Onset T2DM Research Articles

Reduced Lipotoxicity Following Triple Therapy for 3 Years in New Onset T2DM

Reduced Lipotoxicity Following Triple Therapy for 3 Years in New Onset T2DM

Pediatric diabetes mellitus hospitalizations and COVID-19 pandemic response measures

AimsIn the United States, evidence suggests that during the COVID-19 pandemic, admissions of patients with diabetes mellitus (DM) have increased. This study assessed hospital admission rates for pediatric type 1 (T1DM) and type 2 (T2DM) diabetes mellitus during 2019–2021, and the potential influence of the timing of various pandemic response measures. MethodsRetrospective chart reviews were conducted of 854 T1DM and 135 T2DM hospital admissions between January 2019 and December 2021 in patients < 20 years old to collect demographic data, admission type, body mass index (BMI), and area deprivation index (ADI, a measure of socioeconomic vulnerability). Patients were divided into three cohorts based on their admission year: 2019 (Pre-pandemic), 2020 (Pandemic, Pre-vaccine), and 2021 (Pandemic, Post-vaccine). Admissions were categorized within each cohort by diagnosis (T1DM or T2DM) and clinical presentation (new onset, diabetic ketoacidosis: DKA). Cohorts were compared using an independent samples t-test for continuous variables or a chi-square test for categorical variables. ResultsThe incidence of T2DM hospitalizations tripled during the pandemic, increasing from 18 in 2019 (Pre-pandemic), to 55 in 2020 (Pandemic, Pre-vaccine), and 62 in 2021 (Pandemic, Post-vaccine). The rate of patients presenting with DKA was 15.4 % (95 % CI: 4 %-26.9 %) higher in 2020 (Pandemic, Pre-vaccine) among patients with new-onset T1DM (72/139 vs. 52/143), and 22.5 % (95 % CI: 9.6 %-35.4 %) higher in 2020 (Pandemic, Pre-vaccine) among T2DM patients (9/40 vs. 0/14). This increased rate of new onset T2DM significantly correlated with younger age (P = 0.046) and higher ADI score (P = 0.017), but not with BMI. ConclusionThe incidence of T1DM hospitalizations did not increase during the pandemic; however, they tripled for T2DM patients. All new onset DM pediatric patients during the pandemic were more likely to present in DKA. Patients admitted with new onset T2DM were socioeconomically more vulnerable. For T1DM, the peak of local pediatric diabetes admissions in 2020 occurred slightly later coinciding with the reopening of primary care physicians (PCP) offices and schools.

1289-P: Predictors of New-Onset Type 2 Diabetes after Infection with COVID-19 in the COVID-OUT Randomized Trial

Background: There are mixed data on whether COVID-19 infection is associated with increased incidence of type 2 diabetes (T2DM). The majority of data have been derived from retrospective datasets. We sought to identify predictors of new onset T2DM in a prospective cohort enrolled in the multi-site phase 3 randomized quadruple-blinded placebo-controlled COVID-OUT clinical trial. Methods: Adults with overweight or obesity aged 30-85 were enrolled within 3 days of a positive SARS-CoV-2 test and &amp;lt;7 days of symptoms. Participants were randomized to 1 or 2 of 3 oral medications (immediate-release metformin increasing over 6 days to 1500 mg daily for a total of 14 days; ivermectin 430mcg/kg/day for 3 days; fluvoxamine 50mg day 1 then 50mg twice daily through 14 days) or placebo using a two by three parallel treatment factorial design. Starting 60 days after randomization we sent automated email surveys every 30 days through 300 days about new diabetes diagnoses, as well as changes in weight and sleep. We conducted univariable analyses to determine predictors of T2DM diagnosis. Results: Among 1093 subjects, 25 reported a new diagnosis of diabetes within 300 days of COVID-19 infection. There were no significant differences in incidence by treatment arm or vaccination in univariate analysis. Participants with new onset T2DM had a higher baseline BMI (OR 1.08, 95% CI 1.03 to 1.13), and were more likely to report weight gain between the start of the pandemic and their first infection and more likely to report difficulty sleeping, OR 1.04 (95% CI 1.01 to 1.07) and OR 2.86 (95% CI 1.16 to 7.06), respectively. Multivariate analysis is pending. Conclusions: Patients with higher BMIs at baseline, those who gained weight between the onset of the pandemic and their first COVID-19 infection, or had difficulty sleeping were more likely to develop T2DM. Covid treatment with metformin, ivermectin, and fluvoxamine and vaccination status were not significant predictors of new T2DM. Disclosure J.M.Nicklas: None. E.J.Lemus wirtz: None. T.A.Murray: None. D.Liebovitz: None. S.Fenno: None. B.Anderson: None. N.Avula: None. N.Reddy: None. C.Bramante: None. Funding Rainwater Foundation; Parsemus Foundation; United Health Foundation; National Center for Advancing Translational Sciences (KL2TR002492, UL1TR002494); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK124654-01-A1); National Heart, Lung, and Blood Institute (K23HL133604)

885-P: Impact on Glycaemic Variability in Newly Onset T2DM Patients Initiating Dapagliflozin Plus Metformin vs. Metformin Alone, a Randomized Open Label Clinical Study—The MAGNNIFY Trial

Background: The aim of this study is to compare the effect of dapagliflozin (DAPA) in addition to metformin (MET) at maximum tolerated dose in glycaemic variability (GV) on drug naïve T2DM patients. ClinicalTrials.gov Identifier: NCT04090580 Methods: Newly diagnosed T2DM patients with HbA1c ≥ 7.5% - ≤ 12%, BMI &amp;gt; 25 - &amp;lt;45 kg/m2, were randomized 1:1 to receive DAPA 10 mg + MET or MET alone for 12 weeks. Both groups were monitored using a CGM system for 7 days at baseline and week 12. Primary outcome was defined as the mean difference of MAGE (Mean Amplitude of Glycaemic Excursions). Additional secondary endpoints included mean difference of serum insulin, HbA1c, weight, and time in range. Results: 80 patients completed follow-up at week 12 (DAPA+MET, n=41; MET, n=39). Baseline characteristics included mean age 52.2±10.4 years, weight 80.6±16.5 kg, SBP 133.3±19.3 mmHg, HbA1c 9.3±1.5 %, eGFR 100.5±15.4 ml/min/1.73m2, MAGE 4.2±1.4 mmol/L. Patients treated with DAPA+MET had lower GV at week 12 measured by MAGE (-0.79 [-0.86 DAPA+MET vs -0.06 MET; p=0.018]) and higher time in range (+22.9% [35.8 DAPA+MET vs 12.9 MET; p=0.002]). DAPA group had lower insulin plasma levels (-4.5 µU/mL [-2.8 DAPA+MET vs +1.6 MET; p=0.029]) and body weight (-3.2 kg [-3.22 DAPA+MET vs -0.6 MET; p&amp;lt;0.001]); nominal reductions were observed in HbA1c (-1.82 DAPA+MET vs -1.61 MET; p=0.919) and SBP (-4.96 mmHg [-4.35 DAPA+MET vs +0.60 MET; p=0.277]. Conclusions: Patients with new onset T2DM treated with DAPA + MET during a 12-week period had improvements in glycaemic variability measured by MAGE (-19.63%) and achieved longer periods within target range for glycaemic control in comparison with patients treated only with MET. Plasmatic insulin levels, and weight reduction were also significantly reduced with DAPA; nominal reductions in HbA1c and SBP were observed. All these findings support the early dapagliflozin use in patients with newly onset T2DM. Disclosure A.P.Guerrero-castillo: None. S.C.Juarez-comboni: Employee; AstraZeneca. F.J.Gómez-perez: None. M.A.Gomez-samano: Research Support; AstraZeneca. A.Benitez-renteria: Employee; AstraZeneca. D.Cuevas-ramos: None. M.López-carrasco: None. A.Silva: Stock/Shareholder; AstraZeneca. G.X.Brito: None. L.Palacios-baez: None. I.Manjarrez-martínez: None. S.I.Rodriguez-carranza: None. Funding AstraZeneca Mexico

PS-C01-4: ASSOCIATIONS OF ARTERIAL STIFFNESS ONSET AGE WITH TYPE 2 DIABETES RISK: A LARGE-SCALE CHINESE COHORT STUDY

Objective: To explore the associations between arterial stiffness (AS) onset age and type 2 diabetes (T2DM) risk. Design and Method: This study enrolled 22,588 participants free of T2DM at baseline. All participants take an annual physical examination from 2012 to 2016, with fasting blood glucose and brachial-ankle pulse wave velocity measurements. Cox proportional model was used to investigate the association between AS onset age and T2DM risk. Sex specific analysis was also performed, as well as examining the association between early vascular aging (EVA), normal vascular aging (NVA), supernormal vascular aging (SUPERNOVA) onset age, and diabetes risk. Results: Totalling 757 (3.4%) participants were diagnosed with T2DM. Compared with participants free of AS in each specific age group, the earlier AS onset age was more strongly associated with T2DM risk, especially for the middle age, with the fully adjusted hazard risk (HR) and 95% confidence interval (CI) of 4.63 (2.79, 7.67) for AS onset age at 50. Similar results were observed both in males and females, with the fully adjusted HR and 95% CI of 4.54 (2.60, 7.93) for males and 4.86 (1.48, 16.01) for females, with AS onset age at 50. Such association was also observed in the exploration of EVA, NVA, and SUPERNOVA onset age and incident T2DM risk. Conclusions: This study revealed that middle-aged onset of AS was more significantly associated with a higher risk of T2DM. Early screening of AS, especially in middle age, may assist in T2DM detection and postpone diabetic vascular complications developing.

Insulin secretion is a strong predictor for need of insulin therapy in patients with new-onset diabetes and HbA1c of more than 10%: A post hoc analysis of the EDICT study.

To identify predictors of response to glucose-lowering therapy in patients with new-onset diabetes and very high HbA1c (>10%). The study included EDICT participants with an initial HbA1c of more than 10% (N = 104). All subjects received a 75-g oral glucose tolerance test (OGTT) before initiation of therapy, and then were randomized to receive: (a) initial triple therapy with metformin, pioglitazone and exenatide versus (b) stepwise conventional therapy with metformin followed by glipizide and then glargine insulin to reduce HbA1c to less than 6.5%. Insulin secretion and insulin resistance were calculated with OGTT-derived indices. Sixty-one per cent of participants in the conventional therapy group achieved HbA1c of less than 6.5% at 6 months without need of insulin therapy compared with 78% in the triple therapy group (P = NS). Insulin secretion at baseline was the strongest predictor of subjects who did not require insulin therapy; a cut point of CPEP120 /CPEP0 -the ratio between plasma C-peptide concentration at 120 minutes during the OGTT and fasting plasma C-peptide concentration-of more than 1.7 predicted subjects who achieved the treatment target without insulin, irrespective of the fasting plasma glucose (FPG) concentration and whether or not they were started on conventional or triple therapy. Subjects with a CPEP120 /CPEP0 of less than 1.7 plus FPG of 269 mg/dL or less (≤14.9 mmoL/L) also achieved the treatment goal with triple therapy. Insulin secretion in response to a 75-g OGTT predicts the need for insulin therapy at the time of type 2 diabetes (T2D) diagnosis. A cut point of 1.7 of CPEP120 /CPEP0 provides a useful clinical tool to individualize glucose-lowering therapy in patients with new-onset T2D and HbA1c of more than 10%.

Female African Green Monkeys Exhibit Higher Insulin Sensitivity and Lower Blood Pressure than Age‐matched Males

Type 2 Diabetes (T2DM) has become the most prevalent form of diabetes worldwide. In some studies, females have increased insulin sensitivity with greater glucose tolerance than males. Pre-menopausal females may also be protected from early onset T2DM, hypertension and early onset end stage renal disease. A subpopulation of African Green Monkeys (AGM; Chlorocebus aethiops sabaeus) exhibit spontaneous glucose intolerance and co-morbidities such as insulin insensitivity, and spontaneous hypertension. The AGM’ similarities to human pathologies make them an optimal experimental model for diabetes. Thus, we hypothesize that female AGM may differ in insulin sensitivity compared to age-matched males. Healthy, middle-aged AGM were utilized (n= 22 female, n=13 male). Systolic blood pressure (SBP) was measured by forearm plethysmography. Glucose tolerance was assessed via conscious and anesthetized oral glucose tolerance tests (OGTT). All AGM were fasted 12-18 hours with water provided ad libitum. Blood glucose was measured via standard glucometry at 0, 15, 30, 60, 90, and 120 min after an oral glucose load. Conscious AGM’ OGTT were delivered as 0.75g glucose/kg body weight. Anesthetized AGM (ketamine, 15mg/kg, i.m.), received 5g/dl glucose and 15 ml/kg in water. Venous blood samples were taken at 0, 30, 90 and 120 min after glucose administration in anesthetized AGM. All data between conscious and anesthetized OGTT were similar. All AGM were normotensive, however, male SBPs averaged 117.6 ± 4.2 mmHg compared with female SBPs of 104.1 ± 4.1 mmHg (p< 0.05). Female AGM area under the curve (AUC) for glucose was 12,102±466.9 min*mg/dl compared to 13,799.4±564.1 min*mg/dl for males over the 120 min after the glucose load. The peak blood glucose AUC response for females was 6,211.4 ± 219.5 min*mg/dl and 7,482 ±600.1 min*mg/dl in males (p<0.05). Insulin and C-peptide were also compared at the same time points. There were no differences in insulin or C-peptide responses between males and females. Overall renal glomerular function was assessed by measuring fasted, plasma creatinine concentrations. Average plasma creatinine was not different between males and females. These data demonstrate that middle-aged, males have decreased glucose tolerance compared to age-matched females despite similar OGTT induced changes in plasma insulin and C-peptide. Thus, middle-aged males have decreased insulin sensitivity in their response to glucose following an oral glucose load compared to females. All AGM in this study were normotensive however, females had significantly lower SBP than males, indicating that reduced glucose tolerance in males may contribute to elevated SBP. Together, the glucose and SBP data may suggest early onset of T2DM in males compared to age-matched females. This potential early onset T2DM has yet to induce overt alterations in renal glomerular filtration. Long-term studies are needed to assess whether further blood pressure elevation can lead to a decline in renal function and renal injury. Future studies will include differentiation of renal function in males and females including proteinuria, glomerular filtration, and kidney histology of AGM.

Painless foot drop: an unusual acute presentation of new onset type 1 diabetes mellitus.

SummaryA 26-year-old Caucasian female with no past medical history or family history of auto-immune disease presented to the emergency department with new onset painless left foot drop. A panel of blood tests revealed blood glucose of 49.9 mmol/L and raised blood ketone levels. The patient was referred to the diabetes team who made a clinical diagnosis of type 1 diabetes (T1DM) and insulin treatment was initiated. Elevated levels of diabetes auto-antibodies were subsequently detected. Nerve conduction studies demonstrated a left common peroneal nerve lesion with conduction block at the fibular head. After 2 weeks of insulin treatment, a significant improvement of her foot drop was observed and after 8 weeks she was walking normally. The most probable cause of her foot drop was acute diabetic mononeuropathy. To our knowledge, there are no similar cases in adult patients reported in the literature. Our case highlights the importance of physicians being aware of atypical presentation of new onset T1DM.Learning points There is an increasing incidence of T1DM with more than half of patients presenting after the age of 20. Diabetic peripheral neuropathy can present both acutely and as a mononeuropathy. Although rare, clinicians should be aware of mononeuropathy as a presenting symptom of T1DM to avoid delay in the treatment initiation. This case highlights an unusual presentation of T1DM and illustrates the importance of the early diagnosis and management of T1DM.

The Role of Intermediate Monocytes (CD14+CD16+) in Development and Diagnosis of Recent Type 1 Diabetes in Children

Background: Monocytes play an important role in antigen presentation and cytokine production to achieve a proper immune response and are therefore largely implicated in the development and progression of autoimmune diseases such as Type 1 diabetes mellitus. Objectives: To determine the significance of expanded intermediate monocytes as a predictive factor for the poor residual islet β−cell function in children with recent-onset Type 1 diabetes mellitus. Subjects and methods: This study was a case- control study carried out at Pediatric Endocrinology Outpatient Clinic and Clinical Pathology Department, Zagazig University Hospital. It included 20 patients with recent onset T1DM and 20 age and sex matched healthy children as a control group. All studied groups were subjected to full history taking, thorough clinical examination and laboratory investigations in the form of CBC, fasting blood glucose, C-peptide and serum HbA1c levels. Cell-surface monocyte phenotypic analysis was performed after staining with human anti-CD14 and anti-CD16 by flow cytometry. Results: There were highly significant increase in the ratio of intermediate monocytes and significant increase in the ratio of classical, non-classical monocytes in T1DM group compared to control group. Conclusion: The intermediate monocyte population was expanded in pediatric patients with T1DM. As these cells were shown to have pro-inflammatory activity, they are likely to be implicated in the impaired function of β-cells, with deleterious consequences for the development of T1DM.

Early intensification of glucose-lowering therapy: VERIFY lessons and real clinical practice on the example of the Moscow region diabetes register data

The prevalence of T2DM is steadily increasing not only among the elderly, but also at a young age. T2DM is preceded by a long period of significant metabolic changes with the development of insulin resistance and в-cell dysfunction. To reduce the prevalence of complications, treatment is needed which affects several pathophysiological mechanisms underlying the disease. Monotherapy with metformin at the onset of T2DM is often insufficient. The VERIFY study demonstrated the advantage of early administration of a combination of vildagliptin and metformin in relation to the glycemic durability compared to the sequential intensification of metformin with vildagliptin in patients with type 2 diabetes. To assess the current situation in terms of the incidence of T2DM complications and the structure of the prescribing glucose lowering drugs based on the data from the Diabetes Register (DR) of the Moscow Region. To demonstrate the advantages of early combination therapy in patients with newly diagnosed T2DM using clinical cases. The data from the DR of the Moscow region, which is part of the National Diabetes Register of the Russian Federation, were used for the analysis. The data of 6,096 patients with T2DM who died in 2019 were evaluated for building the structure of the causes of death of patients with T2DM. The pattern of glucose-lowering therapy was analyzed based on data of 226,327 patients with T2DM (for 2020), as well as separately of 14,379 patients with newly diagnosed T2DM in 2019. Clinical cases are described based on the data of two patients with T2DM, available in the DR database and outpatient records. In patients with young onset T2DM (&lt;40 years), the prevalence of severe complications is higher than in the general population of patients with T2DM: blindness is in 5.9 times, end-stage chronic renal failure in 2.9 times, lower limb amputations in 6.4 times more. When prescribing glucose lowering drugs, monotherapy is prevalent, mostly metformin. In double combination, metformin is used in 96.22% of cases. In the structure of glucose lowering drugs, with newly diagnosed T2DM, combination therapy is used less frequently than in patients with T2DM in general. Of the drugs of the IDP-4 group, vildagliptin is most often prescribed - 46.25% (including of a fixed combination with metformin - 12.22%). Clinical cases reflect a rapid clinical outcome: a decrease in HbA1c to the target in 6 months, the absence of hypoglycemia or other side effects, and positive weight dynamics. A fairly large propotion of patients with T2DM are on monotherapy with glucouse lowering drugs. Early prescription of the combination of metformin plus vildagliptin provides a longer maintenance of glycemic control without increasing the risk of hypoglycemia and weight gain for patients with newly diagnosed T2DM.

2253-PUB: A Rare Case of Fulminant Type 1 Diabetes Postpartum

Amongst women with gestational diabetes (GDM), the incidence of type 1 diabetes (T1DM) was 3.4% at 9 months post-partum and 6.6% at 2 years post-partum in one prospective study. Higher number of autoantibodies (Abs) during pregnancy is associated with a higher risk of T1DM. In rare cases, women with GDM can develop antibody-negative T1DM post-partum. The presentation of fulminant T1DM defined as rapid onset ketoacidosis, undetectable C-peptide, A1C&amp;lt;8.5%, elevated pancreatic enzymes and often negative antibodies has only rarely been reported in the post-partum period and predominantly in individuals of Japanese descent. In our case, a 34-year-old woman of Indian descent presented for GDM which required low dose Detemir 6 units nightly. She had an uncomplicated delivery and stopped insulin. On post-partum day 8 she was hospitalized for 1 day of non-specific malaise symptoms and was incidentally found to have elevated lipase 398 U/L, serum glucose 93 mg/dL and mildly bulky pancreas by ultrasound imaging. Initially she clinically improved, but on post-partum day 15 she developed symptoms of fatigue, polyuria, polydipsia, and weight loss which progressed to vomiting, tachycardia and tachypnea. She was readmitted on post-partum day 19 with glucose 482 mg/dL, arterial pH 6.95, anion gap 34, and moderate ketones consistent with severe Diabetic Ketoacidosis. Hemoglobin A1C was 6% and lipase was normal. New onset T1DM was diagnosed based on undetectable C-peptide, though GAD and ICA Abs were negative. She was treated with an insulin infusion and later transitioned to a basal-bolus subcutaneous insulin regimen. Repeat labs at 12 months post-partum confirmed persistent undetectable C-peptide and negative Abs. We present a unique case of a woman of Indian descent with GDM found to have fulminant T1DM in the early post-partum period. To our knowledge, this is the first case of fulminant diabetes post-partum reported in a patient of Indian ethnicity. Our case highlights the importance of consideration of this rare diagnosis in diverse populations. Disclosure K. Lane: None. R. Oxman: None.

2163-PUB: Prevalence of Multiple Stress Factors in Young Adults with Type 2 Diabetes

Introduction: Incidence of type 2 diabetes (T2DM) among young adults (age &amp;lt;= 40) has been increasing rapidly. We hypothesize that this could be due to increasing levels of stress seen in this age group due to demographic, economic and environmental shifts that have occurred in the past 30 years. Method: Modifiable vs. non-modifiable risk factors were evaluated at a specialist diabetes and endocrinology clinic. Consecutive patients meeting the inclusions criteria (T2DM between the ages of 18 to 40), were provided with study questionnaire at their appointment over a 3 month period. The questionnaire assessed socio-economic factors, self-reported levels of stress, dietary habits, sleep duration and physical activity. Results: 52 patients (Males = 38 (73%)) completed the study questionnaire. Mean age (± SD) at diagnosis of T2DM was 31 (± 5.8). Thirty five (79%) were immigrants to Canada, of which 47% had immigrated to Canada within the last 10 years (2010-2019). Of the study participants, mean stress level (on a scale of 1-10) was 5.9 (± 2.7). Work stress was reported by 79.1%, financial stress by 43.7%, family related stress by 39.5%, and unemployment related stress by 10.4% of the patients. Other stressors reported were weight management and medication coverage. Twenty (38%) participants reported sleeping an avg of ≤ 6 hrs/day. Moderate intensity physical activity (≥ 150 mins per week) prior to diagnosis was reported by 36% patients. Discussion: High prevalence of modifiable risk factors such as stress, decreased physical activity, inadequate sleep was found in young adults with T2DM. Immigrants are at high risk of T2DM at a young age likely due to stressors as well as diet and lifestyle changes involved in relocating to a new country. Education regarding higher risk of T2DM at an early age, and interventions to reduce modifiable risk factors is paramount at an individual and societal level, in order to stem the epidemic of young onset T2DM. Disclosure S. Dave: None. K. Suntharamoorthy: None. S. Mohyiddin: None. U. Muhammad: None. S. Malik: None. N. Gupta: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi.

MON-LB128 Phosphoinositide 3-Kinase (PI3K) Inhibitor Induced Hyperglycemia With Alpelisib

Intorduction: Breast cancer is estimated to be the third leading cause of cancer-related death in women. A commonly mutated pathway in breast cancer is the phosphoinositide-3-kinase (PI3K) pathway. Newer agents inhibiting PI3K are now available for the treatment of advanced cancers. Metabolic complications of new onset diabetes/hyperglycemia and hyperlipidemia are commonly seen. The precise mechanism through which PI3K inhibitors cause hyperglycemia is unknown. We present a patient who developed hyperglycemia within 2 weeks of starting alpelisib. Clinical Case: A 68 y.o female with history of metastatic invasive lobular carcinoma of the right breast HR-positive, HER-2 negative who presents for evaluation of hyperglycemia. She was diagnosed with metastatic breast carcinoma and failed multiple treatment options. She was started on alpelisib 2 weeks prior and had no history of glucose intolerance. Her pretreatment HbA1c was 5.5% (n <5.7%). After initiation of alpelisib, fasting blood glucose ranged between 100-140 mg/dL (n 100-125 mg/dL), while post-prandial blood glucose ranged between 150-300 mg/dL (n <140 mg/dl). Her HbA1c rose to 7% (n <5.7%). She did not manifest any macrovascular or microvascular complications, but did have a family history of type 2 diabetes mellitus. After initially being started on metformin, the dose increased to 1500 mg daily with the addition of glimepiride 1 mg. She eventually achieved stable euglycemia on metformin alone.Conclusion: Hyperglycemia has been reported to commonly occur with PI3K inhibitor therapy, the mechanism of which is poorly understood. One purposed mechanism is the effect on AMP kinase pathway which may also affect the efficacy of metformin. Here, we present a case of new onset T2DM in the setting of HR-positive, HER-2 negative breast cancer effectively treated with metformin. Future studies are needed to establish the prevalence and incidence of drug-induced hyperglycemia in patients administered PI3K inhibitors, as well as the best management approach to ensuing hyperglycemia. Reference: André F, Ciruelos EM, Rubovszky G, et.al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940.Guena, E, Roda, D, Rafii, S. Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on phase I clinical trials. Br J Cancer. 2015;113:1541-1547Busaidy, NL, Farooki, A, Dowlati, A. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol. 2012;30:2919-2928.

ESC/EASD guideline sheds light on diabetes and cardiovascular disease management

ESC/EASD guideline sheds light on diabetes and cardiovascular disease management

Prediction of Type II Diabetes Onset with Computed Tomography and Electronic Medical Records.

Type II diabetes mellitus (T2DM) is a significant public health concern with multiple known risk factors (e.g., body mass index (BMI), body fat distribution, glucose levels). Improved prediction or prognosis would enable earlier intervention before possibly irreversible damage has occurred. Meanwhile, abdominal computed tomography (CT) is a relatively common imaging technique. Herein, we explore secondary use of the CT imaging data to refine the risk profile of future diagnosis of T2DM. In this work, we delineate quantitative information and imaging slices of patient history to predict onset T2DM retrieved from ICD-9 codes at least one year in the future. Furthermore, we investigate the role of five different types of electronic medical records (EMR), specifically 1) demographics; 2) pancreas volume; 3) visceral/subcutaneous fat volumes in L2 region of interest; 4) abdominal body fat distribution and 5) glucose lab tests in prediction. Next, we build a deep neural network to predict onset T2DM with pancreas imaging slices. Finally, motivated by multi-modal machine learning, we construct a merged framework to combine CT imaging slices with EMR information to refine the prediction. We empirically demonstrate our proposed joint analysis involving images and EMR leads to 4.25% and 6.93% AUC increase in predicting T2DM compared with only using images or EMR. In this study, we used case-control dataset of 997 subjects with CT scans and contextual EMR scores. To the best of our knowledge, this is the first work to show the ability to prognose T2DM using the patients' contextual and imaging history. We believe this study has promising potential for heterogeneous data analysis and multi-modal medical applications.

Wingless-type MMTV integration site family member 5a: a novel biomarker regulated in type 2 diabetes mellitus and diabetic kidney disease

ObjectivesType 2 diabetes mellitus (T2DM) is sustained by insulin resistance (IR) and reduced β-cell mass, which is largely due to insulin secretory dysfunction. Wnt5a protein is essential to islet formation and β-cell migration in the development of pancreas in vertebrates. Levels of the Wnt5a protein antagonist plasma secreted frizzled-related protein 5 (Sfrp5) were elevated in patients with T2DM. However, the association between Wnt5a, T2DM patients and diabetic kidney disease (DKD) is unknown. We aim to investigate the circulating Wnt5a levels in in different clinical stages of T2DM and evaluate its correlation of duration of diabetes mellitus chronic complication.MethodsA total of 329 participants (187 males, 142 females; age range 40 to 80 years) were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters evaluated in subjects with new onset T2DM, onset T2DM after treatment and DKD at different clinical phases.ResultsWnt5a was significantly down-regulated in newly diagnosed T2DM patients and gradually increased after 3 months of treatment. Interesting, serum wnt5a was gradually increased in patients with long-term diabetes and kidney disease compared to patients with T2DM and onset DKD.ConclusionsWe speculated that the Wnt5a protein might regulate islet function and be involved in the onset of diabetes as a protective factor. It may be one of the inflammatory factors adversely involved in the progression of diabetic nephropathy.

1047 Changes in Liver Fibrosis Scores in Patients With New Onset Type 2 Diabetes on Triple Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy: Year Two Results

INTRODUCTION: Patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are at higher risk of developing advanced fibrosis. Certain diabetes medications such as pioglitazone and GLP1 agonists have shown some efficacy against NAFLD in small clinical trials. The Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM trial is an ongoing interventional trial assessing the effects of two different approaches to treating T2D (ClinicalTrials.gov Identifier: NCT01107717). The aim of the current study was to evaluate the effects of these two approaches on liver fibrosis scores after two years of treatment. METHODS: Newly diagnosed, drug-naïve T2DM patients were enrolled into the study. Medical history, clinical characteristics were obtained, and blood was drawn for the measurement of plasma glucose concentration, HbA1c, CBC, and blood chemistries. Subjects were randomized to receive in an open label fashion an initial combination therapy with metformin (2000 mg) plus pioglitazone (45 mg) and exenatide 10 µg BID (triple therapy) or sequential addition of metformin followed by sulfonylurea and insulin (conventional therapy) to maintain HbA1c &lt; 6.5%. Subjects were seen every 3 months for follow-up visits and at 2 years all baseline measurements were repeated. Liver fibrosis scores that were calculated included AST/ALT ration, APRI, FIB-4 and NFS. RESULTS: Baseline characteristics are listed in Table 1; patients were well matched. Liver fibrosis scores at baseline and at 2 years are listed in Table 2. To compare the effect of each therapy on liver fibrosis scores, the ratio between the 2-year values of liver fibrosis scores to the baseline values was compared amongst the two treatment groups with ANOVA. Both therapies significantly reduced liver fibrosis scores but no significant difference was noted between the two treatment arms. CONCLUSION: In this randomized trial in patients with new-onset T2D, good control of HbA1c was associated with reduction in liver fibrosis scores at 2 years but the use of pioglitazone and GLP1 agonist did not have an added benefit over conventional therapy. The effects of longer duration of treatment are currently being evaluated in addition to assessment of fibrosis by Fibroscan and MR elastography.

Screening of HNF1A and HNF4A mutation and clinical phenotype analysis in a large cohort of Chinese patients with maturity-onset diabetes of the young

The study aimed to screen the HNF1A and HNF4A mutation in a large Chinese cohort of high clinical suspicion of maturity-onset diabetes of the young (MODY) patients and characterize the clinical features of those patients. The performance of hsCRP as a biomarker to differentiate MODY3 from early onset T2DM was also evaluated. A total of 74 patients with a strong clinical suspicion of MODY from 59 families and 33 newly diagnosed early-onset T2DM were included. HNF1A and HNF4A mutations were analyzed by Sanger sequencing. ROC curves were used to identify the optimal cutoff of hsCRP. One novel (c.864_865insG) and six recurrent HNF1A mutations (R203H, R263H, P379T, L422P, P519L and c.873delC) in 17 patients from 8 families (13.6%), as well as one novel HNF4A (R331H) mutation were identified. Nonspecific clinical presentations were observed in MODYX compared to MODY3 patients. MODY3 subjects exhibited with younger, lower BMI, TG, fasting and postprandial C-peptide, higher HDL than T2DM. Particularly, we confirmed serum hsCRP was lower in MODY3 than T2DM. ROC curve showed a good discrimination with an AUC of 0.852 and identified a cutoff hsCRP of 0.79 (75% sensitivity and 83% specificity). Good glycemic control was observed in all identified patients after switching to glimepiride therapy. The prevalence of HNF1A mutation was relatively lower in Mainland China and HNF4A mutation was rare. Serum hsCRP concentrations performed well in discriminating MODY3 from T2DM. Molecular diagnosis of MODY3/1 did transform management in clinical practice and facilitated the glycemic control.

Increasing risk of psychiatric morbidity after childhood onset T1DM: a population-based cohort study

Increasing risk of psychiatric morbidity after childhood onset T1DM: a population-based cohort study

Gastrin—A Potential Predictor of Glucoregulation in Newly Diagnosed Type 2 Diabetes Patients

Background and Aims: Experimental data demonstrated that activation of GLP-1 and gastrin signaling induces beta cell neogenesis, resulting in a promotion of glucose-induced insulin secretion. In addition, treatment with proton pump inhibitors is associated with greater glycemic control in patients with type 2 diabetes (T2DM), particularly in those on insulin- or GLP-1-based therapy. The aim of this study was to assess gastrin as a potential predictor of beta cell function and glucoregulation in newly diagnosed T2DM patients. Materials and Methods: In this cross sectional study 190 patients (64 males and 126 females) with new onset T2DM were included. Patients treated with IPPs were excluded. Fasting plasma glucose (FPG), postprandial PG, HbA1c, fasting insulin, pancreatic B cell function (HOMA-B), insulin resistance index (HOMA-IR), fasting c-peptide and gastrin levels were measured at the time of diagnosis. Results: Baseline HbA1c was 7.53±2.08%, average age of patients was 61.8±10.years and body mass index (BMI) was 31.25±5.73 kg/m2. Parameters of glucoregulation were not significantly correlated with gastrin (all p&amp;gt;0.05), while there was moderate negative correlation with HOMA-B (HbA1c, FPG and PPG; p &amp;lt;0.01 for all) and positive correlation with HOMA-IR (HbA1c, FPG and PPG; p&amp;lt;0.01 for all). Patients with higher baseline measures of glucose regulation had lower HOMA-B and higher HIMA-IR as was expected. There was no association between gastrin and HOMA-B (p&amp;gt;0.05) or HOMA-IR. Furthermore, no association was established between c-peptide, insulin levels and gastrin (p&amp;gt;0.05). Conclusion: Baseline gastrin levels are not sufficient to have a significant effect on glucoregulation or HOMA-B and HOMA-IR in newly diagnosed T2DM, therefore it could be postulated that further stimulation of gastrin secretion (e.g., with IPPs or GLP-1 based therapy) is needed in order to influence beta cell function and glycemic control. Disclosure M. Cigrovski Berkovic: None. D. Herman Mahecic: None. I. Bilic-Curcic: None.