Acute and Chronic Complications

2014 Diabetes  
Exenatide BID (ExBID) improves postprandial glucose and A1C with low hypoglycemia (hypo) risk. Two 30-wk studies evaluated insulin glargine (IG; titrated per algorithm based on fasting glucose [goal <100 mg/dL]) + ExBID. In Study 1 (N=627), ExBID or insulin lispro (IL) was added to IG + metformin. In Study 2 (N=259), ExBID or placebo was added to IG ± metformin and/or pioglitazone. IL was titrated based on pre-meal glucose (goal =100 mg/dL with no hypo). We quantifi ed the benefi t-risk
more » ... ship between A1C lowering and hypo risk versus comparators using Poisson regression models to evaluate hypo exposureadjusted event rates (EAER) adjusted for the lowest A1C observed over 30 wks. In both studies, IG + ExBID signifi cantly reduced A1C and weight. Study 1: With the same A1C achieved, hypo EAER was 58% less with IG + ExBID vs. IG + IL (risk ratio [RR] 0.42; p<.0001; Figure 1A ). IG + ExBID reduced daytime (RR 0.19; p<.0001) and nocturnal hypo EAER (0.86; p=.076) vs. IG + IL. Overall, being female, lower BMI or longer diabetes duration resulted in signifi cantly higher hypo EAER. Study 2: hypo EAER was slightly lower for IG + ExBID than IG + placebo (RR=0.75; p=.107; Figure 1B ). IG + ExBID signifi cantly reduced A1C and weight, and the modeled A1C and hypo ben efi t-risk relationship further supported use of ExBID with IG for patients with T2DM not at goal with titrated IG. Glucagon is used in diabetic patients for treatment of severe episodes of hypoglycemia. Pharmaceutically, however, native glucagon possesses poor physicochemical properties, making convenient dosing in a ready-to-use rescue pen or the development of an artifi cial pancreas diffi cult. Accordingly the development of novel glucagon analogues such as ZP-GA-1 is pursued. The solubility of ZP-GA-1 at physiological pH was shown to be >25 mg/mL and thus highly superior to that of native glucagon ~0.2 mg/mL. In addition, the stability data suggests that ZP-GA-1 is suitable for long term storage as a liquid formulation. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of ZP-GA-1 and native human glucagon were investigated in dogs. Animals were administered either subcutaneously (SC, 20 and 120 nmol/ kg) or intravenously (IV, 75 nmol/kg). Our data demonstrated overall similar PK profi les as well as blood glucose (BG) profi les of ZP-GA-1 and glucagon. Further, the SC effect of ZP-GA-1 on BG in a rat model of hypoglycemia was investigated (Figure) . Both ZP-GA-1 and glucagon restored BG to baseline levels or above in a dose-dependent manner during insulin-induced hypoglycemia. In conclusion, ZP-GA-1 displays improved physicochemical properties while maintaining similar PK and PD profi les compared to native glucagon. A history of SH has been associated with increased mortality in type 2 diabetes. While in T1D up to 10% of deaths can be attributable to acute hypoglycemia, the role of a history of SH is unclear. We thus examined data from the ongoing Epidemiology of Diabetes Complications study of childhood onset T1D (mean age 28 and duration 19 years, n=658 at baseline (1986-88)) to determine if a self reported history of SH in the prior 2 years, is associated with total (n=76), CAD (no renal, n=27), renal (no CAD, n=14) or CAD+renal (n=19) mortality, in 443 participants attending the 1990-92 exam when these questions were fi rst asked. SH was defi ned as unconsciousness, requiring assistance and/or having a low blood sugar (<50 mg/dl) without recognition. Death was classifi ed according to Diabetes Epidemiology Research International (DERI protocol) by a physician committee. Baseline (1990Baseline ( -1992 and most recent history of SH analyses were performed. Separate multivariable Cox models were determined for each outcome based on univariate signifi cance of previously established predictors. Baseline or recent history of SH was forced into each model. The median time from last follow up to death was 1.5 years. SH 2 years before baseline was not independently related to total, CAD, renal, or CAD+renal mortality. SH in the prior 2 years at most recent exam was not related to CAD or CAD+renal mortality but was independently related to total mortality (HR=1.79, 1.1-2.9); other predictors were diabetes duration, estimated glomerular fi ltration rate (eGFR), HbA1c, hypertension, smoking, albumin excretion rate (AER), and nonHDLc. A univariate association with renal mortality (HR=3.84, 1.3-10.9 was weakened (HR=2.57, .89-7.4, p=0.08) with the addition of eGFR and AER. We conclude that SH in the last 1-4 years doesn't increase CAD mortality risk but may increase total and renal mortality, though that latter is partially explained by diminished renal function. Objective: The aim of this study was to investigate whether hypoglycaemia at admission correlates with the outcomes in Japanese septicemia. Research Design and Methods: We collected data anonymously from electronic medical records and analyzed them retrospectively. Initially, 818 positive blood culture sets were screened for participation in the study. Patients without diagnostic criteria of systemic infl ammatory response syndrome or clinically diagnosis as a contamination of blood culture were excluded. So, 311 patients were diagnosed with bacterial septicemia. 5 patients were excluded because of missing blood glucose data. In the end, 306 patients were evaluated in this study. Results: Hypoglycemia under 70 mg/dl was detected in 12 patients. Severe hypoglycemia under 40 mg/dl was observed in 6 patients. Of the hypoglycemic patients, 3 had diabetes mellitus. The prevalence of hypoglycemia was 3.9 %. Mortality within 30 days and total of inhospital mortality from all 306 patients was 13.3 % and 23.5 %, respectively. The prevalence of within 30 days mortality according to blood glucose levels at admission in patients with bacterial septicemia was 83.3, 66.3, 22.8, 7.8, 11.5, 12.9 percent for under 40 mg/dl, 41-70 mg/dl, 71-110 mg/dl, 111-170 mg/ dl, 171-200 mg/dl, over 201 mg/dl of blood glucose at admission, respectively. The Kaplan-Meier curves demonstrated higher mortality in hypoglycemic patients than in those without hypoglycemia (log rank test P<0.001). Conclusion: The mortality of hypoglycemic Japanese patients with sepsis patients within 30 days was signifi cantly higher than that of normoglycemic, or hyperglycemic patients with sepsis. Acute and Chronic Complications POSTERS COMPLICATIONS-MACROVASCULAR-ATHEROSCLEROTIC CARDIOVASCULAR DISEASE AND HUMAN DIABETES required transferring patients to the emergency room or hospital. The overall mortality was 0.32% (28 cases). The estimated cost for each hypoglycemic event was €702, with an emergency service total cost of €6.093.507. Hypoglycemic events requiring emergency room care accounted for 49% of the total healthcare cost. Hypoglycemia is a common emergency associated with high rate of emergency medical service EMS utilization and health care cost. These results indicate the need of treatment protocols to improve outcome, avoid hospitalizations, and reduce costs of patients with hypoglycemic emergencies.
doi:10.2337/db14-389-664 fatcat:stvrgo2ukrcglba7yjzt3sjfjy