Real-world use of Control-IQ™ technology automated insulin delivery in pregnancy: A case series with qualitative interviews.

BACKGROUND: Most commercially available automated insulin delivery (AID) systems are not approved for pregnancy use. Information regarding use of the Tandem t:slim X2 insulin pump with Control-IQ™ technology in pregnancy is lacking. AIMS: This case series aimed to explore glycaemic and qualitative experiences of four early adopters of Control-IQ technology in pregnancy. METHODS: Participants used Control-IQ technology in pregnancy and postpartum and consented to analysis of glycaemic data and semi-structured interviews. RESULTS: Case 1 began Control-IQ technology at 10 weeks gestation. Her pregnancy glucose time-in-range (3.5-7.8 mmol/L [63-140 mg/dL]) increased from 58.7% to 73.3% by third trimester. Cases 2-4 began using Control-IQ technology 0-2 months preconception. Pregnancy time-in-range glucose increased from 73.4% to 78.7%, 78% to 83.6%, and 46.5% to 71.9% between first and third trimesters, respectively. A mid-pregnancy decline in time-in-range glucose was observed in two of the four participants related to suboptimal pump setting adjustments and delays in sensor and infusion set replacement. No diabetic ketoacidosis or severe hypoglycaemia occurred. All participants reported reduced diabetes management burden and improved sleep with Control-IQ technology use. CONCLUSIONS: Early adopters of Control-IQ technology safely used this system off-label in pregnancy and reported reduced diabetes management burden and improved sleep. The largest glycaemic improvements were observed among those with the lowest pregnancy time-in-range glucose at the beginning of pregnancy. Participants with low pregnancy glucose time-in-range increased their time-in-range with Control-IQ technology use and participants with high pregnancy glucose time-in-range maintained and increased their time-in-range with less diabetes management burden.

A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells.

GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H(+)-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca(2+) influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion.