Episode 179: Impact of intermittent fasting Impact on T2DM

Future Dr. Carlisle explains the physiology of fasting and how it can help revert type 2 diabetes. Dr. Arreaza adds details on how to do intermittent fasting.

Written by Cameron Carlisle, MSIV, Ross University School of Medicine. Comments and edits by Hector Arreaza, MD, FAAFP.

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What is type 2 Diabetes Mellitus (T2DM)?

-Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and impaired glucose regulation.

-This impaired regulation can lead to hyperglycemia, contributing to complications in a myriad of organs: heart, kidneys, eyes, nerves, etc. (target organs). According to the CDC, more than 38 million Americans have T2DM (about 1/10 people).

-Multiple mechanisms are believed to contribute to insulin resistance in obese patients with T2DM, such as increased lipid deposition throughout the body and systemic inflammation.

What is Intermittent Fasting (IF)?

Intermittent fasting (IF) has recently gained popularity as a dietary approach for health benefits, but it has been around for thousands of years. IF is an eating pattern that alternates between eating and fasting (no calories consumed) over a specific period of time. When you are fasting, you are allowed and encouraged to keep drinking water and non-caloric drinks, like coffee, tea, and even homemade bone broth.

-According to the International Food Information Council Foundation (IFIC), 10% of Americans engage in IF daily.

-According to Mark Mattson, a neuroscientist and IF expert for over 25 years, a mechanism called “metabolic switching” is seen with IF. This is when your body runs out of glucose and starts burning fat (i.e., fatty oxidation). These metabolic changes can help protect your organs and reduce the risk of chronic conditions, like T2DM.

Common IF methods:

Time-restricted eating: Most common method, involves eating within a specific time frame (e.g., the 16:8, 18:6, 12:12 method is also common. [16:8 means you have 16 hours of fasting and 8 hours of eating.]
Alternate-day fasting: Alternating between fasting days and normal eating days. [Find more info in The Complete Guide to Fasting, by Jason Fung, who is a nephrologist, he explains that alternate-day is basically eating every other day, which would give 36 hours of fasting, but if you are a beginner you can try a 24 hours fasting, in short, not eating breakfast any day of the week and having lunch 4 days a week, and dinner every night.]
5:2 diet (aka periodic fasting): Maintaining a normal diet for 5 days, with 2 days (usually non-consecutive) of caloric restriction (25% of normal caloric intake; e.g., 500 calorie meal).

IF is strongly believed to improve metabolic health in individuals with T2DM by reducing insulin resistance via increasing insulin sensitivity, promoting weight loss (patients with obesity and DM… AKA patients with diabesity), and enhancing lipolysis via fat oxidation.

While fasting, the body goes through several phases that affect how energy is metabolized. Between 0 and 4 hours after eating, the body enters a feeding state, using glucose as its main energy source. After fasting for 12-16 hours, the body enters ketosis and starts to use fat for energy. Within 24-36 hours, autophagy begins, a process that recycles damaged cells and allows for cellular repair. This process can have great benefits for people with T2DM, such as improved insulin sensitivity and glucose regulation.

Pathophysiology of Implementing IF in T2DM.

-IF is thought to increase insulin sensitivity by decreasing fatty tissue in the body (i.e., visceral adipose tissue), which is correlated to insulin resistance. Insulin resistance is defined as higher than normal circulating insulin levels needed for a glucose lower response, which is thought to be the culprit for the generation of T2DM. It means you need high levels of insulin to keep glucose normal.

-Obesity is an important risk factor for T2DM. Visceral adipose tissue functions as an organ via the secretion of adipokines (cytokines or cellular messengers produced by adipose tissue): leptin and adiponectin.

Leptin: proinflammatory, leading to chronic inflammation. Patients with higher BMI levels and increased insulin resistance were found to have increased leptin levels.

[Leptin is a good hormone at normal levels, but there is leptin resistance]

Adiponectin: anti-inflammatory and antidiabetic effects. Higher adiponectin levels result in decreased hepatic gluconeogenesis, enhanced glucose absorption, and enhanced skeletal muscle and hepatic fatty acid oxidation. Levels drop as visceral fat increases.

-Dr. López-Jaramillo, a Colombian endocrinologist and researcher, and colleagues published a review in 2014 examining the imbalance in the levels of leptin and adiponectin in individuals with metabolic syndrome. This imbalance (increase in leptin and decrease in adiponectin) is linked to obesity and insulin resistance, which has been shown to increase the risk of T2DM. It has been shown that IF has resulted in the reduction of leptin levels and increased levels of adiponectin, which leads to decreased insulin resistance and increased insulin sensitivity.

-IF allows pancreatic beta-cells to rest by not having to secrete insulin constantly. This allows the beta-cells of the pancreas to improve in function over time. In addition, IF has been shown to lead to noticeable weight loss and loss in body fat, both of which play an important contribution in managing T2DM. Research demonstrates that this weight loss increases insulin sensitivity and decreases the need for insulin therapy, making IF a powerful approach for improving metabolic health.

AMP-Activated Protein Kinase (AMPK) and Its Role in IF and T2DM

Recent research has highlighted an important enzyme seen in IF, AMP-activated protein kinase (AMPK), which plays a vital role as an important energy sensor in cells. It is activated when cellular energy levels are low, such as during IF. A 2020 research study in Nature Reviews Endocrinology explains that activation of AMPK aids in suppressing gluconeogenesis and stimulates fatty acid oxidation, leading to optimal energy balance and reduction of visceral adipose tissue accumulation, a major contributor to insulin resistance and T2DM progression. AMPK is upregulated during fasting, which enhances glucose metabolism and reduces insulin resistance. This is imperative in managing T2DM, as it counters the effects of insulin resistance associated with T2DM.

Exercise, which also promotes AMPK activation, complements IF and can promote a synergistic effect in improving insulin sensitivity and promoting fat burning,

New Research Findings on IF and T2DM

-The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized clinical trial published in JAMA Network Open (2024). Findings In this randomized clinical trial study found that a time-restricted eating window significantly improved fasting glucose levels and HbA1c levels in individuals with T2DM. The study examined the effect of a 16-week 5:2 meal replacement (5:2 MR) fasting plan that consisted of five days of normal eating and 2 days, nonconsecutive of restricted diet (500-600 calories). This group was examined alongside a group of patients who took metformin 0.5 g BID and empagliflozin 10 mg QD. The study wanted to investigate the changes in HbA1c in Chinese adults with early T2DM.

-The study was a randomized clinical trial of 405 adults, and a study showed that the 5:2 MR approach led to better glycemic control at 16 weeks compared to the counter treatments with metformin and empagliflozin. The 5:2 MR group had the greatest reduction in HbA1c (-1.9%), followed by metformin (-1.6%), and empagliflozin (-1.5%). The 5:2 MR plan also revealed the greatest weight loss (-9.7 kg), followed by empagliflozin (-5.8 kg), and metformin (-5.5 kg).

-This research suggests IF, such as 5:2 MR, can be a powerful tool in the management of T2DM and improving metabolic health. This study can potentially open doors for healthcare providers to provide the 5:2 MR approach for individuals as an effective initial lifestyle intervention. However, follow-up studies are needed to assess the effectiveness and durability of the 5:2 MR.

Safety and Risks of IF in T2DM.

-IF when combined with glucose-lowering medications (e.g., insulin, sulfonylureas, GLP-1 agonists) can increase the risk of hypoglycemia. Also, prolonged fasting can lead to nutrient deficiencies if not planned carefully. Patients should be counseled on maintaining a balanced, nutritious diet during non-fasting days.

-IF is not suitable for everyone. Children under the age of 18 should not try IF due to needing proper calories for adequate development and proper growth. Also, it is recommended that pregnant or breastfeeding women do not undergo IF. It is advised that people with eating disorders should not try IF.

-Individuals with certain medical conditions, such as kidney stones or gastroesophageal disease should speak with their doctor before trying IF....

Episode 179: Impact of intermittent fasting on T2DM.