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3/2006
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Original paper
Short-term lifestyle intervention significantly increases fasting adiponectin and induces a decline in serum adiponectin during oral glucose tolerance test, without changes in insulin resistance

Krzysztof C. Lewandowski
,
Konrad Szosland
,
Rudiger Horn
,
Georg Brabant
,
Andrzej Lewiński

Arch Med Sci 2006; 2, 3: 179-184
Online publish date: 2006/09/26
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Introduction
Metabolic syndrome is associated with central obesity, dyslipidaemia, hypertension, type 2 diabetes and atheroslerotic cardiovascular disease [1]. Adipose tissue is now considered to represent not only an energy storage organ, but is also a source of several adipocytokines, such as leptin, resistin and adiponectin, known to be involved in regulation of energy homeostasis, insulin resistance, atherosclerosis and inflammatory processes [2–4]. Adiponectin is an adipose tissue-specific adipocytokine [5] that circulates in human plasma in high concentrations, and in addition to its anti-diabetic effects [6] adiponectin is also anti-atherogenic [7] and anti-inflammatory [8]. Plasma levels of adiponectin have been found to be decreased in obesity [5], dyslipidaemia [9] and type 2 diabetes [10, 11], i.e. in conditions typically associated with the metabolic syndrome. Previous studies have demonstrated that reduced circulating adiponectin levels are partially reversible by weight reduction in obese and in insulin-resistant subjects [11–13]. Such an increase in circulating adiponectin may therefore potentially attenuate increased cardiovascular risk associated with the metabolic syndrome. Patients with the metabolic syndrome are typically encouraged to lose weight and to undertake regular exercise. There is, however, conflicting evidence on the minimum duration of such intervention that may result in any appreciable changes in circulating adiponectin. In our study, we have therefore endeavoured to assess whether short-term, but highly supervised, lifestyle intervention consisting of diet and exercise may lead to a change in circulating adiponectin concentrations in severely obese subjects with the metabolic syndrome. Additionally, we assessed whether adiponectin levels are altered following oral administration of glucose during standardised 75 gram oral glucose tolerance test.
Material and methods
The study involved 16 subjects (4 males) (age mean±SD 42±14.18 years, BMI 42.65±7.14 kg/m2) who were recruited from the Obesity and Metabolic Syndrome Outpatient Clinic of the Medical University of Lodz, Poland. Following initial assessment in the clinic (history, full clinical examinations, assessment of baseline fasting glucose, lipids, TSH and free T4, ECG) they were admitted to our department for a two-week lifestyle modification programme. This involved dietary advice followed by a weight-reducing hypocaloric diet of 1200±200 kcal/24 hours for female subjects and 1400±200 kcal/24 hours for males. Individual caloric content was calculated according to the FAO/WHO criteria which take into account sex, age and individually calculated ideal body weight. According to these recommendations, calculated protein intake should be 1 gram/kg of ideal body mass, with 20-25% of total energy derived from fat, limitation of saturated fats intake and complete elimination of fried foods. In addition to dietary intervention each subject participated in a physical exercise programme that included swimming for 45 minutes a day and three 15 min sessions on a cycloergometer per day. All subjects were also encouraged to take regular walks throughout the day. 75 gram oral glucose tolerance test was performed in each subject before behavioural intervention (day 1) and after completion of a two-week period (day 15). During oral glucose tolerance test (0, 60, 120 minutes) blood samples were taken for the assessment of serum glucose, insulin and adiponectin. Exclusion criteria included treated diabetes mellitus, treated dyslipidaemia, and active ischaemic heart disease, lung disease or heart failure that precluded participation in the exercise programme because of anginal pain or dyspnoea. None of the studied subjects received any medication that could significantly influence insulin sensitivity (such as metformin or thiazolidinediones). The study received ethical approval of the Ethics Committee of the Medical University of Lodz, Poland. Insulin resistance indices [Homeostasis Model Assessment (HOMA), Quantitative Insulin-Sensitivity Check Index (QUICKI) and Insulin Resistance Index (IRI)] were calculated as specified below. HOMA: was calculated as G0 (mmol/l)* I0 (µU/ml)/ 22.5 [14]. QUICKI: was also calculated from fasting glucose and insulin values, according to the formula: 1/[log(I0) + log(G0)], where I0 is fasting insulin (microunits per millilitre) and G0 is fasting glucose (milligrams per decilitre). QUICKI is the reciprocal of the log-transformed product of fasting glucose and insulin; it is a dimensionless index without units. Some authors believe that QUICKI is superior to HOMA [15, 16]. Insulin Resistance Index is a method based on changes of glycaemia and insulinaemia during an oral glucose tolerance test (OGTT) [17]. IRI was calculated through the formula: 2/[1/(INSp x GLYp)]+1, where INSp and GLYp are the measured insulin and glycaemic areas. This method is based on changes of glycaemia and insulinaemia during OGTT, and correlates well with the euglycaemic hyperinsulinaemic glucose clamp technique [18]. According to the same authors the assessment of free fatty acids (FFA) during OGTT is equally effective for the purpose of calculation of the insulin resistance index [18]. During the OGTT blood was sampled at 0, 60 and 120 min for determination of plasma insulin and FFA. Tubes were immediately transported to the laboratory. Serum insulin was determined by an immunoenzymatic assay (IMMULITE, DPC) and serum concentrations for total FFA were determined by an enzymatic method (Boehringer Mannheim). The samples for FFA determination were spun down with minimal delay and frozen at -20°C until analysis. Serum adiponectin levels were measured as previously described [19]. Briefly, adiponectin antiserum was generated in rabbits using a C-terminal fragment of adiponectin (aa189-202, Biotrend). The amino acid sequence for antibody generation had a 93% homology between human and murine adiponectin. Full-length recombinant human and murine adiponectin or adiponectin-fragment was used as a standard (data not shown). The inter- and intra-assay CV was <6.5%.
Statistical analysis
Statistical analysis of the data was performed with simple descriptive statistics. Paired-samples t-tests were used to compare the means of two variables for a single group. It computes the differences between values of the two variables for each case and tests whether the average differs from 0. The one-way ANOVA procedure produced a one-way analysis of variance for a quantitative dependent variable by a single factor (independent) variable. Analysis of variance was used to test the hypothesis that several means are equal. This technique is an extension of the two-sample t-test. The assessment of bivariate correlations was performed by Pearson’s correlation coefficient. In all analyses p<0.05 was considered to indicate statistical significance.
Results
Results of the study are presented in Tables 1-3 and Figure 1. There was a highly significant fall of BMI, from 42.65±7.82 kg/m2 to 40.21±7.14 kg/m2, p<0.001. This was accompanied by a significant rise in fasting adiponectin from 32.11±13.25 nmol/l to 35.38±11.04 nmol/l (t-test: p=0.007) (Figure 1). There was, however, only a trend towards improvement of QUICKI, from 0.34±0.04 to 0.34±0.04, p=0.063, and no significant change of HOMA (p=0.64) or IRI (p=0.88) as assessed by paired t-test (Table I). Seven out of 16 subjects were found to have impaired glucose tolerance during OGTT before lifestyle intervention. None of the study subjects had glucose levels in the diabetic range during OGTT. After a two-week period of lifestyle intervention only four subjects still had evidence of impaired glucose tolerance during OGTT. There was no significant change in adiponectin concentrations during OGTT before lifestyle intervention, but there was a significant fall in adiponectin concentrations during OGTT after a two-week period of lifestyle intervention (see Table II). There was, however, no significant correlation between serum adiponectin and insulin resistance indices, with the exception of a trend towards a positive correlation between serum adiponectin and IRI obtained both from the measurements of glucose and insulin or glucose and FFA during OGTT (see Table III).
Discussion
Our study demonstrates a significant increase in adiponectin levels after two weeks of lifestyle intervention that resulted in moderate weight loss in obese subjects; BMI before lifestyle modification programme was 42.65±7.82 kg/m2 and after lifestyle modification programme was 40.21±7.14 kg/m2 (p<0.001), average decline of BMI of 2.4 kg/m2 (average weight loss of 6 kg). This weight loss was accompanied by mild but not significant improvement in insulin resistance indices. The lack of significant change in insulin resistance indices is not surprising given the relatively short intervention period, and given that body composition studies [20] indicate that initial weight loss is related mostly to the loss of glycogen and water with only minor reduction of fat mass. In our study, we did not detect a clear association between serum adiponectin and insulin resistance indices though there was a trend towards positive correlation between serum adiponectin and a dynamic measure of insulin resistance, i.e. the insulin resistance index. There is a possibility that a larger number of subjects might be needed to detect a significant association between insulin resistance indices and total adiponectin, given that a recent study on adiponectin levels in polycystic ovary syndrome, based on data from 62 subjects, showed in multiple linear regression analysis that insulin resistance explained only 13% of the variability of plasma total adiponectin, suggesting a significant role of other, as yet unexplained factors in determination of plasma adiponectin concentrations [21]. Another possible explanation of the lack of correlation between serum adiponectin and insulin resistance might be related to the polymeric structure of adiponectin, where higher molecular weight isoforms tend to correlate better with insulin resistance [22]. Indeed, a recent study of Lara-Castro et al. [23] also confirms that higher molecular weight adiponectin complexes and not total adiponectin are responsible for the association between adiponectin and increased insulin sensitivity. Interestingly, we have demonstrated a significant increase in serum adiponectin after a relatively short period of intervention (diet and exercise) in a closely supervised hospital environment. Though long-term intervention studies (over 6 months) demonstrated a significant increase in adiponectin levels [24–26], the effects of shorter interventions in most cases failed to demonstrate a significant change in serum adiponectin [27–30]. In contrast to these studies, Balagopal et al. [31] reported a 34% increase in adiponectin concentrations in a 3-month randomised trial, where, similar to our design, intervention consisted both of dietary advice and an exercise programme. Hotta et al. [32] also described a significant (about 50-60%) increase in adiponectin in hospitalised patients after gradual decrease in caloric content from 2000 kcal/day to 800 kcal/day over a two-month period. Though adiponectin levels were measured in that study only after two months, it is possible that a significant increase in adiponectin might have been detected at a much earlier stage. In this context it is interesting to note that beneficial changes in serum adiponectin were observed in our study after only a two-week intervention period. What, however, might be the reason behind the lack of significant changes in adiponectin levels in some other short duration (4-week to 3-month) studies mentioned above? We point out that our study was conducted in a highly supervised hospital environment. This ensured almost 100% compliance with the diet and exercise programme. Though exercise is not invariably associated with changes in serum adiponectin [11, 33], other studies show increase in adiponectin after about one week of exercise programme in obese and overweight males [34] as well as after a longer (6 month) period of lifestyle modification consisting of diet and moderate physical activity [24]. Furthermore, because of our hospital regulations all subjects were forbidden to smoke, and smoking is known to reduce adiponectin levels [35]. In our case 3 out of 4 males and 3 out of 12 women were smokers, but it should be noted that some increase in adiponectin was present in almost all our subjects, regardless of their smoking habits. Another potentially interesting aspect of our study might be related to the significant change in adiponectin during the oral glucose tolerance test after intervention. The effect of oral glucose tolerance test on adiponectin levels is controversial. Osei et al. [36] showed a non-significant rise in plasma adiponectin during OGTT in subjects with BMI <30 kg/m2 (from 10.75±5.82 µg/ml to 13.01±5.55 µg/ml, p=0.08, n=8) and no change in those with BMI>30 kg/m2 and normal glucose tolerance (8.79±4.61 vs 8.71±4.59 µg/ml, n=11, p=0.42). Peake et al. [37] also reported no change in adiponectin isoforms (high molecular weight, hexameric adiponectin and trimers) after oral glucose. In contrast, Panidis et al. [38] showed a significant decrease in serum adiponectin in both overweight and normal weight women with and without the polycystic ovary syndrome (PCOS) (overweight: controls n=38, PCOS n=25, normal weight: controls n=10, PCOS n=21). In this context, our study demonstrates that adiponectin response to oral glucose tolerance test may be altered by lifestyle intervention. The mechanism behind this response and its clinical significance remain unclear, though it is known that weight loss not only influences fasting adiponectin levels, but may also restore adiponectin pulsatility [39]. Formal studies on the effects of glucose administration on adiponectin pulsatility before and after weight loss are needed, however, to establish whether such a mechanism might be related to the change in response to oral glucose tolerance after a diet and exercise programme.
Conclusions
In summary, our study demonstrates a significant rise in fasting adiponectin after a two-week lifestyle modification period in a supervised environment. This suggests that even relatively short intervention might be enough to induce favourable changes in concentrations of this adipocytokine. Such intensive intervention might be potentially more effective in inducing favourable and lasting changes in lifestyle than repeated consultations in an outpatient clinic. It remains, however, to be established whether the observed changes may be maintained after discharge from the hospital, i.e. during standard outpatient management.
References
1. Scott CL. Diagnosis, prevention, and intervention for the metabolic syndrome. Am J Cardiol 2003; 92: 19i-26i. 2. Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 2002; 13: 51-5. 3. Arner P. The adipocyte in insulin resistance: key molecules and the impact of thiazolidinediones. Trends Endocrinol Metab 2003; 14: 137-45. 4. Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, et al. Direct reciprocal effects of resistin and adiponectin: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun 2004; 314: 415-9. 5. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein adiponectin in obesity. Biochem Biophys Res Commun 1999; 257: 79-83. 6. Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002; 13: 84-89. 7. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002; 106: 2767-70. 8. Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 100: 2473-6. 9. Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidaemia. J Clin Endocrinol Metab 2002; 87: 2764-9. 10. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hypoinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930-5. 11. Nassis GP, Papankakou K, Skenderi K, Triandafillopoulou M, Kavoural SA, Yannakoulia M, et al. Aerobic exercise improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls. Metabolism 2005; 54: 1472-1479. 12. Yang WS, Lee WJ, Funahashi T, Tanaka S, Mtsuzawa Y, Chao CL, et al. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001; 86: 3815-9. 13. Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert MO, Mohlig M, Pfeiffer AFH, Spranger J. Changes in adiponectin oligomer composition by moderate weight reduction. Diabetes 2005; 54: 2712-2719. 14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-9. 15. Abbasi F, Reaven GM. Evaluation of the quantitative insulin sensitivity check index as an estimate of insulin sensitivity in humans. Metabolism 2002; 51: 235-7. 16. Chen H, Sullivan G, Quon MJ. Assessing the Predictive Accuracy of QUICKI as a Surrogate Index for Insulin Sensitivity Using a Calibration Model. Diabetes 2005; 54: 1914-25. 17. Belfiore F, Iannello S, Volpicelli G. Insulin sensitivity indices calculated from basal and OGTT-induced insulin, glucose, and FFA levels. Mol Genet Metab 1998; 63: 134-41. 18. Matsuda M, DeFronzo R. Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 1999; 9: 1462-70. 19. Tacke K, Wustefeld T, Horn R, Luedde T, Srinivas Rao A, Manns MP, et al. High adiponectin in chronic liver disease and cholestasis suggests biliary route of adiponectin excretion in vivo. J Hepatol 2005; 42: 666-73. 20. van Kreel BK, Cox-Reyven N, Soeters P. Determination of total body water by multifrequency bio-electric impedance: development of several models. Med Biol Eng Comput 1998; 36: 333-45. 21. Spranger J, Mohlig M, Wegewitz U, Ristow M, Pfeiffer AFH, Schill T, et al. Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome Clin Endocrinol (Oxf) 2004; 61: 738-46. 22. Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279: 12152-62. 23. Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey TW. Adiponectin multimeric complexes and the metabolic syndrome trait cluster Diabetes 2006; 55: 249-59. 24. Monzillo LU, Hamdy O, Horton ES, Ledbury S, Mullooly C, Jarema C, et al. Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res 2003; 11: 1048-54. 25. Despres JP, Golay A, Sjostrom L. Rimonabant in Obesity-Lipids Study Group (2005) Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidaemia. N Engl J Med 2005; 353: 2121-34. 26. Lazzer S, Vermorel M, Mountaurier C, Meyer M, Boire Y. Changes in adipocyte hormones and lipid oxidation associated with weight loss and regain in severely obese adolescents. Int J Obes (Lond) 2005; 29: 1184-91. 27. Wolfe BE, Jimerson DC, Orlova C, Mantzoros CS. Effect of dieting on plasma leptin, soluble leptin receptor, adiponectin and resistin levels in healthy volunteers. Clin Endocrinol (Oxf) 2004; 61: 332-8. 28. Xydakis AM, Case CC, Jones PH, Hoogeveen RC, Liu MY, Smith EO, et al. Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction. J Clin Endocrinol Metab 2004; 89: 2697-703. 29. Manigrasso MR, Ferroni P, Santilli F, Taraborelli T, Guagnamo MT, Michetti N, et al. Association between circulating adiponectin and interleukin-10 levels in android obesity: effects of weight loss. J Clin Endocrinol Metab 2005; 90: 5876-9. 30. Abbasi F, Chang SA, Chu JW, Ciaraldi TP, Lamendola C, McLaughlin T, et al. Improvements in insulin resistance with weight loss, in contrast to rosiglitazone, are not associated with changes in plasma adiponectin or adiponectin multimeric complexes. Am J Physiol Regul Integr Comp Physiol 2006; 290: R139-144. 31. Balagopal P, Geprge D, Yarandi H, Funanage V, Bayne E. Reversal of obesity-related hypoadiponectinaemia by lifestyle intervention, randomised study in obese adolescents. J Clin Endocrinol Metab 2005; 90: 6192-7. 32. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20: 1595-9. 33. Marcell TJ, McAuley KA, Traustadottir T, Reaven PD. Exercise training is not associated with improved levels of C-reactive protein or adiponectin. Metabolism 2005; 54: 533-41. 34. Kriketos AD, Gan SK, Poynten AM, Furler SM, Chrisholm DJ, Campbell LV. Exercise increases adiponectin levels and insulin sensitivity in humans. Diabetes Care 2004; 27: 629-30. 35. Iwashima Y, Katsuya T, Ishikawa K, Kida I, Ohishi M, Horio T, et al. Association of hypoadiponectinemia with smoking habit in men. Hypertension 2005; 45: 1094-100. 36. Osei K, Gaillard T, Schuster D. Plasma adiponectin levels in high risk African-Americans with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. Obesity Res 2005; 13: 179-85. 37. Peake PW, Kriketos AD, Campbell LV, Shen Y, Charlesworth JA. The metabolism of isoforms of human adiponectin: studies in human subjects and experimental animals. Eur J Endocrinol 2005; 153: 409-17. 38. Panidis D, Farmakiotis D, Rousso D, Koliakos G, Kaltsas T, Krassas G. Decrease in adiponectin levels in women with polycystic ovary syndrome after an oral glucose tolerance test. Fertil Steril 2005; 83: 232-4. 39. Calvani M, Scarfone A, Granato L, Mora EV, Nanni G, Castagneto M, et al. Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes 2004; 53: 939-47.
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