Diabetes

Dr Paul Clayton, Medical Pharmacologist, Former President of the Forum on Food and Health at the Royal Society of Medicine

My life in nutritional science

My science

DIABETES
SUMMARY

All the drugs used today to treat diabetes operate at a single site, but as the disease is the result of multiple metabolic errors, it makes much more sense to rectify all the imbalances. Improved diet, increased exercise and a well-designed supplement all contribute to improving the situation.

Something very like this multiple intervention programme has already been tested. Australian Aborigines do not develop diabetes when living a traditional hunter-gatherer lifestyle, but are very susceptible to diabetes once they are exposed to the modern high-glycemic, micronutrient-poor diet and low physical activity environment.

If they return to their traditional way of life, however, they return to high levels of physical activity, and a diet which is low-GI, but high in micronutrients. And their diabetes largely disappears.

We don’t quite need to go back to being hunter-gatherers, as we are (thanks to many generations of farming) innately less insulin-resistant than the Aborigines. But we do need to improve our diet and increase our levels of physical activity. If we can do this we will all live longer, healthier and happier lives.

Diabetes

The number of adults with diabetes has risen spectacularly – between 6-8% of adults are known to have diabetes, with the true incidence probably closer to 10%, when undiagnosed diabetes is also taken into consideration (Harris et al ’98, Mokdad et al ’00).

By 2050 as many as 1 person in 5 is projected to have the disease.

Even more worryingly, the disease has begun to affect growing numbers of children. In the US, experts predict that on current trends, one out of every three children born in 2000 will develop Type 2 diabetes.

The global increase in Type 2 diabetes parallels the increasing tides of overweight, obesity and physical inactivity that are known to drive the disease.

The human and economic costs are vast, and predicted to increase dramatically over the next decade (Must et al ’99, Engelgau et al ’04, Ford et al ’04). If we include people with Impaired Glucose Tolerance, a pre-diabetic condition, the projected costs in the UK will rise to the point that diabetes will represent over 50% of the National Health budget which would have to be expanded to consume 12% of our entire GDP! It’s totally unsustainable.

It also represents a near future, where 1 in 6 of us will be chronically ill and where life expectancy will go into a sharp decline. It’s the catastrophic failure of the pharmaceutical model of health ie. treat the symptoms of the disease when they surface, rather than prevent the disease from happening.

Health costs, Pharma profits

Diabetes accelerates the ageing process. It increases the risk of ill health and shortens life, doubling or trebling the risk of dying prematurely (Panzram ’87). The diabetic is up to 4 times more likely to die of heart disease, up to 6 times more likely to die of stroke (Panzram ’87); at increased risk of kidney failure, blindness and lower limb amputation (Stephenson et al ’95).

Some of this increased risk can be reduced by stringent blood sugar control through a restricted diet (UKPDS ’98), but in practical terms this is a difficult target and one which most diabetics are unable to achieve (Lusignan et al ’05). So we are left on the whole with drugs such as metformin, and on current trends 1 in 6 of us can expect to be dependent on metformin and related drugs for the rest of our lives! A bitter pill for us to swallow – and sweet profits for Big Pharma.

Is there an alternative? According to the drugs industry literature there is, but I’m deeply sceptical. ‘Glittering’ new drugs such as the glitazones carry such adverse effects as weight gain, fluid retention, liver damage (NPS ’05). There is also a possible increased risk of heart failure (Anon ’02), although this is disputed (Karter et al ’05).
Pharmaceutical ‘puffs’ about gene therapy are wide of the mark. The epidemic of diabetes that has been gathering momentum over the last few decades is nothing to do with genes – which have not altered in such a short period of time – and everything to do with our lifestyle.

The Lifestyle Case

The most important risk factors for developing Type 2 diabetes are obesity and physical inactivity (Sullivan et al ’05). Evidence from randomised controlled trials on three continents has clearly demonstrated that maintenance of modest weight loss through diet, combined with physical activity, reduces the incidence of Type 2 diabetes in high-risk individuals by between 40-60% over 3-4 years (Pan et al ’97, Tuomilheto et al ’01, Knowler et al ’02, Williamson et al ’04).

Would you rather take pills? In one crucial study (Knowler et al ’02), a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week reduced the incidence of diabetes in high-risk patients by 58 percent. This was approximately TWICE as effective as taking prophylactic metformin, which reduced the incidence of diabetes by 31%.

Since the diabetic is at significantly increased risk of heart attacks and stroke, you could also, if you wanted, take pills for that. Step forward one of the drug industry’s biggest earners, the statins. They lower cholesterol, and the risk of heart attack and stroke. But not by much … In a number of large-scale trials the statins reduced the risk of heart attacks and stroke by 1.4%! (Shepherd et al ’95, Downs et al ’98, ALLHAT ’02, Shepherd et al ’02, Sever et al ’03)
In contrast, a group of patients at high risk of heart attack was given dietary advice, which over a period of 4 years, reduced the incidence of heart attack by 67% – and also the risk of cancer (de Lorgeril et al ’99, Leaf ’99). In other words improved diet can be many times more effective than drugs.

The 3-phase model of diabetes

As the name implies, this model consists of three different phases, which describe how glucose is handled in the body.

Phase 1 is the glucose source (the diet)

Phase 2 involves the bloodstream (which carries glucose derived from the diet to where it is needed)

Phase 3 involves glucose ‘sinks’. These are uptake/storage sites where glucose is taken up from the blood and utilised. Apart from the brain and central nervous system, which require a constant glucose supply, there are two main glucose sinks. The best-known is skeletal muscle which ‘burns’ glucose to fuel muscular exertion. The other is brown adipose tissue (or brown fat), which is designed to ‘burn’ glucose to provide body heat.

Hunter-gatherers ate a diet with a low glycemic load; it contained relatively little carbohydrate, and what there was, tended to be only slowly or partially digestible. The amount of glucose entering the bloodstream was therefore restricted and used for activity and heat.

These folk had well-exercised muscle, and, in the cold season, functional brown fat. Any excess glucose in the blood was quickly taken up and used by muscle for energy, and brown fat for heat. So blood glucose levels remained low.

The mechanism whereby glucose is actively pulled out of the bloodstream and into the tissue is a complex process and requires a number of nutritional co-factors, including adequate amounts of the trace elements manganese (Baly et al ’90) and chromium (Davis & Vincent ’97); and the B vitamin inositol (Romero et al ’88, Ostlund et al ’93, Fonteles et al ’96).

If all these nutrients are present in the diet, the insulin receptors and glucose uptake pumps work properly, and all is well. The Stone Age diet had these nutrients because it had a high micronutrient density (from fruits, vegetables, berries, nuts and offal meats) and very few refined carbohydrates. Consequently our hunter-gatherer ancestors did not suffer from Type 2 diabetes.

STONE AGE = HEALTHY GLUCOSE CONTROL

The situation today is different in every respect. Our diet has a glycemic load (from refined sugars and starches) that is almost ten times greater than that of our Stone-Age ancestors (Cordain et al ’05). We are very much less physically active, so much so that the muscles and muscle attachments of an average male office worker are smaller than those of an average Victorian female manual worker!

This means that the capacity of our muscles as glucose ‘sinks’ and their ability to remove glucose from the bloodstream is very limited. And our reduced exposure to cold means that our brown fat function is suppressed, so this is also ineffective in removing glucose from the bloodstream.

In this situation, glucose is pouring into the bloodstream in unprecedented amounts, and there is nowhere for it to go; so levels in the bloodstream rise. More and more insulin is secreted by the pancreas in a progressively failing attempt to get it out of the bloodstream.

To make matters worse, the glucose uptake pumps are compromised, as our diet is very likely to be low in chromium (Anderson et al ’85), and may well be low in manganese and inositol also.

Furthermore, sustained high levels of glucose in the blood lead to everything in the bloodstream becoming glycated, or sugar-coated. This includes insulin itself, and the insulin receptors.
Once these elements have become glycated, the insulin is no longer able to activate the insulin receptor as effectively as it should (Hunter et al ’03) and a morbid (ie. disease-state) form of insulin resistance develops.

Here is the sequence in diagram form:

Blood sugar rises after a meal – the higher the glycemic index (ie sugar content) of the meal, the more sugar enters the bloodstream.

The pancreas produces insulin in an attempt to counteract and lower blood sugar levels.

If the diet includes insufficient levels of chromium and manganese, the body’s natural blood sugar uptake mechanisms are compromised.

Blood glucose is used in the muscles for energy and in the brown fat areas for warmth. Excess sugar is converted to body fat.

Over time and with a high GI diet, the pancreas’s ability to produce insulin may be overwhelmed and degraded. The body is now becoming ‘insulin resistant’.

Now excessive blood sugar levels coat (glycate) insulin receptors, which means that insulin becomes less and less effective.

The patient may now develop Type 2 diabetes.

Symptoms of diabetes

are:
You are very thirsty a lot of the time.
You pass a lot of urine.
Tiredness, weight loss, and feeling generally unwell.

The above symptoms tend to develop quite quickly, over a few days or weeks.

Diet and exercise

The three-phase model helps to explain why diabetes can be improved by so many different interventions. An improved diet which reduces refined sugars and starches therefore reduces the amount of glucose pouring into the bloodstream. – and in turn reduces the probability of glucose being used to create body fat.

Increased exercise increases lean body mass and therefore up-regulates the glucose sink in muscle, and pulls glucose out of the bloodstream.

Chromium supplements – of about 120 mcg a day – help in those cases where chromium depletion has left the glucose uptake mechanism significantly impaired (Anderson et al ’97).

All the drugs used today to treat diabetes operate at a single site, but as the disease is the result of multiple metabolic errors, it makes much more sense to rectify all the imbalances. Improved diet, increased exercise and a well-designed supplement all contribute to improving the situation.

Something very like this multiple intervention programme has already been tested. Australian Aborigines do not develop diabetes when living a traditional hunter-gatherer lifestyle, but are very susceptible to diabetes once they are exposed to the modern high-glycemic, micronutrient-poor diet and low physical activity environment.

If they return to their traditional way of life, however, they return to high levels of physical activity, and a diet which is low-GI, but high in micronutrients. And their diabetes largely disappears (O’Dea ’80, ’82, ’84, ’91, Hodgson & Wahlquist ’93).

Dr Kerin O’Dea’s valuable research has been almost forgotten – probably because the answers it produced cannot be used to sell drugs. But it is very clear that the way forward for us is a return to a healthier, more active and more self-reliant life.

We don’t quite need to go back to being hunter-gatherers, as we are (thanks to many generations of farming) innately less insulin-resistant than the Aborigines. But we do need to improve our diet and increase our levels of physical activity. If we can do this we will all live longer, healthier and happier lives.

DIETARY RECOMMENDATIONS for today

Various diets such as the faddish Atkins diet have recommended reducing intakes of carbohydrates, but there are problems associated with this approach including increased risks of kidney damage and, very probably, colorectal cancer.

More recent diets have integrated a low-GI approach with increased intakes of the valuable fermentable carbohydrates; and combined this with increased intakes of fruits and vegetables, as per the W.H.O. guidelines, all within a satisfying but low-calorie eating plan.

The recommendations in the ‘Staying Well’ section of this site, if combined with a moderate exercise regime, should lead to improved blood glucose control in the majority of cases. For extra detail see After Atkins by Paul Clayton (Constable & Robinson ‘05).