Fatty pancreas HYPERINSULINEMIA CAUSES FATTY liver, and to relieve the backup, this newly created fat is exported out of the liver to other parts of the body. Some of
it ends up in adipocytes, and some in the skeletal muscle.
The pancreas also becomes heavily infiltrated with fat.
The relationship between pancreatic weight and total body weight was first noted in 1920.
Pancreases from obese cadavers contained almost double the fat of lean cadavers.29 By the 1960s, advances in non- invasive imaging allowed direct 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 type 2 diabetes.30 Type 2 diabetic patients have more pancreatic and hepatic fat than nondiabetics.31 The more fat found in the pancreas, the less insulin it secretes.32 Simply put, fatty pancreas and fatty liver is the difference between a type 2 diabetic and a nondiabetic.
The difference is obvious during bariatric (weight-loss) surgery, which is used to reduce the size of the stomach or bypass the small intestine (more on this in Chapter 13).
This surgery does not directly remove fat, like liposuction, which has no metabolic benefits.33 Obese nondiabetics have a normal amount of pancreatic fat, which remains unchanged after surgery despite the weight loss.
Obese type 2 diabetics have excess pancreatic fat, but bariatric surgery reduces it and restores normal insulin-secreting ability.
The result is successful reversal of type 2 diabetes within weeks of their surgery, even if they are still hundreds of kilograms overweight.
The excess pancreatic fat is only found in type 2 diabetics.
The pancreatic beta cells were clearly not burnt out; they were clogged with fat.
The removal of only 0.6 grams of pancreatic fat successfully reverses type 2 diabetes.
Eight weeks after bariatric surgery, liver fat also normalizes, as does insulin resistance.
Bariatric surgery is not the only method of achieving these benefits.
Sudden severe caloric restriction in the COUNTERPOINT Study34 decreased the amount of fat in the pancreas and re-established its ability to secrete insulin within weeks.
Ectopic fat, the accumulation of fat in places other than fat cells, plays a critical role in the development of insulin resistance.
This includes fatty liver, fatty muscle, and fatty pancreas.
Even in severely obese patients, insulin resistance does not develop in the absence of ectopic fat
accumulation.35 This fact explains how an estimated 20 percent of obese individuals may have no insulin resistance and normal metabolic profiles.36 Conversely, normal-weight subjects may develop type 2 diabetes if the fat is deposited in the organs instead of in the fat cells.
Fat inside fat cells is okay.
Fat inside organs is not.
First noted in the 1950s,37 visceral obesity, also called central obesity or abdominal obesity, is metabolically damaging.
In the absence of insulin, these ectopic fat deposits, and hence insulin resistance, cannot develop.38 Indeed, accumulated fat deposits melt away under conditions of sustained low insulin levels.
Insulin is required to convert excess calories to fat and also to sustain it as fat.
Developing type 2 diabetes is not simply a function of increased body fat but the accumulation of intra-organic fat.
The problem is not just the fat, it’s the ectopic fat.
Fatty liver and muscle drives the insulin resistance seen in the first phase of development of type 2 diabetes.
Fatty pancreas drives the beta cell dysfunction seen in the second phase.
The twin defects of type 2 diabetes include • insulin resistance caused by fatty liver and fatty skeletal muscle, and • beta cell dysfunction caused by fatty pancreas.
Importantly, these two fundamental defects are not caused by two completely different mechanisms.
They are manifestations of the same essential problem: intra-organic fat accumulation driven by hyperinsulinemia, which is caused ultimately by excessive dietary glucose and fructose.
Essentially, too much sugar causes type 2 diabetes.
This answer is the simplest, most intuitive, and most correct.
Ockham’s razor cuts through the confusion.
THE DUAL CYCLES: A SUMMARY
TWO VICIOUS CYCLES sustain type 2 diabetes: the hepatic and the pancreatic. The hepatic cycle develops first. Excessive glucose and fructose ingestion leads to hyperinsulinemia, fatty liver, and then insulin resistance. The vicious cycle has begun. High insulin resistance further stimulates hyperinsulinemia, perpetuating the cycle. This dance goes around and around, gradually worsening each time. Figure 7.4. The hepatic cycle (insulin resistance)
The hepatic cycle may continue for many years before the start of the pancreatic cycle.
The fatty liver decompresses itself by exporting newly created fat as very low, density lipoprotein (VLDL) to other organs, including the skeletal muscles and pancreas.
As fatty muscle develops, whole body insulin resistance worsens further.
As the pancreas becomes clogged with fat, it becomes 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.
Even though insulin drops, it stays maximally stimulated by the high blood glucose.
This is the body’s attempt to break this vicious cycle, as we shall soon discuss.
Figure 7.5.
The pancreatic cycle (beta cell dysfunction)
The hepatic (insulin resistance) cycle and the pancreatic (beta cell dysfunction) cycle together form the vicious twin cycles responsible for the development of type 2 diabetes. But they have the same underlying mechanism. Excessive insulin drives ectopic fat production and organ infiltration. The underlying cause of the entire cascade of type 2 diabetes
is hyperinsulinemia. This is driven in turn by excessive dietary consumption of sugar, primarily glucose and fructose. Simply put, type 2 diabetes is a disease entirely caused by too much sugar. To understand fully, we need to consider the deadly effect of fructose.
THE FRUCTOSE, INSULIN RESISTANCE CONNECTION
IN 2009, DR.
Robert Lustig, a pediatric endocrinologist at the University of California, San Francisco, delivered a ninety-minute lecture entitled “Sugar: The Bitter Truth.1 The university posted it on YouTube as part of a medical education series.
Then a funny thing happened.
It went viral.
It was not a humorous cat video.
It was not a video of a toddler throwing a baseball into Dad’s groin.
It was a nutrition lecture filled with biochemistry and complicated graphs.
This particular lecture grabbed the world’s attention and refused to let go.
It has now been viewed more than seven million times.
What was its attention-grabbing message?
Sugar is toxic.
Dr.
Lustig was not the first physician to warn about the dangers of eating too much sugar.
In 1957, prominent British nutritionist Dr.
John Yudkin warned that sugar played a prominent role in the growing incidence of heart disease.
However, the world chose to follow Dr.
Ancel Keys’s condemnation of dietary fat instead.
After leaving academic medicine, Yudkin wrote an eerily prescient book entitled Pure, White and Deadly,2 but his warnings have largely gone unheeded.
The 1977 Dietary Guidelines for Americans distinctly warned the general public about the dangers of eating too much sugar, but this
message got lost in the anti-fat hysteria that followed.
Dietary fat was public enemy number one, and concerns about excess sugar faded like the last rays of sunset.
Sugar consumption rose steadily from 1977 to 2000, paralleled by rising obesity rates.
Ten years later, type 2 diabetes followed doggedly, like a bratty little brother.
Obesity alone does not fully explain the recent upsurge in diabetes.
Some countries with low obesity rates have high diabetes rates, while the opposite is true, too.3 Sri Lanka’s obesity rates rose only 0.1 percent between 2000 and 2010, while diabetes rose from 3 percent to 11 percent.
Over the same time period, in New Zealand, obesity rose from 23 percent to 34 percent while diabetes fell from 8 percent to 5 percent.
Sugar consumption explains much of this discrepancy.