Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women

Escobar‐Morreale, Héctor F.; Villuendas, Gemma; Botella-Carretero, José I.; Sancho, José; Millán, José L. San

doi:10.1007/s00125-003-1090-z

Cited by 130 publications

(100 citation statements)

References 49 publications

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“…Linear regression models, however, revealed that BMI rather than insulin resistance as indicated by HOMA is the dominant parameter determining IL-6 and CRP values in PCOS, which is consistent with a recent report from a cohort of premenopausal women (28). Since the models explain less than 30% of the variability of plasma IL-6 and CRP, additional factors controlling IL-6 and CRP concentrations in PCOS must be assumed, which are, however, distinct from PCOS-associated endocrine factors such as hyperandrogenemia because none of the parameters of hyperandrogenism correlated with IL-6 or CRP.…”

Section: Discussionsupporting

confidence: 90%

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

Möhlig

Spranger

Osterhoff

et al. 2004

European Journal of Endocrinology

158

122

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Objective: The syndrome of polycystic ovaries (PCOS) is a known risk factor for type 2 diabetes. It is not known, however, whether the increase in diabetes risk is related to endocrine abnormalities associated with PCOS such as hyperandrogenemia, or whether it is a consequence of the anthropometric or metabolic alterations frequently observed in PCOS women. Design: Since markers of inflammation are supposed to predict type 2 diabetes, interleukin-6 (IL-6) and C-reactive protein (CRP) in combination with parameters of obesity, insulin resistance and hyperandrogenism were determined in 57 PCOS women and in 20 age-matched healthy controls. In addition, the C-174G IL-6 promoter polymorphism was analyzed as a determinant in influencing IL-6, obesity, and androgen levels in women. Results: Neither CRP nor IL-6 were significantly elevated in lean or obese PCOS women compared with age-matched lean or obese controls. In PCOS patients, variables of body composition (body mass index (BMI), waist to hip ratio, dual-energy X-ray-absorptiometry fat mass) and of insulin resistance were correlated with IL-6 or CRP, while parameters of hyperandogenism were not. Multivariate linear regression analysis revealed that obesity is the dominant force, thus explaining 18% and 24% of the IL-6 or CRP levels, respectively, in PCOS women. No association of IL-6 or BMI to a certain genotype at C-174G could be demonstrated in 50 PCOS patients. The heterozygous GC genotype, however, was associated with lower androstendione levels. Metformin treatment of 9 obese, insulin-resistant PCOS patients over a period of 6 months caused a significant decrease in body weight, body fat mass and total testosterone, but showed no significant decline in IL-6 or CRP concentrations. Conclusions: In PCOS women, plasma levels of IL-6 and CRP were not increased when compared with age-and BMI-matched controls. BMI was, however, the parameter most strongly related to IL-6 and CRP in PCOS; thus PCOS-related endocrine abnormalities do not appear to activate inflammatory parameters thereby enhancing the risk of diabetes. In PCOS, the type 2 diabetes risk may, therefore, be confined to those with obesity and/or metabolic alterations rather than affecting all women suffering from the syndrome.European Journal of Endocrinology 150 525-532

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Section: Discussionsupporting

confidence: 90%

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

Möhlig

Spranger

Osterhoff

et al. 2004

European Journal of Endocrinology

158

122

View full text Add to dashboard Cite

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“…Therefore, it is in good accordance that in the tree restricted to parameters derived from the medical history and clinical examination, BMI was the most important discriminator. Although BMI is well correlated to the degree of insulin resistance in general [47], it is, however, known that insulin resistance is not only observed in obese PCOS women but also occurs in a substantial proportion of lean PCOS patients as reported by us [29] and others [48]. It is therefore of no surprise that the decision tree which used the unrestricted dataset, including more direct parameters and indices of insulin resistance and altered beta cell function, was superior, and did not include BMI.…”

Section: Discussionmentioning

confidence: 84%

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling

et al. 2006

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Aims/hypothesis Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. Materials and methods Consecutive PCOS patients (n=118) with fasting glucose <6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value ≥7.8 mmol/l) from those with NGT. Results According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone: follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. Conclusions/interpretation Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.

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“…[23][24][25] In a recent study of the polycystic ovary syndrome, obesity was reported to be the major determinant in driving the production of markers CRP, IL-6, and tumour necrosis factor. 9 Others found that CRP, in addition to BMI, 26 also correlated with the metabolic syndrome as indicated by insulin resistance, obesity, hypertension, impaired glucose tolerance, low HDL-cholesterol and hypertriglyceridaemia. 26 Similarly, the risk of developing type 2 diabetes in lean and overweight women could be explained by the strong correlation between CRP and fasting hyperinsulinaemia, 27 as CRP correlated independently with insulin sensitivity in healthy non-diabetic subjects.…”

Section: Discussionmentioning

confidence: 99%

“…In a study of CRP, IL-6 and TNF-a in healthy women and women with polycystic ovary syndrome, obesity and not insulin resistance was found to be the major determinant of the inflammatory markers. 9 In contrast, in a study of obese women in which CRP was measured before and after 3 months of reduced energy intake, the relation between CRP concentrations and insulin resistance appeared independent of obesity. 10 The medical treatment of obesity, in particular morbid obesity (BMI Z40 kg/m 2 ), is unsatisfactory and has led to the increased use of surgery worldwide.…”

Section: Introductionmentioning

confidence: 90%

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

et al. 2005

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OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers. DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects. SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m 2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m 2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r ¼ À0.36, P ¼ 0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4 (insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.

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Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women

Cited by 130 publications

References 49 publications

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

The polycystic ovary syndrome per se is not associated with increased chronic inflammation

Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

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