The presence of obesity-related metabolic disturbances varies widely among obese individuals. Accordingly, a unique subset of obese individuals has been described in the medical literature, which seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as a favorable lipid, inflammation, hormonal, liver enzyme and immune profile. However, recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality. Mechanisms that could explain the favorable metabolic profile of MHO individuals are poorly understood. However, preliminary evidence suggests that differences in visceral fat accumulation, birth weight, adipose cell size and gene expression-encoding markers of adipose cell differentiation may favor the development of the MHO phenotype. Despite the uncertainty regarding the exact degree of protection related to the MHO status, identification of underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping us understand factors that predispose, delay or protect obese individuals from metabolic disturbances. Collectively, a greater understanding of the MHO individual has important implications for therapeutic decision making, the characterization of subjects in research protocols and medical education. Keywords: metabolically healthy but obese; insulin sensitivity; body composition; metabolic risk factors; cardiovascular diseases Introduction Obesity has been increasing at a rapid rate over the past decades and has now reached epidemic proportions. Recent data suggest that 65% of US adult are overweight (body mass index425 kg m À2) and 30% are obese (body mass index430 kg m À2).1 Obesity is associated with numerous metabolic complications such as Type 2 diabetes, dyslipidemia, hypertension, cardiovascular diseases and several forms of cancer. 2 The risk of developing obesity-related complications is proportional to the degree of obesity, and more specifically to android fat accumulation. 3 However, the presence of these obesity-related metabolic disturbances varies widely among obese individuals. 4,5 Accordingly, a unique subset of obese individuals has been described in the medical literature that seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. 6-12 These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display favorable metabolic profiles characterized by high levels of insulin sensitivity, no hypertension, as well as favorable lipid, inflammation, hormonal, liver enzyme and immune profiles 7,9,[13][14][15] ( Figure 1). This phenomenon has also been observed in adolescents. 16 Despite a clinical awareness of the MHO individu...

IntroductIonObesity is widely recognized as an important risk factor for the development of metabolic complications such as insulin resistance, hypertension, and dyslipidemia, which may increase the risk of cardiovascular diseases and type 2 diabetes (1-3). However, the presence of these obesity-related metabolic disturbances varies widely among obese individuals (4-8). Accordingly, a unique subset of obese individuals has been described in the medical literature that appears to be protected or more resistant to the development of metabolic abnormalities associated with obesity (9-11). These individuals, now known as "metabolically healthy but obese" (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as normal lipid, inflammation, hormonal and immune profiles (12-16). Moreover, a recent longitudinal study reported that the protective metabolic profile observed in MHO individuals was associated with lower incidences of type 2 diabetes and cardiovascular diseases (17). Furthermore, evidence suggests that MHO individuals may account for as much as 30-40% of the obese population (4,5,10,18,19 The purpose of this study was to compare different methods to identify metabolically healthy but obese (MHO) individuals in a cohort of obese postmenopausal women. We examined the anthropometric and metabolic characteristics of 113 obese (age: 57.3 ± 4.8 years; BMI: 34.2 ± 2.7 kg/m 2 ), sedentary postmenopausal women. The following methods were used to identify MHO subjects: the hyperinsulinemic-euglycemic clamp (MHO: upper quartile of glucose disposal rates); the Matsuda index (MHO: upper quartile of the Matsuda index); the homeostasis model assessment (HOMA) index (MHO: lower quartile of the HOMA index); having 0-1 cardiometabolic abnormalities (systolic/diastolic blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, glucose ≥5.6 mmol/l, HOMA >5.13, high-sensitive C-reactive protein (hsCRP) >0.1 mg/l, high-density lipoprotein-cholesterol (HDL-C) <1.3 mmol/l); and meeting four out of five metabolic factors (HOMA ≤2.7, TG ≤1.7 mmol/l, HDL-C ≥1.3 mmol/l, low-density lipoproteincholesterol ≤2.6 mmol/l, hsCRP ≤3.0 mg/l). Thereafter, we measured insulin sensitivity, body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography scan), energy expenditure, plasma lipids, inflammation markers, resting blood pressure, and cardiorespiratory fitness. We found significant differences in body composition (i.e., peripheral fat mass, central lean body mass (LBM)) and metabolic risk factors (i.e., HDL-C, hsCRP) between MHO and at risk individuals using the different methods to identify both groups. In addition, significant differences between MHO subjects using the different methods to identify MHO individuals were observed such as age, TG/HDL, hsCRP, and fasting insulin. However, independently of the methods used, we noted some recurrent characteristics that identify MHO subjects such as TG, a...

Context: Few studies have recently re-examined the efficacy of neurosurgery in prolactinoma patients operated for various indications. Objective: To analyze outcomes of patients with a prolactinoma treated by transsphenoidal surgery, to identify factors associated with remission and relapse, and to evaluate if surgical debulking allows for better hormonal control in patients with preoperative resistance to dopamine agonists (DAs). Patients and methods: This was a retrospective review of patients with a benign prolactinoma followed preoperatively and postoperatively in our department and treated by transsphenoidal surgery (nZ63; 45 women; mean age: 31G14 years). Results: Postoperative remission was obtained in 63% of microprolactinomas, 60% of noninvasive macroprolactinomas, and none of the invasive macroprolactinomas. Better remission rate was independently predicted by lower diagnostic prolactin (PRL) levels and by the lack of abnormal postoperative residual tissue (P!0.05). A recurrence of hyperprolactinemia was observed in 34% of patients after a median follow-up period of 36 (7-164) months. In patients with preoperative DA resistance treated again after surgery, there was a significant reduction in PRL levels postoperatively (26 (6-687) ng/ml) vs preoperatively (70 (22-1514) ng/ml; P!0.01) under a lower DA dose, and about half of the patients had PRL normalization. Conclusions: Recurrence of hyperprolactinemia is observed in one-third of prolactinoma patients after surgical remission and may occur as late as 13 years after surgery. Resistance to DA can be considered as a good surgical indication, as partial tumor resection allows for better hormonal control with a lower dose of DAs.

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