The type 2 diabetes gene product STARD10 is a phosphoinositide-binding protein that controls insulin secretory granule biogenesis.

OBJECTIVE: Risk alleles for type 2 diabetes at the STARD10 locus are associated with lowered STARD10 expression in the ß-cell, impaired glucose-induced insulin secretion, and decreased circulating proinsulin:insulin ratios. Although likely to serve as a mediator of intracellular lipid transfer, the identity of the transported lipids and thus the pathways through which STARD10 regulates ß-cell function are not understood. The aim of this study was to identify the lipids transported and affected by STARD10 in the ß-cell and the role of the protein in controlling proinsulin processing and insulin granule biogenesis and maturation. METHODS: We used isolated islets from mice deleted selectively in the ß-cell for Stard10 (ßStard10KO) and performed electron microscopy, pulse-chase, RNA sequencing, and lipidomic analyses. Proteomic analysis of STARD10 binding partners was executed in the INS1 (832/13) cell line. X-ray crystallography followed by molecular docking and lipid overlay assay was performed on purified STARD10 protein. RESULTS: ßStard10KO islets had a sharply altered dense core granule appearance, with a dramatic increase in the number of "rod-like" dense cores. Correspondingly, basal secretion of proinsulin was increased versus wild-type islets. The solution of the crystal structure of STARD10 to 2.3 Å resolution revealed a binding pocket capable of accommodating polyphosphoinositides, and STARD10 was shown to bind to inositides phosphorylated at the 3' position. Lipidomic analysis of ßStard10KO islets demonstrated changes in phosphatidylinositol levels, and the inositol lipid kinase PIP4K2C was identified as a STARD10 binding partner. Also consistent with roles for STARD10 in phosphoinositide signalling, the phosphoinositide-binding proteins Pirt and Synaptotagmin 1 were amongst the differentially expressed genes in ßStard10KO islets. CONCLUSION: Our data indicate that STARD10 binds to, and may transport, phosphatidylinositides, influencing membrane lipid composition, insulin granule biosynthesis, and insulin processing.

Depressive Symptoms, Co-Morbidities, and Glycemic Control in Hong Kong Chinese Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: Undiagnosed depression is an important comorbidity in type 2 diabetes (T2D) which can be detected using the Geriatric Depression Scale (GDS-15) questionnaire. In this cross-sectional study, we examined the associations of depression using GDS score with control of cardiometabolic risk factors and health status in elderly patients with T2D. SETTING AND PARTICIPANTS: Between February and December 2013, patients aged ≥65 years who underwent structured comprehensive assessment as a quality improvement program at the Diabetes Center of a teaching hospital were invited to complete the GDS-15 questionnaire. MAIN OUTCOME MEASURES: Depression was defined as a GDS score ≥7. Demographic data, prior history of co-morbidities, frequency of self-reported hypoglycemia, and attainment of treatment targets defined as HbA1c, <7%, blood pressure <130/80 mmHg, and LDL-C <2.6 mmol/L were documented. RESULTS: Among 325 participants (65% male, median [interquartile range] age: 69 [8] years), 42 (13%) had depression. Patients with depression had longer disease durations (mean ± SD: 15.1 ± 9.1 vs. 11.6 ± 8.1 years, P = 0.02), more frequent self-reported hypoglycemic events (17 vs. 6%, P = 0.03) and were less likely to attain all three treatment targets (0 vs. 16%, P = 0.004) than those without depression. On multivariable analysis, patients with depression had an odds ratio of 2.84 (95% confidence intervals: 1.35-6.00, P = 0.006) of reporting prior history of co-morbidities. CONCLUSION: In elderly patients with T2D, depression was not uncommon especially in those with poor control of risk factors, hypoglycemia, and co-morbidities. Inclusion of GDS-15 questionnaire during structured assessment for complications and risk factors can identify these high-risk patients for more holistic management of their physical and mental health.

The Longitudinal Effects of Persistent Apnea on Cerebral Oxygenation in Infants Born Preterm.

OBJECTIVE: To assess the incidence and impact of persistent apnea on heart rate (HR), oxygen saturation (SpO2), and brain tissue oxygenation index (TOI) over the first 6 months after term equivalent age in ex-preterm infants. STUDY DESIGN: Twenty-four preterm infants born between 27 and 36 weeks of gestational age were studied with daytime polysomnography at 2-4 weeks, 2-3 months, and 5-6 months post-term corrected age. Apneas lasting ≥3 seconds were included and maximal percentage changes (nadir) in HR, SpO2, and tissue oxygenation index (TOI, NIRO-200 Hamamatsu) from baseline were analyzed. RESULTS: A total of 253 apneas were recorded at 2-4 weeks, 203 at 2-3 months, and 148 at 5-6 months. There was no effect of gestational age at birth, sleep state, or sleep position on apnea duration, nadir HR, SpO2, or TOI. At 2-4 weeks, the nadirs in HR (-11.1 ± 1.2 bpm) and TOI (-4.4 ± 1.0%) were significantly less than at 2-3 months (HR: -13.5 ± 1.2 bpm, P < .05; TOI: -7.5 ± 1.1 %, P < .05) and at 5-6 months (HR: -13.2 ± 1.3 bpm, P < .01; TOI: -9.3 ± 1.2%, P < .01). CONCLUSIONS: In ex-preterm infants, apneas were frequent and associated with decreases in heart rate and cerebral oxygenation, which were more marked at 2-3 months and 5-6 months than at 2-4 weeks. Although events were short, they may contribute to the adverse neurocognitive outcomes that are common in ex-preterm children.