Reductions in A1C with pump therapy in type 2 diabetes are independent of C-peptide and anti-glutamic acid decarboxylase antibody concentrations.

Insulin therapy is often necessary for patients with type 2 diabetes mellitus (T2DM) to achieve good glycemic control. However, insulin initiation is often delayed, and patients may spend 8 or more years with worsening glycosylated hemoglobin (A1C) values as they progress through treatment regimens including diet and exercise, metformin, and combinations of oral agents. Fear of injections, hypoglycemia, and weight gain, along with the perception that insulin will add to the burden of managing diabetes, all contribute to clinical inertia prior to initiation of insulin therapy. Although many T2DM patients reach A1C targets with the addition of basal insulin therapy, others require therapy intensification to a multiple daily injection (MDI) regimen. However, even with MDI, about 30% of T2DM patients do not meet A1C targets. These T2DM patients are potential candidates for insulin pump treatment, which offers several advantages compared with MDI. These advantages include adjustable basal rates, fewer needle insertion procedures, ability to deliver precise and convenient boluses, and reductions in both glycemic variability and severe hypoglycemia. Moreover, the ability to download and display information stored in the pump allows tracking of insulin use and assessment of adherence. Some evidence suggests that prompt initiation of pump therapy in T2DM preserves b-cell function; however, the therapeutic value of pump therapy in terms of A1C reduction has been poorly evaluated in T2DM until recently. Whether favorable glycemic response to pump therapy is restricted to the more severe insulin-deficient T2DM patients or to the late-onset autoimmune diabetes subset of T2DM-like patients remains questionable. The recently completed OpT2mise trial (registered at ClinicalTrials.gov with clinical trial registration number NCT01182493) established that in poorly controlled T2DM patients on optimized MDI regimens, intensification to insulin pump treatment resulted in significant reductions in A1C values. The study population included patients with a wide age range (30–75 years), using MDI regimens and high insulin doses (0.5–1.8 U/kg/day) titrated during a 2-month run-in phase. All oral diabetes medications were stopped except for metformin. Patients were randomized if their A1C value was in the 8–12% range to either pump therapy (n = 168) or to remain on MDI (n = 163). At the end of the 6month study phase, glucose control improved more in the pump group (A1C dropped from 9% to 7.9%), with a between-group A1C difference of 0.7% in favor of pump therapy (P < 0.001). Moreover, the total insulin daily dose was reduced by 20% with pump compared with MDI, suggesting an increase in insulin sensitivity driven by its continuous subcutaneous infusion. Investigational centers were required to collect plasma from fasting subjects for C-peptide and anti-glutamic acid decarboxylase (anti-GAD) antibody (Ab) determinations as part of each subject’s baseline (before randomization) and end-of-study (6-month) assessments; assays were carried out at a central laboratory (Covance, Inc. [corporate headquarters, Princeton, NJ]). C-peptide level was measured via direct chemiluminescence (Siemens Healthcare Diagnostics, Tarrytown, NY), and anti-GAD Ab level was measured via radioimmunoassay (Kronus, Boise, ID). Subjects were retrospectively grouped according to anti-GAD and C-peptide concentrations to explore associations between these biomarkers and baseline A1C values, A1C changes, or A1C changes attributable to treatment group assignment. Significance tests comparing betweenand within-group A1C changes were performed using an analysis of covariance that used treatment group assignment, analyte concentration category, and baseline A1C as covariates. Baseline A1C values and changes in A1C at 6 months for patients who were categorized according to baseline antiGAD Ab levels ( < 1 or ‡ 1 U/mL) or according to baseline C-peptide levels chosen such that the population was stratified into quartiles ( < 156 pmol/L [ < 0.47 ng/mL], ‡ 156 to