T2DM Subjects Research Articles

Clinical presentation and outcome of COVID-19 infection in Type 2 Diabetes Mellitus: a preliminary data from a tertiary hospital in Jakarta during the early days of the pandemic

Introduction. This study aimed to review the clinical characteristics and outcomes of COVID-19 patients presented with in-hospital hyperglycemia or pre-existing type 2 diabetes (T2DM).Methods. This is a retrospective study conducted in Fatmawati General Hospital, Indonesia, from March 18th-Apr 30th, 2020. We reviewed medical records of 27 COVID-19 patients presented with either in-hospital hyperglycemia (11, 12.2%) or pre-existing T2DM (16, 17.8%) from a total of 90 confirmed COVID-19 cases admitted in our hospital.Results. Critical conditions occurred in 50% of T2DM and 54.55% of the in-hospital hyperglycemia group. Mortality was documented in 68.75% of T2DM and 81.82% of in-hospital hyperglycemia group. Hypoglycemia, diabetic ketoacidosis, lactic acidosis and ketosis were found in 12.5%, 25%, 18.75%, and 25% of individuals with T2DM, respectively, resulting in a high mortality rate. Meanwhile, diabetes-related complications were rare among the in-hospital hyperglycemia group. However, respiratory failure (45.45% vs. 6.25%) and septic shock (27.27% vs. 6.25%) were more frequent than in the T2DM group.Conclusion. In this preliminary study, a high mortality rate was documented among COVID-19 patients with preexisting T2DM and in-hospital hyperglycemia. In T2DM subjects, diabetes related-complications contributed to a higher mortality rate, while in-hospital hyperglycemia group, respiratory failure and septic shock were more frequent.

Effect of community-based intervention on lifestyle in the concentration of adipoquines and branched amino acid in subjects with high risk of developing diabetes: Feel4diabetes study

Background and Aims: Type 2 diabetes (T2DM) is one chronic diseases with high prevalence in developed countries and high number of associated comorbidities. Feel4Diabetes study was a school and community-based intervention that aimed to reduce the prevalence of T2DM in European families. Plasmatic concentrations of branched amino acid (BCAA) and RBP4, have been shown to be elevated in T2DM subjects in cross-sectional studies. However, the effect of lifestyle community-based intervention on BCAA and RBP4 concentrations has not been yet analysed

High glucose load and endotoxemia among overweight and obese Arab women with and without diabetes: An observational study.

Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ± 2.2 kg/m2]; overweight [n = 16, non-T2DM, BMI = 28.5 ± 1.5 kg/m2] and T2DM [n = 34, BMI = 35.2 ± 7.7 kg/m2]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values <.01) whereas significantly lower HDL-cholesterol levels (P < .01) were observed in T2DM subjects compared to other groups. Baseline endotoxin levels were highest in the overweight group (3.2 ± 1.1 mmol/L) as compared to control (2.0 ± 0.5 mmol/L) and T2DM (2.7 ± 1.2 mmol/L) (P = .046). HDL-cholesterol, LDL-cholesterol and triglycerides, significantly decreased in the T2DM group after 2 hours (P values <.05), whereas unremarkable changes observed in other groups. Lastly, endotoxin levels significantly increased only in the overweight group (3.2 ± 1.1 vs 4.2 ± 1.4 mmol/L; P < .05), 4 hours postprandial.High glucose meal elevates endotoxemia only among overweight subjects and impairs dysbiosis.

Analysis of the Exonic Single Nucleotide Polymorphism rs182428269 of the NRF2 Gene in Patients with Diabetic Foot Ulcer

The pivotal role of Nuclear factor erythroid-2-related factor 2 (NRF2) in redox homeostasis and wound healing has been well documented. However, the genetic mechanisms that regulate NRF2 in type 2 diabetes and diabetic foot ulcers remain unexplored. The present study investigated the association of single nucleotide polymorphism rs182428269 (-127C/T) in subjects with type 2 diabetes and diabetic foot ulcers. This cross-sectional study comprised 400 participants that included group I: normal glucose tolerant subjects (NGT, n=150), group II: type 2 diabetes mellitus subjects (T2DM, n=150) and group III: infected diabetic foot ulcer subjects (DFU, n=100). The non-synonymous SNP rs182428269 was selected based on in silico analysis and genotyped by PCR-restriction fragment length polymorphism (RFLP) followed by bidirectional Sanger sequencing. In addition, the gene expression of NRF2 in patients with polymorphism was analyzed by qPCR to evaluate the functional impact of the SNP. NRF2 expression was significantly decreased among the T2DM and DFU subjects when compared to the NGT subjects. Of particular interest, the homozygous mutant (TT) genotype of rs182428269 polymorphism was significantly associated with an increased risk for the development of T2DM (OR=1.95 (1.02-3.72), p=0.04) and DFU (OR=5.66 (2.98-10.76), p=0.0001). Furthermore, a progressive decline in NRF2 expression was observed among the T2DM and DFU subjects with "TT" genotype compared to the "CC" and "CT" genotypes. NRF2 polymorphism rs182428269 is associated with the pathogenesis of T2DM and DFU.

Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells.

Let7b-5p is a member of the Let-7 miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of Let7b-5p in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of let7b-5p in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of let7b-5p in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of let7b-5p are significantly (p<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of let7b-5p increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of let7b-5p reduced insulin content and secretion. Modulation of the expression levels of let7b-5p did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in let7b-5p transfected cells revealed a marked dysregulation of Insulin, Pancreatic And Duodenal Homeobox 1 (PDX1), glucokinase (GCK), glucose transporter 2 (GLUT2), and INSR. In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.

Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date. This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into two subgroups of sufficient (SGC-DM; HbA1c ≤6,5%,n = 15) and poor glycaemic control (PGC-DM; HbA1c >6,5%,n = 6). Evaluation of the whole blood thrombogenicity we assessed using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan). Blood clot formation initiation time (T10) was significantly shortened in PGC-DM subgroup when compared to SGC-DM subgroup (p = 0,03). The area under the curve (AUC30) of blood clot time formation and the MPV (mean platelet volume) values were substantially higher in the PGC-DM subgroup in comparison to the SGC-DM group (p = 0,03). Negative correlations were noted between HbA1c and T10 values (p = 0,02) and between T10 and MPV values in the T1DM group (p = 0,04). Poor glycaemic control in T1DM subjects triggers a shift towards a prothrombotic and antifibrinolytic state. This phenomenon can be detected using the novel system for quantitative assessment of the platelet thrombus formation process under flow conditions in vitro. The alteration of T-TAS values in PGC-DM subgroup proves that a poor glycemic control-related shift of the equilibrium toward thrombogenesis occurs in this group of patients. Our findings need a further elucidation in research on more massive data sets to be confirmed.

Intensive Insulin Therapy (Basal-Bolus).

Intensive insulin therapy (IIT) aims at achieving near-normal glycemic control and usually uses a basal-bolus (BB) schema to mimic physiologic insulin secretion. The treatment burden of IIT should be outweighed by improved glycemic control and reduction of chronic complications, but reviews summarizing the effects of IIT in subjects with T1DM and T2DM in glycated hemoglobin, hypoglycemia, insulin doses, and weight are limited. We performed a PubMed search to identify relevant randomized control trials (RCTs) comparing IIT and conventional insulin treatment in T1DM and T2DM subjects and addressing glycated hemoglobin, hypoglycemia, insulin requirements, and weight. We have identified 11 RCTs in T1DM subjects, published years ago and very heterogenous in design. Throughout the studies there was a consistent superiority of IIT in glycated hemoglobin reduction, a higher rate of severe hypoglycemia and more weight gain in the IIT group without a clear effect on insulin doses. We have identified 2 RCTs in T2DM subjects, only one of them using a definite BB schema in the IIT group. IIT induced more hypoglycemia and better HbA1c, but not more weight gain. IIT is the best option for treatment of subjects with T1DM in HbA1c reduction with a cost in the rate of hypoglycemia and weight gain. In subjects with T2DM, IIT also yields improvement in HbA1c versus conventional treatment, also at the cost of more hypoglycemic episodes, but not of higher weight gain. RCT treatment arms did not only differ in the insulin schema, but also in treatment goals, therapeutic education, and frequency of clinical visits among other characteristics. However, most evidence was gained using a BB insulin schema in the intensive arm and it is likely that the insulin schema had a relevant contribution in the results.

Evaluation of miR-181b and miR-126-5p expression levels in T2DM patients compared to healthy individuals: Relationship with NF-κB gene expression

BackgroundType 2 diabetes mellitus (T2DM) is a progressive metabolic disorder whose prevalence is rising very fast across the world. Diagnosis of this disease in early stages (pre-diabetic stage) plays an important role in reducing mortality associated with this disorder. miRNAs, as key players in the pathogenesis of T2DM, have been investigated in several studies. Furthermore, their expression profile changes in the early stages of diabetes mellitus in body fluids such as serum, peripheral blood, and peripheral blood mononuclear cell (PBMC) have been studied. Due to their high stability and the presence of non-invasive sensitive methods for their measurement, such as real-time PCR, they can be used for early diagnosis of T2DM as a biomarker. In this experimental study, the expression levels of miR-181b, miR-126-5p, and NF-κB were measured in patients with T2DM, pre-diabetic subjects, and healthy controls in a Yazd population. Material and methodNinety asymptomatic subjects including 30 T2DM, 30 pre-diabetic, and 30 healthy subjects (diagnosis based on WHO criteria) were included in this study. Real-time PCR was used to measure the expression levels of miR-181b and miR-126-5p. Moreover, the NF-κB expression level was also measured to determine its relationship with these two microRNAs. ResultIn this study, the expression level of miR-181b and miR-126-p decreased gradually in pre-diabetic as well as T2DM subjects compared to healthy controls. Furthermore, our study showed a significant negative correlation between these two miRNAs and NF-κB for the first time. ConclusionThese results introduce these anti-inflammatory miRNAs as powerful tools for early diagnosis of T2DM.

CDKAL1 (rs10946398) and TCF7L2 (rs7903146) gene polymorphisms and their association with risk of type-2 diabetes mellitus in population of Uttarakhand, India

PurposeType 2 diabetes mellitus (T2DM), a non- insulin dependent form of diabetes is predominantly the outcome of multivariate factors ranging from genetic, hereditary to environmental factors. CDKAL1 ((rs10946398)), gene play a permissive role in β-cell function by inhibiting activity of CDK5, the decrease of insulin gene expression. TCF7L2 ((rs7903146)) gene involved in the Wnt signalling pathway, has its direct effects on glucose-induced, which may risk prevalence of T2DM. The present study aims to understand the association of CDKAL1 and TCF7L2 Gene polymorphism in T2DM patients among the population of Uttarakhand, India. Materials and methodsThe present study included 400 T2DM subjects and 400 healthy controls. DNA extraction done from blood serum collected in plain vials and CDKAL1, TCF7L2 gene polymorphism was done by the PCR-RFLP method. ResultsSignificant differences were observed in BMI (kg/m2), FPG (mg/dl), PPG (mg/dl), HbA1c, FPI, systolic BP (mmHg), diastolic BP (mmHg) among the subjects and controls (all p < .0001). Genotypes of CDKAL1 and TCF7L2 genes among T2DM and healthy controls was found to be statistically significantly (p < .0001).Among the T2DM subjects, CDKAL1 genotypes GG, GC and CC were 32.5%, 60% and 7.5% while in healthy control, CDKAL1 genotypes GG, GC and CC were 58%, 39% and 3% respectively. Among the T2DM subjects, TCF7L2 genotype CC, CT and TT were 35%, 63% and TT 2.5% while in healthy control CC, CT, TT were 53%, 46% and 1% respectively. Higher heterozygous GC genotype and mutant CC genotype. Higher C allele frequency (0.37%) noticed in patients as compare to control C allele (0.22%). Odd ratio with 95% CI were calculated for CDKAL1, GC and CC had 2.79 (2.08–3.75) and 4.13 (2.08–8.20) risk taking GG as reference and TCF7L2, CT and TT had 2.09 (1.57–2.78), 3.04 (1.01–9.09) risk taking CC in T2DM subjects. ConclusionStudy concluded that CDKAL1 heterozygous GC, mutant CC were higher in among T2DM and TCF7L2 heterozygous CT, mutant TT were higher among T2DM subjects suggested connected with T2DM. Higher odds and relative risk was found with CDKAL1, TCF7L2 heterozygous GC, CT and mutant CC, TT genotypes respectively.

Deranged Fractional Excretion of Magnesium and Serum Magnesium Levels in Relation to Retrograde Glycaemic Regulation in Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes (T2DM) has been associated with deficiencies in serum magnesium level, decreasing insulin sensitivity and glucose metabolism. Glycosylated hemoglobin (Hb1Ac) is a biomarker of glucose values within the half-life of the erythrocyte, that is, 3 months. Low circulating and intracellular magnesium levels can modify glucose metabolism and insulin sensitivity. Renal solute management is a parameter little used to estimate circulating and excreted concentrations of elements such as magnesium. The purpose of this study was to assess and associated fractional excretion of magnesium (FEMg) and serum magnesium with metabolic parameters, especially Hb1Ac percent, in a group of well characterized subjects with T2DM and non-diabetics subjects (ND). According to Hb1Ac, two groups were compared and associated with existing biochemical parameters, included Hb1Ac, fasting glucose, lipid profile, serum creatinine, serum magnesium and urinary creatinine for FEMg. HbA1c levels were explained by serum magnesium in 25%. Serum magnesium levels in the ND group were higher than in the T2DM group and this was a statistically significant difference. Serum magnesium ≤1.8 is a risk factor (OD 16.1; P=0.021) for an HbA1c ≥ 6.5%. In this study, hypomagnesemia was a parameter strongly associated with the diagnosis and progression of T2DM, while FEMg showed no significant association.

Relationship among Frailty, Muscle Volume, Protein Intake in Patients with Chronic Kidney Disease (CKD)

Maintenance of muscle mass and protein intake are closely related. Insufficient protein intake in each meal or a total of three meals causes a decrease in muscle mass. For the elderly, protein intake has been insufficient at breakfast and then a large amount of protein is necessary for stimulating muscle protein synthesis. Consequently, there is a need to more actively and consciously take protein in older age. There have been conflicting results concerning the effect of protein restriction diet on glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) from the data of various meta-analyses. A beneficial effect and also no significant effect was found. One of the perspectives suggested that protein restriction diet may make slower CKD progression in T1DM and non-DM subjects, but not for T2DM patients. However, further studies will be necessary in the future.

Shortening of the leucocytes’ telomeres length in T2DM independent of age and telomerase activity

This study aimed to examine the role of plasma telomerase (TE), plasma insulin, patient's age and disease duration in determination of the leucocytes' telomeres length (LTL) in T2DM. Blood samples from Kuwaiti patients with T2DM (110) and non-diabetic subjects (94) were analyzed by SYBR Green Quantitative PCR for estimation of the Absolute Human Telomere Length and by ELISA for estimation of the TE activity and insulin level. The body mass index (BMI) and HOMA-IR were calculated. The results revealed marked shortening of the LTL in T2DM compared with the non-diabetic subjects (6.068, 2.276-11.652 vs. 10.979, 6.495-23.402kb), p < 0.001, while the TE concentration was comparable between the two groups (3.16, 0.00-6.02 vs. 4.16, 1.38-7.94 U/L, respectively), p 0.100. Importantly, in T2DM the LTL did not vary significantly with the disease duration (1month to 40years), p 0.959, and did not correlate with age, BMI, insulin-resistance, or glycemic parameters. Interestingly, there was a positive correlation between the LTL and insulin levels in T2DM (CC 0.211, p 0.0419). Finally, in non-diabetic subjects, HbA1c ≥ 6% was associated significantly with shorter LTL, this observation together with the lack of association of the LTL with the disease duration, suggests a causal role of short telomeres in T2DM development. This study confirmed the LTL shortening in T2DM in Kuwaiti Arabs, and showed that the LTL was independent of age and TE activity but positively influenced by insulin levels. Furthermore, the study suggested that telomeres shortening could be a risk factor for T2DM.

1070-P: Bromocriptine-QR (BQR) Ameliorates a Pro-oxidative Stress/Proinflammatory (POS/PI) Monocyte Phenotype in Poorly Controlled T2DM Subjects

Background: Elevated sympathetic tone stimulates a POS/PI leucocyte phenotype that promotes cardiovascular disease (CVD) and augments postprandial hyperglycemia in T2D. BQR, a sympatholytic dopamine agonist for treatment of T2DM, improves postprandial dysglycemia and reduces CVD events. Aim: To examine the effect of BQR on POS/PI phenotype of blood monocytes in T2DM. Study Design: 15 T2DM subjects treated with a GLP-1 RA received BQR (3.2 mg/day) for 16 weeks. Endothelial function was measured by post-occlusion hyperemia. Blood monocytes were isolated and expression (PCR) of the following genes was quantitated: (i) master antioxidant gene regulators that increase in response to systemic oxidative stress (OS) (oxidation resistance gene 1 [OXR1] and nuclear factor erythroid 2 like 2 [NRF2]); (ii) genes known to induce a proinflammatory profile in T2DM (toll like receptor 2 [TLR2], nuclear factor kappa B p65 [NFkBp65], and L-selectin, a surface adhesion protein that stimulates transendothelial migration and PI biochemistry); (iii) glucocorticoid receptor [GCR] that produces a PI environment. Results: BQR significantly improved HbA1c (-0.6%; baseline HbA1c=8.3%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). BQR reduced OS response gene transcript levels of OXR1 and NRF2 by 30% (P&amp;lt;0.03) and of PI genes TLR2, NFkBp65, GCR, and L-selectin by 40, 33, 26, and 32% respectively (P&amp;lt;0.05). Plasma levels of OS markers (TBARS and nitrotyrosine) and PI cytokines (MCP1 and IL-18) also were significantly reduced (p&amp;lt;0.01-0.05) by BQR. Conclusion: BQR reduces postprandial dysglycemia, improves endothelial function, and improves multiple aspects of the POS/PI state in T2DM, providing a potential mechanism for BQR’s cardiovascular protective effect. Disclosure M. Ezrokhi: Employee; Self; VeroScience LLC. A. Cincotta: Employee; Self; VeroScience LLC. E. Cersosimo: None. J.M. Adams: None. M. Alatrach: None. C. Agyin: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. N. Cominos: Employee; Self; VeroScience LLC. R.A. DeFronzo: None.

585-P: Effect of Hydroxychloroquine on HbA1c and Lipid Parameters in T2DM Subjects with Diabetic Neuropathy Who Are on Statins

Aim: We decided to explore the effects of HCQ in combination with rosuvastatin on Lipid profile and HbA1c of patients with DKD. Method: This is a real world study. T2DM (N=67, Age 52± 09), HbA1c ≥ 7%, with clinical evidence of DKD) were selected and alternatively divided into two groups with one group taking HCQ 400 mg in addition to their regular medications and other group without HCQ. Both groups were followed for next 3 months and changes in their serum creatinine(S.Cr), eGFR, Urine ACR, HbA1C,FPG, PPG, LDL, HDL, TG were noted. All patients were on DPP-4i and metformin along with short acting insulin with dosage modified according to daily insulin need and changes in insulin requirement with changing renal function for at least 3months prior to the study. Results: TG levels were reduced by 25.01% and 10.69% in the HCQ and Non - HCQ Gr respectively, LDL-cholesterol levels were reduced in HCQ while it increase in the Non HCQ. TC declined more with HCQ and significant increase in HDL. SCr. was decline in HCQ Gr, while it increased in Non-HCQ. Similarly, eGFR was rising in the HCQ and decreased in the Non-HCQ. Also, Urinary ACR decreased with HCQ, but continued to increase in Non-HCQ. Conclusion: Therefore, we concluded that HCQ can be an option in patients of early stages of DKD in such patients and it may be combined with rosuvastatin for better lowering of lipid levels and better control of HbA1c. Disclosure A. Baidya: None. S. Guha: None. S. Kumar: None. A. Shankar: None.

1772-P: Reversibility of Altered Brain Glucose Kinetics in T2DM

Poor glycemic control is associated with central nervous system complications. We have previously shown that compared to healthy controls, individuals with uncontrolled T2DM have a blunted rise in brain glucose levels measured by 1H magnetic resonance spectroscopy (MRS). In this study, we investigate whether reduction in HbA1C improves intracerebral glucose levels. Six T2DM subjects with poor glycemic control were recruited (4F, age 46.0 ± 8.8 yrs, BMI 34.2 ± 4.1 kg/m2, HgbA1c 9.6 ± 1.1%) to participate in 1HMRS scanning at 4 Tesla during a hyperglycemic clamp (∼220 mg/dl) before and after a 12-week intervention to improve glycemic control through use of continuous glucose monitoring, intensification of diabetes regimen, and frequent visits with an endocrinologist and nutritionist. Following the intervention, HbA1c decreased by 2.1%±1.5 (P=0.02) with minimal BMI changes (P=0.10). Using a hierarchical linear regression model to compare glucose time courses during the clamp pre and post intervention, brain glucose levels were modestly and significantly higher during the clamp after the intervention (P=0.02) despite no differences in plasma glucose levels during the clamp (P=0.45). These findings suggest that brain glucose levels increase after improvement of glycemic control and provide evidence that reducing HbA1C may improve brain glucose transport and/or metabolism. Disclosure E. Sanchez Rangel: None. F. Gunawan: None. L. Jiang: None. M. Savoye: None. F. Dai: None. D.L. Rothman: None. G.F. Mason: None. J.J. Hwang: Research Support; Self; General Electric. Funding National Institutes of Health (DK109284)

717-P: The Levels and Related Factors of Advanced Glycation End Products in Korean Patients with Type 2 Diabetes Mellitus

Advanced glycation end-products (AGEs) are known to be produced by the Maillard reaction, ingested through food. AGEs are actively generated and accumulated in the circulating blood and various tissues in diabetes mellitus patients by chronic hyperglycemia. AGEs play an important role in the development of diabetic vascular complications. The aim of this study was to assess levels and related factors of AGEs in Korean patients with type 2 diabetes mellitus. A total of 310 Korean men (n=177) and women (n=133) with T2DM subjects were participated. This study was measured and analyzed anthrometric data, body composition, and biochemical parameters. Tissue accumulated AGEs can be evaluated a non-invasive methodology by skin autofluorescence reader. The means age of total subjects was 58.9 ± 11.0 years, BMI was 25.8 ± 4.5 kg/m2. There is no difference between male and female patients in levels of AGEs, pulse wave velocity (PWV) and vein age. There is a significant correlation among AGEs, height, weight, body mass index, skeletal muscle mass, diastolic blood pressure and HDL cholesterol for male patients and among fasting blood sugar, glycated hemoglobin A1c, total cholesterol, LDL cholesterol, and systolic blood pressure for female patients. The correlation of AGEs for both male and female subjects is highly associated with age, duration of diabetes and PWV. This study shows possibility of using AGEs as an index for clinical diagnosis, complications prediction, and diabetes management in Korean patients with type 2 diabetes mellitus. However, it is considered that a change in AGEs may be influenced by gender, age, and duration of diabetes. Disclosure J. Yim: None. Y. Kim: None. J. Park: None.

130-LB: Retrospective Evaluation of Treatment Patterns in a Real-Life Setting Environment with Dapagliflozin or DPP-4 Inhibitors as Add-On Therapy in Uncontrolled DM2 Patients Who Previously Failed on Other Regimens

Mexico is one of LatinAmerica countries with the highest prevalence (14.4%) of DM. Medical institutions face the challenge to provide medical care to T2DM patients that failed to several antidiabetic regimens. We conducted a retrospective study to assess the response to dapagliflozin (Dapa) or DPP-4-inhibitors (DPP-4i) as added-on therapy in T2DM patients with failure to previous medications. Objectives: Compare subjects with ≥5% improvement of the weighted sum of the three variables of the composite variable (HbA1c plus body weight (BW) plus blood pressure (BP) by the end of the 74-week observation period from index date) and proportion of patient achieving HBA1c of 7%. Inclusion Criteria: T2DM subjects ≥18 years old with failure to any previous antidiabetic medication and HbA1c% ≥7 that started Dapa or DPP-4i as add-on to other antidiabetic drugs from August 2014 to Jun 2018. Statistical Methods and Analysis: A propensity score matching model (nearest neighbor algorithm) was used, covariates included were treatment regimen, TC, LDL-c, HbA1c, BW, systolic BP and age. Results: Of 1800 subjects, 221 met statistical matching criteria. No differences in basal characteristics of age, SBP, CrCl, but DAPA group had higher basal HbA1c (8.68±1.59 vs. 8.19±1.4, p&amp;lt;0.01). Dapa group had a significant improvement (&amp;gt;5%) in the composite variable compared to DPP-4i at 24 (76.9% vs. 46%, p&amp;lt;0.01), 52 (82.4% vs. 49.5%, p&amp;lt;0.01) and 76 weeks(84.6% vs. 39.2%, p&amp;lt;0.01). Patients with HbA1c goal of &amp;lt;7% in Dapa group compared to iDPP-4 at 24 (44.3% vs. 29.9%, p&amp;lt;0.01), 52 (48.9% vs. 29.1%, p&amp;lt;0.01) and 76 weeks (51.9% vs. 21.8%, p&amp;lt;0.01). Conclusion: In patients with uncontrolled T2DM who have failed to previous antidiabetic therapies, the add-on of dapagliflozin significantly provides reductions of HbA1c, glucose, weight and blood with more patients achieving glucose control goals compared to iDPP-4. Disclosure D. Espinoza-Peralta: None. A. González-Cantú: None. A.I. Silva: Employee; Self; AstraZeneca. J.G. Collado: None. J. Rogel-Manzanares: None. J.H. Hernández-Alarcón: None. A.G. Noriega-Muñoz: None.

1603-P: Changes in Age- and Gender-Specific All-Cause Mortality Rates and Ratios in People with T2DM in Hungary between 2001-2016: A Nationwide Cohort Study

T2DM is associated with a higher risk of all-cause mortality; however, detailed analyses of age- and gender-specific subgroups are rare. The aim of the study was to analyze the changes of age- and gender-specific all-cause mortality rates and ratios (excess risk) in T2DM subjects (aged &amp;gt;40 years) in Hungary between 2001 and 2016. We used the central database of the National Institute of Health Insurance Fund. Annual all-cause mortality rates and ratios (T2DM/non-T2DM) were determined in males/females and in different age-groups (41-50, 51-60, 61-70, &amp;gt;71 years). Age-adjusted values were used for evaluating standardized mortality rates. Among pharmacologically treated T2DM subjects we found 117,700 and 329,845 males, 232,143 and 391,382 females in 2001 and 2016, respectively. Standardized all-cause mortality rate was higher in males than females in 2001 (4540/100,000 vs. 3365/100,000) which decreased to 4125/100,000 in males (change: -11.8%, p&amp;lt;0.0001) and to 2977/100,000 in females (change: -9.2%; p=0.0558) in 2016. The standardized all-cause mortality ratio was higher in females (1.39) than in males (1.13) in 2001. We found a significant increase (8.35%; p=0.0272) in standardized mortality ratios in our cohort between 2001 and 2016 which was higher in males (11.44%; p=0.0096) than females (2.78%; p=0.3288). We observed the most pronounced increase in all-cause mortality ratios between 2001 and 2016 in age-groups of 41-50 and 51-60 years in both genders (change varied from 54.2% to 101.8%; p&amp;lt;0.05) which was due to distinct tendencies in changes of mortality curves (more impressive decrease in non-T2DM subjects than in T2DM patients). Pharmacologically treated T2DM subjects in lower age-groups (41-60 years) had the highest increase in all-cause mortality ratios between 2001 and 2016 in Hungary. These data indicate that younger patients with T2DM need special attention for improving long-term outcomes. Disclosure G. Jermendy: None. Z. Kiss: None. G. Rokszin: None. I. Fábián: None. I. Wittmann: None. P. Kempler: None. Funding Hungarian Diabetes Association (2019)

2313-PUB: Alterations in Basal State of Insulin and mTOR-Dependent Signalings Closely Related to Impaired Incretin Profile and Type 2 Diabetes in Subcutaneous Adipose Tissue of Obese Patients

Objective: In our study we have compared basal insulin and mTOR signaling in subcutaneous fat of obese T2DM vs. obese subjects with normal glucose tolerance (NGT). We have performed correlation analysis of phosphorylation’s parameters against clinical parameters of carbohydrate metabolism and incretin secretion profiles. Methods: 22 patients with long (&amp;gt;10 years) and morbid (BMI &amp;gt; 35 kg/m2) obesity, 12 of which had NGT and 10 had T2DM were enrolled in this study. Hyperinsulinemic-euglycemic clamp test and HOMA-IR were used to measure insulin resistance. Blood samples taken at 0, 30 and 120 min of food load test were used to assess incretin profile, insulin and glucose levels. Amount of total and visceral fat was determined by bioelectrical impedance analysis. Subcutaneous fat biopsies were obtained during bariatric surgery for all patients and signaling state was analyzed by western blots. Results: As assessed by western blots of insulin receptor substrate (IRS), Akt, Raptor, Rictor, mTOR and S6K1, the basal insulin signaling and mTORC activities were comparable in NGT and T2DM groups, whereas phosphorylation of AS160 (pAS160-S318) was significantly lower and serum and glucocorticoid-induced kinase (SGK; pSGK-S422) was significantly higher in T2DM group. Various correlations were found between the degree of insulin resistance and amount of visceral fat, changes in incretin profile, glucose metabolic parameters and phosphorylation level of AS160, incretin secretion profile and phosphorylated levels of AS160 or SGK1. Conclusions: Altered phosphorylation of AS160 and SGK1 is associated with obese T2DM phenotype and impaired incretin profile. We think that AS160 and SGK1 phosphorylations can be important markers of the prediabetes-to-diabetes transition. Disclosure I. Stafeev: None. I. Sklyanik: None. S. Michurina: None. E. Shestakova: Employee; Spouse/Partner; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharma K.K., Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. A. Yurasov: None. K. Yahyaev: None. A. Karmadonov: None. E. Ratner: None. M. Menshikov: None. A.V. Vorotnikov: None. Y.V. Parfyonova: None. M.V. Shestakova: None. Funding Russian Science Foundation (17-15-01435)

414-P: Hand-Grip Strength and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events and of Mortality in Patients with Established Cardiovascular Disease

Impaired skeletal muscle function is involved in the pathogenesis of type 2 diabetes (T2DM) as well as of cardiovascular disease (CVD). Hand grip strength (HGS) is a simple, inexpensive and non-invasive diagnostic parameter for muscle function. Its association with cardiovascular events and mortality in patients with established CVD is unclear and is addressed in the present study. We prospectively recorded cardiovascular events over a mean follow up time of 8.9±3.2 years in a cohort of 876 patients with established CVD (672 patients with angiographically proven coronary artery disease and 204 patients with sonographically proven peripheral artery disease). From our patients, 274 (31.3%) had T2DM at baseline; HGS did not differ significantly between patients with T2DM and nondiabetic subjects (35.3±11.9 vs. 36.6±11.9 kg; p=0.082). Prospectively, cardiovascular events occurred in 387 patients, and 278 patients died during follow-up. T2DM and low HGS after multivariate adjustment in Cox regression models proved to be mutually independent predictors of cardiovascular events (adjusted HR 1.52 [1.23-1.89]; p&amp;lt;0.001 and standardized adjusted HR 0.85 [0.74-0.99]; p=0.032, respectively) as well as mortality (adjusted HR 1.79 [1.39-2.29]; p&amp;lt;0.001 and standardized adjusted HR 0.69 [0.58-0.83]; p&amp;lt;0.001, respectively). We conclude that low HGS and T2DM are mutually independent predictors of cardiovascular events as well as of mortality in patients with established CVD. Disclosure B. Larcher: None. A. Vonbank: None. A. Mader: None. M. Maechler: None. L. Sprenger: None. A. Leiherer: None. D. Purin: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.