Browsing by Author "Žarković, Miloš (7003498546)"

Background: The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown. Methods: We conducted a cross-sectional electronic survey of American and European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions. Results: Two hundred fifty-two eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%, 114/227), white (79.7%, 181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%, 106/227), caring for 10 or more TED patients over the last 12 months (40.5%, 92/227), and reported not having a multidisciplinary TED clinic in their institution (52.8%, 120/227). The majority reported that new TED cases per annum have not changed in the past 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported a higher use of selenium (73%[96/132] vs. 32%[20/62] of respondents from North America and 24%[8/33] of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous (IV) steroids (73%[96/132], and 42%[14/33]) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important"concerns about TED management according to participants were: the cost of TED treatment (31.3%, 71/227), lack of effective TED treatments (19.8%, 45/227), and difficulty in predicting whether TED will develop (18.9%, 43/227). Conclusions: There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies. © Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.

Background: The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown. Methods: We conducted a cross-sectional electronic survey of American and European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions. Results: Two hundred fifty-two eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%, 114/227), white (79.7%, 181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%, 106/227), caring for 10 or more TED patients over the last 12 months (40.5%, 92/227), and reported not having a multidisciplinary TED clinic in their institution (52.8%, 120/227). The majority reported that new TED cases per annum have not changed in the past 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported a higher use of selenium (73%[96/132] vs. 32%[20/62] of respondents from North America and 24%[8/33] of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous (IV) steroids (73%[96/132], and 42%[14/33]) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important"concerns about TED management according to participants were: the cost of TED treatment (31.3%, 71/227), lack of effective TED treatments (19.8%, 45/227), and difficulty in predicting whether TED will develop (18.9%, 43/227). Conclusions: There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies. © Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.

Objective: Information on the impact of SARS-COV-2 on the daily life of thyroid patients during lockdown is sparse. The main objective was explorative, focusing on how SARS-COV-2 affected thyroid patients. Design: Cross-sectional, questionnaire-based, using an online platform. Patients: Patients >18 years with a history of thyroid disease. Measurements: Demographic data, psychological impact of SARS-COV-2, medical care during the pandemic. Results: Valid responses were received from 609 responders. The median age was 50 years, 94% were female and 98.5% were UK residents. The commonest diagnosis was primary hypothyroidism (52.2%). Negative psychological effects following the lockdown were reported by 45.6%–58.7%. Cancellations of appointments with thyroid specialists were reported by 43.8%, although cancellations of thyroid investigations and treatments were relatively infrequent (12.9%–14.1%). Overall satisfaction rates for thyroid services were low (satisfaction score 40.1–42.8 out of 100), but nearly 80% were satisfied with remote consultations. Responder ratings of online information sources about SARS-COV-2 and thyroid diseases were lowest for government sites. Unmet needs during lockdown were: more remote access to thyroid specialists, more online information in ‘plain English’, and psychological support. In multivariate analyses, younger age, female gender, history of depression, hyperthyroidism, not having contracted SARS-COV-2 and multiple comorbidities were risk factors for a negative psychological impact of lockdown. Conclusions: This survey identified a significant negative impact of SARS-COV-2 and lockdown on psychological wellbeing, particularly in some groups of patients defined by demographic factors, history of hyperthyroidism and comorbidities. Low satisfaction with healthcare services among thyroid patients was noted, but remote consultations were rated favourably. © 2021 John Wiley & Sons Ltd.

Objective: Information on the impact of SARS-COV-2 on the daily life of thyroid patients during lockdown is sparse. The main objective was explorative, focusing on how SARS-COV-2 affected thyroid patients. Design: Cross-sectional, questionnaire-based, using an online platform. Patients: Patients >18 years with a history of thyroid disease. Measurements: Demographic data, psychological impact of SARS-COV-2, medical care during the pandemic. Results: Valid responses were received from 609 responders. The median age was 50 years, 94% were female and 98.5% were UK residents. The commonest diagnosis was primary hypothyroidism (52.2%). Negative psychological effects following the lockdown were reported by 45.6%–58.7%. Cancellations of appointments with thyroid specialists were reported by 43.8%, although cancellations of thyroid investigations and treatments were relatively infrequent (12.9%–14.1%). Overall satisfaction rates for thyroid services were low (satisfaction score 40.1–42.8 out of 100), but nearly 80% were satisfied with remote consultations. Responder ratings of online information sources about SARS-COV-2 and thyroid diseases were lowest for government sites. Unmet needs during lockdown were: more remote access to thyroid specialists, more online information in ‘plain English’, and psychological support. In multivariate analyses, younger age, female gender, history of depression, hyperthyroidism, not having contracted SARS-COV-2 and multiple comorbidities were risk factors for a negative psychological impact of lockdown. Conclusions: This survey identified a significant negative impact of SARS-COV-2 and lockdown on psychological wellbeing, particularly in some groups of patients defined by demographic factors, history of hyperthyroidism and comorbidities. Low satisfaction with healthcare services among thyroid patients was noted, but remote consultations were rated favourably. © 2021 John Wiley & Sons Ltd.

[No abstract available]

[No abstract available]

Insulin resistance is believed to be an integral component of the polycystic ovary syndrome (PCOS). Beta (ß) cell dysfunction is also found in PCOS. In the study, we determined the influence of age, body mass index (BMI), and waist-to-hip ratio (WHR) on insulin response to oral glucose load (OGTT) and on insulin sensitivity (Si) and ß-cell function in young women with PCOS. One hundred fourteen patients with PCOS and 41 controls with normal basal plasma glucose were studied. A 75-g OGTT was performed to determine glucose tolerance and insulin response. Insulin sensitivity and ß-cell function were studied using a modified frequently sampled IV glucose tolerance test (FISGTT) to determine the acute insulin response (AIRG), as well as Si by minimal model analysis. Si was decreased in PCOS women (2.49 0.18 vs. 3.41 ± 0.36, p<0.05), but no difference in AIRG existed between the PCOS and control group (75.1 ± 4.6 vs. 63.4 ± 4.6, p<0.05). BMI and WHR correlated negatively with Si (r = -0.43; r = -0.289, p<0.001, respectively), but not with AIRG (r = 0.116; r = -0.02, p>0.05, respectively). Increasing age correlated negatively with AIRG (r = -0.285, p<0.001). There was a significant interaction between disease (PCOS), BMI, and WHR on Si as well as between age and PCOS on AIRG. Thus, patients below the age of 25 with PCOS showed enhanced AIRG (89.5 ± 7.1 vs. 65.1 ± 6.7, p<0.05) and decreased Si (2.43 ± 0.25 vs. 4.52 ± 0.62, p<0.05) compared to age-matched controls. In conclusion, these data suggest that not all patients with PCOS have basal and stimulated hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Based on these data in young PCOS subjects, the development of insulin resistance and T2DM may be prevented with appropriate treatment strategies. © 2022 Mirjana Šumarac-Dumanović et al.

Insulin resistance is believed to be an integral component of the polycystic ovary syndrome (PCOS). Beta (ß) cell dysfunction is also found in PCOS. In the study, we determined the influence of age, body mass index (BMI), and waist-to-hip ratio (WHR) on insulin response to oral glucose load (OGTT) and on insulin sensitivity (Si) and ß-cell function in young women with PCOS. One hundred fourteen patients with PCOS and 41 controls with normal basal plasma glucose were studied. A 75-g OGTT was performed to determine glucose tolerance and insulin response. Insulin sensitivity and ß-cell function were studied using a modified frequently sampled IV glucose tolerance test (FISGTT) to determine the acute insulin response (AIRG), as well as Si by minimal model analysis. Si was decreased in PCOS women (2.49 0.18 vs. 3.41 ± 0.36, p<0.05), but no difference in AIRG existed between the PCOS and control group (75.1 ± 4.6 vs. 63.4 ± 4.6, p<0.05). BMI and WHR correlated negatively with Si (r = -0.43; r = -0.289, p<0.001, respectively), but not with AIRG (r = 0.116; r = -0.02, p>0.05, respectively). Increasing age correlated negatively with AIRG (r = -0.285, p<0.001). There was a significant interaction between disease (PCOS), BMI, and WHR on Si as well as between age and PCOS on AIRG. Thus, patients below the age of 25 with PCOS showed enhanced AIRG (89.5 ± 7.1 vs. 65.1 ± 6.7, p<0.05) and decreased Si (2.43 ± 0.25 vs. 4.52 ± 0.62, p<0.05) compared to age-matched controls. In conclusion, these data suggest that not all patients with PCOS have basal and stimulated hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Based on these data in young PCOS subjects, the development of insulin resistance and T2DM may be prevented with appropriate treatment strategies. © 2022 Mirjana Šumarac-Dumanović et al.

Purpose: Graves’ orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients’ lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Conclusions: Alterations in patients’ lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. © The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2025.

Purpose: Graves’ orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients’ lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Conclusions: Alterations in patients’ lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. © The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE) 2025.

Purpose: Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (−) subgroups of GO patients. Methods: Study included consecutive patients with GO (66 with Graves’ (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. Results: aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). Conclusion: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Purpose: Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (−) subgroups of GO patients. Methods: Study included consecutive patients with GO (66 with Graves’ (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. Results: aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). Conclusion: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

We describe a 50-year-old patient with four episodes of recurrent bilateral chorea-ballism (BCB) and associated hyperthyroidism. Reappearance of BCB, associated with increased serum levels of thyroid hormones and lack of relevant changes on brain computed tomography/magnetic resonance imaging scans, suggested that the involuntary movements were likely due to thyrotoxicosis-induced biochemical changes. © 2004 Movement Disorder Society.

We describe a 50-year-old patient with four episodes of recurrent bilateral chorea-ballism (BCB) and associated hyperthyroidism. Reappearance of BCB, associated with increased serum levels of thyroid hormones and lack of relevant changes on brain computed tomography/magnetic resonance imaging scans, suggested that the involuntary movements were likely due to thyrotoxicosis-induced biochemical changes. © 2004 Movement Disorder Society.

Introduction In interpreting thyroid hormones results it is preferable to think of interference and changes in concentration of their carrier proteins. Outline of Cases We present two patients with discrepancy between the results of thyroid function tests and clinical status. The first case presents a 62-year-old patient with a nodular goiter and Hashimoto thyroiditis. Thyroid function test showed low thyroid-stimulating hormone (TSH) and normal to low fT4. By determining thyroid status (TSH, T4, fT4, T3, fT3) in two laboratories, basal and after dilution, as well as thyroxine-binding globulin (TBG), it was concluded that the thyroid hormone levels were normal. The results were influenced by heterophile antibodies leading to a false lower TSH level and suspected secondary hypothyroidism. The second case, a 40-year-old patient, was examined and followed because of the variable size thyroid nodule and initially borderline elevated TSH, after which thyroid status showed low level of total thyroid hormones and normal TSH. Based on additional analysis it was concluded that low T4 and T3 were a result of low TBG. It is a hereditary genetic disorder with no clinical significance. Conclusion Erroneous diagnosis of thyroid disorders and potentially harmful treatment could be avoided by proving the interference or TBG deficiency whenever there is a discrepancy between the thyroid function results and the clinical picture. © 2016, Serbia Medical Society. All rights reserved.

Background: Systemic inflammatory response syndrome (SIRS) changes cortisol dynamics and indicates dissociation between the adrenal cortex and the hypothalamo-pituitary unit. The aim of this study was to assess the cortisol response after stimulation with ACTH1-24 in patients with SIRS at admission to the Respiratory Intensive Care Unit (RICU) and seven days later. Methods: Fifty-four subjects were included in the study, and SIRS was defined according to the Consensus Conference criteria from 1992. Severity of the disease was determined using the APACHE II score, and organ dysfunction using the SOFA score. Low-dose (1 μg) ACTH test (LDT) was performed in all patients, and cortisol was determined along with basal ACTH. Data were analyzed using parametric and nonparametric tests and regression analysis. The results are presented as mean ± standard deviation, and P<0.05 was considered statistically significant. Results: There were no differences in cortisol values between the two LDTs. Cortisol increment lower than 250 nmol/L during the LDT was found in 14/54 (25.9%) subjects at the onset of SIRS. Five out of 54 (9.6%) patients died within 7 days from the onset of SIRS. Female sex and maximal cortisol response (Δ max) on LDT predicted the duration of hospitalization in RICU, while APACHE II and SOFA scores best predicted the duration of hospitalization, mortality outcome as well as overall survival outcome. Conclusions: A difference was found in Δ max at the diagnosis of SIRS and seven days later. Δ max, and primarily the clinical scores APACHE II and SOFA predicted the outcomes of hospitalization and overall survival. © 2016 Jelica Bjekić-Macut et al.

Background: Systemic inflammatory response syndrome (SIRS) changes cortisol dynamics and indicates dissociation between the adrenal cortex and the hypothalamo-pituitary unit. The aim of this study was to assess the cortisol response after stimulation with ACTH1-24 in patients with SIRS at admission to the Respiratory Intensive Care Unit (RICU) and seven days later. Methods: Fifty-four subjects were included in the study, and SIRS was defined according to the Consensus Conference criteria from 1992. Severity of the disease was determined using the APACHE II score, and organ dysfunction using the SOFA score. Low-dose (1 μg) ACTH test (LDT) was performed in all patients, and cortisol was determined along with basal ACTH. Data were analyzed using parametric and nonparametric tests and regression analysis. The results are presented as mean ± standard deviation, and P<0.05 was considered statistically significant. Results: There were no differences in cortisol values between the two LDTs. Cortisol increment lower than 250 nmol/L during the LDT was found in 14/54 (25.9%) subjects at the onset of SIRS. Five out of 54 (9.6%) patients died within 7 days from the onset of SIRS. Female sex and maximal cortisol response (Δ max) on LDT predicted the duration of hospitalization in RICU, while APACHE II and SOFA scores best predicted the duration of hospitalization, mortality outcome as well as overall survival outcome. Conclusions: A difference was found in Δ max at the diagnosis of SIRS and seven days later. Δ max, and primarily the clinical scores APACHE II and SOFA predicted the outcomes of hospitalization and overall survival. © 2016 Jelica Bjekić-Macut et al.

Objective: The aim of the study was to determine whether derangements in insulin pulsatility are related to the presence of insulin resistance or whether these changes occur only in non-insulin-dependent diabetes mellitus (NIDDM). Design and methods: The study included 26 obese, 11 NIDDM and 10 control subjects. The obese group was divided into a low insulin (plasma insulin <20 mU/l, OLI, 14 subjects) and a high insulin (OHI, 12 subjects) group. For pulsatility analysis blood was sampled every 2 min for 90 min. Pulsatility analysis was carried out using the PulsDetekt program. The insulin secretion randomness was quantified using interpulse interval deviation (IpID) and approximate entropy (ApEn). ApEn and ApEn normalized by s.p. of the individual insulin time series (nApEn) were calculated. Lower values of ApEn and IpID indicate more regular secretion. Homeostasis model assessment (HOMA) was used to quantify insulin sensitivity. Results: Insulin pulses were significantly less regular in the OHI and the NIDDM groups compared with the control and the OLI groups (control: ApEn 0,54 ± 0.16, nApEn 0.69 ± 0.19, IpID 2.53 ± 0.99; OLI: ApEn 0.64 ± 0.12, nApEn 0.79 ± 0.15, IpID 2.92 ± 1.09; OHI: ApEn 0.88 ± 0.07, nApEn 0.92 ± 0.07, IpID 3.95 ± 0.84; NIDDM: ApEn 0.92 ± 0.16, nApEn 0.99 ± 0.09, IpID 4.41 ± 0.53; means ± s.p.). There was no difference in the pulse regularity between the OHI and the NIDDM groups. Conclusions: Decrease in insulin sensitivity was correlated with the reduction of insulin secretion regularity. Therefore irregular insulin secretion is related to a reduction in insulin sensitivity, and it is not unique to NIDDM.

Objective: The aim of the study was to determine whether derangements in insulin pulsatility are related to the presence of insulin resistance or whether these changes occur only in non-insulin-dependent diabetes mellitus (NIDDM). Design and methods: The study included 26 obese, 11 NIDDM and 10 control subjects. The obese group was divided into a low insulin (plasma insulin <20 mU/l, OLI, 14 subjects) and a high insulin (OHI, 12 subjects) group. For pulsatility analysis blood was sampled every 2 min for 90 min. Pulsatility analysis was carried out using the PulsDetekt program. The insulin secretion randomness was quantified using interpulse interval deviation (IpID) and approximate entropy (ApEn). ApEn and ApEn normalized by s.p. of the individual insulin time series (nApEn) were calculated. Lower values of ApEn and IpID indicate more regular secretion. Homeostasis model assessment (HOMA) was used to quantify insulin sensitivity. Results: Insulin pulses were significantly less regular in the OHI and the NIDDM groups compared with the control and the OLI groups (control: ApEn 0,54 ± 0.16, nApEn 0.69 ± 0.19, IpID 2.53 ± 0.99; OLI: ApEn 0.64 ± 0.12, nApEn 0.79 ± 0.15, IpID 2.92 ± 1.09; OHI: ApEn 0.88 ± 0.07, nApEn 0.92 ± 0.07, IpID 3.95 ± 0.84; NIDDM: ApEn 0.92 ± 0.16, nApEn 0.99 ± 0.09, IpID 4.41 ± 0.53; means ± s.p.). There was no difference in the pulse regularity between the OHI and the NIDDM groups. Conclusions: Decrease in insulin sensitivity was correlated with the reduction of insulin secretion regularity. Therefore irregular insulin secretion is related to a reduction in insulin sensitivity, and it is not unique to NIDDM.

The aim of the study was to assess whether pulsatile insulin secretion is variable in the same individual and is related to changes in insulin sensitivity. Insulin sensitivity and pulsatility were measured before and after weight reduction in nine obese subjects. A pulsatility analysis was done using the PulsDetekt program. Blood was sampled every 2 min over a period of 90 min. The secretion randomness was quantified using approximate entropy (ApEn), and ApEn normalized by SD of the insulin time series (nApEn). Lower values indicate more regular secretion. Insulin sensitivity was measured using the homeostasis model assessment. Data are presented as median, minimum-maximum. After weight loss insulin sensitivity was increased (12.16, 7.60-76.70 vs. 38.96, 19.88-74.96%), the number of insulin pulses was reduced (11, 8-16 vs. 9, 6-12), and they were more regular (ApEn, 0.92, 0.53-133 vs. 0.69, 0,40-1.27; nApEn, 1.07, 0.74-1.33 vs. 0.97, 0.54-1.42). Before and after the weight loss there was a correlation between ApEn and nApEn and insulin sensitivity. Therefore, insulin secretion regularity is variable in the same individual and is related to insulin sensitivity.