Metabolically Healthy Obesity Is a Misnomer: Components of the Metabolic Syndrome Linearly Increase with BMI as a Function of Age and Gender.

OBJECTIVES: We aimed to examine the relationships between body mass index (BMI) and metabolic syndrome (MS) components as a function of age and gender across weight categories. METHODS: This cross-sectional study included 19,328 subjects who participated in a health-screening program. We analyzed 14,093 apparently healthy subjects with a BMI ≥ 18.5 kg/m2 (ranging from 18.5 to 46 kg/m2). RESULTS: At a BMI of 18.5 kg/m2, 16% of subjects had one or more MS components (MS ≥ 1). The number of MS components increased linearly with BMI. The most prevalent components for MS1-4 were hypertension (in men) and increased waist circumference (in women). Among 6391 non-obese subjects with MS = 0, there was a linear increase in blood pressure, glucose, and triglycerides, as well as a decline in high-density lipoprotein cholesterol, as BMI increased. In 2087 subjects with a BMI ≥ 30 kg/m2, a true normometabolic state (MS = 0) was observed in only 7.5%, declining to less than 1% at a BMI ≥ 36 kg/m2 (ATP criteria). Women were metabolically protected relative to men between the ages of 30 and 50 years. CONCLUSIONS: (A) MS components increase linearly with BMI from the lowest normal BMI and continue to increase with age and BMI; (B) metabolically healthy obesity is rare in subjects with a high BMI and declines with age; (C) hypertension is the most common component in men; and (D) in women, MS components are seen at older ages than in men for the same BMI. Metabolic health declines with age and BMI in nearly all subjects with obesity.

Increment in Dietary Potassium Predicts Weight Loss in the Treatment of the Metabolic Syndrome.

BACKGROUND: In the treatment of obesity/metabolic syndrome, dietary measures traditionally focus on reducing carbohydrate/fat-related caloric intake. The possibility that changes in potassium consumption may be related to the achieved weight loss has not been previously explored. METHODS: Sixty-eight participants, with a mean age of 51.6 ± 11.0 years (F/M-30/38), who fulfilled the ATPIII criteria for the metabolic syndrome (MS) were enrolled into a 1-year intensive multidisciplinary program. Nutritional recommendation consisted of a moderate low calorie/high protein Mediterranean diet. Baseline assessment included clinical and biochemical profiling, and body composition. Nutritional components were registered over 7 days before and at the end of 1 year of treatment. RESULTS: Mean baseline body mass index (BMI) was 35 ± 4 kg/m², which declined by 9.4 ± 0.1% after one year of combined intervention. Linear stepwise regression analysis revealed that 45% of the predicted variance of the % decline in BMI was related to increased consumption of dietary potassium (ß = -0.865) and caproic acid (ß = -0.423) and reduction in the consumption of dietary vitamin B6 (ß = 0.542), calcium (ß = 0.335), total carbohydrates (ß = 0.239) and total caloric intake (ß = 0.238; p < 0.001). Notably, the strongest correlate of the decline in BMI was the increase in dietary potassium intake (ß = -0.865). Subjects whose achieved decrease in BMI was above the average (n = 30) increased potassium intake by 25% as compared to an increase in dietary potassium intake of only 3% by those whose decline in BMI was below the average (n = 36; p < 0.05). The change in dietary potassium was related to the percent increase in dietary protein (r = 0.433; p < 0.001). CONCLUSION: An increase in dietary potassium consumption is a previously unrecognized predictor of the achieved reduction in BMI in a weight-loss-oriented multidisciplinary intervention in obesity/MS. Prospective trials are underway to confirm this post-hoc finding.

Cardiovascular risk factors and arterial rigidity are similar in asymptomatic normocalcemic and hypercalcemic primary hyperparathyroidism.

OBJECTIVE: It is still uncertain whether mild primary hyperparathyroidism (PHPT) carries the same risk for increased cardiovascular (CV) morbidity as the more severe symptomatic form. In recent years, the even more subtle normocalcemic (NC) variant is being increasingly recognized. We sought to compare the prevalence of CV risk factors in patients with NC- and hypercalcemic (HC)-PHPT, and to examine whether they differ on a battery of non-invasive vascular parameters. DESIGN/SUBJECTS/METHODS: A retrospective study of two cohorts of patients with PHPT in a referral center: 32 subjects with NC-PHPT and 81 subjects with HC-PHPT, compared for the presence of clinical and biochemical risk factors, and CV morbidity. Non-invasive parameters of arterial stiffness (augmentation index; pulse wave velocity; and vascular compliance indices, C1 and C2) were extracted from the data of gender- and age-matched subsets of these patients, and were related to those of a group of matched control subjects. RESULTS: Despite a similar prevalence of hypertension (approximately 62%), hyperlipidemia (approximately 30%), and impaired glucose metabolism in both PHPT groups, CV or cerebrovascular disease was more common in the HC-PHPT group (24.7 vs 3.1%, P=0.007). Arterial stiffness parameters did not differ in the three groups, and were unrelated to serum calcium or parathyroid hormone concentration. CONCLUSIONS: NC-PHPT and HC-PHPT subjects exhibit similar high rates of traditional CV risk factors, and have comparable indices of arterial stiffness. The lower clinical CV morbidity observed with NC-PHPT remains unexplained, and requires confirmation. Until then, the CV risk associated with NC-PHPT should not be underestimated.

Idiopathic intracranial hypertension is associated with lower body adiposity.

OBJECTIVE: To characterize the obesity phenotype(s) in patients with idiopathic intracranial hypertension (IIH). DESIGN: Database study. PARTICIPANTS: We studied 44 consecutive patients with IIH, in addition to 184 women attending the obesity clinic of the same medical center and 199 obese women participating in the first Israeli national survey on health and nutrition conducted in 1999 and 2000. METHODS: Anthropometric parameters were compared with those of 2 control groups of the same age range. MAIN OUTCOME MEASURES: Weight, height, and waist and hip circumference were measured. RESULTS: Forty subjects, comprising 91.0% of this cohort, were either overweight (body mass index, 25.0-29.9 kg/m(2)) or obese (body mass index > or = 30 kg/m2). Mean waist circumference was 95.3 cm for IIH, 99.8 cm for the national survey, and 114.5 cm for the obesity clinic cohort (P<0.001), whereas hip circumference was 121 cm for IIH, 118.4 cm for the national survey, and 125.8 cm (P = not significant) for the obesity clinic cohorts. Waist-to-hip ratio, a descriptive measure of body fat distribution approximately reflecting upper to lower body fat ratio, was 0.79 in the patients with IIH, 0.84 in the national survey group, and 0.91 in the obesity clinic cohort (P<0.001; all comparisons were adjusted for age and body mass index). CONCLUSIONS: In IIH, fat tends to preferentially accumulate in the lower body relative to other obese women of the same range. Whereas most complications of obesity, such as hypertension, diabetes, dyslipidemia, and the metabolic syndrome, are linked to upper body adiposity, IIH may represent a unique condition potentially induced by nonvisceral fat-related mechanisms. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men.

OBJECTIVE: To assess arterial stiffness in a cohort of hypogonadal males and to investigate the effect of testosterone replacement therapy on arterial properties in this specific group. DESIGN: Eighteen male patients with untreated acquired hypogonadism due to either adult-onset idiopathic hypogonadotropic hypogonadism (n=9) or pituitary tumor (n=9) and 12 age-, sex, and weight-matched eugonadal healthy controls were recruited for the study. Arterial properties, plasma glucose, lipid profile, total, and bioavailable testosterone (BT) levels were measured in fasting state. In the hypogonadal subjects, the effect of transdermal testosterone replacement therapy on arterial properties was studied by repeat noninvasive measurements at baseline, as well as 48 h and 90 days following the initiation of treatment. METHODS: Arterial stiffness was evaluated using applanation tonometry and pulse wave analysis by three different standard devices that assess various measures of arterial stiffness: pulse wave velocity (PWV), augmentation index (AIx), and large/small artery compliance (C1 and C2). RESULTS: Age- and blood pressure-adjusted PWV was significantly higher in hypogonadal men (8.90+/-2.29 vs 6.78+/-1.16 m/s in the control group; P=0.025). Testosterone therapy increased BT level from 2.01+/-1.04 to 4.68+/-2.43 and 7.83+/-6.2 nmol/l after 48 h and 3 months respectively (P=0.001). PWV decreased from 8.9+/-2.29 to 8.24+/-1.39 and 8.25+/-1.82 m/s after 48 h and 3 months of treatment respectively (P=0.03). CONCLUSIONS: Male hypogonadism is associated with increased PWV, which is rapidly but incompletely ameliorated by normalization of circulating testosterone levels.

Platelet counts and platelet activation markers in obese subjects.

OBJECTIVE: In this work we studied the correlation between platelet count, platelet activation, and systemic inflammation in overweight, obese, and morbidly obese individuals. METHODS AND SUBJECTS: A total of 6319 individuals participated in the study. Complete blood counts, high sensitivity C-reactive protein (hs-CRP) serum levels, and body mass index (BMI) were measured during routine checkups. Platelet activation markers were studied among 30 obese (BMI = 41 +/- 8 kg/m(2)) and 35 nonobese (BMI = 24 +/- 3 kg/m(2)) individuals. Platelet activation status was evaluated by flow cytometry using specific antibodies against the activated platelet membrane glycoprotein IIb/IIIa, p-selectin (CD-62 p), and binding of Annexin-V to platelet anionic phospholipids. RESULTS: Overweight, obese, and morbidly obese females had significantly elevated platelet counts ( P < .0001) compared with normal-weight females. No significant elevation of platelet counts was observed in the male subgroups. A significant age adjusted correlation between BMI and platelet counts ( P < .0001) was found among females. This correlation was attenuated (P = .001) after adjustment for hs-CRP concentrations. The flow cytometry analysis of platelets showed no significant differences in activation marker expression between nonobese and obese individuals. DISCUSSION: Obesity may be associated with elevated platelet counts in females with chronic inflammation. Obesity is not associated with increased platelet activation.

Attempted forced titration of blood pressure to <130/85 mm Hg in type 2 diabetic hypertensive patients in clinical practice: the diastolic cost.

The authors assessed the practicality and results of forced titrating of blood pressure to <130/85 mm Hg based on guidelines of the sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in the setting of a clinical practice in 257 diabetic, hypertensive patients. Goal diastolic pressure was achieved in 90% of the patients, but goal systolic pressure was achieved in only 33%. In 57% of the patients, the attained diastolic pressure was < or =70 mm Hg, and in 20% of the cohort diastolic pressure was reduced to <70 mm Hg (mean, 60+/-1 mm Hg). Patients with final diastolic pressure <70 mm Hg were older, had a higher prevalence of coronary artery disease, and higher initial systolic and pulse pressures compared with patients with final diastolic pressure of 71-85 mm Hg. Thus, attempted lowering of blood pressure to <130/85 mm Hg is associated with excessive lowering of diastolic pressure in a significant number of patients. Whether the benefits of tight systolic control outweigh the risks of excessive diastolic reduction requires further prospective assessment.

The appearance of aggregated erythrocytes in the peripheral blood of individuals with insulin resistance.

BACKGROUND: Insulin resistance is associated with low-grade inflammatory response. The probability that the acute-phase response is associated with enhanced erythrocyte adhesiveness/aggregation was not explored. METHODS: The degree of erythrocyte adhesiveness/aggregation was evaluated by using a simple slide test. The insulin resistance was evaluated by insulin and glucose concentrations after a night of fasting. The inflammatory response was evaluated by variables of acute-phase response. RESULTS: A significant correlation (r = -0.2, p = 0.02) was noted between insulin resistance expressed as the HOMA index and the degree of erythrocyte adhesiveness/aggregation. This was probably due to the concomitant acute-phase response and the presence of increased amounts of inflammation-sensitive proteins that were found to correlate significantly with the degree of erythrocyte adhesiveness/aggregation. In the multiple linear regression analysis, erythrocyte sedimentation rate and fibrinogen concentration but not HOMA index were found to correlate significantly (p < 0.0001 and p = 0.0007 respectively) with the degree of red blood cell adhesiveness/aggregation. CONCLUSIONS: Insulin resistance is associated with an enhanced degree of erythrocyte adhesiveness/aggregation and this is related to the presence of enhanced inflammation-sensitive plasma proteins that are part of the acute-phase response. These findings might have hemorheological consequences and might contribute to the pathophysiology of the insulin-resistance syndrome.

Enhanced erythrocyte adhesiveness/aggregation in obesity corresponds to low-grade inflammation.

OBJECTIVE: Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and to assess phosphatidylserine expression on erythrocyte surface membrane of obese vs. nonobese individuals. RESEARCH METHODS AND PROCEDURES: Erythrocyte adhesiveness/aggregation in the peripheral venous blood was evaluated by using a new biomarker, phosphatidylserine expression was assessed by means of flow cytometry, and markers of inflammation were measured in 65 subjects: 30 obese [body mass index (BMI) = 41 +/- 7.7 kg/m(2)] and 35 nonobese (BMI = 24 +/- 2.7 kg/m(2)) individuals. Pearson correlations and Student's t test were performed. RESULTS: A highly significant difference was noted in the degree of erythrocyte adhesiveness/aggregation and markers of inflammation between the study groups. BMI correlated with erythrocyte adhesiveness/aggregation (r = 0.42, p = 0.001), erythrocyte sedimentation rate (r = 0.42, p = 0.001), high-sensitive C-reactive protein (r = 0.55, p < 10(-4)), fibrinogen (r = 0.37, p = 0.004), and white blood cell count (r = 0.45, p < 10(-4)). The degree of erythrocyte adhesiveness/aggregation correlated with erythrocyte sedimentation rate (r = 0.5, p < 10(-4)), high-sensitive C-reactive protein (r = 0.56, p < 10(-4)), fibrinogen (r = 0.54, p < 10(-4)), and white blood cell count (r = 0.32, p = 0.01). DISCUSSION: Our results suggest that obesity-related erythrocyte adhesiveness/aggregation is probably mediated through increased concentrations of adhesive macromolecules in the circulation and not necessarily through hyperlipidemia or phosphatidylserine exposure on erythrocyte's membrane.