Hospitalization For Hypoglycemia Research Articles

Severe Hypoglycemia Risk With Long-Acting Insulin Analogs vs Neutral Protamine Hagedorn Insulin

Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use. To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings. This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019. Insulin glargine, insulin detemir, and NPH insulin. The primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age. Of the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use. In this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.

Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial.

ContextDulaglutide reduced major adverse cardiovascular events (MACE) in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial. Its efficacy and safety in older vs younger patients have not been explicitly analyzed.ObjectiveThis work aimed to assess efficacy and safety of dulaglutide vs placebo in REWIND by age subgroups (≥ 65 and < 65 years).MethodsA post hoc subgroup analysis of REWIND was conducted at 371 sites in 24 countries. Participants included type 2 diabetes patients aged 50 years or older with established cardiovascular (CV) disease or multiple CV risk factors, and a wide range of glycemic control. Patients were randomly assigned (1:1) to dulaglutide 1.5 mg or placebo as an add-on to country-specific standard of care. Main outcomes measures included MACE (first occurrence of the composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV or unknown causes).ResultsThere were 5256 randomly assigned patients who were 65 years or older (mean = 71.0), and 4645 were younger than 65 years (mean = 60.7). Baseline characteristics were similar in randomized treatment groups. Dulaglutide treatment showed a similar reduction in the incidence (11% vs 13%) of MACE in older vs younger patients. The rate of permanent study drug discontinuation, incidence of all-cause mortality, hospitalizations for heart failure, severe hypoglycemia, severe renal or urinary events, and serious gastrointestinal events were similar between randomized treatment groups within each age subgroup. The incidence rate of serious cardiac conduction disorders was numerically higher in the dulaglutide group compared to placebo within each age subgroup but the difference was not statistically significant.ConclusionDulaglutide had similar efficacy and safety in REWIND in patients65 years and older and those younger than 65 years.

Glucose Control, Sulfonylureas, and Insulin Treatment in Elderly People With Type 2 Diabetes and Risk of Severe Hypoglycemia and Death: An Observational Study.

To estimate the relative and absolute risk of severe hypoglycemia and mortality associated with glucose control, sulfonylureas, and insulin treatment in elderly people with type 2 diabetes. We identified elderly subjects (≥70 years old) with type 2 diabetes between 2000 and 2017 in the U.K. Clinical Practice Research Datalink primary care database with linkage to hospitalization and death data. Subjects with three consecutive HbA1c values <7% (53 mmol/mol) while on insulin and/or sulfonylureas within 60 days prior to the third HbA1c value (exposed) were matched with subjects not exposed. Hazard ratios (HRs) and absolute risks were estimated for hospitalizations for severe hypoglycemia and cardiovascular and noncardiovascular-related mortality. Among 22,857 included subjects (6,288 [27.5%] exposed, of whom 5,659 [90.0%] were on a sulfonylurea), 10,878 (47.6%) deaths and 1,392 (6.1%) severe hypoglycemic episodes occurred during the follow-up. In comparison with nonexposed subjects, the adjusted HR in exposed subjects was 2.52 (95% CI 2.23, 2.84) for severe hypoglycemia, 0.98 (0.91, 1.06) for cardiovascular mortality, and 1.05 (0.99, 1.11) for noncardiovascular mortality. In a 70-, 75-, 80-, and 85-year-old subject, the 10-year risk of severe hypoglycemia was 7.7%, 8.1%, 8.6%, and 8.4% higher than in nonexposed subjects, while differences for noncardiovascular mortality ranged from 1.2% (95% CI -0.1, 2.5) in a 70-year-old to 1.6% (-0.2, 3.4) in an 85-year-old subject. Sulfonylurea and insulin use were more relevant predictors of severe hypoglycemia and death than were glucose levels. Elderly subjects with type 2 diabetes and low HbA1c on sulfonylurea or insulin treatment experienced a substantially higher risk of hospitalization for severe hypoglycemia but had no clear evidence of increased risks of mortality.

Determinants of mental health outcomes among people with and without diabetes during the COVID-19 outbreak in the Arab Gulf Region.

To determine the prevalence and factors associated with depression and anxiety among people with and without diabetes during the coronavirus disease 2019 (COVID-19) outbreak. A cross-sectional questionnaire-based study collecting demographic and mental health data from 2166 participants living in the Arab Gulf region (568 with diabetes, 1598 without diabetes). Depression and anxiety were assessed using the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale, respectively. The prevalence of depression and anxiety symptoms were 61% and 45%, in people with diabetes (PWD) and 62% and 44%, respectively, in people without diabetes. PWD who have had their diabetes visit canceled by the clinic were more likely to report depression and anxiety symptoms than those without diabetes (odds ratio [95% confidence interval]: 1.37 [1.02, 1.84] and 1.37 [1.04, 1.80], for depression and anxiety; respectively). PWD who had no method of telecommunication with their health care providers (HCP) during the pandemic, PWD with A1C of ≥ 10%, women, employees (particularly HCPs), students, unmarried individuals, and those with lower income were more likely to report depression and/or anxiety symptoms (all P < 0.01). Fear of acquiring the coronavirus infection; running out of diabetes medications; or requiring hospitalization for hypoglycemia, hyperglycemia, or diabetic ketoacidosis; and lack of telecommunication with HCPs were all associated with significantly higher odds of having depression and anxiety symptoms among PWD. The remarkably high prevalence of depression and anxiety symptoms during the COVID-19 pandemic, particularly among subgroups of PWD, calls for urgent public health policies to address mental health during the pandemic and reestablish health care access for PWD.

Dietary intake and hospitalisation due to diabetic ketoacidosis and hypoglycaemia in individuals with type 1 diabetes

We investigated the association between diet and risk of hospitalisation for diabetic ketoacidosis (DKA) or hypoglycaemia in type 1 diabetes. Food records were used to assess dietary intake. Data on DKA and hypoglycaemia hospitalisations, within two years of dietary assessments, were obtained from registries. Analyses were conducted with and without macronutrient substitution. Data were available from 1391 participants, 28 (2.0%) and 55 (4.0%) of whom were hospitalised due to DKA or hypoglycaemia, respectively. In the adjusted model, self-reported alcohol intake was associated with increased (per 10 g: B = 1.463, 95% CI = 1.114–1.922, p = 0.006; per E%: B = 1.113, 95% CI = 1.027–1.206, p = 0.009), and fibre intake with reduced (per g/MJ: B = 0.934, 95% CI = 0.878–0.995, p = 0.034) risk of DKA hospitalisation. Substituting carbohydrates for fats was associated with increased risk for hypoglycaemia hospitalisation (B = 1.361, 95% CI = 1.031–1.795, p = 0.029), while substituting alcohol for carbohydrates (B = 1.644, 95% CI = 1.006–2.685, p = 0.047) or proteins (B = 2.278, 95% CI = 1.038–4.999, p = 0.040) increased the risk for DKA hospitalisation. In conclusion, refraining from alcohol intake is a preventable risk factor for DKA, while higher fibre intake seems rather protective. Increasing carbohydrate intake while decreasing that of fats, is associated with higher hypoglycaemia risk. Whether this is a cause or effect of hypoglycaemia remains to be established.

Incidence and Risk Factors Associated with Outpatient Hypoglycemia in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Nationwide Study

ABSTRACT Background Chronic kidney disease and hypoglycemia are common complications in individuals with diabetes. Currently, the association of renal function with hypoglycemic complications in type 2 diabetes mellitus (T2DM) is inconclusive. This study aims to assess the associations between estimated glomerular filtration rate (eGFR) and cumulative incidence of hypoglycemia, hypoglycemia-related hospitalizations, and incidence of outpatient hypoglycemia among T2DM patients in Thailand using a nationwide patient sample. Methods We conducted a nationwide retrospective cohort study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study assessed adult T2DM patients from 831 public hospitals in Thailand in the year 2012–2013. eGFR was categorized into ≥90, 60–89, 30–59, 15–29, and <15 mL/min/1.73 m2. The associations between eGFR and hypoglycemia, hypoglycemia-related hospitalizations, and incidence of outpatient hypoglycemia were assessed using multivariate logistic regression and Poisson regression. Results A total of 25,056 T2DM patients with available eGFR were included in the analysis. The mean age was 60.9 ± 10.5 years. The cumulative incidence of hypoglycemia and hypoglycemia-related hospitalizations was 3.6% and 1.7%, respectively. Incidence of outpatient hypoglycemia, mild hypoglycemia, and severe hypoglycemia was 2.99 (2.59–3.43), 2.47 (2.11–2.88), and 0.52 (0.36–0.72) per 100 patient-years, respectively. Patients with eGFR of 30–59, 15–29, and <15 mL/min/1.73 m2 were significantly associated with an increased risk of hypoglycemia, hypoglycemia-related hospitalizations, and incidence of outpatient hypoglycemia when compared to patients with eGFR of ≥90 mL/min/1.73 m2. Conclusion Reduced eGFR was independently associated with increased hypoglycemia, hypoglycemia-related hospitalizations, and risk of outpatient hypoglycemia. Increasing awareness of the heightened risk of hypoglycemia with declining renal function may prompt changes to diabetic management for at-risk individuals.

Persistence with Basal Insulin and Frequency of Hypoglycemia Requiring Hospitalization in Patients with Type 2 Diabetes.

IntroductionA second-generation basal insulin analogue insulin glargine 300 U/mL (Gla-300) has been marketed in France since June 2016. This real-world study was designed to assess persistence with Gla-300 and the prevalence of related hypoglycemia requiring hospitalization as compared to first-generation basal insulins, in patients with type 2 diabetes mellitus (T2DM). MethodsA retrospective study was conducted using data in the large French comprehensive national healthcare system claims databases. Patients with T2DM newly treated with insulin in 2016 and 2017 (2-year period) were included. Three basal insulins [Gla-300, glargine 100 U/mL (Gla-100; both branded and biosimilar) and insulin detemir (IDet)] were compared for (1) persistence until treatment discontinuation using adjusted Cox models and (2) hypoglycemia requiring hospitalization over the period of insulin exposure.ResultsDuring the 2-year study period, in France, 181,263 patients initiated basal insulin therapy (in a basal scheme or a more complex insulin scheme), of whom 74% initiated Gla-100, 14.2% initiated IDet and 11.8% initiated Gla-300. Patient characteristics varied according to the insulin regimen in terms of age, gender, social coverage, insulin scheme, and Charlson Comorbidity Index. Overall, 72% of patients were still treated with any basal insulin after 1 year (75% in basal scheme). In all insulin treatment regimens, patients were less likely to discontinue Gla-300 as compared to Gla-100 [adjusted odds ratio (OR) 0.39, 95% confidence interval (CI) 0.37–0.41], with similar results when only the basal scheme was considered (adjusted OR 0.38, 95% CI 0.35–0.40). Persistence with IDet was similar to that with Gla-100. Patients treated with Gla-100 had higher crude hospitalization rates for hypoglycemia than those receiving Gla-300 (1.4 for 100 patients-years; OR 0.67, 95% CI 0.55–0.81); however, this difference was not statistically significant after adjustment for patient characteristics. Emergency Room (ER) visits were less frequent in patients treated with Gla-300 versus Gla-100 with or without adjustment for patient characteristics (p < 0.0001).ConclusionReal-world persistence for basal insulin therapy in patients with T2DM was significantly better in those on Gla-300 compared with those on Gla-100 and IDet. A trend to a lower frequency of hospitalization for hypoglycemia and ER visits, whatever the cause, was also observed in patients on Gla-300.

Impact of flash glucose monitoring on glucose control and hospitalization in type 1 diabetes: A nationwide cohort study.

We evaluated the impact of flash continuous glucose monitoring (FCGM) on glycemic control and healthcare burden in a large real-world cohort of patients with type 1 diabetes (T1D) initiating FCGM technology. In this retrospective cohort study, we included adults (age ≥18 years) with T1D from a large Health Maintenance Organization in Israel, who initiated FCGM during 2018. Primary outcomes included change in HbA1c ≥3 months following FCGM commencement and change in rate of internal-medicine hospitalization. Additional outcomes included changes in glucose test strip purchases, diabetes related outpatient health care visits and hospitalization for diabetic ketoacidosis (DKA) and/or severe hypoglycemia. The study included 3490 patients, followed for a median of 14 (inter-quartile range 11-15) months after FCGM commencement. Among 2682 patients with an HbA1c measured both at baseline and ≥3 months after FCGM initiation, average HbA1c declined from 8.1% ± 1.46% to 7.9% ± 1.31% (P < .001) at first measurement and was maintained during follow up. Specifically, in those with HbA1c ≥8%, a mean decline of 0.5% (P < .001) was observed. A clinically significant HbA1c reduction of ≥0.5% was experienced by 25.5% of the patients. The rate of internal medicine hospitalization, visits to primary care, or visits to endocrine/diabetes specialists in the period following FCGM commencement vs the 6 months prior was significantly reduced (P < .001). Hospitalization for DKA and/or hypoglycemia declined as well (P = .004). FCGM was associated with significant and durable improvement in glycemic control as well as reduced consumption of healthcare services.

1512-P: Severe Hypoglycemia and Hyperglycemia among U.S. Adults with Diabetes and ESRD on Dialysis, 2010-2015

Glycemic management in patients with diabetes and end-stage renal disease (ESRD) is challenging. There is limited evidence about the incidence of severe hypoglycemia and hyperglycemia in this population. Here, we examine rates of emergency department visits and hospitalizations for severe hypoglycemia and hyperglycemia (ascertained using validated ICD-9/10 codes) in a national cohort of adults with diabetes and incident ESRD, included in the United States Renal Data System, between 2010-2015. We then examine risk factors for these events using logistic regression. Among 678,376 patients with ESRD, 59.5% (n=403,490) had diabetes (63.6±13.0 years, 56.4% male, 26.8% Black, and 18.0% Hispanic). Rates of severe hypoglycemia and hyperglycemia were 126.2 and 35.5 per 1000 person-years, respectively. Strongest risk factors for hypoglycemia were insulin therapy (OR 4.5 [95% CI, 4.4-4.6] vs. no medications) and non-insulin diabetes medications (OR 3.7 [3.6-3.8]); Black race (OR 1.3 [1.3-1.4] vs. Caucasian); older age: 65-74 years (OR 1.2 [1.1-1.3] and ≥75 years OR 1.1 [1.1-1.1] vs. 18-44 years); and history of amputation (OR 1.4 [1.4-1.5]) or retinopathy (OR 1.2 [1.2-1.3]). Strongest risk factors for hyperglycemia were insulin (OR 7.7 [7.4-8.2]) and non-insulin diabetes medication use (OR 2.8 [2.6-3.1]) and retinopathy (OR 1.5 [1.4-1.5]). Older age was protective for hyperglycemia (OR 0.1 [0.1-0.1] for age ≥75 and 0.2 [0.2-0.2] for age 65-74 vs. 18-44 years). Patients on peritoneal dialysis had a lower risk (OR 0.8 [0.8-0.9]) of hypoglycemia, but no difference in odds of hyperglycemia, compared to patients on hemodialysis. Hypoglycemia requiring ED/hospital care was 3.6-fold more prevalent than severe hyperglycemia, greatly exceeding rates previously reported for older adults and those with non-end stage chronic kidney disease. There is a critical need for proactive interventions to reduce hypoglycemia and related ED/hospital use in this high-risk population. Disclosure R.J. Galindo: Advisory Panel; Self; Lilly Diabetes. Consultant; Self; Valeritas, Inc. Research Support; Self; Novo Nordisk Inc. Other Relationship; Self; UpToDate. M.K. Ali: Research Support; Self; Merck &amp; Co., Inc. N. Shah: None. S. Funni: None. G.E. Umpierrez: None. R.G. McCoy: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024)

396-P: Investigating the Risk of Severe Hypoglycemia in Elderly Patients with Type 2 Diabetes Mellitus

In Japan, The prevalence of type 2 diabetes mellitus (T2DM) is increasing, especially in the elderly population. Many of these patients have co-morbidities like renal insufficiency and personalized blood sugar goals, increasing the risk of hypoglycemia. This study was conducted to examine the associations of patients characteristics such as HbA1c level, BMI and use of glucose level-lowering medication with hypoglycemia-related hospitalizations. This study was cross sectional study conducted over 6 years January 2014 and March 2019. We recruited 9,798 patients with elderly patients over 65 years with T2DM. To assess the odds ratio (OR) of hypoglycemia-related hospitalizations, we constructed a logistic regression analysis, having adjusting for age, gender, BMI, eGFR, baseline HbA1c levels, use of hypoglycemic agents. Hypoglycemia was documented in 124 (1.27%) patients. In multivariate logistic regression analysis, age≧75years and gender were not significantly. DPP-4I (OR: 0.52, 95%CI: 0.28-0.96) showed lower odds ratio. BMI≦25kg/m2 (OR: 2.94, 95%CI: 1.26-6.86), baseline HbA1c&amp;lt;6.0% (OR: 4.43, 95%CI: 2.25-8.73), eGFR 15-≦30 mL/min(OR: 2.54, 95%CI: 1.05-6.10), &amp;lt;15mL/min(OR: 3.01, 95%CI: 1.26-7.16), Insulin (OR: 2.05, 95%CI: 1.22-3.43) showed higher odds ratio. In this study of elderly patients with T2DM, the risk of hospitalization for hypoglycemia appeared to be highest among patients with too low Hba1c and BMI, decreased renal function, and sulfonylurea and/or insulin use. On the other hand, DPP-4I have been shown to reduce the risk of hospitalization for hypoglycemia. By leveraging the results of this study, at-risk elderly patients can benefit from individualized treatment plans to reduce the risk of hypoglycemia. Disclosure T. Horii: None. K. Atsuda: None.

MON-599 Post-Bariatric Hypoglycemia: A Clinical Vignette on an Increasingly Recognized Disease

Introduction: Previously referred to as late dumping syndrome, post-bariatric hypoglycemia (PBH) is thought to represent at least 1% of all hospitalizations for hypoglycemia and 10% of all clinically recognized hypoglycemia cases. However, through the advent of CGM and more strict criteria over the last decade these numbers are likely an underestimate. As obesity continues to remain prevalent and with rising bariatric centers to help deal with this epidemic, endocrinologists will play an increasing role in managing PBH patients.Clinical Case: A 39-year female with a PMH of hypothyroidism and bariatric surgery (BS) in 2009 presented to our ER for a seizure. She has been having seizures nearly every 2 weeks for one year. Neurology started her on Keppra; however, no etiology was identified. EMS had documented a blood glucose of 40 mg/dL; the patient was given an amp of D50 with resolution of neuroglycopenic symptoms. TSH and cortisol levels were within normal range. A sulfonylurea panel in the ED was negative. The patient states the symptoms can occur while fasting but also mainly post-prandial. A 72-hr fast was conducted with the patient nadir POC glucose of 77. Subsequently, the patient had a mixed meal tolerance performed and after 2 hours had a seizure and was found to have a BG of 50 mg/dL with an insulin level of 49 uIU/mL and a c-peptide of 18.8 ng/mL. The patient was diagnosed with PBH, and was discharged with a CGM, started on acarbose and was seen by nutrition to discuss dietary modifications. She is now seen in our clinic with control of her symptoms with the addition of diazoxide.Conclusion: Altered anatomy after bariatric surgery, particularly after gastric bypass and sleeve gastrectomy is thought to play a major role in developing PBH. By bypassing normal anatomy, gastric emptying is increased 2–3 x, which leads to a higher and more rapid appearance of glucose in the distal foregut. This subsequently leads to an amplified incretin response leading to a hyperinsulinemic response in patients who have had bariatric surgery; however, for unclear reasons some patients develop an even more amplified hyperinsulinemic response that leads to subsequent hypoglycemia. History of neuroglycopenic symptoms 1–3 hours after eating in a patient who had a gastric bypass > 6–12 months and with relief of symptoms with carbohydrates should raise an endocrinologist’s suspicion of PBH. Fasting hypoglycemia is an atypical feature that should raise one’s suspicion of a broader differential. Altered nutrition habits is the cornerstone of therapy with which the primary aim is to reduce post-prandial glucose spikes in these patients after they eat carbohydrates. These spikes in turn lead to hyperinsulinism leading to subsequent hypoglycemia. Primary diet modifications include controlled carbohydrate consumption of less than 30g per meal, avoiding high glycemic carbs, and always taking in ample fat and proteins with every meal.

SUN-906 To Function or Not to Function: A Rare Case of Metachronous Hormone Syndrome

This is a 51-year-old female with a history of metastatic neuroendocrine tumor of the pancreas diagnosed four years ago who was admitted to the to the hospital for hypoglycemia. She initially had come to the hospital for alternative treatment of her disease using PRRT (peptide receptor radionuclide therapy). Prior to receiving treatment the patient had been asymptomatic. After receiving her first dose of PRRT the patient developed acute encephalopathy. Upon evaluation she was noted to be oriented only to person, lethargic and confused. Finger stick blood glucose at the time of her symptoms had read 17. The patient was immediately placed on D10 with improvement of her symptoms and increase of glucose to the 70s. An attempt was made to wean the patient off of dextrose however the patient continued to experience persistent hypoglycemia. Thus investigation of an insulin-secreting tumor was done. C-peptide was 3.98 ng/mL (0.81 - 5.30 ng/mL), insulin level was 26.7 uU/mL (3.0-16 uU/mL) and proinsulin level was 556 pmol/L (<22 pmol/L), while her serum glucose was below 45. Given her biochemical markers as well as improvement in glucose when treated the patient was started on Diazoxide for presumed insulinoma. Due to intolerance to the medication she was switched to Octreotide with success.Here we present an unusual case of Metachronous Hormone Syndrome (MHS) in a patient who at presentation of her diagnosis was already found to have metastatic pancreatic neuroendocrine tumor. Typically NET present in the 4th to 6th decades of life and have the potential to secrete peptide hormones. Occasionally patients with tumors that appear to be nonfunctional develop symptoms of hormone secretion later in their disease such as our patient. Furthermore it is uncommon for a patient to present with metastatic NET; such was not the case for our patient. Metachronous hormone syndrome is not fully understood but may be an indication of tumor progression. In addition its mechanism of action is unknown and its been theorized to be induced by anti-tumor treatments. Perhaps this case may allow us to better understand MHS in a broader context, as this patient was found to have progression of her disease when she initially was diagnosed 4 years ago and recently presented with symptoms consistent with an insulinoma. Lastly her case may further guide us in studying various treatments for NET and their role in triggering MHS.

Association of Cumulative Multimorbidity, Glycemic Control, and Medication Use With Hypoglycemia-Related Emergency Department Visits and Hospitalizations Among Adults With Diabetes

Severe hypoglycemia is a serious and potentially preventable complication of diabetes, with some of the most severe episodes requiring emergency department (ED) care or hospitalization. A variety of health conditions increase the risk of hypoglycemia. People with diabetes often have multiple comorbidities, and the association of such multimorbidity with hypoglycemia risk in the context of other risk factors is uncertain. To examine the associations of age, cumulative multimorbidity, glycated hemoglobin (HbA1c) level, and use of glucose level-lowering medication with hypoglycemia-related ED visits and hospitalizations. Cohort study of claims and laboratory data from OptumLabs Data Warehouse, an administrative claims database of commercially insured and Medicare Advantage beneficiaries in the United States. Participants were adults (aged ≥18 years) with diabetes who had an available HbA1c level result in 2015. Data from January 1, 2014, to December 31, 2016, were analyzed. Final analyses were conducted from December 2017 to September 2018. This study calculated rates of hypoglycemia-related ED visits and hospitalizations during the year after the index HbA1c level was obtained, stratified by patient demographic characteristics, diabetes type, comorbidities (from 16 guideline-specified high-risk conditions), index HbA1c level, and glucose level-lowering medication use. The association of each variable with hypoglycemia-related ED and hospital care was examined using multivariable Poisson regression analysis overall and by diabetes type. The study cohort was composed of 201 705 adults with diabetes (mean [SD] age, 65.8 [12.1] years; 102 668 [50.9%] women; 118 804 [58.9%] white; mean [SD] index HbA1c level, 7.2% [1.5%]). Overall, there were 9.06 (95% CI, 8.64-9.47) hypoglycemia-related ED visits and hospitalizations per 1000 persons per year. The risk of hypoglycemia-related ED visits and hospitalizations was increased by age 75 years or older (incidence rate ratio [IRR], 1.56 [95% CI, 1.23-2.02] vs 18-44 years), black race/ethnicity (IRR, 1.30 [95% CI, 1.16-1.46] vs white race/ethnicity), lower annual household income (IRR, 0.63 [95% CI, 0.53-0.74] for ≥$100 000 vs <$40 000), number of comorbidities (increasing from IRR of 1.66 [95% CI, 1.42-1.95] in the presence of 2 comorbidities to IRR of 4.12 [95% CI, 3.07-5.51] with ≥8 comorbidities compared with ≤1), prior hypoglycemia-related ED visit or hospitalization (IRR, 6.60 [95% CI, 5.77-7.56]), and glucose level-lowering treatment regimen (IRR, 6.73 [95% CI, 4.93-9.22] for sulfonylurea; 12.53 [95% CI, 8.90-17.64] for basal insulin; and 27.65 [95% CI, 20.32-37.63] for basal plus bolus insulin compared with other medications). Independent of these factors, having type 1 diabetes was associated with a 34% increase in the risk of hypoglycemia-related ED visits or hospitalizations (IRR, 1.34 [95% CI, 1.15-1.55]). The index HbA1c level was associated with hypoglycemia-related ED visits and hospitalizations when both low (IRR, 1.45 [95% CI, 1.12-1.87] for HbA1c level ≤5.6% vs 6.5%-6.9%) and high (IRR, 1.24 [95% CI, 1.02-1.50] for HbA1c level ≥10%). In this cohort study of adults with diabetes, the risk of an ED visit or hospitalization for hypoglycemia appeared to be highest among patients with type 1 diabetes, multiple comorbidities, prior severe hypoglycemia, and sulfonylurea and/or insulin use. At-risk patients may benefit from individualized treatment regimens to decrease their risk of hypoglycemia.

Cost of hospitalisation and length of stay due to hypoglycaemia in patients with diabetes mellitus: a cross-sectional study

Objective:This study aims to estimate the length of stay and hospitalisation cost of hypoglycaemia, and to identify determinants of variation in the length of stay and hospitalisation cost among individual patients with type 1 or 2 diabetes mellitus.Methods:A cross-sectional study was conducted using inpatients records for patients with diabetes mellitus who had been hospitalised due to hypoglycaemic events in two private hospitals in Amman, Jordan between January 2009 and May 2017. All hospitalisation costs were inflated to the equivalent costs in 2017. Hospitalisation cost was estimated from the patient’s perspective in Jordanian dinars (JOD). Descriptive analyses and correlation between sociodemographic or clinical characteristics with the cost and length of stay were explored. Predictors of hypoglycaemic hospitalisation cost and length of stay were determined using logistic regression.Results:During the study period a total of 126 patients with diabetes mellitus were hospitalised due to an incident of hypoglycaemia. The mean patient age was 64.2 (SD=19.6) years; half were male. Patients admitted for hypoglycaemia stayed in hospital for a median duration of two days (IQR=2 days). The median cost of hospitalisation for hypoglycaemia was 163.2 JOD (USD 230.1) (IQR=216.3 JOD). We found that the Glasgow coma score was positively associated with length of stay (0.345, p=0.008), and older age was correlated with higher hospitalisation cost (0.207, p=0.02). Patients with a family history of diabetes had higher hospitalisation costs and longer duration of stay (0.306 and 0.275, p<0.05). In addition, being a male patient (0.394, p<0.05) and with an absence of smoking history was associated with longer duration of stay (0.456, p<0.01), but not with higher hospitalisation cost.Conclusions:Costs associated with the incidence of hypoglycaemic events are not low and constitute a large cost component of managing and treating diabetes mellitus. Male patients and patients having a family history of diabetes should receive extra care and education on the prevention of hypoglycaemic events, and a treatment de-intensification approach should be considered if necessary, so we can prevent its associated hospitalisation costs and length of stay.

Self-Monitoring of Blood Glucose and Hypoglycemia-Related Hospitalization in a Population-Based Cohort of Canadian Patients With Type 1 or Type 2 Diabetes

ObjectivesThe aim of this work was to determine whether: 1) blood glucose test strip use in the population is associated with hypoglycemia hospitalization rates, and 2) blood glucose test strip use among individuals is associated with a reduced risk of hypoglycemia hospitalization. MethodsAdministrative databases from Saskatchewan, Canada, were used to ascertain population-level hypoglycemia hospitalizations and test strip utilization over the period from 1996 to 2014. For objective 1, a generalized linear model with generalized estimating equations was fit to provincial data stratified by age group, sex and year. For objective 2, a nested case-control study was conducted for a cohort of insulin users with diagnosed diabetes. Multivariable conditional logistic regression was used to test the association of test strip use with hospitalization, after adjusting for clinical and demographic factors and health services use. Odds ratios (ORs) and 95% confidence intervals (95% CIs) are reported. ResultsA total of 5,166 hospitalizations for hypoglycemia were identified in the observation period. Annual glucose test strip use increased by over 350%; however, no association was found with provincial hypoglycemia hospitalization rate during the same period, even after controlling for all-cause hospitalizations and population demographics. In the case-control analysis, test strip use was not associated with hospitalization for hypoglycemia among insulin users (n=10,617; adjusted OR, 1.08; 95% CI, 0.88 to 1.31). A sensitivity analysis in an independent cohort of noninsulin users produced a similar finding (n=47,501; adjusted OR, 1.04; 95% CI, 0.55 to 1.94). ConclusionOur findings add to the body of evidence against a protective effect of blood glucose test strip use for serious hypoglycemia.

Drug price, dosage and safety: Real-world evidence of oral hypoglycemic agents

ObjectivesDrug price reduction is one of the major policies to restrain pharmaceutical expenses worldwide. This study explores whether there is a relationship between drug price and clinical quality using real-world data. MethodsPatients with newly-diagnosed type 2 diabetes receiving metformin or sulfonylureas during 2001 and 2010 were identified using the claim database of the Taiwan universal health insurance system. Propensity score matching was performed to obtain comparable subjects for analysis. Pharmaceutical products were categorized as brand-name agents (BD), highpriced generics (HP) or low-priced generics (LP). Indicators of clinical quality were defined as the dosage of cumulative oral hypoglycemic agents (OHA), exposure to other pharmacological classes of OHA, hospitalization or urgent visit for hypoglycemia or hyperglycemia, insulin utilization and diagnosis of diabetic complications within 1 year after diagnosis. ResultsA total of 40,152 study subjects were identified. A generalized linear mix model showed that HP and BD users received similar OHA dosages with comparable clinical outcomes. By contrast, LP users had similar outcomes to BD users but received a 39% greater OHA dosage. A marginally higher risk of poor glycemic control in LP users was also observed. ConclusionsDrug price is related to indicators of clinical quality. Clinicians and health authorities should monitor the utilization, effectiveness and clinical safety indicators of generic drugs, especially those with remarkably low prices.

397-P: Relationship between HbA1c and Declines in Racial Differences of Serious Hypoglycemia in the Veteran Health Administration (VHA) 2004-2015

Annual rates of emergency department visits or hospitalizations for hypoglycemia (HYPO) were evaluated using a serial cross-sectional study design (2004-2015) of VHA/Medicare enrolled patients. Subjects were ≥65 years receiving secretagogues only (Secr), or insulin with or without Secr (Ins), and who had HbA1c value(s). Separately for Secr/Ins groups and by race/ethnicity, we assessed age/sex adjusted HYPO rates (per 1000 patients) and A1c values (from prior to an event or end of year for those without an event). In 2015, subjects were 99% men, 10% [B]lack, 6% [H]ispanic, and 75% [W]hite; 75% had major comorbidity categories; 24% had cardiovascular conditions only, and 9% advanced diabetes only. Ins use increased by 88%, similar among B/H/W. HYPO rates markedly declined for Ins and Secr in all races but remained higher for B. The percent of patients with A1c &amp;lt;7% decreased: 44.2%/32.9%[B], 51.0%/32.6%[W], and 41.3%/28.4%[H]; the percentage for A1c 7.0-7.9% increased: 28.6%/31.6%[B], 30.6%/35.8%[W], and 30.8%/32.4%[H]; the percentage for &amp;gt;9% also increased: 11.9%/15.8%% [B], 6.4/12.2%[W], and 12.0/17.6%[H]. Mean A1c values also increased in B/H/W, and were similar (difference ≤0.2%) between patients with and without HYPO. Guideline recommendations (post 2008) for individualized A1c goals may have mediated reductions in racial disparities for HYPO rates. Disclosure C. Tseng: None. O. Soroka: None. C.E. Myers: None. D.C. Aron: None. L.M. Pogach: None. Funding U.S. Department of Veterans Affairs (IIR14-082)

379-P: Changes in Diabetes Management after a Hospital Visit for Severe Hypoglycemia

Clinical guidelines recommend reevaluation of glucose-lowering medications and relaxation of HbA1c targets in patients with diabetes after a severe hypoglycemic event. We compared diabetes management before and after hypoglycemia requiring emergency department (ED) visit or hospital admission. Using data from OptumLabs® Data Warehouse, we identified privately insured and Medicare Advantage enrollees 18+ years with pharmacologically-treated type 2 diabetes and an ED visit or hospitalization for hypoglycemia between July 1, 2013 and June 30, 2014. We assessed the differences in the number of physician office visits, glucometer test strips filled, continuous glucose monitor (CGM) use, diabetes medication fills, and HbA1c levels (available for 1582 [27.7%]), within 6 months prior to and 6 months after hypoglycemia. Among 5721 patients with type 2 diabetes and severe hypoglycemia, mean age was 67.8 (SD 12.3), 51% women, 63% white, and 68% used insulin. Changes in management are summarized in Table 1. After an event, the proportion of patients filling insulin increased, but the proportion filling sulfonylureas declined. Less than one third of patients with a baseline HbA1c &amp;lt;7% had a substantially higher post-event HbA1c. Few of the recommended changes in diabetes management occur after a severe hypoglycemic event. These findings suggest the need for better post-event care to improve the safety of glucose-lowering therapy. Disclosure P. Vijayakumar: None. S. Liu: None. P.A. Kahn: None. R.G. McCoy: None. A.J. Karter: None. K.J. Lipska: Consultant; Self; Health Services Advisory Group (HSAG). Research Support; Self; National Institute on Aging. Other Relationship; Self; Centers for Medicare and Medicaid Services. Funding National Institute of Diabetes and Digestive and Kidney Diseases (T35DK104689); National Institute on Aging; American Federation for Aging Research; National Institutes of Health (K23AG048359)

Proximal HbA1C Level and First Hypoglycemia Hospitalization in Adults With Incident Type 2 Diabetes.

Hemoglobin A1C (HbA1C) is an important predictor of severe hypoglycemia. To determine the association of proximal HbA1C level with first hypoglycemia hospitalization (HH) in adults with incident type 2 diabetes (T2D). A nested case-control study was designed using linked data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England in 1997 to 2014. The first hypoglycemia event as primary diagnosis for hospitalization after T2D diagnosis was identified. Proximal HbA1C was measured within 90 days before the first HH. OR for developing HH. The association of proximal HbA1C level with first HH was similar between HbA1C levels of 6.0% (OR, 1.54; 95% CI, 1.12 to 2.11) and 9.0% [1.48 (1.01 to 2.17)] compared with the reference HbA1C level of 7.0%. For proximal HbA1C level of 4.0% to 6.5%, every additional 0.5% increase in HbA1C was associated with lower first HH risk, with ORs (95% CI) ranging between 0.37 (0.20 to 0.67) and 0.86 (0.76 to 0.98). For proximal HbA1C level of 8.0% to 11.5%, every additional 0.5% increase in HbA1C was associated with higher first HH risk, with ORs (95% CI) ranging between 1.16 (1.04 to 1.29) and 1.34 (1.18 to 1.52). The U-shaped association between proximal HbA1C level and first HH did not exist among current sulfonylurea users but persisted among current insulin users (Pinteraction = 0.002). Among current noninsulin nonsulfonylurea users who had a first HH, 78% took insulin or sulfonylureas before the HH. Having either poor or near-normal HbA1C was associated with a higher risk of first HH within 3 months in T2D.

Proximal HbA 1c level and first hypoglycemia hospitalization in adults with incident type 2 diabetes

Proximal HbA 1c level and first hypoglycemia hospitalization in adults with incident type 2 diabetes