovascular, thermogenic and metabolic responses to the glucose clamp. Clin Sci (Lond) 1994; 87: 697–706.

    Article  CAS  Google Scholar 

  9. Gallen IW, Macdonald IA . The effects of underfeeding for 7 d on the thermogenic and physiological response to glucose and insulin infusion (hyperinsulinaemic euglycaemic clamp). Br J Nutr 1990; 64: 427–437.

    Article  CAS  Google Scholar 

  10. Nygren J, Thorell A, Brismar K, Karpe F, Ljungqvist O . Short-term hypocaloric nutrition but not bed rest decrease insulin sensitivity and IGF-I bioavailability in healthy subjects: the importance of glucagon. Nutrition 1997; 13: 945–951.

    Article  CAS  Google Scholar 

  11. Seevaratnam N, Bennett AJ, Webber J, Macdonald IA . The effects of underfeeding on whole-body carbohydrate partitioning, thermogenesis and uncoupling protein 3 expression in human skeletal muscle. Diabetes Obes Metab 2007; 9: 669–678.

    Article  CAS  Google Scholar 

  12. Brons C, Jensen CB, Storgaard H, Hiscock NJ, White A, Appel JS et al. Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men. J Physiol 2009; 587: 2387–2397.

    Article  Google Scholar 

  13. Cornier MA, Bergman BC, Bessesen DH . The effects of short-term overfeeding on insulin action in lean and reduced-obese individuals. Metabolism 2006; 55: 1207–1214.

    Article  CAS  Google Scholar 

  14. Erdmann J, Kallabis B, Oppel U, Sypchenko O, Wagenpfeil S, Schusdziarra V . Development of hyperinsulinemia and insulin resistance during the early stage of weight gain. Am J Physiol Endocrinol Metab 2008; 294: E568–E575.

    Article  CAS  Google Scholar 

  15. Mott DM, Lillioja S, Bogardus C . Overnutrition induced decrease in insulin action for glucose storage: in vivo and in vitro in man. Metabolism 1986; 35: 160–165.

    Article  CAS  Google Scholar 

  16. Olefsky J, Crapo PA, Ginsberg H, Reaven GM . Metabolic effects of increased caloric intake in man. Metabolism 1975; 24: 495–503.

    Article  CAS  Google Scholar 

  17. Johnson NA, Stannard SR, Rowlands DS, Chapman PG, Thompson CH, O′Connor H et al. Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men. Exp Physiol 2006; 91: 693–703.

    Article  CAS  Google Scholar 

  18. Weiss EP, Racette SB, Villareal DT, Fontana L, Steger-May K, Schechtman KB et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am J Clin Nutr 2006; 84: 1033–1042.

    Article  CAS  Google Scholar 

  19. Ahren B, Pacini G . Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies. Eur J Endocrinol 2004; 150: 97–104.

    Article  CAS  Google Scholar 

  20. Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993; 42: 1663–1672.

    Article  CAS  Google Scholar 

  21. Stumvoll M, Tataranni PA, Stefan N, Vozarova B, Bogardus C . Glucose allostasis. Diabetes 2003; 52: 903–909.

    Article  CAS  Google Scholar 

  22. White CL, Purpera MN, Ballard K, Morrison CD . Decreased food intake following overfeeding involves leptin-dependent and leptin-independent mechanisms. Physiol Behav 2010; 100: 408–416.

    Article  CAS  Google Scholar 

  23. Roberts SB, Fuss P, Heyman MB, Evans WJ, Tsay R, Rasmussen H et al. Control of food intake in older men. JAMA 1994; 272: 1601–1606.

    Article  CAS  Google Scholar 

  24. Mars M, de Graaf C, de Groot LC, Kok FJ . Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake. Am J Clin Nutr 2005; 81: 570–577.

    Article  CAS  Google Scholar 

  25. Korth O, Bosy-Westphal A, Zschoche P, Gluer CC, Heller M, Muller MJ . Influence of methods used in body composition analysis on the prediction of resting energy expenditure. Eur J Clin Nutr 2007; 61: 582–589.

    Article  CAS  Google Scholar 

  26. Knutzen J, Bosy-Westphal A, Maurer I, Borngässer J, Müller MJ . Estimation of the relative validity of assessment of body composition by hydrodensitometry compared with air-displacement plethysmography]. Akt Ernährungsmedizin 2008; 33: 237–246.

    Article  Google Scholar 

  27. Ma J . Dixon techniques for water and fat imaging. J Magn Reson Imaging 2008; 28: 543–558.

    Article  Google Scholar 

  28. Bader N, Bosy-Westphal A, Dilba B, Muller MJ . Intra- and interindividual variability of resting energy expenditure in healthy male subjects -- biological and methodological variability of resting energy expenditure. Br J Nutr 2005; 94: 843–849.

    Article  CAS  Google Scholar 

  29. Weir JB . New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 1949; 109: 1–9.

    Article  Google Scholar 

  30. Frayn KN . Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 1983; 55: 628–634.

    Article  CAS  Google Scholar 

  31. DeFronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–E223.

    CAS  PubMed  Google Scholar 

  32. Bosy-Westphal A, Kossel E, Goele K, Blocker T, Lagerpusch M, Later W et al. Association of pericardial fat with liver fat and insulin sensitivity after diet-induced weight loss in overweight women. Obesity (Silver Spring) 2010; 18: 2111–2117.

    Article  CAS  Google Scholar 

  33. Muller MJ, von Schutz B, Huhnt HJ, Zick R, Mitzkat HJ, von zur Muhlen A . Glucoregulatory function of thyroid hormones: interaction with insulin depends on the prevailing glucose concentration. J Clin Endocrinol Metab 1986; 63: 62–71.

    Article  CAS  Google Scholar 

  34. Matthews JN, Altman DG, Campbell MJ, Royston P . Analysis of serial measurements in medical research. BMJ 1990; 300: 230–235.

    Article  CAS  Google Scholar 

  35. Muniyappa R, Lee S, Chen H, Quon MJ . Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294: E15–E26.

    Article  CAS  Google Scholar 

  36. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  37. Hoffman RP . Indices of insulin action calculated from fasting glucose and insulin reflect hepatic, not peripheral, insulin sensitivity in African-American and Caucasian adolescents. Pediatr Diabetes 2008; 9: 57–61.

    Article  CAS  Google Scholar 

  38. 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  Google Scholar 

  39. Retnakaran R, Shen S, Hanley AJ, Vuksan V, Hamilton JK, Zinman B . Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity (Silver Spring) 2008; 16: 1901–1907.

    Article  CAS  Google Scholar 

  40. Tschritter O, Fritsche A, Shirkavand F, Machicao F, Haring H, Stumvoll M . Assessing the shape of the glucose curve during an oral glucose tolerance test. Diabetes Care 2003; 26: 1026–1033.

    Article  CAS  Google Scholar 

  41. Reaven GM . Hypothesis: muscle insulin resistance is the (″not-so″) thrifty genotype. Diabetologia 1998; 41: 482–484.

    Article  CAS  Google Scholar 

  42. Tomiyama AJ, Mann T, Vinas D, Hunger JM, Dejager J, Taylor SE . Low calorie dieting increases cortisol. Psychosom Med 2010; 72: 357–364.

    Article  CAS  Google Scholar 

  43. Fryburg DA, Barrett EJ, Louard RJ, Gelfand RA . Effect of starvation on human muscle protein metabolism and its response to insulin. Am J Physiol 1990; 259: E477–E482.

    CAS  PubMed  Google Scholar 

  44. Lettner A, Roden M . Ectopic fat and insulin resistance. Curr Diab Rep 2008; 8: 185–191.

    Article  CAS  Google Scholar 

  45. Eckel RH . Insulin resistance: an adaptation for weight maintenance. Lancet 1992; 340: 1452–1453.

    Article  CAS  Google Scholar 

  46. Raphael FJ, Rodin DA, Peattie A, Bano G, Kent A, Nussey SS et al. Ovarian morphology and insulin sensitivity in women with bulimia nervosa. Clin Endocrinol (Oxf) 1995; 43: 451–455.

    Article  CAS  Google Scholar 

  47. Karelis AD, Messier V, Brochu M, Rabasa-Lhoret R . Metabolically healthy but obese women: effect of an energy-restricted diet. Diabetologia 2008; 51: 1752–1754.

    Article  CAS  Google Scholar 

  48. Maki KC, McKenney JM, Farmer MV, Reeves MS, Dicklin MR . Indices of insulin sensitivity and secretion from a standard liquid meal test in subjects with type 2 diabetes, impaired or normal fasting glucose. Nutr J 2009; 8: 22.

    Article  Google Scholar 

  49. Mari A, Ahren B, Pacini G . Assessment of insulin secretion in relation to insulin resistance. Curr Opin Clin Nutr Metab Care 2005; 8: 529–533.

    Article  Google Scholar 

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Acknowledgements

We are grateful to Anne Morgenstern, Lena Vogt and Ruth Apolony for their tireless assistance in data collection. We also thank Birgit Rümcker for the assistance with the food preparation, Jutta Schwanbom for assisting with the laboratory analyses and the study subjects for their participation. The study was supported by a grant of Deutsche Forschungsgemeinschaft (DFG-GZ: Bo 3296/1-1).

Author contributions

Study design (ABW, MJM), data collection (ML, ABW), laboratory analyses (AP), data analyses (ML, BK), discussion of data (ML, ABW, BK, MJM), writing of the manuscript (ML, ABW, MJM).

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Correspondence to M J Müller.

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Lagerpusch, M., Bosy-Westphal, A., Kehden, B. et al. Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men. Int J Obes 36, 1094–1101 (2012). https://doi.org/10.1038/ijo.2011.211

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