The physiology of Prediabetes
Prediabetes also known as Impaired glucose tolerance (IGT) or Impaired Fasting Glycaemia (IFG) is a serious health condition where blood sugar levels are higher than normal, but not high enough yet to be diagnosed as Type 2 Diabetes.
What Causes Prediabetes?
In our body pancreas produces Insulin, a hormone that helps glucose (obtained from the food that we eat) in our blood to enter our muscle, fat, and liver cells, to be used for energy. Our liver also makes glucose when we need it, such as when we’re fasting. When blood glucose levels rise after we eat, pancreas releases insulin into the blood, which lowers blood glucose (by helping it to enter body cells) to keep it in the normal range.
Which factors lead to development of Prediabetes and Diabetes?
Inflammation – Chronic low-level inflammation in pancreas, blood vessels and other specific body cells (associated with obesity and diabetes) can affect the functioning of pancreas and slow down the production of insulin thus reducing the capacity of body cells to take up glucose for energy production resulting in high blood glucose levels.
Insulin Resistance is a condition in which muscles, fat, and liver cells don’t respond well to insulin and can’t easily take up glucose from the blood. So while there is sufficient insulin present, it can’t be used by the body cells to take up glucose for energy, which leads to rising blood sugar levels. To compensate, pancreas makes more insulin to help glucose enter the body cells. Over a period of time pancreas can no longer make enough insulin to overcome our cells’ weak response to insulin, and thus blood glucose levels start rising.
Abdominal obesity – Having too much belly fat and not getting enough physical activity is known to lead to insulin resistance. A waist measurement of 40 inches or more for men and 35 inches or more for women is linked to insulin resistance.
Oxidative Stress or Free radical induced damage is another key factor involved in the development of diabetes and its complications. Increased production of free radicals and reduced availability of antioxidants that can neutralise free radicals have been repeatedly shown in people with Type 2 diabetes.
What is Insulin Resistance?
Earlier it was believed that, fat tissue was only for energy storage. However, studies have shown that belly fat makes hormones and other substances that can contribute to chronic, or long-lasting, inflammation in the body. Inflammation plays a major role in insulin resistance, Type 2 Diabetes and cardiovascular disease.
The development of diabetes from normal glucose tolerance (NGT) is a continuous process. Studies in high-risk individuals suggest that insulin resistance is a very early phenomenon, occurring years before any evidence of glucose intolerance or β-cell failure – predicting the development of Type 2 Diabetes. Accumulation of visceral adipose (Fat) correlates with insulin resistance, glucose intolerance, and other components of the metabolic syndrome.
Link between inflammation and insulin resistance
In normal state, adipocytes (Fat cells) produce hormones called adipokines, which include leptin and adiponectin both of which have potential immunomodulatory effects. Adiponectin is an anti-inflammatory cytokine. It has been shown that a higher adiponectin level is associated with a lower risk of Type 2 Diabetes.
Overnutrition along with inactive lifestyle leads to accumulation of visceral fat.
A rapidly growing fat tissue can expand faster than the vasculature (blood vessels) that supports its oxygen and nutrient requirements. Oxygen supplies to this tissue becomes limited leading to hypoxia and subsequent adipocyte death.The resultant chronic low-grade inflammation due to adipose tissue hypertrophy attracts macrophage (Macrophage – a large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, especially at sites of infection) infiltration of adipocytes. Macrophages accumulate at sites of hypoxia, providing a link between adipose tissue expansion and the induction of inflammation.
Macrophages that accumulate in adipose tissue during diet-induced obesity are not only an important source of adipose tissue inflammation but also mediate insulin resistance in adipocytes. They are a major reservoir of pro-inflammatory molecules in adipose tissue, leading to a state of chronic subclinical inflammation (metaflammation) associated with both insulin resistance and type-2 diabetes.
This macrophage infiltration leads to release of inflammation causing cytokines TNF α and IL-1β. TNF α is responsible for insulin resistance and IL-1βfor beta cell damage and apoptosis (cell death).
