bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Aging on Risk of Hypoglycemia in Patients with Type 1 Diabetes
Authors: MUNSHI MEDHA , SLYNE CHRISTINE , ATAKOV-CASTILLO ASTRID , GREENBERG JORDAN , GREAVES TORI , CARL SAM P. , TOSCHI ELENA
Published: June 2018

Background: As T1D patients routinely reach older age, more information is needed to understand the impact of aging on the risk of hypoglycemia and its interaction with other age-related issues.

Methods: We evaluated 2 groups of patients with T1D: older (age >65 years) and younger (age 18-35 years). All patients were subjected to either blinded CGM for 2 weeks or assessment of personal CGM. A hypoglycemia fear survey (HFS II), and a Clarke hypoglycemia unawareness survey were completed. Patients were also assessed for cognitive function by the Montreal Cognitive Assessment (MoCA). Glycemic control was measured by A1C.

Results: We evaluated 56 patients with T1D; 23 in the older and 33 in the younger group. The average age was 70 vs. 28 years; diabetes duration 36 vs. 14 years; A1C 8.0% vs. 7.9%, respectively. Clinically significant hypoglycemia (glucose ?54 mg/dL for > 15 mins/episode) occurred equally in 91% of older (mean 28 minutes/day) and 88% of younger (mean 23 mins/day) patients. Older patients reported hypoglycemia unawareness more (39% vs. 30%), with similar scores on HSF II (34 vs. 33). However, 61% of older patients had cognitive impairment (MoCA score <26) compared to 12% in younger adults. There was a higher comorbidity burden in older patients (average number of comorbidities 4 vs. 1), with a higher number of daily medications (10 vs. 4).

Conclusion: The risk of hypoglycemia is similar in older and younger patients with T1D. However, higher incidence of comorbidities including cognitive dysfunction and polypharmacy may increase the risk of poor outcomes due to hypoglycemia.

Disclosure

M. Munshi: Consultant; Self; Sanofi. C. Slyne: None. A. Atakov-Castillo: None. J. Greenberg: None. T. Greaves: None. S.P. Carl: None. E. Toschi: None.
Factors Associated with Severe Hypoglycemia among Patients with Type 2 Diabetes Treated with Insulin
Authors: PAWASKAR MANJIRI , LIU JINAN , RAVI SHANKAR R. , RAJPATHAK SWAPNIL
Published: June 2018

We have previously reported that rates of severe hypoglycemic events (SHEs, defined as events that required hospitalization or an emergency department visit) are higher in patients with type 2 diabetes (T2D) on insulin alone (3.4%) or insulin+SU (2.5%) compared to those on insulin+other anti-hyperglycemic agents (AHA) (1.6%). The present analyses were conducted to further evaluate the independent risk factors of SHE after accounting for differences in two treatment groups based on propensity for SHE: Insulin±SU and Insulin+Other AHA. This retrospective analysis using MarketScan database included T2D adults (n=202,147; mean age: 54.0 years; 53% females) with a first prescription of insulin from 1/1/2013 to 12/31/2013 (index period). SHE was measured from the index date to the end of follow-up (12/31/2013). Multivariable Poisson regression was performed to compare the risk of SHE between insulin±SU vs. insulin+other AHA users and assess other predictors. The unadjusted SHE rate per 100 person years was 2.2% among all patients; 2.8% among those on insulin±SU and 1.3% among those on insulin+other AHA. After adjusting for patient’s baseline characteristics, the risk of SHE was 84% higher in patients on insulin±SU compared to those on insulin+other AHA [Hazard ratio (HR):1.84; 95% confidence interval (CI): 1.68- 2.01]. In addition to the treatment type, other factors predictive of SHE were previous history of SHE (HR: 4.73; 95% CI: 4.33- 5.17); and history of comorbidities including chronic kidney disease (HR: 1.75; 95% CI: 1.60-1.92), cardiovascular disease (HR: 1.60; 95% CI: 1.46-1.75), and neuropathy (HR: 1.55; 95% CI: 1.43-1.69). Our results suggest the risk of SHE is lower in patients on insulin with other AHA compared to patients on insulin alone or with SU. Healthcare professionals should take into account the risk of having SHE while making treatment choices especially for vulnerable populations such as patients with prior history of SHE, and other comorbidities.

Disclosure

M. Pawaskar: Employee; Self; Merck & Co., Inc. J. Liu: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Anthem, Inc.. Employee; Self; Janssen Scientific Affairs, LLC. R. Shankar: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; NGM Biopharmaceuticals. S. Rajpathak: Employee; Self; Merck & Co., Inc..
Impact of Switching from Sulfonylureas to Dipeptidyl Peptidase-4 Inhibitors on Hypoglycemia Burden in the United States—A Predictive Modeling Approach
Authors: LIU JINAN , TANG YUEXIN , HANNACHI HAKIMA , ENGEL SAMUEL S. , RAJPATHAK SWAPNIL
Published: June 2018

Hypoglycemia requiring medical care represents significant burden for patients with T2DM and health systems. Therefore, minimizing risk of hypoglycemia needs to be considered in treatment decision making, in addition to attaining glycemic goal. Using a predictive modeling approach, we conducted a study to estimate reduction in hypoglycemia event rates and costs that may result from switching from sulfonylureas (SU) to dipeptidyl peptidase-4 inhibitors (DPP-4i) in the United States.

A large commercial claims database was used to identify adult T2DM patients newly treated with SU or DPP-4i in 2014. Rates and costs of hypoglycemia were assessed within one year after drug initiation. A Poisson model, built and developed based on DPP-4i users, was applied in SU users to estimate hypoglycemia rate if they had been switched to DPP-4i adjusting for patient demographics, comorbidities and medication use at baseline. Using National Health and Nutrition Examination Survey, the observed and predicted hypoglycemia costs were then projected on the national level for SU users, and the cost difference represented the change of total hypoglycemia costs had they switched to DPP-4 instead on the national level.

Among patients who initiated SU (n=38,913) and DPP-4i (n=23,956), average age was 52 years; 44% were female. The observed hypoglycemia rates per 100-person years were 6.4 (95% CI: 6.0, 6.9) and 10.6 (95% CI: 10.1-11.1) in DPP-4i and SU groups, respectively. The predicted rate of hypoglycemia was 6.4 (95% CI: 6.1-6.8) in SU group had they switched to DPP-4i. At a national level, this switching could result in potential costs savings of $586 million (from $699 million to $113 million) within one year period.

Our study suggests that switching patients from SU to DPP-4i could reduce hypoglycemia event rates by almost 40% and also result in substantial cost savings associated with hypoglycemia in the United States.

Disclosure

J. Liu: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Anthem, Inc.. Employee; Self; Janssen Scientific Affairs, LLC. Y. Tang: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. Employee; Spouse/Partner; GlaxoSmithKline plc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc. H. Hannachi: Employee; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Merck & Co., Inc..
Limited Availability of Glucagon by Emergency Personnel
Authors: KAHN PETER , WAGNER NICOLE , GABBAY ROBERT A.
Published: June 2018

Hypoglycemia causes more than 100,000 emergency department visits per year costing over $120 million. Glucagon can reduce the number and severity of hypoglycemic episodes requiring emergency medical attention and hospital admission. However, EMS personnel are often unable to administer glucagon.

U.S. EMS offices were queried for glucagon administration and blood glucose testing protocols. Only paramedics are able to administer glucagon in most states, whereas the 198,200 EMT-Basics personnel nationally cannot. The average response time to calls was 15.34 minutes. Dispatchers correctly coded 44.67% of these calls as a “diabetic problem,” increasing the likelihood of dispatching providers who cannot administer glucagon. The National Emergency Management Information System (NEMIS) (2013- 2015) indicates 89, 263 cases in which glucagon was administered with only 3,944 events with side effects.

Despite its’ favorable safety profile, glucagon cannot be administered by EMT-basics in most states, even though family members can often with minimal training. 3 out of 4 emergency personnel are unable to use glucagon. The likelihood of the correct personnel being dispatched based on dispatcher information alone is poor. Increasing the availability of glucagon in the prehospital setting will likely result in reduced cost burden and adverse consequences of severe hypoglycemia.

EMS Policies Regarding Use of Glucagon and Blood Glucose Testing.

Disclosure

P. Kahn: None. N. Wagner: None. R.A. Gabbay: Consultant; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Onduo, health reveal.
Insulin Acts in Ventromedial Hypothalamus to Regulate the Sympathoadrenal Response to Hypoglycemia in Rats
Authors: AGRAWAL RAHUL , ABREU ADRIANA VIEIRA DE , DURUPT GRIFFIN T. , FISHER SIMON J.
Published: June 2018

We tested the hypothesis that the correction of ventromedial hypothalamus (VMH) insulin deficiency was sufficient to restore the impaired sympathoadrenal response to hypoglycemia in diabetic rats. Sprague-Dawley rats were injected with either vehicle (nondiabetic controls; CON) or streptozotocin (STZ; 65 mg/kg IP). STZ diabetic rats received osmotic mini-pumps to infuse either artificial cerebrospinal fluid (DIAB) or insulin (3mU/day; DIAB+InsVMH) into the VMH bilaterally. Two weeks later, all three groups underwent hyperinsulinemic (50 mU.kg-1.min-1) hypoglycemic (∼50 mg/dl) clamps. As expected, STZ-diabetic rats showed blunted epinephrine response to hypoglycemia as compared to nondiabetic controls. Chronic infusion of insulin into VMH of diabetic rats normalized the epinephrine response to hypoglycemia and lowered the glucose infusion rate required to maintain hypoglycemia. Examining brain insulin action, it was noted that STZ diabetic rats had decreased Akt phosphorylation and decreased expression of insulin dependent glucose transporter 4 (GLUT4) in VMH by 44 and 40% respectively as compared to the nondiabetic controls. Notably, chronic infusion of insulin to the VMH normalized Akt phosphorylation and GLUT4 expression.

In summary, insulin acts chronically in the VMH to preserve the sympathoadrenal response to hypoglycemia, possibly by regulating GLUT4 expression.

Disclosure

R. Agrawal: None. A. Vieira de Abreu: None. G.T. Durupt: None. S.J. Fisher: None.
Sustainability of a Real-Time Informatics Alert to Prevent Inpatient Severe Hypoglycemia
Authors: ELLIOTT MICHAEL , BLACKBURN MARY C. , HEARD KEVIN M. , MILLIGAN PAUL E. , BRAVO PAULINA CRUZ , TOBIN GARRY S.
Published: June 2018

Inpatient severe hypoglycemia (SH), blood glucose (BG) <40 mgs/dl, is associated with morbidity. We previously piloted a predictive model to identify and intervene in inpatients at risk for SH that decreased the rate of SH by 68%. Expanding the alert system-wide to 9 hospitals, succeeded in reducing the occurrence of severe hypoglycemia from 2.9% to 1.7% per 1000 at risk patient days during all visits, and from 4.4% to 2.5% during visits where an alert occurred across all hospitals (both p-values<.001). There were 4142 alerts in 2013; number increased to 5171 in 2014, and stayed steady in 2015 (5161), 2016 (5649), and 2017 (4964).

This study reflects a retrospective analysis of system-wide data from 2011 to 2017. Results show BG levels post alert are higher on average (mean 92.83) than pre-alert (mean 74.43). This magnitude of difference occurs in each year (pre-post differences range from 14.7 to 19.3), suggesting that the alert system led to a sustained beneficial effect over time. A decreasing trend in SH rate over time was observed, which differed by hospital (Figure). System-wide electronic surveillance and alerts improve safety in patients with diabetes across a range of clinical settings. This study proves ongoing efficacy of the alert process and variables.

Disclosure

M. Elliott: None. M.C. Blackburn: None. K.M. Heard: None. P.E. Milligan: None. P. Cruz Bravo: None. G.S. Tobin: Speaker's Bureau; Self; Novo Nordisk Inc., MannKind Corporation. Advisory Panel; Self; Novo Nordisk Inc..
C-Peptide Levels Are Associated with Glycemic Variability and Hypoglycemia in Insulin-Treated Type 2 Diabetes
Authors: CHRISTENSEN MERETE B. , GOTFREDSEN ANDERS , NØRGAARD KIRSTEN
Published: June 2018

Objective: Emerging evidence has suggested that glycemic variability plays an important role in the development of diabetes complications. We aimed to evaluate the influence of c-peptide levels on glycemic variability and hypoglycemia in patients with GAD-antibody negative, insulin-treated type 2 diabetes.

Methods: We enrolled 80 patients with insulin-treated type 2 diabetes (mean age 62.6 ± 9.4 years, mean HbA1C 71.9 ± 11.9 mmol/mol, mean BMI 33.1 ± 5.7 kg/m2). All patients were GAD-antibody negative, had long diabetes duration (18.9 ± 7.4 years) and were treated with basal-bolus insulin. Glycemic variability and hypoglycemia duration were assessed from continuous glucose monitoring data recorded over 6 consecutive days. Glycemic variability was assessed by calculating mean Coefficient of Variation (CV). Hypoglycemia was defined as BG ≤70 mg/dl (3.9 mmol/L) or BG <54 mg/dl (3.0 mmol/L). Fasting c-peptide and fasting glucose were measured on day 1.

Results: Mean fasting c-peptide was 647 ± 493 pmol/L. Low levels of fasting c-peptide were correlated to higher CV (r = -0.44, P=0.001). In a multivariate regression model with HbA1C, BMI, diabetes duration and total daily insulin dose only c-peptide was significantly associated with CV. 47,5% of the patients had at least one episode of hypoglycemia (BG ≤70 mg/dl) and 23.7% had at least one episode of BG <54 mg/dl. Patients with at least one episode of hypoglycemia had significant lower c-peptide than patients without hypoglycemia (494 ± 460 pmol/L vs. 821 ± 479 pmol/L, P=0.004). There was no significant difference in c-peptide between patients with BG ≤70mg/dl and patients with BG <54mg/dl.

Conclusion: Low levels of c-peptide are associated with higher glycemic variability and risk of hypoglycemia in GAD-antibody negative patients with insulin treated type 2 diabetes, suggesting a role for c-peptide in optimizing treatment and prevention of hypoglycemia in insulin-treated type 2 diabetes.

Disclosure

M.B. Christensen: None. A. Gotfredsen: None. K. Nørgaard: Research Support; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic, Zealand Pharma A/S, Novo Nordisk A/S. Research Support; Self; Zealand Pharma A/S.
Incidence of Hypoglycemia Events in a Large, Real-World Diabetes Population
Authors: BOLLYKY JENNIFER , LU WEI , SCHNEIDER JENNIFER
Published: June 2018

Background: It is difficult to accurately determine the frequency of hypoglycemic events in a clinical setting. Remotely captured glucose data from connected meters offers an opportunity to understand real-world treatment effects outside of a clinical trial setting. The Livongo for Diabetes Program provides over 50,000 commercially-insured people with diabetes a cellular-enabled, two-way messaging device that measures and records blood glucose. Free, unlimited blood glucose test strips are also provided.

Methods: We obtained blood glucose (BG) values directly from 35,436 individuals who had been using Livongo connected meters over 3 months. Frequency of BG checking, hypoglycemia event rates (BG<70 mg/dL) and clinically significant hypoglycemia event rates (BG<54mg/dL) were characterized by age, gender, race, diabetes type, estimated HbA1c and medication use.

Results: The mean percentage of total BG checks <70mg/dL and <54mg/dL by medication use and diabetes type are reported in Table below.

Conclusions: In a heterogeneous population with type 1 and type 2 diabetes we captured many hypoglycemic episodes, the frequency of which was associated with medication use and diabetes type. The Livongo platform provides an opportunity to understand real-world treatment effects outside of a clinical trial setting.

No meds (N=3181)Oral Meds Only (N=19,135)Insulin Once Daily (N=5,315)insulin > Once Daily - T2D (N=4,606)insulin > Once Daily - T1D (N=2834)MeanSDMeanSDMeanSDMeanSDMeanSDBG<70 mg/dL1.08%3.95%1.14%4.16%3.21%7.34%3.59%6.44%10.45%10.80%BG<54 mg/dL0.20%1.24%0.26%1.85%0.89%2.83%1.19%3.92%4.36%5.88%

Disclosure

J. Bollyky: Employee; Self; Livongo Health. Stock/Shareholder; Self; Livongo Health. W. Lu: None. J. Schneider: Employee; Self; Livongo Health. Stock/Shareholder; Self; Livongo Health.
Mild Physiologic Hyperglycemia Induces Hepatic Insulin Resistance in Healthy Normal Glucose Tolerant Subjects–Role of Glucagon and Gluconeogenic Substrates
Authors: TRIPATHY DEVJIT , MEROVCI AURORA , CORCHADO ENRIQUE R. MALDONADO , RITA BASU , DEFRONZO RALPH A.
Published: June 2018

The aim of the present study was to evaluate the effect of a physiologic increase in plasma glucose concentration on endogenous glucose production (EGP) in healthy NGT individuals. 16 NGT subjects [8 with and 8 without family history of T2DM (9M/7F, age = 44± 3 years, BMI = 26 ± 1 kg/m2)] participated in a 3-step hyperinsulinemic (10, 20, 40 mU/m2 min) euglycemic clamp before and after a 48 hour glucose infusion to increase plasma glucose conc by ∼45 mg/dl above baseline (89±4 to 136±4.9 mg/dl). EGP was measured with [3-3H] glucose and gluconeogenic rate was measured following administration of deuterated water. Plasma FFA, glucagon, lactate, glycerol and alanine concentrations also were measured. Following 48 hours of glucose infusion basal EGP increased from 2.05±0.09 to 3.06±0. mg/kg min (p=0.003) and hepatic insulin resistance index (EGP X Fasting Plasma Insulin) increased markedly and similarly (25.1±1.0 vs. 48.3± 3.2, p<0.005). The baseline plasma glucagon concentration tended to be higher following 48 hours of glucose infusion (64±3 vs. 77± 8 pg/ml, p=0.2) while the product of the plasma glucagon and insulin concentrations was markedly increased (540 ± 56 vs. 1336 ± 262, p=0.004). Although the baseline plasma FFA concentration was markedly reduced following 48 hours of glucose infusion (0.482 ±0.to 0.055± 0.01mM), there was no difference in plasma glycerol concentration (13.4±1.2 vs. 13.3 ± 2.2 mg/L p=ns). There were small increases in both the plasma lactate and alanine concentrations. Total body insulin sensitivity declined from 8.75±2.1 to 6.92± 6 mg.kg/min (p<0.05).

Conclusion: Chronic (48 hr) physiologic hyperglycemia to levels seen in T2DM increases basal hepatic glucose production and induces hepatic and skeletal muscle insulin resistance in healthy NGT subjects. These results demonstrate, for the first time that glucotoxicity causes resistance to the suppressive effect of insulin on hepatic glucose production.

Disclosure

D. Tripathy: None. A. Merovci: None. E.R. Maldonado Corchado: None. R. Basu: Research Support; Self; AstraZeneca. R.A. DeFronzo: Speaker-s Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc..
The Effect of Bariatric Surgery on Neprilysin and Vasoactive Factors
Authors: DANDONA PARESH , GHANIM HUSAM , MONTE SCOTT , GREEN KELLY , CARUANA JOSEPH A.
Published: June 2018

Objective: Since morbid obesity is associated with congestive cardiac failure and hypertension, and gastric bypass surgery is followed by a reduction in blood pressure and a reduction in the risk of congestive cardiac failure, we hypothesized that weight loss following bariatric surgery in morbidly obese patients is associated with a decrease in plasma concentrations of neprilysin, mediators of renin angiotensin system, catecholamines and endothelin-1 with an increase in the concentrations of vasodilators.

Method: Fasting blood samples were obtained from fourteen patients with morbid obesity and diabetes prior to and 6 months after Roux-en-Y gastric bypass (RYGB) surgery. Plasma and serum were separated for the measurement of neprilysin; vasoconstrictors, angiotensinogen, renin, angiotensin II, endothelin-1, epinephrine and norepinephrine; and vasodilators, ANP, BNP, cGMP, and cAMP. The mRNA expression of angiotensin converting enzyme (ACE) and adenylate and guanylate cyclases in circulating mononuclear cells (MNC) was also measured.

Results: Six months after RYGB, BMI fell from 52.1±4.8 to 40.4±4.0 kg/m2 and there were significant improvements in the HbA1c. Plasma concentrations of neprilysin, angiotensinogen, angiotensin II, renin and endothelin-1 fell significantly by 27±16%, 22±10% 22±8%, 35±13% and 17±6% (p<0.for all) respectively, while ANP concentrations increased significantly by 24±13% at 6 month following surgery. There was no significant change in aldosterone, BNP, cAMP or cGMP concentrations and ACE mRNA expression.

Conclusion: RYGB suppressed neprilysin concentrations, which may contribute the observed increase in plasma ANP concentrations. In addition, RYGB resulted in a reduction in plasma angiotensinogen, angiotensin II, renin and endothelin-1 concentrations. These changes may contribute to the reduction in the risk of congestive cardiac failure and blood pressure after RYGB.

Disclosure

P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. H. Ghanim: None. S. Monte: Stock/Shareholder; Self; Mobile Pharmacy Solutions (Community Pharmacy). Employee; Self; Synergy Bariatrics, a Department of ECMC. K. Green: None. J.A. Caruana: None.
Contribution of Serum FGF-21 Level to the Identification of Left Ventricular Systolic Dysfunction and Cardiac Death
Authors: BAO YUQIAN , SHEN YUN , ZHANG XUELI , PAN XIAOPING , XU YITING , XIONG QIN , LU ZHIGANG , MA XIAOJING
Published: June 2018

Aim: This study aimed to investigate the relationship between fibroblast growth factor 21 (FGF-21) and left ventricular systolic dysfunction and cardiac death.

Methods: The optimal cutoff of FGF-21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF-21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves.

Results: A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32±10.10 years. The optimal cutoff values of FGF-21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/ml and 131.3 ng/l, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF-21, NT-pro-BNP and FGF-21+NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF-21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P=0.043, OR 9.207 [2.036-41.643], P=0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF-21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years (RR5.000 (1.326-18.861), P=0.026; RR 9.643 (2.596-35.825), P=0.009, respectively).

Conclusion: Serum FGF-21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF-21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF-21. The identification of FGF-21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP.

Disclosure

Y. Bao: None. Y. Shen: None. X. Zhang: None. X. Pan: None. Y. Xu: None. Q. Xiong: None. Z. Lu: None. X. Ma: None.
Serum FGF-21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease—Results from a Median Follow-Up of 4.8 Years Study
Authors: BAO YUQIAN , SHEN YUN , ZHANG XUELI , XU YITING , XIONG QIN , LU ZHIGANG , MA XIAOJING
Published: June 2018

Objectives: To investigate whether the serum fibroblast growth factor (FGF) 21 levels can be used to predict the future development of major adverse cardiovascular events (MACEs).

Methods: 253 patients at baseline received subsequent follow-up, 234 of whom finished the data collection. Independent predictors of MACEs were identified using Cox proportional hazards regression analysis. The prognostic value of FGF-21 levels for MACEs was evaluated by Kaplan-Meier survival analysis.

Results: Of 229 patients finally enrolled in the analysis, 27 of 60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132 of 169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF-21 levels were significantly higher in patients with MACEs (P<0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed a significantly lower event-free survival (P=0.001) among patients with a higher serum FGF-21 level than in those with a lower serum FGF-21 level. Further Cox proportional hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF-21 was one of the independent predictors of the occurrence of MACEs.

Conclusions: In patients with CAD at baseline, an elevated serum FGF-21 level was associated with the development of a MACE in the future.

Disclosure

Y. Bao: None. Y. Shen: None. X. Zhang: None. Y. Xu: None. Q. Xiong: None. Z. Lu: None. X. Ma: None.
Long-Term Prognostic Value of Coronary Computed Tomography Angiography in Asymptomatic Elderly Population Including Diabetic Patients
Authors: MOON SUN JOON , LEE DONG-HWA , TOH AE JUNG , KIM KYOUNG MIN , CHOI SUNGHEE , JANG HAK CHUL , LIM SOO
Published: June 2018

Objectives: There is still controversy about the long-term prognostic value of coronary computed tomography angiography (CCTA) for coronary heart disease (CHD) in asymptomatic individuals including diabetic patients. Also, long term CCTA’s role among elderly population has not been established. We investigated the long-term prognostic value of CCTA in asymptomatic elderly patients with or without diabetes.

Methods: A community based-cohort study of 470 asymptomatic elderly individuals (mean age 75.1 ± 7.3 years) who underwent CCTA was conducted. Among them, there were 156 [33.2%] diabetic patients and 55 [11.7%] patients with HbA1c of more than 7% (HbA1c >7%). Major adverse cardiac events (MACE) defined as composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization and coronary revascularization were measured. CCTA findings were categorized by various means including the presence of proximal LAD or left main disease (pLAD/LM). Coronary calcium score (CACS) and Framingham risk score (FRS) were adjusted for analysis.

Results: There were 57 individuals (12.1%) with pLAD/LM finding for overall population and 8 (14.5%) for diabetic patients with HbA1c >7%. During median follow-up of 8.1 years (interquartile range: 7.7-8.2), MACE occurred in 28 (6%) subjects among overall population and 6 (10.9%) among diabetic patients with HbA1c >7%. Compared to individuals with negative pLAD/LM finding, positive group was significantly associated with MACE for overall population (HR 2.817 [95% CI 1.044-7.601], p = 0.041). Among diabetic patients with HbA1c >7%, there is more significant association between pLAD/LM finding and MACE (HR 6.525 [95% CI 1.147-37.121], p = 0.034).

Conclusion: Among asymptomatic elderly population, CCTA showed considerable prognostic value additive on CACS and FRS over 8 years. And this result was more significant in elderly diabetic patients with poor glycemic control.

Disclosure

S. Moon: None. D. Lee: None. T. Oh: None. K. Kim: None. S. Choi: None. H. Jang: None. S. Lim: None.
Elevated Fibroblast Growth Factor-21 Protect Endothelial Function in Type 2 Diabetes Patients
Authors: HU YANJIN , XU YUAN , WANG GUANG
Published: June 2018

Background: Fibroblast growth factor 21 (FGF-21) is a metabolic regulator with multiple effects on improving glucose metabolism and energy utilization. Recent researches pointed that FGF-21 protect endothelial function against high glucose induced cell damage. Our research tried to detect the relationship of FGF-21 and endothelial dysfunction in newly diagnosed type 2 diabetes (T2D) patients.

Methods: Fifty newly diagnosed T2D patients and fifty healthy controls were recruited in the research. Clinical and biological data, FGF-21 were measured. Endothelial function was tested by reactive hyperaemia index (RHI) approved by American Food and Drug Administration.

Results: T2DM patients had higher FGF-21 levels (155.57±85.3 vs. 117.39±68.9ug/l,P<0.05) and more serious endothelial dysfunction (1.73±0.51 vs. 2.05±0.52,P<0.05) than controls. RHI was negatively related with low density lipoprotein cholesterol (LDL-C) (r=-0.322, P<0.05) and positively with FGF-21 (r=0.543, P<0.01). In the multivariate linear analysis, FGF-21 (β=0.551,P<0.01) and LDL-C (β=-0.188,P<0.01) were independently predictors of RHI. FGF-21 was the protective factor of endothelial function in the T2D patients.

Conclusions: T2D patients had endothelial dysfunction even in the early period. Elevated FGF-21 might protect endothelial dysfunction.

Disclosure

Y. Hu: None. Y. Xu: None. G. Wang: None.
Prevalent Prediabetes at Admission due to Acute Myocardial Infarction Does Not Affect One-Year Mortality Rates of Patients Who Were Discharged Alive
Authors: PARK IE BYUNG , LEE DAE HO , YU SEUNG HEE , LEE KIYOUNG
Published: June 2018

Background: Although prediabetes increases AMI risk, long-term clinical implication for prevalent prediabetes in AMI patients is not clear. The present study aimed to evaluate whether prediabetes at admission increases long-term cardiovascular (CV) and total mortalities in AMI patients who were discharged alive.

Methods: We obtained AMI patient data from The Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry. Total and CV mortalities at 12 months after AMI were assessed.

Results: A total of 13104 patients with AMI from the registry database were analyzed. 552 patients (4.2%) were destined to in-hospital mortality or hopeless discharge. We classified the remaining patients into control, prediabetes, and diabetes groups according to one of fallowing parameters: prevalent diabetes by past history, diabetes medication during hospitalization, or in the remaining cases with no diabetes history or medication data by hemoglobin A1c level at admission. Patients without any data about above-mentioned parameters were excluded in this study (n= 3583), and a total of 8969 AMI patients were available for analysis (control group, n=2379; prediabetes group, n=2321; and diabetes, n=4269). After adjustment for multiple factors, hazard ratios (HRs) (95% CI) for total mortality in prediabetic group vs. control group and diabetic group vs. control group were 1.536 (0.879-2.685, p=0.132) and 1.94 (1.184-3.190), p<0.01), respectively. However, CV mortality were not different between the three groups.

Conclusions: Our results show that that prediabetic state at AMI admission do not increase CV mortality and all-cause mortalities at 1-year after survival discharge, whereas diabetes increase 1-year all-cause mortality.

Disclosure

I. Park: None. D. Lee: None. S. Yu: None. K. Lee: None.
Glycemic Variation and Cardiovascular Risk during the VADT
Authors: ZHOU JIN , SCHWENKE DAWN , REAVEN PETER
Published: June 2018

There is uncertainty about the importance of visit-to-visit glycemic variability in cardiovascular disease (CVD) complications in type 2 diabetes (T2D) patients. Using the Veteran Affairs Diabetes Trial (VADT), we investigated this relationship, and assessed whether it is influenced by intensive or standard glucose control. During the VADT, fasting glucose and HbA1c were measured every 3 months for up to 84 months in 1791 individuals. Visit-to-visit variability measures included coefficient of variation (CV) and average real variability (ARV). By Cox proportional hazard models, variability measures of fasting glucose showed significant association with CVD even after adjusting for other risk factors, including mean fasting glucose. This relationship was evident in the intensive treatment group but not in the standard group (Figure 1). Additional adjustment for severe hypoglycemic episodes, did not alter the effect of glucose variability on CVD. Interestingly, HbA1c variability was not associated with CVD after adjusting for multiple baseline risk factors. Our analysis indicates that in the VADT, variability of fasting glucose plays a role in the development of CVD complications beyond the influence of the mean glucose measures. The adverse consequences of glucose variability on CVD appear greatest in those receiving intensive glucose control.

Figure 1 Hazard ratio (HR) estimates for quintiles of Log(CV)-glucose and ARV-glucose for the primary composite CVD outcome adjusted for ethnicity, baseline HbA1c, baseline HDL and LDL cholesterol, baseline total cholesterol and triglycerides, history of hypertension, diabetes duration, prior CVD event, and the cumulative mean of glucose. Vertical bars are the 95% confidence interval (95% CI) associated with HR estimates. “***” indicates estimated HR in the related variability quintile is significantly higher than the HR of lowest variability quintile (quintile 1). Figure 1. Hazard ratio (HR) estimates for quintiles of Log(CV)-glucose and ARV-glucose for the primary composite CVD outcome adjusted for ethnicity, baseline HbA1c, baseline HDL and LDL cholesterol, baseline total cholesterol and triglycerides, history of hypertension, diabetes duration, prior CVD event, and the cumulative mean of glucose. Vertical bars are the 95% confidence interval (95% CI) associated with HR estimates. “***” indicates estimated HR in the related variability quintile is significantly higher than the HR of lowest variability quintile (quintile 1).

Disclosure

J. Zhou: None. D. Schwenke: None. P. Reaven: Research Support; Self; AstraZeneca, Amgen Inc., Bristol-Myers Squibb Company.
Relationship between Fasting Insulin Concentration as a Risk Factor for Cardiovascular Disease and High-Density Lipoprotein Cholesterol Levels in Patients with Chronic Hepatitis C
Authors: DRAGUT RAMONA MARIA , RUSU EMILIA , CURSARU RALUCA , RUSU FLORIN , CURSARU ADRIAN , POPESCU HORATIU , RADULIAN GABRIELA
Published: June 2018

The objective of this study was to evaluate the association between fasting insulin concentration—as a cardiovascular risk factor—and the high density lipoprotein level (HDL-c) in patients with chronic hepatitis C.

Material and Methods: In this cross-sectional study, were included 171 patients from Bucharest, to which were followed anthropometric indexes. Biochemical parameters followed were glucose fasting insulin, glycosylated hemoglobin, lipid profile, liver profile, blood counts. The 10-year coronary heart disease (CHD) was calculated for each patient using the UKPDS risk engine.

Results: The mean age of patients was evaluated 53.14 ± 8.3 years, females representing 53.8% (n=92) of total. Using the UKPDS score 24% (n=41) and 20.5% (n=44) presented moderate and high risk of cardiovascular disease. Levels of fasting insulinemia was significantly high in patients with increase (12.2 uUI/ml) and moderate risk (16.4 uUI/ml) of cardiovascular disease (p<0.001). Level of HDL-cholesterol was significantly lower in patients with increase cardiovascular risk (34.41 mg/dl) vs. patients with reduce (43.03 mg/dl) or moderate cardiovascular risk (39.59 mg/dl) (p<0.001). UKPDS score was positively correlated with age (r=0.62, p=0.001), Forns index (r=0.55, p=0.001), BMI (r=0.39, p=0.001), smoking status (r=0.52, p=0.001), HbA1c (r=0.41, p=0.001), triglycerides (r=0.43, p=0.001), LDL-c (r=0.43, p=0.001), AST (r=0.33, p=0.001), ALT (r=0.26, p=0.001) and GGT (r=0.31, p=0.001) and negative with HDL-c (r=-0.44, p=0.001) and albumin (r=-0.29, p=0.001).

Conclusions: A higher fasting insulin concentration or hyperinsulinemia was significantly associated with an increased cardiovascular risk. This study suggests that early fasting insulin ascertainment in the patients with HCV may help clinicians identify those who are potentially at high risk of CVD.

Disclosure

R. Dragut: None. E. Rusu: None. R. Cursaru: None. F. Rusu: None. A. Cursaru: None. H. Popescu: None. G. Radulian: None.
Severe Hypoglycemia and Clinical Cardiovascular Events in Cohorts with No vs. Early Microvascular Complications
Authors: FAHRMANN ELKE R. , ADKINS LAURA J. , DRISCOLL HENRY
Published: June 2018

Based on basic research it might be intuitive that the relationship between hypoglycemia requiring assistance (SH) and clinical cardiovascular events (CVE) differs in cohorts with no vs. early microvascular complications (PRIM vs. SEC) in type 1 diabetes (T1DM). We analyze Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) data to examine whether PRIM vs. SEC differences exist in effect of cumulative SH on CVE. At DCCT baseline, 726 PRIM and 715 SEC (with minimal to moderate nonproliferative retinopathy and < 200 mg / 24 h of albuminuria) volunteers were enrolled. Otherwise, subjects (ages 13-39) were in overall good health. Mean follow-up was 27 years. Cox proportional hazard models assessed the effects of time-dependent updated mean SH rate per 100 years on CVE risk. Two outcomes were analyzed: MAJOR (fatal or nonfatal myocardial infarction (MI) or stroke) and ANYCVE (MAJOR, subclinical MI, angina, revascularization, or congestive heart failure). All models were adjusted for clinical covariates. Due to skewness, SH rate was log transformed: ln(SH rate+1). Interaction between mean updated SH rate and ANYCVE (or MAJOR) was significant with p<0.001 (p<0.01). In further analyses by cohort, SH emerged as an independent CVE factor in SEC with hazard ratios of 1.19 (CI95% 1.08-1.31), p<0.001, for ANYCVE and 1.32 (CI95% 1.14-1.53), p<0.001, for MAJOR. No associations were found for PRIM. To get additional insight, DCCT-SH and updated mean EDIC-SH effects on CVE were analyzed during EDIC period (1994-2013). In SEC, DCCT-SH emerged as a significant ANYCVE and MAJOR factor; EDIC-SH was associated with MAJOR but did not reach significance with ANYCVE (p∼0.09). To our best knowledge, this is the first T1DM analysis demonstrating an association of cumulative SH with clinical CVE for SEC patients. In addition to HbA1c, SH in T1DM should be considered as a non-traditional chronic CVE risk factor in SEC and managed accordingly.

Disclosure

E.R. Fahrmann: None. L.J. Adkins: None. H. Driscoll: None.
Coronary Artery Calcium Trajectory Predicts Coronary Artery Disease Events—The CACTI Study
Authors: SNELL-BERGEON JANET K. , KESHAWARZ AMENA , KINNEY GREGORY L. , SCHAUER IRENE E. , SHAH VIRAL N. , PYLE LAURA
Published: June 2018

Coronary artery calcium (CAC), a marker of subclinical atherosclerosis, predicts coronary artery disease (CAD) events, but the best use of CAC in risk prediction remains unclear. We examined whether group-based trajectory modeling of CAC in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study could independently predict CAD events. Four CAC trajectory groups (Figure 1a) were identified using longitudinal CAC in people free from CAD (Proc TRAJ in SAS Version 9.4), and these groups were used to predict a subsequent CAD event (myocardial infarction or coronary revascularization) using survival analysis. People with type 1 diabetes (T1D) were more likely to be in higher CAC trajectory groups than those without diabetes (non-DM, p<0.0001). Over 17,417 person-years of follow-up, 75 CAD events occurred (56 in T1D and 19 in non-DM individuals). Higher CAC trajectory group predicted CAD events in a dose-response manner (Figure 1b). In cox proportional hazards adjusted for age, sex, T1D, smoking, LDL, HDL, triglycerides and systolic blood pressure, being in a higher CAC group increased CAD risk, with a 33-fold increased risk in Group 4 (95% CI 12-91). A 3.3-fold excess risk (95% CI 1.7-6.4) for CAD remained for people with T1D. CAC trajectory group modeling can identify individuals at very high risk for a CAD event. However, T1D increases CAD risk independently of traditional risk factors and CAC trajectory.

Disclosure

J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. A. Keshawarz: None. G.L. Kinney: None. I.E. Schauer: None. V.N. Shah: None. L. Pyle: None.
Virtual Diabetes Prevention Program—Effects on Medicare Advantage Health Care Costs and Utilization
Authors: CHIGULURI VINAY , BARTHOLD DOUGLAS , GUMPINA RAJIV , SWEET CYNTHIA CASTRO , PIERATT JASON , CORDIER TRISTAN A. , MATANICH ROGER , RENDA ANDREW , PREWITT TODD G.
Published: June 2018

This study evaluated the impact of a virtual version of the Diabetes Prevention Program (DPP) on healthcare utilization and costs in a Medicare Advantage population. The program was offered during 2015 to a random sample of 9,497 individuals who had metabolic syndrome or prediabetes. Program enrollees (n=501) received a 12-month virtual DPP including a wireless scale, pedometer, nutrition tracker, educational lessons, health coaching, and peer group support through an online platform. Participants with available administrative claims data during the 12 months before and 24 months following program start (n=495, mean age=69 years; 64% female; 85% white) were propensity-score matched on demographic, behavioral, and clinical factors in a ratio of 1:1 to a comparison group (n=495, selected from 6,490; mean age=69 years; 58% female; 87% white) who did not receive the DPP. In the 24 months following DPP enrollment, participants averaged 0.2 inpatient admissions, 0.3 emergency department visits, and 12.2 physician visits, compared to 0.2, 0.4, and 12.0 for controls. While the utilization values do not show a large change, a difference-in-differences regression analysis of total medical and pharmacy cost for 24 months following program start showed cost savings. The adjusted difference-in-differences effect on average cumulative cost difference was $1,110 per participant, or $46.25/month. Medical and pharmacy costs were consistently lower for participants in the post-program year. Pharmacy savings were statistically significant during the last 6 months, with a 24-month cumulative adjusted savings of $408. These cost estimates do not include the cost of the program. Results suggest that a virtual DPP can change the pattern of utilization and reduce costs in a Medicare population.

Disclosure

V. Chiguluri: None. D. Barthold: None. R. Gumpina: None. C. Castro Sweet: Employee; Self; Omada Health, Inc.. J. Pieratt: None. T.A. Cordier: Employee; Self; Humana Inc.. Stock/Shareholder; Self; Humana Inc.. R. Matanich: None. A. Renda: None. T.G. Prewitt: None.
Wavelet Phase Coherence Analysis between the Respiratory Activity and the Microcirculation—The Effects of Type 1 Diabetes
Authors: PERRELLA ANTONIA , SORELLI MICHELE , FRANCIA PIERGIORGIO , CAPIRCHIO LAURA , ANICHINI ROBERTO , BELLIS ALESSANDRA DE , GULISANO MASSIMO , BOCCHI LEONARDO
Published: June 2018

The microvascular perfusion is modulated by physiological functions, which have been associated with specific frequency ranges. Although cardio-respiratory interactions have been widely analyzed at a macrocirculation level, only few studies have been conducted with the aim to understand the effect of breathing on the peripheral circulation. Diabetic microangiopathy is characterized by structural and functional alterations of the blood microvessels, which reflect in a modification of the physical properties of peripheral microvascular beds, such as vascular stiffness. A wavelet phase coherence (WPC) analysis was performed to elucidate the time-phase relationship between the respiratory activity and vascular-dependent features of the peripheral pulse, reconstructed by means of a novel multi-Gaussian modeling algorithm. The present WPC analysis was conducted on a group of 24 healthy volunteers, mean age 30±15 years, in comparison with 21 type-1 diabetic (T1D) subjects, mean age 26±3 years, in order to detect the effects of T1D on the physiological coupling between breathing and microcirculation. The peripheral cutaneous perfusion was assessed on the pulp of the index finger with the laser Doppler flowmetry (LDF) technique, while the respiratory signal was simultaneously recorded with a wearable chest band. In 17 out of the 24 control subjects involved (i.e., 71%), significant WPC values were identified in the respiratory frequency range (0.145-0.6 Hz), with respect to the area beneath the diastolic portion of the peripheral pulse (median WPC: 77.9%). This outcome indicates that the diastolic phase of the pulse exhibits a marked periodicity linked to the breathing activity. The analysis conducted on the T1D group highlighted a loss of synchronization, with significant WPC levels found in only 33% of the investigated subjects. These results suggest that the proposed method is able to detect the detrimental effects of T1D on the blood microcirculation.

Disclosure

A. Perrella: None. M. Sorelli: None. P. Francia: None. L. Capirchio: None. R. Anichini: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation, Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company, AstraZeneca. Speaker's Bureau; Self; Merck & Co., Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Sanofi, Janssen Pharmaceuticals, Inc.. Research Support; Self; Grünenthal Group. A. de Bellis: Speaker's Bureau; Self; Eli Lilly and Company, AstraZeneca, Novo Nordisk A/S. Research Support; Self; Grünenthal Group. M. Gulisano: None. L. Bocchi: None.
Effects of Early Intensive Insulin Therapy on Endothelial Progenitor Cells in Patients with Newly Diagnosed Type 2 Diabetes
Authors: WANG HONGDONG , BI YAN , LIU FANGCEN
Published: June 2018

Objective: Reduced level of endothelial progenitor cells (EPCs) is a critical event in the pathogenesis of vasculopathy in type 2 diabetes. This study aimed to investigate circulating EPCs alteration in newly diagnosed type 2 diabetic patients and how they are affected by early intensive insulin therapy.

Methods: Twenty-one newly diagnosed type 2 diabetic patients and 22 control subjects matched by age, gender, and BMI were enrolled. All of the diabetic patients received intensive insulin therapy. EPC numbers were assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor.

Results: Level of EPC was higher in diabetic patients compared to control subjects (0.071±0.08% vs. 0.016±0.017%, P<0.001). Notably, EPC number was significantly decreased after therapy (0.007±0.005%, P<0.001 vs. pre-treatment). Level of vascular endothelial growth factor (VEGF), a major contributor of EPC mobilization, was significantly higher in diabetic patients compared to control subjects (26.34±9.15 vs. 17.91±6.6, P=0.002), and decreased dramatically after insulin therapy (21.01±4.64, P=0.0039). Moreover, compared with control subjects, pro-inflammatory cytokines were significantly higher in diabetic patients (TNF-α: 18.74±1.65 vs. 15.7±2.16, P<0.001; IL-1β: 14.04±5.6 vs. 9.41±1.94, P=0.017; IFN-γ: 16.47±3.37 vs. 11.71±3.39, P=0.013) and decreased markedly after insulin therapy (17.27±1.78, P=0.009; 10.81±1.35, P<0.001; 13.72±3.21, P<0.001).

Conclusions: These results showed that type 2 diabetes is associated with increased circulating EPC level at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserved effect on EPC level partly through improving inflammation status, thereby implying a putative long term beneficial effect on vascular integrity via suspending excessive EPC exhaustion.

Disclosure

H. Wang: None. Y. Bi: None. F. Liu: None.