US Pharm. 2023;48(11):29-31.

Diabetes May Accelerate Blood Cancer Growth More in Whites Than in Blacks

Patients with multiple myeloma who also have diabetes have a reduced overall survival compared with those without diabetes. In a subgroup analysis, this difference in survival due to diabetes was seen in white patients but not in black patients, according to a study published in Blood Advances.

According to the CDC, diabetes affects 13% of the U.S. population, and this prevalence is growing rapidly. Multiple myeloma is the second most common blood cancer in the U.S. and disproportionately affects non-Hispanic black adults, in whom it is the most common blood cancer. While investigators have long been aware of the increased risk of multiple myeloma in patients with diabetes, this is the first study to examine racial disparities in survival rates among those living with these comorbid conditions.

“We knew from prior studies that patients with multiple myeloma and diabetes have lower survival rates,” explained Urvi Shah, MD, a multiple myeloma specialist at Memorial Sloan Kettering Cancer Center. “But what we did not know is how these outcomes differ between races. Diabetes is much more common in black individuals versus white individuals, and we wanted to understand whether this difference may play a role in health outcomes among patients with both conditions.”

Researchers conducted a retrospective study, collecting data from electronic healthcare records of 5,383 patients with multiple myeloma from two academic medical centers: Memorial Sloan Kettering Cancer Center and Icahn School of Medicine at Mount Sinai. Fifteen percent of patients included had a diabetes diagnosis (12% of white and 25% of black patients).

Across the board, Dr. Shah and colleagues observed that among patients with myeloma, those with diabetes had poorer survival rates than those without. When analyzing results by race, however, they found that while white patients with myeloma and diabetes had lower survival rates than those without diabetes, they did not observe this finding among black patients.

“What we did not expect to see here was that diabetes was actually associated with worse survival outcomes among white individuals with myeloma, but not black individuals,” said Dr. Shah.

She added that generally one’s risk of developing diabetes increases with age. Study findings also show that overall survival decreased with age. Notably, however, in this cohort diabetes was 50% more prevalent among black patients aged 45 to 60 years than white patients older than 60 years. Younger patients may tolerate multiple myeloma treatments better than older individuals, and these differences could explain some of the racial differences investigators observed in survival outcomes.

When investigating the mechanisms behind these findings, Dr. Shah and colleagues observed that in genetically engineered mouse models, multiple myeloma tumors grew more rapidly in nonobese diabetic mice than in nondiabetic controls.

After studying the biological mechanisms underlying tumor growth in these mice, researchers found that an insulin-related signal was overactivated in the diabetic mice, leading them to believe that higher insulin levels associated with diabetes may accelerate cancer growth.

“In my own practice, I work with many patients with both multiple myeloma and diabetes. And usually treating multiple myeloma involves many rounds of chemotherapy,” said Dr. Shah. “But this study suggests that we may also improve patient outcomes further by treating diabetes at the same time.”

Season, Time of Day, and Patient Experience Central to Managing Type 1 Diabetes

A new Dartmouth study published in the journal Science Advances suggests that how well people with diabetes manage their blood sugar depends on their experience with the condition and their overall success in controlling their glucose levels, as well as on the season and time of day. The findings could help physicians identify those patients who could benefit from more guidance in regulating their blood sugar, particularly at certain times of the year.

The researchers accessed data from wearable glucose monitors that showed how 137 people in the United States aged 2 to 76 years living primarily with type 1 diabetes managed their blood sugar on a daily basis. By analyzing more than 91,000 days of data, the study provides the most detailed look yet at how diabetes management can vary by month, day, and age, and even how experienced a patient is with the condition.

Patients in the study tended to maintain healthier blood sugar levels from April to September, the researchers found. In these warmer months when activity levels tend to be higher, glucose levels stayed in the healthy range through a larger part of the day than average. In the colder months from October to February, however, the time spent within the normal range was lower than average.

This effect was amplified during the holidays for participants of all ages, with New Year’s Day and Christmas topping the list of days when sugar levels strayed outside the desired target range more often. Despite being a warm-weather holiday, Independence Day was third on the list of days when poor glucose control was recorded.

“We’re looking for specific patterns that could potentially inform clinical guidelines and set the stage for targeted interventions,” said Temiloluwa Prioleau, assistant professor of computer science, one of the study coauthors. The authors note that the majority of their study participants had type 1 diabetes, so it is not clear how these findings might generalize to people with type 2 diabetes.

Some researchers and providers have hypothesized that changes in activity levels, lifestyle, and food intake during different seasons impact blood-glucose management, said coauthor Prajakta Belsare, an assistant professor at James Madison University who worked on the study while she was a postdoctoral fellow in Dartmouth’s Department of Computer Science.

Given the granularity of their data, the researchers also were able to investigate daily and weekly variations. They found that patients’ glucose levels were more likely to stay normal from Monday to Friday and during the working hours from 9 am to 5 pm, than on weekends, suggesting that workweek routines have a positive effect.

For Dr. Belsare, one of the more interesting results was how effectively different age groups manage their blood sugar. “We found that young adults in the 19 to 34 age range were less proficient at managing blood glucose,” she said. “It’s likely that this reflects the struggle that newly independent adults face in taking care of their own health without the oversight of parents or caregivers,” she added.

The study does not examine the factors driving the patterns they see. “I think the answer for the ‘why’ would be different for different people,” Dr. Prioleau said. “Our goal is to highlight what we’re observing at a population level. Hopefully, this will encourage people to leverage their own past data to inform and shape their future care, through behavioral changes when feasible or through other types of intervention.”

Exercise and Implications for Reversing Prediabetes

Prediabetes is a condition that precedes type 2 diabetes and increases the risk of heart attack, kidney and eye disease, and several types of cancer. Currently, there is no approved drug therapy for prediabetes available. Scientists at the German Center for Diabetes Research (DZD) have demonstrated how and by which mechanisms prediabetes can be brought into remission, i.e., into a state in which blood glucose levels return to normal.

The multicenter study of the DZD also shows that remission of prediabetes protects against type 2 diabetes and is associated with better kidney and vascular function in the long term. Interestingly, the underlying mechanisms are different from those in type 2 diabetes remission, the researchers report in The Lancet Diabetes & Endocrinology.

People with type 2 diabetes have an increased risk of heart attack, kidney disease, and stroke and a higher mortality risk. Type 2 diabetes was thought to be irreversible until a few years ago. We now know that type 2 diabetes can be put into remission in a significant number of individuals through substantial weight loss. However, this remission rarely lasts, as most people typically develop type 2 diabetes again within a few years.

“We aimed to explore the feasibility of commencing earlier and implementing preventive measures already at a stage that precedes type 2 diabetes, namely prediabetes, with the aim of reversing it,” said senior author Andreas Birkenfeld, medical director of Medical Clinic IV at Tübingen University Hospital and director of the Institute for Diabetes Research and Metabolic Diseases at Helmholtz Munich, University of Tübingen, in Germany. This could be crucial for patients with prediabetes, as they are at increased risk to develop type 2 diabetes, according to the researchers, as well as heart, kidney, and eye complications, among others.

The scientists conducted a post hoc analysis on participants with prediabetes from the Prediabetes Lifestyle Intervention Study. In this randomized, controlled multicenter study conducted by the DZD, 1,105 individuals with prediabetes underwent a lifestyle intervention involving a healthy diet and increased physical activity for 1 year. The researchers then assessed the 298 participants who had achieved a minimum weight loss of 5% as a result of the intervention. Responders were the participants whose fasting blood glucose, 2-hour glucose, and HbA1c levels had normalized within 12 months, indicating that they had gone into remission. Nonresponders were individuals who did not achieve remission despite losing weight and still had prediabetes.

Contrary to the researchers’ initial assumptions, it was not weight loss that distinguished those who went into remission from those who did not. However, individuals who achieved remission demonstrated a notable improvement in insulin sensitivity compared with nonresponders. In essence, they were able to enhance their sensitivity to insulin significantly more than those who did not respond.

Nonetheless, the quantity of insulin secreted remained unaltered in both groups. This difference is critical compared with type 2 diabetes remission, which depends primarily on enhanced insulin secretion.

To determine the cause of increased insulin sensitivity in responders, the researchers conducted a comparative analysis of the two groups. The responders had lost more abdominal fat compared with nonresponders despite losing the same amount of body weight. The impact of visceral fat on insulin sensitivity is partially attributed to an inflammatory response in adipose tissue.

Participants who went into remission also had fewer inflammatory proteins in their blood. “Since the responders showed a reduction in abdominal fat in particular, it will be important in the future to identify the factors that promote the loss of this fat depot,” said Arvid Sandforth, one of the lead authors of the study. Surprisingly, there were no differences between the two groups in the reduction of liver fat, which is also an important risk factor for the development of diabetes.

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