Where to begin when treating patients with obesity, diabetes and depression

When treating a patient with multiple diagnoses, it can be difficult to know which to address first.

The intricacy of obesity, diabetes and depression specifically can create confusion due to the “complex pathophysiologic pathways involved,” according to a speaker at the Obesity Medical Association Spring Conference.

During her presentation, Nowreen Haq, MD, MPH, FACP, FACE, the director of the Endocrinology, Diabetes and Obesity Management Clinic at the University of Maryland Midtown Professionals, reviewed interventional strategies to manage patients with depression, obesity and diabetes.

Intersectionality of diseases

At the beginning of the presentation, Haq admitted that she herself doesn’t know the answer to the question of “which to address first.” One thing that can be especially tricky about the intersectionality of these diseases is that, occasionally, a symptom of one can fuel the other. For example, Haq noted that patients with a serious mental illness like major depression are at an increased risk for obesity compared with the general population, as they are more likely to be physically inactive and have unhealthier diets. She also pointed out that depression is a risk factor for the onset of type 2 diabetes.

“Depression affects quality of diet, but quality of diet also can induce depression,” she said.

Haq referenced a meta-analysis of 24 independent cohorts that showed adherence to a high-quality diet, regardless of the type — “a good portion of vegetable, fruits, Mediterranean diet” — was associated with a lower risk for depressive symptoms over time.

“The odds ratio was actually ranging from 0.64 to 0.78, with a P value of less than 0.01, showing the significance of just the dietary effect really promoting mental health,” she said.

Aside from lifestyle choices, the diseases can also be linked on the molecular level. According to Haq, glycogen synthase kinase-3 (GSK-3) is known to be “very active in a resting cell state and promote hyperglycemia.”

“It is possible that an overactivation of this GSK-3 molecule plays an important role in the pathogenesis of the development of schizophrenia and mood disorders like bipolar disorders and major depression with patients with type 2 diabetes mellitus,” she said.

Treatment strategies

Haq presented a flow chart outlining an algorithm of metabolic risk management in patients with a serious mental illness and at least one CVD risk factor, including obesity and diabetes. The first recommended steps for a physician are education and encouragement on nutrition, diet and physical activity. If the patient is taking an antipsychotic drug, physicians should try switching from weight-gaining antipsychotics to weight-neutral or weight-reducing antipsychotics, such as the antidepressant drug bupropion. If the abnormalities do not improve after 2 months, physicians should treat risk factors individually, Haq said. For abdominal obesity, there is a choice of treatment for weight loss based on availability and patient preferences, motivation and capabilities. On the psychosocial side of things, lifestyle intervention customized to the patient is recommended. After 3 months, if the interventions are ineffective, the chart recommends moving to medication.

For patients with type 2 diabetes, GLP-1 agonists are a class of drugs that enhance glucose control and can also help reduce body weight, which in turn may help improve depressive symptoms, according to Haq. Last year, the GLP-1 agonist Wegovy (semaglutide; Novo Nordisk) was approved for chronic weight management in adults with obesity or with overweight and at least one weight-related condition. SGLT2 inhibitors have also shown to reduce weight, and metformin has been linked to a “modest reduction” in BMI.

Cognitive behavioral therapy should also be considered as a treatment option for people with diabetes and depression, Haq said, adding that studies found “statistically significant improvements in HbA1c through this approach.”

However, some questions remain, Haq said, like the fact that some studies used one-on-one treatment while others had groups or different therapeutic approaches. Additionally, it is not clear if cognitive behavioral therapy must be combined with other intervention strategies such as motivational enhancement therapy.

“Research is needed to identify subgroups of patients because I feel we cannot have one size fits all,” she said. “It has to be catered to each individual patient’s needs, and there is yet a big gap that is still not met.”

Ultimately, though, Haq said that self-care is one of the most critical elements of treatment.

“Self-care is an essential part of maintaining good health,” she said. “No matter how many times we counsel them in our office, in our clinical practice, at the end of the day, patients need to take ownership and leadership ... of their health management by having really the active, healthy choice of the diet and ... by having daily exercise.”