Exercise and brain insulin resistance

A November 2022 study by DZD, Tübingen University Hospital and Helmholtz Munich said, 

• "The exercise intervention increased the insulin-stimulated activity in brain regions that are responsible, among other things, for the perception of hunger and satiety and for the interaction of motivation, reward, emotion and exercise behavior," 

• "The study suggests that insulin resistance in the brain may be reversible and could be a viable therapeutic target to restore central nervous system regulation of metabolism and body weight and counteract adverse effects of obesity," 

sucrose and high fructose corn syrup and health risks

An August 2021 study by University of California, Davis, said,

• “This is the first dietary intervention study to show that consumption of both sucrose- and high fructose corn-sweetened beverages increase liver fat and decrease insulin sensitivity,” 

• “People often have a skewed perspective of aspartame and give sucrose a pass, but this study suggests that consumers should be equally concerned about both major added sugars in our food supply.”

• “Within the span of two weeks, we observed a significant change in liver fat and insulin sensitivity in the two groups consuming sucrose- or high fructose corn syrup-sweetened beverages,” 

• “That’s concerning because the prevalence of fatty liver [nonalcoholic fatty liver disease] and Type 2 diabetes continues to increase globally.”

• “It’s all physiologically connected, although we’re not sure [in what] direction it goes,” 

• “It’s very likely that the mechanism by which we develop metabolic syndrome goes through liver fat and insulin resistance. An increase in liver fat can be benign for a certain amount of time and for certain people. But it can also progress to associated inflammation in liver cells that causes fibrosis and negatively impacts liver function, which can make an individual more prone to liver cancer.”

Diabetes type 2: New Treatment pathway

A June 2021 study from University of Arizona College of Agriculture and Life Sciences and BIO5 Institute, and  Washington University in St. Louis, the University of Pennsylvania and Northwestern University,

• "All current therapeutics for Type 2 diabetes primarily aim to decrease blood glucose. So, they are treating a symptom, much like treating the flu by decreasing the fever,”

• "Obesity is known to be a cause of Type 2 diabetes and, for a long time, we have known that the amount of fat in the liver increases with obesity,”

• "As fat increases in the liver, the incidence of diabetes increases."

• "We found that fat in the liver increased the release of the inhibitory neurotransmitter Gamma-aminobutyric acid, or GABA," 

• "We then identified the pathway by which GABA synthesis was occurring and the key enzyme that is responsible for liver GABA production - GABA transaminase."

• "When the liver produces GABA, it decreases activity of those nerves that run from the liver to the brain. Thus, fatty liver, by producing GABA, is decreasing firing activity to the brain," 

• "That decrease in firing is sensed by the central nervous system, which changes outgoing signals that affect glucose homeostasis."

• "Inhibition of excess liver GABA production restored insulin sensitivity within days," 

• "Longer term inhibition of GABA-transaminase resulted in decreased food intake and weight loss."

Sitting, Insulin Resistance, and Heart Disease

A February 2020 study by the Arizona State University College of Health Solutions said,

“We were surprised to observe such a strong negative link between the amount of time spent sitting and insulin resistance, and that this association was still strong after we accounted for exercise and obesity,"

"The findings of this study build upon earlier research including our own, which showed, among older women, that too much time in sedentary behaviors was associated with higher risk for diabetes and heart disease. Reducing sitting time improves glucose control and blood flow, and engaging in physical activities, even light-intensity daily life activities like cooking and shopping, show favorable associations with reduced mortality risk and prevention of heart disease and stroke."

"Health care providers should encourage patients, including older adults, to reduce their sitting time, take breaks in their sitting time and replace sitting with brief periods of standing or light physical activity."

Diabetes Management, Young & Old

A February 2020 study by the Mayo Clinic said,

"Patients who are older or who have serious health conditions are at high risk for experiencing hypoglycemia, which, for them, is likely to be much more dangerous than a slightly elevated blood sugar level … At the same time, the benefits of intensive treatment usually take many years, even decades, to realize. So many patients may be treated intensively and risk hypoglycemia for no real benefit to them."

But younger people, who are less likely to experience severe hypoglycaemia, "should be treated more aggressively, meaning that we should not shy away from using insulin or multiple medications to lower the A1C … We need to ensure that all our patients with diabetes receive high-quality care and are able to manage their disease to prevent complications both now and in the future."

"Patients who are treated intensively are those who are most likely to be harmed by it … But at the same time, patients who would benefit from more intensive treatment are not receiving the basic care that they need. The paradox and misalignment of treatment intensity with patients' needs is really striking."

"Patients least likely to benefit from intensive glycemic control and most likely to experience hypoglycemia with insulin therapy were most likely to achieve low HbA1c levels and to be treated with insulin to achieve them…These HbA1c levels reflect HbA1c levels achieved by the patient, not necessarily HbA1c levels pursued by the clinician."

"Most importantly, clinicians should continue to engage their patients in shared and informed decision-making, weighing the risks and benefits of glucose-lowering treatment regimens in the specific context of each patient, carefully considering the patient's comorbidity burden, age, and goals and preferences for care."

“We have a great opportunity to simplify and de-intensify the treatment regimens of our more elderly patients, which would reduce their risk of hypoglycemia and treatment burden without spilling over into hyperglycemia,"

"At the same time, we need to better engage younger, healthier patients, work with them to identify barriers to diabetes management, and support them to improve their glycemic control."

“As clinicians, we need to be current on the guidelines and the evidence, know our patients, and work closely with them to do what is right for them."

Visceral Fat, Obesity, Heart Disease and Diabetes

A January 2019 study by the Smithsonian Tropical Research Institute looked at visceral adipose tissue – visceral fat – (VAT).  

One theory, the "VAT prioritization hypothesis", suggests that a fetus that is undernourished makes the decision to store fat (energy) in visceral fat instead of in fat under the skin – subcutaneous fat.  Visceral fat (VAT) is designed to protect from infection. This prioritizing has a major impact on later life obesity, diabetes, blood pressure. VAT is, in part, stored in the omentum (we wrote about that recently).

An increase in visceral fat causes inflammation. This can lead to insulin resistance. A feed-back loop starts: even more visceral fat is stored.

The researchers said,

• “Trying to understand diseases related to obesity without understanding the abdominal structures [the omentum] that become obese is like trying to understand circulatory diseases without knowing the functions of the heart,"

• "The fact that visceral fat tissue evolved to fight visceral infections provides a causal hypothesis for how high fructose sweeteners and saturated fats contribute to chronic diseases such as type 2 diabetes,"

• "They influence which bacteria grow inside the intestines [called the microbiome], making the intestinal walls more permeable and releasing more toxins into the bloodstream, stimulating the visceral immune system and potentially leading to chronic inflammatory disease."

• "I think the combination of malnutrition early in life coupled with modern diets of saturated and trans-fats and high-fructose foods available on a global scale is leading to a situation that is toxic for individuals in many different cultures."

• "People's body shape--apple versus pear--is based on the way their bodies allocate fat. Even in ancient societies, poor nutrition leading to investment in VAT contributed to apple-shaped bodies, versus more 'beautiful,' voluptuous, pear-shaped bodies associated with SAT fat storage by better-nourished babies. Social upheaval (war, conquest and disease) would have favored flexibility in fat allocation because social rank and food availability would occasionally have changed."

Insulin Resistance and Fibromyalgia

An August 2019 study by the University of Texas Medical Branch at Galveston stated,

• “Earlier studies discovered that insulin resistance causes dysfunction within the brain's small blood vessels. Since this issue is also present in fibromyalgia, we investigated whether insulin resistance is the missing link in this disorder.”

• “We showed that most - if not all - patients with fibromyalgia can be identified by their A1c levels, which reflects average blood sugar levels over the past two to three months."

• “Pre-diabetics with slightly elevated A1c values carry a higher risk of developing central (brain) pain, a hallmark of fibromyalgia and other chronic pain disorders."

• "Considering the extensive research on fibromyalgia, we were puzzled that prior studies had overlooked this simple connection,"

• "The main reason for this oversight is that about half of fibromyalgia patients have A1c values currently considered within the normal range. However, this is the first study to analyze these levels normalized for the person's age, as optimal A1c levels do vary throughout life. Adjustment for the patients' age was critical in highlighting the differences between patients and control subjects."