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Article ; Online: β-Cell Function, Incretin Effect, and Glucose Kinetics in Response to a Mixed Meal in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin.

Daniele, Giuseppe / Tura, Andrea / Brocchi, Alex / Saba, Alessandro / Campi, Beatrice / Sancho-Bornez, Veronica / Dardano, Angela / Del Prato, Stefano

Diabetes care

2024

Abstract: Objective: To explore the complementary effects of a combination of dipeptidyl peptidase 4 and sodium-glucose cotransporter 2 inhibitors added to metformin on hormonal and metabolic responses to meal ingestion.: Research design and methods: Forty- ... ...

Abstract	Objective: To explore the complementary effects of a combination of dipeptidyl peptidase 4 and sodium-glucose cotransporter 2 inhibitors added to metformin on hormonal and metabolic responses to meal ingestion. Research design and methods: Forty-five patients (age 58 ± 8 years; HbA1c 58 ± 6 mmol/mol; BMI 30.7 ± 3.2 kg/m2) with type 2 diabetes uncontrolled with metformin were evaluated at baseline and 3 and 28 days after 5 mg saxagliptin (SAXA), 10 mg dapagliflozin (DAPA), or 5 mg saxagliptin plus 10 mg dapagliflozin (SAXA+DAPA) using a mixed-meal tolerance test (MMTT) spiked with dual-tracer glucose to assess glucose metabolism, insulin secretion, and sensitivity. Results: At day 3, fasting and mean MMTT glucose levels were lower with SAXA+DAPA (-31.1 ± 1.6 and -91.5 ± 12.4 mg/dL) than with SAXA (-7.1 ± 2.1 and -53 ± 10.5 mg/dL) or DAPA (-17.0 ± 1.1 and -42.6 ± 10.0 mg/dL, respectively; P < 0.001). Insulin secretion rate (SAXA+DAPA +75%; SAXA +11%; DAPA 3%) and insulin sensitivity (+2.2 ± 1.7, +0.4 ± 0.7, and +0.4 ± 0.4 mg ⋅ kg-1⋅ min-1, respectively) improved with SAXA+DAPA (P < 0.007). Mean glucagon-like peptide 1 (GLP-1) was higher with SAXA+DAPA than with SAXA or DAPA. Fasting glucagon increased with DAPA and SAXA+DAPA but not with SAXA. Fasting endogenous glucose production (EGP) increased with SAXA+DAPA and DAPA. During MMTT, EGP suppression was greater (48%) with SAXA+DAPA (vs. SAXA 44%; P = 0.02 or DAPA 34%; P = 0.2). Metabolic clearance rate of glucose (MCRglu) increased more with SAXA+DAPA. At week 4, insulin secretion rate, β-cell glucose sensitivity, and insulin sensitivity had further increased in the SAXA+DAPA group (P = 0.02), with no additional changes in GLP-1, glucagon, fasting or MMTT EGP, or MCRglu. Conclusions: SAXA+DAPA provided superior glycemic control compared with DAPA or SAXA, with improved β-cell function, insulin sensitivity, GLP-1 availability, and glucose clearance.
Language	English
Publishing date	2024-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc23-2051
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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 365: Show issues

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Article ; Online: SIRT1 rs7896005 polymorphism affects major vascular outcomes, not all-cause mortality, in Caucasians with type 2 diabetes: A 13-year observational study.

Dardano, Angela / Lucchesi, Daniela / Garofolo, Monia / Gualdani, Elisa / Falcetta, Pierpaolo / Sancho Bornez, Veronica / Francesconi, Paolo / Del Prato, Stefano / Penno, Giuseppe

Diabetes/metabolism research and reviews

2022 Volume 38, Issue 4, Page(s) e3523

Abstract: Aims: SIRT1 exerts effects on ageing and lifespan, as well cardiovascular (CV) disease risk. SIRT1 gene is very polymorph with a few tagging single nucleotide polymorphisms (SNPs) so far identified. Some SNPs, including rs7896005, were associated with ... ...

Abstract	Aims: SIRT1 exerts effects on ageing and lifespan, as well cardiovascular (CV) disease risk. SIRT1 gene is very polymorph with a few tagging single nucleotide polymorphisms (SNPs) so far identified. Some SNPs, including rs7896005, were associated with type 2 diabetes (T2DM). We aimed to ascertain whether this SNP may be associated with CV disease at baseline as well with these same outcomes and all-cause mortality over a 13-year follow-up. Materials and methods: Genotypes of SIRT1 gene were determined using TaqMan SNP assay. Results: Out of 905 T2DM, 9.1% had the AA genotype, 43.2% the AG, and 47.7% the GG. Hardy-Weinberg Equilibrium was met (minor allele frequency 0.306; p = 0.8899). At baseline, there was no difference across genotypes for sex, age, diabetes duration, CV risk factors, treatments, and microangiopathy. Major CV outcomes, myocardial infarction (MI), any coronary heart disease (CHD), and peripheral artery disease (PAD) were more frequent in GG than in AA/AG (p from 0.013 to 0.027), with no association with cerebrovascular events. By fully adjusted regression, GG remained independently related to major CV outcomes, MI, CHD, and PAD. Over follow-up, we recorded 258 major CV events (28.5%; AA/AG 25.2%, GG 32.2%; p = 0.014) with an adjusted hazard ratio (HR) of GG versus AA/AG of 1.296 (95% CI 1.007-1.668, p = 0.044); 169 coronary events (18.7%; AA/AG 15.4%, GG 22.2%; p = 0.006) with HR 1.522 (1.113-2.080, p = 0.008); 79 (8.7%) hospitalisation for heart failure (AA/AG 7.0%, GG 10.6%; p = 0.045) and HR 1.457 (0.919-2.309, p = 0.109); 36 PAD (4.0%; AA/AG 2.3%, GG 5.8%; p = 0.007) with HR 2.225 (1.057-4.684, p = 0.035). No association was found with cerebrovascular events, end stage renal disease, and all-cause mortality. Conclusions: The rs7896005 SNP of SIRT1 might play a role in cardiovascular disease, mainly CHD risk in T2DM. Results call for larger association studies as well as studies to ascertain mechanisms by which this variant confers increased risk.
MeSH term(s)	Cardiovascular Diseases/genetics ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Sirtuin 1/genetics
Chemical Substances	SIRT1 protein, human (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-)
Language	English
Publishing date	2022-02-07
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	1470192-3
ISSN	1520-7560 ; 1520-7552
ISSN (online)	1520-7560
ISSN	1520-7552
DOI	10.1002/dmrr.3523
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Zs.A 2119: Show issues

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Article ; Online: Effect of fasting on short-term visual plasticity in adult humans.

Animali, Silvia / Steinwurzel, Cecilia / Dardano, Angela / Sancho-Bornez, Veronica / Del Prato, Stefano / Morrone, Maria Concetta / Daniele, Giuseppe / Binda, Paola

The European journal of neuroscience

2022 Volume 57, Issue 1, Page(s) 148–162

Abstract: Brain plasticity and function is impaired in conditions of metabolic dysregulation, such as obesity. Less is known on whether brain function is also affected by transient and physiological metabolic changes, such as the alternation between fasting and ... ...

Abstract	Brain plasticity and function is impaired in conditions of metabolic dysregulation, such as obesity. Less is known on whether brain function is also affected by transient and physiological metabolic changes, such as the alternation between fasting and fed state. Here we asked whether these changes affect the transient shift of ocular dominance that follows short-term monocular deprivation, a form of homeostatic plasticity. We further asked whether variations in three of the main metabolic and hormonal pathways affected in obesity (glucose metabolism, leptin signalling and fatty acid metabolism) correlate with plasticity changes. We measured the effects of 2 h monocular deprivation in three conditions: post-absorptive state (fasting), after ingestion of a standardised meal and during infusion of glucagon-like peptide-1 (GLP-1), an incretin physiologically released upon meal ingestion that plays a key role in glucose metabolism. We found that short-term plasticity was less manifest in fasting than in fed state, whereas GLP-1 infusion did not elicit reliable changes compared to fasting. Although we confirmed a positive association between plasticity and supraphysiological GLP-1 levels, achieved by GLP-1 infusion, we found that none of the parameters linked to glucose metabolism could predict the plasticity reduction in the fasting versus fed state. Instead, this was selectively associated with the increase in plasma beta-hydroxybutyrate (B-OH) levels during fasting, which suggests a link between neural function and energy substrates alternative to glucose. These results reveal a previously unexplored link between homeostatic brain plasticity and the physiological changes associated with the daily fast-fed cycle.
MeSH term(s)	Humans ; Adult ; Glucagon-Like Peptide 1 ; Glucose/metabolism ; Obesity ; Fasting ; Insulin
Chemical Substances	Glucagon-Like Peptide 1 (89750-14-1) ; Glucose (IY9XDZ35W2) ; Insulin
Language	English
Publishing date	2022-12-09
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.15873
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Zs.A 2548: Show issues

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Article ; Online: Brain effect of bariatric surgery in people with obesity.

Dardano, Angela / Aghakhanyan, Gayane / Moretto, Carlo / Ciccarone, Annamaria / Bellini, Rosario / Sancho Bornez, Veronica / Ceccarini, Giovanni / Santini, Ferruccio / Volterrani, Duccio / Del Prato, Stefano / Daniele, Giuseppe

International journal of obesity (2005)

2022 Volume 46, Issue 9, Page(s) 1671–1677

Abstract: Background/objectives: The link between obesity and brain function is a fascinating but still an enigmatic topic. We evaluated the effect of Roux-en-Y gastric bypass (RYGB) on peripheral glucose metabolism, insulin sensitivity, brain glucose utilization ...

Abstract	Background/objectives: The link between obesity and brain function is a fascinating but still an enigmatic topic. We evaluated the effect of Roux-en-Y gastric bypass (RYGB) on peripheral glucose metabolism, insulin sensitivity, brain glucose utilization and cognitive abilities in people with obesity. Subjects/methods: Thirteen subjects with obesity (F/M 11/2; age 44.4 ± 9.8 years; BMI 46.1 ± 4.9 kg/m Results: RYGB resulted in significant weight loss (from 46.1 ± 4.9 to 35.3 ± 5.0 kg/m Conclusions: Bariatric surgery improves CMRg directly related to a better cognitive testing result. This study highlights the potential pleiotropic effects of bariatric surgery. Trial registry number: NCT03414333.
MeSH term(s)	Adult ; Bariatric Surgery ; Brain/metabolism ; Female ; Gastric Bypass ; Glucose/metabolism ; Humans ; Insulin ; Insulin Resistance ; Leptin/metabolism ; Male ; Middle Aged ; Obesity/surgery ; Positron Emission Tomography Computed Tomography
Chemical Substances	Insulin ; Leptin ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-06-21
Publishing country	England
Document type	Clinical Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/s41366-022-01162-8
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Zs.A 1325: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Albuminuric and non-albuminuric chronic kidney disease in type 1 diabetes: Association with major vascular outcomes risk and all-cause mortality.

Garofolo, Monia / Russo, Eleonora / Miccoli, Roberto / Lucchesi, Daniela / Giusti, Laura / Sancho-Bornez, Veronica / Daniele, Giuseppe / Del Prato, Stefano / Penno, Giuseppe

Journal of diabetes and its complications

2018 Volume 32, Issue 6, Page(s) 550–557

Abstract: Aims: Albuminuric and non-albuminuric phenotypes of chronic kidney disease (CKD) may have different cardiovascular risk and survival in type 1 diabetes (T1DM). Herein we estimated risk of major vascular outcomes by the EURODIAB PCS score and determined ... ...

Abstract	Aims: Albuminuric and non-albuminuric phenotypes of chronic kidney disease (CKD) may have different cardiovascular risk and survival in type 1 diabetes (T1DM). Herein we estimated risk of major vascular outcomes by the EURODIAB PCS score and determined all-cause mortality rate in 774 T1DM according to CKD phenotypes. Methods: We evaluated the distribution of CKD phenotypes [no CKD, stages 1-2, non-albuminuric stage ≥3 (Alb Results: Out of 774 subjects, 692 (89.4%) had no CKD, 53 (6.8%) CKD stages 1-2, 17 (2.2%) Alb Conclusions: In our T1DM cohort, one fifth of those with CKDs were non-albuminuric. This phenotype was associated with higher risk of major outcomes and similar rate of mortality as compared to CKD stages 1-2. The greatest risk and highest mortality occur in patients with Alb
MeSH term(s)	Adult ; Aged ; Albuminuria/complications ; Albuminuria/epidemiology ; Albuminuria/mortality ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/mortality ; Cause of Death ; Cohort Studies ; Cross-Sectional Studies ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/mortality ; Diabetic Angiopathies/epidemiology ; Diabetic Angiopathies/etiology ; Diabetic Angiopathies/mortality ; Diabetic Nephropathies/complications ; Diabetic Nephropathies/epidemiology ; Diabetic Nephropathies/mortality ; Female ; Humans ; Male ; Middle Aged ; Mortality ; Prognosis ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/mortality ; Risk Factors
Language	English
Publishing date	2018-04-03
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1105840-7
ISSN	1873-460X ; 1056-8727
ISSN (online)	1873-460X
ISSN	1056-8727
DOI	10.1016/j.jdiacomp.2018.03.012
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Article ; Online: Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus.

Penno, Giuseppe / Russo, Eleonora / Garofolo, Monia / Daniele, Giuseppe / Lucchesi, Daniela / Giusti, Laura / Sancho Bornez, Veronica / Bianchi, Cristina / Dardano, Angela / Miccoli, Roberto / Del Prato, Stefano

Diabetologia

2017 Volume 60, Issue 6, Page(s) 1102–1113

Abstract: Aims/hypothesis: In a retrospective, observational, cross-sectional, single-centre study, we assessed the prevalence and correlates of different CKD phenotypes (with and without albuminuria) in a large cohort of patients of white ethnicity with type 1 ... ...

Abstract	Aims/hypothesis: In a retrospective, observational, cross-sectional, single-centre study, we assessed the prevalence and correlates of different CKD phenotypes (with and without albuminuria) in a large cohort of patients of white ethnicity with type 1 diabetes. Methods: From 2001 to 2009, 408 men and 369 women with type 1 diabetes (age 40.2 ± 11.7 years, diabetes duration 19.4 ± 12.2 years, HbA Results: Normo- (ACR <3.4), micro- (ACR 3.4-34) or macroalbuminuria (ACR ≥34 mg/mmol) were present in 91.6%, 6.4% and 1.9% of individuals, respectively. eGFR categories 1 (≥90 ml min Conclusions/interpretation: The Alb
Language	English
Publishing date	2017-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-017-4251-1
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Zs.A 279: Show issues

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Article ; Online: Normoalbuminuric chronic kidney disease in type 1 diabetes: is it real and is it serious? Reply to Rigalleau V, Blanco L, Alexandre L et al [letter].

Diabetologia

2017 Volume 60, Issue 10, Page(s) 2123–2125

MeSH term(s)	Albuminuria ; Diabetes Mellitus, Type 1 ; Glomerular Filtration Rate ; Humans ; Renal Insufficiency, Chronic
Language	English
Publishing date	2017-08-02
Publishing country	Germany
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-017-4387-z
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