Publications by authors named "Simona Frontoni"

56 Publications

Metformin Benefits: Another Example for Alternative Energy Substrate Mechanism?

Diabetes Care 2021 Mar;44(3):647-654

Section of Metabolic Diseases and Diabetes, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Since the UK Prospective Diabetes Study (UKPDS), metformin has been considered the first-line medication for patients with newly diagnosed type 2 diabetes. Though direct evidence from specific trials is still lacking, several studies have suggested that metformin may protect from diabetes- and nondiabetes-related comorbidities, including cardiovascular, renal, neurological, and neoplastic diseases. In the past few decades, several mechanisms of action have been proposed to explain metformin's protective effects, none being final. It is certain, however, that metformin increases lactate production, concentration, and, possibly, oxidation. Once considered a mere waste product of exercising skeletal muscle or anaerobiosis, lactate is now known to act as a major energy shuttle, redistributed from production sites to where it is needed. Through the direct uptake and oxidation of lactate produced elsewhere, all end organs can be rapidly supplied with fundamental energy, skipping glycolysis and its possible byproducts. Increased lactate production (and consequent oxidation) could therefore be considered a positive mechanism of action of metformin, except when, under specific circumstances, metformin and lactate become excessive, increasing the risk of lactic acidosis. We are proposing that, rather than considering metformin-induced lactate production as dangerous, it could be considered a mechanism through which metformin exerts its possible protective effect on the heart, kidneys, and brain and, to some extent, its antineoplastic action.
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http://dx.doi.org/10.2337/dc20-1964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896249PMC
March 2021

Glycemic Status Assessment by the Latest Glucose Monitoring Technologies.

Int J Mol Sci 2020 Nov 3;21(21). Epub 2020 Nov 3.

Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita, Fatebenefratelli Hospital, 00186 Rome, Italy.

The advanced and performing technologies of glucose monitoring systems provide a large amount of glucose data that needs to be properly read and interpreted by the diabetology team in order to make therapeutic decisions as close as possible to the patient's metabolic needs. For this purpose, new parameters have been developed, to allow a more integrated reading and interpretation of data by clinical professionals. The new challenge for the diabetes community consists of promoting an integrated and homogeneous reading, as well as interpretation of glucose monitoring data also by the patient himself. The purpose of this review is to offer an overview of the glycemic status assessment, opened by the current data management provided by latest glucose monitoring technologies. Furthermore, the applicability and personalization of the different glycemic monitoring devices used in specific insulin-treated diabetes mellitus patient populations will be evaluated.
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http://dx.doi.org/10.3390/ijms21218243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663245PMC
November 2020

Microvascular impairment as a biomarker of diabetic retinopathy progression in the long-term follow up in type 1 diabetes.

Sci Rep 2020 10 26;10(1):18266. Epub 2020 Oct 26.

Department of Ophthalmology, IRCCS-Fondazione Bietti, Rome, Italy.

This study aimed to explore differences in vascular and structural parameters using optical coherence tomography angiography in patients with type 1 diabetes (DM1) with mild signs of diabetic retinopathy (DR) over a two-year follow-up period. Parafoveal vessel density (PVD) and foveal avascular zone (FAZ) area were analyzed. The thickness of three predefined retinal slabs was measured, including the inner limiting membrane (ILM)-inner plexiform layer (IPL), IPL-inner nuclear layer (INL), and the IPL-outer nuclear layer (ONL). Twenty-two patients with DM1 and 21 controls were included. There was no significant difference in the FAZ area, perimeter and acircularity index between cohorts over time. Baseline superficial capillary plexus PVD was approximately 10% lower in patients with diabetes than in controls (p = 0.001), and was 12% lower at 2 years (p = 0.002). There was no difference in the annual linear trend between the groups (- 0.5% in diabetics vs. controls, p = 0.736). Baseline deep capillary plexus (DCP) PVD was slightly lower in diabetics than in controls (- 4.4%, p = 0.047) and the difference increased at 2 years (- 12.6%, p < 0.001). The annual linear trend was - 2.7% in diabetic patients compared to controls (p = 0.009) In addition, the PVD of the DCP and the intermediate capillary plexus (ICP) were evaluated separately. Regarding the DCP PVD, no statistically significant difference at any time points in diabetic patients compared to controls and no statistically significant difference in the linear trend was found (p > 0.1). Conversely, no difference was recorded for parafoveal ICP density at individual time points (p > 0.1), but a statistically significant difference in the linear trend over time in diabetic patients compared to controls was recoded (- 3.2% per year, p = 0.001). Despite the apparent intergroup differences at baseline in structural OCT parameters, the differences including ILM-IPL (p = 0.273), IPL-INL (p = 0.708), and IPL-ONL (p = 0.054) were modest and not statistically significant with time. Therefore, the microvascular change of the deeper vessels might be a robust biomarker to evaluate the clinical progression of DR in DM1.
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http://dx.doi.org/10.1038/s41598-020-75416-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589477PMC
October 2020

Neuropathic damage in the diabetic eye: clinical implications.

Curr Opin Pharmacol 2020 12 12;55:1-7. Epub 2020 Sep 12.

Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita, Fate Bene Fratelli Hospital, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

In recent years, emerging evidence support that the eye is target of diabetes neuropathy. There are two components of the eye that are mainly involved in the neurodegenerative process induced by diabetes: the retina and the cornea. The study of functional and structural changes in these components of the eye will provide useful information to identify subjects with diabetes at risk of diabetic peripheral neuropathy and dementia. In this review the state of the art regarding the evidence and clinical implications of this emerging concept will be provided. In addition, the relationship between retinal and corneal neurodegeneration with peripheral neuropathy and cognitive decline will be analyzed. Finally, the scientific gaps than need to be covered and will be critically examined.
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http://dx.doi.org/10.1016/j.coph.2020.08.013DOI Listing
December 2020

Early Alterations of Corneal Subbasal Plexus in Uncomplicated Type 1 Diabetes Patients.

J Ophthalmol 2019 2;2019:9818217. Epub 2019 Jul 2.

Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Purpose: The purpose of our study is to describe the in vivo corneal confocal microscopy characteristics of subbasal nerve plexus in a highly selected population of patients affected by type 1 diabetes mellitus (T1DM) without any microvascular diabetes complications.

Methods: We included 19 T1DM patients without diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria. All patients underwent in vivo corneal confocal microscopy and blood analysis to determine subbasal nerve plexus parameters and their correlation with clinical data. We compared the results with 19 healthy controls.

Results: The T1DM group showed a significant decrease of the nerve fiber length (=0.032), the nerve fiber length density (=0.034), the number of fibers (=0.005), and the number of branchings (=0.028), compared to healthy subjects. The nerve fiber length, nerve fiber length density, and number of fibers were directly related to the age at onset of diabetes and inversely to the duration of DM. BMI (body mass index) was highly related to the nerve fiber length ( = -0.6, =0.007), to the nerve fiber length density ( = -0.6, =0.007), and to the number of fibers ( = -0.587, =0.008). No significant correlations were found between the corneal parameters and HbA1c.

Conclusions: Early subclinical fiber corneal variation could be easily detected using in vivo corneal confocal microscopy, even in type 1 diabetes without any microvascular diabetes complications, including diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria.
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http://dx.doi.org/10.1155/2019/9818217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636466PMC
July 2019

Activation of retinal Müller cells in response to glucose variability.

Endocrine 2019 09 20;65(3):542-549. Epub 2019 Jul 20.

Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.

Purpose: In the earliest stages of diabetic retinopathy (DR), a dysfunction of Müller cells, characterized by high levels of glial fibrillary acidic protein (GFAP), and aquaporins (AQP), has been observed. Although chronic hyperglycemia causes the activation of Müller cells, the effect of glycemic fluctuations is yet unknown. The aim of the study was to analyze the impact of glucose variability on rat retinal Müller cells (rMC-1) adapted to either normal (5 mM) or high (25 mM) glucose levels.

Methods: rMC-1 were cultured in a medium containing either 5 mM (N cells) or 25 mM of glucose (H cells) and then incubated for 96 h in a medium containing (a) low glucose (either 1-3 or 5 mM), (b) basal glucose (either 5 or 25 mM), (c) high glucose (either 25 or 45 mM), (d) basal and high glucose alternated every 24 h; (e) low- and high glucose alternated every 24 h; (f) basal glucose with episodes of low glucose for 30 min twice a day. Müller cells activation was evaluated by measuring the levels of GFAP, AQP4, and phospho-active extracellular signal-regulated kinase (pERK).

Results: Under both basal and high glucose concentrations rMC-1 were viable, but their response to glucose excursions was different. In N cells kept under normal (5 mM) glucose, a significant glial activation was measured not only in response to constant high glucose but also to alternating low/high glucose. In H cells, adapted to 25 mM glucose, a significant response was observed only after exposition to a lower (5 mM) glucose concentration.

Conclusion: Our results highlight Müller cells activation in response to glucose variability and a different susceptibility depending on the basal glucose conditions.
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http://dx.doi.org/10.1007/s12020-019-02017-5DOI Listing
September 2019

Urban diabetes: the case of the metropolitan area of Rome.

Acta Biomed 2019 05 23;90(2):209-214. Epub 2019 May 23.

Center for Outcomes Research and Clinical Epidemiology - CORESEARCH.

Background: The world is rapidly urbanizing, causing alarming health problems to their citizens. The Cities Changing Diabetes program aims to address the social factors and cultural determinants that can increase type 2 diabetes (T2D) vulnerability among people living in cities.

Methods: Public data of Italian Institute for Statistics (ISTAT) and available scientific reports were reviewed and findings integrated. The prevalence of T2D in the 8 health districts of Rome was mapped and the correlation between prevalence and social and cultural determinants was assessed.

Results: The metropolitan area of Rome has 4.3 million inhabitants. People over 65 has increased by 136,000 units in the last decade, reaching 631,000 citizens in 2015. Elderly people living alone are 28.4%. The obesity prevalence is 9.3%, as compared to 8.2% in the year 2000. The prevalence of T2D is 6.6%, varying in the different 8 health districts between 5.9% and 7.3%. A linear correlation exists between the prevalence of diabetes in the districts, unemployment rate and use of private transportation rate (Pearson R 0.52 and 0.60, respectively), while an inverse correlation is present with aging index, school education level, and slow mobility rate (Person R -0.57, -0.52, and -0.52, respectively).

Conclusions: Important socio-demographic changes have occurred in Rome during the last decades with a raise in the prevalence of obesity and diabetes. A wide variation exists in the prevalence of T2D among the districts of Rome, associated with social and cultural determinants. This study model can help rethinking diabetes in an urban setting.
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http://dx.doi.org/10.23750/abm.v90i2.8345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776202PMC
May 2019

Flavonoids and Insulin-Resistance: From Molecular Evidences to Clinical Trials.

Int J Mol Sci 2019 Apr 26;20(9). Epub 2019 Apr 26.

Unit of Endocrinology, Diabetes and Metabolism, S.Giovanni Calibita, Fatebenefratelli Hospital, 00186 Rome, Italy.

Insulin-resistance is one of the main factors responsible for the onset and progression of Metabolic Syndrome (MetS). Among all polyphenols, the effects of flavonoids and their main food sources on insulin sensitivity have been widely evaluated in molecular and clinical studies. The aim of this review is to analyse the data observed in vitro, in vivo and in clinical trials concerning the effects of flavonoids on insulin resistance and to determine the molecular mechanisms with which flavonoids interact with insulin signaling.
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http://dx.doi.org/10.3390/ijms20092061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539502PMC
April 2019

Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus.

Acta Diabetol 2019 Jun 2;56(6):605-617. Epub 2019 Jan 2.

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Achieving and maintaining recommended glycemic targets without causing adverse e ffects, including hypoglycemia, is challenging, especially in older patients with type 2 diabetes mellitus (T2DM). The introduction of dipeptidyl peptidase-4 (DPP-4) inhibitors, more than 10 years ago, has provided an alternative to conventional medications for the intensification of glucose-lowering treatment after failure of metformin monotherapy, and therefore, marked an important advance in the management of T2DM. By prolonging the activity of incretin hormones, DPP-4 inhibitors induce insulin release and decrease glucagon secretion in a glucose-dependent manner. This results in a more physiologic glycemic control as compared to that ensured by insulin secretagogues (sulfonylureas and glinides). Overall, DPP-4 inhibitors have a favorable safety profile and can be used without dose adjustments in older adults and in patients with mild renal impairment; they have a neutral effect on body weight and do not cause hypoglycemia by themselves. Safety issues, reported mainly in post-marketing surveillance programs and including cardiovascular outcomes and the risk of acute pancreatitis, are being extensively investigated. The aim of this review is to discuss the impact of DPP-4 inhibitors on the treatment of T2DM, after 10 years of experience, with an emphasis on diabetes care in Italy. We will first describe T2DM treatment in Italy and then provide an overview of the main findings from randomized controlled trials, real-world studies and post-marketing surveillance programs with DPP-4 inhibitors.
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http://dx.doi.org/10.1007/s00592-018-1271-3DOI Listing
June 2019

Association between Early Neuroretinal Dysfunction and Peripheral Motor Unit Loss in Patients with Type 1 Diabetes Mellitus.

J Diabetes Res 2018 4;2018:9763507. Epub 2018 Oct 4.

Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Objectives: It has been already confirmed that retinal neurodegeneration has a predictive value in the development of microvascular alterations in diabetic retinopathy. However, no data are available on the association between neuroretinal dysfunction and peripheral motor unit loss. Our study, therefore, was aimed at investigating the hypothesis that retinal neurodegeneration could be considered an early marker of diabetic peripheral neuropathy (DPN).

Methods: 20 T1DM patients with no symptoms/signs of peripheral polyneuropathy, without DR or with very mild nonproliferative DR, and 14 healthy controls (C) age- and gender-matched were enrolled. The following electrophysiological tests were performed: standard nerve conduction studies (NCS) and incremental motor unit number estimation (MUNE) from the abductor hallux (AH) and abductor digiti minimi (ADM). Neuroretinal function was studied by multifocal electroretinogram (MfERG) recordings, measuring response amplitude density (RAD) and implicit time (IT) from rings and sectors of superior (S)/inferior (I)/temporal (T)/nasal (N) macular sectors up to 10 degrees of foveal eccentricity.

Results: MfERG RADs from rings and sectors were significantly reduced in T1DM ( < 0.05) vs. C. ADM MUNE and AH MUNE were significantly decreased in T1DM ( = 0.039 and < 0.0001, respectively) vs. C. A positive correlation between mean MfERG RADs from the central 5 degrees of the four (S, I, T, and N) macular sectors and lower limb motor unit number ( = 0.50, = 0.041; = 0.64, = 0.005; = 0.64, = 0.006; and = 0.61, = 0.010, respectively) was observed in T1DM patients. No abnormalities of NCS were found in any subject.

Conclusions: The motor unit loss on the one hand and neuroretinal dysfunction on the other hand are already present in T1DM patients without DPN. The relationship between neuroretinal dysfunction and motor unit decline supports the hypothesis that neuroretina may represent a potential "window" to track the early neurogenic damage in diabetes.
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http://dx.doi.org/10.1155/2018/9763507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193343PMC
January 2019

Early and localized retinal dysfunction in patients with type 1 diabetes mellitus studied by multifocal electroretinogram.

Acta Diabetol 2018 Nov 28;55(11):1191-1200. Epub 2018 Aug 28.

IRCCS-Fondazione Bietti, Via Livenza 1, 00198, Rome, Italy.

Aims: To investigate the function of localized retinal areas in highly selected type 1 diabetes mellitus patients (DM1) with no or mild signs of diabetic retinopathy (NO DR and NPDR, respectively) and its correlation with age, diabetes duration and glycemic control.

Methods: Multifocal electroretinograms (mfERG) were recorded in 35 eyes of 18 NO DR patients and 38 eyes of 19 NPDR patients. Thirty-one eyes of 17 normal subjects were enrolled as controls. N1-P1 response amplitude densities (RADs) and P1 implicit times (ITs) from isolated (R1: 0°-2.5°, R2: 2.5°-5°, R3: 5°-10°) and combined (R1 + R2, R2 + R3 and R1 + R2 + R3) annular rings and from four retinal sectors (nasal, N; temporal, T; superior, S and inferior, I) with increasing eccentricities up to 10° (S1, S2, S3, S1 + S2, S1 + S2 + S3) were measured. The statistical differences between DM1 groups and controls were tested by ANOVA. The electrophysiological data were correlated with age, duration of diabetes and glycated hemoglobin (HbA1c) level using the Pearson's test.

Results: MfERG RADs, but not ITs, from all isolated and combined rings and sectors up to 10° of foveal eccentricity were statistically different between DM1 groups compared to controls. No significant differences were found between NO DR and NPDR patients. The mfERG abnormalities of the central retinal areas were correlated significantly with age in both DM1 groups and with diabetes duration mainly in NPDR group.

Conclusions: In DM1 patients, localized retinal dysfunction, described by reduced mfERG RAD, can be observed also in the absence of clinical signs of DR and it is related to aging.
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http://dx.doi.org/10.1007/s00592-018-1209-9DOI Listing
November 2018

Cardiovascular Autonomic Neuropathy and Glucose Variability in Patients With Type 1 Diabetes: Is There an Association?

Front Endocrinol (Lausanne) 2018 19;9:174. Epub 2018 Apr 19.

First Department of Medicine, University of Szeged, Szeged, Hungary.

Introduction: The oxidative stress associated with glucose variability might be responsible for neuronal damage while autonomic neuropathy (AN) has a detrimental effect on metabolism. The aim of the study was to find relationship between AN and GV in type 1 diabetic patients and to identify further factors that affect GV.

Patients And Methods: Twenty type 1 diabetic patients were involved (age: 39.5 ± 3.4 years, duration of diabetes: 17.5 ± 2.5 years; HbA1c: 8.1 ± 0.2%, mean ± SE). AN was assessed by the cardiovascular reflex tests. The interstitial glucose levels were determined following insertion of a subcutaneous electrode during the continuous glucose monitoring (CGM) method on six consecutive days. GV was characterized by calculation of four parameters.

Results: SD of interstitial glucose values correlated positively with the overall AN score and the degree of the orthostatic reduction of systolic blood pressure (AN-score-SD ρ = 0.47,  < 0.05; orthostasis-SD: ρ = 0.51,  < 0.05). Mean absolute glucose (MAG) correlated with three parameters of AN (AN-score-MAG: ρ = 0.62,  < 0.01; 30/15 ratio-MAG: ρ = -0.50,  < 0.05; orthostasis-MAG: ρ = 0.59,  < 0.01). The HbA1c also correlated with two parameters of GV (HbA1c-continuous overlapping net glycemic action: ρ = 0.56,  < 0.05; HbA1c-MAG: ρ = 0.45,  < 0.05). The frequency of hypoglycemia did not exhibit any correlation with measures of GV.

Conclusion: Severity of glucose variability but not overall glucose load correlates with both parasympathetic and sympathetic dysfunctions in type 1 diabetes. Higher HbA1c is associated with more severe glucose variability. The observed correlation between increased glucose variability and the severity of AN necessitates the further exploration of this relationship.
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http://dx.doi.org/10.3389/fendo.2018.00174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916962PMC
April 2018

Effect of the GSTM1 gene deletion on glycemic variability, sympatho-vagal balance and arterial stiffness in patients with metabolic syndrome, but without diabetes.

Diabetes Res Clin Pract 2018 Apr 13;138:158-168. Epub 2018 Feb 13.

Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Dept. of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. Electronic address:

Aims: An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance.

Methods: A hundred metabolic syndrome patients without diabetes underwent GST gene polymorphism analysis and a sub-sample 36 patients were randomly selected to investigate the correlation between GST gene polymorphisms and GV, and sympatho-vagal (SV) balance and arterial stiffness.

Results: GSTM1 showed a significant association with several GV, arterial stiffness, and SV balance indexes. In particular, the GSTM1 deletion positively correlates with lower values of these indexes when compared to the presence of the gene.

Conclusions: Therefore, we suggested a global influence of GSTM1 deletion on the GV, arterial stiffness, and SV balance pathways in MetS patients, probably also interacting with AMP-activated protein kinase (AMPK) regulation. Our novel findings indicate GSTM1 could be a risk locus in MetS development and shed light novel scenarios on the role of glucose fluctuations in neurological impairments.
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http://dx.doi.org/10.1016/j.diabres.2018.02.006DOI Listing
April 2018

Long-Term Effectiveness of Liraglutide for Treatment of Type 2 Diabetes in a Real-Life Setting: A 24-Month, Multicenter, Non-interventional, Retrospective Study.

Adv Ther 2018 02 21;35(2):243-253. Epub 2017 Dec 21.

CORESEARCH-Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy.

Introduction: The aim of the study was to evaluate whether the reduction in glycated hemoglobin (HbA1c) observed in clinical trials with liraglutide in type 2 diabetes (T2D) could be attained in routine clinical practice.

Methods: ReaL was a multicenter, non-interventional, observational, retrospective, longitudinal study on the effectiveness of liraglutide, a human glucagon-like peptide-1 analog, in individuals with T2D treated in daily practice in Italy. Between 26 March and 16 November 2015, data were taken from clinical records of patients aged ≥ 18 years with treatment follow-up data of up to 24 months and who received their first prescription of liraglutide in 2011.

Results: A total of 1723 patients were included in the analysis. At baseline, mean age was 58.9 years, duration of diabetes was 9.6 years, and HbA1c was 8.3%. At 12 months, 36.1% of patients were prescribed the maximum 1.8 mg dose; 43.5% [95% confidence interval (CI): 40.9; 46.2] of patients attained the primary outcome of a reduction in HbA1c of ≥ 1% point at 12 months. At 24 months, 40.9% (95% CI 38.1; 43.7) of patients had attained the HbA1c target of ≤ 7%. Additionally, body weight significantly decreased by 3.4 kg (95% CI - 3.6; - 3.1, p < 0.0001).

Conclusion: In this observational study conducted in routine clinical practice for up to 2 years, treatment with liraglutide improved HbA1c and reduced body weight in a similar fashion to that observed under randomized clinical trial conditions. The data support the use of liraglutide as an effective treatment for T2D in clinical practice.

Funding: Novo Nordisk S.p.A.

Trial Registration: ClinicalTrials.gov identifier, NCT02255266.
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http://dx.doi.org/10.1007/s12325-017-0652-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818560PMC
February 2018

Single Retinal Layer Evaluation in Patients with Type 1 Diabetes with No or Early Signs of Diabetic Retinopathy: The First Hint of Neurovascular Crosstalk Damage between Neurons and Capillaries?

Ophthalmologica 2017 8;237(4):223-231. Epub 2017 Apr 8.

Department of Ophthalmology, G.B. Bietti Eye Foundation-IRCCS, Rome, Italy.

Purpose: To analyze the retinal-choroidal changes in type 1 diabetes mellitus (DM1) patients with no or early signs of diabetic retinopathy (DR).

Methods: Seventy-six eyes of 38 DM1 patients and 26 control eyes were included. Nine individual retinal layer thickness measurements were obtained using the spectral domain-optical coherence tomography automated segmentation algorithm.

Results: The retinal nerve fiber layer was slightly thinner in all explored quadrants, even if the reduction was not significant in DM1 eyes versus control eyes. The inner nuclear layer (INL) thickness was thicker in all DM1 eyes versus control eyes in all quadrants (p < 0.050). Analyses adjusting for inner retinal thickness in all sectors confirmed INL thickening by about 4%, and also found a significant thinning of the ganglion cell layer (GCL) by about 3.5% in all DM1 subjects versus controls (p < 0.050).

Conclusion: DM1 patients with no or early signs of DR present retinal changes particularly at the INL and GCL that might be correlated to initial findings of neurodegeneration.
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http://dx.doi.org/10.1159/000453551DOI Listing
September 2017

Retinal neurodegeneration in patients with type 1 diabetes mellitus: the role of glycemic variability.

Acta Diabetol 2017 May 25;54(5):489-497. Epub 2017 Feb 25.

Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Aims: Recent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified.

Methods: To explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants (C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal (N)/temporal (T)/superior (S)/inferior (I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring.

Results: The difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant (F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (-3.9 for noDR and -4.9 for NPDR), without any relevant difference between them (-1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32-15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33-15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index (r = -0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action -1, -2, -4 h (r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL (r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides resulted both independent predictors of increased INL thickness. No correlation was found with HbA1c.

Conclusions: Early structural damage of neuroretina in persons with Type 1 DM patients is related to glucose fluctuations. GV should be addressed, even in the presence of a good metabolic control.
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http://dx.doi.org/10.1007/s00592-017-0971-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385321PMC
May 2017

Early microvascular retinal changes in optical coherence tomography angiography in patients with type 1 diabetes mellitus.

Acta Ophthalmol 2017 Dec 16;95(8):e751-e755. Epub 2017 Feb 16.

Fondazione G.B.Bietti-IRCCS, Rome, Italy.

Purpose: Diabetic retinopathy (DR) can lead to significant vision loss and blindness and has a particularly high prevalence in patients with type 1 diabetes (DM1). In this study, we investigate quantitative differences in optical coherence tomography angiography (OCTA) data between DM1 patients with no or mild signs of retinopathy and non-diabetic subjects.

Methods: Optical coherence tomography angiography (OCTA) imaging was performed on DM1 patients with no or mild nonproliferative diabetic retinopathy and healthy, age-matched controls. Parafoveal vessel density and foveal avascular zone (FAZ) area in the deep capillary plexus (DCP) and superficial capillary plexus (SCP) were calculated with automated quantification software and compared between patient cohorts.

Results: A significant decrease in parafoveal vessel density was seen in the DCP of DM1 patients compared to non-diabetic controls (57.0 ± 3.3% versus 60.7 ± 2.4%, p < 0.001). There was no significant difference in SCP parafoveal vessel density, DCP FAZ area, or SCP FAZ area between cohorts.

Conclusion: M1 patients with no or mild signs of retinopathy have reduced parafoveal vessel density in the DCP on OCTA when compared to non-diabetic controls. These OCTA findings suggest that parafoveal capillary nonperfusion is an early process in DM1-related retinal changes and occurs initially at the level of the DCP. Further investigation is needed to understand the prognostic role of these vascular changes.
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http://dx.doi.org/10.1111/aos.13404DOI Listing
December 2017

Position Statement on the management of continuous subcutaneous insulin infusion (CSII): The Italian Lazio experience.

J Diabetes 2016 Jan 26;8(1):41-4. Epub 2015 Oct 26.

Department of Experimental Medicine, University Sapienza, Rome, Italy.

This document has been developed by a group of Italian diabetologists with extensive experience in continuous subcutaneous insulin infusion (CSII) therapy to provide indications for the clinical management of CSII in diabetic patients (both type 1 and type 2) based on delivery mode operating in Italy. Although the potential benefits of pump therapy in achieving glycemic goals is now accepted, such results cannot be obtained without specific knowledge and skills being conveyed to patients during ad hoc educational training. To ensure that these new technologies reach their full effectiveness, as demonstrated theoretically and clinically, a careful assessment of the overall therapeutic and educational process is required, in both qualitative and quantitative terms. Therefore, to ensure the cost-effectiveness of insulin pump therapy and to justify reimbursement of therapy costs by the National Health System in Italy, in this article we present a model for diabetes and healthcare centers to follow that provides for different levels of expertise in the field of CSII therapy. This model will guarantee the provision of excellent care during insulin pump therapies, thus representing the basis for a successful outcome and expansion of this form of insulin treatment in patients with diabetes while also keeping costs under control.
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http://dx.doi.org/10.1111/1753-0407.12321DOI Listing
January 2016

The social burden of hypoglycemia in the elderly.

Acta Diabetol 2015 Aug 8;52(4):677-85. Epub 2015 Feb 8.

Italian Barometer Diabetes Observatory, Università Tor Vergata, Rome, Italy,

Aims: The study aimed to evaluate the frequency of episodes of symptomatic hypoglycemia (SH) in elderly patients with type 2 diabetes and their impact on quality of life.

Methods: The study was conducted in 12 Italian regions. Participants filled in a questionnaire collecting data on socio-demographic and clinical characteristics and episodes of SH occurred in the last 4 weeks. The questionnaire included validated scales measuring fear of hypoglycemia (FHQ), psychological well-being (WHO-5), and diabetes-related distress (PAID-5).

Results: Overall, 1,323 participants were involved (mean age 70.0 ± 8.7, 47.6 % male, disease duration 15.6 ± 11.7, 63.2 % treated with oral agents, 16.9 % with insulin alone, 14.4 % with insulin plus oral agents), of whom 44.6 % reported 1-3 episodes of SH and 23.8 % reported more than 3 episodes. Patients who reported SH had significantly higher levels of fear of hypoglycemia, lower psychological well-being, and higher diabetes-related distress (p < 0.0001 for all the scales). At multivariate analysis, the experience of more than 3 episodes of hypoglycemia was associated with a 13-fold higher risk of high fear of hypoglycemia (aOR = 13.3; CI 95 % 8.4-21.0), an almost 60-fold higher risk of high diabetes-related distress (PAID-5 score ≥40) (aOR = 59.1; CI 95 % 29.2-119.8), and a higher risk of low psychological well-being (WHO-5 <50) (aOR = 1.5; CI 95 % 0.9-2.4).

Conclusions: The occurrence of symptoms of hypoglycemia is very common among older adults with diabetes and their presence is associated with an extremely negative impact on quality of life. Minimizing the risk of hypoglycemia represents a high priority in the diabetes treatment of elderly people.
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http://dx.doi.org/10.1007/s00592-015-0717-0DOI Listing
August 2015

Acute hyperglycemia reduces cerebrovascular reactivity: the role of glycemic variability.

J Clin Endocrinol Metab 2014 Aug 30;99(8):2854-60. Epub 2014 May 30.

Unit of Endocrinology, Diabetes, and Metabolism (I.G., A.D.F., F.P., I.M., D.Y., S.F.); Department of Neurology (P.Pal., F.P.); and Fatebenefratelli Association for Research Unit of Internal Medicine (S.D., P.Pas.) and Service of Medical Statistics and Information Technology (S.D., P.Pas.), S. Giovanni Calibita Fatebenefratelli Hospital, 00186 Rome, Italy; Department of Systems Medicine (I.G., A.D.F., F.P., I.M., D.Y., D.L., S.F.), University of Rome Tor Vergata, 00133 Rome, Italy; Department of Neurology (P.Pal., R.A., F.V.), Campus Bio-Medico University, 00128 Rome, Italy; and Unit of Health Management (S.D.), Ministry of Health, Viale Giorgio Ribotta 5, 00144 Rome, Italy.

Context: Cerebral vasomotor reactivity (CVR) is reduced in patients with diabetes mellitus (DM), and glucose variability (GV) might be responsible for cerebrovascular damage.

Objective: Studying patients with insulin resistance without DM, we explored the role of GV in impairing CVR.

Patients: We studied 18 metabolic syndrome (MS) patients without DM, 9 controls (C), and 26 patients with DM.

Main Outcome Measures: Groups were compared in terms of CVR, GV, and 24-hour blood pressure. To evaluate the impact of acute hyperglycemia on CVR, a hyperglycemic clamp was performed in MS patients and controls.

Results: Baseline CVR was reduced in DM vs C and MS (C vs DM = 20.2, 95% CI = 3.5-36.9, P = .014; and MS vs DM = 22.2, 95% CI = 8.6-35.8, P = .001), but similar between MS and C (MS vs C = 2.0, 95% CI = -14.7 to 18.7, P = .643). During acute hyperglycemia, CVR fell in MS and C to values comparable to DM. GV progressively increased from C to MS to DM. In MS, CVR at 120 minutes and GV displayed a negative correlation (r = -0.48, P = .043), which did not change after controlling for mean 24-hour systolic and diastolic blood pressure. In MS, the CVR reduction was significantly correlated to GV (r = 0.55, P = .02).

Conclusions: GV is increased in patients with MS but without DM and is the major predictor of CVR reduction induced by acute hyperglycemia, possibly representing the earliest cause of cerebrovascular damage in DM.
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http://dx.doi.org/10.1210/jc.2014-1087DOI Listing
August 2014

Cerebral hemodynamics and systemic endothelial function are already impaired in well-controlled type 2 diabetic patients, with short-term disease.

PLoS One 2013 31;8(12):e83287. Epub 2013 Dec 31.

Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, University of Rome Tor Vergata, Rome, Italy.

Objective: Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN).

Research Design And Methods: Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also.

Results: FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05).

Conclusions: In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083287PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877017PMC
August 2014

Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

PLoS One 2013 23;8(10):e77440. Epub 2013 Oct 23.

Department of Systems Medicine, University of Rome-Tor Vergata, Rome, Italy.

Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl) at 1 h during an oral glucose tolerance test (OGTT) can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high). The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low). To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001) and insulin clearance (P = 0.006) after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02) in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077440PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806727PMC
February 2015

Glucose variability: An emerging target for the treatment of diabetes mellitus.

Diabetes Res Clin Pract 2013 Nov 25;102(2):86-95. Epub 2013 Sep 25.

Dipartimento di Medicina dei Sistemi, Università degli Studi di Roma "Tor Vergata", Italy.

Alterations in glucose metabolism in individuals with diabetes have been considered for many years, as they appear at first glance, i.e., simply as hyperglycemia, and its surrogate marker, glycated hemoglobin (HbA1c), used both to estimate the risk of developing diabetic complications and to define the targets and measure the efficacy of diabetes treatments. However, over time diabetes-related glycemic alterations have been considered in more complex terms, by attempting to identify the role of fasting glycemia, postprandial glycemia and hypoglycemia in the overall assessment of the disease. This set of evaluations has led to the concept of glucose variability. Although intuitively easy to understand, it cannot be equally simply translated into terms of definition, measuring, prognostic and therapeutic impact. The literature available on glucose variability is extensive yet confused, with the only common element being the need to find out more on the subject. The purpose of this manuscript is not only to review the most recent evidence on glucose variability, but also to help the reader to better understand the available measurement options, and how the various definitions can differently be related with the development of diabetic complications. Finally, we provide how new and old drugs can impact on glucose variability.
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http://dx.doi.org/10.1016/j.diabres.2013.09.007DOI Listing
November 2013

Differences in insulin clearance between metabolically healthy and unhealthy obese subjects.

Acta Diabetol 2014 Apr 30;51(2):257-61. Epub 2013 Aug 30.

Department of Systems Medicine, University of Rome-Tor Vergata, Rome, Italy.

Metabolically healthy obese (MHO) are relatively insulin sensitive and have a favorable cardio-metabolic risk profile compared with metabolically abnormal obese (MAO). To evaluate whether MAO individuals have a decreased insulin clearance compared with MHO individuals, 49 MHO, 147 MAO, and 172 non-obese individuals were analyzed in this cross-sectional study. Insulin clearance and insulin sensitivity were assessed through euglycemic hyperinsulinemic clamp. MHO subjects exhibited significant lower triglycerides, total cholesterol, 2-h post-challenge glucose, fasting and 2-h post-challenge insulin, steady-state plasma insulin, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase as compared with MAO individuals. Disposition index was higher in MHO subjects as compared with MAO individuals after adjusting for gender and age (P = 0.04). Insulin clearance was significantly lower in MAO individuals as compared with MHO and non-obese individuals. The difference between the two obese subgroups remained significant after adjusting for gender, age, waist circumference, fat mass, and insulin-stimulated glucose disposal (P = 0.03). The hepatic insulin extraction (C-peptide/insulin) in the fasting state was significantly higher in MHO subjects as compared with MAO individuals (P < 0.0001). In univariate analysis adjusted for gender and age, insulin clearance was correlated with hepatic insulin extraction (P = 0.01). In conclusion, insulin clearance differs among obese subjects with different metabolic phenotypes. Impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia observed in MAO individuals.
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http://dx.doi.org/10.1007/s00592-013-0511-9DOI Listing
April 2014

Insulin clearance is associated with carotid artery intima-media thickness.

Atherosclerosis 2013 Aug 22;229(2):453-8. Epub 2013 Jun 22.

Department of Systems Medicine, University of Rome-Tor Vergata, Rome, Italy.

Objective: The aim of this study was to investigate whether insulin clearance is independently associated with carotid artery intima-media thickness (IMT), a well-recognized index of vascular damage.

Methods: 361 Non-diabetic Caucasian subjects were subjected to euglycemic hyperinsulinemic clamp to assess insulin sensitivity, and insulin clearance. IMT of the common carotid was measured by ultrasonography.

Results: Among the study group, 270 subjects had normal glucose tolerance, 33 had impaired fasting glucose, and 58 had impaired glucose tolerance. Univariate correlations showed that age, BMI, waist, blood pressure, triglycerides, fasting and 2-h post-load glucose and insulin levels were positively correlated with carotid IMT whereas HDL, insulin clearance, and insulin-stimulated glucose disposal were negatively correlated with IMT. A multivariate regression analysis in a model including, in addition to insulin clearance, age, gender, BMI, waist, blood pressure, triglycerides, HDL, fasting and 2-h post-load glucose, insulin-stimulated glucose disposal, fasting and 2-h post-load insulin showed that the traits independently associated with carotid IMT were BMI (β = 0.42, P < 0.0001), insulin clearance (β = -0.29, P < 0.0001), age (β = 0.19, P < 0.0001), waist (β = 0.18, P = 0.01), diastolic blood pressure (β = 0.17, P = 0.01), and 2-h post-load glucose (β = 0.12, P = 0.03). These factors explained 26% of the variance in carotid IMT. Subjects in the lowest tertile of insulin clearance had a 4.06-fold higher odds of having vascular damage (IMT > 0.9 mm) as compared with those in the highest tertile (OR 4.06, 95%CI 1.15-13.24).

Conclusions: Insulin clearance is independently associated with carotid IMT in adult non-diabetic subjects. Individuals with lower levels of insulin clearance have a higher odds of vascular damage.
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http://dx.doi.org/10.1016/j.atherosclerosis.2013.06.011DOI Listing
August 2013

Preliminary evidence that obese patients with obstructive sleep apnea/hypopnea syndrome are refractory to the acute beneficial metabolic effects of a very low calorie diet.

Acta Diabetol 2013 Aug 6;50(4):639-43. Epub 2013 Jun 6.

Department of Medicina dei Sistemi, University of Rome Tor Vergata, Rome, Italy.

Since obesity seems to play a causal role in both obstructive sleep apnea/hypopnea syndrome (OSAHS) and type 2 diabetes, the question arises whether diet-induced weight loss is equally efficacious in type 2 diabetic patients with and without OSAHS. The present study was aimed to investigate the effect of 1 week very low calorie diet (VLCD) on oxygen desaturation index (ODI) and on glucose regulation in OSAHS versus non-OSAHS patients. Fourteen patients with type 2 diabetes mellitus and morbid obesity were enrolled. According to ODI, patients were divided into 2 groups (with and without OSAHS) and evaluated by a hyperglycemic clamp study, before and after a 7 day-VLCD. After a VLCD, a significant reduction of anthropometric parameters, in the overall group and in subgroups, was observed. M-value and acute insulin response increased significantly only in patients without obstructive sleep apnea (990.10 ± 170.19 vs. 1,205.22 ± 145.73 μmol min(-1) m(-2), p = 0.046; -1.05 ± 8.40 vs. 48.26 ± 11. 90 pmol/L, p = 0.028, respectively). The average 24-h heart rate (24-h HR) fell significantly (p = 0.05), primarily because of a decrease during daytime (p = 0.041), in the whole group. In conclusion, we observed that morbidly obese patients with type 2 diabetes and OSAHS are specifically resistant to the acute beneficial effects of VLCD on metabolic parameters. Our preliminary observation deserves further investigation to clarify the pathogenetic mechanisms involved.
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http://dx.doi.org/10.1007/s00592-013-0487-5DOI Listing
August 2013

Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

J Clin Endocrinol Metab 2013 May 28;98(5):2100-5. Epub 2013 Mar 28.

Department of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, 56124 Pisa, Italy.

Context: In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis.

Objective: The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL.

Patients And Methods: The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well.

Results: A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function.

Conclusions: Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.
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http://dx.doi.org/10.1210/jc.2012-3971DOI Listing
May 2013