The English friar and philosopher William of Ockham (1287-1347) is credited with developing the fundamental problem solving principle known as lex parsimoniae or Occam’s Razor. This principle holds that the hypothesis with the fewest assumptions is most often right. The simplest explanation is usually the most correct.

Albert Einstein is quoted as saying, “Everything should be made as simple as possible, but not simpler.” With that in mind, let’s remember that type 2 diabetes reflects two fundamental problems:

  1. Insulin resistance
  2. Beta cell dysfunction

Insulin resistance, an overflow phenomenon, is caused by fatty infiltration of the liver and muscle. Without dietary intervention, defect #2 virtually always follows #1, albeit by many years. Also, #2 is almost never found without #1. Yet somehow, we are asked to believe that the mechanism behind insulin resistance and beta cell dysfunction are completely and utterly unrelated? Occam’s razor suggests that both defects must be caused by the same underlying mechanism.


Searching for the mechanism

Hyperinsulinemia stimulates de novo lipogenesis transforming excess dietary carbohydrate into new fat. The liver packages and exports this new fat as VLDL making it widely available for other organs. The new fat deposits in skeletal muscles takes up much of this fat, as do the fat cells in and around the abdominal organs leading to the central obesity that is an important component of metabolic syndrome.

As fat begins to deposit within the organs, specifically the liver and muscles, insulin resistance develops, gradually leading to rising blood glucose. In response, the body secretes even more insulin to bring the renegade blood glucose back down. The extra insulin ‘overcomes’ the rising insulin resistance, but sets up a vicious cycle. To relieve fatty congestion in the liver, it is exported out. Some ends up in the muscle and some around the organs to create central obesity. Recent research has revealed that the pancreas also becomes heavily infiltrated with fat and this plays a pivotal role in the development of type 2 diabetes.

The relationship between pancreatic weight and total body weight was first noted in 1920. In 1933, researchers first discovered that pancreases from obese cadavers contained almost double the fat of lean cadavers. By the 1960s, advances in computed tomography (CT) and magnetic resonance imaging (MRI) allowed non-invasive measurement of pancreatic fat and firmly established the connection between fatty pancreas, obesity, high triglycerides and insulin resistance. Virtually all patients with fatty pancreas also had fatty liver.

Most importantly, fatty pancreas is clearly associated with increasing degrees of diabetes. Type 2 diabetic patients have more pancreatic fat than non-diabetics. The more fat found in the pancreas, the less insulin is secreted. Pancreatic and hepatic fat content is much higher in diabetics even if they are of equal age and weight. Simply put, the presence of fatty pancreas and fatty liver is the difference between an obese diabetic patient and an obese non-diabetic one.

Bariatric surgery can normalize pancreatic fat content accompanied by restoration of normal insulin secreting ability. Despite weighing an average of 100 kg, patients successfully reversed type 2 diabetes within weeks of surgery. By comparison, obese non-diabetic patients that had pancreatic fat was normal to start and unchanged despite similar levels of weight loss. The excess pancreatic fat is only found in type 2 diabetics and is not related to the weight loss of surgery.

The insulin secreting beta cells of the pancreas were clearly not ‘burnt out’. They were merely clogged with fat! They merely needed a good cleaning out. What is shocking is that it only took the removal of 0.6 grams of pancreatic fat to reverse type 2 diabetes. In addition to fatty pancreas, type 2 diabetic patients differ from non-diabetics by the presence of fatty liver. Eight weeks after bariatric surgery, this liver fat had decreased to normal levels accompanied by normalization of insulin resistance.

The COUNTERPOINT study established these same benefits using a very low calorie (600 calories/day) diet. Over the eight-week study period, pancreatic fat content slowly decreased associated with restoration of insulin secretory ability.

The difference between having type 2 diabetes or not is not simply the total weight of a person. Instead, fatty liver drives insulin resistance, and fatty pancreas drives the beta cell dysfunction. These are the twin cycles of type 2 diabetes.

  1. Insulin resistance caused by fatty liver, fatty skeletal muscle
  2. Beta cell dysfunction caused by fatty pancreas

The two fundamental defects of type 2 diabetes were not caused by two completely different mechanisms. They are one and the same. Both are problems related to fat deposits within organs, ultimately relating back to hyperinsulinemia.


The twin cycles

The natural history of type 2 diabetes mirrors the development of the twin cycles. Insulin resistance develops long before the high blood sugar clinches the diagnosis. The Whitehall II study plotted the trajectory of blood glucose in the years prior to the clinical diagnosis of type 2 diabetes. Insulin resistance emerges almost fourteen years prior to type 2 diabetes. The mounting insulin resistance produces the long slow rise in blood glucose. The compensatory hyperinsulinemia prevents the rapid rise in blood glucose. For over a decade, blood glucose stays relatively normal.

Underneath the surface of normality, the body is trapped in a vicious cycle, the first of the twin cycles – the hepatic cycle. Excessive carbohydrates intake provokes excessive insulin secretion, leading to de novo lipogenesis. The vicious cycle has begun. High insulin generates fatty liver, which increases insulin resistance. In turn, this increases insulin, which only perpetuates the cycle. This dance goes on for more than a decade gradually worsening each time we go around.

The pancreatic cycle

Approximately three years before the diagnosis of type 2 diabetes, blood glucose takes a sudden sharp upswing. This heralds the beginning of the second of the twin cycles – the pancreatic cycle.

The liver decompresses its growing fat stores by exporting it as VLDL transferring this newly created fat to other organs including the pancreas. As the pancreas becomes clogged with fat, it is unable to secrete insulin normally. Insulin levels, previously high to offset the high blood glucose, begin to fall.

The loss of this compensation results in a rapid rise in blood glucose and ultimately, the diagnosis of type 2 diabetes. Glucose spills over into the urine causing the symptoms of frequent urination and thirst. Even though insulin drops, it stays maximally stimulated by the high blood sugars.

The hepatic (insulin resistance) cycle and the pancreatic (beta cell dysfunction) cycle together form the twin vicious cycles responsible for the development of type 2 diabetes. But they have the same underlying mechanism. Excessive insulin drives fatty organ infiltration. The underlying cause of the entire cascade of type 2 diabetes is hyperinsulinemia. Simply put, type 2 diabetes is a disease caused by too much insulin.

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