In our previous post, we were reviewing the link between insulin and obesity. It appears that insulin is not merely associated with obesity but causes obesity.
For decades we believed the Caloric Reduction as Primary (CRaP) hypothesis of obesity that turned out to be as useful as a half-built bridge. Study after study showed that reducing calories did NOT lead to weight loss. Patient after patient tried to lose weight by restricting calories with consistent failure. But we couldn’t abandon the calorie model so what was left to do? Blame the patient, of course!
Since patients were not losing weight, there was only 2 possibilities. Either the advice to eat a low fat, calorie restricted diet and exercise more was wrong or the patient was not following this advice.
So the doctors and dieticians berated, ridiculed, belittled, rebuked, chided and reprimanded. We said – Eat less, Move more – as if that would cure their problems. After all, the food pyramid couldn’t be wrong, could it? But the excess weight was still as persistent as a nagging tooth.
Doctors, of course, were drawn to this CRaP hypothesis as bathers to a seashore. Obesity was now not our failure to understand it, but their lack of willpower and/or laziness (gluttony or sloth). It was our favourite game – blame the patient.
But, of course, the problem was the CRaP hypothesis. It was just wrong. Increased calories did not cause obesity so reducing calories didn’t cause weight loss. Exercise didn’t work either, as we will see in a future series. So, what was the real aetiology of obesity? Insulin.
What happens when we give high doses of insulin to patients? Insulin makes you gain weight. The more insulin you take, the more weight you gain. It almost doesn’t matter how much you eat or how much you try to exercise. The weight just keeps coming on.
An interesting experiment that demonstrated this exact principle involved intensive treatment of diabetic patients.
Diabetes Care 16:23-31 Henry RR
The researchers took 14 diabetics and increased insulin until sugars were almost normal. At the beginning, they were on pills only. Over the 6 months, insulin was increased until the were taking an average of 100 units per day.
Body Weight increased by 8.7 kg (19 lbs). Yet, if we were to look at daily caloric intake, we can see that the average patient decreased by almost 300 calories/ day! In other words, despite eating less patients were gaining weight like crazy. That means that it was not the calories that was driving the weight gain. It was the insulin!
Think about it this way. Insulin is the hormonal signal to the body to increase weight – the Body Set Weight (BSW). If insulin is increased, we increase our BSW. In order to reach this new, higher weight, we will need to eat more or decrease total energy expenditure (TEE). So the insulin makes us fat. In order to get fat, we will eat more or reduce TEE. The behavior of eating more is in response to the hormonal signal to get fat.
In this study, insulin dose was massively increased. Under this hormonal signal, the body tries to gain weight (increase the BSW). As weight increased, patients tried to restrict calories. Since they weren’t eating more, their body is forced to ‘shut down’ in order to conserve energy to increase weight. TEE is lowered. We feel tired, cold, and hungry. And the weight still keeps going up. Sounds like most conventional low fat low calorie diets. Diet, exercise, feel lousy and still can’t lose weight.
There is, in fact, a direct correlation between total dosage and weight gain. The more insulin given, the more weight gained. The higher the insulin levels, the more weight gained. Insulin causes obesity.
A more recent study (N Engl J Med 2007;357:1716-30 Holman RR) showed this exact same effect.
In this study, 708 diabetics on oral medications got insulin added to their treatment. What happened to weight? It went up. That is really no surprise – every clinician already knows that insulin makes you gain weight.
Those who got the highest doses gained the most weight. Those who got the least, gained the least weight.
Insulin can not only cause generalized obesity, but it can also cause localized fat growth. Those who regularly inject insulin may occasionally experience lipohypertrophy. This just to reinforce the notion that insulin is the signal to gain fat.
There are those who might argue that it is simply the treatment of diabetes that causes weight gain. As we reduce blood sugars, that sugar is taken out of the blood and into the body as fat.
If this were true, then any treatment of diabetes should cause equal weight gain.
We can compare treatment of type 2 diabetes with different agents. Luckily for us, these studies have already been done. This was the large UKPDS (UK Prospective Diabetes Study).
Let me explain here. There are several pills for diabetes (oral hypoglycemics).
Sulphonylureas (SU) are a class of medication that will stimulate the pancreas to produce more insulin. If insulin causes obesity, as the hormonal obesity theory holds, then this class of drugs should indeed increase weight.
Metformin is another class of medication. This is an entirely different kettle of fish. It is considered to be an insulin sensitizer. That is, it helps the insulin in the body work more efficiently. It does not raise serum insulin levels.
This is great. Now we can compare the different effects of the 3 types of drugs – insulin, SU, and metformin. They all have the effect of reducing blood sugars, but the effect on insulin levels in the body are completely different. Insulin will raise blood levels the most, SU will raise levels but not as much as insulin, and metformin not at all.
What are the effects on weight?
As we expected, the insulin group increased weight by the most.
The Chlorpropamide and gliburide (sulphonyureas) increased weight as well, but not as much as insulin.
So insulin, and gliburide (which raises insulin levels) both increase weight. Metformin, which treats the blood sugar but does NOT raise insulin levels does not raise weight.
Since the publication of the UKPDS there has been the introduction of a new class of drugs to treat diabetes. These are the DPP4 class of medications.
The mechanism of action of these drugs is to increase insulin levels in response to a meal. It does not cause a persistent elevation of insulin levels. As we would expect, the DPP4′s are weight neutral.
In this study, glipizide (a sulphonylurea that raises insulin levels), causes weight gain. Januvia, which does not persistently raise insulin levels does not. This is despite the fact that sugars are treated to the same level.
The results are very consistent. Raising insulin levels causes weight gain. Lowering insulin levels causes weight loss. Increasingly, we are recognizing the importance of these hormonal factors on obesity. Just recently, another study entitled “Insulin resistance and inflammation predict kinetic body weight changes” showed that the strongest predictor of weight regain is insulin resistance. Not willpower. Not caloric intake. Not peer support. Insulin. Insulin. Insulin. It is all about the insulin.
The question is NOT how to balance calories, the question is how to balance our hormones. In most cases, the crucial question is not how to reduce calories but how to reduce insulin.
Continue to Hormonal Obesity part V here
Begin here with Calories I
Click here to watch the entire lecture – The Aetiology of Obesity 1/6 – A New Hope