Medical Bulletin 11/ May/ 2024

According to a new study by researchers in the Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center at the University of Colorado Anschutz Medical Campus, young people with diabetes may have a significantly higher risk of developing Alzheimer’s disease later in life.

In the study, published in the journal Endocrines, scientists showed the presence of specific blood biomarkers indicating early signs of neurodegeneration and Alzheimer’s disease (AD) in young people with youth-onset diabetes.

Youth-onset diabetes, particularly type 2 diabetes, is associated with various metabolic abnormalities and vascular complications that can contribute to the development of Alzheimer's pathology. Additionally, insulin resistance and chronic hyperglycemia, common features of diabetes, may impair brain function and promote the accumulation of amyloid plaques and tau tangles, characteristic hallmarks of Alzheimer's disease.

Moreover, diabetes-related vascular damage can disrupt blood flow to the brain, exacerbating cognitive decline and increasing the risk of brain-related disease.

The study examined approximately 80 individuals, utilizing blood biomarkers and PET scans to detect signs of neurodegenerative disease in young adults living with diabetes. Participants comprised individuals with type 1 diabetes, type 2 diabetes, and those without diabetes, sourced from the SEARCH for Diabetes in Youth Study, a widespread registry and cohort study.

The results revealed that young individuals with youth-onset diabetes not only exhibited elevated blood biomarkers associated with Alzheimer's disease but also showed increased deposition of amyloid proteins in brain regions affected by Alzheimer's disease.

These findings raised concerns among researchers, particularly in light of the escalating rates of obesity among young people and the trend of diabetes onset occurring at younger ages.

“Preliminary evidence shows that preclinical AD neuropathology is present in young people with youth-onset diabetes. We are about to enter into a different world of health care because of the obesity epidemic in young people. Young people are catching up with adults. We are now seeing more ageing-related diseases in young people. The field of diabetes care is beginning to recognize the importance of cognitive testing as a part of clinical follow-up. And it should be something we consider in youth-onset diabetes as well,” said the study’s lead author, Allison Shapiro, assistant professor of paediatrics and endocrinology at the University of Colorado School of Medicine.

Reference: Shapiro, A.L.B.; Coughlan, C.; Bettcher, B.M.; Pauley, M.E.; Kim, J.; Bjornstad, P.; Rajic, B.; Truong, J.; Bell, C.; Choi, Y.J.; et al. Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study. Endocrines 2024, 5, 197-213. https://doi.org/10.3390/endocrines5020014

In a study published in the journal Cell Metabolism, researchers identified a population of cells in human omental adipose tissue that hinders the formation of new fat cells, a process known as adipogenesis.

Understanding how fat tissue forms and functions is crucial for addressing obesity and related metabolic diseases. However, adipose tissue, or body fat, behaves differently based on its location in the body.

Adipose cells, commonly known as fat cells, exhibit distinct behaviors depending on their location in the body. Subcutaneous fat, found just beneath the skin, serves as an energy reserve and provides insulation against temperature changes. This type of fat tends to be more metabolically active and can readily release fatty acids for energy when needed.

In contrast, visceral fat, which surrounds internal organs such as the liver, pancreas, and intestines, is more hormonally active and secretes inflammatory substances that can contribute to insulin resistance, metabolic syndrome, and cardiovascular disease. Visceral fat is less responsive to signals that regulate fat breakdown and tends to accumulate more easily in individuals with obesity or metabolic disorders.

In the study, the researchers used advanced single-cell RNA sequencing to analyse cells from various human fat depots, isolating different cellular subpopulations and testing their ability to turn into new fat cells. The study, supported by several medical institutions, involved over thirty human donors to make a detailed comparison across different fat locations.

The study revealed a subset of mesothelial cells within adipose tissue that transitioned towards mesenchymal properties, potentially influencing the tissue's adipogenic potential. This dynamic shift between cellular states allows these cells to regulate the microenvironment, limiting adipose tissue expansion and mitigating metabolic complications associated with fat accumulation.

“Importantly, we also uncovered at least part of the molecular mechanism by which this new cell population affects adipogenesis. Specifically, the cells express high levels of Insulin-like Growth Factor Binding Protein 2, a protein known to inhibit adipogenesis, and secrete this protein in the cells’ microenvironment. This in turn affects specific receptors on nearby adipose stem and progenitor cells, effectively preventing them from developing into mature fat cells,” said Radiana Ferrero, one of the study’s lead authors.

Reference: Radiana Ferrero, Pernille Yde Rainer, Marie Rumpler, et al.; A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion, Cell Metabolism, 2024; https://doi.org/10.1016/j.cmet.2024.04.017.

A study published in the journal Science suggested that adjusting eating times to manipulate the circadian rhythm, which governs our sleep-wake cycles, may protect muscle function among older individuals.

Our bodies operate on an internal clock called the circadian rhythm, which orchestrates our sleep-wake cycles. This rhythm is finely tuned by exposure to light and darkness, and disruptions to it, such as those experienced by shift workers, can have significant health ramifications.

As we age, changes in our sleep-wake cycle often accompany the loss of muscle mass. Research suggests a close interplay between these two phenomena. While most individuals experience a shift towards earlier sleep hours with age, some, particularly those with neurodegenerative conditions, may encounter severe irregularities in their sleep patterns.

Clock genes play a crucial role in regulating circadian rhythms. As animals age, studies have observed a decline in the expression of these genes, potentially leading to disruptions in their circadian rhythms. While human research in this area is still limited, similar mechanisms could be at play.

In their study, researchers utilized a mouse model with a Bmal1 knockout, preventing the expression of this critical clock gene which regulates circadian rhythms, particularly in the brain. However, they were able to reintroduce Bmal1 in various tissues, including skeletal muscle.

They observed abnormal patterns in activity, oxygen consumption, energy expenditure, and glucose/lipid metabolism in the knockout mice compared to the wild-type, indicating circadian rhythm disruption due to the absence of this clock gene.

However, when the researchers restored the expression of the gene in both muscle and brain tissues in certain mice, they managed to preserve muscle mass and strength, highlighting the significance of Bmal1 in maintaining muscle health.

The findings indicated that by implementing time-restricted feeding, rhythmic gene expression in the muscles can be restored, which prevented the deterioration of muscle function.

“These findings help to explain some of the physiological changes that might be occurring as we age, and how time-restricted eating might help correct this, but this needs to be confirmed in human trials before we can make too many conclusions on the impacts of the circadian clock on aging in humans,” said Amy Hutchison, postdoctoral researcher at The University of Adelaide, Australia.

Reference: Arun Kumar et al.,Brain-muscle communication prevents muscle aging by maintaining daily physiology.Science384,563-572(2024).DOI:10.1126/science.adj8533

The Indian Council of Medical Research (ICMR) has released new dietary guidelines, advising the public on healthier nutrition practices, including recommendations on protein intake. A key point from the guidelines is the recommendation against the frequent use of protein powders and supplements for muscle building and dietary purposes.

According to the ICMR, while protein is an essential nutrient for muscle and overall body health, the regular consumption of protein supplements can be unnecessary and potentially harmful. Protein powders, which are derived from sources like dairy, eggs, whey, and plants such as soybeans, peas, and rice, often contain added sugars, artificial sweeteners, and other additives that may not be advisable for regular consumption.

The guidelines emphasized that obtaining high-quality proteins and essential amino acids through a balanced diet is more beneficial than supplementing with protein powders. This approach not only prevents the risks associated with high protein intake, such as bone mineral loss and kidney damage, but also ensures that the protein consumed is effectively utilized for bodily functions.

The ICMR also highlighted recent research indicating that excessive intake of branched-chain amino acids (BCAAs), commonly found in whey protein, may increase the risk of non-communicable diseases (NCDs).

For athletes and fitness enthusiasts, the ICMR advised that the daily protein requirements can typically be met through a well-rounded diet alone, without the need for supplements. They recommend a diet that includes a combination of cereals and pulses (in a 3:1 ratio) or by substituting a portion of pulses with meat to achieve the necessary protein quality.

“Dietary protein supplementation is associated with only a small increase in muscle strength and size during prolonged resistance exercise training (RET) in healthy adults; and protein intake levels greater than ~1.6 g/kg/day do not contribute any further to RET-induced gains in muscle mass,” the guidelines stated.