Risk Factor For Severe Hypoglycemia Research Articles

A cross-sectional questionnaire study: Impaired awareness of hypoglycaemia remains prevalent in adults with type 1 diabetes and is associated with the risk of severe hypoglycaemia.

Impaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors. Adults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records. 189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p = 0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p = 0.036). Socio-economic deprivation was associated with IAH (p = 0.032) and SH (p = 0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p = 0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p = 0.04). Insulin pump and continuous glucose monitor use was comparable in IAH versus aware groups. Despite this, IAH remains a risk factor for SH and is prevalent in females and in older people. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions.

Risk factors of severe hypoglycemia among patients with type 2 diabetes mellitus in outpatient clinic of tertiary hospital in Indonesia

This study aimed to describe risk factors of severe hypoglycemia in type 2 diabetes mellitus (T2DM) patients in a tertiary care hospital in Indonesia. This study was a retrospective cohort study in the Endocrinology Outpatient Clinic of Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia. All subjects more than 18 years old who had been visiting the clinic for at least a year were included. Subjects were interviewed whether they had any severe hypoglycemia events within the past year, while data on risk factor variables of severe hypoglycemia was taken from medical records one year before data collection. We recruited 291 subjects, among whom 25.4% suffered at least one episode of severe hypoglycemia within one year. History of severe hypoglycemia (OR 5.864, p ≤ 0.001), eGFR less than 60 mL/min/1.73m2 (OR 1.976, p = 0.028), and insulin use (OR 2.257, p = 0.021) were associated with increased risk of severe hypoglycemia. In conclusion, history of previous severe hypoglycemia, eGFR less than 60 mL/min/1.73m2, and insulin use were associated with severe hypoglycemia.

Multimorbidity, Polypharmacy, Severe Hypoglycemia, and Glycemic Control in Patients Using Glucose-Lowering Drugs for Type2 Diabetes: A Retrospective Cohort Study Using Health Insurance Claims in Japan.

This study aimed to understand the actual status of multimorbidity and polypharmacy among patients with type2 diabetes using glucose-lowering drugs, and to assess the effects of patient characteristics on severe hypoglycemia and glycemic control. We designed a retrospective cohort study using health insurance claims and medical checkup data in Japan from April 2016 to February 2021 and identified patients with type2 diabetes who were prescribed glucose-lowering drugs. We analyzed data on patient characteristics, including multimorbidity and polypharmacy, calculated the incidence rate for severe hypoglycemic events, applied a negative binomial regression model to explore factors that affected severe hypoglycemia, and analyzed the status of glycemic control in the subcohort for which HbA1c data were available. Within the analysis population (n = 93,801), multimorbidity was present in 85.5% and mean ± standard deviation for oral drug prescriptions was 5.6 ± 3.5 per patient, while for those aged 75years or older these numbers increased to 96.3% and 7.1 ± 3.5, respectively. The crude incidence rate for severe hypoglycemia was 5.85 (95% confidence interval 5.37, 6.37) per 1000 person-years. Risk factors for severe hypoglycemia included younger and older age, prior severe hypoglycemia, use of insulin, sulfonylurea, two-drug therapy including sulfonylurea or glinides, three-or-more-drug therapy, excessive polypharmacy, and comorbidities including end-stage renal disease (ESRD) requiring dialysis. Subcohort analysis (n = 26,746) showed that glycemic control is not always maintained according to guidelines. Patients with type2 diabetes, particularly older patients, experienced high multimorbidity and polypharmacy. Several risk factors for severe hypoglycemia were identified, most notably younger age, ESRD, history of severe hypoglycemia, and insulin therapy. The University Hospital Medical Information Network Clinical Trials Registry (UMIN000046736).

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

376-P: The Hypoglycemia Awareness Questionnaire (HypoA-Q) Demonstrates Concurrent and Convergent Validity in Adults with Type 1 Diabetes and Hypoglycemia Unawareness

Introduction: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in type 1 diabetes (T1D) . Current tools to identify IAH are limited in their ability to characterize unawareness and evaluate hypoglycemia severity. The Hypoglycemia Awareness Questionnaire, including the 5-item Short Form awareness subscale (HypoA-Q SF) , was developed to identify IAH and characterize problematic hypoglycemia. We aimed to evaluate HypoA-Q SF’s concurrent and convergent validity. Methods: Adults with T1D (n=23, 48% male; median age: 36 years, disease duration: 21 years) completed the (a) HypoA-Q SF, (b) Clarke score and (c) hypoglycemia severity (HYPO) score. Those with IAH defined by Clarke score ≥4 (n=12) and HYPO score ≥90th% were established on hybrid-closed loop insulin delivery as part of an ongoing 18-month clinical trial with 6-monthly completion of HypoA-Q, Clarke and HYPO scores. Mann-Whitney U Test was used to evaluate the HypoA-Q SF’s ability to differentiate between those with and without IAH. Repeated measures correlation was used to assess concordance between HypoA-Q SF score and Clarke / HYPO scores over the 18-month period. Results: At baseline, HypoA-Q SF demonstrated concurrent validity as scores were significantly different between those with and without IAH (W= 110.5, p &amp;lt; .001) . Over the trial, HypoAQ-SF demonstrated convergent validity as repeated measures correlation analysis revealed significant positive relationships with both Clarke (r = 0.62 p &amp;lt; .001) and HYPO (r = 0.48, p&amp;lt;.01) scores. Conclusion: These findings support the HypoA-Q SF as a tool to identify IAH and evaluate hypoglycemia severity. Further assessment of the HypoA-Q SF alongside gold-standard clamp-derived measures of autonomic symptom and counterregulatory response to hypoglycemia would be of value to determine score thresholds. Disclosure A.M.Matus: None. A.Flatt: None. A.J.Peleckis: None. C.V.Dalton-bakes: None. B.Riegel: None. M.R.Rickels: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Consultant; L-Nutra Inc. Funding National Institutes of Health (R01DK091331; UL1 TR001878; P30 DK19525)

Adherence to healthy lifestyle behaviors as a preventable risk factor for severe hypoglycemia in people with type 2 diabetes: A longitudinal nationwide cohort study.

We investigated the associations between a combination of lifestyle factors and changes to these factors and the subsequent risk of severe hypoglycemia (SH) in type 2 diabetes patients. Individuals with adult type 2 diabetes who underwent consecutive 2-year interval health screening programs from 2009 to 2012 from the Korean National Health Insurance Service database were included and followed up until 2018. Information on history of smoking status, alcohol consumption and physical activity, as well as changes to these factors, was obtained. The primary outcome was incident SH. Of the 1,490,233 type 2 diabetes patients, 30,539 (2.1%) patients developed SH. Current smokers and heavy drinkers had increased risk of SH, compared with non-smokers and non-drinkers, respectively (hazard ratio 1.28, 95% confidence interval 1.23-1.34; hazard ratio 1.22, 95% confidence interval 1.15-1.30). However, regular physical activity was associated with reduced SH risk (hazard ratio 0.79, 95% confidence interval 0.77-0.82). A combination of unhealthy lifestyle habits was associated with increased SH risk in a dose-dependent fashion (P for trend <0.001). Compared with participants without changes in their unhealthy lifestyles, participants who improved lifestyles had decreased risk of SH. Greater adherence to healthy lifestyle factors and any improvement in unhealthy lifestyle habits were associated with a substantially lower risk of SH in individuals with type 2 diabetes.

Previously unrecognized risk factors for severe hypoglycaemia requiring emergency medical care in insulin-treated type 2 diabetes: Results from a real-world nested case-control study.

AimSeveral risk factors for severe hypoglycaemia (SH) are associated with insulin‐treated diabetes. This study explored potential risk factors in adults with insulin‐treated type 2 diabetes mellitus (T2DM).Materials and MethodsIn this case‐control study, adults with T2DM initiating insulin were identified in the IQVIA PharMetrics® Plus database. The index date was the date of the first SH event (cases). Using incidence‐density sampling, controls were selected from those who had been exposed ‘at risk’ of SH for the same amount of time as each case. After exact‐matching on the well‐established factors, previously unreported risk factors were evaluated through conditional logistic regression.ResultsIn 3153 case‐control pairs, pregnancy [odds ratios (OR) = 3.20, p = .0003], alcohol abuse (OR = 2.43, p < .0001), short‐/rapid‐acting insulin (OR = 2.22/1.47, p < .0001), cancer (OR = 1.87, p < .0001), dementia/Alzheimer′s disease (OR = 1.73, p = .0175), peripheral vascular disease (OR = 1.59, p < .0001), antipsychotics (OR = 1.59; p = .0059), anxiolytics (OR = 1.51, p = .0012), paralysis/hemiplegia/paraplegia (OR = 1.51, p = .0416), hepatitis (OR = 1.50, p = .0303), congestive heart failure (OR = 1.47, p = .0002), adrenergic‐corticosteroid combinations (OR = 1.45, p = .0165), β‐adrenoceptor agonists (OR = 1.40, p = .0225), opioids (OR = 1.38, p < .0001), corticosteroids (OR = 1.35, p = .0159), cardiac arrhythmia (OR = 1.29. p = .0065), smoking (OR = 1.28, p = .005), Charlson Comorbidity Index score 2 (OR = 1.28, p = .0026), 3 (OR = 1.41, p = .0016) or ≥4 (OR = 1.57, p = .0002), liver/gallbladder/pancreatic disease (OR = 1.26, p = .0182) and hypertension (OR = 1.19, p = .0164) were independently associated with SH.ConclusionsAlthough all people with insulin‐treated diabetes are at risk of SH, these results have identified some previously unrecognized risk factors and sub‐groups of insulin‐treated adults with T2DM at greater risk. Scrutiny of current therapies and comorbidities are advised as well as additional glucose monitoring and education, when identifying and managing SH in vulnerable populations.

Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study

SummaryBackgroundOlder adults with type 1 diabetes have distinct characteristics that can make optimising glycaemic control challenging. We sought to test our hypothesis that hybrid closed-loop glucose control is safe and more effective than sensor-augmented pump (SAP) therapy in older adults with type 1 diabetes.MethodsIn an open-label, multicentre, multinational (UK and Austria), randomised, crossover study, adults aged 60 years and older with type 1 diabetes using insulin pump therapy underwent two 16-week periods comparing hybrid closed-loop (CamAPS FX, CamDiab, Cambridge, UK) and SAP therapy in random order. Block randomisation by means of central randomisation software to one of two treatment sequences was stratified by centre. The primary endpoint was the proportion of time sensor glucose was in target range between 3·9 and 10·0 mmol/L. Analysis for the primary endpoint and adverse events was by intention-to-treat. The study has completed and is registered at ClinicalTrials.gov NCT04025762.Findings38 participants were enrolled. One participant withdrew during run-in because of difficulties with the study pump infusion sets. 37 participants (median [IQR] age 68 [63–70] years, mean [SD] baseline glycated haemoglobin [HbA1c]; 7·4% [0·9%]; 57 [10] mmol/mol) were randomly assigned between Sept 4, 2019, and Oct 2, 2020. The proportion of time with glucose between 3·9 and 10·0 mmol/L was significantly higher in the closed-loop group compared to the SAP group (79·9% [SD 7·9] vs 71·4% [13·2], difference 8·6 percentage points [95% CI 6·3 to 11·0]; p<0·0001). Two severe hypoglycaemia events occurred during the SAP period. There were two non-treatment related serious adverse events: cardiac arrest from pulmonary embolism associated with COVID-19 during the SAP period resulting in death, and a hospital presentation for parenteral hydrocortisone because of COVID-19 in a participant with adrenal insufficiency during the run-in period.InterpretationHybrid closed-loop insulin delivery is safe and achieves superior glycaemic control to SAP therapy in older adults with long duration of type 1 diabetes. Importantly this was achieved without increasing the risk of hypoglycaemia in this population with risk factors for severe hypoglycaemia. This suggests that hybrid closed-loop therapy is a clinically important treatment option for older adults with type 1 diabetes.

A Cross-Sectional study on risk factors for severe hypoglycemia among Insulin-Treated elderly type 2 diabetes Mellitus (T2DM) patients in Singapore

ObjectiveThis study investigates the risk factors for severe hypoglycemia among Southeast Asian T2DM patients. MethodsInsulin-treated T2DM patients greater than 65 years old with HbA1c < 8% were recruited. They completed questionnaires detailing their experience of hypoglycemia and presence of impaired hypoglycemia awareness (IAH). Data on insulin treatment regimens, glycated haemoglobin (Hba1c) and comorbidities were also collected. ResultsOf the 92 participants, 15.2% had at least one episode of severe hypoglycemia over the past year. Comparison between both groups showed that patients with severe hypoglycemia had lower Hba1c, higher Gold score (3.9 ± 1.9 vs. 2.5 ± 1.4; p < .05) and higher Hypoglycemia Fear Survey (HFS) worry score (39.1 ± 14.3 vs. 31.8 ± 11.8; p < .05). There were no significant differences in duration of diabetes and insulin treatment, treatment regimens and diabetes associated comorbidities except peripheral vascular disease. Furthermore, no significant differences were noted in HFS behavior score, hypoglycemia risk modifying behavior and social economic status. ConclusionsPatients with severe hypoglycemia had tighter glycemic control, greater IAH and higher worry scores regardless of treatment regimens. Clinicians may play a significant role in tightening glycemic control and influencing the risk of severe hypoglycemia. Standard structured diabetes education may help reduce the risk of severe hypoglycemia among this group of patients.

The Risk Factors of Severe Hypoglycemia in Older Patients with Dementia and Type 2 Diabetes Mellitus.

Background: The adequate glycemic control and risk factors for hypoglycemia in older patients with dementia and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to analyze the status of glycemic control and determine the risk of hypoglycemia among these groups. Methods: A hospital admission record due to hypoglycemia through an emergency room with glucose supplementation in the Chang Gung Memorial Hospital was identified as a hypoglycemic event. Patients with dementia and T2DM without hypoglycemic events throughout the study period were defined as the control group. We gathered patients aged ≥65 years with a diagnosis of Alzheimer’s dementia (AD) and T2DM between 2001 and 2018 in the Chang Gung Research Database (CGRD). We extracted data included medication use, diagnoses, and biochemistry data from hospital records. Results: A total of 3877 older patients with dementia and T2DM with regular visits to the outpatient department were enrolled in this study. During the two-year follow-up period, 494 participants (12.7%) experienced hypoglycemia. Multivariable logistic multivariable regression models for hypoglycemic events showed that metformin had a protective effect (odds ratio (OR) = 0.75, p = 0.023), insulin had the highest risk (OR = 4.64, p < 0.001). Hemoglobin A1c (HbA1c) levels were not correlated with hypoglycemic events (OR = 0.95, p = 0.140). Patients with hypoglycemic episodes had a significantly higher proportion of ≥2 Charlson Comorbidity Index scores than those without hypoglycemic episodes (83.2% versus 56.4%, p < 0.001). Conclusions: Drug regimen affects hypoglycemic episodes but not HbA1c in older patients with dementia and T2DM. In addition, patients with more comorbidities experience an increased risk of hypoglycemia.

Hypoglycemia in diabetes: An update on pathophysiology, treatment, and prevention

Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. Episodes of hypoglycemia are associated with physical and psychological morbidity. The fear of hypoglycemia constitutes a barrier that impairs the patient’s ability to reach good glycemic control. To prevent hypoglycemia, much effort must be invested in patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control. In this review, we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.

Risk factors for hypoglycaemia in people with diabetes admitted to the Emergency Department of a Hospital in French Guiana.

Strict management of glucose levels in elderly people with diabetes or with comorbidities exposes them to the risk of severe hypoglycaemia (capillary or venous glucose ≤3.3mmol/L) and the associated morbidity and mortality. We aimed to describe the clinical, laboratory, and epidemiological characteristics of people with diabetes admitted to the Emergency Department in Cayenne, French Guiana for severe hypoglycaemia and identify avoidable behaviours in this population. An observational epidemiological study of adults with diabetes who presented to the Emergency Department with severe hypoglycaemia was conducted between 2015 and 2018. Their medical history, clinical and laboratory data were collected. The primary outcome was the association between therapeutic misuse and age ≥65years. Overall, 178 admissions were analysed. The main cause of hypoglycaemia was insulin dosing-error or inappropriate glycaemic targets. Among those ≥65years, 59% had a glycated haemoglobin ≤48mmol/mol (6.5%), and the median duration of their diabetes was 20years. Among them, 60% were treated with sulfonylurea, repaglinide, biphasic insulin, or mixed drugs, and 48% were on non-diabetes related treatments that had a hypoglycaemic effect. Furthermore, 23% of the elderly treated with oral antidiabetics had chronic kidney disease. Many avoidable risk factors for severe hypoglycaemia have been highlighted, in particular insulin dosing errors or non-compliance with recommendations for participants≥65years. Primary care physicians and homecare nurses need to provide preventive interventions and undergo training.

Potential overtreatment of type 2 diabetes therapy in real clinical practice: Omsk Oblast register data

Backgraund: The total number of patients with type 2 diabetes mellitus (T2DM) in the Russian Federation as of 01.01.2019 is 4.24 million. The majority of patients with T2DM are elderly people and older, forming groups with high comorbidity and the risk of severe hypoglycemia, including those associated with excess hypoglycemic therapy. Foreign studies indicate that a significant proportion of older adults with diabetes are potentially exposed to excessive sugar-lowering therapy.Aims: to study the frequency of excessive decrease in HbA1c in a group of patients with T2DM according to a sample from the regional diabetes register.Materials and methods: A content analysis of the regional register of diabetes mellitus was carried out as of ­December 31, 2019. Based on the register data, an individual target level of HbA1c was calculated and the compliance of the achieved HbA1c level with the target level was assessed.Results: The analysis included data from 1202 patients with T2DM, which amounted to 2.35% of the total number of patients with T2DM in the region (n = 51,163). The age of the included individuals was 66 years (LQ 60.0; UQ 72), 360 men (29.95%). The duration of T2DM 8.0 years. The HbA1c level in the general group was 7.1%. Persons over 60 years of age accounted for 75.21% (n = 904). When analyzing HbA1c in the age groups, there were no statistically significant differences (p&gt; 0.05). HbA1c was above the target level in 43.34% of cases (n = 521). The level of HbA1c &lt;6.5% was noted in a quarter of cases (24.62%), including HbA1c &lt;6.0% was recorded in 97 cases, which accounted for a third of all cases of tight glycemic control. At the same time, the majority of observations of HbA1c &lt;6.5% were in patients 60 years and older (79.73%). Among young and middle-aged patients with HbA1c &lt;6.5%, 8.33% of cases had risk factors for severe hypoglycemia in the presence of SU and / or insulin therapy. In the older age group (in comparison with young and middle-aged patients), HbA1c &lt;7% (p &lt;0.05) was significantly more often detected, there was a tendency for a higher frequency of HbA1c &lt;6.5% (p = 0.067). Among elderly and senile patients with HbA1c &lt;6.5%, in 41.53% of cases there were risk factors for severe hypoglycemia, in a quarter of cases in T2DM therapy SU and / or insulin were used (24.58%), almost every fifth patient (19.07%), risk factors for severe hypoglycemia, received SU and / or insulin.Conclusion: According to our data, at least a quarter of patients in the older age group (24.58%) had overtreatment and need de-intensification of therapy. Perhaps that in this group of patients, the risks associated with treatment may outweigh the benefits of tight glycemic control, and these patients require planned de-intensification of glucose-lowering therapy. Taking into account the position of some expert communities on determining the target range of HbA1c in the older age group, the need for de-intensification of antihyperglycaemic therapy may be even higher. Further research is required in order to develop a full-fledged domestic concept of de-intensification of hypoglycemic therapy.

Trends and risk factors in severe hypoglycemia among individuals with type 2 diabetes in Korea

AimsBecause of the development of new classes of antidiabetic drugs, hypoglycemic events were expected to decrease. We investigated the trends and risk factors for severe hypoglycemia in subjects with type 2 diabetes in Korea. MethodsWe conducted repeated cross-sectional analyses using a Korean National Health Insurance Service–National Sample Cohort from 2006 to 2015. Severe hypoglycemia was defined as hospitalization or a visit to an emergency department with diagnosis of hypoglycemia using ICD-10 codes. ResultsDuring the study period, the prevalence of type 2 diabetes continuously increased. The percentage of patients prescribed metformin and dipeptidyl peptidase-4 inhibitor increased, while the use of sulfonylurea decreased considerably, especially since 2009. The proportion of patients prescribed ≥3 classes of drugs continually increased. Age-standardized incidence of severe hypoglycemia per 1000 patients with diabetes increased from 6.00 to 8.24 between 2006 and 2010, and then fell to 6.49 in 2015. Predictors of severe hypoglycemia included female, older age, comorbidities, polypharmacy, and sulfonylurea or insulin usage. ConclusionsTrends of severe hypoglycemia were associated with changes in drug classes rather than number of antidiabetic drugs. Relentless efforts to reduce the prescription of drugs with a high risk of hypoglycemia should be implemented, particularly for older women with multiple comorbidities.

1039-P: Potential Risk Factors for Severe Hypoglycemia in Insulin-Treated Adults with Type 2 Diabetes (T2DM)

Background: In insulin-treated patients (pts) with T2DM, untreated severe hypoglycemia (SH) can be life-threatening. We used a healthcare claims database (db) to identify less established SH risk factors in this group. Methods: Adults with T2DM and ≥1 insulin claim (2012-2018) were identified in IQVIA’s PharMetrics® Plus db. Cases with SH were matched to controls using incidence density sampling and exact matched on well‑known factors (age, sulfonylurea pharmacy claim, prior SH, renal disease). A conditional logistic regression model tested associations between potential risk factors and SH occurrence. Results: In 3153 cases/3153 matched controls, mean ± SD age was 56.2 ± 10.9 years. Identified risk factors included pregnancy (odds ratio for exposure ≤1 mo before SH = 3.2, 95% CI 1.7-6.0) and pharmacy claims: short-acting insulin (2.2, 1.6-3.1), rapid-acting insulin (1.5, 1.3-1.7), anxiolytics (1.5, 1.2-1.9), antipsychotics (1.6, 1.1-2.2), corticosteroids (1.4, 1.1-1.7), opioids (1.4, 1.2-1.6), β-adrenergic agonists (1.4, 1.1-1.9). Higher comorbidity score, alcohol abuse and certain comorbidities also raised SH risk (Fig 1). Conclusion: Acknowledging limitations of claims db analyses, our study identified certain comorbidities and medications (primarily within 1 mo of SH) as additional risk factors for SH. Such data may help facilitate interventions for pts with T2DM at increased SH risk. Disclosure J. Settles: Employee; Self; Eli Lilly and Company. C. J. Child: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Gorritz: Consultant; Self; Amgen Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Otsuka America Pharmaceutical, Inc., Takeda Pharmaceutical Co. J. K. Multani: Other Relationship; Self; Eli Lilly and Company. C. Mcguiness: Research Support; Self; AbbVie Inc., Allergan plc, Amgen Inc., Astellas Pharma Inc., Eli Lilly and Company, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Sanofi, Takeda Pharmaceutical Co. R. Wade: Research Support; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company

Restoration of Hypoglycemia Awareness Alters Brain Activity in Type 1 Diabetes.

Impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D) is a major risk factor for severe hypoglycemia (SH) and is associated with atypical responses to hypoglycemia in brain regions involved in arousal, decision making, and memory. Whether restoration of hypoglycemia awareness alters these responses is unknown. We sought to investigate the impact of awareness restoration on brain responses to hypoglycemia. Twelve adults with T1D and IAH underwent pseudocontinuous arterial spin labeling functional MRI during a hypoglycemic clamp (5-2.6 mmol/L) before and after a hypoglycemia avoidance program of structured education (Dose Adjustment for Normal Eating), specialist support, and sensor-augmented pump therapy (Medtronic MiniMed 640G). Hypoglycemic cerebral blood flow (CBF) responses were compared pre- and postintervention using predefined region-of-interest analysis of the thalamus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and hippocampus. Postintervention, Gold and Clarke scores fell (6.0 ± 1.0 to 4.0 ± 1.6, P = 0.0002, and 5.7 ± 1.7 to 3.4 ± 1.8, P = 0.0008, respectively), SH rates reduced (1.5 ± 2 to 0.3 ± 0.5 episodes per year, P = 0.03), hypoglycemic symptom scores increased (18.8 ± 6.3 to 27.3 ± 12.7, P = 0.02), and epinephrine responses did not change (P = 0.2). Postintervention, hypoglycemia induced greater increases in ACC CBF (P = 0.01, peak voxel coordinates [6, 40, -2]), while thalamic and OFC activity did not change. Increased blood flow is seen within brain pathways involved in internal self-awareness and decision making (ACC) after restoration of hypoglycemia awareness, suggesting partial recovery of brain responses lost in IAH. Resistance of frontothalamic networks, involved in arousal and emotion processing, may explain why not all individuals with IAH achieve awareness restoration with education and technology alone.

Development of a hypoglycaemia risk score to identify high-risk individuals with advanced type 2 diabetes in DEVOTE.

AimsThe ability to differentiate patient populations with type 2 diabetes at high risk of severe hypoglycaemia could impact clinical decision making. The aim of this study was to develop a risk score, using patient characteristics, that could differentiate between populations with higher and lower 2‐year risk of severe hypoglycaemia among individuals at increased risk of cardiovascular disease.Materials and methodsTwo models were developed for the risk score based on data from the DEVOTE cardiovascular outcomes trials. The first, a data‐driven machine‐learning model, used stepwise regression with bidirectional elimination to identify risk factors for severe hypoglycaemia. The second, a risk score based on known clinical risk factors accessible in clinical practice identified from the data‐driven model, included: insulin treatment regimen; diabetes duration; sex; age; and glycated haemoglobin, all at baseline. Both the data‐driven model and simple risk score were evaluated for discrimination, calibration and generalizability using data from DEVOTE, and were validated against the external LEADER cardiovascular outcomes trial dataset.ResultsBoth the data‐driven model and the simple risk score discriminated between patients at higher and lower hypoglycaemia risk, and performed similarly well based on the time‐dependent area under the curve index (0.63 and 0.66, respectively) over a 2‐year time horizon.ConclusionsBoth the data‐driven model and the simple hypoglycaemia risk score were able to discriminate between patients at higher and lower risk of severe hypoglycaemia, the latter doing so using easily accessible clinical data. The implementation of such a tool (http://www.hyporiskscore.com/) may facilitate improved recognition of, and education about, severe hypoglycaemia risk, potentially improving patient care.

155-OR: ADA Presidents’ Select Abstract: Symptom Responses to Hypoglycemia Are Related to Connectivity Change between the Thalamus and Frontal Lobes

Neuroimaging studies highlight the importance of thalamic activation in response to hypoglycemia in people with and without type 1 diabetes (T1D). This activation is characteristically attenuated in impaired awareness of hypoglycaemia (IAH), a major risk factor for severe hypoglycemia. We investigated changes in connectivity of the thalamus with other brain regions during hypoglycemia. Methods: Fourteen people without diabetes (no diabetes, ND), 15 with T1D and normal awareness of hypoglycemia (NAH) and 22 with IAH, all right-handed, age, sex and gender matched, underwent a hyperinsulinemic glucose clamp during which we acquired blood oxygen level dependent fMRI at euglycemia (90mg/dL) and at onset of hypoglycemia (48mg/dL). Connectivity was studied using the CONN toolbox in SPM12. A thalamic seed was used in a seed-to-voxel analysis with and without the increase in symptoms at hypoglycemia as an explanatory regressor variable. Results: Symptom scores in response to hypoglycemia rose earliest and to the greatest levels in NAH (11.0 to 18.3, p= 0.029). The rise in symptom scores in ND was not significant at this timepoint (9.2 to 13.8, p= 0.057), whilst IAH showed no symptom change (10.5 to 9.8, p= 0.7). In ND, hypoglycemia increased thalamic connectivity with the right frontal pole (pFDR = 0.018). This did not occur in diabetes, either in NAH or IAH. The NAH group demonstrated a positive relationship between change in symptoms with change in connectivity of the thalamus and a left frontal pole region (pFDR = 0.035), whereas an overlapping area had a negative correlation in ND (pFDR = 0.001). There was no correlation in IAH. Conclusion: During hypoglycemia, those with T1D display aberrantly enhanced thalamic connectivity with brain regions responsible for complex behavior. Disruption of this network occurs in IAH and may be the mechanism for failure of perception of the onset of hypoglycemia and reduced hypoglycemia avoidance behaviors, increasing severe hypoglycemia risk. Disclosure P. Jacob: None. M. Nwokolo: Other Relationship; Self; Sanofi. O. ODaly: None. F.O. Zelaya: None. S.A. Amiel: Advisory Panel; Self; Medtronic, Novo Nordisk A/S, Roche Pharma. Other Relationship; Self; Diabetes UK. P. Choudhary: Advisory Panel; Self; Abbott, Eli Lilly and Company, Insulet Corporation, Medtronic. Research Support; Self; European Union, JDRF. Speaker’s Bureau; Self; Dexcom, Inc., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis. Funding JDRF (3-SRA-2017-484-S-B)

1619-P: Trends in Severe Hypoglycemia and Mortality in Individuals with Type 1 Diabetes

Background: Hypoglycemia is one of the major complications in the management of individuals with type 1 diabetes, and severe hypoglycemia increases the risk of mortality. Objective: To investigate trends and risk factors for severe hypoglycemia and mortality in individuals with type 1 diabetes. Methods: We evaluated age- and sex-standardized annual incidence rates of severe hypoglycemia requiring hospitalization and mortality in individuals with type 1 diabetes using the Korean National Health Insurance Service Database from 2002 to 2016. Results: Age- and sex-standardized incidence rates of severe hypoglycemia have increased from 2002 to 2016 in individuals with type 1 diabetes (5.79 per 1,000 in 2002-2004 to 12.57 per 1,000 in 2015-2016, P for trend &amp;lt; 0.0001). Individuals with severe hypoglycemia had significantly lower body weight (64.8 ± 12.4 kg vs. 57.7 ± 9.5 kg; P &amp;lt; 0.0001) and higher proportions of chronic kidney disease (2.5% vs. 5.3%, P = 0.0012) and end-stage renal disease (0.6% vs. 2.0%, P = 0.0071) compared with those without severe hypoglycemia. However, age- and sex-standardized mortality has decreased in both individuals with and without severe hypoglycemia (P for trends &amp;lt; 0.001). The use of new-generation insulin analogs was associated with a lower risk of severe hypoglycemia and mortality. Conclusion: The incidence rates of severe hypoglycemia have significantly increased, while the mortality has significantly decreased in Korean individuals with type 1 diabetes from 2002 to 2016. Disclosure J. Bae: None. K. Kim: None. J. Kim: None. S. Kim: None. N. Kim: None.

The use of statins in the elderly is associated with less severe hypoglycemia in patient with diabetes

Three hundred and eighty-nine older patients with diabetes attending an ambulatory diabetes center were included to determine risk factors of severe hypoglycemia (SH). Thirty-three (8.5%) patients had at least one severe hypoglycemia. In multivariate analyze, statin was associated with lower risk and insulin was associated with higher risk of SH.