Glycometabolic Control Research Articles

Нарушение углеводного обмена после перенесенной новой коронавирусной инфекции (COVID-19): акцент на контроль уровня гликемии

Diabetes mellitus (DM) is one of the most important comorbidities associated with the severity of all three known pathogenic human coronavirus infections, including the SARS-CoV-2 (COVID-19) virus. The implementation of regular monitoring of plasma glucose is important during a pandemic for patients with type I and type II diabetes. Less studied within the framework of COVID-19 is the problem of developing diabetes after a coronavirus infection. The first part of the review discusses the etiopathogenesis of DM in the post-COVID syndrome and presents clinical observations indicating an increased risk of developing diabetes after SARS-CoV-2 infection, which predetermines the need for glycometabolic control in the post-COVID syndrome. Hyperglycemia is a leading factor in the development of complications of DM. Glycated hemoglobin is the "gold standard" for monitoring glycemic control, but this indicator does not provide complete information about daily and intraday changes in glucose levels. An important place in the prevention of complications in patients with DM, especially during the pandemic of a new coronavirus infection, is occupied by regular self-monitoring of glucose levels. An important aspect of the technical impact on the adherence of patients to self-control and treatment of DM is the availability of convenient communication between the patient and the doctor, in particular, the possibility of contact remotely via a computer and mobile phone. In the second part of the review, the capabilities of the new model of the Contour glucometer line, the Contour Plus One glucometer, are considered.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

Effects of cerebellar tDCS on glycometabolic control

Effects of cerebellar tDCS on glycometabolic control

No Evidence of Long-Term Disruption of Glycometabolic Control After SARS-CoV-2 Infection.

PurposeTo assess whether dysglycemia diagnosed during severe acute respiratory syndrome coronavirus 2 pneumonia may become a potential public health problem after resolution of the infection. In an adult cohort with suspected coronavirus disease 2019 (COVID-19) pneumonia, we integrated glucose data upon hospital admission with fasting blood glucose (FBG) in the year prior to COVID-19 and during postdischarge follow-up.MethodsFrom February 25 to May 15, 2020, 660 adults with suspected COVID-19 pneumonia were admitted to the San Raffaele Hospital (Milan, Italy). Through structured interviews/ medical record reviews, we collected demographics, clinical features, and laboratory tests upon admission and additional data during hospitalization or after discharge and in the previous year. Upon admission, we classified participants according to American Diabetes Association criteria as having (1) preexisting diabetes, (2) newly diagnosed diabetes, (3) hyperglycemia not in the diabetes range, or (4) normoglycemia. FBG prior to admission and during follow-up were classified as normal or impaired fasting glucose and fasting glucose in the diabetes range.ResultsIn patients with confirmed COVID (n = 589), the proportion with preexisting or newly diagnosed diabetes, hyperglycemia not in the diabetes range and normoglycemia was 19.6%, 6.7%, 43.7%, and 30.0%, respectively. Patients with dysglycemia associated to COVID-19 had increased markers of inflammation and organs’ injury and poorer clinical outcome compared to those with normoglycemia. After the infection resolved, the prevalence of dysglycemia reverted to preadmission frequency.ConclusionsCOVID-19–associated dysglycemia is unlikely to become a lasting public health problem. Alarmist claims on the diabetes risk after COVID-19 pneumonia should be interpreted with caution.

Adult Pig Islet Isolation.

Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of pancreatic β cells, which results in little or no insulin production. Islet transplantation plays an important role in the treatment of T1DM, with the improved glycometabolic control, the reduced progression of complications, the reduction of hypoglycemic episodes when compared with traditional insulin therapy. The results of phase III clinical trial also demonstrated the safety and efficacy of islet allotransplantation in T1DM. However, the shortage of pancreas donors limits its widespread use. Animals as a source of islets such as the pig offer an alternative choice. Because the architecture of the pig pancreas is different from the islets of mice or humans, the pig islet isolation procedure is still challenging. Since the translation of alternative porcine islet sources (xenogeneic) to the clinical setting for treating T1DM through cellular transplantation is of great importance, a cost-effective, standardized, and reproducible protocol for isolating porcine islets is urgently needed. This manuscript describes a simplified and cost-effective method to isolate and purify adult porcine islets based on the previous protocols that have successfully transplanted porcine islets to non-human primates. This will be a beginners guide without the use of specialized equipment such as a COBE 2991 Cell Processor.

Biliverdin reductase-A protein levels are reduced in type 2 diabetes and are associated with poor glycometabolic control

AimBiliverdin reductase-A (BVR-A) other than its canonical role in the degradation pathway of heme as partner of heme oxygenase-1 (HO1), has recently drawn attention as a protein with pleiotropic functions involved in insulin-glucose homeostasis. However, whether BVR-A expression is altered in type 2 diabetes (T2D) has never been evaluated. Main methodsBVR-A protein levels were evaluated in T2D (n = 44) and non-T2D (n = 29) subjects, who underwent complete clinical workup and routine biochemistry. In parallel, levels HO1, whose expression is regulated by BVR-A as well as levels of tumor necrosis factor α (TNFα), which is a known repressor for BVR-A with pro-inflammatory properties, were also assessed. Key findingsBVR-A levels were significantly lower in T2D subjects than in non-T2D subjects. Reduced BVR-A levels were associated with greater body mass, systolic blood pressure, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglycerides, transaminases and TNFα, and with lower high-density lipoprotein (HDL) levels. Lower BVR-A levels are associated with reduced HO1 protein levels and the multivariate analysis showed that BVR-A represented the main determinant of HO1 levels in T2D after adjustment. In addition, reduced BVR-A levels were able to predict the presence of T2D with AUROC = 0.69. for potential confounders. SignificanceOur results demonstrate for the first time that BVR-A protein levels are reduced in T2D individuals, and that this alteration strictly correlates with poor glycometabolic control and a pro-inflammatory state. Hence, these observations reinforce the hypothesis that reduced BVR-A protein levels may represent a key event in the dysregulation of intracellular pathways finally leading to metabolic disorders.

Renal and metabolic effects of SGLT-2i and DPP-4i according to basal estimated glomerular filtration rate: Analysis from GIOIA, an observational prospective study

In the GIOIA study, users of both SGLT-2i and DPP-4i improved glycometabolic control, after 12 months, independently from baseline eGFR levels. Moreover, both classes led to a significant decrease in eGFR in participants with eGFR ≥ 90 ml/min/1.73 m2 and no deterioration in case of mild impairment of renal function.

Biomarkers of Glyco-Metabolic Control in Hemodialysis Patients: Glycated Hemoglobin vs. Glycated Albumin.

Background and Objectives: Glycated hemoglobin (HbA1c) dosage is considered the gold standard in glycol-metabolic monitoring, but it presents limits, which can underestimate the glycemia trend. In this regard, it was introduced the glycated albumin (GA). The aim of the study is to verify the predictivity of the GA compared to HbA1c in identifying glyco-metabolic alterations in non-diabetic and diabetic hemodialysis (HD) patients. Materials and Methods: For this purpose, we conducted a multicenter study involving one analysis laboratory and six dialysis centers in the Lazio region (Rome, Italy). Both diabetic and non-diabetic HD patients represent the study population, and the protocol included five time points. Results: The analyzed data highlighted the ability of GA to predict changes in glycemic metabolism in HD patients, and GA values are not significantly influenced, like HbA1c, by dialysis therapy itself and by comorbidities of the uremic state, such as normochromic and normocytic anemia. Thus, GA seems to reflect early glyco-metabolic alterations, both in patients with a previous diagnosis of diabetes and in subjects without diabetes mellitus. As part of this study, we analyzed two HD patients (one diabetic and one non-diabetic) in which GA was more predictive of glycol-metabolic alterations compared to HbA1c. Our study confirms the need to compare classical biomarkers used for the monitoring of glyco-metabolic alterations with new ones, likely more reliable and effective in specific subgroups of patients in which the classic biomarkers can be influenced by the preexisting pathological conditions. Conclusions: In conclusion, our evidence highlights that in uremic patients, GA shows a better ability to predict glyco-metabolic alterations allowing both an earlier diagnosis of DM and a prompt modulation of the hypoglycemic therapy, thus improving the clinical management of these patients.

How COVID-19 disrupts glycometabolic control.

How COVID-19 disrupts glycometabolic control.

Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection.

Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.

In vivo confocal microscopy study of corneal nerve alterations in children and youths with Type 1 diabetes.

ObjectiveTo determine whether children and youths with Type 1 diabetes (T1D) have early alterations of the corneal subbasal nerve plexus detectable with in vivo confocal microscopy (IVCM) and to investigate the role of longitudinally measured major risk factors for diabetes complications associated with these alterations.MethodsOne hundred and fifty children and youths with T1D and 51 age‐matched controls were enrolled and underwent IVCM. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal fiber total branch density (CTBD), and corneal fiber fractal dimension (CNFrD) were measured. Risk factors for diabetes complications (blood pressure, BMI, HbA1c, lipoproteins, urinary albumin‐creatinine ratio) were recorded at IVCM and longitudinally since T1D onset. Unpaired t‐test was used to compare variables between the groups. Multiple regression models were calculated using IVCM parameters as dependent variables and risk factors as independent variables.ResultsAll IVCM parameters, except CTBD, were significantly lower in the T1D patients. Glycometabolic control (HbA1c, visit‐to‐visit HbA1c variability, and mean HbA1c), and blood pressure were inversely correlated with IVCM parameters. Multiple regression showed that part of the variability in CNFL, CNFD, CTBD, and CNFraD was explained by HbA1c, blood pressure percentiles and age at IVCM examination, independent of diabetes duration, BMI percentile and LDL cholesterol. Comparable results were obtained using the mean value of risk factors measured longitudinally since T1D onset.ConclusionsEarly signs of corneal nerve degeneration were found in children and youths with T1D. Glycometabolic control and blood pressure were the major risk factors for these alterations.

The impact of direct-acting antiviral treatment on glycemic homeostasis in patients with chronic hepatitis C.

There is robust epidemiological evidence suggesting the link of chronic hepatitis C virus (HCV) infection with type 2 diabetes mellitus (DM). Viral clearance achieved by direct acting antiviral agents (DAAs) has been associated to significant improvements in glycometabolic control but data on the long-term effect of sustained virological response (SVR) on diabetic disease are limited. The aim of this review is to evaluate the influence of SVR after DAA-based therapy on insulin resistance (IR) and DM incidence in non-diabetic patients, on the glycemic homeostasis in diabetic patients and on their long-term hepatic and metabolic outcomes. An electronic search of Embase, PubMed, MEDLINE, Ovid and the Cochrane Database of Systematic Reviews was performed for papers regarding the effect of DAA-induced SVR on the glycometabolic control and clinical outcomes of HCV-positive diabetic patients up to September 30, 2020. Among non-diabetic patients, a significant reduction in the risk of IR and DM was reported by the vast majority of the studies; the glycometabolic control significantly improved in diabetic patients during and immediately after the end of antiviral treatment. However, whether this beneficial effect is long lasting is still matter of debate. Furthermore, at variance with data obtained during the Interferon era, DM does not seem to be an unfavorable predictive factor of hepatocellular carcinoma in cured patients. A favorable influence of DAA-induced SVR on IR and DM incidence and on glycemic control is reported by several studies. However, the long-term biochemical, metabolic and clinical impact of this endocrine benefit remains largely unknown.

Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies.

Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)–OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.

Long-term follow-up of diabetic and non-diabetic patients with chronic hepatitis C successfully treated with direct-acting antiviral agents.

Clearance of hepatitis C virus (HCV) is associated with improved glycometabolic control in patients with diabetes mellitus (DM) but whether this effect is maintained over the long term with a reduction in liver-related events (LRE) is still debated. To address these issues, we conducted a long-term prospective study on diabetic and non-diabetic patients with chronic hepatitis C cured by direct antiviral agents (DAAs). Among 893 recruited patients, 15.7% were diabetic (Group 1) and 84.3% non-diabetic (Group 2); changes in fasting glucose (FG) and glycated haemoglobin (HbA1c) levels were assessed in Group 1 while the incidence of LRE was established in the whole cohort. Differences between groups were evaluated and independent predictors of unfavourable clinical outcome were established. After a mean follow up of 44.5months, a significant reduction in FG and HbA1c values was found in Group 1. Death was reported in 5.7% of patients in Group 1 vs 1.6% in Group 2 (P=.003), hepatocellular carcinoma (HCC)-free survival was significantly lower in Group 2 (P=.015) as well as LRE-free survival in Group 1 cirrhotic patients (P=.0006). After adjustment for baseline variables, cirrhosis and albumin levels emerged as independent predictors of LRE; low albumin levels, DM and central obesity were associated with HCC risk in cirrhotic patients while insulin therapy emerged as unfavourable predictor among diabetics. SVR achieved by DAAs is associated with long-term improvement of glycometabolic control in diabetic patients, but among cirrhotics DM still exerts a detrimental effect on the liver.

Liraglutide treatment and acylcarnitine profiles in Egyptian obese insulin-resistant females

Using metabolomics technique to investigate the response to liraglutide treatment produces helpful information regarding the effects of drug on metabolic regulation. This study tested whether loss of weight by liraglutide combined with decreasing acylcarnitines (AcylCNs) represent an effective strategy to improve insulin sensitivity in obese insulin-resistant females. AcylCN profiles by tandem mass spectrometry, plasma glycosylated hemoglobin, lactate, pyruvate, serum fasting glucose, creatinine, and insulin were assessed for obese insulin-resistant females before and after treatment with liraglutide for 3 months and non-obese females. All studied parameters in obese insulin-resistant females before treatment were significantly higher than control subjects except C0 and C3 levels which were significantly low. Liraglutide treatment was effective in weight loss, increased C0 and C3 levels and decreased values of all other studied parameters comparing with before treatment but still higher than control. However, creatinine level was unaffected by treatment. This study can conclude that circulating AcylCN profiles can reflect mitochondrial overload that happen in response to obesity. Also, AcylCNs can be used as markers for diagnosis of metabolic disorders. Liraglutide treatment leads to durable improvements in weight reduction and glycometabolic control and the utilization of intracellular glucose.

Long-term glycemic control and glucose variability assessed with continuous glucose monitoring in a pediatric population with type 1 diabetes: Determination of optimal sampling duration.

No studies have assessed if 2-week of continuous glucose monitoring (CGM) data provide good estimation of long-term glycemic control and glucose variability (GV) in pediatric patients with type 1 diabetes (T1D) as in adults. Six hundred fifty-four T1D pediatric patients were enrolled and 12-weeks of CGM data, before HbA1c measurement, were collected. Metrics of glycemic control and GV in incremental sampling periods were calculated. The agreement between metrics calculated in the sampling periods and the full 12-week period was assessed with correlation analysis (R2 ), median relative absolute difference (RAD) or absolute difference in the entire study populations and subjects stratified by age, pubertal status, insulin therapy (MDI,CSII), type of CGM (intermittently scanned [isCGM], real-time [rtCGM]), and HbA1c level. Correlations with metrics of the full 12-week period improved by extending the sampling periods. R2 values close to 0.90 using 4-week period were significantly higher than 2-week period, particularly for coefficient of variation, mean glucose SD, percentage of time below the range <70 mg/dL. A significant difference was found comparing the median RAD of 2- and 4-week, especially for mean glucose and coefficient of variation. Similar results were obtained analyzing subjects according to age and pubertal status, whereas in patients with HbA1c ≤7%, using rtCGM and CSII significant correlations were found for 2-week period. In T1D pediatric subjects, 4-week CGM data better reflects long-term glycemic control and GV in MDI and isCGM users. The 2-week period may be acceptably accurate in CSII and rtCGM users, especially in those with good glycometabolic control.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial.

Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60mmol/mol to 7.1% or 54mmol) at 6 months compared to baseline, and to placebo (p<0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p=0.037, p=0.048, and p=0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p=0.031, p=0.037, and p=0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

Heart failure therapy in patients with diabetes

The great interest in the problem “Heart failure” (HF) by the diabetolo­gist has been born in recent years and is mainly linked to the availabil­ity of new antidiabetic drugs which have shown a significant benefit in reducing hospitalizations for heart failure and cardiovascular mortality. Diabetes patients have more than double the risk of developing HF compared to patients without diabetes. The Framingham study has shown that diabetes increases the risk of heart failure up to 2 times in men and 5 times in women compared to controls over age. In addition, 12% of patients with DMT2 have heart failure and 30% of patients with heart failure are diabetic. Hospitalization for HF is associated with very high rates of both post-dis­charge mortality and new hospitalizations. Readmission rates for clinically stable patients discharged after recent hospitalization for HF are approximately 25% at 6 months and all-cause mortality exceeds 30% at 1 year. In particular, a worse prognosis and a longer hospital stay are associated with hospitalized diabetes patients. There is a close correlation between metabolic compensation and HF. In fact, in patients with diabetes a 1% increase in HbA1c is associated with an 8% increase in the risk of HF and still the improvement of the glycometabolic control reduces the risk of HF (in the UKPDS the 1% re­duction in HbA1c was associated with a 16% reduction in the risk of HF occurring). KEY WORDS T2DM; heart failure; SGLT2-inhibitors; diabetic cardiomyopathy.

Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis.

Low testosterone (T) in Klinefelter's syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls. We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search. Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls. TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.

1124-P: SGLT2 Inhibitors as Adjuvant Therapy for Type 1 Diabetes: An Italian Center Experience

Background and Aim: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are effective in improving glycemic control in both type 2 (T2D) and type 1 diabetes (T1D). Despite dapaglifozin has been recently approved as an adjunctive therapy in T1D, its use is still limited due to the increased risk of diabetic ketoacidosis (DKA). Aim of this study was to assess the effectiveness of SGLT2 inhibitors in combination with insulin in poorly controlled T1D patients. Methods: In this retrospective observational study, data from 46 adults [M/F 29/17] affected by T1D treated with insulin plus dapaglifozin were collected. Glycated hemoglobin (A1c), anthropometrics, insulin daily requirement and time in range (TIR) were studied at baseline, 3 and 6 months after starting of treatment. Results: At baseline, mean ± SD age was 32.7 ± 10.2 years, disease duration was 21.4 ± 9.3 years, A1c was 8.3 % ± 1.6. Insulin daily requirement was 0.9 ± 0.38 UI/Kg, whereas BMI was 26.7 ± 1.6 Kg/m2. After 6 months, Dapaglifozin 5 mg/day had significantly decreased A1c levels (change [Δ] -0.86%, p &amp;lt; 0.01), body weight (Δ -2.5 kg, p &amp;lt; 0.001) and insulin daily requirement (Δ -0.17 UI/kg, p &amp;lt; 0.01) from baseline. Moreover, in a subgroup of patients (n=16) using continuous glucose monitoring (CGM) systems, statistically significant improvement of TIR (Δ +9%, p &amp;lt; 0.01) has been observed, while time spent in hypoglycaemia did not change. No significant changes in C-peptide levels was observed (p = 0.09). No serious adverse events occurred during the study period. Discontinuation (10%) was mainly related to genitourinary infections, polyuria or limited effectiveness perceived. Conclusion: Our real world experience confirms clinical benefits of SGLT2 inhibitors as an adjunctive therapy in poorly controlled T1D patients, ameliorating overall glycometabolic control as well as glycemic variability. Clinical characterization and proper education remain essential in order to identify the right candidate and to minimize DKA risk. Disclosure S. Pieralice: None. D. Tuccinardi: None. S. Kyanvash: None. D. Maggi: None. L. Monte: None. S. Briganti: None. S. Manfrini: None. P. Pozzilli: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company. Research Support; Self; Medtronic, Sanofi.