The promise of personalized diabetes care

Future

Written by Michael Seringer

The work of UT Health Science Center San Antonio faculty has transformed the medical community’s understanding of Type 2 diabetes, while helping usher in new therapies and improved protocols.

Type 2 diabetes is rampant in South Texas, and its rates are rapidly growing across the country as well.

According to a new analysis by the Centers for Disease Control and Prevention, one out of five U.S. adults will have diabetes by 2050. Today, close to 30% of the population on the Texas and Mexico border suffers from it. Currently, 12.4% of Texas has Type 2 diabetes — and more than 600,000 Texans don’t even know they have the disease, according to a study by the American Diabetes Association.

Against the backdrop of these sobering numbers, the Texas Diabetes Institute is not only sounding the alarm, but is also making great strides in discovering the causes and potential treatments of this global health epidemic.

The Texas Diabetes Institute, an arm of University Health, the primary hospital partner of UT Health Science Center San Antonio, is located on San Antonio’s West Side. It is at the leading edge of research and discovery in Type 2 diabetes. The institute’s deputy director, Ralph DeFronzo, MD, professor of medicine and chief of the diabetes division at UT Health Science Center San Antonio, has transformed the medical community’s understanding of Type 2 diabetes, while helping usher in new therapies and improved protocols.

“Our work completely revolutionized the understanding of the etiology of Type 2 diabetes by unequivocally demonstrating for the first time that insulin resistance was the earliest detectable disturbance present in individuals with Type 2,” DeFronzo said. “The stress placed on the pancreatic beta cells to secrete insulin to overcome the insulin resistance, in combination with a genetic predisposition for progressive beta cell failure, results in a relative deficiency of insulin and onset of diabetes.”

Diabetes in older adults 

Most people experience the onset of diabetes between the ages of 40 and 50, and many suffer comorbidities that can place them as older adults in a precarious health situation. Comorbidities such as hypertension, cardiovascular disease, dyslipidemia, kidney disease, cancer, obesity, neuropathy and non-alcoholic fatty liver disease make diagnosing and treating diabetes a priority.

For instance, poorly controlled blood sugar levels are closely associated with cardiovascular disease among older adults due to the impact of diabetes on blood vessels. Elevated blood sugar levels can lead to the buildup of fatty deposits in the arteries, narrowing them and reducing blood flow to the heart. High blood pressure, stroke, peripheral artery disease, heart failure, arrhythmias, atherosclerosis, microvascular complications and inflammation are all cardiovascular risks that increase significantly with diabetes.

“Type 2 diabetes and atherosclerotic cardiovascular disease [ASCVD] are closely intertwined,” DeFronzo said. “ASCVD represents the major cause of mortality in Type 2 diabetes. In a recent analysis of all major cardiovascular prevention trials by UT Health Science Center San Antonio, the unexplained cardiovascular conditions remain at about 50%. We have demonstrated that the molecular etiology of insulin resistance is a major factor that explains much of this unexplained cardiovascular risk.”

Associate Professor Carolina Solis-Herrera, MD, chief of endocrinology and medical director of the Endocrinology, Diabetes, Obesity and Metabolic Health Clinics at the Long School of Medicine, suggests that according to national guidelines, it is recommended to use the newest classes of medications that have shown cardiovascular and renal protection in patients with diabetes. These drugs have different mechanisms of action that are complementary in providing cardiovascular and metabolic health to patients by decreasing complications and mortality.

“We currently have very novel and effective therapies to control diabetes that also provide cardiovascular protection to prevent patients with diabetes from heart attacks and strokes as well as to prevent or decrease the progression of diabetic renal disease,” Solis-Herrera said. “These classes of drugs called glucagon-like peptide-1 receptor agonists [GLP-1 RA] and sodium-glucose cotransporter 2 [SGLT-2] inhibitors are available in the market and covered by most commercial insurance plans and Medicare. We widely prescribe them to our patients to keep their sugars controlled and provide them with cardiac and renal protection.”

Other concerning comorbidities 

One common comorbidity among older diabetic adults is the increased rate of obesity.

“Obesity is the primary driving force for the epidemic of Type 2 diabetes,” DeFronzo said.

Metabolism naturally slows down with age and, combined with a sedentary lifestyle and greater access to highly caloric foods, contributes significantly to weight gain among older adults.

“The accumulation of excess weight can further exacerbate metabolic changes and increase the risk of additional chronic health conditions,” Solis- Herrera said. “Obesity distinctively affects all aspects of physiology, thus shortening lifespan and health span through effects in multiple hallmarks of aging, such as cellular senescence.”

University researchers continue to actively study the mechanism of action and efficacy of the newer, more potent GLP-1 RAs and are working on the development of novel, non-drug approaches to treat obesity, DeFronzo said.

Depression is another notable comorbidity linked to diabetes among older adults and is emerging as a significant factor that directly impacts quality of life. Biological factors such as chronic inflammation, insulin resistance and changes in neurotransmitter levels may contribute to the relationship between diabetes and depression, Solis-Herrera said.

Living with diabetes also takes a psychological toll on older adults who are expected to change their lifestyle and manage multiple medications as they confront declining physical health. Furthermore, some diabetes medications may contribute to mood disorders and depression. Undiagnosed depression can harm diabetics because they tend to exercise less and are prone to not adhere to their treatment plans.

“Patients may sometimes feel discouraged, worried, frustrated and tired of dealing with diabetes care daily,” Solis-Herrera said. “People with diabetes are two to three times more likely to have depression than people without diabetes. Only 25% to 50% of people with diabetes who have depression get diagnosed and treated. Counseling and medication may be quite effective in helping patients handle the burden that having diabetes may cause in their lives.”

A patient-focused future

The treatment of diabetes among older adults once seemed bleak, but current innovations in care offer new hope. Novel research has provided a much greater understanding of the mechanisms behind the disease and yielded more effective treatments — reversing the trend of this epidemic.

Developments in genetics, metabolomics and artificial intelligence are paving the way for precise approaches to diabetes treatment. Tailoring treatments to an individual’s genetic and metabolic profile could lead to more effective, personalized interventions, Solis-Herrera said.

“The convergence of artificial intelligence and precision medicine promises to revolutionize health care,” Solis-Herrera said. “Precision medicine methods identify phenotypes of patients with less common responses to treatment or unique health care needs. Ideally, if we can identify specific phenotypes of diabetes, we could possibly tailor new targeted therapies to improve — or hopefully cure — diabetes.”

The emergence of various Type 2 diabetes subclusters, each characterized by different clinical and physiological features, will also help direct more effective precision treatments. The identification of subclusters within Type 2 diabetes is an ongoing area of research and has been the subject of many publications authored by DeFronzo and others at UT Health Science Center San Antonio.

The genetic origins of Type 2 diabetes are important in uncovering subclusters as they reveal the interplay of multiple genetic factors that contribute to an individual’s risk of developing the disease. Although lifestyle and environmental factors play a significant role in the development of diabetes, researchers are seeking to understand the genetic predisposition for the disease.

Some genetic variants associated with diabetes risk are more prevalent in specific populations, leading to differences in disease propensity. Understanding the genetic mechanisms of diabetes is key to understanding how the disease disproportionately impacts Hispanic populations, Solis-Herrera said. Identifying the genes responsible for Type 2 diabetes within Hispanic populations is an active area of research at UT Health Science Center San Antonio and could potentially improve existing inequalities in health care.

“In the next decade, I expect that we will make major advances in elucidating the genetic etiology of Type 2 diabetes,” DeFronzo said. Such advances include the development of novel insulin sensitizing and beta cell enhancing medications for the treatment of Type 2 diabetes and the introduction of novel combination peptide/hormones for the treatment of obesity that will stem the obesity epidemic, noted DeFronzo. “I also anticipate that identifying subclusters of Type 2 diabetes will allow a personalized approach to therapy.”

Reversing diabetes trends 

Should the diabetes rate projections noted earlier come to fruition, researchers warn that the volume of cases could overwhelm health care systems. However, even as these projections provide a window into the potential future of this epidemic, they fail to account for the impact of revolutionary discoveries occurring at institutions like UT Health Science Center San Antonio.

“We are the leading group worldwide in defining the etiology of prediabetes and developing therapeutic interventions for preventing the progression of prediabetes to diabetes,” DeFronzo said.

With decades of research focused on the biomarkers of prediabetes, university investigators say they are well positioned to develop therapies designed to prevent prediabetes and to begin to reverse these disturbing diabetes trends.

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