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Serum leptin is associated with cardiometabolic risk and predicts metabolic syndrome in Taiwanese adults

Abstract

Background

Leptin is associated with cardiovascular disease (CVD); however, few studies have assessed its relationship with metabolic syndrome, especially in an Asian population. Therefore, the aim of the present study was to assess leptin levels and evaluate its association with CVD and metabolic syndrome.

Methods

In 2009, 957 subjects, who underwent a routine physical examination and choose leptin examination, were selected to participate. Participants (269 females and 688 males) were stratified according to leptin level quartiles. Metabolic syndrome was defined by NCEP ATP III using waist circumference cutoffs modified for Asian populations, and CVD risk was determined using the Framingham Heart Study profile.

Results

Leptin levels were correlated with CVD risk in men and women. With the exception of fasting plasma glucose, increased leptin levels were observed as factors associated with metabolic syndrome increased in both males and females. After adjusting for age, an association between leptin levels and metabolic syndrome was observed. After adjusting for age alone or with tobacco use, subjects in the highest leptin quartile had a higher risk of having metabolic syndrome than those in the lowest quartile (OR = 6.14 and 2.94 for men and women, respectively). After further adjustment for BMI, metabolic syndrome risk remained significantly increased with increasing leptin quartiles in men. Finally, increased leptin levels were a predictor of metabolic syndrome in men and women.

Conclusions

Serum leptin levels are correlated with CVD risk and metabolic syndrome. Analysis of leptin as part of routine physical examinations may prove beneficial for early diagnosis of metabolic syndrome.

Introduction

Metabolic syndrome is a major risk factor for type 2 diabetes mellitus and cardiovascular disease (CVD). Specifically, a three-fold increase in the prevalence of metabolic syndrome is associated with a two-fold increased risk of cardiovascular disease fatality, 150% increase in total mortality, and a five-fold increased risk of diabetes mellitus [1]. Because metabolic syndrome is associated with increased risk for CVD and diabetes mellitus [2–5], early diagnosis of metabolic syndrome and resultant intervention strategies may help reduce the incidence of these associated diseases.

Leptin is important for body weight regulation. In mice, mutations of the OB gene on chromosome 7, which encodes the leptin protein, results in obesity and type 2 diabetes [6]. The amount of leptin secreted by white adipose tissue is proportional to the volume of body adipose tissue; therefore, adiposity greatly influences leptin levels. In addition, other factors, including rapid or excessive food intake, sleep, body temperature, gender, circadian rhythm, and other hormones such as insulin, growth hormone, glucocorticoids, testosterone, and thyroid hormone, impact leptin secretion and expression.

Elevated serum leptin concentration is a feature of obesity and abdominal adiposity, a risk factor for metabolic syndrome. Although elevated serum leptin is not considered among the diagnostic criteria for metabolic syndrome, it is increased in subjects with metabolic syndrome [7–9].

Because leptin has a certain degree of influence on appetite, energy consumption, adipose synthesis, and insulin function, elevated serum leptin levels are common in human obesity. The higher the body mass index (BMI) or the waist circumference, the higher the serum leptin level [10]. The elevated concentration of circulating leptin has been consistently associated with other cardiometabolic risk factors, such as hypertension, insulin resistance, and type 2 diabetes [11–18]; however, few studies have analyzed its association with metabolic syndrome [7–9]. Of the few conducted, few have analyzed Asian populations. Thus, the objective of the present study was to assess the association of leptin with metabolic syndrome and CVD risk in Taiwanese adults as well as the predictive value of leptin levels for identifying patients with metabolic syndrome. Leptin levels were measured in adult participants undergoing a routine physical examination, and their relationship with metabolic syndrome as well as CVD risk was assessed.

Materials and methods

Study participants

In 2009, 988 subjects > 18 years of age, who underwent a routine physical examination and choose leptin examination in Chang-Gung Memorial Hospital-Linkou (North Taiwan) and Chiayi (South Taiwan), were selected to participate in this retrospective study. Questionnaires were completed at the Health Examination Centers in the Linkou and Chiayi branches of Cheng-Gung Memorial Hospital; the physical examination and venous blood sampling was obtained at the same time. Analysis excluded subjects that did not fast for more than 10 h prior to blood sampling, were pregnant, those with chronic diseases that significantly impact the metabolic functions, such as thyroid diseases, chronic hepatitis, liver cirrhosis, hypothalamus disease, etc., and those with a history of illness or medication use in the questionnaires. There were 31 subjects excluded from this study based on the exclusion criteria. Therefore, a total of 957 participants (688 males, average age of 35.2 y [SD = 7.2 y] and 269 females, average age of 38.5 y [SD = 11.8 y]) were included for this study. The study protocol was approved by the Institutional Review Board of Chang-Gung Memorial Hospital.

Clinical and biochemical measurements

Participants were interviewed using questionnaires by trained nurses. Information regarding demographic (e.g., age, gender, etc.) and life style (e.g., experience of smoking, drinking, etc.) characteristics, history of illness and medication use, and physiologic status (pregnancy, fasting time, etc.) was collected.

Blood pressure was measured after the participants were at rest for 10 min using an automatic sphygmomanometer to the right arm while the individuals were in a sitting position. An additional 5-minute break was given between measurements for participants with systolic blood pressure > 140 mmHg or the diastolic blood pressure > 90 mmHg. The lowest value was used after 2 to 3 measurements. The participant's weight and height was measured without shoes and after fasting. BMI was calculated as weight (kg) divided by the square of height (m2). Waist circumference was measured midway between the iliac crest and the lower margin of the 12th rib.

After a 12-h fast, venous blood samples were obtained from 5:30 to 11:00 a.m. and stored at 4°C. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), uric acid, homocysteine, and leptin levels were determined for each participant.

Definition of metabolic syndrome

A diagnosis of metabolic syndrome was defined as a subject presenting at least 3 of the 5 factors for metabolic syndrome described by the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program (NCEP) [19]. The diagnostic criteria were defined as follows: 1) high blood pressure (a systolic blood pressure ≥ 130 mmHg and/or diastolic pressure ≥ 85 mmHg, under treatment, or already diagnosed with hypertension); 2) high serum triglyceride (≥ 150 mg/dL or under treatment); 3) decreased HDL-C (< 40 mg/dL for males and < 50 mg/dL for females or under treatment); 4) hyperglycemia (FBG ≥ 100 mg/dL, under treatment, or previously diagnosed with diabetes mellitus); and abdominal obesity. Waist circumference cutoffs were modified for Asian populations [20]. A waist circumference ≥ 90 cm for men and ≥ 80 cm for women plus the other two risk factors or the waist circumstance within the threshold plus the other three or more risk factors resulted in a diagnosis of metabolic syndrome.

Cardiovascular disease risk percentage definition

CVD risk was analyzed based upon the profile described by D'Agostino et al. [21]. This profile predicts the risk of developing all CVD events, including coronary death, myocardial infarction, coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease, heart failure, using sex-specific multivariable risk functions that incorporated age, total cholesterol, HDL-C, systolic blood pressure, treatment for hypertension, smoking, and diabetes status.

Statistical analysis

Serum leptin levels were categorized into quartiles (Q1-4) according to the leptin levels (Q1, < 2.4 ng/mL; Q2, 2.4 to < 4.2 ng/mL; Q3, 4.2 to < 6.65 ng/mL; and Q4 ≥ 6.65 ng/mL for males and Q1, < 6.8 ng/mL; Q2, 6.8 to <9.0 ng/mL; Q3, 9.0 to < 13.1 ng/mL; and Q4, ≥ 13.1 ng/mL for females). The data were presented as mean ± standard deviation (SD) for continuous variables and n (%) for categorical variables. Clinical characteristics were compared using one-way ANOVA for continuous variables and Chi-sqaure or Fisher's exact test for categorical variables. Spearman's rank correlation was performed for each gender to assess the relationship between leptin levels and cardiometabolic risk factors. General linear model analysis was applied to identify the association of leptin levels with cardiometabolic risk factors after adjusting for age and tobacco usage. In addition, a binary logistic regression model was used to evaluate the association of leptin levels with metabolic syndrome after adjusting for age, tobacco usage, and BMI. A received operating curve (ROC) for leptin level as a predictor of metabolic syndrome was also carried out. Statistical analyses were performed using the SPSS 15.0 software package (SPSS, Inc., Chicago, IL). A P-value < 0.05 was considered statistically significant.

Results

The characteristics of male and female participants stratified by leptin quartiles are shown in Table 1. The mean leptin level for the study participants was 1.42 ng/mL. The prevalence of metabolic syndrome was 61% in the study population. In men and women, participants in Q4 were more likely to have factors associated with metabolic syndrome, including increased waist circumference, triglyceride, and blood pressure and decreased HDL-C. No significant differences in FBG were observed. In addition, no differences in tobacco usage and homocysteine level were observed (Table 1). Furthermore, those with metabolic syndrome were more likely to be in the upper leptin quartiles. Finally, percentage of CVD risk significantly increased with increasing leptin levels in both men and women.

Table 1 General characteristics of the study population according to sex-specific leptin levels.

The relationship between increased leptin levels and CVD risk percentage was also analyzed using the Kruskal Wallis test. Increased CVD risk percentage was observed in Q4 as compared to patients with leptin levels within Q1 and Q2 in both men and women (Figure 1, p < 0.05).

Figure 1
figure 1

The distribution of CVD risk percentage by sex-specific leptin levels. Data represent mean with standard error of mean for each leptin quartile. a significantly different (P < 0.0167) in CVD risk % as compared with Q1. b significantly different (P < 0.0167) in CVD risk % as compared with Q2.

As shown in Table 2, Spearman's rank correlation (r s ) analysis of leptin level with cardiometabolic risk factors for men and women was undertaken. In both men and women, leptin levels were positively correlated with BMI, waist circumference, blood pressure, total cholesterol, triglyceride, FPG, uric acid, LDL cholesterol, and percentage of CVD risk, but negatively correlated with HDL cholesterol. In addition, age was positively correlated with leptin levels in women (Table 2).

Table 2 aSpearmen's correlation of leptin levels with cardiometabolic risk factors in men and women.

Univariate linear regression analysis after adjusting for age or multiple variables, including age, tobacco usage, and BMI, to determine the association of leptin levels with cardiometabolic risk factors was assessed (Table 3). After adjusting for age, leptin levels were significantly positively associated with BMI, waist circumference, blood pressure, total cholesterol, triglyceride, uric acid, LDL cholesterol, percentage CVD risk, and metabolic syndrome, but were negatively associated with HDL cholesterol in both men and women. After adjusting for age, BMI, and tobacco usage, leptin levels were positively associated with metabolic syndrome in females (Table 3).

Table 3 aUnivariate analysis of leptin levels with cardiometabolic risk factors after adjusting for age and tobacco usage in men and women.

The correlation between metabolic syndrome and serum leptin quartiles was calculated independent of age, tobacco usage, and BMI in three models using binary logistic regression analysis (Table 4). Specifically, model 1 adjusted for age whereas models 2 and 3 adjusted for age and tobacco usage and age, tobacco usage, and BMI, respectively. In men, compared to the lowest leptin quartile, the odds ratio (OR) and 95% confidence intervals (95% CI) for metabolic syndrome after adjusting for age were 3.28 (2.06 - 5.20) in Q2, 5.12 (3.13 - 8.37) in Q3 and 6.14 (3.70 - 10.19) in Q4 (p < 0.001). A similar increase in odds ratio was observed in women (Q4 vs. Q1, 2.94 (1.36 - 6.37), p = 0.037). Further adjusting for tobacco usage and BMI revealed increased odds ratio of metabolic syndrome in men only (Q4 vs. Q1, 6.15 (3.71 - 10.21) and 2.66 (1.39 - 5.11), p ≤ 0.001 for models 2 and 3, respectively); a significantly increased odds ratio was only seen in model 2 for women (Table 4).

Table 4 aOdds ratio of metabolic syndromes with leptin levels by sex-specific quartiles.

The relationship between leptin levels and metabolic syndrome was further explored using ROC analysis to determine the predictive value of leptin levels for metabolic syndrome in men and women (Figure 2). As leptin levels increased, the incidence of metabolic syndrome also significantly increased in both men (0.676 [SE = 0.022]) and women (0.627 [SE = 0.035]); Figure 2a-1 and 2b-1, respectively). The predictive value of leptin levels for metabolic syndrome was not diminished upon adjusting for age (Figure 2a-2 and 2b-2), age and tobacco usage (Figure 2a-3 and 2b-3), and age, tobacco usage, and BMI (Figure 2a-4 and 2b-4) in either sex.

Figure 2
figure 2

Receiver Operating Curve (ROC) analyses for leptin levels as a predictor of metabolic syndrome. ROC analysis was undertaken in (a) men, and (b) women. a-1 and b-1, Leptin vs. Metabolic syndrome without adjustment. a-2 and b-2, age-adjusted. a-3 and b-3, age and tobacco usage-adjusted. a-4 and b-4, age, tobacco usage, and BMI-adjusted. The area under the ROC curves were 0.676 (SE = 0.022), 0.907 (SE = 0.012), 0.906 (SE = 0.012), and 0.900 (SE = 0.013) in men and 0.627 (SE = 0.035), 0.729 (SE = 0.035), 0.735 (SE = 0.035), and 0.714 (SE = 0.035) in women.

Discussion

In the present study, serum leptin levels were associated with metabolic syndrome as well as cardiovascular risk in an adult Taiwanese population. Specifically, participants with higher leptin levels had increased metabolic risk factors as compared to those with lower leptin levels. Correlation between leptin levels and metabolic syndrome was observed in both male and female participants. Moreover, serum leptin levels were predicative of metabolic syndrome in both sexes.

Although few, population studies describing the relationship between leptin levels and metabolic syndrome have been reported [7–9]. For example, in obese and nonobese Caucasian children, leptin levels were associated with metabolic syndrome [8]. In the Cyprus Metabolism Prospective Cohort Study, leptin as well as its soluble receptor was not only associated with baseline adiposity and metabolic risk factors, but also predicted adiposity, metabolic syndrome, and glucose levels in eighteen-year-old men [22]. Furthermore, in the Framingham Third Generation Cohort, leptin concentrations were associated with increased odds of metabolic syndrome [23]. Importantly, reductions in leptin levels in obese children (mean age: 14.1 y) predicted short- and long-term reductions in body fat and improved lipid levels and insulin sensitivity, suggesting that children retain leptin sensitivity [24]. Reducing daily caloric intake by 500 kilocalories resulted in a 5-10% decrease in body weight, decreased BMI, and a 25% fall in leptin plasma concentrations [25].

The present study is one of the few studies to analyze the relationship between leptin levels and metabolic syndrome in an Asian population. In nondiabetic Taiwanese adolescents, plasma leptin levels were positively correlated to BMI, waist circumference, waist-to-hip ratio, body fat mass, body fat mass percentage, and triglycerides [7]. Furthermore, serum leptin was associated with metabolic syndrome in obese and nonobese [26] as well as diabetic [27] Korean populations. In addition, in a 3-year follow-up study of Japanese children ages 9-10 years, leptin levels increased in those subjects whose BMI increased during the follow-up period [28].

In the present study, increased odds of metabolic syndrome with increasing leptin levels were observed in both sexes upon adjusting for age and tobacco usage. However, after further adjustment for BMI, increased odds of metabolic syndrome with increased leptin levels were only observed in men. Yun et al. [26] reported that leptin levels were more strongly correlated to risk of metabolic syndrome in men compared to women after controlling for confounding variables. It remains possible that gender differences in body fat distribution or effects of sex steroids may account for this result; another possibility is many Taiwanese women keep their weight on a diet, not performing exercise. That might increase the body fat and the leptin level, but not influents the body weight or BMI. However, further studies are necessary to determine the role in adipose distribution (visceral versus subcutaneous) or reproductive hormones and metabolic syndrome.

Leptin levels were also predictive of metabolic syndrome in both sexes, which is similar to other studies. For example, in adult males participating in the Olivetti Prospective Heart Study, leptin levels were predictor of developing metabolic syndrome at 8-year follow-up [29]. In addition, Franks et al. [30] reported that leptin levels predict worsening of metabolic syndrome over time.

Leptin has a certain degree of influence on appetite, energy consumption, adipose synthesis, and insulin function. Acting as a hormone, leptin has a broad spectrum of biological function; the main effects are the regulation of adipose tissue and body weight [31–34]. First, the inhibition of appetite and the consumption of body energy are achieved through decreased neuropeptide Y (NPY) secretion and hormone secretion of melanocytes, resulting from the combination of leptin and its receptor within the hypothalamus. Second, the increased consumption of energy is achieved by releasing the heat, transformed from the massive storage of energy. The process is due to the increased activities of sympathetic nerves induced by leptin and the activation of the epinephrine receptor on the membranes of the adipose cells. Third, the synthesis of the adipose tissue is directly influenced by leptin, and the resorption can be accelerated. Other researchers suspect that leptin can promote the maturation of adipose cells [35]. Finally, leptin may influence other hormones; insulin can accelerate the secretion of leptin and, inversely, leptin has negative feedback on the synthesis and secretion of insulin [14, 15, 36–38].

Because leptin influences appetite, energy consumption, adipose synthesis, and insulin function, investigators have explored the use of recombinant leptin as a treatment for obesity. For example, in two severely obese children, a genetic mutation in the leptin coding region was observed [39]. Improvements in fasting serum glucose, insulin levels and glycosylated hemoglobin were observed upon recombinant methionyl human leptin therapy [39]. In addition, leptin therapy corrected the excess appetite and promoted weight loss and puberty initiation in one of the children [40]. However, the single-leptin gene mutation only explains rare cases of human obesity; only 5% of obese patients lack leptin. Most patients are genetically stable and without the single-gene mutation [41]. Despite the lack of leptin mutations, leptin mRNA expression level in the adipose tissue and the serum leptin levels have been positively associated with the degree of obesity [42], suggesting that leptin resistance might be one of the causes for human obesity. However, use of recombinant leptin for obesity has been relatively ineffective.

Obese individuals often have hyperleptinemia, suggesting the presence of leptin resistance which is characterized by the persistence of overweight despite high leptin concentrations. In leptin resistance, the higher leptin concentrations muted the responses to decrease weight [43]. It remains possible that the individuals with upper quartile leptin levels had leptin resistance; however, further studies are necessary to determine if these individuals were leptin resistant and if so, the mechanism by which the leptin resistance manifests (e.g., the presence of leptin neutralizing antibodies or antagonists [44], decreased leptin transport across the blood-brain barrier [45], defective leptin signaling [46], etc.).

This study has some limitations that warrant discussion. Firstly, the retrospective nature of the study prevents determining the direction of causality for the relationship between leptin and metabolic syndrome. Secondly, leptin level is selective item of routine physical examination, usually was chosen by subjects who are aware of overweight or hyperlipidemia. So the prevalence of metabolic syndrome was a litter higher than other studies. Furthermore, because the study population consisted of only Taiwanese adults, the findings may not carry over to other racial or ethnic groups.

In conclusion, serum leptin levels are correlated with CVD risk and metabolic syndrome in Taiwanese adults. Serum leptin levels could also predict metabolic syndrome; therefore, analysis of leptin as part of routine physical examinations may prove beneficial in the early diagnosis of metabolic syndrome.

Abbreviations

ATP III:

Adult Treatment Panel

BMI:

Body mass index

CVD:

Cardiovascular diseases

FBG:

Fasting blood glucose

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

OR:

Odds ratio

ROC:

Received operating curve

NPY:

Neuropeptide Y

Q:

Quartile

TG:

Triglyceride

References

  1. Eckle RH, Grundy SM, Zimmet PZ: The metabolism syndrome. Lancet. 2005, 365 (9468): 1415-28. 10.1016/S0140-6736(05)66378-7.

    Article  Google Scholar 

  2. Galassi A, Reynolds K, He J: Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med. 2006, 119 (10): 812-9. 10.1016/j.amjmed.2006.02.031.

    Article  CAS  PubMed  Google Scholar 

  3. Ninomiya T, Kubo M, Doi Y, et al: Impact of metabolic syndrome on the development of cardiovascular disease in a general Japanese population: the Hisayama study. Stroke. 2007, 38 (7): 2063-9. 10.1161/STROKEAHA.106.479642.

    Article  CAS  PubMed  Google Scholar 

  4. Sattar N, Gaw A, Scherbakova O, et al: Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003, 108 (4): 414-9. 10.1161/01.CIR.0000080897.52664.94.

    Article  CAS  PubMed  Google Scholar 

  5. Scuteri A, Najjar SS, Morrell CH, et al: The metabolic syndrome in older individuals: Prevalence and prediction of cardiovascular events. Diabetes Care. 2005, 28 (4): 882-7. 10.2337/diacare.28.4.882. The Cardiovascular Health Study

    Article  PubMed  Google Scholar 

  6. Zhang Y, Proenea R, Maffei M, et al: Positional cloning of the mouse obese gene and its human homologue. Nature. 1994, 372 (6505): 425-32. 10.1038/372425a0.

    Article  CAS  PubMed  Google Scholar 

  7. Huang KC, Lin RC, Kormas N, et al: Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents. Int J Obes Relat Metab Disord. 2004, 28 (4): 470-5. 10.1038/sj.ijo.0802531.

    Article  CAS  PubMed  Google Scholar 

  8. Moreno LA, Pineda I, Rodriguez G, et al: Leptin and metabolic syndrome in obese and non-obese children. Horm Metab Res. 2002, 34 (7): 394-9. 10.1055/s-2002-33472.

    Article  CAS  PubMed  Google Scholar 

  9. Hodge AM, Boyko EJ, de Courten M, et al: Leptin and other components of the Metabolic Syndrome in Mauritius--a factor analysis. Int J Obes Relat Metab Disord. 2001, 25 (1): 126-31. 10.1038/sj.ijo.0801522.

    Article  CAS  PubMed  Google Scholar 

  10. Considine RV, Sinha MK, Heiman ML, et al: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996, 334 (5): 292-5. 10.1056/NEJM199602013340503.

    Article  CAS  PubMed  Google Scholar 

  11. Beltowski J: Role of leptin in blood pressure regulation and arterial hypertension. J Hypertens. 2006, 24 (5): 789-801. 10.1097/01.hjh.0000222743.06584.66.

    Article  CAS  PubMed  Google Scholar 

  12. Soderberg S, Zimmet P, Tuomilehto J, et al: Leptin predicts the development of diabetes in Mauritian men, but not women: a population-based study. Int J Obes (Lond). 2007, 31 (7): 1126-33. 10.1038/sj.ijo.0803561.

    Article  CAS  Google Scholar 

  13. Ruhl CE, Everhart JE: Leptin concentrations in the United States: relations with demographic and anthropometric measures. Am J Clin Nutr. 2001, 74 (3): 295-301.

    CAS  PubMed  Google Scholar 

  14. Zimmet P, Hodge A, Nicolson M, et al: Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ. 1996, 313 (7063): 965-9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Widjaja A, Stratton IM, Horn R, et al: UKPDS 20: plasma leptin, obesity, and plasma insulin in type 2 diabetic subjects. J Clin Endocrinol Metab. 1997, 82 (2): 654-7. 10.1210/jc.82.2.654.

    Article  CAS  PubMed  Google Scholar 

  16. Franks PW, Brage S, Luan J, et al: Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obes Res. 2005, 13 (8): 1476-84. 10.1038/oby.2005.178.

    Article  CAS  PubMed  Google Scholar 

  17. Leyva F, Godsland IF, Ghatei M, et al: Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. Arterioscler Thromb Vasc Biol. 1998, 18 (6): 928-33.

    Article  CAS  PubMed  Google Scholar 

  18. Valle M, Gascon F, Martos R, et al: Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children. Int J Obes Relat Metab Disord. 2003, 27 (1): 13-8. 10.1038/sj.ijo.0802154.

    Article  CAS  PubMed  Google Scholar 

  19. Grundy SM, Cleeman JI, Daniels SR, et al: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005, 112 (17): 2735-52. 10.1161/CIRCULATIONAHA.105.169404.

    Article  PubMed  Google Scholar 

  20. Tan CE, Ma S, Wai D, et al: Can we apply the national cholesterol education program adult treatment panel definition of the metabolic syndrome to Asians. Diabetes Care. 2004, 27 (5): 1182-6. 10.2337/diacare.27.5.1182.

    Article  PubMed  Google Scholar 

  21. D'Agostino RB, Vasan RS, Pencina MJ, et al: General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008, 117 (6): 743-53. 10.1161/CIRCULATIONAHA.107.699579.

    Article  PubMed  Google Scholar 

  22. Hamnvik OP, Liu X, Petrou M, et al: Soluble leptin receptor and leptin are associated with baseline adiposity and metabolic risk factors, and predict adiposity, metabolic syndrome, and glucose levels at 2-year follow-up: the Cyprus Metabolism Prospective Cohort Study. Metabolism. 2010

    Google Scholar 

  23. Ingelsson E, Larson MG, Yin X, et al: Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample. J Clin Endocrinol Metab. 2008, 93 (8): 3149-57. 10.1210/jc.2008-0207.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Murer SB, Knöpfli BH, Aeberli I, et al: Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program. Am J Clin Nutr. 2011.

    Google Scholar 

  25. Westerink J, Visseren FL: Pharmacological and non-pharmacological interventions to influence adipose tissue function. Cardiovasc Diabetol. 2011, 10: 13-10.1186/1475-2840-10-13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Yun JE, Kimm H, Jo J, Jee SH: Serum leptin is associated with metabolic syndrome in obese and nonobese Korean populations. Metabolism. 2010, 59 (3): 424-9. 10.1016/j.metabol.2009.08.012.

    Article  CAS  PubMed  Google Scholar 

  27. Kim SK, Kim HJ, Ahn CW, et al: Hyperleptinemia as a robust risk factor of coronary artery disease and metabolic syndrome in type 2 diabetic patients. Endocrine J. 2008, 55 (6): 1085-92. 10.1507/endocrj.K08E-182.

    Article  CAS  Google Scholar 

  28. Nishimura R, Sano H, Matsudaira T, et al: Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study. Cardiovasc Diabetol. 2009, 8: 30-10.1186/1475-2840-8-30.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Galletti F, Barbato A, Versiero M, et al: Circulating leptin levels predict the development of metabolic syndrome in middle-aged men: an 8-year follow-up study. J Hypertens. 2007, 25 (8): 1671-7. 10.1097/HJH.0b013e3281afa09e.

    Article  CAS  PubMed  Google Scholar 

  30. Franks PW, Brage S, Luan J, et al: Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obes Res. 2005, 13 (8): 1476-84. 10.1038/oby.2005.178.

    Article  CAS  PubMed  Google Scholar 

  31. Houseknecht KL, Spurlock ME: Leptin regulation of lip homeostasis: dietary and metabolic implications. Nutrition research reviews. 2003, 16 (1): 83-96. 10.1079/NRR200256.

    Article  CAS  PubMed  Google Scholar 

  32. Caro JF, Sinha MK, Kolaczynski JW, et al: Leptin: the tale of an obesity gene. Diabetes. 1996, 45 (11): 1455-62.

    Article  CAS  PubMed  Google Scholar 

  33. Shek EW, Brands MW, Hall JE: Chronic leptin infusion increases arterial pressure. Hypertension. 1998, 31 (1Pt2): 409-14.

    Article  CAS  PubMed  Google Scholar 

  34. Lord GM, Matarese G, Howard JK, et al: Leptin modulate the T -cell immune response and reverses starvation induced immunosuppression. Nature. 1998, 349 (6696): 897-901.

    Google Scholar 

  35. Myers MG, Cowley MA, Münzberg H: Mechanisms of leptin action and leptin resistance. Annu Rev Physiol. 2008, 70: 537-56. 10.1146/annurev.physiol.70.113006.100707.

    Article  CAS  PubMed  Google Scholar 

  36. Fischer S, Hanefeld M, Haffner SM, et al: Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass. Acta Diabetol. 2002, 39 (3): 105-10. 10.1007/s005920200027.

    Article  CAS  PubMed  Google Scholar 

  37. Segal KR, Landt M, Klein S: Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes. 1996, 45 (7): 988-91. 10.2337/diabetes.45.7.988.

    Article  CAS  PubMed  Google Scholar 

  38. Zimmet PZ, Collins VR, de Courten MP, et al: Is there a relationship between leptin and insulin sensitivity independent of obesity? A population-based study in the Indian Ocean nation of Mauritius. Mauritius NCD Study Group. Int J Obes Relat Metab Disord. 1998, 22 (2): 171-7. 10.1038/sj.ijo.0800559.

    Article  CAS  PubMed  Google Scholar 

  39. Elaine C, Janice RY, Nancy S, et al: Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the rabson mendenhall syndrome. J Clin Endocrinol Metab. 2004, 89 (4): 1548-54. 10.1210/jc.2003-031952.

    Article  Google Scholar 

  40. Farooqi IS, Jebb SA, Langmack G, et al: Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999, 341: 879-84. 10.1056/NEJM199909163411204.

    Article  CAS  PubMed  Google Scholar 

  41. Cara BE, Dorota BP, David SL: Childhood obesity: public health crisis, common sense cure. Lancet. 2002, 360 (8): 473-82.

    Google Scholar 

  42. Considine RV, Sinha MK, Heiman ML, et al: Serum immunoreactive-leptin concentrations in normal weight and obese humans. N Engl J Med. 1996, 334: 292-5. 10.1056/NEJM199602013340503.

    Article  CAS  PubMed  Google Scholar 

  43. El-haschimi K, Pierroz DD, Hileman SM, et al: Two defects contribute to hypothalamic leptin resistance in mice with diet - induced obesity. J Clin Invest. 2000, 105 (12): 18272-321.

    Article  Google Scholar 

  44. Carrpfield LA, Smith FJ, Guisez Y, et al: Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995, 269 (5223): 546-9. 10.1126/science.7624778.

    Article  Google Scholar 

  45. Van Heek M, Compton D, France C, et al: Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest. 1997, 99: 385-90. 10.1172/JCI119171.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. William B, Alan C, Sandra R, et al: Triglycerides induce leptin resistance at the blood - brain barrier. Diabetes. 2004, 53 (5): 1253-60. 10.2337/diabetes.53.5.1253.

    Article  Google Scholar 

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Acknowledgements

We thank the staffs of the Health Examination Centers in the Linko and Chiayi branches of Cheng Gung Memorial Hospital for the assistance of data collection.

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Correspondence to Wen-Cheng Li.

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The authors declare that they have no competing interests.

Authors' contributions

WCL and KYH contributed to Study Design; WCL, KYH, YCC and KHW contributed to Conduct/data collection; ICC and SHW contributed to Data Analysis; WCL and KYH contributed to Manuscript Writing. All the authors have read and approved the final version of the manuscript.

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Li, WC., Hsiao, KY., Chen, IC. et al. Serum leptin is associated with cardiometabolic risk and predicts metabolic syndrome in Taiwanese adults. Cardiovasc Diabetol 10, 36 (2011). https://doi.org/10.1186/1475-2840-10-36

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  • DOI: https://doi.org/10.1186/1475-2840-10-36

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