Medical Bulletin 24/ June/ 2024

In a study published in the journal JAMA Network Open, researchers evaluated the effect of the 5:2, that is 2 non-consecutive fasting days and 5 days of habitual intake per week, and meal replacement diet on glycemic control among patients with early type 2 diabetes compared with metformin and empagliflozin.

According to the International Diabetes Federation in 2021, 537 million adults worldwide have diabetes, affecting roughly 1 in 10 adults.

Overweight and obesity are major risk factors for type 2 diabetes, and appropriate weight loss can improve glycemic control and reduce the need for antidiabetic medications. However, achieving weight loss can be challenging, requiring strategies like meal replacement (MR) or dietary restriction which involves substituting prepackaged food or beverages for one or more meals to provide energy.

The 5:2 intermittent fasting diet, which includes two non-consecutive fasting days (with one-fourth the usual energy intake) and five days of regular eating per week, has shown promise. Previous studies found that a 12-month 5:2 intermittent fasting diet significantly reduced HbA1c levels in overweight or obese patients with type 2 diabetes, compared to a continuous energy restriction diet.

The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study was analysed which screened 509 eligible patients, with 405 randomly assigned to three groups for an intention-to-treat analysis. Participants were allocated in a 1:1:1 ratio to receive either metformin, empagliflozin, or a 5:2 meal replacement (MR) diet for 16 weeks, followed by an 8-week follow-up. The primary endpoint was the change in haemoglobin A1c (HbA1c) levels from baseline to 16 weeks. Secondary endpoints included changes in body weight, anthropometric measurements, and biochemical parameters.

The result showed that of the 405 randomized participants, 332 completed the 16-week treatment. From baseline to week 16, participants in the 5:2 MR group showed the greatest reduction in HbA1c, significantly greater than patients receiving metformin and empagliflozin. At week 16, the mean weight loss in the 5:2 MR group was greater than that in the metformin group and empagliflozin group.

The findings revealed that, for patients with newly diagnosed type 2 diabetes, a 16-week intervention with 5:2 MR could improve glycemic control and weight loss while also improving blood pressure, triglyceride levels, and HDL-C levels. Therefore, 5:2 MR may serve as an initial lifestyle intervention for patients with type 2 diabetes, providing an alternative to the use of metformin and empagliflozin medications.

Reference: Guo L, Xi Y, Jin W, et al. A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes: The EARLY Randomized Clinical Trial. JAMA Netw Open. 2024;7(6):e2416786. doi:10.1001/jamanetworkopen.2024.16786

Researchers at the University of California San Diego School of Medicine conducted an advanced study demonstrating the potential of tirzepatide, known to manage type 2 diabetes, as the first effective drug therapy for obstructive sleep apnea (OSA), a sleep-related disorder characterized by repeated episodes of irregular breathing due to complete or partial blockage of the upper airway.

The results, published in the New England Journal of Medicine, highlighted the treatment’s potential to improve the quality of life for millions around the world affected by obstructive sleep apnea.

Obstructive sleep apnea can result in reduced oxygen levels in the blood and can also be associated with an increased risk of cardiovascular complications, such as hypertension and heart disease. Recent studies suggested that the number of OSA patients worldwide is close to 936 million.

Tirzepatide is a novel medication primarily used to manage type 2 diabetes. It is a dual agonist that targets both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. By activating these receptors, tirzepatide enhances insulin secretion, reduces glucagon levels, and slows gastric emptying, which helps regulate blood sugar levels. Additionally, tirzepatide has shown promising results in promoting weight loss, making it a potentially beneficial treatment for conditions associated with obesity.

In two Phase III, double-blinded, randomized controlled trials, 469 participants with clinical obesity and moderate-to-severe OSA were studied over 52 weeks to evaluate the effects of tirzepatide.

Participants, including some using continuous positive airway pressure (CPAP) therapy, were administered either 10 or 15 mg of tirzepatide by injection or a placebo.

The results demonstrated that tirzepatide significantly reduced the number of breathing interruptions during sleep, a crucial indicator of OSA severity, compared to the placebo group. Remarkably, some participants on tirzepatide reached a level of improvement where CPAP therapy might no longer be needed.

The drug also improved cardiovascular risk factors and body weight, highlighting the advantage of addressing both sleep apnea and obesity simultaneously.

“Historically, treating OSA meant using devices during sleep, like a CPAP machine, to alleviate breathing difficulties and symptoms. However, its effectiveness relies on consistent use. This new drug treatment offers a more accessible alternative for individuals who cannot tolerate or adhere to existing therapies. We believe that the combination of CPAP therapy with weight loss will be optimal for improving cardiometabolic risk and symptoms. Tirzepatide can also target specific underlying mechanisms of sleep apnea, potentially leading to more personalized and effective treatment,” said Atul Malhotra who led the study.

Reference: Sanjay R. Patel, Entering a New Era in Sleep-Apnea Treatment, New England Journal of Medicine, 0, 0, (undefined). /doi/full/10.1056/NEJMe2407117

According to a study published in JAMA Network Open, a critical part of the brain linked to risks for anxiety later in life – the left amygdala – was significantly smaller by volume in babies of mothers who reported stress during the COVID-19 pandemic.

The right hippocampus, which governs spatial, visual and verbal memories, and the white matter were also reduced in children whose mothers reported stress.

Intrauterine stressors have been shown to influence fetal brain development and affect how the child, once born, grows and develops. Maternal psychological distress during pregnancy, including stress, anxiety, and depression, is recognized as one such stressor on early brain development. Available evidence shows that maternal anxiety during pregnancy is associated with altered brain growth and microstructure development in the amygdala and white matter in the offspring as well as lower cognitive scores and increased negative temperament from infancy to 2 years of age.

For the study, researchers from Children’s National Hospital used magnetic resonance imaging (MRI) to compare the brains of 103 babies born between 2014 and 2019, before the pandemic, with those of 59 babies born between 2020 and 2022. Mothers who had COVID-19 or other pregnancy complications were excluded from the study. The babies underwent MRI scans while still in utero and again shortly after birth.

Mothers were assessed for stress and anxiety using the Spielberger State-Trait Anxiety Inventory and other validated scoring methods.

Before the pandemic, 21% of mothers reported high anxiety levels; this figure rose sharply to nearly 62% in the pandemic cohort.

The study found that the babies' brains were affected as well, with regions known to regulate emotion and anxiety showing smaller volumes on MRI scans.

The findings showed an association between maternal psychological distress during the COVID-19 pandemic and offspring neonatal brain development. It suggested that an increase in maternal mental health symptoms during the COVID-19 pandemic are associated with subsequent lower volumetric brain growth in newborn offspring.

Reference: Weiner S, Wu Y, Kapse K, et al. Prenatal Maternal Psychological Distress During the COVID-19 Pandemic and Newborn Brain Development. JAMA Netw Open. 2024;7(6):e2417924. doi:10.1001/jamanetworkopen.2024.17924