Effects Of Antidiabetic Medications Research Articles

Microphysiological pancreas-on-chip platform with integrated sensors to model endocrine function and metabolism.

Pancreatic in vitro research is of major importance to advance mechanistic understanding and development of treatment options for diseases such as diabetes mellitus. We present a thermoplastic-based microphysiological system aiming to model the complex microphysiological structure and function of the endocrine pancreas with concurrent real-time read-out capabilities. The specifically tailored platform enables self-guided trapping of single islets at defined locations: β-cells are assembled to pseudo-islets and injected into the tissue chamber using hydrostatic pressure-driven flow. The pseudo-islets can further be embedded in an ECM-like hydrogel mimicking the native microenvironment of pancreatic islets in vivo. Non-invasive real-time monitoring of the oxygen levels on-chip is realized by the integration of luminescence-based optical sensors to the platform. To monitor insulin secretion kinetics in response to glucose stimulation in a time-resolved manner, an automated cycling of different glucose conditions is implemented. The model's response to glucose stimulation can be monitored via offline analysis of insulin secretion and via specific changes in oxygen consumption due to higher metabolic activity of pseudo-islets at high glucose levels. To demonstrate applicability for drug testing, the effects of antidiabetic medications are assessed and changes in dynamic insulin secretion are observed in line with the respective mechanism of action. Finally, by integrating human pancreatic islet microtissues, we highlight the flexibility of the platform and demonstrate the preservation of long-term functionality of human endocrine pancreatic tissue.

Association Between Antidiabetic Drugs and Delirium: A Study Based on the Adverse Drug Event Reporting Database in Japan.

Several associations between diabetes mellitus and delirium have been reported; however, they have been inconsistent, and evidence on the effects of antidiabetic medications on delirium is also limited. This study aimed to investigate whether the use of antidiabetic drugs is a risk factor for delirium development. Using the Japanese Adverse Event Reporting Database, we analyzed 662,899 reports between 2004 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (CIs) for delirium associated with diabetes and using each antidiabetic medication were calculated after adjusting for potential confounders. Overall, 8892 of the reports analyzed were associated with delirium. A comparison of the incidence of delirium between patients with and without diabetes showed no significant difference, with 1.34% in patients without diabetes and 1.37% in those with diabetes. In each antidiabetic medication, signals for delirium were detected for sulfonylurea (crude ROR, 1.35; 95% CI 1.21-1.51) and insulin (crude ROR, 1.28; 95% CI 1.13-1.44). These results were maintained even after adjusting for factors with potential confounders (sulfonylurea: adjusted ROR, 1.75; 95% CI 1.54-2.00, insulin: adjusted ROR, 1.35; 95% CI 1.20-1.54). Our results suggest no association between diabetes and delirium; however, using sulfonylurea and insulin may be associated with delirium development. Nonetheless, these findings should be validated in future studies.

The interplay between antidiabetic medications and cancer risk

Diabetes mellitus (DM) refers to a group of metabolic disorders marked by chronic hyperglycemia. Its primary cause usually involves impaired insulin secretion or impaired insulin action. Its prevalence is escalating globally. Type II DM (T2DM) is becoming more common, and it is expected to afflict 7.7% (439 million) of persons aged 20 to 79 by 2030. Diabetes appears to be linked to an increased risk of a variety of cancers, ranging from a 20 to 30% greater risk of breast or colorectal cancer to a 97% increased chance of intrahepatic cholangiocarcinoma or endometrial cancer. Shared risk factors and potential biochemical pathways have prompted investigations into the effect of antidiabetic medications (ADMs) on cancer risk. We intend to investigate the link between diabetes drugs and cancer development.

Effects of antidiabetic medications on metabolic-associated fatty liver disease

Metabolic-Associated Fatty Liver Disease (MAFLD) is a prevalent metabolic complication among patients with obesity and type 2 diabetes, associated with bad prognosis. Classical antidiabetics have little effects on this complication, except pioglitazone that exerts a positive impact but with uncertain safety. Gliptins are almost neutral, whereas glucagon-like peptide-1 receptor agonists showed benefits, the most potent ones being those associated with a greater weight loss such as liraglutide or semaglutide. Gliflozins also reduce hepatic fat content and liver enzymes used as biomarkers of steatosis. However, histological data remain scarce, especially those focusing on inflammation and fibrosis, and direct comparative data between available therapies are still lacking.

Effect of Anti-Diabetic Medications on Dental Implants: A Scoping Review of Animal Studies and Their Relevance to Humans.

Animal studies have ascertained that hyperglycemia adversely affects bone metabolism and dental implant osseointegration. However, diabetic patients show low occurrence of unfavorable hard or soft peri-implant tissue changes, differences that are possibly due to treatment with anti-diabetic medications. This scoping review aimed to systematically examine the effects of these drugs on implant outcomes and explore the predictive modality of animal studies for clinical practice according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Three electronic databases (MEDLINE, EBSCOHost, and Cochrane) were searched according to the PRISMA-ScR standards for studies on diabetic animals that received titanium implants and anti-diabetic treatments. Risk assessment was performed using the SYRCLE Risk-of-Bias (RoB) tool. Twenty-one papers were included, encompassing six types of medications. Fifteen studies were on T1DM animals, and only six involved T2DM models. T1DM animals were treated with non-insulin drugs in four investigations, while insulin was utilized in 11 other studies. In T2DM experiments, five administered non-insulin drugs, and only one applied locally delivered insulin. Only insulin in T1DM studies produced a positive influence on bone-implant contact (BIC), bone mineral content, and removal torque values. Inappropriate drug selection, inadequate glycemic control, and high RoB depict a mismatch between the research focus and the translational rationale to clinical practice. There remains a knowledge gap regarding T2DM investigations due to the lack of studies. More data are needed concerning intraoral implants and the performance of osseointegrated implants in patients with a later onset of diabetes. Future research should reflect the pathophysiology and treatment of each type of diabetes to ensure clinical applicability.

Magnetic Resonance Imaging and Spectroscopy Methods to Study Hepatic Glucose Metabolism and Their Applications in the Healthy and Diabetic Liver.

The liver plays an important role in whole-body glucose homeostasis by taking up glucose from and releasing glucose into the blood circulation. In the postprandial state, excess glucose in the blood circulation is stored in hepatocytes as glycogen. In the postabsorptive state, the liver produces glucose by breaking down glycogen and from noncarbohydrate precursors such as lactate. In metabolic diseases such as diabetes, these processes are dysregulated, resulting in abnormal blood glucose levels. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are noninvasive techniques that give unique insight into different aspects of glucose metabolism, such as glycogenesis, glycogenolysis, and gluconeogenesis, in the liver in vivo. Using these techniques, liver glucose metabolism has been studied in regard to a variety of interventions, such as fasting, meal intake, and exercise. Moreover, deviations from normal hepatic glucose metabolism have been investigated in both patients with type 1 and 2 diabetes, as well as the effects of antidiabetic medications. This review provides an overview of current MR techniques to measure hepatic glucose metabolism and the insights obtained by the application of these techniques in the healthy and diabetic liver.

Expert consensus on personalized initiation of glucose-lowering therapy in adults with newly diagnosed type 2 diabetes without clinical cardiovascular disease or chronic kidney disease.

Since it is difficult for clinicians to make a decision among the various types of antidiabetic medications due to their great discrepancy in mechanisms, pharmacological properties, and cardiovascular/renal protection, a relatively "precision" or personalized hypoglycemic treatment suggestion is practical for type 2 diabetes (T2D) management in adults. This expert consensus makes some recommendations based on the characteristics of adult T2D patients without clinical cardiovascular disease (CVD) or chronic kidney disease (CKD) by evidence from large-scale clinical trials. The main consideration for initiating antidiabetic medications is the safety and benefits for prevention of target organ damage, such as CVD and CKD. The choice of personalized glucose-lowering therapy regarding target organ protection is based on the various effects of antidiabetic medications, patients' clinical characteristics and their key risks, as well as the sociological factors. According to the effects on glucose reduction, cardiovascular protection, renal benefit, body weight change, hypoglycemic risk, and liver function impact, the antidiabetic medications are recategorized in this consensus. Combined with the glucose control target and the different effects of hypoglycemic agents, a significant body of recommendations have been developed for optimal T2D management according to the risk factors for atherosclerotic CVD, heart failure, CKD, primary fatty liver, and hypoglycemia. This consensus gives detailed guidance on personalized antidiabetic therapy initiation in newly diagnosed T2D adults, which attaches great importance to both glucose control and target organ protection.

Effects of anti-diabetes medications on cardiovascular and kidney outcomes in Asian patients with type 2 diabetes: a rapid evidence assessment and narrative synthesis

ABSTRACT Background The cardiovascular and kidney safety of glucose-lowering drugs is a key concern in type 2 diabetes (T2D). We evaluated cardiorenal outcomes with glucose-lowering drugs in Asian patients, who comprise over half of T2D cases globally. Research design and methods A rapid evidence assessment was conducted for phase III or IV, double-blind, randomized clinical trials of glucose-lowering drugs reporting cardiovascular or kidney outcomes for Asian T2D patients (Embase, Medline, Cochrane Library databases: 1 January 2008–14 June 2020). Results Fifty-four publications reported exploratory data for Asians from 18 trials of dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin analogs. SGLT2 inhibitors and several GLP-1 receptor agonists were associated with reduced cardiovascular risk in Asian T2D patients, while DPP-4 inhibitors exhibited cardiovascular safety. SGLT2 inhibitors also appeared to reduce renal risk; however, kidney outcomes were lacking for DPP-4 inhibitors other than linagliptin and GLP-1 receptor agonists in Asian patients. Insulin data were inconclusive as the only trial conducted used different types of insulin as both treatment and comparator. Conclusions Cardiorenal outcomes with glucose-lowering drugs in Asian T2D patients were similar to outcomes in the overall multinational cohorts of these trials. DPP-4 inhibitors appear to demonstrate cardiovascular safety in Asians, while SGLT2 inhibitors and some GLP-1 receptor agonists may reduce cardiorenal and cardiovascular risk, respectively.

Diabetes and Stroke

Stroke is one of the major complications of diabetes and increases morbidity and mortality. Hyperglycemia confers increased risk of stroke occurrence. Furthermore, cardiometabolic risk factors such as hypertension and dyslipidemia frequently coexist in patients with diabetes and increase the risk of stroke. Some recent cardiovascular outcome trials of newer anti-diabetic medications have shown beneficial effects on cardiovascular complications. Prevention and improving outcomes of stroke in patients with diabetes requires proper management of hyperglycemia and additional risk factors. This review is an evidence-based approach to the epidemiology, glycemic control, effects of anti-diabetic medications on stoke, and risk factor management for prevention and improving outcomes of stroke for patients with diabetes. Keywords: Diabetes mellitus; Glycemic control; Risk factors; Stroke

Effect of metformin on outcomes of catheter ablation for atrial fibrillation

Diabetes mellitus (DM) is a risk factor for atrial fibrillation (AF). The effect of antidiabetic medications on AF or the outcomes of catheter ablation (CA) has not been well described. We sought to determine whether metformin treatment is associated with a lower risk of atrial arrhythmias after CA in patients with DM and AF. A first CA was performed in 271 consecutive patients with DM and AF (age: 65 ± 9 years, women: 34%; and paroxysmal AF: 51%). At a median of 13 months after CA (interquartile range: 6-30), 100/182 patients (55%) treated with metformin remained in sinus rhythm without antiarrhythmic drug therapy, compared with 36/89 patients (40%) not receiving metformin (p = .03). There was a significant association between metformin therapy and freedom from recurrent atrial arrhythmias after CA in multivariable Cox hazards models (hazard ratio [HR]: 0.66; ±95% confidence interval [CI]: 0.44-0.98; p = .04) that adjusted for age, sex, body mass index, AF type (paroxysmal vs. nonparoxysmal), antiarrhythmic medication, obstructive sleep apnea, chronic kidney disease, coronary artery disease, left ventricular ejection fraction, and left atrial diameter. A Cox model that also incorporated other antidiabetic agents and fasting blood glucose demonstrated a similar reduction in the risk of recurrent atrial arrhythmias with metformin treatment (HR: 0.63; ±95% CI: 0.42-0.96; p = .03). In patients with DM, treatment with metformin appears to be independently associated with a significant reduction in the risk of recurrent atrial arrhythmias after CA for AF. Whether this effect is due to glycemic control or pleiotropic effects on electroanatomical mechanisms of AF remains to be determined.

Impact of Type 2 Diabetes Mellitus and Antidiabetic Medications on Bone Metabolism.

This review focuses on the complex interactions between hyperglycemia and bone fragility and the effects of antidiabetic medications on bone metabolism. Type 2 diabetes (T2D) is associated with increased risk of bone fracture even in those with increased or normal bone mineral density (BMD). The pathophysiology of diabetic bone disease is not completely understood, but it is thought to be multifactorial and associated with complex cross talk among factors such as AGEs, IGF-1, enteric hormones, and pro-inflammatory cytokines. Treatment for T2D may have an impact on bone metabolism. Diabetic bone disease should be considered a serious complication of long-standing T2D.

Diabetic Control Agents and Their Impact on Cardiac Surgery Patients: A Clinical Overview.

Chronic hyperglycemia is associated with poor cardiovascular surgical outcomes due to microvascular and macrovascular complications. This is a major concern as over one third of cardiovascular surgical patients have diabetes mellitus which greatly increases their risk of experiencing adverse cardiovascular events. A literature review was performed to identify articles discussing the effects of anti-diabetic medications (ADMs) on cardiovascular outcomes and surgical mortality and morbidity rates. Optimizing perioperative glucose levels remains a key factor in producing good surgical outcomes. In addition, recognizing gender differences, increasing patient satisfaction, and implementing dedicated diabetic teams all improve surgical mortality and morbidity rates in the diabetic population.

Effects of antidiabetic medications on cardiovascular outcomes.

Hyperglycemia is associated with an increased risk of adverse cardiovascular outcomes, such as heart failure, coronary heart disease, stroke, and in-hospital mortality. For those receiving cardiac surgery, up to half develop hyperglycemia while 30% have a diagnosis of diabetes, which is defined by chronic hyperglycemia. Due to a prothrombic state and endovascular damage, patients with diabetes have a twofold increased risk of cardiovascular events. Electronic literature search was done to identify articles that have discussed antidiabetic medications and how it is impacting the glycemia status as well as cardiovascular outcomes. No limits were placed on timing of the publication or type of the article. Key words and MeSH terms were used to conduct the search and the results are summarized in a narrative manner within each relevant section. Antidiabetic medications play a key role in lowering blood glucose levels to reduce adverse cardiovascular outcomes. However, it is a challenge to assess their cardiovascular safety due to confounding factors, such as age, obesity, smoking, hyperlipidemia, and high blood pressure. Further research in this field is required to understand this correlation closely. Optimizing blood glucose level during the perioperative period with correct medication and dose have a significant role in reducing morbidities. Measures should be taken to provide a safe blood glucose level for optimum outcomes.

Effects of Metformin and Sitagliptin Monotherapy on Expression of Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat Model of Type 2 Diabetes

Disordered intestinal sweet taste receptors (STRs) are implicated in glucose homeostasis by involving in incretin secretion and glucose absorption. However, the effects of antidiabetic medications on STRs, downstream molecules, and glucose transporters expression are unknown. In our study, ZDF rats (n=24) were randomly treated by metformin (MET, 215.15 mg/kg), sitagliptin (SIT, 10.76 mg/kg), or saline for 4 weeks. Fasting blood glucose and insulin levels were measured, and HOMA-IR and QUICKI index were calculated. One week later, we detected relative mRNA expression of T1R2/T1R3, α-gustducin, TRPM5 and glucose transporters including SGLT1, SGLT2, and GLUT2 in the small intestine and kidney. We found that though both metformin and sitagliptin effectively decreased fasting blood glucose, only metformin improved HOMA-IR and QUICKI (p<0.05). MRNA levels of STRs and sweet taste molecules in duodenum and jejunum were not different among three groups, but those in ileum were dramatically upregulated after SIT (vs. MET p<0.05; vs. CON p<0.01). SGLT1 and GLUT2 in ileum were markedly increased after SIT (p<0.01). In the kidney, expression of SGLT2 and GLUT2 were downregulated in both SIT and MET group (p<0.05). In conclusion, metformin and sitagliptin exerted different effects on expression of STRs and glucose transporters in the gut and kidney. STRs, downstream molecules, and glucose transporters in distal small intestinal were sensitively increased in response to sitagliptin than metformin treatment. Renal glucose transporters were downregulated after metformin and sitagliptin treatment.

Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Bone Metabolism and Fracture Risk

The effect of anti-diabetic medications on bone metabolism has received increasing attention, considering that type 2 diabetes mellitus is a common metabolic disorder with adverse effects on bone metabolism. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel anti-diabetic medications that prevent glucose resorption at the proximal convoluted tubules in the kidney, increasing urinary glucose excretion, and decreasing the blood glucose level. The superiority of SGLT2 inhibitors shows in reducing the glucose level independent of insulin secretion, lowering the risk of hypoglycemia, and improving cardiovascular outcomes. SGLT2 inhibitors have been associated with genital mycotic infections, increased risk of acute kidney injury, dehydration, orthostatic hypotension, and ketoacidosis. Moreover, the effect of SGLT2 inhibitors on bone metabolism and fracture risk has been widely taken into consideration. Our review summarizes the results of current studies investigating the effects of SGLT2 inhibitors on bone metabolism (possibly including increased bone turnover, disrupted bone microarchitecture, and reduced bone mineral density). Several mechanisms are probably involved, such as bone mineral losses due to the disturbed calcium and phosphate homeostasis, as confirmed by an increase in fibroblast growth factor 23 and parathyroid hormone levels and a decrease in 1,25-dihydroxyvitamin D levels. SGLT2 inhibitors might indirectly increase bone turnover by weight loss. Lowering the blood glucose level might ameliorate bone metabolism impairment in diabetes. The effect of SGLT2 inhibitors on bone fractures remains unclear. Evidence indicating the direct effect of SGLT2 inhibitors on fracture risk is lacking and increased falls probably contribute to fractures.

The effect of antidiabetic medications on non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is prevalent in more than 50% of patients with type II diabetes. At present, there is no approved therapy for NASH. Until now, the only proven effective interventions in improving biochemical and histological features of NASH, including fibrosis, are weight loss and physical activity even without weight loss. Because of the common epidemiological and pathophysiological features between NAFLD and T2DM, many antidiabetics drugs have been tested in patients with NAFLD over the years. Among these, pioglitazone and liraglutide seem to improve some histological features of NASH but have no clear effect on fibrosis. Metformin has been largely studied in the past years without convincing evidence of improving NAFLD. Data on other compounds such as DDP-4 and SGLT-2 inhibitors are limited. The rational and results of such studies are discussed in the present review.

The effect of antidiabetic medications on the cardiovascular system: a critical appraisal of current data.

Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results. Briefly, metformin is still considered safe and confers a beneficial effect on CVD risk. Conflicting data exist as concerns sulfonylureas, although the second and third generation representatives are regarded as relatively safe. Pioglitazone use seems to be associated with a reduction in CVD risk, whereas the dipeptidyl-dipeptidase-4 inhibitors (DPP-4i), lixisenatide and exenatide-LAR [from the category of glucagon-like-peptide-1 receptor (GLP-1R) agonists], confer a neutral effect. Two other GLP-1R agonists, liraglutide and semaglutide, as well as the sodium-glucose transporter-2 (SGLT2)-inhibitors, empagliflozin and cangliflozin, have shown an additional effect on CVD risk reduction, although their safety is in doubt. Insulin analogues and newer long-acting compounds are also safe for the cadiovascular system. The aim of this narrative review is to present and critically analyse the current data for each antidiabetic drug category with regard to their effect on CVD risk.

Abstract A28: Type 2 diabetes and risk of colorectal polyps in a colonoscopy-based study

Abstract Background: Type-2 diabetes mellitus (T2DM) and colorectal cancer (CRC) are both relatively common diseases among the adult population in the US; both diseases also share similar risk factors, including obesity, chronic inflammation, sedentary lifestyle, and selected dietary factors. Estimates suggest that 14% of CRC patients have T2DM as a comorbid condition at diagnosis. T2DM has also been identified as an independent risk factor for colorectal cancer. Most colorectal cancers arise from polyp precursor lesions, including advanced adenomas and a subset of serrated polyps, termed sessile serrated polyps. There is limited evidence regarding the association between T2DM and specific subtypes of colorectal polyps. We investigated the relationship between T2DM and the risk of subsets of colorectal polyps in a colonoscopy-based study in western Washington State. Methods: Study participants were a subset of 20-79 year-old enrollees at Group Health, a population-based integrated health care system in the greater Puget Sound area in Washington State, who underwent a colonoscopy for any indication from 1998-2007. Eligible study participants completed a structured questionnaire to collect risk factor information, including self-report of clinically-diagnosed diabetes, and whether it was treated with medications. Participants were diagnosed as having adenomas (n=633), serrated polyps (n=602), synchronous presence of both adenomas and serrated polyps (n= 244) or as polyp-free controls (n=1052) on the basis of a standardized pathology review. Multivariable polytomous logistic regression was used to compare case groups with polyp-free controls and other case groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated, overall and by subtype, adjusted for age, sex, race, educational status, body mass index, smoking, alcohol intake, aspirin and nonsteroidal anti-inflammatory drug use, physical activity, history of previous endoscopy, and diet (fruits, vegetables and red meat intake). Results: About 10% of the study population reported a history of clinically diagnosed T2DM, and 77% of those with T2DM took anti-diabetic medications. T2DM was not associated with the risk for colorectal polyps overall (adjusted OR 0.84; 95% CI 0.61-1.15). When evaluated by polyp subtype, T2DM diagnosis was not associated with the risk for adenomas (adjusted OR 1.02; 95% CI 0.70-1.48), but it was inversely associated with the risk for serrated polyps (adjusted OR 0.61, 95% CI 0.40-0.95). There was significant heterogeneity between adenomas and serrated polyps for their association with T2DM (P for heterogeneity=0.0001); however, the associations did not vary by lesion severity within each polyp subtype (advanced vs. non-advanced adenomas, sessile serrated vs. hyperplastic polyps). Also, associations did not differ statistically significantly between treated and non-treated diabetics for either adenomas or serrated polyps, but there was an increased risk for polyps overall among those not taking anti-diabetic medications (adjusted OR 1.26; 95% CI 0.63-2.53). This association was suggestive but did not reach statistical significance. Conclusions: We observed that the risk for serrated polyps was significantly lower among those with a history of diabetes, while there was no observed association between colorectal adenomas and T2DM. This differential association may possibly be due to a variable effect of anti-diabetic medications on serrated pathway lesions, as suggested by the increased risk for polyps among untreated diabetics. Further studies are needed to better understand the mechanistic processes through which diabetes and its treatment may be differentially associated with the development of adenomas and serrated polyps. Citation Format: Sheetal Hardikar, Andrea N. Burnett-Hartman, Stacey A. Cohen, Polly A. Newcomb. Type 2 diabetes and risk of colorectal polyps in a colonoscopy-based study. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A28.

Diabetes mellitus and hypertension: a dual threat.

The following is a review of the current concepts on the relationship between hypertension (HTN) and diabetes mellitus with a focus on the epidemiology and cardiovascular prognostic implications of coexistent HTN and diabetes mellitus, shared mechanisms underlying both conditions and pathophysiology of increased risk of cardiovascular disease, treatment of HTN in individuals with diabetes mellitus, and effects of anti-diabetic medications on blood pressure (BP). Diabetes mellitus and HTN often coexist in the same individual. They share numerous risk factors and underlying pathophysiologic mechanisms, most important of which are insulin resistance and inappropriate activation of the rennin-angiotensin-aldosterone system. Recently updated guidelines recommend a BP goal of 140/90 mmHg in most individuals with diabetes mellitus. A new class of anti-diabetic medications, sodium-glucose co-transporter 2 inhibitors, has shown favorable effects on BP. HTN affects the majority of individuals with diabetes mellitus. Coexistence of diabetes mellitus and HTN, especially if BP is not well controlled, dramatically increases the risk of morbidity and mortality from cardiovascular disease. BP control is an essential part of management of patients with diabetes mellitus, because it is one of the most effective ways to prevent vascular complications and death.

Mo1424 Effect of Anti-Diabetic Medications on the Presentation of Pancreatic Adenocarcinoma in Diabetic Patients

Background: Reports on the presence of insulin-like growth factor receptor pathways in pancreatic intraepithelial neoplasia (PanIN) lesions in mouse models and human pancreatic adenocarcinomas (PC) along with present controversy regarding the use of glucagon-like peptide-1 (GLP-1) agonists, highlights new concerns that diabetic (DM) treatments that increase insulin levels may accelerate the development of PC. To determine if this concern is of clinical significance, we hypothesized that those DM PC patients who were exposed to increased systemic insulin levels through the use of exogenous insulin or insulin-stimulating medications should have an earlier age of PC diagnosis or present at a more advanced stage than non-DM PC patients or insulin-independent treated DM PC patients. Methods: DM histories from patients enrolled in our PC Registry were reviewed. DM treatment history was obtained by a self-reported questionnaire filled out at time of registry enrollment. Electronic medical records were reviewed for confirmation and clarification of DM duration and anti-DM treatment regimens. Patients were stratified according to whether they were treated with insulin only, insulin-stimulating medications (eg. oral sulfonylureas, incretin mimetics, or meglitinides) only, or managed by insulin-independent strategies (eg. dietcontrolled, biguanides, or thiazolidinediones); those exposed to multiple classes of anti-DM medications were excluded from analysis. Eligible patients were analyzed by years between DM and age of PC diagnoses and PC stage using one-way ANOVA and chi-square test of association, respectively. Smoking and alcohol use were controlled during analysis with multivariable regression models. Results: Among 531 eligible PC patients (mean age: 66.3 ± 10.4 years): 132 DM (mean age:67.4 ± 10.3 years) were identified. The mean ages of PC diagnosis for patients within the insulin-only (n=46), insulin-stimulating (n=13), insulinindependent (n=73) and non-DM (n=318) cohorts were 69.0 ± 11.0 years, 68.8 ± 12.3 years, 66.2 ± 9.5 years, and 65.5 ± 10.5 years, respectively. As shown in Table, no significant difference among the age of PC diagnosis was seen based on duration or type of anti-DM treatment. Statistical analysis did not find any correlation between PC stage and DM treatments. Conclusions: Anti-diabetic medications that increase exposure to endogenous insulin do not appear to accelerate PC development as measured by the age of PC diagnosis or stage. These findings suggest that avoidance of certain drug classes used in DM treatments based on concerns for accelerating the presentation of PC are unjustified.