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2013 ADA Posters 386-1338.Indd COMPLICATIONS—HYPOGLYCEMIA COMPLICATIONS—HYPOGLYCEMIA tolerance during 1g/kg glucose intraperitoneal glucose tolerance tests (p<0.05). During 160 minute hyperinsulinemic hypoglycemic clamp studies, HET and Guided Audio Tour: Hypoglycemia—From Basic Science to Private Practice HOM-KO mice needed signifi cantly less dextrose than controls (table 1). It is not (Posters: 388-P to 395-P), see page 19. clear yet whether this was due to reduced hepatic insulin sensitivity, increased CRR or both with plasma epinephrine responses being non-signifi cantly greater & 388-P in HOM-KO than controls(1130 ± 364 vs 642 ± 137 pg/ml). Our data suggest that neuronal GK, presumably through its role in glucose- Achieving FPG Target Without Nocturnal Hypoglycemia: A Pooled POSTERS sensing, plays a central role in maintaining blood glucose. Complications Analysis of Studies in T2D Comparing Insulin Degludec vs. Insulin Acute and Chronic Glargine Table 1 BERNARD ZINMAN, JITEN VORA, MARCUS NIEMEYER, MARI-ANNE GALL, *=p<0.001 Genotype n Dextrose Infusion Plasma glucose CHANTAL MATHIEU, Toronto, ON, Canada, Liverpool, United Kingdom, Søborg, Rate (mg/kg/min) - at end of clamp Denmark, Leuven, Belgium last 20 minutes (mM) Insulin degludec (IDeg), a new basal insulin that forms soluble multi- of clamp hexamers after sc injection, has an ultra-long and stable glucose-lowering Clamp Study 1 HET-KO 8 7.2 ± 1.3* 2.57 ± 0.14 effect. These properties may lead to less nocturnal hypoglycemia compared to other basal insulin analogues, and should allow more patients to reach Controls 10 12.0 ± 2.7 2.69 ± 0.13 fasting plasma glucose (FPG) target safely. In this pooled analysis we investigated the proportion of patients with T2D Clamp Study 2 HOM-KO 7 4.9 ± 1.6 *** 2.87 ± 0.06 achieving target FPG (<90 mg/dL [5 mmol/L]) without nocturnal confi rmed hypoglycemia in 4 open-label, randomized, treat-to-target trials where Controls 12 13.3 ± 1.9 2.99 ± 0.07 patients (N=2380) received either IDeg or insulin glargine (IGlar), both once- daily in combination with OADs, for 26 or 52 weeks. Confi rmed hypoglycemia Supported by: Yousef Jameel MRC Wellcome Trust was defi ned as PG < 56 mg/dL (3.1 mmol/L) or severe episodes requiring assistance, and nocturnal confi rmed hypoglycemia defi ned as episodes from 00:01 to 05:59. & 390-P A greater proportion of patients achieved the FPG target, and fewer Simplifi cation of Insulin Regimens in Older Adults With Diabetes patients experienced nocturnal confi rmed hypoglycemia with IDeg than Decreases Hypoglycemia, while Maintaining Glycemic Control with IGlar (table). The chance of achieving FPG target without confi rmed MEDHA N. MUNSHI, ALISSA R. SEGAL, COURTNEY RYAN, CHRISTINE SLYNE, nocturnal hypoglycemia was 82% higher with IDeg: estimated odds ratio NORA SAUL, Boston, MA IDeg/IGlar = 1.82 [1.49; 2.22]95%CI. Older adults with diabetes on complex insulin regimens are known to have In conclusion, T2D patients are more likely to reach FPG target without high risk of hypoglycemia at all levels of glycemic control. We evaluated the nocturnal confi rmed hypoglycemia with IDeg than with IGlar. These fi ndings effect of simplifi cation of insulin regimen on frequency (number of excursions may have important implications for achieving target levels of glycemic <70) and duration (total time spent <70) of hypoglycemia measured by control in clinical practice. continuous glucose monitoring (CGM), and glycemic control (A1C) in older adults with type-2 diabetes. Thirty patients (mean age 77±6 years, duration Trial ID; Number (%) Number (%) Number (%) meeting Statistical diabetes 20±10 years and A1C 7.6±1%) taking ≥2 insulin injections and with N FAS IDeg/ meeting FPG target without nocturnal FPG target without Analysis ≥1 episode of hypoglycemia over 5-day CGM are enrolled. At present, 17 IGlar (<90 mg/dL) confi rmed nocturnal confi rmed Est. odds ratio patients have completed a simplifi cation protocol which entails switching hypoglycemia hypoglycemia to once daily glargine + other non-insulin agents. At study entry, patients IDeg IGlar IDeg IGlar IDeg IGlar IDeg/IGlar were taking average 3.4±1.3 insulin injections per day. Simplifi cation was 3579; 773/257 302 (39.1) 62 (24.1) 667 (86.3) 218 (84.8) 254 (32.9) 50 (19.5) 1.82 achieved in all patients; all receiving only one injection of glargine with 8 patients requiring one and 9 requiring 2 additional non-insulin agents. The 3672; 228/229 86 (37.7) 66 (28.8) 214 (93.9) 209 (91.3) 79 (34.6) 56 (24.5) [1.49; 2.22]95%CI number of hypoglycemic episodes declined in 15 (88%), with no episodes 3586; 289/146 124 (42.9) 53 (36.3) 231 (79.9) 111 (76.0) 100 (34.6) 40 (27.4) detected in 7 patients during CGM. The overall frequency of hypoglycemia 3668; 228/230 109 (47.8) 72 (31.3) 204 (89.5) 181 (78.7) 97 (42.5) 59 (25.7) decreased from 5.2±3 to 1.6±2 (p<0.001), and the overall duration of Total; 1518/862 621 (40.9) 253 (29.4) 1316 (86.7) 719 (83.4) 530 (34.9) 205 (23.8) hypoglycemia decreased from 339±314 to 106±188 (p<0.02) minutes after The endpoint was analyzed using a logistic regression model with logit link. The model included treatment, simplifi cation. Simplifi cation did not adversely affect A1C which was 7.4±1% sex, trial, antidiabetic treatment at screening, and region as fi xed factors, and age and baseline FPG as covari- at baseline and 7.3±1% after simplifi cation (p=NS). In 11 of 17 (65%) patients ates. Subjects were insulin-naïve in trials 3579, 3672, 3586. Trial 3668 included both insulin-naïve and non- A1C remained stable or improved, with mean lowering of 0.32%. In the 6 naïve subjects. In trial 3668, subjects in the IDeg fl exible-dosing group were excluded. N FAS = number of sub- patients whose A1C worsened after simplifi cation, 5 patients showed jects in the full analysis set. In all trials, subjects were treated with basal insulin once daily + OADs. improvement in the duration of hypoglycemia and the increase in A1C was ≤0.5% in 4 patients. Diabetes related distress measured by Problem Areas Supported by: Novo Nordisk, Inc. in Diabetes (PAID) improved in 13 of 17 patients and remained same in 1 patient after simplifi cation. In conclusion, simplifi cation of insulin regimens & 389-P in older adults with type-2 diabetes decreases hypoglycemia and diabetes- Brain Glucokinase Plays a Central Role in Blood Glucose Homeo- related stress, while maintaining glycemic control. stasis Supported by: Sanofi EMMANUEL O. OGUNNOWO-BADA, CHRISTINE RICHES, WILLIAM J. MARSH, JING XIA, JEFFREY W. DALLEY, MARK L. EVANS, Cambridge, United Kingdom Glucose sensing in specialised brain areas helps maintain blood glucose & 391-P by triggering counterregulatory responses (CRR) to hypoglycemia and/ Improved Hypoglycemic Accuracy, Alerts and Detection With the or controlling hepatic glucose fl ux. We investigated the role of brain G4 PLATINUM CGM System glucokinase (GK) in control of blood glucose by crossing mice expressing Cre THOMAS PEYSER, LUCAS BOHNETT, KATHERINE NAKAMURA, San Diego, CA recombinase under nestin promotor with GK-fl oxed mice to create neuronal Use of continuous glucose monitoring (CGM) devices improves glycemic GK knockout (KO) mice. We anticipated greater CRR during hypoglycemia control. Previous generations of CGM devices have reported acceptable and/or impaired glucose tolerance. performance, but accuracy in the hypoglycemic range has been a Mice were born at Mendelian ratios and studied 5-8 weeks old. Data shortcoming of earlier systems. We report here the accuracy of the Dexcom below are for heterozygote (HET-KO; nes-cre+/- GKlox/WT ) or homozygote KO G4 PLATINUM (DG4P) CGM in the hypoglycemic range and compare the (HOM-KO; nes-cre+/- GKlox/lox) compared with littermate controls (nestin- results to the previous generation. cre-/- or GKWT/WT). The performance of the DG4P was evaluated in a multicenter study with Confi rming a brain specifi c GK KO, ex vivo hypothalamic but not liver GK 72 diabetic subjects. CGM values were compared with Yellow Springs activity was reduced in HET-KO compared with controls (n=6-9, Vmax 10 vs Instrument (YSI) blood glucose measurements every 15 minutes. There were 13 mU/mg, p<0.01). As predicted, HET-KO mice showed impaired glucose 1,373 paired points with YSI values below 80 mg/dL. There were 83% of CGM ADA-Funded Research & Guided Audio Tour poster For author disclosure information, see page 829. A99 COMPLICATIONS—HYPOGLYCEMIA values within 20 mg/dL of the YSI values, as shown in a density intensifi ed Bland-Altman Bias plot, compared to a 73% in the previous generation. & 393-P The true hypoglycemia alert rate is the percentage of time the CGM Hypoglycemia Increases Platelet Reactivity in Patients With Type alarmed when the YSI was at or below the alert setting within a 15 minute 2 Diabetes window before or after the event. The true alert rate for the DG4P at an 80 ELAINE Y.K. CHOW, AHMED IQBAL, EMMA WALKINSHAW, ALEXANDRA LUBI- mg/dL alert setting was 87%, a 16% increase to the previous generation. NA SOLOMON, REBECCA DALY, HEATHER M. JUDGE, ROBERT F. STOREY, SIMON Similarly, when the YSI indicated severe hypoglycemia (55 mg/dL or less), R. HELLER, Sheffi eld, United Kingdom the DG4P indicated biochemical hypoglycemia (70 mg/dL or less) 88% of Increased cardiovascular (CV) mortality has been reported in trials of POSTERS Complications the time, a 15% increase to the previous generation. Improved accuracy intensive glycemic control in patients with Type 2 diabetes.
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