Fasting insulin at baseline influences the number of cardiometabolic risk factors and R-R interval at 3years in a healthy population: the RISC Study.

AIM: This was a cross-sectional and longitudinal study of factors contributing to the number of cardiometabolic risk factors, common carotid artery intima-media thickness (CCA-IMT) and R-R interval in clinically healthy subjects without diabetes. METHODS: Anthropometric and cardiometabolic parameters were measured in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study cohort at baseline (n=1211) and 3years later (n=974). At baseline, insulin sensitivity was assessed by the euglycaemic clamp technique. The CCA-IMT was echographically measured and the R-R interval was electrocardiographically evaluated at baseline and at the 3-year follow-up. RESULTS: Higher baseline BMI, fasting insulin and tobacco use as well as greater changes in BMI and fasting insulin but lower adiponectin levels, were associated with a greater number of cardiometabolic risk factors at the 3-year follow-up independently of insulin sensitivity (all P<0.02). The CCA-IMT increased with the number of cardiometabolic risk factors (P=0.008), but was not related to fasting insulin, whereas higher fasting insulinaemia and its 3-year changes were significantly associated with a smaller R-R interval (P=0.005 and P=0.002, respectively). These relationships were independent of baseline age, gender, BMI, adiponectin, insulin sensitivity, tobacco use and physical activity. CONCLUSION: In clinically healthy subjects, fasting insulinaemia, adiponectin and lifestyle parameters are related to the presence of one or two cardiometabolic risk factors before criteria for the metabolic syndrome are met. These results underline the importance of fasting insulinaemia as an independent cardiometabolic risk factor at an early stage of disease development in a healthy general population.

[What is the evolution of metabolically normal obesity?]. / Que deviennent tes sujets obèses "métaboliquement" normaux?

A subgroup of obese subjects which could be protected from the cardiometabolic complications of obesity is described in the literature as "metabolically normal obese subjects". However, the lack of a joint definition of metabolic normality makes the available data difficult to interpret and to compare. A recent analysis of more than 1200 subjects in a prospective study showed that 21% of obese metabolically normal subjects at baseline developed the metabolic syndrome after three years. The obese subjects who remained metabolically normal showed, at three years, significantly higher values of cardiometabolic parameters as compared to subjects with normal body weight. In conclusion, the obese subjects even without any metabolic abnormality should benefit of a closer medical monitoring as well as a regular follow-up to avoid further weight gain.

Metabolic normality in overweight and obese subjects. Which parameters? Which risks?

OBJECTIVES: The objective of this study was to define metabolic normality and to investigate the cardiometabolic profile of metabolically normal obese. DESIGN: Cross-sectional study conducted at 21 research centers in Europe. SUBJECTS: Normal body weight (nbw, n=382) and overweight or obese (ow/ob, n=185) subjects free from metabolic syndrome and with normal glucose tolerance, were selected among the Relationship between Insulin Sensitivity and Cardiovascular Disease study participants. MAIN OUTCOME MEASURES: Insulin sensitivity was assessed by the clamp technique. On the basis of quartiles in nbw subjects, the limits of normal insulin sensitivity and of normal fasting insulinemia were established. Subjects with normal insulin sensitivity and fasting insulin were defined as metabolically normal. RESULTS: Among ow/ob subjects, 11% were metabolically normal vs 37% among nbw, P<0.0001. Ow/ob subjects showed increased fasting insulin (P=0.0009), low-density lipoprotein cholesterol (LDL-cholesterol) (P=0.004), systolic (P=0.0007) and diastolic (P=0.001) blood pressure, as compared with nbw. When evaluating the contribution of body mass index (BMI), hyperinsulinemia and insulin resistance, BMI showed an isolated effect on high-density lipoprotein (P=0.007), high-sensitivity C-reactive protein (P<0.0001), systolic (P=0.002) and diastolic (P=0.008) blood pressures. BMI shared its influence with insulinemia on total cholesterol (P=0.04 and 0.003, respectively), LDL-cholesterol (P=0.003 and 0.006, respectively) and triglycerides (P=0.02 and 0.001, respectively). CONCLUSION: In obese subjects, fasting insulin should be taken into account in the definition of metabolic normality. Even when metabolically normal, obese subjects could be at increased risk for cardiometabolic diseases. Increased BMI, alone or with fasting insulin, is the major responsible for the less favorable cardio-metabolic profile.

Open questions about metabolically normal obesity.

Subsets of obese subjects without any cardiometabolic risk factors have been repeatedly described. This raises questions whether obesity 'per se' enhances the risk for cardiovascular or metabolic diseases and whether healthy obese subjects would benefit from a medical treatment. In order to answer these questions, as a first step, an expert consensus should be reached for the definition of metabolic normality. In fact, up to now, different parameters related to the metabolic syndrome and/or to insulin sensitivity have been utilized across studies. Once an agreement is reached, population-based studies should be undertaken to establish the incidence of metabolic normality among obese subjects. Furthermore, many other parameters such as age, sex, race, fat distribution and physical activity should be monitored to obtain results representative of a general population. Longitudinal studies aimed at investigating the evolution of the cardiometabolic profile of healthy obese subjects are also needed. In conclusion, data from the literature strongly suggest that a regular surveillance of the cardiometabolic parameters and a prevention of any further weight gain should be applied to healthy obese individuals, whereas possible benefits of a weight loss treatment are still a matter of debate.

A 2-year multifactor approach of weight loss maintenance.

The overarching problem in the treatment of obesity is the consistency with which weight in treatment is regained. The aim of this study is to follow-up the patient using a multifactor approach (cognitive-behavioral therapies, diet and physical activity counselling, an "on-off" prescription of orlistat) during 4 years in order to assess the efficacy of this specific long-term weight loss maintenance programme. Weight maintenance is defined as a weight change of <2.5% of the study entry body weight. Fifty obese patients having previously lost at least 10% of their weight by any weight loss programme before entering the maintenance multifactor approach were enrolled. Ninety percent of the patients maintained more than 10% weight loss after 2 years. All the physical characteristics remained similar between study entry and 2 years after the weight loss maintenance programme. Waist and hip as well as fat mass did not show any significant differences and the mean fat mass remained stable 2 years later. In addition, all the psychological parameters analysed remained stable and in a normal range. In conclusion, this multifactor approach shows promising interim results at year-2. The multifactor approach with an "on-off" prescription of orlistat seems to be appropriate for the long term weight loss maintenance. But considering the clinical and psychological diversity of the patients, this approach has to be individually adapted for patients presenting eating behavior disorders which need a particular follow-up.

[Can an obese patient be metabolically normal?]. / Un patient obèse peut-il être métaboliquement normal?

Obesity is well recognized as a cardiovascular risk factor and being associated with cardio-metabolic diseases. However, certain authors describe the existence of metabolically benign obesity or not-complicated obesity. By examining various studies, one of the encountered difficulties is the criteria of normality among obese patients and the evaluated metabolic parameters. Even if traditional cardio-metabolic parameters such as the lipid profile, glycemia or blood pressure can be in normal ranges, the subjects in overweight or obesity are different from the subjects of normal body weight in terms of these parameters which are at the limit of normality. The purpose of this article is to summarize the current concepts of metabolic normality in obese subjects. We conclude that the body weight is the most important factor in the development of the cardio-metabolic consequences of obesity.

[Long term weight loss maintenance]. / Maintien de la perte de poids à long terme.

A successful weight loss program leads to a new metabolic and endocrine balance that needs new long term management. Recent researches have shown some predictors as well as some barriers of the long term weight management. Predictors and barriers are linked to the lost weight, to the subject's habits and to the patient's psychosocial sphere. During the four-year follow-up, 78% of patients maintained 10% or more of their initial weight loss. The patients who maintained their weight presented less binge eating disorder, good motivation in diet and physical activity.

Obesity: a complex growing challenge.

The prevalence of overweight and obesity is increasing worldwide. The physiological mechanisms involved in body weight regulation are complex and incompletely understood. Increasing evidence suggests that obesity is a multifactorial disease where many, if not all, organs of the body are involved. The adipose tissue was considered as a simple fat accumulation for a long period of time. However, nowadays it is fascinating to progressively discover its involvement in hormonal, inflammatory or immune system dysregulation. Adipokines and cytokines are involved in control and regulation of appetite and energy balance, glucose and lipid metabolism, neuroendocrine function, reproduction, immunity, and cardiovascular function. The inflammatory background associated with obesity is closely related to insulin resistance. Moreover, the inhibitory effect of endocannabinoids on the expression of adiponectin could be involved in insulin resistance. Gut microbiota related factor may be responsible for the development of diet-induced obesity and diabetes through metabolic endotoxemia which triggers the inflammatory tone. Based on recent research, several physiopathological mechanisms involved in the development of obesity are reviewed.

Fat distribution influences the cardio-metabolic profile in a clinically healthy European population.

BACKGROUND AND AIMS: Waist and hip circumferences are largely influenced by Fat Mass and several other determinants. To evaluate the specific effects of a preferential fat distribution, we corrected the waist and hip circumferences for all their determinants. We then examined the association between fat distribution and several cardio-metabolic parameters in a clinically healthy population. SUBJECTS AND METHODS: In a subgroup of 625 females (F) and 490 males (M) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, we evaluated insulin sensitivity by hyperinsulinaemic euglycaemic clamp and intima-media thickness (IMT) of the common (CCA) and internal (ICA) carotid artery by ultrasound imaging. Waist and hip circumferences were adjusted for age, height, fat and fat-free mass; in males, waist was also adjusted by hip and vice versa. RESULTS: Both F and M with enlarged waist showed significantly increased plasma insulin, C-peptide, total cholesterol, non-high density lipoprotein-cholesterol, low density lipoprotein cholesterol and triglycerides, when compared with subjects with a smaller waist circumference. Males also showed lower glucose uptake and higher heart rate and ICA-IMT. A larger hip in both females and males was linked to a significantly greater inhibition of free fatty acids during the clamp test. CONCLUSION: Adjustment of waist circumference for its determinants permits the detection of early impairment of cardiovascular function and of glucose and lipid metabolism in a clinically healthy population, in particular in normal body weight subjects. Enlarged hip adjusted values are associated with greater insulin sensitivity.

Impact of body fat mass extent on cardiac autonomic alterations in women.

BACKGROUND: Obesity has been associated with significant abnormalities of the cardiac autonomic regulation. However, the precise impact of increasing body weight on cardiac autonomic function and the metabolic and hormonal contributors to these changes are presently unclear. The aim of our study was to explore in subjects with increasing values of body mass index (BMI) the alterations of cardiac autonomic function and to establish the potential role of various metabolic and hormonal contributors to these alterations. MATERIALS AND METHODS: We investigated time and frequency domain heart rate variability (HRV) parameters taken from 24-h Holter recordings, and several anthropometric, metabolic and hormonal parameters (plasma glucose, insulin, triglycerides, free fatty acids, leptin and adiponectin) in 68 normoglycaemic and normotensive women (mean age of 40 +/- 3 years), subdivided according to their BMI into 15 normal body weight (controls), 15 overweight, 18 obese and 20 morbidly obese. RESULTS: Heart rate was increased and HRV was decreased in the morbidly obese group as compared with controls. In overall population, a negative association linked body fat mass (FM) to HRV indices. None of the metabolic and hormonal parameters were significantly related to the HRV indices, after they were adjusted for the body FM. CONCLUSIONS: Morbidly obese, normoglycaemic and normotensive young women have increased HR and low HRV, indicating an abnormal cardiac autonomic function and representing a risk factor for adverse cardiovascular events. A decrease of HRV parameters is associated with a progressive increase of body FM. Other metabolic and hormonal factors, characterising obesity, do not show an independent influence on these HRV alterations.

Persistent correlation of ghrelin plasma levels with body mass index both in stable weight conditions and during gastric-bypass-induced weight loss.

BACKGROUND: Studies done on serial changes in plasma ghrelin levels after gastric bypass (GBP) have yielded contrasting results since decreased, unchanged, or increased levels have been reported in the literature. This study investigates whether or not GBP has an inhibitory effect on fasting ghrelin levels independently of weight loss. METHODS: Fasting ghrelin levels were measured in 115 stable body weight females, classified as normal body weight (NW; body mass index (BMI)<25 kg/m2), overweight (OW; BMI 25-30 kg/m2), and obese subjects, divided in three subgroups with increasing BMI (BMI 30-40 kg/m2; BMI 40-50 kg/m2; BMI>50 kg/m2). RESULTS: Each obese subgroup showed significantly lower ghrelin levels as compared to both NW (p<0.0001) and OW subjects (p<0.05 or 0.005); however, no significant differences were observed within the three obese subgroups. Forty-nine obese patients underwent a GBP. Plasma ghrelin, measured at 3, 6, and 12 months after GBP, significantly increased from the sixth month on (p<0.0001). When patients were classified, at each postoperative time point, according to their actual BMI, ghrelin was significantly (p=0.0002) related to postoperative BMI and not significantly different from ghrelin measured in stable body weight conditions. CONCLUSIONS: Fasting ghrelin displays an inversely significant correlation with BMI in both stable body weight conditions and after GBP. No evidence was found that GBP had an effect on fasting ghrelin levels, independent of weight loss.

Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene (PGC1A) during weight loss is related to insulin sensitivity but not to energy expenditure.

AIMS/HYPOTHESIS: We investigated whether skeletal muscle peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1A; also known as PPARGC1A) and its target mitofusin-2 (MFN2), as well as carnitine palmitoyltransferase-1 (CPT1; also known as carnitine palmitoyltransferase 1A [liver] [CPT1A]) and uncoupling protein (UCP)3, are involved in the improvement of insulin resistance and/or in the modification of energy expenditure during surgically induced massive weight loss. MATERIALS AND METHODS: Seventeen morbidly obese women (mean BMI: 45.9 +/- 4 kg/m(2)) were investigated before, and 3 and 12 months after, Roux-en-Y gastric bypass (RYGB). We evaluated insulin sensitivity by the euglycaemic-hyperinsulinaemic clamp, energy expenditure and substrate oxidation by indirect calorimetry, and muscle mRNA expression by PCR. RESULTS: Post-operatively, PGC1A was enhanced at 3 (p = 0.02) and 12 months (p = 0.03) as was MFN2 (p = 0.008 and p = 0.03 at 3 and 12 months respectively), whereas UCP3 was reduced (p = 0.03) at 12 months. CPT1 did not change. The expression of PGC1A and MFN2 were strongly (p < 0.0001) related. Insulin sensitivity, which increased after surgery (p = 0.002 at 3, p = 0.003 at 12 months), was significantly related to PGC1A and MFN2, but only MFN2 showed an independent influence in a multiple regression analysis. Energy expenditure was reduced at 3 months post-operatively (p = 0.001 vs before RYGB), remaining unchanged thereafter until 12 months. CPT1 and UCP3 were not significantly related to the modifications of energy expenditure or of lipid oxidation rate. CONCLUSIONS/INTERPRETATION: Weight loss upregulates PGC1A, which in turn stimulates MFN2 expression. MFN2 expression significantly and independently contributes to the improvement of insulin sensitivity. UCP3 and CPT1 do not seem to influence energy expenditure after RYGB.

The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass.

AIMS/HYPOTHESIS: The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass. METHODS: A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic-hyperinsulinaemic clamp, during which a continuous recording of the ECG was performed. The effect of insulin on cardiac autonomic balance was evaluated by performing power spectral analysis of heart rate variability. The low-to-high frequency ratio was calculated before and during the clamp and its modifications were expressed as % delta low-to-high frequency ratio (%Delta L: H). RESULTS: Preoperative %Delta L: H showed a significant (p=0.0009, r2=0.43), positive relationship to the reduction of body weight, measured 1 year after surgery and expressed as % excess weight loss (% EWL). Preoperative BMI was also significantly (p=0.0009, r2=0.43) negatively related to the 12-month % EWL. In a multiple regression analysis, %Delta L: H remained a significant (p=0.003), independent predictor of body weight loss, even when preoperative BMI or age, % fat mass, insulinaemia and glucose disposal were taken into account. CONCLUSIONS/INTERPRETATION: The best correction of excess body weight was achieved by those obese subjects who had a preserved capacity to shift their cardiac autonomic balance towards a sympathetic prevalence in response to an euglycaemic-hyperinsulinaemic clamp. Further studies are needed to elucidate the mechanisms through which the autonomic nervous system influences weight reduction.

Relationship between sympathetic reactivity and body weight loss in morbidly obese subjects.

OBJECTIVE: To investigate the possible role of peripheral sympathetic activity in gastric bypass-induced body weight loss. SUBJECTS AND METHODS: In 42 morbidly obese patients (sex: 36 f/6 m; BMI: 46.0+/-0.7 kg/m(2)) undergoing a gastric bypass, the skin vasoconstrictor reflex in answer to a deep inspiration was measured by laser Doppler fluximetry. The extent of vasoconstriction, measured at the second finger of the left hand, was expressed as percent reduction of the basal blood flux (% vasoconstriction). Insulin sensitivity was assessed before surgery in a subset of patients (n=11), by the method of euglycemic, hyperinsulinemic clamp. Body weight and composition were evaluated before, and 3, 6 and 12 months after surgery. At the same time points, energy intake (kJ/day) was evaluated by means of both food record diary and alimentary anamnesis. RESULTS: The % vasoconstriction, which was significantly (P=0.01) greater in normoglycemic subjects than in diabetic ones, was also significantly (P=0.03) related to the extent of insulin sensitivity measured during the euglycemic clamp. The % vasoconstriction showed a significant (P>0.0001), positive correlation with weight reduction obtained between the 6th and 12th months following surgery; as a consequence, % vasoconstriction was significantly (P=0.0004) related to the overall body weight loss achieved during the year following the operation. These correlations remained significant in multiple regression analysis with adjustment for age, initial body weight, plasma glucose and insulin (P=0.0007 and 0.006, respectively). The % vasoconstriction was also significantly (P=0.0006), negatively related to energy intake measured 12 months after surgery. CONCLUSIONS: In conditions of stable body weight, the sympathetic nervous system (SNS) reactivity is influenced by the degree of insulin resistance. A high capacity to activate the SNS, measured before surgery, is associated with both a larger gastric bypass-induced weight loss and a lower energy intake, at the phase of weight stabilization.

Relationship between peripheral vascular disease and high plantar pressures in diabetic neuro-ischaemic patients.

BACKGROUND: It has been shown that high foot pressure in diabetic patients plays a crucial role in plantar ulcer development. The purpose of the study is to analyze the relationship between foot arterial pressures and plantar pressures in diabetic patients with both peripheral neuropathy vascular disease. METHODS: We have evaluated the relationship between foot arterial pressures and plantar pressure parameters (Peak Plantar Pressure, Foot-Floor Contact and Plantar Pressure Integral) in eleven diabetic patients with both peripheral neuropathy and peripheral vascular disease. Peripheral neuropathy was defined as a tuning fork score<4/8 measured at the great toe and internal malleolus with a Tuning fork (Rydel-Seiffer 128 Hz), the absence of both patellar and ankle reflexes and with a temperature discrimination more than +5 degrees C (Thermocross). The peripheral vascular disease (PVD) was evaluated by Doppler technique. Peak Plantar Pressure (PPP) and Foot-Floor Contact (FFC) were measured by Force-Sensing Resistive (FSR 174) sensors under the 1st, 3rd and 5th metatarsal heads as well as under the heel and big toe of both feet. The Plantar Pressure Integral (PPI) was defined by the integral of the pressure over the time. RESULTS: We have found significant relationship between plantar pressure parameters (PPP, FFC, and PPI) under the first metatarsal heads and Doppler arterial pressures of both tibial posterior and dorsalis pedis artery. However, there was no relationship between Doppler arterial pressures and plantar pressure parameters (PPP, FFC, PPI) under 3rd and 5th metatarsal heads or under both the heel and the big toe. CONCLUSION: According to our results, the peripheral vascular disease could contribute to the elevation of plantar pressures and to the prolonged duration of foot floor contact at each step in diabetic patients with both peripheral neuropathy and peripheral vascular disease. In such patients, severe ischaemia could lead to an increased risk of foot ulceration and consecutive lower extremity amputation.

Acarbose improves indirectly both insulin resistance and secretion in obese type 2 diabetic patients.

BACKGROUND: Acarbose is an oral antidiabetic mainly acting on postprandial blood glucose, inhibiting alphaglucosidase. Through this mechanism, it could improve the peripheral insulin sensitivity and/or increase the insulin secretion. The aim of the present study is to assess the therapeutic efficacy of Acarbose in obese type 2 diabetic patients on both insulin resistance and insulin secretion. METHODS: 17 obese non insulin-dependent diabetic patients, well controlled with diet alone were randomized into 2 groups: acarbose (2 x 50 mg) or placebo during 16 weeks. A glucagon test allowed to evaluate insulin secretion before and after treatment as well as a triple test (glucose-insulin-somatostatin) with indirect calorimetry allowed to evaluate insulin sensitivity. RESULTS: A significant improvement in post-prandial plasma glucose was detected only in the Acarbose group (8.0 +/- 0.5 mmol/l before vs 6.5 0.5 mmol/l after, p<0.05). Basal C-peptide secretion was similar between groups and remained unchanged after treatment. However, stimulated insulin secretion was significantly increased by 30%, p<0.05, in the Acarbose group while no change was detected in the placebo group. Interestingly, the group receiving Acarbose disclosed a 15% reduction in insulin resistance (15.0 +/- 1.8 mmol/l before vs 12.8 +/- 1.4 mmol/l after). CONCLUSIONS: Our results show that a treatment with Acarbose is efficient even in diabetic patients presenting a good glucose control without any other associated treatment. By decreasing post-prandial blood glucose, acarbose improves both insulin sensitivity and secretion.

Factors influencing energy intake and body weight loss after gastric bypass.

OBJECTIVE: The gastric bypass-induced quantitative and qualitative modifications of energy intake (En In, kcal/day) and their impact on body weight (bw) loss were evaluated. The factors influencing energy intake and body weight loss were also investigated. DESIGN: Longitudinal study. SETTING: University Hospital of Geneva. SUBJECTS: Fifty obese women undergoing a Roux-en-Y gastric bypass. RESULTS: The reduction of EnIn was significantly related to bw loss expressed either in kg or as percentage correction of excess bw (P<0.01 for both), whereas the post-operative modifications of diet composition did not play a role. Age and initial bw significantly influenced bw loss (P<0.0001 and P<0.001, respectively), as shown by multiple regression analysis. Patients were divided into four sub-groups according to their age (under or over 35 y) and initial bw (under or over 120 kg). ANOVA showed that under 35-y-old subjects reduced their EnIn significantly more than their older counterparts having similar bw (P<0.02 and P<0.05); consequently, bw loss, expressed in kg, was significantly (P<0.0001 and P<0.0005) larger in younger patients. Subjects with an initial bw over 120 kg lost significantly (P<0.001 and P<0.02) more weight as compared to patients with a smaller degree of obesity (under 120 kg) and similar age. CONCLUSIONS: Gastric bypass-induced body weight loss is mainly due to the reduction of EnIn, whereas the qualitative modifications of the diet do not play a role. Younger subjects have a greater capacity to reduce EnIn and, therefore, lose more weight. Pre-operative high degree of obesity leads to a larger weight reduction, probably because of a greater energy deficit.

Energy economy hampers body weight loss after gastric bypass.

The impact of energy economy on body weight loss was investigated in 20 obese women, submitted to Roux-en-Y gastric bypass. Resting energy expenditure (REE), substrate oxidation rates, plasma glucose, free fatty acid, and insulin and leptin levels were measured before and 3, 6, and 12 months after surgery. Predicted REE was obtained from linear regression analysis of REE and fat free mass, in a group of 85 women, whose body mass index ranged between 20 and 60 kg/m(2). The deviation from predicted REE, calculated as area under the curve (AUC) over the 12-month period for each patient, was considered as the expression of energy economy. Energy economy AUC was significantly (P: < 0.005) negatively related to the weight lost during 12 months after surgery. Energy intake, calculated from self-reported food consumption, was also expressed as AUC. Energy intake AUC showed a significant (P: < 0.002) positive correlation with weight loss. Lipid oxidation rate, also calculated as AUC, significantly correlated, negatively, with energy economy (P: < 0. 001) and, positively, with energy intake (P: < 0.002). Preoperative leptin values were significantly (P: < 0.01) linked to individual energy economy capacity. In conclusion, after Roux-en-Y gastric bypass, energy economy hampers the weight loss process, probably through a low fat oxidation rate.

Leptin plasma levels as a marker of sparing-energy mechanisms in obese women.

OBJECTIVE: To investigate possible relationships between leptin and energy expenditure (EE), both in the condition of stable body weight and during weight loss. SUBJECTS: Seventy four Caucasian, adult obese women with stable body weight (including 10 obese women studied before and during a body weight-reducing program). MEASUREMENTS: Resting EE (REE) and substrate oxidation rates by indirect calorimetry; plasma leptin concentrations by radioimmunoassay (RIA). RESULTS: In conditions of stable body weight, leptin values showed a significant, negative relationship with REE, as expressed in absolute values (P = 0.030) and as adjusted for the variation in lean body mass (LBM) (P = 0.017). This negative relationship was independent of both LBM and fat mass (FM). Linear regression analysis was used to obtain the equation linking REE and LBM; then both predicted REE and the percent deviation from predicted REE were calculated for each subject. Leptin values were negatively related (P < 0.0001) to the deviation from predicted REE. During active body weight loss, the modifications of both REE (delta REE) and lipid oxidation (delta lipid oxidation) were significantly negatively related to leptin concentrations, which were measured before the dieting period (P < 0.03 for both). CONCLUSION: In obese women, high plasma leptin concentrations are associated with a low rate of REE, when body weight is stable, and with a reduction of REE and lipid oxidation, in response to a hypocaloric diet. This suggests that, in severely obese women, leptin is a marker of sparing energy mechanisms operating in both basal and reducing weight conditions.