Excerpts from Book – ‘The Diabetes Code’ by Jason Fung
Indicators of Metabolic Syndrome
- Abdominal obesity, measured by waist circumference: men over 40 inches, women over 35 inches;
- Low high-density lipoprotein (HDL): men less than 40 mg/ dL or women less than 50 mg/ dL or taking medication;
- High triglycerides: over 150 mg/ dL or taking medication;
- High blood pressure: over 130 mmHg systolic (top number) or over 85 mmHg diastolic (bottom number) or taking medication;
- Fasting blood glucose > 100 mg/ dL or taking medication.
The liver lies at the nexus of metabolism and nutrient flow, particularly for carbohydrates and proteins. Situated immediately downstream from the intestines, nutrients enter the blood in the portal circulation and pass directly to the liver. The major exception is dietary fat, which is absorbed directly into the lymphatic system as chylomicrons. These chylomicrons empty into the bloodstream without first passing through the liver.
When carbohydrates and proteins are absorbed, the pancreas releases insulin. It travels in the portal vein, an expressway to the liver.
The liver prefers to store extra glucose in long glycogen chains since it is an easily accessible form of energy. However, there is limited space inside the liver for that glycogen.
It transforms this glucose through de novo lipogenesis (DNL) into newly created molecules of triglycerides, also known as body fat.
Hypertriglyceridemia
THESE NEWLY CREATED triglycerides are made from the substrate glucose, not from dietary fat. This distinction is important because fats made by DNL are highly saturated. Eating dietary carbohydrates, not dietary saturated fat, increases saturated fat levels in the blood. Saturated fats in the blood, not the diet, are highly associated with heart disease.
These two forms of storage fulfill different and complementary roles. The stored glucose, or glycogen (fridge), is easily accessible but limited in capacity. The stored body fat, or triglycerides (freezer), are hard to access but unlimited in capacity. The two main activators of DNL are insulin and excessive dietary fructose. High dietary intake of carbohydrates— and to a lesser extent, protein— stimulates insulin secretion and provides the substrate for DNL. With DNL running at full production, large amounts of new fat are created. Excessive DNL can overwhelm the export mechanism, resulting in abnormal retention of this new fat in the liver. As you stuff more and more fat into the liver, it becomes noticeably engorged and can be diagnosed on ultrasound as fatty liver. But if the liver is not the appropriate place to store this new fat, where should it go?
Your glycogen “fridge” is full, so the only remaining option is to export the newly created fat (excess food) somewhere else. This mechanism is known as the endogenous pathway of lipid transport. Essentially, triglycerides are packaged with special proteins to create very low– density lipoproteins (VLDL), which are released into the bloodstream to help decompress the congested liver. More dietary glucose and fructose means more DNL which means more VLDL must be released. This mass export of triglyceride-rich VLDL particles is the major reason for high plasma triglyceride levels, which are detectable in all standard blood tests for cholesterol. Ultimately, eating too much glucose and too much fructose causes this hypertriglyceridemia.
Simply put, higher insulin levels and fructose ingestion produce higher blood triglyceride levels. There’s just too much sugar.
Low high-density lipoproteins (HDL)
AS VLDL PARTICLES circulate through the bloodstream, insulin stimulates the hormone lipoprotein lipase (LPL), which is found in the small blood vessels of muscles, adipocytes, and the heart. This LPL transports the triglycerides out of the blood into adipocytes for safe storage. As VLDL releases its triglycerides, the particles become smaller and denser; now called VLDL remnants, the liver reabsorbs them. In turn, the liver releases these remnants back into the bloodstream as low-density lipoproteins (LDL), which are measured by standard blood cholesterol panels and are classically considered the “bad” cholesterol. High blood triglycerides strongly and independently predict cardiovascular disease. High levels of LDL are pointedly not one of the criteria for developing metabolic syndrome.
Low levels of HDL are found in close association with high levels of triglycerides. High levels of triglycerides activate the enzyme cholesterol ester transfer protein (CETP), which reduces HDL levels. Given this close association with triglycerides, it should be no surprise that low-carbohydrate diets raise HDL, even independent of weight loss.
What is clear, however, is that the lipid profile typical of the metabolic syndrome— high triglycerides and low HDL— results from the excess of VLDL, which ultimately stems from hyperinsulinemia, which ultimately stems from eating too much glucose and fructose. Again, too much sugar.
Abdominal obesity
THE ADIPOCYTES GET larger as they take up the triglycerides for storage. This is not particularly dangerous to our health since adipocytes are designed to store fat. But being too fat is dangerous from an evolutionary standpoint, because fat animals get eaten. The adipocytes protect themselves against overexpansion by releasing the hormone leptin. This signals the hypothalamic area of the brain that we need to lose fat. We stop eating, insulin drops, and we lose weight. In this way, obesity serves as the first line of defense against hyperinsulinemia. Insulin encourages fat storage, whereas leptin strives to reduce it.
If you have too much body fat, leptin is released, which decreases food intake. Insulin should fall, and you should lose weight. In insulin-resistant states, insulin levels stay persistently high, which tells the body to keep storing fat. Leptin therefore stays persistently high too. As with all hormones, exposure creates resistance, so persistently high leptin creates the leptin resistance found in common obesity. It’s a tug of war between insulin and leptin, and if you are eating too much sugar, ultimately, insulin wins. Insulin allows glucose to move from the blood into the cells. Persistent hyperinsulinemia crams even more glucose into the liver, creating even more new fat.
When hyperinsulinemia persists, the pedal-to-the-metal production of new fat overwhelms the adipocytes. Fat backs up, causing fatty liver. Fructose is directly converted to liver fat and leads to the next stage, insulin resistance. If allowed to continue, the engorged liver will become distended and injured. The liver cell cannot safely handle any more glucose, yet insulin is still pushing really, really hard to shove more inside. The liver’s only option is to refuse entry. This is known as insulin resistance, and it develops as the body’s second line of defense against hyperinsulinemia.
The liver feverishly tries to relieve the fatty congestion by exporting triglycerides, and blood levels increase in a classic sign of metabolic syndrome. Ectopic fat accumulates in other organs, such as the pancreas, kidneys, heart, and muscle. The predominance of fat around the abdomen becomes noticeable as an increase in waist size, which can be described as a beer belly
High blood glucose
IN ADDITION TO accumulating in the abdominal region, fat accumulates within organs that are not designed to store it. Distention of the liver and skeletal muscles with fat increases insulin resistance, even though the pancreas increases insulin to keep blood glucose levels relatively normal. But that’s not the end of the story. Ectopic fat clogs the pancreas and interferes with normal functioning, so insulin levels fall. When the fatty pancreas fails to produce the compensatory hyperinsulinemia, blood glucose skyrockets and becomes symptomatic when it exceeds the renal threshold. Glucose spills out into the urine, and the classic symptoms of diabetes— excessive urination, thirst, and weight loss— appear.
High blood pressure (hypertension)
Insulin increases blood pressure through multiple mechanisms. Insulin increases the cardiac output— the contractile force of the heart— and the volume of blood in circulation by enhancing the kidney’s ability to reabsorb sodium (salt). In addition, insulin stimulates the secretion of anti-diuretic hormone, which helps the body to reabsorb water. Together, this salt and water retention mechanism increases blood volume and thus causes higher blood pressure. Insulin also constricts blood vessels, increasing the pressure inside.
Insulin resistance and type 2 diabetes cannot cause metabolic syndrome because they are part of the syndrome. Hyperinsulinemia causes it. The very core of the problem is hyperinsulinemia from excessive fructose and glucose, but especially fructose intake.
Metabolic syndrome, of which obesity and type 2 diabetes are a key part, are ultimately caused by— you guessed it— too much sugar. Obesity, insulin resistance, and beta cell dysfunction are all protective mechanisms. Obesity tries to prevent DNL from overwhelming the liver by safely storing the newly created fat in the adipocytes.
Fat cells actually provide protection against metabolic syndrome rather than causing it. Why? Because without adipocytes, fat must be stored inside the organs, where it causes metabolic syndrome. If fat can be stored inside adipocytes instead, no metabolic damage results. Obesity is the first line of defense against the root problem of hyperinsulinemia/ insulin resistance. Similarly, insulin resistance is the body’s attempt to prevent fat from amassing in the internal organs by preventing it from entering. The liver refuses to allow more glucose to enter because it is already overfilled, and the result is visible as insulin resistance, which represents a second protective mechanism. The final line of defense lies in shutting down pancreatic production of insulin. Blood glucose rapidly rises above the renal threshold and causes all the classic symptoms of diabetes. But this toxic load of glucose has been safely discharged out of the body, and is unable to cause further metabolic damage.
All the conditions we thought were problems— obesity, insulin resistance, and beta cell dysfunction— are actually the body’s solutions to a single root cause— too much sugar. And when we understand the root cause, the answer to all of these problems— and to type 2 diabetes— becomes immediately obvious. We need to get rid of the sugar and lower insulin.
*Do read the Disclaimer