Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity.

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

GLP-1: 10-year follow-up after Roux-en-Y gastric bypass.

PURPOSE: Glucagon-like peptide-1 (GLP-1) is a hormone widely studied in the short-term postoperative follow-up of Roux-en-Y gastric bypass due to its elevation and association with improvement of the glucose metabolism, but there are few studies in 10 years after RYGB follow-up with the same patient. METHODS: Twenty morbidity obesity patients were submitted to RYGB; these patients were divided into two groups: normal glucose-tolerant morbidly obese patients (NGT) 11 patients and abnormal glucose metabolism morbidly obese patients (AGM) 9 patients. Oral glucose tolerance test (OGTT) was done during four different periods: T1 (first evaluation), T2 (pre-surgery), T3 (9 months after surgery) and T4 (10 years after surgery). RESULTS: Groups were matched for age and gender, and as NGT and AGM had BMI of 46.31 ± 5.03 kg/m2 and 50.87 ± 10.31 kg/m2. After 10 years of RYGB, they were obesity grade I with BMI for NGT 32.45 ± 4.99 kg/m2 and AGM 34.85 ± 4.46 kg/m2. Plasma glucose levels decreased NGT group at T4 period had a significant reduction at 120 min after OGTT for NGT 55.49 ± 17.15 mg/dL (p˂0.001). Insulin levels changed from T1 to T4 for the NGT group. GLP-1 curves were statistically different between the NGT and AGM groups. The AGM group had a higher mean for GLP-1 secretion at T4 period and at 30 min of OGTT 63.85 ± 37.98 pmol/L when compared to NGT 50.73 ± 24.82 pmol/L with AGM > NGT with p˂0.001. CONCLUSION: Evaluation of the same patient during 4 different periods shows that, even with weight regain, after 10-years of RYGB high levels of GLP-1 remained which can be associated with metabolic improvement especially at the NGT group.

Insulin Sensitivity Is Not Decreased in Adult Patients With Hypopituitarism Without Growth Hormone Replacement.

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, (p = 0.0913) and by the area under the glucose infusion rate curve, (p = 0.0628). These patients showed lower levels of fasting glycemia (p = 0.0128), insulin (p = 0.0007), HOMA-IR (p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass (p = 0.0381) and lower values of percentage of free fat mass (p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fat mass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR.

Influence of weight loss on pulmonary function and levels of adipokines among asthmatic individuals with obesity: One-year follow-up.

BACKGROUND: Individuals with obesity are more likely to develop asthma, but the exact mechanism is still uncertain and several hypotheses have been raised, such as the release of inflammatory mediators secreted by adipose tissue. OBJECTIVE: To assess the effects of weight loss in patients submitted to bariatric surgery on pulmonary and systemic inflammation. METHOD: The study evaluated patients undergoing bariatric surgery (Roux-en-Y gastric bypass) with the diagnosis of asthma, except smokers. The patients were evaluated at the time of entry into a preoperative weight loss group (T1), just before bariatric surgery (T2), six months after surgery (T3), and 12 months after surgery (T4). The following were measured: anthropometric data, dosage of systemic inflammatory markers by means of blood collection, pulmonary inflammatory markers obtained by induced sputum collection, pulmonary function parameters, and asthma activity assessed by a Asthma Control Test (ACT) questionnaire. RESULTS: Nineteen patients participated in the study. There were significant reductions in the systemic levels of interleukin (IL)-8 (p = 0.002), C-reactive protein (CRP) (p = 0.003), leptin (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.007), and significant increase in the systemic levels of IL-6 (p = 0.004) over time and adiponectin in T2 (p = 0.025). In regards to pulmonary inflammation, there were significant reductions in the sputum levels of TNF-α (p < 0.001). There was no significant improvement of the pulmonary function parameters (p > 0.05) and significant improvement in asthma activity scores (p < 0.0001). CONCLUSION: Weight loss was associated with significant changes in the systemic and pulmonary inflammatory profiles of individuals with asthma, leading to a better asthma control as a result of an increase in some anti-inflammatory mediators and a reduction of pro-inflammatory mediators.

Hyperinsulinemic-euglycemic clamp over the first year of use of depot-medroxyprogesterone acetate as a contraceptive.

OBJECTIVE: The literature lacks data on the use of the gold-standard hyperinsulinemic-euglycemic clamp (HEC) technique for the evaluation of insulin resistance (IR) in depot-medroxyprogesterone acetate (DMPA) users. This study assessed carbohydrate metabolism in non-obese users of DMPA using the HEC technique. STUDY DESIGN: A prospective, non-randomized, comparative study conducted at the Family Planning Clinic/Metabolic Unit, University of Campinas, Brazil. Forty-eight women aged 18-39 years underwent HEC: 30 initiating use of DMPA and 18 initiating use of a copper intrauterine device (IUD). Data from 15 women in each group, who completed the follow-up and underwent HEC at12 months, were compared using repeated measures ANOVA. All women were advised to perform aerobic physical exercise for 150 min/week; body composition and total energy intake were evaluated. Main outcome measures were IR defined by M-value <4 mg/kg/min, and blood levels of insulin. Additional outcomes were total cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol, adipokines and free fatty acids. RESULTS: At 12 months, two women in the DMPA group and none in the IUD group had developed IR. The groups were similar in in M-values and in blood levels of insulin, total cholesterol, HDL-cholesterol, LDL-cholesterol, adipokines or free fatty acids. Triglyceride levels increased in the DMPA group when compared to the IUD group, 80.0 (SD 47.8) versus 61.8 (SD 35.8) mg/dL respectively, (p=.033); and increased the total daily energy intake, 1828.3 (SD 518.9) versus 1300.8 (SD 403.4) kilocalories/24hs, respectively in the same groups, (p=.041). All the DMPA users showing higher insulin sensitivity at 12 months reported performing physical activity regularly. CONCLUSIONS: Changes occurred in carbohydrate metabolism in DMPA users in the first year of use of the method. It is possible that the regular aerobic exercise may exert a beneficial and protective effect against the factors that trigger these changes. IMPLICATIONS STATEMENT: Carbohydrate metabolism undergoes adverse changes in few young non-obese women during the first year of DMPA use and regular aerobic exercise may exert a beneficial and protective effect against these changes.

Massage therapy in cortisol circadian rhythm, pain intensity, perceived stress index and quality of life of fibromyalgia syndrome patients.

We investigate the effects of a massage therapy program (MTP) in cortisol concentration (CC), intensity of pain, quality of life and perceived stress index of fibromyalgia patients. Volunteers (n = 24, aged 26-55 years) were treated with MT, twice a week for three months. They answered the Fibromyalgia Impact Questionnaire (FIQ), Perceived Stress Questionnaire (PSQ) and McGill Pain Questionnaire (MPQ-Br), and collected saliva to evaluate CC before and after the end of each month. The MT had improvement in quality of life, according to the FIQ results, and promoted reduction in PSQ values after the second (PSQ2-0.62 ± 0.04vsPSQ0-0.71 ± 0.04) and third month (PSQ3-0.64 ± 0.04vsPSQ0-0.71 ± 0.04). The MTP also promoted reduction in pain after the third month (MQP-Br1-44.50 ± 2.15vsMQP-Br4-35.38 ± 3.71). Despite PSQ reduction, the CC were not affected by the program. This pilot suggests that this treatment improved quality of life, reduced perceived stress index and pain in these volunteers.

Assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp: Comparison with the spectral analysis of photoplethysmography.

AIMS: We compare spectral analysis of photoplethysmography (PTG) with insulin resistance measured by the hyperinsulinemic euglycemic clamp (HEC) technique. MATERIAL AND METHOD: A total of 100 nondiabetic subjects, 43 men and 57 women aged 20-63years, 30 lean, 42 overweight and 28 obese were enrolled in the study. These patients underwent an examination with HEC, and an examination with the PTG spectral analysis and calculation of the PTG Total Power (PTG-TP). Receiver-operating characteristic (ROC) curves were constructed to determine the specificity and sensitivity of PTG-TP in the assessment of insulin resistance. RESULTS: There is a moderate correlation between insulin sensitivity (M-value) and PTG-TP (r=- 0.64, p<0.0001). The ROC curves showed that the most relevant cutoff to the whole study group was a PTG-TP>406.2. This cut-off had a sensitivity=95.7%, specificity =84,4% and the area under the ROC curve (AUC)=0.929 for identifying insulin resistance. All AUC ROC curve analysis were significant (p<0.0001). CONCLUSION: The use of the PTG-TP marker measured from the PTG spectral analysis is a useful tool in screening and follow up of IR, especially in large-scale studies.

Binge eating and biochemical markers of appetite in new users of the contraceptive depot medroxyprogesterone acetate.

PURPOSE: Weight gain has been cited by women as one of the main reasons for discontinuation of the contraceptive depot medroxyprogesterone acetate (DMPA). This study aimed to evaluate binge eating and the biochemical markers of appetite in new DMPA users. METHODS: In this prospective non randomized study with adult healthy women, twenty-eight users of DMPA and twenty-five users of a copper intrauterine device (IUD) were paired for age (±1 year) and body mass index (BMI) (±1 kg/m2). We evaluated binge eating using the Binge Eating Scale (BES), the serum levels of neuropeptide Y, leptin and adiponectin, and the BMI at baseline and after 12 months in both groups. For statistical analysis was used ANOVA for to compare the means of the repeated measurements. RESULTS: Mean age was 29.6 and 28.6 years and BMI was 23.9 and 24.5 kg/m2 for the DMPA and IUD groups, respectively. After 12 months, the frequency of the scores of binge eating remained low in both groups. There were no significant differences between the groups at 12 months with respect to BMI, levels of NPY, leptin, adiponectin, and BES scores. CONCLUSIONS: Healthy adult women did not present with central stimulation of appetite or binge eating disorder in their first year after starting use of DMPA. This study reinforces the use of the contraceptive DPMA and the need for guidance related to living a healthy lifestyle for women who attribute the increase of body weight to the use of the method.

Evaluation of patients with head and neck cancer performing standard treatment in relation to body composition, resting metabolic rate, and inflammatory cytokines.

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) usually emerges as a set of signs and symptoms that, either alone or in combination with standard treatment, may lead to malnutrition and weight loss. METHODS: This study evaluated patients with SCCHN before day 0 and 30 days after the end of treatment, with/without tumor resection. Each individual patient underwent analyses of body composition and resting metabolic rate, as well as assessment of serum glucose, insulin, leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1ß, and insulin sensitivity. RESULTS: There was body mass loss during treatment and significant reduction in body fat and free fat mass. Early nutritional monitoring and tumor resection before treatment led to a better nutritional status and reduced inflammatory state. CONCLUSION: Early nutritional monitoring and resection of the tumor by surgery may be important factors for patients to better tolerate treatment.

[Stress among nurses: an examination of salivary cortisol levels on work and day off]. / Estresse em enfermeiros: o uso do cortisol salivar no dia de trabalho e de folga.

The present study evaluates the use of salivary cortisol concentration as a physiological index of the stress level among nurses on their work day and day off and correlates it with the questionnaire used to measure occupational stress in nurses (Inventário de Estresse em Enfermeiros - IEE). This is a comparative, cross-sectional descriptive study in which sociodemographic data, IEE results and salivary cortisol levels were used. Fifty-seven nurses participated in the study (80.7% females and a mean age of 37.1 years old). The IEE average score was 124.5. The average cortisol level was 564.1 ng/m on work day and 354.1 ng/mL on day off. Nurses who had double workdays presented high values of salivary cortisol during the work day (638.1 ng/mL). In conclusion, salivary cortisol identified the nurses' stress level, and differences were found between a work day and day off. On the nurses' day off, their salivary cortisol levels and stress scores were lower.

GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism.

BACKGROUND: It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery. METHODS: Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1+/-2.27 g/m2] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m2) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). RESULTS: Insulin levels improved after surgery. T1 was 131.1+/-17.60 pmol/l in the NGT group and 197.57+/-57.94 pmol/l in the AGM group, and T3 was 72.48+/-3.67 pmol/l in the NGT group and 61.2+/-9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06+/-6.18 pmol/l) when compared to the NGT group (22.69+/-4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2. CONCLUSIONS: Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.

Salivary cortisol levels in Brazilian citizens of distinct socioeconomic and cultural levels.

We have analyzed the perceived stress index, the basal salivary cortisol levels, and the awakening cortisol response (ACR) in 86 volunteers of low (LSES) and high socioeconomic status (HSES). The LSES presented higher perceived stress index and basal salivary cortisol levels, nonaltered ACR, or cortisol diurnal rhythm. We have concluded that the LSES is associated with high perceived stress index and salivary cortisol levels, which could impact negatively in health, and that it is related to the daily life stress experienced by individuals in the LSES group. Because the LSES corresponds to about 30% of the total Brazilian population, this conclusion might have a great impact on public health policies and costs.

Insulin resistance in nondiabetic morbidly obese patients: effect of bariatric surgery.

OBJECTIVE: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. RESEARCH METHODS AND PROCEDURES: Thirteen obese patients (four men/nine women; BMI = 56.3 +/- 2.7 kg/m2) and 13 lean subjects (five men/eight women; BMI = 22.4 +/- 0.5 kg/m2) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after ( approximately 40% relative to initial body weight; Study II) weight loss induced by Roux-en-Y Gastric bypass with silastic ring surgery. RESULTS: The obese patients were insulin resistant (whole-body glucose use = 19.7 +/- 1.5 vs. 51.5 +/- 2.4 micromol/min per kilogram fat-free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 +/- 86 vs. 85 +/- 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole-body glucose use increased (35.5 +/- 3.7 micromol/min per kilogram fat-free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow-up period. Insulin-induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). DISCUSSION: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.