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Tag: type 2 diabetes

The Impact of Major Depressive Disorder on Cardiometabolic Disease Risk

Driven by a widespread change in lifestyle factors, such as dietary patterns and physical activity levels, as well as heightened stress levels, the global prevalence of cardiometabolic disease continues to rise. A burgeoning body of evidence suggests the potential impact of mental health factors, specifically the presence of major depressive disorder (MDD) on the development of cardiometabolic conditions. Affecting an estimated 322 million people, MDD has a high comorbidity rate with other medical disorders and in particular, type 2 diabetes. Although the mechanisms underlying the potential causal associations between the two are unknown, both cardiometabolic disease and major depressive disorder place a significant burden on population health.

Past observational studies have reported an association between MDD and an increased risk for type 2 diabetes, caused by biological alterations – such as elevated counter-regulatory hormone release and activity – as well as poor lifestyle factors, including smoking and alcohol consumption. Research has shown that brain regions involved in mood regulation also control metabolism, hypothalamic-pituitary-adrenal (HPA) axis, inflammatory responses, and autonomic nervous system (ANS) thus, controlling heart rate and blood pressure. These factors may influence the relationship between MDD and certain cardiometabolic conditions, however, evidence remains limited.

Adding to the growing body of evidence, a recent bidirectional Mendelian randomization study published in Diabetologia aimed to assess the causal relationships between major depressive disorder, type 2 diabetes, coronary artery disease, and heart failure to further elucidate the connections.

MDD and Cardiometabolic Disease

A team of researchers utilized the Mendelian randomization method – used for assessing causal inference of exposures on outcomes based on genetic variants as instrumental variables for exposures – to diminish chances of residual confounding and eliminate reverse causality due to the fixed nature of genetic variants regardless of disease progression or development.

In conducting their investigation, researchers extracted summary-level data for MDD, T2D, CAD, and heart failure from corresponding large genome-wide association studies; they used 96 single-nucleotide polymorphisms (SNPs) for MDD, 202 SNPs for type 2 diabetes, 44 SNPs for CAD, and 12 SNPs for heart failure. To perform their main analyses, the random-effects inverse-variance weighted method used.

Impact of MDD on Cardiometabolic Risk

Overall, the study’s authors found that the genetic liability to MDD was significantly associated with type 2 diabetes and coronary artery disease; they also found a suggestive association between MDD and heart failure. In examining the causal relationship, the research team found limited evidence in support of the causal effects of cardiometabolic disease on MDD risk, indicating that the presence of these conditions may not increase the likelihood of major depressive disorder.

However, meta-analyses did prove that the presence of MDD had an impact on type 2 diabetes development with the potential to increase risk by up to 60%. Additionally, the team found evidence of MDD having a causal association with the risk of CAD and HF. As diabetes and CAD have been known risk factors for HF and CAD may explain over 60% of heart failure cases, the relationship between major depressive disorder and heart failure may possibly be mediated via type 2 diabetes and coronary artery disease.

The latest findings further validate previous evidence that MDD is a potential risk factor for both type 2 diabetes and CAD, however, additional research needs to be conducted to determine whether MDD is causally related to heart failure. Future studies are likely to continue investigating the correlation to determine the significance of the impact of MDD on cardiometabolic health as well as to assess potential therapeutic interventions.

Due to the high disease burden related to causal association, the study’s authors recommend “that MDD prevention, management, and treatment should be enhanced for type 2 diabetes prevention.” Implications for the clinical practice may include more targeted strategies for the prevention and treatment of cardiometabolic diseases in the future with an increased focus on the mental health of patients.

 

Intermittent Fasting in Patients with Type 2 Diabetes

Currently experiencing a surge in popularity, intermittent fasting has become an increasingly adopted dietary regimen due to its many purported health benefits. The concept of intermittent fasting refers to a spectrum of nutritional behaviors that aim to intentionally disrupt energy consumption for extended periods of time, for example, for between 16 and 24 hours on a regular intermittent schedule. In some intermittent regimens, individuals restrict food consumption to a 6- to 8-hour period, while in others they fast for a full 24 hours during several days of the week.

Some individuals may be inclined to adopt these dietary patterns as a means of weight loss or for their promised health benefits supported by anecdotal evidence, including the treatment of type 2 diabetes which remains unproven and untested entirely. While caloric restriction and weight loss are known to beneficially influence health outcomes in patients with type 2 diabetes – leading to improved glucose control, hypertension, and abnormal lipid levels – achieving them with intermittent fasting presents concerns.

Published on July 2, 2020 in JAMA, a new viewpoint underscores the limited body of evidence of the health benefits of intermittent fasting among type 2 diabetes patients and reveals the potential adverse complications that may result from this approach if patients are not carefully monitored.

Intermittent Fasting and T2D

To date, intermittent fasting in patients with T2D has only been studied in a few small, short-term trials yielding limited evidence of its benefit. Recently, a team of researchers examined the evidence for the health benefits and safety of intermittent fasting in this group of patients specifically. For the purposes of the study, intermittent fasting was defined as time-restricted feeding, or fasting on alternate days or during 1-4 days of the week, with only water, juice, or bone broth and no more than 700 calories consumed on fasting days.

In total, the study’s authors found seven published studies of fasting in T2D patients – only one trial had over 63 patients. Most studies were short in duration, occurring over 4 months or less, and evaluated five different fasting frequencies. All reported a connection between intermittent fasting and weight loss, while the majority also noted decreased A1c and improved glucose levels, quality of life, and blood pressure. Due to the lack of homogeneity in design, measures, and regimen styles, clinically meaningful conclusions could not be drawn.

In addition, only one study addressed the safety of two intermittent fasting regimens, finding that both increased the incidence of hypoglycemic events despite the use of a medication dose-change protocol.

Improved Glucose, Heightened Risks

The primary implication of the latest findings is that intermittent fasting may be less safe than caloric restriction, although it could be equivalently effective. Patients with existing diabetes who experienced weight loss saw a benefit of improved glucose, blood pressure, and lipid levels, according to the researchers.

While weight loss associated with intermittent fasting appears to be similar to that attained with caloric restriction, in the case of type 2 diabetes patients it can pose a risk of glycemic variability. Hypoglycemia can occur during fasting and hyperglycemia during feeding times, researchers note, and presents potentially dangerous clinical implications.

“Studies have raised concern that glycemic variability leads to both microvascular (eg, retinopathy) and macrovascular (eg, coronary disease) complications in patients with type 2 diabetes,” the authors cautioned. As such, the report highlights the need for continuous glucose monitoring aimed at detecting glycemic variability in susceptible patients as well as throughout studies of clinical interventions involving intermittent fasting in T2D patients.

Recommendations

Although further evidence is needed, the study’s lead author, Benjamin D. Horne, PhD, MStat, MPH, concluded that he would recommend intermittent fasting for patients with type 2 diabetes with caveats due to safety issues. These can include factors such as low blood pressure, weakness, headaches, dizziness – all of which are important considerations alongside the risk for hypoglycemia. Thus, caloric restriction may be a safer choice for certain patients.

Horne recommends giving patients intervention options to choose from as some may be better positioned to handle intermittent fasting. Until intermittent fasting is proven more effective at controlling diabetes, the currently available study data implicate that such regimens for patients with type 2 diabetes should be approached with caution, the risk of hypoglycemia closely monitored, and medications carefully adjusted to ensure both safety and efficacy of nutritional interventions.