F.M. Malita

Association of cardiorespiratory fitness with insulin sensitivity in overweight and obese postmenopausal women : a Montreal Ottawa New Emerging Team study.

The purpose of this study was to examine the relation between insulin sensitivity and cardiorespiratory fitness in overweight and obese postmenopausal women. The study population consisted of 127 overweight and obese postmenopausal women (age, 57.7 +/- 4.8 years; body mass index, 32.7 +/- 4.7 kg/m(2)). Subjects were classified by dividing the entire cohort into tertiles (T) based on insulin sensitivity expressed per kilograms of lean body mass (LBM) (T1, <10.9; T2, 10.9-12.9, T3, >12.9 mg/min per kilogram of LBM, respectively). Outcome measures were body composition (dual-energy x-ray absorptiometry), visceral adipose tissue (computed tomography), insulin sensitivity (hyperinsulinemic-euglycemic clamp), cardiorespiratory fitness (indirect calorimetry), lower-body muscle strength (1 maximal repetition), physical activity energy expenditure (doubly labeled water), fasting lipids, and inflammatory profile. We found a significant positive relationship between insulin sensitivity and cardiorespiratory fitness (r = 0.25, P = .005). Moreover, cardiorespiratory fitness was higher in the T3 group compared to the T1 group (36.2 +/- 6.1 vs 33.1 +/- 5.0 mL/kg LBM per minute, respectively; P = .028). However, the difference was no longer significant after controlling for visceral adipose tissue or muscle strength. Finally, cardiorespiratory fitness was an independent predictor of insulin sensitivity. High levels of cardiorespiratory fitness are associated with higher levels of insulin sensitivity in overweight and obese postmenopausal women. Moreover, visceral adipose tissue accumulation or muscle strength may be potential mediators of this relationship.

Association of insulin sensitivity and muscle strength in overweight and obese sedentary postmenopausal women

The objective of this study was to examine the relationship between insulin sensitivity and lower body muscle strength in overweight and obese sedentary postmenopausal women. The design of the study was cross-sectional. The study population consisted of 82 non-diabetic overweight and obese sedentary postmenopausal women (age: 58.2 +/- 5.1 y; body mass index (BMI): 32.4 +/- 4.6 kg.m-2). Subjects were classified by dividing the entire cohort into quartiles based on relative insulin sensitivity expressed per kilograms of lean body mass (LBM) (Q1, < 10.3, vs. Q2, 10.3-12.4, vs. Q3, 12.5-14.0, vs. Q4, >14.0 mg.min-1.kg LBM-1). We measured insulin sensitivity (using the hyperinsulinemic-euglycemic clamp technique), body composition (using dual-energy X-ray absorptiometry), visceral fat and muscle attenuation (using computed tomography), and a lower-body muscle strength index expressed as weight lifted in kilograms per kilogram of LBM (kg.kg LBM-1) (using weight-training equipment). A positive and significant relationship was observed between insulin sensitivity and the muscle strength index (r = 0.37; p < 0.001). Moreover, a moderate but significant correlation was observed between the muscle strength index and muscle attenuation (r = 0.22; p < 0.05). Finally, the muscle strength index was significantly higher in the Q4 group compared with the Q2 and Q1 groups, respectively (3.78 +/- 1.13 vs. 2.99 +/- 0.77 and 2.93 +/- 0.91 kg.kg LBM-1; p < 0.05). Insulin sensitivity is positively associated with lower-body muscle strength in overweight and obese sedentary postmenopausal women.

Surrogate indexes vs. euglycaemic-hyperinsulinemic clamp as an indicator of insulin resistance and cardiovascular risk factors in overweight and obese postmenopausal women

BACKGROUND There is considerable interest in validating the most convenient method to estimate insulin sensitivity in clinical research protocols that could best indicate cardiovascular risk factors. To address this issue we examined the interrelationships of several cardiovascular risk factors with surrogate indexes such as fasting insulin, the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI) and the revised QUICKI vs the euglycaemic-hyperinsulinemic (EH) clamp in a non-diabetic overweight or obese postmenopausal female population. DESIGN Cross-sectional study involving 88 obese postmenopausal women (age: 57.5+/-5.0 yrs; body mass index: 32.52+/-4.4 kg/m2; percent body fat: 46.35+/-4.9%). METHODS Insulin sensitivity was determined by the EH clamp technique as well as by surrogate indexes such as fasting insulin, HOMA, log HOMA, QUICKI and revised QUICKI. Body composition and body fat distribution were measured using dual energy x-ray absorptiometry and computed tomography, respectively. RESULTS Correlations between insulin resistance indexes (fasting insulin, revised QUICKI, QUICKI, log HOMA, HOMA) vs glucose disposal were similar (range of rs=0.40 to 0.49), suggesting that no index was superior to another with respect to its relationship with the EH clamp. Correlations between the insulin resistance indexes with plasma lipids were comparable among all indexes, however, systolic blood pressure, visceral fat and C-reactive protein were moderately superior with index vs the EH clamp. CONCLUSION Surrogate measures of insulin resistance, in particular fasting insulin, are simple tools appropriate for epidemiological studies that can be used as substitutes for the EH clamp to estimate glucose disposal and cardiovascular risk factors in overweight and obese postmenopausal women.

Comparison between several insulin sensitivity indices and metabolic risk factors in overweight and obese postmenopausal women: a MONET study.

BACKGROUND AND AIMS The purpose of this study was to compare the relationship of several insulin sensitivity indices with cardiometabolic risk factors in overweight and obese postmenopausal women. METHODS AND RESULTS This was a cross-sectional study involving 137 overweight and obese postmenopausal women (age: 57.7+/-4.8 yrs; body mass index: 32.4+/-4.6 kg/m(2); body fat: 38.6+/-9.2 kg). Insulin sensitivity was determined by the euglycaemic-hyperinsulinemic (EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived indices (Stumvoll, Matsuda and SI(is)) and fasting surrogate indices (HOMA, QUICKI). Cardiometabolic risk factors included: body composition and visceral fat that were measured using dual energy X-ray absorptiometry and computed tomography, respectively. Peak oxygen consumption, lower body muscle strength (using weight training equipment), physical activity energy expenditure (doubly labeled water), plasma lipids and C-reactive protein were also measured. Correlations of insulin sensitivity indices with metabolic risk factors showed some similarities, however, a wide range of variations were also observed. Furthermore, our results showed that visceral fat was the primary predictor for surrogate and OGTT indices, explaining 15-28% of the variance and the triglycerides/HDL-C ratio was the primary predictor for the EH clamp indices, explaining 15-17% of the variance. CONCLUSION The present study indicates that the different methods of measuring and/or expressing insulin sensitivity display variations for associations with cardiometabolic risk factors. Therefore, interpretations of relationships between insulin sensitivity indices and cardiometabolic risk factors should take into account the method used to estimate and express insulin sensitivity.

Association of acylated ghrelin profiles with chronic inflammatory markers in overweight and obese postmenopausal women: a MONET study

OBJECTIVE Recent reports have suggested that the existence of associations between hormonal dysregulation and chronic upregulation of inflammatory markers, which may cause obesity-related disturbances. Thus, we examined whether acylated ghrelin (AcylG) and total ghrelin (TotG) levels could be associated with the following inflammatory markers: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1). DESIGN Cross-sectional study consisting of 50 overweight and obese postmenopausal women. METHODS AcylG and TotG levels were assessed at 0, 60, 160, 170, and 180 min of the euglycemic/hyperinsulinemic clamp (EHC). We evaluated insulin sensitivity, body composition, and blood lipid profiles as well as fasting concentrations of CRP, TNF-alpha, and sTNF-R1. RESULTS In fasting conditions, sTNF-R1 was negatively correlated with AcylG (r = -0.48, P < 0.001) levels. In addition, AcylG/TotG was associated negatively with sTNF-R1 (r = -0.44, P = 0.002) and positively with TNF-alpha (r = 0.38, P = 0.009) values. During the EHC, TotG (at all time points) and AcylG (at 60 and 160 min) values were significantly decreased from fasting concentrations. AcylG maximal reduction and area under the curve (AUC) values were correlated to sTNF-R1 (r = -0.35, P = 0.02 and r = -0.34, P = 0.02, respectively). Meanwhile, the AcylG/TotG AUC ratio was associated negatively with sTNF-R1 (r = -0.29, P < 0.05) and positively with TNF-alpha (r = 0.36, P = 0.02). Following adjustments for total adiposity, sTNF-R1 remained correlated with fasting and maximal reduction AcylG values. Similarly, AcylG/TotG ratios remained significantly correlated with sTNF-R1 and TNF-alpha. Importantly, 23% of the variation in sTNF-R1 was independently predicted by fasting AcylG. CONCLUSION These results are the first to suggest that both fasting and EHC-induced AcylG profiles are correlated with fasting values of sTNF-R1, a component of the TNF-alpha system. Thus, AcylG may act, at least in part, as one mediator of chronic inflammatory activity in human obesity.

Comparison of insulin sensitivity values using the hyperinsulinemic euglycemic clamp: 2 vs 3 hours.

nsulin sensitivity is one of the major determinants of the progression and development of type 2 diabetes and cardiovascular disease [1]. The hyperinsulinemic euglycemic clamp is considered the “gold standard” in the assessment of insulin sensitivity because it directly measures insulin action on glucose utilization under steady-state conditions [2, 3]. It is performed by infusing insulin at a constant rate to achieve high physiological levels of plasma insulin. In addition, glucose is monitored frequently while 20% dextrose is administered at variable rates to maintain near-constant glycemia (~5 mmol/l). There is no present consensus as to the duration of the clamp that is appropriate for the measurement of insulin sensitivity. Investigators use different lengths and types of clamps depending on the research question [4, 5]. Therefore, given the central importance of insulin sensitivity in several diseases, including type 2 diabetes, obesity, hypertension, dyslipidemia, and cardiovascular disorders, we compared the values of glucose disposal determined at 120 and 180 min and its correlation with several cardiovascular risk factors. We examined results from an on going study in our laboratory in 51 obese postmenopausal women. These women had an average age of 57.4 5.6, fasting glucose of 5.0 0.5 mmol/L, BMI of 33.2 4.8 kg/m and percentage body fat of 46.4 4.9. The mean glucose infusion rate in the last 30 min of insulin infusion (75 mU/m/min~ 2 mU/kg/min) was used to determine the insulin sensitivity index and was then expressed in relative levels (per kg of fat free mass). Results showed that insulin sensitivity at 180 min was 10% higher than at 120 min, whereas glycemia at 180 min was not significantly different from glycemia at 120 min (Tab I). Forty-one out of the 51 subjects (~80%) had higher insulin sensitivity values at 180 min than at 120 min. Insulin sensitivity at 120 min was significantly correlated with insulin sensitivity at 180 min (r = 0.893; P < 0.01), whereas glycemia at 120 min was not related to glycemia at 180 min (r = 0.127; NS). Finally, insulin sensitivity values at 120 and 180 min were significantly correlated with HOMA (r = -0.582 and r = -0.519, respectively) and triglycerides (r = -0.386 and r = -0.401, respectively), however, waist circumference and percentage of body fat were not significantly correlated with insulin sensitivity at min 120 and 180. These results suggest that 2 and 3 hours clamp values are different and cannot be used interchangeably. It is not our intention to convey the notion that a 3 hour clamp is the most accurate duration for the determination of insulin sensitivity, but rather that higher values (10%) are observed at 3 hours than at 2 hours. Researchers should consider the duration of the clamp as a potential variable responsible for the variation in glucose disposal. Standardization for the glucose clamp technique could be essential in the attempt to define threshold values for the metabolic syndrome as a potential cardiovascular risk factor [5]. Until prospective studies are conducted the most pertinent clamp duration will remain unknown.