In This Issue of Diabetes Care

A closed-loop insulin delivery system (artificial pancreas) appears to deliver comparable glucose control but significantly less hypoglycemia than sensor-augmented pump therapy in pregnant women with type 1 diabetes. The study by Stewart et al. (p. 1391) suggests that with longer-duration studies, including pivotal trials in larger populations, clinical efficacy of the system might be proven and also might help assess the impact on longer-term neonatal outcomes. The authors recruited 16 pregnant women for the open-label, randomized, crossover trial where they used either day-and-night closed-loop or sensor-augmented pump insulin delivery systems for 28 days, separated by a washout period. The primary end point was time within range for glucose levels set at 63–140 mg/dL. They report that glucose levels remained in the target range for _∼60% of the time with both insulin delivery approaches. Use of the closed-loop approach did however result in fewer episodes of hypoglycemia (8 vs. 12.5 over 28 days) and less time spent with hypoglycemia defined at <63 mg/dL blood glucose (1.6% vs. 2.7%). While no severe adverse events reportedly occurred, there were apparently high rates of issues with the devices involved in the closed-loop system. In terms of obstetric and neonatal outcomes, there were a number of complications reported with both mothers and children, which the authors say is suboptimal and should be investigated further. Commenting further on the study, author Helen R. Murphy told Diabetes Care: “Women in both groups spent _∼60% time in target range but closed-loop reduced the extent and duration of hypoglycemia, suggesting that it is potentially safer than sensor-augmented pump therapy. Women who entered pregnancy with near-optimal HbA_1c levels consistently achieved 70–75% time in target range. Women with suboptimal glucose control (HbA_1c levels >7.5%) in early pregnancy never achieved comparable glycemia, reaching 65–70% time in target range only in the third trimester. Automated insulin delivery still requires high-quality dietary and prandial insulin dosing. It is not yet a hands-off option.”

Stewart et al. Day-and-night closed-loop insulin delivery in a broad population of pregnant women with type 1 diabetes: a randomized controlled crossover trial. Diabetes Care 2018;41:1391–1399

The long-term outcomes of a lifestyle intervention diabetes prevention program in American Indian and Alaska Native communities are reported by Jiang et al. (p. 1462). The authors suggest that even moderate weight loss can result in substantial reductions in risk for diabetes. However, with high participant attrition rates, issues with reaching eligible individuals in the first place (men, in particular), and suboptimal weight loss in the program, they suggest further research is still needed to optimize the approach. Beginning in January 2006, the program started enrolling target-population adults with prediabetes into a 16-session diabetes prevention curriculum in combination with a thorough clinical assessment. The program consisted of group-based weekly coaching focused on healthy diet and physical exercise promotion. Then, over the following 10 years, participants received annual clinical assessments as well as individual lifestyle coaching sessions every quarter. Following the completion of the curriculum, approximately one-third of the participants managed to achieve weight loss of >5% while one-fifth of the participants managed weight loss of 3–5%. Just under half of the participants did not achieve weight loss of more than 3%. In comparison to this last group, participants who achieved >5% weight loss reportedly had 64% lower risk of developing diabetes during the first six years of follow-up. Meanwhile those who achieved weight loss of 3–5% had 40% lower risk. According to author Luohua Jiang: “As one of the largest diabetes prevention translational efforts implemented in a racial/ethnic minority population, our results demonstrate the long-term effectiveness of lifestyle intervention among those who managed to lose moderate to small amounts of weight in the intensive phase of the intervention. We hope the results and lessons revealed by this study will inform the diffusion of this evidence-based intervention to U.S. health care systems to combat the diabetes epidemic that plagues many underserved populations.”

Jiang et al. Long-term outcomes of lifestyle intervention to prevent diabetes in American Indian and Alaska Native communities: the Special Diabetes Program for Indians Diabetes Prevention Program. Diabetes Care 2018;41:1462–1470

Dietary interventions are associated with improved glycemic outcomes and lower infant birth weights in women with gestational diabetes mellitus (GDM), according to Yamamoto et al. (p. 1346). Using a systematic review and meta-analysis, they reveal that intervening after a diagnosis of GDM is likely to improve maternal glycemic and infant adiposity outcomes. The authors screened just under 2,300 sources and identified 18 randomized controlled trials that used some sort of dietary intervention and examined outcomes relating to glucose levels and also maternal and neonatal health. In pooled analyses with 1,151 participants, they found that compared to control subjects, dietary interventions in general resulted in reductions in fasting and postprandial glucose levels. There was also a lower need for medication when using the dietary approaches in comparison with control subjects. In terms of neonatal outcomes, the diets were associated with lower infant birth weights and less macrosomia. While the data point towards improved outcomes in GDM, they suggest that there is still room for improvement in the dietary advice given to women. They also point out that the quality of evidence is low to very low and that baseline differences between groups in terms of glucose levels may have influenced the results. They also highlight that, in general, small study populations were used, making comparisons between the diets difficult. Author Helen R. Murphy commented further on the research: “As one in six pregnant women are affected by gestational diabetes, these data are really important to remind women and clinicians that dietary interventions started during pregnancy are effective for improving neonatal health outcomes. Furthermore, intervening after a diagnosis of gestational diabetes is not too late to improve maternal glycemia and infant birth weight outcomes. More attention is now needed to compare the risks and benefits of different dietary interventions such as energy restriction, low glycemic index, and the Mediterranean diet, so that women and clinicians can make informed decisions about which diets work best for reducing the immediate and longer-term consequences of gestational diabetes.”

Yamamoto et al. Gestational diabetes mellitus and diet: a systematic review and meta-analysis of randomized controlled trials examining the impact of modified dietary interventions on maternal glucose control and neonatal birth weight. Diabetes Care 2018;41:1346–1361

The long-term trajectory of C-peptide decline in type 1 diabetes appears to have two distinct phases. Over the first seven years following diagnosis, C-peptide levels appear to fall exponentially, after which levels appear stable with no further decline, according to Shields et al. (p. 1486). As a result, they suggest that this seven-year inflection point in C-peptide levels may be representative of unrecognized changes in immune and/or β-cell function and that might mean there are opportunities to intervene pharmacologically in the disease. According to the authors, they used regression approaches and cross-sectional data from just over 1,500 individuals with type 1 diabetes to assess patterns of association between urinary C-peptide creatinine ratio (UCPCR) and diabetes duration. They then attempted to replicate associations with longitudinal follow-up data using the same approach or with plasma C-peptide levels in other individuals with the disease. The authors reportedly identified two clear phases in the cross-sectional data where C-peptide fell exponentially in the first seven years at a rate of _∼47% per year, followed by a stable period after that. The two phases had similar duration and slopes in patients above and below the median age at diagnosis of 10.8 years. Meanwhile in the longitudinal data, patterns were similar, with UCPCR declining at 48% per year up to seven years followed by stability. Plasma C-peptide levels after seven years similarly remained stable. While the study could not uncover any of the underlying biological processes at play, the research suggests that the inflection at seven years might reflect the existence of a less susceptible population of β-cells or some kind of change in the immune-mediated attack at that point. On that basis, the authors suggest that there are unrecognized opportunities for interventions in the disease.

Shields et al. C-peptide decline in type 1 diabetes has two phases: an initial exponential fall and a subsequent stable phase. Diabetes Care 2018:41:1486–1492