Insulin Treatment Regimens Research Articles

1817-PUB: CGM-Derived Metrics and HbA1c in Adults with Type 2 Diabetes (T2D) on Different Insulin Treatment Regimens Not Meeting Glycemic Targets

Objective: Despite advances in treatment strategies, many individuals with T2D treated with insulin still struggle with inadequate glycemic control. The aim was to describe CGM-derived metrics and HbA1c for adults with T2D and HbA1c ≥7.5% (≥58 mmol/l) using different insulin treatment regimens; basal insulin only or multiple daily injections (MDI). Methods: Baseline characteristics of participants with T2D entering a randomized controlled trial on the efficacy of using CGM were analyzed including CGM-derived metrics from 10 days blinded CGM (Dexcom G6). Results: Included were 96 adults (men 61.5%, age 61 (54-67) years and BMI 30.7 (26.7-35.7) kg/m2, all median (+IQR)). Compared to adults on basal insulin only, the MDI treated had a longer diabetes duration of 22 (19-25) vs 18 (14-22) years, a higher HbA1c 9.2 (8.6-9.7) vs 8.3 (7.8-9.1) % and a lower C-peptide 396 (217-630) vs 745 (504-1178) pmol/l. There were no differences in time in range or mean sensor glucose. In contrast, the MDI treated had less time above range (28 (21-32) vs 33 (25-42) %) but a higher coefficient of variation (32 (26-36) vs 26 (23-31)%) and a higher time below range (<3.0 mmol/l). Conclusion: These results suggest that while MDI treatment may be associated with higher HbA1c levels and greater glycemic variability, this is not consistently reflected in all CGM-derived metrics. Disclosure N.Lind: None. M.B.Christensen: Speaker's Bureau; Novo Nordisk A/S, Sanofi. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk, Research Support; Medtronic, Dexcom, Inc., Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Novo Nordisk, Stock/Shareholder; Novo Nordisk.

Knowledge, practice, and challenges of diabetes foot care among patients at the University of Benin Teaching Hospital, Benin City: A cross-sectional study.

Foot ulcer is a common complication of diabetes and the most devastating component of diabetes progression that is associated with high morbidity and mortality. The aim of this study was to assess the knowledge, practice, and challenges of diabetes foot care among patients with diabetes mellitus. This descriptive cross-sectional study assessed knowledge and practice of foot care among type I and type II patients with diabetes attending the University of Benin Teaching Hospital, Benin City. The instrument for data collection was a structured questionnaire with a reliability of 0.880. SPSS version 22 was used to analyze the data. The findings revealed that there is good knowledge of foot care, among 110 (50.0%) of the diabetic patients, while the practice of foot care was found to be poor among diabetic patients. It also shows the factor that statistically predicts the development of foot ulcers to include combined diet + oral medications + insulin treatment regimen (adjusted odds ratio [AOR] = 0.181, P = 0.016, confidence interval [CI] = 0.045-0.728), history of renal conditions (AOR = 0.115, P = 0.036, CI = 0.015-0.871), not receiving foot care education (AOR = 116.098, P < 0.001, CI = 12.497-1078.554), and receiving foot care education from nurses (AOR = 0.022, P = 0.001, CI = 0.002-0.216). Furthermore, 201 (91.4%) diabetes patients reported fatigue from completing the same task repeatedly, and 198 (90.0%) reported forgetfulness as obstacles to practicing foot care. When creating DM Patients future care plans, nurses and other health-care administrators must take into account the difficulties and predicting factors related to the practice of diabetes foot care.

Regimen comprising GLP-1 receptor agonist and basal insulin can decrease the effect of food on glycemic variability compared to a pre-mixed insulin regimen

BackgroundIncreasing evidence suggests that glucagon-like peptide 1 (GLP-1) receptor agonists (RA) can stabilize glycemic variability (GV) and interfere with eating behavior. This study compared the impact of insulin, GLP-1 RA, and dietary components on GV using professional continuous glucose monitoring (CGM).MethodsPatients with type 2 diabetes underwent CGM before and after switching from a twice-daily pre-mixed insulin treatment regimen to a GLP-1 RA (liraglutide) plus basal insulin regimen. The dietary components were recorded and analyzed by a certified dietitian. The interactions between the medical regimen, GV indices, and nutrient components were analyzed.ResultsSixteen patients with type 2 diabetes were enrolled in this study. No significant differences in the diet components and total calorie intake between the two regimens were found. Under the pre-mixed insulin regimen, for increase in carbohydrate intake ratio, mean amplitude of glucose excursion (MAGE) and standard deviation (SD) increased; in contrast, under the new regimen, for increase in fat intake ratio, MAGE and SD decreased, while when the protein intake ratio increased, the coefficient of variation (CV) decreased. The impact of the food intake ratio on GV indices disappeared under the GLP-1 RA regimen. After switching to the GLP-1 RA regimen, the median MAGE, SD, and CV values decreased significantly. However, the significant difference in GV between the two regimens decreased during the daytime.ConclusionA GLP-1 RA plus basal insulin regimen can stabilize GV better than a regimen of twice-daily pre-mixed insulin, especially in the daytime, and can diminish the effect of food components on GV.

InsulinAPP application protocol for the inpatient management of type 2 diabetes on a hospitalist-managed ward: a retrospective study.

We assessed metrics related to inpatient glycemic control using InsulinAPP, an application available for free in Brazil, on the hospitalist-managed ward of our hospital. We performed a retrospective study of patients with type 2 diabetes (T2D) admitted from November 2018 to October 2019. InsulinAPP recommends NPH and regular insulins three times a day, in bolus-correction or basal-bolus schemes. Parameters that included BG within range of 70-180 mg/dL, insulin treatment regimen and frequency of hypoglycemia were evaluated. A total of 147 T2D individuals (23% medicine and 77% surgery) were included (mean age 62.3 ± 12.7 years, HbA1c: 8.3 ± 3.0%). The initial insulin regimen was 50% bolus-correction, 47% basal-bolus and 3% with sliding scale insulin. During hospitalization, 71% patients required a bolus-basal regimen. In the first 10 days of the protocol, 71% BG measurements were between 70-180 mg/dL and 26% patients experienced one or more episodes of hypoglycemia < 70 mg/dL, and 5% with BG < 54 mg/dL. The results of this retrospective study indicate the InsulinAPP application using human insulin formulations was effective and safe for the management of hyperglycemia on a hospitalist-managed ward, with more than 70% BG measurements within the therapeutic range and a low rate of hypoglycemia.

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.

LIPODYSTROPHY FREQUENCY ACCORDING TO INSULIN TREATMENT REGIMEN IN TYPE 2 DIABETIC PATIENTS: IS INSULIN INJECTION FREQUENCY MATTERS IN ANALOG INSULIN ERA?

We aimed to determine lipodystrophy frequency according to insulin treatment regimen and insulin injection frequency in type 2 diabetic patients. A total of 345 type 2 diabetic patients under insulin treatment for at least one year were included in this cross-sectional study. Patients were examined for presence of lipodystrophy, insulin injection frequency and dosage. Lipodystrophy was evaluated with visual inspection and palpation of all injection sites. Patients were evaluated into three categories according to daily insulin dose requirement: Group 1= Standard-dose insulin users 0.6 U/kg/day; Group 2= Medium-dose insulin users 0.61-1.9 U/kg/day, Group 3= High-dose insulin users ≥2 U/kg/day. Lipodystrophy was seen in 28% of the patients. Lipodystrophy was significantly higher in group 3. There was no significant difference between the groups in terms of lipodystrophy size. Duration of insulin treatment, daily total insulin dose, daily insulin dose per weight and number of daily insulin injections were significantly higher in the group with lipodystrophy. Daily injection number of long-acting, rapidly-acting analog and total insulin injections were significantly higher in group 3 than group 1 and 2. Number of daily insulin injections and lipodystrophy frequency were significantly higher in basal-bolus insulin user group. Multivariate analysis showed that insulin injection frequency is the independent risk factor for lipodystrophy. Lipodystrophy is still a clinical problem in patients with high-dose insulin requirement and frequent insulin injections. Reducing daily insulin requirement and daily number of injections should be given priority in the management of patients to prevent the development of lipodystrophy.

Clinical Considerations for Insulin Therapy in Older Adults with Type 1 Diabetes.

Type 1 diabetes represents an autoimmune condition with a strong inherited background, and its incidence is increasing worldwide. About 25% of such cases are diagnosed in adulthood, some even as late as the ninth decade of life. The number of older adults with type 1 diabetes is increasing due to improvements in care and decreased mortality rate. However, there is a lack of clinical trials in people older than 70 years of age with type 1 diabetes complicated with comorbidities, frailty, and dependency. The management of type 1 diabetes and the goals of therapy should be individualized based on the patient's health status and life expectancy. In healthier older adults, insulin treatment regimens (multiple daily insulin injections or insulin pump therapy) that approximate the normal physiology of insulin secretion should be used to achieve lower glycemic goals, while reducing the risk of hypoglycemia with frequent glucose monitoring (preferably using continuous glucose monitoring systems). For frail individuals with poor health, simpler insulin regimens and less stringent glycemic targets would be more appropriate. Poor cognition, vision and hearing, impaired mobility, depression, and chronic pain can interfere with complex insulin regimens. In these individuals, the principal goals of therapy are to reduce the acute effects of hyperglycemia, minimize hypoglycemia risk, and optimize quality of life. The newer insulin preparations and technological advances in insulin delivery and blood glucose monitoring have enhanced the management of type 1 diabetes in all age groups.

Ketogenic Diet in a Patient With Type 1 Diabetes Mellitus With Hypoglycemia Unawareness

Abstract Introduction: The high fat, low carbohydrate ketogenic diet has become increasingly popular in recent years for weight loss and glycemic control in patients with type 2 diabetes. Although prior studies have suggested this diet can improve glycemic control and decrease glucose variability, the impact of a ketogenic diet on rates of hypoglycemia in patients with hypoglycemia unawareness is not well described. Case Description: Our patient is a 37 year-old woman with Type 1 diabetes for 13 years complicated by hypoglycemia unawareness with HbA1c of 7.7%. Her insulin treatment regimen included insulin glargine 22 units daily, insulin aspart using a 1:15 carbohydrate ratio for prandial insulin dosing with a correction factor of 90. She had 5 episodes of severe hypoglycemia within the previous 3 months. The patient decided to resume a ketogenic diet given her previous improvement in glycemic control. Ketosis was confirmed using urine ketone strips performed by the patient. After 2 weeks on the ketogenic diet, a professional blinded continuous glucose monitor (CGM) was used for 4 weeks to monitor glycemic control. CGM data for weeks 1 and 2 showed overall stability of time in target glucose range [TIR, 60% and 69%, respectively], with a slight increase in time spent below range [TBR, 13% and 17%, respectively]. During week 3, the patient experienced a significant decline in TIR to 31%, and associated increase in hypoglycemia (TBR, 13% to 28%). In addition, glycemic variability increased during this time [CV (coefficient of variation), 40.6% during week 1 to 58.1% during week 3]. Patient did not experience symptoms concerning for DKA, and continued to have asymptomatic hypoglycemia despite reductions in her insulin doses during week 3. Following these dose adjustments, CGM data during week 4 were similar to week 1 (TIR 65%, TBR 10%, CV 35%). Patient stopped following the ketogenic diet after 6 weeks due to social factors. Conclusion: A ketogenic diet was associated with increased frequency of hypoglycemic events. In a patient with Type 1 diabetes and hypoglycemia unawareness, use of ketogenic diet may further increase the risk of severe hypoglycemia.

Treatment Costs of Basal Insulin Regimens for Type 2 Diabetes Mellitus in France.

ObjectiveOur objectives were to describe the basal insulin treatment regimens most widely used in a real-world setting in France and to estimate the associated treatment costs in people with type 2 diabetes mellitus (T2DM).MethodsA cross-sectional observational study was conducted (November 2017–February 2018) among adult patients with T2DM requiring basal insulin therapy for their own use in a representative sample of pharmacies. Costs were compared between patients treated with three recently marketed insulins (glargine 300 U/ml [Gla-300], biosimilar glargine 100 U/ml [Gla-100] and a fixed-ratio combination of insulin degludec and liraglutide) and those treated with three established basal or intermediate insulins: branded glargine 100 U/ml, insulin detemir and neutral protamine Hagedorn insulin [NPH]).ResultsOverall, 1933 patients were analysed. Gla-300 accounted for 59.9% of novel basal insulin prescriptions, and branded Gla-100 accounted for 67.9% of established insulin prescriptions. Recent insulins were more frequently associated with glucagon-like peptide-1 (GLP-1) analogues. Results confirmed a lower rate of severe hypoglycaemia with Gla-300 than with Gla-100. On average, weekly total costs of treatment with all basal insulins were not significantly different, except with detemir, where they were higher.ConclusionNew basal insulins are expected to be integrated into clinical practice. This analysis shows that their use does not impact upon the management cost of insulin therapy in people with T2DM.Electronic supplementary materialThe online version of this article (10.1007/s41669-020-00237-4) contains supplementary material, which is available to authorized users.

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.

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.

Long-term prognostic role of diabetes mellitus and glycemic control in heart failure patients with reduced ejection fraction: Insights from the MECKI Score database

BackgroundThe prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population. Methods3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70–6.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): <7% (n = 266), 7.1–8% (n = 133), >8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death. ResultsFor all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c >8% patients (Log-Rank p < 0.001), even after correction for confounding factors. All results were replicated by hazard ratio analysis. ConclusionIn HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control.

Safety of lixisenatide plus basal insulin treatment regimen in Indian people with type 2 diabetes mellitus during Ramadan fast: A post hoc analysis of the LixiRam randomized trial

AimsHypoglycemia is one of the most important complications associated with Ramadan fasting in people with type 2 diabetes. LixiRam (NCT02941367) was the first randomized trial comparing safety and efficacy of lixisenatide + basal insulin (BI) vs. sulphonylurea + BI in people with type 2 diabetes who fast during Ramadan. This post hoc analysis focuses on the LixiRam study population from India. MethodsAdults with type 2 diabetes insufficiently controlled with sulphonylurea + BI ± another oral anti-hyperglycemic drug were randomized 1:1 to receive lixisenatide + BI or to continue sulphonylurea + BI treatment. ResultsIn total, 150 participants were randomized in India. One participant (1.3%) with lixisenatide + BI vs. 5 participants (6.8%) with sulphonylurea + BI experienced ≥1 documented symptomatic hypoglycemic event during the Ramadan fast (odds ratio [OR]: 0.22; 95% confidence interval [CI]: 0.02–1.93). Incidence of any hypoglycemia was numerically lower with lixisenatide + BI vs. sulphonylurea + BI during Ramadan fasting (1.3% [1/75] vs. 14.7% [11/75], respectively; OR: 0.09; 95% CI: 0.01–0.69). No new safety signals were identified. ConclusionsA combination of lixisenatide prandial GLP1-RA + BI may be a suitable treatment option for people with type 2 diabetes who elect to fast during Ramadan.Clinical Trial Registry: clinicaltrials.gov (NCT02941367).

Factors predicting poor glycemic control in the first two years of childhood onset type 1 diabetes in a cohort from East London, UK: Analyses using mixed effects fractional polynomial models.

Background/ObjectivePoor early glycemic control in childhood onset type 1 diabetes (T1D) is associated with future risk of acute and chronic complications. Our aim was to identify the predictors of higher glycated hemoglobin (HbA1c) within 24 months of T1D diagnosis in children and adolescents.MethodsMixed effects models with fractional polynomials were used to analyze longitudinal data of patients <19 years of age, followed from T1D diagnosis for up to 2 years, at three diabetes clinics in East London, United Kingdom.ResultsA total of 2209 HbA1c observations were available for 356 patients (52.5% female; 64.4% non‐white), followed from within 3 months of diagnosis during years 2005 to 2015, with a mean ± SD of 6.2 ± 2.5 HbA1c observations/participant. The mean age and HbA1c at diagnosis were 8.9 ± 4.3 years and 10.7% ±4.3% (or expressed as mmol/mol HbA1c mean ± SD 92.9 ± 23.10 mmol/mol) respectively.Over the 2 years following T1D diagnosis, HbA1c levels were mostly above the National Institute for Health, Care and Excellence (NICE), UK recommendations of 7.5% (<58 mmol/mol). Significant (P < .05) predictors of poorer glycemic control were: Age at diagnosis (12‐18 years), higher HbA1c at baseline (>9.5%, ie, >80 mmol/mol), clinic site, non‐white ethnicity, and period (pre‐year 2011) of diagnosis. Additionally in univariable analyses, frequency of clinic visits, HbA1c at diagnosis, and type of insulin treatment regimen showed association with poor glycemic control (P < .05).ConclusionsMajor risk factors of poorer glycemic control during 3‐24 months following childhood onset T1D are: diagnosis prior to 2011, higher HbA1c levels at baseline, age at diagnosis, non‐white ethnicity, and clinic site.

Fasting during the holy month of Ramadan among older children and adolescents with type 1 diabetes in Kuwait.

Background To evaluate the safety of fasting during the holy month of Ramadan among children and adolescent with type 1 diabetes (T1D). Methods A retrospective cohort study of 50 children and adolescents with T1D whose mean age was 12.7 ± 2.1 years was conducted. Twenty-seven patients (54%) were on multiple daily injections (MDI) insulin regimen and 23 (46%) were on insulin pump therapy. Before fasting for Ramadan, children and their families were evaluated and educated about diabetes management during Ramadan. Hemoglobin A1c (HbA1c), weight, number of days fasted, hypoglycemia and hyperglycemia episodes, and emergency hospital visits were collected and analyzed after completing the month. Participants were compared according to the insulin treatment regimen and their glycemic control level before Ramadan. Results The children were able to fast 20 ± 9.9 days of Ramadan, and the most common cause for breaking the fast was mild hypoglycemia (7.8% among all cases). There was no significant difference between the two insulin regimen groups in breaking fast days, frequency of hypo- or hyperglycemia, weight and HbA1c changes post Ramadan. Patients with HbA1c ≤ 8.5% were able to fast more days during Ramadan with significantly less-frequent hypoglycemic attacks as compared to patients with HbA1c > 8.5 (1.2 ± 1.5 vs. 3.3 ± 2.9 days of hypoglycemia, p = 0.01, respectively). Conclusions Fasting for children with T1D above the age of 10 years is feasible and safe in both pump and non-pump users, and well-controlled patients are less likely to develop complications. Education of the families and their children before Ramadan, along with intensive monitoring of fasting children during the month are crucial.

799-P: Vascular Structure and Functional Responses to Consecutive High-Fat Feeding between Insulin Treatment Regimens in Adults with Type 1 Diabetes and Matched Controls

Background: Impaired vascular health is prevalent in type 1 diabetes (T1D); however, it remains unknown whether different insulin treatment regimens mediate indices of vascular structure or function. Methods: Sixteen individuals with T1D receiving either multiple daily injection therapy (MDI; n=8; age: 32±13years; BMI:26.0±5.9kg.m2; HbA1c:53.7±11.2mmol/mol [7.1±3.2%]) or continuous subcutaneous insulin infusion (CSII; n=8; age:35±18years; BMI:26.3±4.6kg.m2; HbA1c: 58.6±9.7mmol/mol [7.5±3.0%]) and ten matched controls (CON; age:31±13years; BMI: 24.3±2.9kg.m2) consumed two high fat (HF) meals at 4-hour intervals. Carotid artery intima-media thickness (CIMT) and flow mediated dilation (FMD) was assessed at baseline, with further FMD assessment at 3-hours following the ingestion of each meal using high resolution B-mode ultrasound. Bolus insulin dose was standardized using the carbohydrate-counting method. Results: CIMT was significantly higher in individuals with T1D compared to controls (p=0.039); treatment stratification within T1D revealed MDI mediated this effect (MDI vs. CON: p=0.049; CSII vs. CON: p=0.112). FMD remained unchanged following the first meal (p=0.204) but was significantly impaired following the second meal (p=&amp;lt;0.001); post hoc analysis revealed MDI mediated this effect of impaired FMD after the second meal (MDI vs. CON: p=0.048; CSII vs. CON: p=0.416). Conclusions: Our findings indicate that patients treated with MDI therapy have higher CIMT (a structural marker of subclinical atherosclerosis) compared to controls but not CSII therapy. FMD was impaired following a second HF meal irrespective of a diabetes status. Considering the pre-existing heightened cardiovascular disease risk in T1D therapeutic strategies to reduce postprandial risk warrants further research. Disclosure L.L. O'Mahoney: None. A. Stavropoulos: None. K. Birch: None. R. Ajjan: Consultant; Self; Abbott. Research Support; Self; Abbott, LifeScan, Inc. O.J. Price: None. M. Campbell: None.

Continuous subcutaneous insulin infusion versus multiple daily injections in children and young people at diagnosis of type 1 diabetes: the SCIPI RCT.

The risk of developing long-term complications of type 1 diabetes (T1D) is related to glycaemic control and is reduced by the use of intensive insulin treatment regimens: multiple daily injections (MDI) (≥ 4) and continuous subcutaneous insulin infusion (CSII). Despite a lack of evidence that the more expensive treatment with CSII is superior to MDI, both treatments are used widely within the NHS. (1) To compare glycaemic control during treatment with CSII and MDI and (2) to determine safety and cost-effectiveness of the treatment, and quality of life (QoL) of the patients. A pragmatic, open-label randomised controlled trial with an internal pilot and 12-month follow-up with 1 : 1 web-based block randomisation stratified by age and centre. Fifteen diabetes clinics in hospitals in England and Wales. Patients aged 7 months to 15 years. Continuous subsutaneous insulin infusion or MDI initiated within 14 days of diagnosis of T1D. Data were collected at baseline and at 3, 6, 9 and 12 months using paper forms and were entered centrally. Data from glucometers and CSII were downloaded. The Health Utilities Index Mark 2 was completed at each visit and the Pediatric Quality of Life Inventory (PedsQL, diabetes module) was completed at 6 and 12 months. Costs were estimated from hospital patient administration system data. The primary outcome was glycosylated haemoglobin (HbA1c) concentration at 12 months. The secondary outcomes were (1) HbA1c concentrations of < 48 mmol/mol, (2) severe hypoglycaemia, (3) diabetic ketoacidosis (DKA), (4) T1D- or treatment-related adverse events (AEs), (5) change in body mass index and height standard deviation score, (6) insulin requirements, (7) QoL and (8) partial remission rate. The economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained. A total of 293 participants, with a median age of 9.8 years (minimum 0.7 years, maximum 16 years), were randomised (CSII, n = 149; MDI, n = 144) between May 2011 and January 2015. Primary outcome data were available for 97% of participants (CSII, n = 143; MDI, n = 142). At 12 months, age-adjusted least mean squares HbA1c concentrations were comparable between groups: CSII, 60.9 mmol/mol [95% confidence interval (CI) 58.5 to 63.3 mmol/mol]; MDI, 58.5 mmol/mol (95% CI 56.1 to 60.9 mmol/mol); and the difference of CSII - MDI, 2.4 mmol/mol (95% CI -0.4 to 5.3 mmol/mol). For HbA1c concentrations of < 48 mmol/mol (CSII, 22/143 participants; MDI, 29/142 participants), the relative risk was 0.75 (95% CI 0.46 to 1.25), and for partial remission rates (CSII, 21/86 participants; MDI, 21/64), the relative risk was 0.74 (95% CI 0.45 to 1.24). The incidences of severe hypoglycaemia (CSII, 6/144; MDI, 2/149 participants) and DKA (CSII, 2/144 participants; MDI, 0/149 participants) were low. In total, 68 AEs (14 serious) were reported during CSII treatment and 25 AEs (eight serious) were reported during MDI treatment. Growth outcomes did not differ. The reported insulin use was higher with CSII (mean difference 0.1 unit/kg/day, 95% CI 0.0 to 0.2 unit/kg/day; p = 0.01). QoL was slightly higher for those randomised to CSII. From a NHS perspective, CSII was more expensive than MDI mean total cost (£1863, 95% CI £1620 to £2137) with no additional QALY gains (-0.006 QALYs, 95% CI -0.031 to 0.018 QALYs). Generalisability beyond 12 months is uncertain. No clinical benefit of CSII over MDI was identified. CSII is not a cost-effective treatment in patients representative of the study population. Longer-term follow-up is required to determine if clinical outcomes diverge after 1 year. A qualitative exploration of patient and professional experiences of MDI and CSII should be considered. Current Controlled Trials ISRCTN29255275 and EudraCT 2010-023792-25. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 42. See the NIHR Journals Library website for further project information. The cost of insulin pumps and consumables supplied by F. Hoffman-La Roche AG (Basel, Switzerland) for the purpose of the study were subject to a 25% discount on standard NHS costs.

Risk of hypoglycemia in youth with type 2 diabetes on insulin.

The objective of this study was to ascertain the risk of hypoglycemia among youth with type 2 diabetes (T2D) on insulin therapy. Twenty-two youth with T2D on insulin therapy (M=12, F=10, age=14.4±4.0 years) were enrolled from a single pediatric endocrine practice. They were followed-up for 3 months with weekly phone calls and monthly in-person visits to review blood glucose logs and document any signs or symptoms of hypoglycemia (defined as finger stick glucose of ≤70 mg/dL). Episodes of hypoglycemia were categorized into five categories: severe, documented symptomatic, asymptomatic, probable symptomatic and relative hypoglycemia. In addition to examining the risk of hypoglycemia, the degree to which hypoglycemia was associated with patient demographics (e.g. age, gender and body mass index [BMI]) or clinical factors (i.e. duration of diabetes, duration of insulin treatment, glycemic control or insulin dose and regimen) was determined. Nine hypoglycemic events occurred during the study period in five patients with an incidence rate of nine events per 5.3 patient-years. Of the hypoglycemic events, five were symptomatic and four were asymptomatic. No severe hypoglycemic events occurred. Hypoglycemia was not associated with age, ethnicity, duration of insulin treatment, insulin dose or initial hemoglobin (HbA1c). However, a significant difference in BMI was noted, with T2D youth who experienced hypoglycemia having a lower BMI than those who did not experience hypoglycemia. The results of this study suggest that the risk of hypoglycemia in youth with T2D on insulin therapy is low.

A Retrospective Cohort Study of Patients with Type 2 Diabetes in China: Associations of Hypoglycemia with Health Care Resource Utilization and Associated Costs.

IntroductionThis study aimed to examine the associations of hypoglycemia with health care resource utilization (HCRU) and health care costs among patients with type 2 diabetes mellitus (T2DM) in China.MethodsThis retrospective cohort study was conducted with 23,680 T2DM patients >18 years old who visited the Second Affiliated Hospital of Nanchang University between 1 January 2011 and 31 December 2015. Univariate descriptive statistics were used to relate the HCRU and associated costs to patient characteristics, and regression analysis was used to examine the association between hypoglycemia and HCRU, controlling for other confounding factors.ResultsIn the T2DM patients with or without insulin treatment, when compared with nonhypoglycemic patients, hypoglycemia was associated with more medical visits (all T2DM patients 19.48 vs. 10.46, insulin users 23.45 vs. 14.12) and higher diabetes-related medical costs (all T2DM patients ¥5187.54 vs. ¥3525.00, insulin users ¥6948.84 vs. ¥3401.15) and medication costs (T2DM patients ¥1349.40 vs. ¥641.92, insulin users: ¥1363.87 vs. ¥853.96). Controlling for age, gender, and Charlson comorbidity index (CCI) score, hypoglycemia and insulin intake were associated with greater health care resource utilization. As compared to nonhypoglycemic patients, hypoglycemic T2DM patients and those on insulin therapy performed more outpatient visits (proportions of hypoglycemic vs nonhypoglycemic T2DM patients performing 3+ visits: 72.69% vs. 65.49%; proportions of hypoglycemic vs nonhypoglycemic patients on insulin therapy performing 3+ visits: 78.26% vs. 71.73%) and were hospitalized more often (proportions of hypoglycemic vs nonhypoglycemic T2DM patients with 3+ admissions 75.90% vs. 50.24%; proportions of hypoglycemic vs nonhypoglycemic patients on insulin therapy with 3+ admissions: 83.19% vs. 58.51%).ConclusionHypoglycemia in diabetes patients was associated with increased healthcare resource utilization and health-related expenditure, especially for patients on insulin treatment. Insulin treatment regimens should be more individualized and account for hypoglycemia risk.

Severe hypoglycemia and diabetic ketoacidosis in young persons with preschool onset of type 1 diabetes mellitus: An analysis of three nationwide population-based surveys.

To describe incidence rates and temporal trends of severe hypoglycemia (SH) and of hospitalizations for SH or diabetic ketoacidosis (DKA) in persons with early-onset, long-term type 1 diabetes (T1D) and associations of these short-term complications with potential risk factors. This study includes data of 1,875 persons 11.2 to 21.9 years of age with early-onset (<5 years) and long-term (>10 years) T1D from 3 cross-sectional nationwide, population-based surveys conducted in 2009/2010, 2012/2013 and 2015/2016 using standardized questionnaires. Negative binomial regression was used to estimate incidence rates per 100 person-years (py), temporal trends and associations between potential risk factors and outcomes. The crude incidence rate of SH showed a decreasing trend over time (P for trend = .004), disappearing after adjustment for confounders (P for trend = .341). In contrast, adjusted rates of SH- and DKA-associated hospitalizations did not change significantly between 2009 and 2016 (P for trend = .306 and .774, respectively). Associations between sex, diabetes duration, insulin treatment regimen, hypoglycemia awareness as well as physical activity and SH were found, while family structure was associated with hospitalizations for SH. Family structure, socioeconomic status (SES), diabetes duration, and hemoglobin A1c values showed associations with DKA-related hospitalizations. After adjustment, rates of SH and SH- or DKA-associated hospitalization showed no significant changes in recent years. Structured education programs focusing on high-risk groups as, for example, persons with T1D living with 1 biological parent and the parents' partner or those with a low SES, should be implemented to reduce incidence rates of hospitalizations.