Leptin and other components of the Metabolic Syndrome in Mauritius—a factor analysis

Hodge, Allison; Boyko, Edward J.; Courten, Maximilian Pangratius J De; Zimmet, Paul; Chitson, Pierrot; Tuomilehto, Jaakko; Alberti, K. G. M. M.

doi:10.1038/sj.ijo.0801522

Cited by 67 publications

(76 citation statements)

References 33 publications

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“…Within factor models, leptin has a pathogenic role in the development of insulin resistance [1,2,3,4,5]. Usually BMI and serum concentrations of leptin and insulin form a distinct factor, as do lipid concentrations and blood pressure.…”

Section: Discussionmentioning

confidence: 99%

“…11, 48129 Münster, Germany, E-mail: nieschl@uni-muenster.de Abbreviations: Ar, Adrogen Receptor; BFM, body fat mass; CAG, cytosin-adenin-guanin; CAGr, CAG repeats; FFM, fat free mass; HDL, high density lipoprotein; SHBG, sex hormone binding globuline; TBW, total body water; WHR, waist-to-hip ratio. Diabetologia (2003) 46:31-39 DOI 10.1007 The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men The term "metabolic syndrome" describes a pre-diabetic and pro-atherogenic state which is characterized by overweight, impaired glucose tolerance, hyperinsulinaemia, arterial hypertension, low concentrations of high density lipoprotein (HDL) cholesterol, hypertriglyceridaemia and disturbed haemostasis [1,2,3,4,5,6]. Several cross-sectional population studies found correlations between serum concentrations of testosterone and these cardiovascular risk factors, which, however, were opposite in men and women and which are profoundly influenced by mutual interrelationships between testosterone, adipose tissue and insulin action.…”

Section: Introductionmentioning

confidence: 99%

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The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

Zitzmann¹,

Gromoll²,

et al. 2003

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Aims/hypothesis. The relationship of androgens to the metabolic syndrome has not been resolved. The polymorphic number of CAG repeats within the androgen receptor gene is inversely associated with the transcriptional activity of target genes.This polymorphism might thus influence testosterone effects on body fat content and serum concentrations of leptin and insulin. The direct and indirect role of androgens within the metabolic syndrome should become clearer if this genetically determined effector is taken into account. Methods. The hypothesis was investigated in a crosssectional study involving 106 healthy 20-50 year old males. Results. Multiple regression models showed a positive independent correlation of the CAG repeat number with body fat content, leptin and insulin (partial r=0.39, 0.36 and 0.28, p<0.001, p<0.001 and p=0.006, respectively). Factor analysis yielded a five-dimensional model: two dimensions were influenced by the androgen receptor polymorphism, namely "body composition" which consisted of leptin, body fat mass, insulin, the number of CAG repeats (positive loadings) and physical activity (negative loading), and "lipid profile" which comprised low density lipoprotein cholesterol, cigarette smoking, triglycerides (positive loadings) as well as high density lipoprotein cholesterol and number of CAG repeats (negative loadings). Conclusions/interpretation. A low number of CAG repeats were independently associated with protective parameters (low body fat mass and plasma insulin) as well as with adverse parameters (low high density lipoprotein cholesterol concentrations). This suggests that the pivotal role of this polymorphism in modulating androgen effects on cardiovascular risk factors is of a complex nature and implies that its clinical impact, similar to that of androgens, is dependent on exogenous cofactors. [Diabetologia (2003) 46:31-39] Keywords Testosterone, body fat, leptin, insulin, androgen receptor, CAG repeat polymorphism. Corresponding author: E. Nieschlag, Institute of Reproductive Medicine of the University, Domagkstr. 11, 48129 Münster, Germany, E-mail: nieschl@uni-muenster.de Abbreviations: Ar, Adrogen Receptor; BFM, body fat mass; CAG, cytosin-adenin-guanin; CAGr, CAG repeats; FFM, fat free mass; HDL, high density lipoprotein; SHBG, sex hormone binding globuline; TBW, total body water; WHR, waist-to-hip ratio. Diabetologia (2003) 46:31-39 DOI 10.1007 The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men The term "metabolic syndrome" describes a pre-diabetic and pro-atherogenic state which is characterized by overweight, impaired glucose tolerance, hyperinsulinaemia, arterial hypertension, low concentrations of high density lipoprotein (HDL) cholesterol, hypertriglyceridaemia and disturbed haemostasis [1,2,3,4,5,6]. Several cross-sectional population studies found correlations between serum concentrations of testosterone and these cardiovascular risk factors, which, however, were opposi...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

Zitzmann¹,

Gromoll²,

et al. 2003

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“…Despite the subjective nature of factor analysis and differences as to which variables are included, results of these studies have shown some consistency. Many of them, like the present study, have identified a four-factor solution with factors representing obesity, insulin-glucose metabolism, lipid metabolism, and blood pressure, with some minor variation in composition of individual factors (7)(8)(9)(10)(11)(12). Others have identified a three-factor solution that combines some of these entities; commonly, obesity is combined with lipid and/or insulin variables (13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, factor analysis is well suited for identifying components of the metabolic syndrome, and several analyses have been undertaken for this purpose (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Prospective epidemiological studies of factor "scores" from these analyses can further determine relations between components of the metabolic syndrome and incidence of diabetes.…”

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confidence: 99%

Components of the “Metabolic Syndrome” and Incidence of Type 2 Diabetes

et al. 2002

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The combination of insulin resistance, dyslipidemia, hypertension, and obesity has been described as a "metabolic syndrome" that is a strong determinant of type 2 diabetes. Factor analysis was used to identify components of this syndrome in 1,918 Pima Indians. Prospective analyses were conducted to evaluate associations of identified factors with incidence of diabetes. Factor analysis identified 4 factors that accounted for 79% of the variance in the original 10 variables. Each of these factors reflected a proposed component of the metabolic syndrome: insulinemia, body size, blood pressure, and lipid metabolism. Among 890 originally nondiabetic participants with follow-up data, 144 developed diabetes in a median follow-up of 4.1 years. The insulinemia factor was strongly associated with diabetes incidence (incidence rate ratio [IRR] for a 1-SD difference in factor scores ‫؍‬ 1.81, P < 0.01). The body size and lipids factors also significantly predicted diabetes (IRR 1.52 and 1.37, respectively, P < 0.01 for both), whereas the blood pressure factor did not (IRR 1.11, P ‫؍‬ 0.20). Identification of four unique factors with different associations with incidence of diabetes suggests that the correlations among these variables reflect distinct metabolic processes, about which substantial information may be lost in the attempt to combine them into a single entity. Diabetes 51:3120 -3127, 2002 T ype 2 diabetes and cardiovascular disease have many risk factors in common, and many of these risk factors are highly correlated with one another (1-3). The relationships among these risk factors may be attributable to a small number of physiological phenomena, perhaps even a single phenomenon. The combination of hypertension, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance, and obesity, particularly central obesity, has been termed the "metabolic syndrome." It has been proposed that this syndrome is a powerful determinant of diabetes and cardiovascular disease (3-6). There are few prospective data, however, on the extent to which this syndrome or its constituent components predict incidence of type 2 diabetes.Factor analysis is a mathematical technique by which a large number of correlated variables can be reduced to fewer "factors" that represent distinct attributes that account for a large proportion of the variance in the original variables. Thus, factor analysis is well suited for identifying components of the metabolic syndrome, and several analyses have been undertaken for this purpose (7-26). Prospective epidemiological studies of factor "scores" from these analyses can further determine relations between components of the metabolic syndrome and incidence of diabetes. In the present study, factor analysis is used to identify components of the metabolic syndrome in Pima Indians, an American Indian population with a high prevalence of type 2 diabetes and obesity (27,28), and relations of these components to incidence of diabetes are examined. RESEARCH DESIGN AND METHODSParticipants and measurements...

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“…23 In exploratory analyses of subjects participating in a current protocol requiring fasting venipuncture, leptin levels adjusted for BMI, age and sex were significantly correlated with insulin, suggesting the potential relevance of this trait in insulin signaling pathways.…”

Section: Discussionmentioning

confidence: 94%

Linkage of serum leptin levels in families with sleep apnea

et al. 2004

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OBJECTIVE:To identify regions on the genome linked to plasma leptin levels. DESIGN: Full genome scan with 402 microsatellite markers, spaced B10 cM apart. Data were analyzed using the HasemanElston regression linkage analysis. SUBJECTS: A total of 160 sibling pairs from 59 predominantly African American, obese families recruited to participate in a genetic-epidemiological study of obstructive sleep apnea. MEASUREMENTS: Serum leptin levels adjusted for age, sex, race and body mass index (BMI). RESULTS: Suggestive linkage peaks were observed on chromosomes 2 (P ¼ 0.00170; marker D2S1384), 3 (P ¼ 0.00007; marker D3S3034), 4 (P ¼ 0.00020; marker D4S1652) and 21 (P ¼ 0.00053; marker D21s1411). CONCLUSION: The peak on chromosome 3 is near the gene for glycogensynthase kinase 2 beta, an important factor in glucose homeostasis. Linkage was generally stronger after BMI adjustment, suggesting the potential influence of a number of metabolic pathways on leptin levels other than those that directly determine obesity levels. The evidence of linkage for leptin levels is consistent with prior linkage analyses for cholesterol, hypertension and other metabolic phenotypes.

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Leptin and other components of the Metabolic Syndrome in Mauritius—a factor analysis

Cited by 67 publications

References 33 publications

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men

Components of the “Metabolic Syndrome” and Incidence of Type 2 Diabetes

Linkage of serum leptin levels in families with sleep apnea

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