Daily Endocrinology Research Analysis
Analyzed 114 papers and selected 3 impactful papers.
Summary
Three randomized clinical trials advance endocrinology practice this cycle: a large international RCT shows automated insulin delivery improves HbA1c and reduces hypoglycemia versus multiple daily injections across ages with strong safety; a randomized bariatric study reveals distinct bile acid signatures and metabolic correlates between Roux-en-Y and one-anastomosis gastric bypass; and a randomized comparison indicates a 5:2 intermittent fasting meal-replacement regimen yields superior body composition and visceral fat reduction versus metformin or empagliflozin in early type 2 diabetes.
Research Themes
- Closed-loop insulin therapy improves glycemic outcomes and safety
- Differential bile acid signaling after alternative gastric bypass procedures
- Intermittent fasting meal-replacement as metabolic therapy in early T2D
Selected Articles
1. Automated basal insulin delivery versus multiple daily injections in type 1 diabetes: results from a randomized parallel controlled trial.
In a 6-month, international randomized trial across 32 centers, automated insulin delivery (MiniMed 670G/770G) significantly improved HbA1c (mean difference −0.7%) and reduced time below 70 mg/dL versus multiple daily injections in both youth and adults, with low rates of severe hypoglycemia and DKA.
Impact: This trial provides high-level evidence that closed-loop insulin delivery confers superior glycemic control and safety versus standard MDI across age groups, supporting broader clinical adoption.
Clinical Implications: Clinicians can preferentially recommend AID systems for eligible T1D patients to improve HbA1c and reduce hypoglycemia, with reassurance on safety across pediatric and adult populations.
Key Findings
- AID reduced HbA1c versus MDI with a mean difference of −0.7% (P=0.0002).
- AID decreased time below 70 mg/dL by 4.8% compared with MDI (P<0.001).
- Severe hypoglycemia and DKA rates were low and met predefined safety criteria.
Methodological Strengths
- Large, multicenter, international randomized controlled design
- Prespecified dual primary endpoints tailored to baseline HbA1c strata
Limitations
- Six-month duration limits long-term durability assessment
- Device-specific intervention (MiniMed 670G/770G) may limit generalizability to other AID systems
Future Directions: Longer-term randomized studies comparing multiple AID platforms and cost-effectiveness analyses across health systems are warranted.
INTRODUCTION: This study evaluated 6-month effectiveness and safety of automated insulin delivery (AID) in comparison with multiple daily injections (MDI) in pediatric and adult type 1 diabetes (T1D). MATERIALS AND METHODS: Individuals with T1D, aged 2-80 years, were enrolled across 32 international centers (in the United States, Europe, Canada, and New Zealand) and randomized 1:1 to AID intervention (MiniMed™ 670G or 770G system) or MDI with or without continuous glucose monitoring. Primary endpoints were change in mean HbA1c for participants with a baseline HbA1c >8.0% (Group 1) and percentage of time spent below 70 mg/dL (%TBR <70 mg/dL [<3.9 mmol/L]) for participants with baseline HbA1c ≤8.0% (Group 2), to show superiority of AID intervention versus MDI. Safety endpoints including rates of severe hypoglycemia and diabetic ketoacidosis (DKA), and difference in diabetes treatment satisfaction score were assessed. RESULTS: For Group 1, N = 56 participants (aged 29.4 ± 17.0 years) were randomized to AID intervention and N = 54 participants (aged 36.8 ± 19.6 years) were randomized to MDI. For Group 2, N = 73 (aged 37.4 ± 21.0 years) and N = 69 (aged 39.2 ± 19.3 years), respectively, were randomized to AID and MDI. Change in HbA1c (mean [95% CI] difference of -0.7% [-1.1, -0.3], P = 0.0002) and difference in %TBR <70 mg/dL (4.8% [-6.4, -3.1], P<0.001) favored AID intervention versus MDI. Rates of severe hypoglycemia (AID: 1.82/100 patient-years) and DKA (MDI: 3.52/100 patient-years) were low and met preestablished success criteria for safety. DISCUSSION: This large, international, multicenter randomized controlled trial demonstrates safety of the MiniMed™ 670G/770G systems. AID significantly improved HbA1c and time spent in hypoglycemia when compared with MDI, in both youth and adults living with T1D. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier NCT02748018.
2. Distinct fasting and postprandial bile acid responses following Roux-en-Y and one-anastomosis gastric bypass.
In a randomized comparison of RYGB versus OAGB with serial mixed-meal BA profiling, RYGB increased postprandial secondary bile acids (notably DCA, GDCA), whereas OAGB increased primary taurine-conjugated bile acids (e.g., TCDCA), with both procedures yielding similar overall metabolic improvements but distinct associations with insulin sensitivity and fat mass preservation.
Impact: This mechanistic RCT clarifies BA pathway differences between two widely used bypasses, informing individualized metabolic expectations and potential adjunct therapies targeting BA signaling.
Clinical Implications: Postoperative metabolic follow-up may consider surgery-specific BA signatures; future adjuncts (e.g., BA modulators) could be tailored by procedure to optimize insulin sensitivity or preserve lean mass.
Key Findings
- RYGB increased postprandial secondary bile acids from baseline to 12 months (overall p=0.004), notably DCA (p<0.001) and GDCA (p=0.006) versus OAGB.
- OAGB increased postprandial primary taurine-conjugated bile acids (p=0.039), especially TCDCA (p=0.036), compared with RYGB.
- BA changes correlated differentially with insulin sensitivity (post-RYGB) and fat mass preservation (post-OAGB), despite similar overall metabolic improvements.
Methodological Strengths
- Randomized allocation to two surgical procedures
- Detailed longitudinal LC-MS profiling of 15 individual bile acids during standardized mixed-meal tests
Limitations
- Modest sample size limits power for clinical endpoints and subgroup analyses
- Exploratory design; not powered to detect between-group differences in hard metabolic outcomes
Future Directions: Larger mechanistic RCTs integrating BA receptors/FGF19/GLP-1 dynamics and testing BA-modulating adjuncts stratified by procedure are warranted.
OBJECTIVE: Bariatric surgery is the most effective long-term treatment for obesity, but how different surgical techniques affect metabolic outcomes remains unclear. Bile acids (BAs), increasingly recognized as metabolic regulators, rise postprandially after surgery and may mediate some of these effects. This exploratory study investigates the differential impact of Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB) on BA profiles and associated metabolic outcomes over one year. METHODS: Forty-five patients with obesity (15 men, 30 women; mean (SD) age 46.6 (7.1) years) were randomized to receive either RYGB (n = 24) or OAGB (n = 20). Clinical assessments, body composition measurements (Dual energy X-ray absorptiometer), fasting blood tests including lipids and inflammation markers, 360-minute mixed meal test, and oral glucose tolerance test were conducted 4-6 weeks before and at 6 and 12 months after operation. Plasma total and 15 individual BAs (LC-MS) were measured at eight time points during the mixed meal test. RESULTS: RYGB led to an increase in postprandial secondary BAs from baseline to 12 months (p = 0.004), particularly deoxycholic acid (DCA; p < 0.001) and glycodeoxycholic acid (GDCA; p = 0.006) compared with OAGB. In contrast, OAGB led to an increase in postprandial primary taurine-conjugated BAs (p = 0.039), especially taurochenodeoxycholic acid (TCDCA; p = 0.036) compared with RYGB. Similarly, RYGB increased unconjugated secondary BAs, especially DCA, whereas OAGB increased conjugated primary BAs, like TCA and GCA during fasting. Metabolic improvements were similar in both groups. Post-RYGB increases in secondary BAs correlated with improved insulin sensitivity and post-OAGB increases in primary taurine-conjugated BAs correlated with higher fat mass preservation during weight loss. CONCLUSIONS: RYGB and OAGB differentially modulate BA profiles over one year, with RYGB increasing secondary BAs and OAGB increasing taurine-conjugated primary BAs. These findings suggest distinct mechanisms contributing to their metabolic benefits.
3. Effects of 5:2 intermittent fasting meal replacement on body composition and abdominal fat distribution in overweight and obese adults with early type 2 diabetes.
In a randomized, active-controlled 16-week trial in early T2D, a 5:2 intermittent fasting meal-replacement regimen produced the largest improvements in BMI, body fat mass, and abdominal fat distribution (including visceral and ectopic fat by energy spectrum CT) compared with metformin or empagliflozin.
Impact: This pragmatic dietary intervention outperformed two standard pharmacotherapies on body composition and visceral adiposity in early T2D, highlighting a potent, scalable lifestyle strategy with metabolic benefits.
Clinical Implications: 5:2 meal-replacement can be considered as a first-line or adjunct metabolic strategy in early T2D to preferentially reduce visceral fat and improve body composition, with structured monitoring.
Key Findings
- Randomized comparison (n=85) showed 5:2 MR achieved the largest BMI reduction over 16 weeks versus metformin and empagliflozin.
- 5:2 MR produced superior reductions in body fat mass and abdominal fat distribution, including visceral and ectopic fat assessed by energy spectrum CT.
- Correlations supported that larger BMI reductions tracked with greater improvements in fat distribution metrics.
Methodological Strengths
- Randomized, active-controlled three-arm design
- Objective assessments of body composition and fat distribution (bioimpedance and energy spectrum CT)
Limitations
- Single-center study with 16-week duration limits generalizability and long-term inference
- Exploratory outcomes; study not powered for cardiovascular or glycemic hard endpoints
Future Directions: Multicenter, longer-duration trials assessing durability, cardiometabolic outcomes, and adherence strategies for 5:2 MR versus contemporary pharmacotherapy are needed.
BACKGROUND AND AIMS: The 5:2 intermittent fasting meal replacement (5:2 MR) improved glycemic control and weight loss in adults with type 2 diabetes mellitus (T2DM). OBJECTIVE: This analysis further investigated the exploratory outcomes related to body composition and abdominal fat distribution. METHODS: This was a single-center analysis of a randomized, active-controlled trial (EARLY), which enrolled overweight and obese patients with early T2DM. A total of 85 participants were randomly assigned to receive metformin (n = 28), empagliflozin (n = 28), or 5:2 MR (n = 29) for 16 weeks. Body composition was assessed using InBody device, and the energy spectrum CT was used to measure abdominal fat distribution. Spearman's correlation coefficient was used to evaluate the associations between change in body mass index (BMI) and change in the exploratory outcomes. RESULTS: Compared with the metformin and empagliflozin groups, the 5:2 MR group showed the most significant reductions in BMI (least-squares mean, -3.41 kg/m CONCLUSION: The 5:2 MR regimen may be more effective than metformin and empagliflozin in improving body composition and abdominal fat distribution in early T2DM, and is proposed as a therapeutic option.