Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester

OBJECTIVE: To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes. RESEARCH DESIGN/METHOD: Post hoc analysis including 91 subjects randomised prior to pregnancy with known outcome in early pregnancy and 259 subjects randomised prior to pregnancy/during pregnancy of <10 weeks’ gestation with known late-pregnancy outcomes. Poor early-pregnancy outcomes included fetal loss <22 gestational weeks and/or congenital malformation (n = 18). Poor late-pregnancy outcomes included: composite endpoint including pre-eclampsia, preterm delivery and perinatal death (n = 78); preterm delivery (n = 63); and excessive fetal growth (n = 88). RESULTS: 18 patients experienced a malformed/lost fetus in early pregnancy – none preceded by severe hypoglycaemia. Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p = 0.012). In the third trimester, elevated HbA(1c), ≥ 1 plasma glucose (PG) measurement >11 mmol/L (198 mg/dL) and %PG values outside 3.9–7.0 mmol/L (70–126 mg/dL) were significant predictors of poor late-pregnancy outcomes (all p < 0.05). CONCLUSIONS: Elevated HbA(1c), high glucose spikes and out-of-range %PG in the third trimester, and albuminuria in early pregnancy, are associated with poor late-pregnancy outcomes

A comparison of two intensification regimens with rapid-acting insulin aspart in type 2 diabetes inadequately controlled by once-daily insulin detemir and oral antidiabetes drugs : the STEP-Wise™ randomized study

Objective: Comparison of the efficacy and safety of two intensification strategies for stepwise addition of prandial insulin aspart (IAsp) in patients with type 2 diabetes treated with insulin detemir (IDet). Methods: This was a randomized, controlled, parallel-group, open-label, 48-week trial comparing stepwise addition of IAsp to either the largest meal (titration based on pre-meal glucose values ‘SimpleSTEP’) or to the meal with the largest prandial glucose increment (titration based on post-meal values ‘ExtraSTEP’) in 296 individuals inadequately controlled on basal insulin and oral antidiabetes drugs (OADs). Following 12 weeks of basal IDet dose optimization, participants with HbA1c ≥7% entered three 12-week treatment periods with stepwise addition of a first IAsp bolus, then a second, and then a third, if HbA1c remained ≥7% after 12 and 24 weeks of treatment, respectively. Endpoints included HbA1c (primary endpoint), fasting plasma glucose (FPG), self-measured plasma glucose (SMPG), adverse events and hypoglycemia. Results: HbA1c decreased by ~1.2% in both groups, to 7.5±1.1% (SimpleSTEP) and 7.7±1.2% (ExtraSTEP) at end-of-trial (estimated treatment difference, SimpleSTEP - ExtraSTEP: -0.06%, (95%CI: -0.29 to 0.17)). SMPG levels decreased with both regimens. At trial end, approximately 75% of patients in each group were using three prandial injections. The frequency of adverse events and hypoglycemia was low, and similar between groups. Conclusion: The SimpleSTEP and ExtraSTEP strategies for stepwise addition of IAsp to one or more meals were equally effective at intensifying therapy in patients with type 2 diabetes not achieving glycemic control on basal insulin and OADs

Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100) for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial - Fig 2

<p><b>(A) Mean HbA</b>_<b>1c</b><b>over time to 52 weeks, (B) mean fasting plasma glucose (FPG) over time to 52 weeks, (C) mean self-measured blood glucose profile at baseline, Week 0 and Week 52, and (D) mean prandial increment at breakfast, lunch, main evening meal and overall at 52 weeks.</b> (A) and (B): Data are mean ± SEM in the full analysis set. Missing data were imputed using last observation carried forward. *Calculated, not measured. Treatment differences are derived from a least square means-based model. (C) and (D): Full analysis set. Missing data were imputed using last observation carried forward. Prandial increment is the difference between SMPG values after meal (90 min) and before meal. Comparisons: estimates adjusted for multiple covariates. *Indicate statistically significant difference at Week 52 before breakfast (p < 0.05), and at 04.00 h and at breakfast the following day (p < 0.0001). **Before breakfast: estimated treatment difference (ETD) 0.81 mmol/L; 95% CI 0.46, 1.17. ^†At 4.00 h: ETD 0.53 mmol/L; 95% CI 0.10, 0.95. ^‡Before breakfast the following morning: ETD 0.89 mmol/L; 95% CI 0.56, 1.23. IDegIAsp, insulin degludec/insulin aspart; HbA_1c, glycosylated hemoglobin; IGlar, insulin glargine (U100); OD, once daily; SEM, standard error of the mean; SMPG, self-measured plasma glucose.</p

Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100) for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial.

The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated.In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221). The primary endpoint was change from baseline to Week 26 in HbA1c.After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was -0.08% (-0.26, 0.09 95%CI), confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p < 0.0001) whereas the rate of nocturnal hypoglycemia was 75% lower (p < 0.0001) for IDegAsp versus IGlar.Nocturnal-confirmed hypoglycemia was higher with IGlar whereas overall and diurnal hypoglycemia were higher with IDegAsp dosed at breakfast. These results highlight the importance of administration of IDegAsp with the main meal of the day, tailored to the individual patient's needs.ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext]

Cumulative frequency of hypoglycemia.

<p><b>* (A) Core phase and (B) extension phase.</b> *Safety analysis set.IDegIAsp, insulin degludec/insulin aspart; IGlar, insulin glargine (U100); OD, once daily.</p

Titration algorithm for IDegAsp or IGlar.

<p>Titration algorithm for IDegAsp or IGlar.</p

Participating countries^*.

<p>Participating countries^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163350#t001fn001" target="_blank">*</a>}.</p