CD4+CD25+CD127hi cell frequency predicts disease progression in type 1 diabetes.

Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune regulation. A better understanding of such natural mechanisms of immune regulation might identify new targets for immunotherapies that reverse type 1 diabetes (T1D). In this study, using Cox model multivariate analysis, we validated our previous findings that patients with the highest frequency of CD4+CD25+CD127hi (127-hi) cells at diagnosis experience the longest partial remission, and we showed that the 127-hi cell population is a mix of Th1- and Th2-type cells, with a significant bias toward antiinflammatory Th2-type cells. In addition, we extended these findings to show that patients with the highest frequency of 127-hi cells at diagnosis were significantly more likely to maintain ß cell function. Moreover, in patients treated with alefacept in the T1DAL clinical trial, the probability of responding favorably to the antiinflammatory drug was significantly higher in those with a higher frequency of 127-hi cells at diagnosis than those with a lower 127-hi cell frequency. These data are consistent with the hypothesis that 127-hi cells maintain an antiinflammatory environment that is permissive for partial remission, ß cell survival, and response to antiinflammatory immunotherapy.

An improved clinical model to predict stimulated C-peptide in children with recent-onset type 1 diabetes.

BACKGROUND: Stimulated C-peptide measurement after a mixed meal tolerance test (MMTT) is the accepted gold standard for assessing residual beta-cell function in type 1 diabetes (T1D); however, this approach is impractical outside of clinical trials. OBJECTIVE: To develop an improved estimate of residual beta-cell function in children with T1D using commonly measured clinical variables. SUBJECTS/METHODS: A clinical model to predict 90-minute MMTT stimulated C-peptide in children with recent-onset T1D was developed from the combined AbATE, START, and TIDAL placebo subjects (n = 46) 6 months post-recruitment using multiple linear regression. This model was then validated in a clinical cohort (Hvidoere study group, n = 262). RESULTS: A model of estimated C-peptide at 6 months post-diagnosis, which included age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), and insulin dose predicted 90-minute stimulated C-peptide measurements (adjusted R2 = 0.63, P < 0.0001). The predictive value of insulin dose and HbA1c alone (IDAA1c) for 90-minute stimulated C-peptide was significantly lower (R2 = 0.37, P < 0.0001). The slopes of linear regression lines of the estimated and stimulated 90-minute C-peptide levels obtained at 6 and 12 months post diagnosis in the Hvidoere clinical cohort were R2 = 0.36, P < 0.0001 at 6 months and R2 = 0.37, P < 0.0001 at 12 months. CONCLUSIONS: A clinical model including age, gender, BMI, HbA1c, and insulin dose predicts stimulated C-peptide levels in children with recent-onset T1D. Estimated C-peptide is an improved surrogate to monitor residual beta-cell function outside clinical trial settings.

Medications for increasing milk supply in mothers expressing breastmilk for their preterm hospitalised infants.

BACKGROUND: Breastmilk remains the optimal form of enteral nutrition for term and preterm infants until up to six months postnatal age. Mothers of preterm infants who have not established suck feeds must express their breastmilk and often have difficulty in maintaining sufficient volume for their infants' needs (Donath 2008). In preterm infants, donor breastmilk reduced the occurrence of necrotising enterocolitis, when compared with formula feeds (McGuire 2003). Also, case-control studies have suggested that breastmilk is associated with an improvement in feeding tolerance, a reduction in significant gastrointestinal infective events (Beeby 1992) and a reduction in late-onset sepsis (Schanler 1999) when compared with formula feeds in preterm hospitalised infants. OBJECTIVES: To assess the effect of medication given for at least seven days to mothers of preterm infants whose breastmilk is insufficient for their infants' needs on the outcomes of expressed milk volume and duration of breastfeeding. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2011). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of breastmilk-augmenting medications (compared with placebo or with other augmenting medications) in mothers with preterm hospitalised infants whose breastmilk volumes failed to meet their infants' requirements. We did not include trials with a cluster-randomised or cross-over design. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed studies for inclusion, assessed risk of bias, and extracted data. Any differences were resolved by consensus. Data were checked for accuracy. MAIN RESULTS: Two trials (involving 59 mothers) that examined the use of domperidone in a total of 59 mother-infant pairs met the inclusion criteria. Meta-analysis of these trials showed a modest increase in expressed breastmilk (EBM) of 99.49 mL/day (95% confidence intervals -1.94 to 200.92; random-effects, T² 3511.62, I² 63%) in mothers given domperidone. Both trials gave the same dose of domperidone (10 mg three times per day) with a duration of seven days in the smaller trial and 14 days in the larger.Neither trial showed significant improvements in longer-term outcomes of breastfeeding in a preterm population and no adverse effects were reported. AUTHORS' CONCLUSIONS: Two studies with a total of 59 mothers suggest modest improvements in short-term EBM volumes when a medication is used after insufficient EBM occurs in mothers following preterm delivery. In both studies, the medication was commenced ≧14 days post delivery and following insufficient EBM supply with other lactation supports.Currently, no studies support prophylactic use of a galactagogue medication at any gestation. Use of any galactagogue medication has only been examined at more than 14 days post delivery and after full lactation support has been given. Further trials should examine larger groups of preterm mothers and consider breastfeeding outcomes over a longer period.