Key points

  • Type 2 is defined as blood glucose levels above a particular level.
  • High blood glucose is only the final outcome of a pathway that originates in a complex package of abnormalities in several organs.
  • The main abnormalities are in the liver and pancreas.
  • In Type 2 the liver overproduces glucose, especially overnight. Insulin, whose main job during the day is to reduce blood glucose levels after meals, isn’t produced in sufficient quantities from the pancreas.
  • Type 2 diabetes has a strong genetic basis, and runs in families.
  • Although over-nutrition is strongly associated with Type 2 diabetes, most people developing Type 2 aren’t obese.

Type 2 diabetes is complicated and still not fully understood, but we’re getting there. Until the late 1980s, we couldn’t even reliably make the distinction between the two major forms of diabetes – Type 1, which usually begins in childhood and requires permanent insulin treatment right from the start, and Type 2 – but it was known that all types of diabetes were characterised by high blood glucose levels. From the late 1980s it gradually became clear that having a high glucose level wasn’t the fundamental problem in Type 2. Much more important was a series of problems occurring in two organs – though these eventually led to high glucose levels.

New ideas on the cause of Type 2 diabetes

Evidence increasingly supports the idea that most cases of Type 2 diabetes are caused by stress on the liver and pancreas resulting from over-nutrition, which usually, but not always, leads to being overweight or obese. This nutritional stress occurs over a long time – many years in some cases – before people develop diabetes. This process is similar to stress on any mechanism – for example, mechanical or even electronic equipment – where small errors and defects accumulate over the years without there being any noticeable problem, but then there is a final stress, which may not be any bigger than the earlier ones, but which precipitates mechanical or electronic failure. In the case of Type 2 diabetes, continuing stress on critical organs, the liver and pancreas, results in the onset of diabetes diagnosed by ‘high’ glucose levels. But the original problem will have started many years earlier, certainly in childhood, and perhaps even earlier. Around the same time as this new idea about the real nature of Type 2 diabetes was being uncovered, it was becoming clear that over-nutrition during pregnancy – and under-nutrition too – were both linked to an increased risk of Type 2 when offspring grew up to be adults. In other words, Type 2 is now considered to be a very long-term condition indeed: not caused by eating too many chocolates as a middle-aged adult, as is popularly thought, but by a series of subtle but continuing stresses that have taken place over at least a generation, and perhaps even longer.

Metabolic stress caused by over-nutrition

Let’s describe in more detail the role of the liver and pancreas, how they become stressed by over-nutrition, and then how they respond to this stress.

In order to do this, and therefore to understand Type 2 diabetes, we need to appreciate that food is metabolised in a very complicated way, and we have to understand that if, for example, you eat sugar, it doesn’t just go straight into the blood and register as a high glucose value. Evolution is much cleverer and more subtle than that, for the simple reason that if sugar in the diet went straight into the circulation, a blow-out on a large amount of fruit, or a box of chocolates, could raise everyone’s blood glucose to dangerous levels. What occurs in the interval between eating and glucose appearing in the circulation is complicated, but it’s worthwhile trying to understand it because that leads to a better understanding of the treatment of Type 2 diabetes, especially non-drug options (see Chapters 5 and 7).

Key point: Overeating, but by no means always to the point of being obese, is the major cause of diabetes. Overeating stresses the function of the liver and pancreas, the two organs most involved in metabolising food.

The liver – a tough organ for tough tasks

Once food has been broken down in the intestine after eating, the products of this chemical breakdown are absorbed into the circulation and transferred to the liver for processing. If we eat a standard Western diet, most of the absorbed products (about 50–60% of the total) is glucose, which is derived from carbohydrates – primarily bread, pasta, rice and potatoes – but also ‘sugar’ in confectionery or sweets. This used to be sucrose, but is now mostly fructose in the form of high-fructose corn syrup and apple juice, which are ferociously sweet and found in almost every pre-prepared food. We eat smaller amounts of fats and protein, but they are also broken down into smaller chemical components and, like glucose, transferred to the liver, where they are eventually converted into glucose. Remember that not all food can be broken down, even in the chemically tough environment of the stomach and intestine. Of the non-absorbed components of food, fibre, especially soluble fibre, is highly relevant to the treatment of diabetes because it can slow down the absorption of food, and delay glucose appearing in the circulation (see Chapter 5).

The liver is the largest organ in the body, and one of the reasons it has to be so big is that it’s the immediate destination of the breakdown products of all food (think about the scale of the task it faces when confronted by an all-you-can-eat buffet or 24-hour eating when its owner is on a cruise). It also processes medications, and does its best to detoxify all kinds of potentially hazardous substances we eat or even absorb from the environment. Whatever you eat – carbohydrate, fat, protein – is transported in broken-down chemical form to the liver. Once there, it’s packaged up into different forms for storage. One form you’re likely to remember from GCSE biology is glycogen, a starch which has been reassembled from absorbed glucose molecules. Glycogen is an efficient storage chemical but it can’t be used directly to generate energy, so it has to be converted in the liver back to glucose – which is the chemical most organs need to generate energy and keep working. Both the storage of glucose as glycogen and its conversion back to glucose are performed by insulin.

High blood glucose levels first thing in the morning (that is, after fasting) are caused by an inefficient liver. Eating our daily meals causes glycogen from excess glucose to be stored in the liver. During the night when we’re not eating, stored glycogen has to be chemically broken down slowly and carefully, in order to prevent our brains being starved of glucose, and to keep up with the low metabolic demands of the sleeping body and generally resting organs. Insulin is the key to ensuring we have just enough glucose circulating during the night, and in people without Type 2 it exerts a gentle braking effect on the liver and prevents too much glucose being released. It doesn’t succeed in doing this in people with Type 2, in part because the liver becomes resistant to its effects, so there is a form of brake failure. The result is that too much glucose is released from the liver overnight, resulting in a high fasting glucose level if you measure it when you wake up.

Celebrating insulin

It’s worthwhile pausing here to pay a brief tribute to insulin. Natural insulin is produced by the beta-cells of the pancreas; it lowers blood glucose levels by ensuring glucose is transported with great efficiency into organs that need it, mostly muscle, but to nearly every other organ as well. But insulin is also the master regulator of nearly all metabolism, and continually changes its function according to which nutrient it is dealing with (carbohydrate, some fats, or protein), which organ it’s acting on, and the time of day – whether we have just finished eating or have been without food overnight. Insulin is without doubt the most versatile substance in the body, and whether naturally produced by the pancreas, or delivered from syringe or pen, deserves serious respect but not fear.

High fasting glucose levels are very common in Type 2 diabetes, and are one of the ways in which Type 2 is diagnosed – see Chapter 2. High blood glucose levels in the morning, after what is effectively a period of overnight fasting, often puzzles people with Type 2. They are understandably at pains to point out that they don’t raid the fridge in the dark hours. It isn’t Type 2s who are misbehaving (unless they really do launch fridge raids); it’s the liver, pancreas and your own insulin produced by the pancreas. I’ll mention this again in other chapters, but if you think that diabetes is caused by eating too much sugar (sucrose, the white stuff added to hot drinks and sweets and confectionery etc.), then a high blood glucose level after eight or more hours without food doesn’t stack up. This simple phenomenon tells us that Type 2 diabetes has very little to do with eating sweet sugary stuff.

Key point: People with Type 2 diabetes tend to have high blood glucose levels when they wake up. This indicates that the liver isn’t working properly.

The pancreas – the insulin factory

In contrast with the liver, the pancreas is less obviously impressive, much smaller and buried at the back of the abdomen. Altogether, 90% of the pancreas produces digestive juices, while only 10% produces insulin. Insulin-producing cells, also known as beta-cells, are grouped together in ‘islets’. The pancreas has important connections: it is the first stop for nutrients, especially glucose, absorbed from food in the gut. In response to these high glucose levels, in non-diabetic individuals insulin levels increase very quickly in order to lower blood glucose levels to normal.

High blood glucose levels after eating are caused by an inefficient pancreas. In people without diabetes, blood glucose levels are usually 4 or 5 mmol/l and even after eating rarely go higher than 7 or 8. If they do, they return to normal very quickly, usually within an hour. Within minutes of starting to eat (possibly even as we catch a glimpse of tempting food before we actually start eating), the pancreas is already starting to produce more insulin, which will keep blood glucose levels down. If you’re eating a high-carbohydrate meal (for example, a large burger meal complete with large fries and milk shake, or lots of pasta, rice or noodles) then the healthy pancreas will go into major overdrive to produce large quantities of insulin to ensure that blood glucose levels don’t rise.

It doesn’t matter what form of diabetes you have; the pancreas can’t produce enough insulin. In Type 1, it can’t produce any at all, because the beta-cells within the islets have been destroyed by an immune process, so Type 1 people always need insulin with each meal, and even with snacks. In Type 2, there is some insulin production, but the pancreas is annoyingly sluggish and can’t produce enough to cope with high carbohydrate meals. The reasons for its inefficiency are not all known, but age, degeneration of the islets and beta-cells, and – recently discovered – too much fat accumulating in the pancreas, just like too much fat in the liver (see Chapter 4), all impair the ability of this wonderful organ to produce insulin.

The result is raised blood glucose levels after meals sometimes up to 15 or 20 mmol/l, or even higher – and they don’t return to pre-meal levels for perhaps four hours or longer. In many Type 2s, blood glucose levels continue to climb throughout the day, progressively higher after each carbohydrate-containing meal.

Key point: In order to keep blood glucose levels down after meals, the pancreas needs to be able to produce very large amounts of insulin.

What about fat?

We can now start putting together a picture of what’s going on in Type 2 diabetes, but before doing so, I need to add one further factor that has become a major live issue in the treatment of Type 2 diabetes and its potential reversal using the stringent dietetic approach of the Newcastle team who have pioneered the approach described in Chapter 4 (see page 47). That factor is fat.

For the moment we’ll leave aside excess belly fat (though that’s important), and focus on fat stored inside the two key organs involved in Type 2: the liver and the pancreas. I will mention this again in future chapters, but excess fat, especially in the liver, is a prominent feature of pre-diabetes or the metabolic syndrome – in people whose blood glucose levels are not far off normal, but who are at very high risk of developing Type 2. We’ll discuss elsewhere (see page 35) the reasons for excess fat in the liver, but in general it’s caused by overloading ourselves with food – and especially carbohydrate (curiously, not fat itself, a very important fact). Excess fat in the liver, called, surprisingly clearly for the medical profession fatty liver (or non-alcoholic fatty liver disease), is another factor that contributes to too much glucose escaping into the circulation overnight. Fat in the liver is a good hint that we are eating too much food.

How fat are we? The Body Mass Index (BMI)

The Body Mass Index is a number that describes how overweight (or underweight) we are, allowing for our height. Your GP record will have your BMI: ask about the number if you don’t already know it. If it is between 18.5 and 25, it is ‘normal’, 25–30 is ‘overweight’, over 30 is ‘obese’.

You can calculate your BMI yourself if you know your weight (in kilograms) and your height (in metres).

  • Multiply your height by itself (e.g. if you are 1.75 m, then 1.75 x 1.75 = 3.1). This is the ‘height squared’ number.
  • Then take your weight (e.g. 88 kg) and divide it by the height squared number (e.g. 88 divided by 3.1)
  • to give 28 – overweight.

Most people who develop Type 2 are overweight, but we need to get this into perspective. While the risk of developing Type 2 increases dramatically in very overweight people, at diagnosis in the UK the average BMI is right in the middle of the ‘overweight’ category, around 28 (as in the example above, which is my own BMI calculation). Just to remind us that, worldwide, Type 2 isn’t always associated even with being overweight, the average BMI in Chinese and other people from south-east Asia is around 26 – barely overweight (see Chapter 3).

Perhaps more important than the BMI measurement of fatness is the distribution of fat, especially around the abdomen. We’ve discussed the critical role of excess fat stored inside organs, but the fat packed around the organs inside the abdomen is also very important in diabetes, and seems to contribute to inflammation that affects the linings of arteries, and perhaps increases the risks of heart attacks and strokes (see Chapter 11). In general, these measures of fat correlate with the amount of fat that contributes more obviously to our waist measurement, but this isn’t always the case. While most people with a large tummy have excess fat inside the abdomen, there are many who don’t look especially overweight but conceal a lot of this metabolically active fat inside (especially Chinese and other people from south-east Asia, and south Asians originating from India, Pakistan and Bangladesh).

Assembling the metabolic jigsaw puzzle

I’ve put together some of the factors we’ve discussed in Figure 1.1. It shows the relationships between overeating, too much fat around the abdomen, and too much fat in the liver and pancreas contributing respectively to high glucose levels first thing in the morning and high levels after meals. It’s not a simple scheme, but it is important because:

Figure 1.1: Factors contributing to Type 2 diabetes, and the relationships between these factors. Experts will argue whether one pathway is more important than the other, and the emphases may change as further evidence emerges, but this is more or less an agreed map of Type 2.

Let’s discuss the two factors noted at the top of Figure 1.1: genetics and environmental causes of being overweight/obese, because they are critical to starting off the process that results in essential organs not working, and finally to high glucose levels.

Genetics – but no ‘gene’ therapy for the foreseeable future

Since most people developing Type 2 diabetes aren’t hugely overweight, other factors must operate. Genetics is an obvious candidate, and family history plays an important part in determining the risk of developing Type 2. For example, if you have one parent with Type 2 diabetes you run a lifetime risk of around 20–30%. That may not seem terribly high, but recall that only about 2% of the general population of the UK has Type 2 diabetes – though there are major ethnic variations which in some parts of the country give a much higher rate. If both parents are affected, the risk increases to 50%. Genetics therefore plays an important part. But if you’re thinking ‘What about gene therapy?’ think again. There are unusual causes of Type 2-like diabetes caused by abnormalities in single genes that can now be easily identified on special blood tests. These are grouped together as ‘Maturity Onset Diabetes of the Young’ (MODY), also known as ‘monogenic’ diabetes, because they are caused by a single (mono) gene abnormality.

However, in the Type 2 that you have, and I might develop, researchers have found minor abnormalities in hundreds, perhaps thousands, of genes. Each contributes a tiny additional risk, and no doubt there are hundreds or thousands more yet to be discovered that will add further small risks. But I can be confident that there will never be genetic treatments for Type 2 diabetes. (The fact that countless genetic abnormalities contribute to Type 2 should make us appreciate that it is a complicated condition.)

Key point: Type 2 diabetes runs very strongly in families. If you have Type 2, be aware of the high risk in first-degree relatives (brothers, sisters and children). Overnutrition is the key problem.

Environmental causes – too much food or lack of exercise?

The food industry is very keen to convince us that overweight and Type 2 diabetes are not the result of eating too much of their high-appeal, high-calorie, high-sugar, high-fat products, but are caused by our not doing enough exercise. This is incorrect. The dramatic increase in diabetes seen in many countries over the past 30–40 years is mostly due to our eating more and gaining weight, and not because we are taking substantially less exercise; weight has increased more rapidly than exercise has decreased. Of course, exercise is important for heart health, can prevent weight gain after dieting has stopped and may help with certain specific diabetes complications – for example, fatty liver – but only the heaviest and most prolonged exercise regimens use sufficient energy to result in meaningful weight loss (see Chapter 8). There’s no evidence that exercise prevents diabetes in susceptible people – except if you’re of Chinese origin – but we’ve already seen that Chinese people with Type 2 diabetes are quite different from people in Westernised countries.

Summary

Overnutrition on a background of genetics is the major factor behind most cases of Type 2 diabetes. Sugars (e.g. glucose, sucrose, fructose and high-fructose corn syrup) aren’t themselves the cause; in most people too much carbohydrate and fats, both high in calories, contribute to weight gain and to stressing the two organs most heavily involved in metabolising our food – the liver and pancreas. Although increasing levels of obesity are strongly associated with a higher risk of developing Type 2, in the UK most people with newly diagnosed diabetes are overweight (e.g. BMI around 28), and not obese. Certain ethnic groups, for example Chinese people, are barely overweight and yet run a high risk of diabetes.