3.12

Insulin resistance is generally accepted as a dominant factor leading to type 2 diabetes, and the most probable single link between obesity, type 2 diabetes, and cardiovascular disease [43]. Different tissues, including those in the brain can manifest insulin resistance. In the brain insulin resistance negatively affects the functioning of the HPA and the Hippo. This in turn can lead to cognitive impairment and a reduced ability to moderate stress responses and regulate appetite [107]. T2 diabetes is a manifestation of insulin resistance at the level of the liver; a key factor to metabolic inflexibility [44].

Metabolic flexibility is a measure of the body’s ability to respond or adapt to conditional changes in metabolic demand, insulin resistance, and the mechanisms that govern energy selection between glucose and fatty acids [44]. When we put on weight, fat not only get stored around our body, but it also gets deposited in organs such as the liver, pancreas, heart and other ectopic regions. Fat impairs the functioning of the pancreas to produce insulin and the liver is one of the organs most affected. Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance [119]. In the brain insulin plays a direct role in how mitochondria respond to stress. A state of insulin resistance impairs effective stress response and inhibits mitochondrial biogenesis [111].

T2 diabetes and metabolic associated fatty liver disease (MAFLD) are directly related (bidirectional). If we have one condition; it’s likely the other will develop.  It’s estimated that 1 in 6 people with T2 diabetes has undetected liver fibrosis [45]. A healthy liver is key to regulating blood sugar, and it’s important to pay attention to the types of sugar we consume. We know the body breaks down glucose in the cells for energy which triggers the pancreas to release energy. This is not true for fructose. Foods high in fructose (reference GI index) and high fructose corn syrup trigger the storage (not the release) of energy. They do not trigger insulin release or the release of hormones like leptin that “tell” us we’re full. Because we don’t feel full, we tend to “overeat” these types of foods.

Cholesterol and Liver Health

Another key factor in liver health relates to cholesterol levels and triglycerides. Cholesterol travels through the blood on proteins called “lipoproteins.” Two types of lipoproteins carry cholesterol throughout the body:

• LDL (low-density lipoprotein) cholesterol, sometimes called “bad” cholesterol, makes up most of your body’s cholesterol. High levels of LDL cholesterol raise your risk for heart disease and stroke.

• HDL (high-density lipoprotein) cholesterol, sometimes called “good” cholesterol, absorbs cholesterol in the blood and carries it back to the liver. The liver then flushes it from the body. High levels of HDL cholesterol can lower your risk for atherosclerotic cardiovascular heart disease (ASCVD) and stroke [121].

The primary component events of ASCVD, (the major cause of death and morbidity in the US are related to the development and consequences of plaque buildup in the arteries. When our body has too much LDL cholesterol, the LDL cholesterol can build up on the walls of blood vessels. For your well-being, if you have a familial history of heart disease, t2 diabetes and similar illnesses, insist on regular screenings for blood health and liver functioning. Adults who consume a diet rich in simple carbohydrates and saturated fats are more likely to develop to cognitive impairment in later life. So…what can we do? We can increase our physical activity and work with a dietician to learn about food habits that support insulin functioning [122]. Three types of foods to avoid are those high in fat, added sugars, and refined carbohydrates.