Browsing by Author "Jotic, Aleksandra (13702545200)"

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.

Background: Previous studies suggested an important role of impairments in T cell subsets in different stages during type 1 diabetes (T1D) development, while data regarding CD25high T cells and transforming growth factor β1 (TGFβ1), both T regulatory associated, remains controversial. We analyzed the level of (a) CD25high T cells (b) TGFβ1 in 17 first-degree relatives of patients with T1D in stage 1 (FDRs1) (GADA+, IA-2+); 34 FDRs in stage 0 (FDRs0) (GADA-, IA-2-); 24 recent-onset T1D in insulin-requiring state (IRS); 10 patients in clinical remission (CR); 18 healthy, unrelated controls (CTR). Methods: T cell subsets were characterized by two-color immunofluorescence staining and flow cytometry; TGFβ1 was determined by ELISA, GADA, and IA-2 by RIA. Results: The percentage of CD25high T cells in FDRs1 was lower than controls, FDRs0, IRS, and CR (p<0.001). Additionally, the cut-off value for CD25high = 1.19%, with a probability of 0.667, for having a higher risk for T1D. TGFβ1 concentration in FDRs1, FDRs0, IRS, and CR, was lower than controls (p<0.001). IRS has a higher TGFβ1 concentration than CR (p<0.001). Conclusions: Stage 1, a higher risk for T1D, is characterized by decreases in CD25high T cells and TGFβ1, partially reflecting impaired T regulatory response, implying that changes of this T cells subset might be a risk marker for T1D. FDRs, irrespective of risk for T1D and T1D patients irrespective of state, had depletion of TGFβ1, suggesting the association of TGFβ1 could have potential with familiar risk and manifestation of T1D. Furthermore, the result suggested that the clinical course of overt T1D might be modulated on the TGFβ1 level. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

Background: Previous studies suggested an important role of impairments in T cell subsets in different stages during type 1 diabetes (T1D) development, while data regarding CD25high T cells and transforming growth factor β1 (TGFβ1), both T regulatory associated, remains controversial. We analyzed the level of (a) CD25high T cells (b) TGFβ1 in 17 first-degree relatives of patients with T1D in stage 1 (FDRs1) (GADA+, IA-2+); 34 FDRs in stage 0 (FDRs0) (GADA-, IA-2-); 24 recent-onset T1D in insulin-requiring state (IRS); 10 patients in clinical remission (CR); 18 healthy, unrelated controls (CTR). Methods: T cell subsets were characterized by two-color immunofluorescence staining and flow cytometry; TGFβ1 was determined by ELISA, GADA, and IA-2 by RIA. Results: The percentage of CD25high T cells in FDRs1 was lower than controls, FDRs0, IRS, and CR (p<0.001). Additionally, the cut-off value for CD25high = 1.19%, with a probability of 0.667, for having a higher risk for T1D. TGFβ1 concentration in FDRs1, FDRs0, IRS, and CR, was lower than controls (p<0.001). IRS has a higher TGFβ1 concentration than CR (p<0.001). Conclusions: Stage 1, a higher risk for T1D, is characterized by decreases in CD25high T cells and TGFβ1, partially reflecting impaired T regulatory response, implying that changes of this T cells subset might be a risk marker for T1D. FDRs, irrespective of risk for T1D and T1D patients irrespective of state, had depletion of TGFβ1, suggesting the association of TGFβ1 could have potential with familiar risk and manifestation of T1D. Furthermore, the result suggested that the clinical course of overt T1D might be modulated on the TGFβ1 level. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

Introduction: We evaluated the effectiveness of long-term continuous subcutaneous insulin infusion (CSII) compared with multiple daily insulin (MDI) injections for glycaemic control and variability, hypoglycaemic episodes and maternal/neonatal outcomes in pregnant women with pre-existing type 1 diabetes (pT1D). Methods: Our observational cohort study included 128 consecutive pregnant women with pT1D, who were treated from 1 January 2010 to 31 December 2017. Of 128 participants, 48 were on CSII and 80 were on MDI. Glycaemic control was determined by glycated haemoglobin (HbA1c) (captured in preconception and each trimester of pregnancy). Glucose variability (GV) was expressed as the coefficient of variation (CV) [calculated from self-monitoring of blood glucose (SMBG) values], and hypoglycaemia was defined as glucose values < 3.9 mmol/l. The data on maternal and neonatal outcomes were collected from obstetrical records. Results: Duration of the treatment was 8.8 ± 5.3 years in the CSII and 12.6 ± 8.0 years in the MDI group. The CSII lowered HbA1c in preconception (7.1 ± 0.1 vs. 7.9 ± 0.2%, p = 0.03) and the first (6.9 ± 0.1 vs. 7.7 ± 0.2%, p = 0.02), second (6.6 ± 0.1 vs. 7.2 ± 0.1%, p = 0.003) and third (6.5 ± 0.1 vs. 6.8 ± 0.1%, p = 0.02) trimesters significantly better than MDI. Significantly lower CV was observed only for fasting glycaemia in the first trimester (17.1 vs 28.4%, p < 0.001) in favour of CSII. Moreover, the CSII group had significantly lower mean hypoglycaemic episodes/week/patient only during the first trimester (2.0 ± 1.7 vs 4.8 ± 1.5, p < 0.01). In early pregnancy, the majority of women on CSII had less hypoglycaemia than on MDI (0–3: 79.1 vs. 29.1%; 4–6: 18.8 vs. 65.8%; ≥ 7: 2.1 vs. 5.1%, p < 0.01, respectively). We found no difference in the incidence of adverse maternal/neonatal outcomes. Conclusions: Treatment with CSII resulted in a favourable reduction of HbA1c in the preconception period and each trimester in pregnancy. Moreover, long-term CSII treatment demonstrated more stable metabolic control with less GV of fasting glycaemia and fewer hypoglyacemic episodes only during early pregnancy. © 2020, The Author(s).

We analyzed the level of (a) CXCR3+ (Th1) and CCR4+ (Th2) T memory cells (b) interferon-γ inducible chemokine (IP-10)(Th1) and thymus and activation-regulated chemokine (TARC)(Th2), in 51 first degree relatives (FDRs) of type 1 diabetics (T1D) (17 high risk FDRs (GADA+, IA-2+) and 34 low risk FDRs (GADA-, IA-2-)), 24 recent-onset T1D (R-T1D), and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., P < 0.001). Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, P < 0.05). Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response. © 2014 Tanja Milicic et al.

We analyzed the level of (a) CXCR3+ (Th1) and CCR4+ (Th2) T memory cells (b) interferon-γ inducible chemokine (IP-10)(Th1) and thymus and activation-regulated chemokine (TARC)(Th2), in 51 first degree relatives (FDRs) of type 1 diabetics (T1D) (17 high risk FDRs (GADA+, IA-2+) and 34 low risk FDRs (GADA-, IA-2-)), 24 recent-onset T1D (R-T1D), and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., P < 0.001). Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, P < 0.05). Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response. © 2014 Tanja Milicic et al.

Background: The growing body of evidence suggests that atherosclerosis risk factors are important in cognitive decline. Objective: To analyse insulin sensitivity, insulin secretion capacity, plasma insulin, adiponectin and lipid levels in normoglycaemic, nonobese patients with Alzheimer’s disease (AD) (group A, n=62), mild cognitive impairment (MCI) (group B, n=41), and healthy controls (group C, n=25). Method: Insulin sensitivity was determined by euglycemic hyperinsulinaemic clamp (M value) and homeostasis model assessment (HOMA-IR), insulin secretion capacity by first-phase insulin response (FPIR), plasma insulin by RIA, adiponectin by ELISA, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides by enzymatic method. Results: Insulin sensitivity was the lowest in group A (M value: A: 6.2±2.5; B:7.7±2.7; C:8.2±1.5 mg/min/kg, p<0.001; HOMA-IR: A: 4.6±2.2; B: 3.3±1.7; C: 1.5±1.0, p<0.001) as well as FPIR (A:68.9±27.8; B:112.5±47.1; C:147.4±56.0 mU/l, p<0.001). Plasma insulin was higher in group A vs B vs C, while adiponectin was lower in group A vs B vs C. Simultaneously, total and LDL-C were higher and HDL-C levels were lower in groups A and B vs C, with no difference between groups A and B. Triglycerides did not differ between the groups. Binary logistic regression analysis identified only M value, FPIR and plasma insulin as independent predictors of AD and MCI. Conclusion: These results imply that in AD and MCI insulin resistance with increased plasma insulin and decreased FPIR may be associated with the development of AD and MCI, accompanied with milder influence of low adiponectin levels and atherogenic lipid profile. © 2017 Bentham Science Publishers.

Background: The growing body of evidence suggests that atherosclerosis risk factors are important in cognitive decline. Objective: To analyse insulin sensitivity, insulin secretion capacity, plasma insulin, adiponectin and lipid levels in normoglycaemic, nonobese patients with Alzheimer’s disease (AD) (group A, n=62), mild cognitive impairment (MCI) (group B, n=41), and healthy controls (group C, n=25). Method: Insulin sensitivity was determined by euglycemic hyperinsulinaemic clamp (M value) and homeostasis model assessment (HOMA-IR), insulin secretion capacity by first-phase insulin response (FPIR), plasma insulin by RIA, adiponectin by ELISA, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides by enzymatic method. Results: Insulin sensitivity was the lowest in group A (M value: A: 6.2±2.5; B:7.7±2.7; C:8.2±1.5 mg/min/kg, p<0.001; HOMA-IR: A: 4.6±2.2; B: 3.3±1.7; C: 1.5±1.0, p<0.001) as well as FPIR (A:68.9±27.8; B:112.5±47.1; C:147.4±56.0 mU/l, p<0.001). Plasma insulin was higher in group A vs B vs C, while adiponectin was lower in group A vs B vs C. Simultaneously, total and LDL-C were higher and HDL-C levels were lower in groups A and B vs C, with no difference between groups A and B. Triglycerides did not differ between the groups. Binary logistic regression analysis identified only M value, FPIR and plasma insulin as independent predictors of AD and MCI. Conclusion: These results imply that in AD and MCI insulin resistance with increased plasma insulin and decreased FPIR may be associated with the development of AD and MCI, accompanied with milder influence of low adiponectin levels and atherogenic lipid profile. © 2017 Bentham Science Publishers.

Background/Objectives: Previous studies reported impairments in insulin secretion during different stages of type 1 diabetes (T1D), while data regarding insulin sensitivity and immunological changes are still controversial. We analyzed the following: (a) insulin secretion, (b) insulin sensitivity, and (c) pro-inflammatory interleukin-17 (IL-17) levels in peripheral blood in 17 healthy first-degree relatives in stage 1 (FDRs1) (GAD+, IA2+), 34 FDRs in stage 0 (FDRs0) (GAD−, IA2A−), 24 recent-onset T1D (R-T1D) patients in the insulin-requiring state (IRS), 10 in clinical remission (CR), and 18 healthy unrelated controls (HC). Methods: Insulin secretion was evaluated by an IVGTT and a glucagon stimulation test, expressed as a first-phase insulin response (FPIR) and a basal/stimulated C-peptide. Insulin sensitivity was tested by the euglycemic hyperinsulinemic clamp, expressed as an M value. Results: FDRs1 had a lower FPIR than FDRs0 (p < 0.05) and HC (p < 0.001) but higher than RT1D-IRS (p < 0.001) and RT1D-CR (p < 0.01). Moreover, FDRs1 had lower basal/stimulated C-peptide than FDRs0 (p < 0.01/p < 0.05) and HC (p < 0.001/p = 0.001) but higher levels than RT1D-IRS (p < 0.001/p < 0.001). However, the M value was similar among FDRs1, FDRs0, and HC (p = 1.0) but higher than RT1D-IRS (p < 0.001) and RT1D-CR (p < 0.01), while RT1D-IRS and RT1D-CR had lower M than HC (p < 0.001; p < 0.001; respectively). FDRs1 had higher IL-17 than FDRs0 (p < 0.001) and HC (p < 0.05). RT1D-IRS had higher IL-17 than FDRs0 (p < 0.001) and HC (p < 0.001), which was similar to RT1D-CR vs. FDRs0 (p < 0.001) and HC (p < 0.05). Conclusions: Early changes in pre-T1D might involve an initial decline of insulin secretion associated with a pro-inflammatory attack, which does not influence insulin sensitivity, whereas later, insulin sensitivity deterioration seems to be associated with the prominent reduction in insulin secretion. © 2025 by the authors.

The aim of this study was to examine the differences in pregnancy complications, delivery characteristics, and neonatal outcomes between women with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). This study included all pregnant women with diabetes in pregnancy in Belgrade, Serbia, between 2010 and 2020. The total sample consisted of 6737 patients. In total, 1318 (19.6%) patients had T1DM, 138 (2.0%) had T2DM, and 5281 patients (78.4%) had GDM. Multivariate logistic regression with the type of diabetes as an outcome variable showed that patients with T1DM had a lower likelihood of vaginal delivery (OR: 0.73, 95% CI: 0.64–0.83), gestational hypertension (OR: 0.47, 95% CI: 0.36–0.62), higher likelihood of chronic hypertension (OR: 1.88, 95% CI: 1.55–2.29),and a higher likelihood ofgestational age at delivery before 37 weeks (OR: 1.38, 95% CI: 1.18–1.63) compared to women with GDM. Multivariate logistic regression showed that patients with T2DM had a lower likelihood ofgestational hypertension compared to women with GDM (OR: 0.37, 95% CI: 0.15–0.92).Our results indicate that the highest percentage of diabetes in pregnancy is GDM, and the existence of differences in pregnancy complications, childbirth characteristics, and neonatal outcomes are predominantly between women with GDM and women with T1DM. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

The aim of this study was to examine the differences in pregnancy complications, delivery characteristics, and neonatal outcomes between women with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). This study included all pregnant women with diabetes in pregnancy in Belgrade, Serbia, between 2010 and 2020. The total sample consisted of 6737 patients. In total, 1318 (19.6%) patients had T1DM, 138 (2.0%) had T2DM, and 5281 patients (78.4%) had GDM. Multivariate logistic regression with the type of diabetes as an outcome variable showed that patients with T1DM had a lower likelihood of vaginal delivery (OR: 0.73, 95% CI: 0.64–0.83), gestational hypertension (OR: 0.47, 95% CI: 0.36–0.62), higher likelihood of chronic hypertension (OR: 1.88, 95% CI: 1.55–2.29),and a higher likelihood ofgestational age at delivery before 37 weeks (OR: 1.38, 95% CI: 1.18–1.63) compared to women with GDM. Multivariate logistic regression showed that patients with T2DM had a lower likelihood ofgestational hypertension compared to women with GDM (OR: 0.37, 95% CI: 0.15–0.92).Our results indicate that the highest percentage of diabetes in pregnancy is GDM, and the existence of differences in pregnancy complications, childbirth characteristics, and neonatal outcomes are predominantly between women with GDM and women with T1DM. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

BACKGROUND: The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, Cpeptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS: Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n 29] underwent oral-glucosetolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, andHDLcholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and 2 test. RESULTS: The novel formula for SPISE was computed as follows: SPISE 600 HDL-C0.185/(TG0.2 BMI1.338), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m2). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg kg1 min1 (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment-insulin resistance) when calculated with M-values. CONCLUSIONS: The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults. © 2016 American Association for Clinical Chemistry.0.

BACKGROUND: The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, Cpeptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS: Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n 29] underwent oral-glucosetolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, andHDLcholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and 2 test. RESULTS: The novel formula for SPISE was computed as follows: SPISE 600 HDL-C0.185/(TG0.2 BMI1.338), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m2). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg kg1 min1 (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment-insulin resistance) when calculated with M-values. CONCLUSIONS: The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults. © 2016 American Association for Clinical Chemistry.0.

Background: Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically. Aims: To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries. Methods: We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data. Results: Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients. Conclusions: Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes. © 2020 Elsevier B.V.

Background: Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically. Aims: To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries. Methods: We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data. Results: Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients. Conclusions: Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes. © 2020 Elsevier B.V.

Introduction. Managing non-communicable diseases (NCDs) requires redesigning health care delivery to achieve better coordination of services at all levels of health care. The aim of this study was improving prevention and strengthening high quality of care for NCDs by using type 2 diabetes as a model disease. Methods. The mix method approach served to analyse the impact of the intervention processes. Source of information were routine health statistics, interviews and observation. Key Performance Indicators in defined Improvement Areas assisted in the quality of diabetes care assessment. Results and discussion. During the study the National Diabetes Centre (NDC) was established. The NDC experts organized numerous educational events, 316 physicians and nurses have participated. New electronic data base was implemented in 20 pilot Primary Health Care Centres (PHCCs) with 38,833 electronic diabetes records. Conclusions. The intervention led to establishment of the NDC, strengthening competences of health care professionals and to the renewal of the Diabetes Care Units in PHCCs included in the study. © 2021 Istituto Superiore di Sanita. All rights reserved.

Aims Treatment burden (TB) refers to self-perceived cumulative work patients do to manage their health. Using validated tools, TB has been documented in several chronic conditions, but not atrial fibrillation (AF). We measured TB and analysed its determinants and impact on quality of life (QoL) in an AF cohort. Methods A single-centre study prospectively included consecutive adult AF patients and non-AF controls managed from 1 and results April to 21 June 2019, who voluntarily and anonymously answered the TB questionnaire (TBQ) and 5-item EQ-5D QoL questionnaire; TB was calculated as a sum of TBQ points (maximum 170) and expressed as proportion of the maximum value. Of 514 participants, 331 (64.4%) had AF. The mean self-reported TB was 27.6% among AF patients and 24.3% among controls, P = 0.011. The mean TB was significantly higher in patients taking vitamin K antagonists (VKAs) vs. those taking non-VKA antagonist oral anticoagulants (NOAC; 29.5% vs. 24.7%, P = 0.006). The highest item-specific TB was reported for healthcare system organization-related items (e.g. visit appointment), diet, and physical activity modifications. On multivariable analyses, female sex, younger age, and permanent AF were associated with a higher TB, whereas NOACs and electrical AF cardioversion exhibited an inverse association; TB was an independent predictor of decreased QoL (all P < 0.05). Conclusion Our study provided clinically relevant insights into self-perceived TB among AF patients. Approximately one in four patients with AF have a high TB. Specific AF treatments and optimization of healthcare system-required patient activities may reduce the self-perceived TB in AF patients. © The Author(s) 2020.

Background: Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). Methods: Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. Results: The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. Conclusions: This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.

Background: Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). Methods: Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. Results: The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. Conclusions: This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.