Browsing by Author "Petakov, Milan S. (7003976693)"

Context: Plasma ghrelin concentration is diminished in gastrectomized patients. Acute ghrelin administration reduces insulin secretion, whereas insulin infusion has been shown to decrease ghrelin levels. Whether ghrelin has any effect on glucose utilization in humans is unknown. Objective: Our objective was to reveal the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized patients. Study and Setting: We conducted a double-blind, randomized, placebo-controlled, hospital-based study. Patients: Seven men and three women who all had a previous total gastrectomy and truncal vagotomy entered and completed the study. Intervention: Each individual received infusion of saline alone or saline with ghrelin (5.0 pmol/kg·min) during a 5-h hyperinsulinemic (80 mU/m2·min) euglycemic clamp on 2 separate days. Main Outcome Measures: We assessed glucose disposal rate and concentrations of C-peptide, ghrelin, GH, IGF-I, IGF-binding protein (IGFBP)-3 and -1, cortisol, leptin, and adiponectin. Results: Glucose disposal rate decreased during ghrelin infusion (control study 8.6 ± 0.2 vs. 7.2 ± 0.1 mg/kg·min P < 0.001). In experiments with saline infusion, levels of ghrelin (P < 0.001), C-peptide (P < 0.001), glucagon (P < 0.001), adiponectin (P = 0.005), cortisol (P = 0.012), IGF-I (P < 0.001), IGFBP-3 (P = 0.038), and IGFBP-1 (P = 0.001) fell in response to euglycemic hyperinsulinemia. GH concentration maintained at baseline, whereas leptin significantly rose (P < 0.001). In the ghrelin infusion study, the plateau level of ghrelin concentration (6963.6 ± 212.9 pg/ml) was maintained from 90 min throughout the experiment. GH (P < 0.001) and cortisol (P = 0.04) concentrations rose, whereas C-peptide levels were more suppressed than in the control study (P < 0.001). Other hormones and IGFBPs changed similarly as in the study with saline infusion. Conclusion: It appears that ghrelin might be involved in the negative control of insulin secretion and glucose consumption in gastrectomized patients, at least after acute administration. Copyright © 2006 by The Endocrine Society.

Context: Plasma ghrelin concentration is diminished in gastrectomized patients. Acute ghrelin administration reduces insulin secretion, whereas insulin infusion has been shown to decrease ghrelin levels. Whether ghrelin has any effect on glucose utilization in humans is unknown. Objective: Our objective was to reveal the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized patients. Study and Setting: We conducted a double-blind, randomized, placebo-controlled, hospital-based study. Patients: Seven men and three women who all had a previous total gastrectomy and truncal vagotomy entered and completed the study. Intervention: Each individual received infusion of saline alone or saline with ghrelin (5.0 pmol/kg·min) during a 5-h hyperinsulinemic (80 mU/m2·min) euglycemic clamp on 2 separate days. Main Outcome Measures: We assessed glucose disposal rate and concentrations of C-peptide, ghrelin, GH, IGF-I, IGF-binding protein (IGFBP)-3 and -1, cortisol, leptin, and adiponectin. Results: Glucose disposal rate decreased during ghrelin infusion (control study 8.6 ± 0.2 vs. 7.2 ± 0.1 mg/kg·min P < 0.001). In experiments with saline infusion, levels of ghrelin (P < 0.001), C-peptide (P < 0.001), glucagon (P < 0.001), adiponectin (P = 0.005), cortisol (P = 0.012), IGF-I (P < 0.001), IGFBP-3 (P = 0.038), and IGFBP-1 (P = 0.001) fell in response to euglycemic hyperinsulinemia. GH concentration maintained at baseline, whereas leptin significantly rose (P < 0.001). In the ghrelin infusion study, the plateau level of ghrelin concentration (6963.6 ± 212.9 pg/ml) was maintained from 90 min throughout the experiment. GH (P < 0.001) and cortisol (P = 0.04) concentrations rose, whereas C-peptide levels were more suppressed than in the control study (P < 0.001). Other hormones and IGFBPs changed similarly as in the study with saline infusion. Conclusion: It appears that ghrelin might be involved in the negative control of insulin secretion and glucose consumption in gastrectomized patients, at least after acute administration. Copyright © 2006 by The Endocrine Society.

Objective: Correction of GH and IGF-I levels are associated with improvements in insulin secretion, cardiac performance and body composition in patients with acromegaly, but whether these parallel post-treatment levels of GH-IGF-I axis activity is undefined. We investigate whether various biochemical outcomes after transsphenoidal pituitary surgery (TSS) in these patients are associated with clinically relevant differences in cardiac performance, insulin resistance and body composition. Design: Cross-sectional study of consecutive patients with acromegaly admitted to the hospital between 2001 and 2002. Patients and methods: Forty-one patients after TSS for somatotroph pituitary adenoma and 23 patients with naive acromegaly serving as positive controls were enrolled in the study. Mean daily GH levels (mGH), IGF-I, leptin and lipid levels, glucose, insulin and GH concentrations during oral glucose tolerance test (oGTT) were measured in all study participants. Insulin resistance was measured by homeostatic model index (R HOMA ). Body composition was assessed by dual-energy X-ray absorptiometry. Left ventricular mass index (LVM i ) and cardiac index (C i ) were determined by echocardiography. Results: We found no difference in cardiac indices, insulin resistance, body composition and leptin levels between patients with complete biochemical remission and those with inadequately controlled disease (P > 0.05 for all) after TSS. Cured patients had lower values (mean ± SD) of cardiac index (2.2 ± 0.7 vs. 3.0 ± 1.0 l/min/m 2 ; P = 0.04) compared with naive patients. A similar decrease in LVM i was observed in controlled (108.4 ± 30.0 g/m 2 ; P = 0.015) and inadequately controlled disease (108.8 ± 30.7 g/m 2 ; P = 0.03) in comparison with naive disease (160.3 ± 80.6 g/m 2 ). Insulin resistance and leptin changed in opposite ways. In controlled and inadequately controlled disease, R HOMA index was lower (2.2 ± 1.4; P = 0.001 and 3.1 ± 2.0; P = 0.05 vs. 5.1 ± 3.1) while leptin concentration was higher (14.9 ± 8.7 μg/l, P = 0.004 and 12.8 ± 7.8 μg/l, P = 0.05 vs. 7.4 ± 3.8 μg/l) than in naive disease. In all patients, leptin correlated negatively with cardiac index (r = -0.46; P = 0.001) and IGF-I levels (r = -0.45; P < 0.001). Independent predictors of biochemical remission, based on normal IGF-I levels only, were cardiac [P = 0.04, odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2-0.9] and R HOMA index (P = 0.009, OR 0.6; 95% CI 0.4-0.8). Similar results were obtained if the definition of cure included both normal IGF-I levels and the ability to achieve GH nadir < 1 μg/l during oGTT. Insulin resistance (P = 0.02, OR 0.6; 95% CI 0.4-0.9) and leptin level (P = 0.002, OR 1.3; 95% CI 1.1-1.6) were independent predictors of normalized mGH values. Conclusion: This study shows that cardiac indices, insulin resistance and body composition were not different between patients with complete biochemical remission and those with discordant GH and IGF-I levels. It appears that even incomplete disease control after TSS can result in improvement of these clinical markers. © 2005 Blackwell Publishing Ltd.

Objective: Correction of GH and IGF-I levels are associated with improvements in insulin secretion, cardiac performance and body composition in patients with acromegaly, but whether these parallel post-treatment levels of GH-IGF-I axis activity is undefined. We investigate whether various biochemical outcomes after transsphenoidal pituitary surgery (TSS) in these patients are associated with clinically relevant differences in cardiac performance, insulin resistance and body composition. Design: Cross-sectional study of consecutive patients with acromegaly admitted to the hospital between 2001 and 2002. Patients and methods: Forty-one patients after TSS for somatotroph pituitary adenoma and 23 patients with naive acromegaly serving as positive controls were enrolled in the study. Mean daily GH levels (mGH), IGF-I, leptin and lipid levels, glucose, insulin and GH concentrations during oral glucose tolerance test (oGTT) were measured in all study participants. Insulin resistance was measured by homeostatic model index (R HOMA ). Body composition was assessed by dual-energy X-ray absorptiometry. Left ventricular mass index (LVM i ) and cardiac index (C i ) were determined by echocardiography. Results: We found no difference in cardiac indices, insulin resistance, body composition and leptin levels between patients with complete biochemical remission and those with inadequately controlled disease (P > 0.05 for all) after TSS. Cured patients had lower values (mean ± SD) of cardiac index (2.2 ± 0.7 vs. 3.0 ± 1.0 l/min/m 2 ; P = 0.04) compared with naive patients. A similar decrease in LVM i was observed in controlled (108.4 ± 30.0 g/m 2 ; P = 0.015) and inadequately controlled disease (108.8 ± 30.7 g/m 2 ; P = 0.03) in comparison with naive disease (160.3 ± 80.6 g/m 2 ). Insulin resistance and leptin changed in opposite ways. In controlled and inadequately controlled disease, R HOMA index was lower (2.2 ± 1.4; P = 0.001 and 3.1 ± 2.0; P = 0.05 vs. 5.1 ± 3.1) while leptin concentration was higher (14.9 ± 8.7 μg/l, P = 0.004 and 12.8 ± 7.8 μg/l, P = 0.05 vs. 7.4 ± 3.8 μg/l) than in naive disease. In all patients, leptin correlated negatively with cardiac index (r = -0.46; P = 0.001) and IGF-I levels (r = -0.45; P < 0.001). Independent predictors of biochemical remission, based on normal IGF-I levels only, were cardiac [P = 0.04, odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2-0.9] and R HOMA index (P = 0.009, OR 0.6; 95% CI 0.4-0.8). Similar results were obtained if the definition of cure included both normal IGF-I levels and the ability to achieve GH nadir < 1 μg/l during oGTT. Insulin resistance (P = 0.02, OR 0.6; 95% CI 0.4-0.9) and leptin level (P = 0.002, OR 1.3; 95% CI 1.1-1.6) were independent predictors of normalized mGH values. Conclusion: This study shows that cardiac indices, insulin resistance and body composition were not different between patients with complete biochemical remission and those with discordant GH and IGF-I levels. It appears that even incomplete disease control after TSS can result in improvement of these clinical markers. © 2005 Blackwell Publishing Ltd.

PURPOSE: We sought to determine the prevalence and characteristics of heart failure in patients with newly diagnosed acromegaly. SUBJECTS AND METHODS: We assessed 102 consecutive patients who had acromegaly (44 men; age range, 22 to 71 years) for signs and symptoms of heart failure. We included a control group of 33 nonobese healthy subjects (13 men; age range, 26 to 70 years). Cardiac morphologic parameters, left ventricular mass index, ejection fraction, end-systolic wall stress, and cardiac index were measured by echocardiography. Endocrinological assessment was performed in all participants. RESULTS: Of the 102 patients, 10 (10%) had overt heart failure at the time of diagnosis of acromegaly, 9 of whom were men (P <0.01). Patients with acromegaly and heart failure had an increased mean (± SD) left ventricular end-diastolic diameter (76 ± 11 mm) compared with those without heart failure (53 ± 6 mm, P <0.001) and control subjects (49 ± 5 mm, P <0.001). Patients with heart failure had higher left ventricular mass index (230 ± 56 g/m 2 vs. 118 ± 40 g/m 2 , P <0.001) and end-systolic wall stress (237 ± 79 × 10 3 dyn/cm 2 vs. 111 ± 42 × 10 3 dyn/cm 2 , P <0.001), but lower ejection fraction (42% ± 17% vs. 66% ± 9%, P <0.001), in comparison with patients without heart failure. The mean cardiac index was significantly higher in patients with heart failure (4.3 ± 1.8 L/min-m 2 ) than in those without heart failure (3.5 ± 0.8 L/min-m 2 , P = 0.04) or in control subjects (3.1 ± 0.6 L/min-m 2 , P = 0.002). Two factors were independently associated with heart failure in acromegalic patients: cardiac index (odds ratio [OR] per SD of 1.0 L/min-m 2 = 16; 95% confidence interval [CI]: 1.8 to 135) and ejection fraction (OR per SD of 12% = 0.7; 95% CI: 0.6 to 0.9). CONCLUSION: High output heart failure with a modest decline in ejection fraction is frequently detected at the time of diagnosis of acromegaly. Left ventricular hypertrophy in these patients is characterized by a dilated ventricle and an increased left ventricular mass that is primarily due to the enlarged chamber diameter. © 2002 by Excerpta Medica, Inc.

In a rare Gaucher disease, reduced activity of lysosomal β-glucocerebrosidase incompletely blocks glucosphingolipid catabolism. Accumulation of the unhydrolyzed substrate glucosylceramide within lysosomes results in progressive, multisystem Gaucher disease, classified into three types. Both parkinsonism and peripheral neuropathy are observed in cases of putative non-neuronopathic type 1 disease. In the current study we investigated whether the peripheral neural response in type 1 Gaucher disease patients, with no neural manifestations is conditioned by the influence of sex hormones. The catalytic activity of β-glucocerebrosidase in peripheral blood leukocytes was determined spectrofluorometrically. Direct sequencing of the GBA1 gene was performed. Somatosensory evoked potentials were recorded after electrical stimulation of the median nerve of both arms. Stimuli of 0.2 ms duration at a frequency of 5 Hz were used. Sex hormones were determined by radioimmunoassay using a gamma scintillation counter. Analysis of the somatosensory evoked potentials revealed significant differences in peak latencies on periphery between men and women in both control and type 1 Gaucher disease groups. Analysis by gender showed significant associations between latencies and sex hormones only in female patients: negative correlation between oestradiol concentration and N9 peak latency, and a strong negative correlation of testosterone levels with all peak latencies on the periphery (N9-N13). A relationship between testosterone concentrations and the latencies of potentials evoked on peripheral nerves exists only in females with type 1 Gaucher disease. We point out sexual dimorphism in the development of this entity. © 2019 Milan B.

In a rare Gaucher disease, reduced activity of lysosomal β-glucocerebrosidase incompletely blocks glucosphingolipid catabolism. Accumulation of the unhydrolyzed substrate glucosylceramide within lysosomes results in progressive, multisystem Gaucher disease, classified into three types. Both parkinsonism and peripheral neuropathy are observed in cases of putative non-neuronopathic type 1 disease. In the current study we investigated whether the peripheral neural response in type 1 Gaucher disease patients, with no neural manifestations is conditioned by the influence of sex hormones. The catalytic activity of β-glucocerebrosidase in peripheral blood leukocytes was determined spectrofluorometrically. Direct sequencing of the GBA1 gene was performed. Somatosensory evoked potentials were recorded after electrical stimulation of the median nerve of both arms. Stimuli of 0.2 ms duration at a frequency of 5 Hz were used. Sex hormones were determined by radioimmunoassay using a gamma scintillation counter. Analysis of the somatosensory evoked potentials revealed significant differences in peak latencies on periphery between men and women in both control and type 1 Gaucher disease groups. Analysis by gender showed significant associations between latencies and sex hormones only in female patients: negative correlation between oestradiol concentration and N9 peak latency, and a strong negative correlation of testosterone levels with all peak latencies on the periphery (N9-N13). A relationship between testosterone concentrations and the latencies of potentials evoked on peripheral nerves exists only in females with type 1 Gaucher disease. We point out sexual dimorphism in the development of this entity. © 2019 Milan B.

The role of cortisol in mediating basal metabolic rate (BMR) changes that accompany the adjustment of maternal body weight (BW) and body composition during pregnancy is unknown. We tested whether increase in BMR during pregnancy is explained by variations in cortisol secretion. Longitudinal changes in BW, fat mass (FM), fat-free mass (FFM), BMR, hormonal, and metabolic parameters in 31 parous Caucasian women at gestational weeks 12, 26, and 36 were examined. Individual differences (Δ) between the last and the first measurement occasions for each variable were calculated. By gestational week 36, BW and BMR increased while both FFM/FM and BMR/BW ratio decreased (P < 0.001 for all) suggesting higher proportion of FM accretion. Cortisol, leptin, and insulin-like growth factor-1 (IGF-1) concentration rose, whereas non-placental growth hormone (GH) and thyroid hormones declined (P < 0.001 for all). Insulin resistance changed; basal glucose (P < 0.001) and ghrelin (P < 0.014) declined, whereas insulin (P < 0.001), homeostatic model index (HOMA-IR) (P = 0.041), and free fatty acid (FFA) concentration (P = 0.007) increased. The elevation in BMR showed inverse correlations with ΔBW (r = 0.37, P = 0.047) and Δcortisol (r = -0.53, P = 0.004). Significant portion (51.6%) of the variation in BMR change was explained by increases of cortisol (27.1%), FFA (13.4%), and free triiodothyronine (11.1%). In conclusion, the changes in maternal cortisol concentration are in relationship with changes in BMR and BW, further suggesting that increased cortisol secretion during pregnancy could be linked with the maintenance of maternal BW and body composition. © 2009 Humana Press Inc.

The role of cortisol in mediating basal metabolic rate (BMR) changes that accompany the adjustment of maternal body weight (BW) and body composition during pregnancy is unknown. We tested whether increase in BMR during pregnancy is explained by variations in cortisol secretion. Longitudinal changes in BW, fat mass (FM), fat-free mass (FFM), BMR, hormonal, and metabolic parameters in 31 parous Caucasian women at gestational weeks 12, 26, and 36 were examined. Individual differences (Δ) between the last and the first measurement occasions for each variable were calculated. By gestational week 36, BW and BMR increased while both FFM/FM and BMR/BW ratio decreased (P < 0.001 for all) suggesting higher proportion of FM accretion. Cortisol, leptin, and insulin-like growth factor-1 (IGF-1) concentration rose, whereas non-placental growth hormone (GH) and thyroid hormones declined (P < 0.001 for all). Insulin resistance changed; basal glucose (P < 0.001) and ghrelin (P < 0.014) declined, whereas insulin (P < 0.001), homeostatic model index (HOMA-IR) (P = 0.041), and free fatty acid (FFA) concentration (P = 0.007) increased. The elevation in BMR showed inverse correlations with ΔBW (r = 0.37, P = 0.047) and Δcortisol (r = -0.53, P = 0.004). Significant portion (51.6%) of the variation in BMR change was explained by increases of cortisol (27.1%), FFA (13.4%), and free triiodothyronine (11.1%). In conclusion, the changes in maternal cortisol concentration are in relationship with changes in BMR and BW, further suggesting that increased cortisol secretion during pregnancy could be linked with the maintenance of maternal BW and body composition. © 2009 Humana Press Inc.