Diabetes Incidence Rising in Spanish Youth

MADRID — Spain has the second-highest number of patients with diabetes in Europe. The main challenges are to address the growing number of cases of type 2 diabetes (which is developing at increasingly younger ages), diabetes-associated complications, lower quality of life, and higher mortality. Researchers reviewed these points as they described the state of diabetes in Spain at the XXXIV National Congress of the Spanish Diabetes Society.

Antonio Pérez, MD, PhD, president of the Spanish Diabetes Society, told Medscape Spanish Edition, “The primary cause is the substantial rise in the prevalence of excess weight and obesity in children and teens. In Spain, 23.3% of people under 16 years old are overweight, and 17.3% are obese. This rise in obesity and the parallel increase in type 2 diabetes among the younger generation is in turn linked to the major shifts in lifestyle that have taken place in recent decades, including sedentary lifestyles and poor diets that are unhealthy and high in calories.”

Pérez also noted that a study published in the BMJ that involved 204 countries indicated that the prevalence of type 2 diabetes among teens and the younger generations (ages 15 to 39 years) has increased by 56.4% during the past three decades.

“This is highly significant because, in addition to the short-term impact on patients and the healthcare system, early onset of type 2 diabetes creates a greater future burden of disease. This is brought on by the longer exposure to hyperglycemia caused by onset in young people and means that overall disease progression will be worse. This often also leads to worse blood sugar control, greater risk of complications, and poorer quality of life,” he continued.

Pérez also noted that underdiagnosis and a lack of early diagnosis are also unsettling aspects of this disease, in addition to the rise prevalence. It is estimated that nearly half of the cases of diabetes in Spain have not been diagnosed.

“The solution lies in screening for the disease using simple blood glucose testing. Screening is recommended in asymptomatic individuals of any age who are overweight or who have other risk factors. In individuals without these risk factors, screening is recommended beginning at specific ages (between 35 to 45 years old),” he added.

Quality of Life

Beyond the challenge of diagnosis, there is a worrisome lack of access to quality education about this disease, as well as a lack of appropriate follow-up. A substantial proportion of patients (from 40% to 50% of those diagnosed) do not achieve blood sugar control targets or goals for other related processes and for cardiovascular risk factors.

Many challenges must be addressed to improve these patients’ quality of life. Patients with diabetes require lifelong treatment, which involves making daily dietary decisions and tailoring medications on the basis of results of blood sugar testing. This regime poses a challenge and requires that patients be aware of the benefits of adequate control. They must also have the information they need to make decisions about how to manage their disease.

“To achieve this, it is vital that all patients with diabetes have access to educational programs about treatment,” said Pérez. “In my opinion, this is the main topic that still must be addressed to improve the quality of life of the people in our country who have type 2 diabetes.”

After reporting the status of this disease in Spain, Pérez mentioned the latest advances in knowledge of type 2 diabetes and its management. These advances are cause for optimism, he said. “Research surrounding this disease is ongoing and has provided new treatments and tools that are improving the prognosis and quality of life of these patients. At some point in the future, these will allow prevention and possibly even a cure. Among these advances, I would highlight the development of technology used in treatment and follow-up with these patients and the availability of new oral and injectable drugs (glucagonlike peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) to treat hyperglycemia and diabetes-associated comorbidities.

“These drugs have brought in a major shift in treatment strategies, because they don’t increase the risk of hypoglycemia, they reduce body weight, and they have beneficial effects on cardiovascular and renal protection in addition to blood sugar control,” added Pérez.

Promising Research Areas

As to advances in research, Pérez emphasized the role of Spanish professionals, “who are outstanding, despite a lack of resources. For example, the presentations given at this conference reflect the scientific output from our country in the various fields relating to diabetes, an output that is substantial and growing both in quantity and quality.”

One session focused on updates from the most promising areas of research being pursued at the Biomedical Research Networking Center in Diabetes and Associated Metabolic Disorders (CIBERDEM). One of these areas of research is being investigated by the group led by Manuel Vázquez, PharmD, PhD, professor of pharmacology and therapeutic chemistry at the University of Barcelona and an investigator at CIBERDEM. His group is seeking to learn more about the mechanism of action of metformin, which is currently the drug most often prescribed to treat type 2 diabetes.

The investigator told Medscape that the group is delving into new mechanisms that could explain the antidiabetic effects of metformin in the two regions where it appears to have its most significant activity: the liver and the gut.

“In the liver, metformin has recently been described as increasing let-7 microRNA levels by modulating the liver redox state. This reduces glucose production in the liver, which is the process that contributes most to fasting hyperglycemia in patients with type 2 diabetes. These results raise the possibility of activating the expression of let-7 microRNAs (which is otherwise reduced in diabetic states) as a new strategy for treating type 2 diabetes.

“Furthermore, a number of studies in recent years have shown that metformin has significant impacts on the gut. One of the most recent studies has shown that metformin activates the conversion of glucose into lactate and acetate in the gut. These two metabolites reach the liver through the portal vein, where they trigger a chain of events that reduces glucose production in the liver. So, the gut–liver crosstalk induced by metformin contributes to its antidiabetic effects,” said Vázquez.

“In summary, all these new studies are providing data that help us understand how metformin reduces glucose production in the liver, which is this drug’s main antidiabetic effect. We just published a study showcasing this drug’s new mechanisms of action.”

GDF15 and NAD+

This research focuses on growth differentiation factor 15 (GDF15), an anorexia-inducing cytokine thought to be a novel mediator of the antidiabetic effects of metformin.

“Our results indicate that GDF15 may play a fundamental role in the antidiabetic effect of this drug, because it’s required to preserve activation of AMPK, the primary target of this drug,” said Vázquez. “If these results are confirmed in patients, it could indicate that those who show a greater increase in GDF15 in response to metformin therapy may respond better to this drug and benefit more from its activity. Also, the results may pave the way for new possibilities for developing GDF15 analogues or inducers to be used to treat type 2 diabetes.”

Another area of research focuses on the positive effect that different nicotinamide adenine dinucleotide (NAD+) precursors have on the development of some diabetes-related neurologic complications. Josep Julve, PhD, a researcher at the Hospital and Research Institute of Santa Cruz and San Pablo in Barcelona and an investigator at CIBERDEM, explained that NAD+ is a vital redox cofactor for the metabolism and production of adenosine triphosphate and a key substrate for multiple enzymes that depend on NAD+ and are involved in various cellular processes.

“There is evidence suggesting that low NAD+ levels may be tightly correlated with the development of several diabetes-associated metabolic complications, including neurological complications,” noted Julve.

“There are different NAD+-dependent cellular enzymes whose activity is necessary for maintaining plasticity and neuronal function and for controlling neuroinflammation. Based on this evidence, we believe that restoring NAD+ levels in nerve tissue by administering different precursors may become a potential therapeutic strategy for combating the progression of neuropathy in patients with diabetes,” he concluded.

Pérez, Vázquez, and Julve have disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish Edition.

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