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The article presents the findings of a study on the effects on mood and cognitive symptoms (Sx) of a basal-prandial versus a basal insulin regimen that influence blood glucose (BG) fluctuations differently. It cites the method used by researchers to analyze carryover and Tx effects. It notes that Beck Depression Inventory-II (BDI-II) score improved with basal-prandial insulin and negative mood/cognitive Sx correlated with BG rate of exchange.

We compared the effects of basal+prandial insulin lispro mid mix (MM) (50% NPL, 50% lispro) ac tid with basal insulin glargine (G) hs, both plus metformin (Met), on postprandial (pp) blood glucose (BG), insulin, and inflammatory markers (IL 6 and TNFα) in T2D patients before and after 24 wks of treatment. This prospective, open-label, parallel group study randomized 315 patients to MM+Met or G+Met after 6 wks of lead-in on lispro low mix (75% NPL, 25% lispro)+Met. Both groups titrated insulins to achieve fasting BG <6.7 mM (< 120 mg/dL) and, for MM+Met only, 2-hr pp BG < 8.0 mM (<144 mg/dL). A subgroup of patients (MM+Met, n=25; G+Met, n=21) participated in the test meal substudy pre-randomization and at endpoint. The night before, patients ate their supper, took their assigned insulin, and fasted overnight. Met was taken 30 min and MM injected 5 min before a standardized McDonald's® breakfast (fat 39 g, CHO 78 g, protein 24 g) followed by sampling over 8 hrs. ANCOVA models included treatment as a fixed effect, '0' hr value as baseline for area under the curve (AUC) analysis, and pre-randomization value as a covariate for all corresponding blood draw time-points. Pre-randomization, the AUC increase in BG, IL 6, and TNFα after breakfast were similar in both groups. At endpoint, the AUC in BG, IL 6, and TNFα were lower in the MM+Met group compared with the G+Met group (see table). Compared with the G+Met group, the MM+Met group had higher serum insulin levels (p<0.0001) at the 1st and 2nd hours and lower BG (p≤0.01), IL 6 (p≤0.002), and TNFa (p≤0.03) at the 3rd and 4th hours after breakfast. Our study shows that a basal+prandial insulin regimen reduced postprandial IL 6 and TNFα significantly more than a basal insulin regimen, extending our report on similar changes in hs-CRP. Whether or not these changes have clinical significance will require a long-term prospective study. [ABSTRACT FROM AUTHOR]

Abstract: Background: In people without diabetes, ∼50% of daily insulin secretion is basal and the remainder is postprandial. Hence, it would be expected that insulin replacement therapy in a 50/50 ratio with each meal would mimic physiologic insulin secretion better than treatment with once-daily basal insulin in patients with diabetes mellitus. Using lispro mix (LM) 50/50 before meals may be a logical approach to achieving glycemic targets (glycosylated hemoglobin [HbAlc] and pre- and postprandial blood glucose [BG] concentrations) in these patients. Objective: The aim of this study was to test the hypothesis that treatment with a premixed insulin analogue containing 50/50 basal + prandial insulins administered before each meal would achieve lower overall and mealtime glycemic control than once-daily basal insulin analogue, both plus metformin (Met), in patients with type 2 diabetes mellitus. Methods: This 24-week, randomized, open-label, parallel-group trial was conducted at 38 sites across Australia, Greece, India, The Netherlands, Poland, Puerto Rico, and the United States. Male and female patients aged 35 to 75 years with type 2 diabetes mellitus and an HbA1c level of 6.5% to 11.0%, who were receiving metformin and/or a sulfonylurea with a stable dose of 0 to 2 daily insulin injections over the previous 3 months were eligible. Patients were randomly assigned to receive LM50/50 (50% insulin lispro protamine suspension [ILPS] and 50% lispro) TID plus metformin (to a maximally tolerated daily dosage of 500-1000 mg BID) (LM50/50 + Met) or insulin glar-gine QD at bedtime plus metformin (500-1000 mg BID) (G + Met) for 24 weeks. With LM50/50 + Met, the insulin dose was titrated to target a fasting BG (FBG) level of <6.7 mmol/L (<120 mg/dL) and a 2-hour post-prandial BG (PPBG) level of <8.0 mmol/L (<144 mg/dL) [Copyright &y& Elsevier]

Introduction: We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF/MEN/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials provides an opportunity for improving the characterization of outcomes., Methods: A retrospective analysis of placebo-controlled, open-label, and compassionate-use trials was conducted. Adult patients received infusions of either DrotAA or placebo. All pediatric patients (<18 years old) received DrotAA. 189 adult and 121 pediatric patients presented with PF/MEN/MD., Results: Fewer adult patients with PF/MEN/MD met cardiovascular (68.3% versus 78.8%) or respiratory (57.8% versus 80.5%) organ dysfunction entry criteria than those without. DrotAA-treated adult patients with PF/MEN/MD (n = 163) had an observed 28-day mortality rate of 19.0%, a 28-day serious bleeding event (SBE) rate of 6.1%, and an intracranial hemorrhage (ICH) rate of 4.3%. Six of the seven ICHs occurred in patients with MEN (three of whom were more than 65 years old with a history of hypertension). DrotAA-treated adult patients without PF/MEN/MD (n = 3,088) had an observed 28-day mortality rate of 25.5%, a 28-day SBE rate of 5.8%, and an ICH rate of 1.0%. In contrast, a greater number of pediatric patients with PF/MEN/MD met the cardiovascular organ dysfunction entry criterion (93.5% versus 82.5%) than those without. DrotAA-treated PF/MEN/MD pediatric patients (n = 119) had a 14-day mortality rate of 10.1%, an SBE rate of 5.9%, and an ICH rate of 2.5%. DrotAA-treated pediatric patients without PF/MEN/MD (n = 142) had a 14-day mortality rate of 14.1%, an SBE rate of 9.2%, and an ICH rate of 3.5%., Conclusion: DrotAA-treated adult patients with severe sepsis presenting with PF/MEN/MD had a similar SBE rate, a lower observed 28-day mortality rate, and a higher observed rate of ICH than DrotAA-treated patients without PF/MEN/MD. DrotAA-treated pediatric patients with severe sepsis with PF/MEN/MD may differ from adults, because all three outcome rates (SBE, mortality, and ICH) were lower in pediatric patients with PF/MEN/MD.