Daily Endocrinology Research Analysis

The 3D human pituitary organoid represents a promising laboratory model for investigating human pituitary diseases. Nonetheless, this technology is still in its nascent stage, with uncertainties regarding the cellular composition, intercellular interactions, and spatial distribution of the human pituitary organoids. To address these gaps, the culture conditions are systematically adjusted and the efficiency of induced pluripotent stem cells' (iPSCs') differentiation into pituitary organoids is successfully improved, achieving results comparable to or exceeding those of previous studies. Additionally, single-cell RNA-sequencing (scRNA-seq) and stereomics sequencing (Stereo-seq) are performed on the pituitary organoids for the first time, and unveil the diverse cell clusters, intricate intercellular interactions, and spatial information within the organoids. Furthermore, the SOX3 gene interference impedes the iPSCs' differentiation into pituitary organoids, thereby highlighting the potential of pituitary organoids as an ideal experimental model. Altogether, the research provides an optimized protocol for the human pituitary organoid culture and a valuable transcriptomic dataset for future explorations, laying the foundation for subsequent research in the field of pituitary organoids or pituitary diseases.

IMPORTANCE: There is a need for additional treatment options for people with type 2 diabetes treated with insulin. Given the limited data on the use of automated insulin delivery (AID) systems in type 2 diabetes, studies evaluating their safety and efficacy are important. OBJECTIVE: To evaluate the association of AID with hemoglobin A1c (HbA1c) levels in a diverse cohort of adults with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This single-arm prospective trial was conducted at 21 clinical centers in the United States among individuals aged 18 to 75 years with type 2 diabetes who had been using insulin for at least 3 months prior to screening. Participants with AID system use were excluded. The study started with a 14-day standard therapy phase, followed by 13 weeks of treatment with the investigational device. The first participant was enrolled April 11, 2023, and the last participant follow-up visit was February 29, 2024. INTERVENTION: Participants used the Omnipod 5 AID System for 13 weeks following the 14-day standard therapy phase. MAIN OUTCOMES AND MEASURES: Primary outcome was change in HbA1c level at 13 weeks, tested sequentially for noninferiority (0.3% margin) and superiority, compared with baseline. RESULTS: Among 305 participants (mean [SD] age, 57 [11] years; 175 [57%] female; 72 [24%] Black, 66 [22%] Hispanic or Latino, and 153 [50%] White), 289 (95%) completed the trial. At baseline, 223 (73%) were using multiple daily injections, 63 (21%) were using basal insulin without bolus, 17 (6%) were using an insulin pump, 188 (62%) were using continuous glucose monitoring, 168 (55%) were using glucagon-like peptide-1 receptor agonists (GLP-1RAs), and 134 (44%) were using sodium-glucose transport protein 2 inhibitors (SGLT-2is). Following AID use, HbA1c levels decreased from a mean (SD) of 8.2% (1.3) at baseline to 7.4% (0.9) at 13 weeks (mean difference, -0.8 [95% CI, -1.0 to -0.7] percentage points; P < .001 for noninferiority and superiority). Improvement was seen across various subgroups (age, sex, race and ethnicity, insurance), and notably with or without use of GLP-1RAs or SGLT-2is and regardless of pretrial mealtime insulin regimen. Time in target glucose range (70-180 mg/dL) increased from a mean (SD) of 45% (25) to 66% (17) (mean difference, 20 [95% CI, 18 to 22] percentage points; P < .001). Percentage of time in hypoglycemic ranges of less than 54 mg/dL and less than 70 mg/dL was noninferior compared with standard therapy. There was 1 episode of severe hypoglycemia and none of diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome. CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, HbA1c levels were lower in a diverse cohort of adults with type 2 diabetes following AID initiation, suggesting that AID may be a beneficial and safe option for people with type 2 diabetes using insulin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05815342.

OBJECTIVE: To assess the relationship between arterial stiffness, an early marker of macrovascular cardiovascular disease, and microvascular complications in adolescents and young adults with youth-onset diabetes. RESEARCH DESIGN AND METHODS: This study included 1,226 individuals (median age at initial visit 18 years; 58% female; 53% non-Hispanic White, 22% non-Hispanic Black, and 20% Hispanic) with youth-onset type 1 or type 2 diabetes from the SEARCH for Diabetes in Youth Study. Arterial stiffness measures included pulse wave velocity for carotid femoral, carotid radial, femoral foot, and augmentation index (AIx). Microvascular complications included microalbuminuria, peripheral neuropathy, and retinopathy. Participants were followed up once at ∼5 years. RESULTS: Cross-sectionally, in type 1 diabetes, AIx was associated with higher odds of having any one microvascular complication (odds ratio [OR] 1.35; 95% CI 1.04-1.76), microalbuminuria (OR 2.76; 95% CI 1.78-4.39), neuropathy (OR 1.63; 95% CI 1.07-2.50), and retinopathy (OR 1.37; 95% CI 1.06-1.79). In type 2 diabetes, AIx was associated with higher odds of microalbuminuria (OR 2.05; 95% CI 1.04-4.33; all P < 0.05). In longitudinal analysis, in type 1 diabetes, a change in AIx was associated with the development of any one microvascular complication (OR 1.45; 95% CI 1.15-1.82), microalbuminuria (OR 5.42; 95% CI 1.98-14.80), neuropathy (OR 2.03; 95% CI 1.22-3.40), and retinopathy (OR 1.48; 95% CI 1.15-1.90). In type 2 diabetes, a change in AIx was associated with the development of microalbuminuria (OR 21.98; 95% CI 1.30-372.88; all P < 0.05). CONCLUSIONS: Arterial stiffness is related to and predicts microvascular complications in youth-onset type 1 and type 2 diabetes.