Basal-bolus Insulin Therapy Research Articles

908-P: Accuracy Comparison of the Freestyle Libre Pro Continuous Glucose Monitoring (CGM) and Point-of-Care (POC) Testing in Noncritically Ill Hospitalized Patients with Type 2 Diabetes Treated with Basal-Bolus Insulin Regimen

Background: There are no published studies assessing the accuracy of the FreeStyle Libre CGM in the inpatient management of patients with type 2 diabetes (T2D). Methods: Adult patients (n: 81) on basal-bolus insulin therapy with a target BG between 70-180 mg/dl were monitored with POC before meals and bedtime and by CGM. The primary outcome was the mean amplitude relative difference (MARD) between matched glucose pairs obtained from POC and CGM. Results: Among 1453 pairs, the overall MARD was 14.4%. The overall percentage of glucose values within ±15% or 15mg/dl, ±20% or 20mg/dl, and ±30% or 30mg/dl of the POC reference value was 63%, 78%, and 92%, respectively. Clarke Error Grid analysis showed acceptable clinical accuracy with 98.0% of glucoses falling into Zones A (76.8%, n: 1,116) and B (22.0%, n: 320). Accuracy was lower for glucoses < 80 mg/dL (Table 1), however; there were limited matched glucose pairs in hypoglycemic range. Conclusions: FreeStyle Libre CGM showed an overall satisfactory performance in hospitalized patients, with lower accuracy observed for glucoses < 80 mg/dL. Larger inpatient studies are needed to confirm its accuracy in non-critically ill hospitalized patients. *Proportion of CGM values within ±15%/±15 mg/dL of POC glucose values, and the analogous %20/20, %30/30 Disclosure R.J. Galindo: Advisory Panel; Self; Abbott, Novo Nordisk Inc., Sanofi US. Research Support; Self; Novo Nordisk Inc. M.A. Urrutia: None. G. Davis: None. A. Khowaja: None. B.S. Albury: None. I. Anzola: None. A.A. Johnson: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. Research Support; Self; National Institutes of Health. S. Cardona: None. M. Fayfman: None. A. Migdal: None. C. Zambrano: None. L. Peng: None. F.J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Funding Sanofi

2459-PUB: Clinical Characteristics and Management of Patients with Type 1 Diabetes—A National Population-Based Spanish Study (SED1)

Introduction: Little is known about the clinical characteristics and management of type 1 diabetes (T1D) in Spain from a national perspective. To sort this lack of information out the Spanish Diabetes Society (SED) promoted a national population-based audit study. (SED1 Study). Material and Methods: Observational, cross-sectional study of a nationally representative sample of patients with DM1 in 78 Spanish sites, including children and adults. Results: A total of 647 participants were included: Aged 36.5+14.4 years (7.6% < 14), 55,3% female, 97.2% Caucasian, time since diagnosis 17.9±12.0 years and a BMI of 24.7±4.4 kg/m2 (40.2% > 25; 12.1% ≥30). 75.0% of the population had secondary or university studies. 20.2% of patients were active smokers and 48.7% had any type of comorbidity, mainly dyslipidemia (25.8%). Any kind of retinopathy and nephropathy was present in 19.3 and 5.9% of patients. Regarding disease management, 75.9% used basal-bolus insulin therapy, 20.4% pump therapy, half of patients used insulin/carbohydrate ratio (ICR), performed 3.0±0.9 blood glucose measurements/day (BG) and 24.9% used continuous-glucose monitoring. Mean last-year HbA1c was 7.6±1.2% (< 7%, 30.6%). The univariate logistic regression indicated that, HbA1c value was determined negatively by BG measurements (-0.045, p=0.03) and frequency of use of ICR (-0.236, p=0.008) and positively by disease duration (0.011, p=0.002) and lack of adherence to diet counseling (0.788, p=0.0001). Conclusion: The management and type of treatment of T1D in Spain is similar to other western countries. There is still a substantial proportion of patients not reaching the recognized A1c target and with either overweight or obesity. Some factors related to T1D management prevent a greater effectiveness of treatment. Disclosure F. Gomez-Peralta: Advisory Panel; Self; Abbott, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. E. Menéndez-Torre: None. S. Conde Barreiro: Other Relationship; Self; Lilly Diabetes, Sanofi. I. Conget: None. A. Novials: None. Funding Sanofi

2327-PUB: Real-World Patient-Reported Outcomes (PROs) with Insulin Glargine 300 U/ml (Gla-300) in Basal Bolus-Treated People with Type 2 Diabetes (T2DM): The MAGE Study

Fear of hypoglycemia and treatment satisfaction both influence therapy adherence. MAGE was a 6-month multicenter, prospective, single-arm, observational study with a 6-month extension conducted in Belgium, mainly assessing patient satisfaction with Gla-300 in people ≥18 years, with T2DM for ≥1 year, HbA1c 7.0-10.0%, receiving a basal-bolus insulin regimen for ≥6 months ± oral antidiabetic therapy, and naïve to Gla-300. Primary objective: change of ≥2 points in Diabetes Treatment Satisfaction Questionnaire Status Version (DTSQs) total score (TS) from baseline (BL) to month 6. Secondary objectives included change in: HbA1c, other DTSQs scores, and hypoglycemia fear scale II (HFS-II). The intent-to-treat population comprised 87 patients (Table). Primary endpoint was achieved; DTSQs TS increased by 2.80 (SD: 5.46; p<0.0001; Table). Significant decreases were seen in total HFS-II scores and worry/behavior subscales (all p<0.05). There was no change from BL in HbA1c (p>0.05); however, more patients reached HbA1c <7% at month 12 versus BL (11.5% vs. 0%). Hypoglycemia occurred at a mean (SD) 34.97 (48.28) events per patient-year. Treatment satisfaction and fear of hypoglycemia significantly improved after switching to Gla-300 in people with T2DM on basal-bolus insulin therapy in a real-life setting. Disclosure A.A. Verhaegen: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck & Co., Inc., Sanofi. Speaker's Bureau; Self; Mylan, Novo Nordisk Inc. A. Scheen: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier. K.C. Alexandre: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Bruhwyler: Other Relationship; Self; Sanofi. I.M. Colin: None. Funding Sanofi

1387-P: Genotyping Cell-Free Fetal DNA to Decide whether to Treat Hyperglycemia during Pregnancy in Women with GCK Monogenic Diabetes—A Case Study

Patients with inactivating glucokinase (GCK) mutation usually do not require treatment except for during pregnancy. The decision to treat hyperglycemia during pregnancy would depend on the fetal GCK genotype. However, it has not been able to noninvasively investigate the fetal genotype antenatally. In this study, we developed a method to determine cell-free fetal genotype of GCK and applied it in a case of pregnant woman with GCK mutation. A 40 years old woman in her second pregnancy presented with hyperglycemia. She was diagnosed with GCK p.Gly411Ser (chr7:44185121C>T; NM_000162 c.G1228A) mutation prior to her second pregnancy. We used targeted linked-read deep sequencing to resolve the haplotypes of GCK for both the women and her husband. Cell-free DNA was extracted from maternal plasma at week 24 of gestation and were subjected to massively parallel sequencing. The allelic fraction of the heterozygous variants that were in maternal mutant-linked haplotype were analyzed. The fetal fraction of the maternal plasma cell-free DNA was 21.8%. In maternal plasma cell-free DNA, a total of 12 heterozygous variants, that were homozygous in paternal genomic DNA, were identified within 40 kb of the disease-causing mutation. The average allelic fraction of the 12 variants in the mutant-linked haplotype and the wild type-linked haplotype in the cell-free DNA was 44.1% and 55.9%, respectively. This significant difference in allelic fraction of the haplotypes suggested that the fetus did not inherit the GCK mutant-linked haplotype (P 0.0081). The inferred fetal genotype was available at week 30 of gestation and the patient was treated with basal-bolus insulin therapy until term at 38 weeks. The fetal birth weight was 2,980 g (25th percentile). The fetal genotype of GCK was confirmed by Sanger sequencing postnatally. This was the first study to use cell-free DNA to determine fetal genotype to guide treatment of hyperglycemia in pregnant women with GCK mutation. Disclosure S. Kwak: None. S. Jang: None. S. Kang: None. H. Jang: None. S. Lee: None. J. Chae: None. K. Park: None. Funding Korean Ministry of Health and Welfare (HI15C3131, HI13C1468)

1045-P: Efficacy and Safety of a 24-Hour Wearable Insulin Delivery Device for Basal-Bolus Therapy in Older Adults

Basal-bolus insulin therapy in older patients is challenging due to the complexities of multiple daily injections and the higher risk of adverse consequences associated with hypoglycemia in this population. The purpose of this analysis was to evaluate the clinical outcomes and prevalence of hypoglycemia in patients 65 years of age or older when delivering basal-bolus therapy with a wearable insulin delivery device (V-Go). A retrospective analysis of electronic medical records in 54 patients with T2DM evaluated change in A1C, weight, insulin total daily dose (TDD) and prevalence of hypoglycemia. Baseline mean ± SD characteristics were age 71 ± 4 years (range 65 to 83), A1C 9.5 ± 1.6%, weight 99 ± 20 kg and TDD 64 ± 41 u/day (range 10 to 224) with 81% of patients prescribed insulin and 83% prescribed concomitant anti-hyperglycemic agents. Baseline hypoglycemia documented in 36% of patients. After a mean duration of 5 months of V-Go use, mean ± SD decreases in A1C (-1.5 ± 1.8%; p<0.0001) and TDD (-9 ± 35 u/day; p=0.107) were observed. Change in weight +0.65 kg; p<0.208. Prevalence of overall and severe hypoglycemia was markedly decreased with V-Go. As people with T2DM age, it may become necessary to simplify complex insulin regimens due to a decline in self-management ability while being mindful of risk factors. In this analysis, use of V-Go in an older population proved safe and efficacious. Disclosure T. Zeidan: Advisory Panel; Self; Corcept Therapeutics. Research Support; Self; Valeritas, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Valeritas, Inc. C.C. Nikkel: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc. E.A. Dziengelewski: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc.

1350-P: Safety and Pharmacokinetics of Technosphere Insulin in Pediatric Patients

Technosphere Insulin (TI) is an ultra-rapid, short-acting inhaled insulin that provides glycemic control in patients with diabetes. This ongoing, 2-part, open-label, interventional study aims to assess the efficacy and safety of TI in children aged 4 to 17 years with type 1 diabetes mellitus (T1DM) who are on a stable regimen of basal-bolus insulin therapy. Part 1 is a single-arm study that includes evaluation of insulin pharmacokinetics (PK) after a single prandial dose of TI (4, 8, or 12 units), followed by a 4-week titration period. Approximately 46 patients will be enrolled across 3 age cohorts: cohort 1 (13-17 years), cohort 2 (8-12 years), and cohort 3 (4-7 years). As of August 16, 2018, 15 patients had enrolled in cohort 1, 14 had received at least 1 dose, and 8 completed the titration period. Overall, 50% of the safety population (n=14) was female, mean duration of T1DM was 6.2 years, mean age was 15 years, and mean body mass index was 22.4 kg/m2. Initial PK results from cohort 1 demonstrated insulin metabolism similar to that in adult patients receiving TI. Insulin concentrations rapidly increased in the first 30 minutes after TI treatment and returned to baseline by 120 minutes for the 4-, 8-, and 12-unit doses. Mean postprandial glucose levels decreased within 1-hour postdose for the 8- and 12-unit dose groups. Seven patients developed treatment-related cough of mild (6 events) or moderate (1 event) severity. Seven patients experienced a total of 41 hypoglycemic events, but no patient required the assistance of another person to administer corrective carbohydrates. No clinically relevant declines in pulmonary function were reported. Two patients discontinued the study due to adverse events (cough, diabetic ketoacidosis). These data will help determine the appropriate age range for inclusion and recommended dosing for part 2, which will be a 1-year efficacy and safety study. Disclosure M.L. Grant: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation. J.A. Krueger: Employee; Self; Eli Lilly and Company, MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company. M. Fineman: Consultant; Self; MannKind Corporation. Employee; Self; Elcelyx Therapeutics, Inc. Stock/Shareholder; Self; Elcelyx Therapeutics, Inc. G. Sharma: Employee; Self; MannKind Corporation. F. Pompilio: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Amgen Inc., MannKind Corporation. D.M. Kendall: Employee; Spouse/Partner; Amgen Inc. Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation. Funding MannKind Corporation

2329-PUB: Transitioning T2DM Patients to Basal-Bolus Insulin Leads to Sustainable A1C Improvement

This is a post hoc analysis of a multi-country study of adults with type 2 diabetes transitioned from basal-only to basal-bolus insulin therapy. Patients were randomized 1:1 to deliver mealtime insulin using either a wearable delivery device (PAQ Meal) or a pen (NovoLog FlexPen®). We report the proportion of patients overall who achieved A1C ≤8% and A1C ≤7% by Week 24 and sustained the improvement through Week 44 when using a basal-bolus regimen. Baseline A1C ranged from 7.0 - 11.8% (patients, n=274). By week 24, 84.7% (232/274) of patients achieved A1C ≤ 8% (LOCF) which continued at 84.8% (184/217 completers) at Week 44. Overall, 77.9% (169/217) of patients saw a reduction of at least 1% in A1C by Week 44. Although, patients with higher baselines achieved a greater reduction of A1C, patients with lower baselines were significantly more likely to achieve A1C ≤ 7%. Reduction in A1C ≤ 7% was sustained by 63.6% (138/217) of patients through Week 44. Initiating a basal-bolus regimen and titrating based on morning and mealtime blood glucose levels saw the mean total daily dose increase from 47IU (basal only) at study entry to 121IU (basal-bolus) at Week 24 (0.8:1 basal:bolus). Only 6 severe hypoglycemic events occurred during the study. This study shows that transitioning from basal insulin-alone to basal-bolus insulin therapy, regardless of delivery mechanism, safely reduces and manages A1C levels in T2DM patients. Disclosure R. Barry: Consultant; Self; CeQur Corporation. D. Johns: Consultant; Self; CeQur Corporation. B. Rees: None.

Treatment Intensification With Insulin Pumps and Other Technologies in Patients With Type 2 Diabetes: Results of a Physician Survey in the United States.

An online survey was conducted to assess the perspectives and use of diabetes technologies by a sample of U.S. primary care physicians (PCPs) and endocrinologists to optimize intensive insulin therapy in patients with type 2 diabetes. Overall, endocrinologists reported using diabetes technologies more frequently than PCPs for patients with type 2 diabetes requiring basal-bolus insulin therapy. PCPs and endocrinologists who were highly focused on diabetes management with insulin therapy reported using insulin delivery devices (insulin pumps and wearable tube-free patches) when patients are not achieving their A1C target while taking basal plus three or more prandial injections of insulin daily.

PDB45 EVALUATING THE SHORT-TERM COST-UTILITY OF INSULIN DEGLUDEC VERSUS INSULIN GLARGINE U100 IN BASAL-BOLUS REGIMENS FOR TYPE 2 DIABETES IN CHINA

Insulin degludec (degludec) is an insulin analog with an ultra-long duration of action, low risk of hypoglycaemia and confirmed cardiovascular safety demonstrated in DEVOTE trial (NCT01959529). The study aimed to evaluate the short-term cost-utility of degludec versus insulin glargine 100 units/mL (glargine) for the treatment of type 2 diabetes (T2DM) receiving basal–bolus insulin therapy in China based on data from subgroup results of the DEVOTE trial. A short-term health economic model programmed in Microsoft Excel was conducted to compare costs in patients receiving once daily degludec or glargine over a 2-year time horizon. Clinical inputs and patient characteristics were taken exclusively from DEVOTE trial, whilst China-specific costs (the most current drug provincial biding price in china) were obtained from the literature. Both costs and health effects had not been discounted annually for such a short time horizon. Sensitivity analyses were conducted to assess the robustness of the results. Degludec was associated with a mean improvement of 0.00649 quality-adjusted life-years (QALYs) compared with glargine, with improvements driven predominantly by lower rates of severe hypoglycaemia with degludec versus glargine. degludec was associated with mean cost savings of 289.35 CNY per patient relative to glargine in patients with type 2 diabetes. Cost savings were primarily driven by the reduction in risk of diabetes-related complications with degludec, which offset the higher treatment costs relative to glargine. Insulin relative cost of degludec was 1040.36 CNY (16.98%) more than glargine. However, the costs of Non-fatal myocardial infarction, Non-fatal stroke, severe hypoglycaemia, and self-monitoring of blood glucose were reduced by 764.56 CNY (28.51%), 119.71 CNY (19.47%), 195.06 CNY (21.35%), and 210.13 CNY (36.94%), respectively. Sensitivity analyses demonstrated that the results were stable to variations in biding price. Among T2DM receiving basal–bolus insulin therapy in China, degludec is a cost saving treatment option compared with glargine.

SUN-131 Improving the Glycemic Control of Women Veterans with Poorly Controlled Diabetes with a Telephone Encounter

Introduction: Despite having a broad range of services available at the Veterans Affairs Healthcare System (VAHS), veterans struggle to control their chronic diseases. At the Miami VAHS, 30% of veterans have diabetes, and of those, 30% are poorly controlled. Women represent a growing number of veterans at the Miami VAHS who face many of the challenges posed by having a diabetes diagnosis. Objective: To improve HbA1c measurements in women veterans (WV) with poorly controlled diabetes following a phone encounter with an endocrinologist addressing diabetes management. Method: This was a prospective intervention study of WV with HbA1c levels ≥ 9%. An endocrinologist attempted up to three telephone calls to reach WV. The phone intervention involved a chart review of co-morbidities to establish a HbA1c target, and management included lifestyle modification counseling, insulin dose adjustment, introduction and/or discontinuation of diabetes medications, and a plan for follow-up. During the following 3-4 months, results of follow-up HbA1c were collected regardless of having had an initial telephone encounter. WV who did not have follow-up HbA1c were excluded from the study. The remaining WV were further divided into 1) those that answered the phone and participated in the assessment (intervention group) and 2) those who did not answer the phone to have an initial encounter (control group). Other variables included BMI, eGFR, type of diabetes, diabetes medication, presence of hypertension, dyslipidemia, coronary artery disease (CAD), smoking, and psychiatric illness. Results: Of 77 WV who were called, 36 WV were assessed by the endocrinologist; 41 did not answer the phone and were regarded as the control. 8 WV from the intervention group and 16 WV from the control group did not have a follow-up HbA1c, and were excluded. 28 intervention and 25 control WV were included in the final analysis. In the intervention group: mean age 55.0 ± 10.3 years, BMI 29.8 ± 5.5, eGFR 57.9 ± 4.5, 86% type 2 diabetes, 61% on basal bolus insulin therapy, 68% HTN, 93% dyslipidemia, 71% smokers, 4% CAD, and 68% psychiatric diagnosis. In the control group: mean age 55.6 ± 9.9 years, BMI 32.5 ± 6.1, eGFR 58.9 ± 4.5, 96% type 2 diabetes, 44% on basal bolus insulin therapy, 80% HTN, 84% dyslipidemia, 16% smokers, 4% CAD, and 68% psychiatric diagnosis. Mean baseline HbA1c was 10.9 ± 1.5 for the intervention and 10.8 ± 1.8 for the control group. After 3-4 months, mean HbA1c was 9.9 ± 2.3 in the intervention group, and 10.6 ± 1.7 in the control group. HbA1c decrease in the intervention group was statistically significant (p = 0.03). Conclusion: This preliminary study demonstrates that a telephone intervention from a diabetes specialist has a positive impact on decreasing HbA1c in WV with poorly controlled diabetes. Findings from this study suggest that this approach should be considered in management of other chronic diseases.

MON-151 Hypertriglyceridemia and Acute Pancreatitis Leading to Ketoacidosis in a Patient with Type 2 Diabetes

Introduction: We describe a case of type 2 diabetes presenting with acute pancreatitis (AP), hypertriglyceridemia, and diabetic ketoacidosis (DKA). Clinical Case: A 34-year-old Caucasian male presented to the emergency room with worsening intractable nausea and vomiting for 2 days. Medical problems included obesity, hypertension, hyperlipidemia, and fatty liver disease. He had a history of polysubstance use (denied recent alcohol intake) and noncompliance with self-care and was a known carrier for hemochromatosis. He gave a history of 30-lb weight loss over the past 6 weeks with associated polydipsia, polyuria, and abdominal pain. Six days prior to admission, the patient had been seen by his primary care physician for headache, nausea and vomiting, found to have a hemoglobin A1c of 13.5% (n=4.2-5.8%) and was started on metformin for newly-diagnosed T2DM. Physical exam revealed him to be afebrile, tachycardic (heart rate 145 bpm), and with a BP of 146/98 mmHg. Laboratory tests were significant for sodium 125 mmol/L (n=135-145mmol/L), potassium 4.0 mmol/L (n=3.5-5.1 mmol/L), anion gap 25 mmol/L (n=2-14 mmol/L), glucose 330 mg/dL (n=70-99 mg/dL), creatinine 1.5 mg/dL (n=0.5-1.3 mg/dL), lipase 268 U/L (n=8-78 U/L), triglyceride 1619 mg/dl (n<150 mg/dL), and negative alcohol and cardiac markers. Urine testing was positive for ketones with a negative drug screen. Arterial blood gas showed a pH of 7.27 (n=7.35-7.45), pCO2 19 mmHg (n= 35-45 mmHg), and pO2 111 mmHg (n=80-100 mmHg). CT of the abdomen revealed inflammation surrounding the pancreatic head, consistent with pancreatitis. The patient was admitted to the intensive-care unit for DKA and AP. He was treated with intravenous fluids and required an insulin drip for 72 hours before transitioning to subcutaneous insulin with resumption of oral nutrition as the pancreatic inflammation and gastrointestinal symptoms resolved. He was discharged on basal-bolus insulin therapy and lipid-lowering medications. Conclusion: Both DKA and AP are serious medical conditions with a high mortality rate when these two disorders occur simultaneously. Treatment requires aggressive fluid resuscitation with replacement of electrolytes and initiation of insulin. Identifying the potential trigger is key to preventing future occurrences. In the case presented, it is likely that primary hypertriglyceridemia, worsened by elevated glucose levels, was the etiologic factor for the onset of AP, which in turn precipitated DKA. However, it is also possible, though less likely, that uncontrolled hyperglycemia, glucose toxicity, and relative insulin deficiency led to increased production of very-low-density lipoprotein (VLDL) in the liver and its reduced clearance from the plasma, thus predisposing to hypertriglyceridemia. Close monitoring and appropriate therapy are required to control the latter and prevent future recurrences of AP and possibly DKA.

MON-130 Optimal Glycemic Control in a Patient with HNF1A MODY with GLP1-RA Monotherapy: Implications for Future Therapy

Background: Among those diagnosed with maturity-onset diabetes of the young (MODY), the most common form is hepatocyte nuclear factor 1α MODY (HNF1A MODY). Individuals with HNF1A MODY typically respond very well to treatment with sulfonylureas (SU) which are recommended as first line therapy. Clinical Case: A 23 year old Caucasian woman with presumed type 1 diabetes since age 14 presented for diabetes care during pregnancy where she maintained an A1c between 5.9% - 7.5% on full basal-bolus insulin therapy. In the immediate post-partum period a diagnosis of MODY was suspected, despite no family history of diabetes, given frequent hypoglycemia on a low total daily dose of insulin of 0.2u/kg/day with minimal basal insulin requirement, absence of development of DKA in the setting of complete cessation of insulin for several days, random c-peptide 2.15 ng/mL (ref. range 0.80-3.10 ng/mL) with concurrent glucose 181mg/dl, and absent anti-GAD and islet cell antibodies. Genetic sequencing revealed a de novo heterozygous mutation for variant c.827C>A; p.Ala276Asp in exon 4 of the HNF1A gene consistent with HNF1A MODY. In 2014, insulin was discontinued and SU therapy was started with A1c ranging 7.1% - 8.8% in the setting of variable adherence. Given consistently elevated A1c, dulaglutide 0.75mg weekly was started in 2017 with subsequent improvement in glycemic control allowing a decrease in SU dose. In early 2018, she discontinued SU therapy entirely given frequent hypoglycemia on glimepiride 1mg daily and dulaglutide 0.75mg weekly. After SU discontinuation, dulaglutide was increased to 1.5mg weekly and her A1c improved to 6.6% without hypoglycemia, the best A1c of her adult life with the exception of during her pregnancy. Conclusion: There is little data on the use of GLP1-RA as monotherapy for patients with HNF1A MODY and no long term studies of GLP1-RA monotherapy or parallel group, head-to-head studies of GLP1-RA vs. SU have been published. In this case, dulaglutide monotherapy was more effective than glimepiride monotherapy in achieving short term glycemic targets in an individual with HNF1A MODY.

Cost of achieving HbA1c and weight loss treatment targets with IDegLira vs insulin glargine U100 plus insulin aspart in the USA.

BackgroundCompared with basal-bolus insulin therapy (insulin glargine U100 plus insulin aspart), IDegLira has been shown to be associated with similar improvements in HbA1c, with superior weight loss and reduced hypoglycemia in patients with type 2 diabetes. The present analysis evaluated the cost per patient with type 2 diabetes achieving HbA1c-focused and composite treatment targets with IDegLira and insulin glargine U100 plus insulin aspart (≤4 times daily).MethodsThe proportions of patients achieving treatment targets were obtained from the treat-to-target, non-inferiority DUAL VII study (NCT02420262). The annual cost per patient achieving target (cost of control) was analyzed from a US healthcare payer perspective. The annual cost of control was assessed for eight prespecified endpoints and four post-hoc endpoints.ResultsThe number needed to treat to bring one patient to targets of HbA1c <7.0% and HbA1c ≤6.5% was similar with IDegLira and insulin glargine U100 plus insulin aspart. However, when weight gain and/or hypoglycemia were included, the number needed to treat was lower with IDegLira. IDegLira and insulin glargine U100 plus insulin aspart had similar costs of control for HbA1c <7.0%. However, cost of control values were substantially lower with IDegLira when the more stringent target of HbA1c ≤6.5% was used, and when patient-centered outcomes of hypoglycemia risk and impact on weight were included.ConclusionIDegLira was shown to be a cost-effective treatment vs insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic targets on basal insulin in the USA.

Clinical and Economic Outcomes of Patients with Type 2 Diabetes on Multiple Daily Injections of Basal-bolus Insulin (MDI) Therapy: A Retrospective Cohort Study

PurposeTherapy for patients with type 2 diabetes (T2DM) not achieving hemoglobin (Hb) A1c targets may progress from an oral antidiabetic drug (OAD) to added basal insulin and then to multiple daily injections of basal-bolus insulin (MDI); however, the relative clinical and economic burden experienced by patients prescribed MDI for T2DM is not well quantified. The intent of this work was to describe direct medical costs, health care resource utilization, and glycemic control in patients with T2DM exposed to MDI in a clinical practice setting. MethodsThis retrospective cohort study used administrative claims data (2012–2015, United States) from patients aged 18 to 64 years with T2DM prescribed OAD, basal insulin, or MDI therapy. Eligible patients had continuous enrollment from ≥6 months before to 12 months after the date of the index prescription drug claim. Patients eligible for inclusion in the MDI cohort had ≥2 pharmacy claims each for basal and bolus insulin from the index date through the postindex period. Glycemic control, defined as an HbA1c value of <7% during the last 9 postindex months, was assessed in a subset of patients with HbA1c data available from that period. Descriptive analyses were performed. FindingsWe identified 225,135 patients with T2DM and claims for an OAD (n = 188,230), basal insulin (n = 23,724), or MDI (n = 13,181). The mean age was 51 or 52 years in each cohort; 54% to 59% of patients in each cohort were men. The mean Charlson comorbidity index scores were 0.8, 1.4, and 1.8, respectively; the percentages of patients with obesity and diabetes-related complications were greatest in the MDI cohort compared with OAD and basal insulin cohorts. The mean direct medical costs (all-cause; year-2015 US $) were $9368 in the OAD cohort, $14,420 in the basal insulin cohort, and $25,624 in the MDI cohort; diabetes-related costs were $3396, $7285, and $13,538. In the OAD, basal insulin, and MDI cohorts, 7%, 9%, and 14% of patients had ≥1 hospitalization, and 17%, 20%, and 24% had ≥1 emergency department visit, while 5%, 7%, and 11% had ≥1 diabetes-related hospitalization, and 8%, 11%, and 15% had ≥1 diabetes-related emergency department visit. Glycemic control was found in 64%, 22%, and 15% of patients in the OAD, basal insulin, and MDI cohorts. ImplicationsThese findings suggest that patients prescribed MDI therapy for T2DM have greater disease burden, experience greater medical costs and health care resource utilization, and exhibit poorer glycemic control than do patients treated with OAD or basal insulin therapy.

Assessment of diabetic patients' adherence to insulin injections on basal-bolus regimen in diabetic care center in Saudi Arabia 2018: Cross sectional survey.

Background:Since insulin became a focal point of diabetes management, several studies have been carried out to monitor and improve patient outcomes. Adherence insulin therapy is an important part of diabetes management.Aim:This study reviews the responses of patients being managed in a diabetic care setting in monitoring their adherence to basal bolus insulin therapy.Method:A pre-validated questionnaire containing 18 questions was administered to patients in the diabetic care unit of the Security Forces Hospital, Riyadh, Saudi Arabia.Results:The levels of adherence with basal bolus insulin therapy was 61.9%. There is no considerable difference in adherence levels of male and female respondents with 31.62% and 31.58% respectively. The younger age groups (14-29) had the highest adherence levels at 65.75%. Higher levels of patient literacy and the location also have a positive relationship with adherence.Conclusion:To improve adherence levels, dosing should be made with consideration for patient convenience, and patients should be encouraged to build positive psychological relationships. Further studies should look to studying outcomes of therapy, and markers should be developed to monitor patient progress on therapy regimen regularly. The aspect of short clinic visits is another major consideration that needs to be look into properly to understand and monitor patients’ proper adherence toward the basal bolus insulin.

Association of diabetic ketoacidosis, severe hypoglycemia and glycemic control among children and young adults with type 1 diabetes mellitus treated with premixed versus basal-bolus insulin therapy

BackgroundThis study compared event rates of diabetic ketoacidosis (DKA) and severe hypoglycemia, as well as glycemic control, among children, adolescents, and young adults with type 1 diabetes mellitus (T1DM) receiving basal-bolus or premixed insulin therapy. MethodsA total of 825 individuals aged ≤ 20 years with T1DM, using either basal-bolus or premixed insulin regimens, were retrospectively recruited from 2001 to 2015. Rates of DKA after diagnosis, severe hypoglycemia, and the level of glycated hemoglobin A1c (HbA1c) improvement during the follow-up period were analyzed. ResultsOf the 825 patients, 226 receiving a premixed regimen were matched to the same number of patients receiving a basal-bolus regimen. In the matched cohort, DKA (10.62% vs. 5.31%; p = 0.037) and severe hypoglycemic episodes (25.22% vs. 10.62%; p < 0.001) were significantly higher in patients receiving a premixed regimen than those receiving a basal-bolus regimen. The median reduction of HbA1c, compared to the treatment-naive level, was better with the basal-bolus regimen than with the premixed regimen in both matched (2.2 vs. 2.1; p = 0.034) and the entire (3.1 vs. 1.9; p < 0.001) cohorts. Regardless of insulin regimen, a higher HbA1c level was significantly linked to higher risk of DKA development (hazard ratio [HR] 1.35 per 1% increase; p < 0.001) once the HbA1c level was ≥7.5%. ConclusionsA premixed insulin regimen may increase the DKA occurrence rate and severe hypoglycemic risk in children, adolescents, and young adults with TIDM, compared to a basal-bolus regimen. Tight glycemic control with HbA1c < 7.5% may prevent the increased risk of DKA.

GLP-1 receptor agonist added to insulin versus basal-plus or basal-bolus insulin therapy in type 2 diabetes: A systematic review and meta-analysis.

Current guidelines recommend that antihyperglycaemic treatment in patients with type 2 diabetes not achieving the HbA1c target on basal insulin should be intensified with a glucagon-like peptide-1 receptor agonist (GLP-1RA) or basal-plus/basal-bolus (BP/BB) insulin regimen. We conducted a systematic review and meta-analysis to compare the effects of GLP-1RA/insulin combinations versus BP/BB. The review was registered on PROSPERO (CRD42017079547). PubMed, Scopus, CENTRAL, and ClinicalTrials.gov were searched until July 2018. All randomized controlled trials (RCTs) reporting HbA1c , body weight, daily insulin dose, hypoglycaemic events, and discontinuation due to lack of efficacy were included. A subgroup analysis on different combinations of GLP-1RA and insulin was performed. Out of 1885 retrieved papers, 13 RCTs were included in the review. Compared with BP/BB, GLP-1RA/insulin combinations were associated with a similar HbA1c reduction (Δ=-0.06%; 95% confidence interval [CI], -0.14 to 0.02; P=0.13; I2 =52%), greater weight loss (Δ=-3.72kg; 95% CI, -4.49 to -2.95; P<0.001; I2 =89%), and lower incidence of hypoglycaemic events (relative risk [RR]=0.46; 95% CI, 0.38-0.55; P<0.001; I2 =99%). The daily insulin dosage among GLP-1RA/insulin users was 30.3IU/day (95% CI, -41.2 to -19.3; P<0.001; I2 =94%), lower than with BP/BB. No difference was found for discontinuation due to lack of efficacy. The present review supports treatment intensification with GLP-1RA added to insulin versus BP/BB in uncontrolled type 2 diabetes. This could provide similar antihyperglycaemic efficacy while leading to weight loss and sparing of hypoglycaemia and insulin dose. As a consequence, a considerable number of patients with type 2 diabetes could be potentially shifted from BP/BB to GLP-1RA/insulin combinations.

Sustained Implementation Success Following Targeted Knowledge Translation Intervention to Improve Glycemic Outcomes with Basal Bolus Insulin Therapy

Purpose: To evaluate the long-term impact of a targeted knowledge translation intervention to address recognized barriers to basal bolus insulin therapy (BBIT) use in a moderate-sized acute care facility staffed predominantly by non-diabetes care providers.

Predictive factors of efficacy of combination therapy with basal insulin and liraglutide in type 2 diabetes when switched from longstanding basal-bolus insulin: Association between the responses of β- and α-cells to GLP-1 stimulation and the glycaemic control at 6 months after switching therapy

AimsTo evaluate the glycaemic control of combination therapy with basal insulin and liraglutide, and to explore the factors predictive of efficacy in patients with type 2 diabetes when switched from longstanding basal-bolus insulin therapy. MethodsWe studied 41 patients who switched from basal-bolus insulin therapy of more than 3 years to basal insulin/liraglutide combination therapy. Glycaemic control was evaluated at 6 months after switching therapy and used to subdivide the patients into good-responders (HbA1c <7.0% or 1.0% decrease) and poor-responders (the rest of participants). To evaluate the glucose-dependent insulin/glucagon responses without/with liraglutide, a 75-g oral glucose tolerance test (OGTT) was performed twice, before (1st-OGTT) and 2-days after (2nd-OGTT) liraglutide administration. ResultsTwenty-eight patients (68.3%) were identified as good-responders. No differences were found in baseline characteristics including insulin/glucagon responses during 1st-OGTT between the groups. 2nd-OGTT revealed that paradoxical hyperglucagonemia were significantly improved in both groups, but significant increases in insulin secretory response were observed only in good-responders. Logistic regression analyses revealed that the improvement of the insulin-response during 2nd-OGTT compared to that during 1st-OGTT is associated with the good-responder. ConclusionsEnhancement of glucose-dependent insulin-response under liraglutide administration is a potential predictor of long-term glycaemic control after switching the therapies.

Severe preeclampsia and gene mutation HNF4A (MODY1): а case report

Preeclampsia is an obstetric complication that is becoming a major cause of maternal and perinatal morbidity and mortality. The rate of preeclampsia in diabetes mellitus is 3 to 5-fold higher than in the population. Heparin is used for prevention of preeclampsia due to its experimentally shown important role in the trophoblast invasion and differentiation, as well as its influence on the production of proangiogenic factors. The paper gives a clinical case report that broadens our understanding on the preeclampsia pathophysiology and possibilities of its prevention. A 30-year old patient with no past history of serious physical illnesses had her two previous pregnancies with severe preeclampsia of early onset (arterial hypertension, massive proteinuria, thrombocytopenia, renal and hepatic insufficiency). Both babies were born extremely preterm (24 to 25 weeks of gestation) and died. Her hereditary background included type 2 diabetes in her maternal grandmother. At early terms of both pregnancies she had her fasting venous plasma glucose of 3.8 to 4.6 mmol/L (normal, &lt; 5.1 mmol/L). Oral glucose tolerance test which had to be performed at 24 to 28 weeks of gestation, according to the protocol, was not performed. While planning for the third pregnancy, her body mass index was 29 kg/m 2 , with normal values of the blood pressure and renal function, no proteinuria and no evidence of the anti-phospholipid syndrome. In the 1 st trimester, she had her fasting venous plasma glucose of 4.4 mmol/L. From the early term of her pregnancy, the patient was administered low molecular weight heparin; from the week 15, she was started with antihypertensive medications due to gestational arterial hypertension. Manifest diabetes was diagnosed at week 24 to 25 based on the results of the oral glucose tolerance test (4.96–10.42–11.46 mmol/L). With diet treatment, she had her postprandial glycaemia of up to 8.9 mmol/L, causing the initiation of basal-bolus insulin therapy from week 25 of gestation (0.4 U/kg), with achievement of good glucose control. At week 16, she had her sFlt1/PlGF level of 44 (high risk of preeclampsia). Molecular genetic assessment identified a HNF4A gene mutation, associated with MODY1. From week 34, she had moderate preeclampsia and fetal growth delay. An elective cesarean section was performed at week 38, with a healthy boy of 2300 g and 48 cm. After delivery, her diabetes was controlled by diet. The baby had an identical mutation. Thus, one cannot exclude a genetically determined link between complications of previous pregnancies and manifest diabetes diagnosed during the current pregnancy. Diagnosis of MODY1 in a pregnant patient would require the earliest initiation insulin treatment to prevent fetal macrosomia and neonatal hypoglycemia, as well as to prevent preeclampsia. The reason of successful outcome of this pregnancy could be related to heparin administration at the early terms of pregnancy that allowed for appropriate implantation and placenta formation, as well as for timely good glucose control.