1,721,035 research outputs found
A Novel Insulin/Glucose Model after a Mixed-Meal Test in Patients with Type 1 Diabetes on Insulin Pump Therapy
Full text linkCurrent closed-loop insulin delivery methods stem from sophisticated models of the glucose-insulin (G/I) system, mostly based on complex studies employing glucose tracer technology. We tested the performance of a new minimal model (GLUKINSLOOP 2.0) of the G/I system to characterize the glucose and insulin dynamics during multiple mixed meal tests (MMT) of different sizes in patients with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion, CSII). The GLUKINSLOOP 2.0 identified the G/I system, provided a close fit of the G/I time-courses and showed acceptable reproducibility of the G/I system parameters in repeated studies of identical and double-sized MMTs. This model can provide a fairly good and reproducible description of the G/I system in T1D patients on CSII, and it may be applied to create a bank of "virtual" patients. Our results might be relevant at improving the architecture of upcoming closed-loop CSII systems
Central role of the β-cell in driving regression of diabetes after liver transplantation in cirrhotic patients
No full textBackground & Aims: Diabetes occurring as a direct consequence of loss of liver function is usually characterized by non-diabetic fasting plasma glucose (FPG) and haemoglobin A 1c (HbA 1c ) levels and should regress after orthotopic liver transplantation (OLT). This observational, longitudinal study investigated the relationship between the time-courses of changes in all 3 direct determinants of glucose regulation, i.e., β-cell function, insulin clearance and insulin sensitivity, and diabetes regression after OLT. Methods: Eighty cirrhotic patients with non-diabetic FPG and HbA 1c levels underwent an extended oral glucose tolerance test (OGTT) before and 3, 6, 12 and 24 months after OLT. The OGTT data were analysed with a mathematical model to estimate derivative control (DC) and proportional control (PC) of β-cell function and insulin clearance (which determine insulin bioavailability), and with the Oral Glucose Insulin Sensitivity (OGIS)-2 h index to estimate insulin sensitivity. Results: At baseline, 36 patients were diabetic (45%) and 44 were non-diabetic (55%). Over the 2-year follow-up, 23 diabetic patients (63.9%) regressed to non-diabetic glucose regulation, whereas 13 did not (36.1%); moreover, 4 non-diabetic individuals progressed to diabetes (9.1%), whereas 40 did not (90.9%). Both DC and PC increased in regressors (from month 3 and 24, respectively) and decreased in progressors, whereas they remained stable in non-regressors and only PC decreased in non-progressors. Insulin clearance increased in all groups, apart from progressors. Likewise, OGIS-2 h improved at month 3 in all groups, but thereafter it continued to improve only in regressors, whereas it returned to baseline values in the other groups. Conclusions: Increased insulin bioavailability driven by improved β-cell function plays a central role in favouring diabetes regression after OLT, in the presence of a sustained improvement of insulin sensitivity. Lay summary: Diabetes occurring in cirrhosis as a direct consequence of loss of liver function should regress after transplantation of a new functioning liver, though the pathophysiological mechanisms are unclear. This is the first study evaluating the contribution of all 3 direct determinants of insulin-dependent glucose regulation using a sophisticated mathematical model. Results show that β-cell function is the key process governing favourable or detrimental changes in glucose regulation in cirrhotic patients undergoing transplantation, pointing to the need to develop therapies to sustain β-cell function in these individuals. Trial registration: ClinicalTrials.gov, NCT02038517
A renal genetic risk score (GRS) is associated with kidney dysfunction in people with type 2 diabetes
No full textThis study aims to investigate whether renal and cardiovascular phenotypes in Italian patients with type 2 diabetes (T2D) could be influenced by a number of disease risk SNPs recently found in genome-wide association studies (GWAS). In 1591 Italian subjects with T2D: (1) 47 SNPs associated to kidney function and/or chronic kidney disease (CKD) and 49 SNPs associated to cardiovascular disease (CVD) risk were genotyped; (2) urinary albumin/creatinine (A/C) ratio, glomerular filtration rate (eGFR) and lipid profile were assessed; (3) a standard electrocardiogram was performed; (4) two genotype risk scores (GRS) were computed (a renal GRS calculated selecting 39 SNPs associated with intermediate traits of kidney damage and a cardiovascular GRS determined selecting 42 SNPs associated to CVD risk phenotypes). After correction for multiple comparisons, the renal GRS was not associated to A/C ratio (p = 0.33), but it was significantly related to decreased eGFR (p = 0.005). No association between the cardiovascular GRS and electrocardiogram was detected. Thus, in Italian patients with T2D a renal GRS might predict the decline in glomerular function, suggesting that the clock of diabetes associated CKD starts ticking long before hyperglycemia. Our data support the feasibility of gene-based prediction of complications in people with T2D
“IGT-like” status in normoglucose tolerant obese children and adolescents: the additive role of glucose profile morphology and 2-hours glucose concentration during the oral glucose tolerance test
No full textObjective: To assess whether combining glucose shape and 2-h glucose concentration during an oral glucose tolerance test (OGTT) may help identifying normal glucose tolerant obese children/adolescents with an impaired glucose tolerant (IGT)-like metabolic profile in term of insulin sensitivity (Matsuda index) and β-cell function (disposition index: DI). Subjects, methods, and main outcome measure: In total, 654 non-diabetic obese children/adolescents underwent a 2 h OGTT. The whole population was classified according to 2-hour plasma glucose (< 100, 100–119, 120–139, 140–200 mg/dL) and glucose shape (monophasic or biphasic). Monophasic morphology was characterized by an increase in OGTT glucose concentration followed by a decline of at least 4.5 mg/dL, a biphasic response was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 4.5 mg/dL. A subset of 69 participants had also a prolonged OGTT to estimate β-cell function in “biphasic” versus “monophasic” patients. Results: Matsuda index and DI decreased across 2-h glucose categories (both p < 0.001) and were lower in monophasic compared with biphasic children, independently of 2-h glucose category (both p < 0.001, both p for glucose category×shape interaction > 0.05). Normal glucose tolerant children with 2-h glucose of 120–139 mg/dl and monophasic glucose shape did not differ from IGT children, as regards Matsuda index and DI (both p > 0.05). Among children undergoing a prolonged OGTT, those with a monophasic glucose shape had worse β-cell function, modeled as proportional control, than those with a biphasic shape (p = 0.031). Conclusions: A monophasic OGTT glucose shape is associated with unfavorable glucose metabolism independently of 2-h glucose concentration. Children combining monophasic shape and normal-high 2-h glucose have an IGT-like glucose metabolism
Treatment intensification in patients with inadequate glycemic control on basal insulin: Rationale and clinical evidence for the use of short-acting and other glucagon-like peptide-1 receptor agonists
Full text linkA substantial proportion of patients with type 2 diabetes mellitus do not reach glycemic targets, despite treatment with oral anti-diabetic drugs and basal insulin therapy. Several options exist for treatment intensification beyond basal insulin, and the treatment paradigm is complex. In this review, the options for treatment intensification will be explored, focusing on drug classes that act via the incretin system and paying particular attention to the short-acting glucagon-like peptide-1 receptor agonists exenatide and lixisenatide. Current treatment guidelines will be summarized and discussed
Identification of an early transcriptomic signature of insulin resistance and related diseases in lymphomonocytes of healthy subjects.
Full text linkInsulin resistance is considered to be a pathogenetic mechanism in several and diverse diseases (e.g. type 2 diabetes, atherosclerosis) often antedating them in apparently healthy subjects. The aim of this study is to investigate with a microarray based approach whether IR per se is characterized by a specific pattern of gene expression. For this purpose we analyzed the transcriptomic profile of peripheral blood mononuclear cells in two groups (10 subjects each) of healthy individuals, with extreme insulin resistance or sensitivity, matched for BMI, age and gender, selected within the MultiKnowledge Study cohort (n = 148). Data were analyzed with an ad-hoc rank-based classification method. 321 genes composed the gene set distinguishing the insulin resistant and sensitive groups, within which the "Adrenergic signaling in cardiomyocytes" KEGG pathway was significantly represented, suggesting a pattern of increased intracellular cAMP and Ca2+, and apoptosis in the IR group. The same pathway allowed to discriminate between insulin resistance and insulin sensitive subjects with BMI >25, supporting his role as a biomarker of IR. Moreover, ASCM pathway harbored biomarkers able to distinguish healthy and diseased subjects (from publicly available data sets) in IR-related diseases involving excitable cells: type 2 diabetes, chronic heart failure, and Alzheimer's disease. The altered gene expression profile of the ASCM pathway is an early molecular signature of IR and could provide a common molecular pathogenetic platform for IR-related disorders, possibly representing an important aid in the efforts aiming at preventing, early detecting and optimally treating IR-related diseases
Sodium-glucose cotransporter 2 inhibitors antagonize lipotoxicity in human myeloid angiogenic cells and ADP-dependent activation in human platelets: potential relevance to prevention of cardiovascular events.
No full textThe clear evidence of cardiovascular benefits in cardiovascular outcome trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes might suggest an effect on atherosclerotic plaque vulnerability and/or thrombosis, in which myeloid angiogenic cells (MAC) and platelets (PLT) are implicated. We tested the effects of SGLT2i on inflammation and oxidant stress in a model of stearic acid (SA)-induced lipotoxicity in MAC and on PLT activation. The possible involvement of the Na+/H+ exchanger (NHE) was also explored.info:eu-repo/semantics/publishe
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Crosstalk between genetic variability of adiponectin and leptin, glucose‐insulin system and subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study 14
No full textAim: To evaluate the relationship of genetic variability of adiponectin (ADIPOQ), leptin (LEP) and leptin receptor (LEPR) genes with glucose-insulin system and markers of subclinical atherosclerosis (ATS) in patients with newly diagnosed type 2 diabetes.Materials and methods: In 794 subjects we performed: 1) euglycemic hyperinsulinemic clamp to assess insulin sensitivity; 2) mathematical modelling of a 5h-OGTT to estimate ss-cell function; 3) resting ECG; 4) carotid artery and lower limb artery ecodoppler sonography to identify ATS; 5) genotyping of tag-SNPs within ADIPOQ, LEP and LEPR gene.Results: Regression analyses showed: 1) adiponectin levels were negatively associated with BMI, waist-to-hip ratio and triglycerides and positively with HDL and insulin sensitivity (p-all<0.03); 2) leptin levels were positively associated with BMI, HDL-cholesterol and plasma triglycerides and negatively with insulin sensitivity (p- all<0.001). Two SNPs (rs1501299 and rs2241767) within ADIPOQ gene were associated with circulating levels of adiponectin. The ADIPOQ-GAACA haplotype was associated with plasma adiponectin (p=0.034; ss=-0.24), ECG abnormalities ( p=0.012; OR=2.76), carotid ATS (p= 0.025; OR=2.00) and peripheral limb artery ATS ( p=0.032; OR=1.90). The LEP-CTA haplotype showed an association with ischemic ECG abnormalities (p=0.017; OR= 2.24). Finally, LEPR-GAACGG was associated with circulating leptin (p=0.005; ss=-0.31) and worst ss-cell function ( p=0.023; ss=-15.10). Omnibus haplotype analysis showed that ADIPOQ haplotypes were associated with levels of adiponectin and common carotid artery ATS, LEP with peripheral limb artery ATS, whereas LEPR haplotypes influenced circulating levels of leptin.Conclusions: Results of this study reinforce knowledge on adipokines' role in regulating glucose metabolism; in particular highlighted the potential atherogenic role of leptin and the anti atherogenic role of adiponectin
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