Think of type 2 diabetes, and you'll probably be able to roll out the usual sequence of events leading up to the diagnosis: poor lifestyle and diet cause weight gain and obesity, and obesity causes insulin resistance—where the body can't break down the sugars in carbohydrates, so the level of sugar (glucose) in the blood starts to rise. If untreated, this will eventually lead to a drastically increased risk of heart disease or stroke.
The treatment for diabetes is also well known: a change of diet to low-sugar carbs and drugs such as metformin. The cost of treating diabetes hit $245 billion in 2012 for American patients alone, and that bill is only going to rise.
Today around 400 million people around the world suffer from type 2 diabetes, but that number is estimated to leap to 500 million by 2030, making it the world's fastest-growing disease.
But there's a sleight of hand in all of this: although we know the sequence of events, where's the evidence that one thing causes another? Even though the authoritative World Health Organization states that obesity is a trigger for diabetes, what's the mechanism that causes insulin resistance, for example?
Doctors can point to some studies showing that when high glucose levels are lowered with drugs, the rates of heart attack and stroke also drop, suggesting a connection. But just as many trials—and some very large ones—have found that diabetics whose glucose levels are lowered well below the danger threshold still suffer damage to their nerves and kidneys, another common consequence of advanced diabetes.
Paradoxically, at least according to the current theory of how diabetes works, they're also as or more likely to suffer from cardiovascular disease than diabetics whose blood sugar isn't as tightly controlled.
That's because there's been a missing link in the diabetes story: a small molecule called methylglyoxal (MG). The primary function of MG is in glucose metabolism, but it also helps to form other molecules that modify proteins, fats and DNA.
When levels of MG get too high, it can stop other molecules from working, and this can cause a range of problems such as atherosclerosis, or hardening of the arteries, which can be a precursor to strokes and heart attacks.
For years, doctors noted that diabetics have highly elevated levels of MG in their blood, but they had assumed the MG was a sidekick, a byproduct of the diabetes disease process. But a groundbreaking study has discovered that it's this very molecule—and not obesity per se—that is causing insulin resistance.
Reduce the levels of MG, and you'll start reversing the symptoms of diabetes—and this can all be achieved with an inexpensive dietary supplement called carnosine.
Clearing up the cause and effect
The idea that MG could be the real cause of diabetes has been floating around research laboratories for years, but it's taken until this year for researchers to prove it, at least in experiments on rats and flies.1
Peter Nawroth and Aurelio Teleman from Heidelberg University in Germany fed MG to healthy rats, which soon started developing the usual symptoms of diabetes, such as insulin resistance.
To understand the biological mechanisms, they tested MG levels in fruit flies, which, on the face of it, was a strange choice. But Teleman points out that they have enough similarities in energy metabolism that "results are nevertheless meaningful and can usually be translated to mammals and humans."
Using genetic engineering, the enzymes that control MG levels were switched off, and the flies became insulin resistant, then obese, and finally their glucose levels rose. "This is clear evidence that MG is not the consequence but rather the cause of type 2 diabetes," said Teleman.
It also reverses the standard view that obesity is a trigger for insulin resistance, where cells can't respond to insulin, the hormone that breaks down the sugars in carbohydrates, which in turn causes glucose levels to rise in the blood.
But now, researchers still don't understand why MG levels can suddenly rise, and that's the next stage of the research going on in Germany.
It may be due to a poor diet, and especially processed foods and their added sugars, but until they know more, the investigators are sticking to the view of researchers from Lund University in Sweden, who described the diabetic process as "a collision between the genes and the environment."2
Stopping damage before it starts
There is one take-home from the new research: the dietary supplement carnosine, an antioxidant, can reverse the symptoms of type 2 diabetes by reducing the levels of MG. Carnosine is found naturally in our brains and muscles, but only at very low levels.
Carnosine also protects other cells from MG damage, as researchers at King's College London pointed out 20 years ago. Even then, it was being heralded as "a possible nontoxic modulator of diabetic complications."3
Last year, researchers from Istanbul University reported the toxic effects of MG in rats and how these could be reversed by giving them carnosine.4
Other researchers have noted that carnosine gets 'super-charged' with high levels of zinc, and the two are especially beneficial when targeting the brain to improve age-related memory loss and generally to combat aging in the body.5
Carnosine doesn't only reverse the symptoms of diabetes, it also acts as a preventative. In one study of 30 overweight or obese people who were also prediabetic, half took 2 grams of carnosine every day for 12 weeks, and the rest took a placebo.
At the end of the study, carried out by researchers from the Monash Centre for Health in Melbourne, Australia, those given the supplement had fewer signs of insulin resistance, and their glucose and insulin scores were lower.6
Monash's lead researcher, Barbora de Courten, is planning a much larger study to establish whether carnosine can reduce the risk factors for diabetes and heart disease and improve glycemic control in people with diabetes and prediabetes.
Filling in the gaps
For years, there's been increasing evidence that we didn't have the complete picture on diabetes, but the research was being ignored. One review, by researchers from the University of Kentucky, points out that three major studies on diabetes—the ACCORD, ADVANCE and VADT trials—found that tightly controlling glucose levels had no positive impact on heart health and, in fact, could even have a detrimental effect.7
Researchers from the Clinic for Hypertension and Nephrology in Hanover, Germany, agree. In a review of the same three trials, plus the UKPDS trial, the researchers found that heart disease deaths were actually more common in the group whose glucose levels were being controlled.8
Researchers from the University of Toronto have gone so far as to conclude that one of the primary goals of diabetes treatment—to control levels of glucose—is "controversial." One real danger of tight glucose control is hypoglycemia, where blood sugar falls dangerously low. 9
Type 2 diabetes may well be the price we pay for the modern Western lifestyle and processed foods, and it's a war that medicine isn't winning.
Glucose control, the standard approach, has only a limited effect, and usually only in the first few months, while drugs like metformin also come with a range of unpleasant side-effects such as stomach problems.
The results of major studies show that lowering glucose levels isn't, on its own, the answer to stopping heart disease—demonstrating yet again that we don't have the complete picture. And without that complete picture, we can't treat the problem effectively. For diabetes, MG could be that missing piece of the puzzle.
What is diabetes?
Diabetes comes in two forms: type 1 and type 2. In type 1, the pancreas is unable to produce insulin, the hormone that breaks down carbohydrates to make the sugar, glucose, that supplies energy to cells. Type 1 diabetes patients need to have regular insulin injections to regulate glucose levels.
Type 2 is usually a more gradual process, where over time, the pancreas doesn't release enough insulin or the cells become insulin resistant. If glucose can't enter the cells, it builds up in the blood, which, unless treated or controlled, can result in heart disease, stroke, kidney failure and even blindness.
The usual suspects
Before the discovery that methylglyoxal (MG) played a vital part in the onset of type 2 diabetes (see main story), several factors had been cited as the likely cause.
• Obesity and being overweight (with a BMI over 25)
• Poor diet, especially sugar-sweetened drinks and processed foods
• Lack of exercise
• Genes: Around 36 gene mutations have been identified that may increase the risk of developing diabetes. Even so, genetic factors have been estimated to account for only 10 percent of all cases.
• Prescription drugs: A range of prescription drugs can put a person at greater risk
They include glucocorticoids, anti-inflammatory steroids, thiazide diuretics to lower blood pressure, beta blockers for regulating the heart rhythm, antipsychotics for stress and anxiety, and cholesterol-lowering statins.
Classic symptoms of diabetes
- Frequent urination
- Blurred vision
- Pins and needles in the fingers and toes