인슐린이 체중을 증가시킵니다 – 호르몬성 비만 (4) Insulin Causes Weight Gain – Hormonal Obesity

by Jason Fung, 한국어 정리 Dr. Hayun Lee

앞에서 우리는 인슐린과 비만간 관계를 검토했습니다. 

인슐린은 비만과 단순히 연결된 것이 아니고 비만의 원인으로 밝혀졌습니다. 

수십 년 동안 미완성으로 판명된 비만의 칼로리(CRaP) 가설을 믿었습니다. 거듭된 연구 후 칼로리가 줄어도 체중이감소되지 않는다는 점을 알게 되었습니다. 환자들이 여러 번 칼로리를 줄여서 체중 감량을 시도하였으나 계속해서실패했습니다. 하지만 칼로리 모델을 포기할 수 없었는데 어떻게 했을까요? 물론, 모든 책임을 환자에게 미루었습니다! 환자의 체중이 줄지 않으면 2개의 가능성이 있습니다. 저지방, 칼로리 제한 식단이 잘못되었거나 환자가 조언에 따르지않았던 것입니다. 그래서 의사와 영양사는 비만 환자를 질책하고, 조롱하고, 힐책하고, 책망하였습니다. 덜 먹고 더움직이라고 말했습니다. 그러면 문제를 치료할 수 있는 것처럼. 결국, 음식 피라미드에는 잘못이 없었는데, 무슨잘못이 있을까요? 하지만 비만은 여전히 계속되었습니다. 물론 의사들도 CRaP가설에 빠졌습니다. 비만의 원인은비만에 대한 우리의 잘못된 이해가 아니고 환자의 의지력 부족 및/또는 게으름(폭식 또는 나태) 이라고 했습니다. 환자에게 책임 전가하기. 그런데 문제는 물론 CRaP 가설이었습니다. CRaP가설은 잘못되었던 것이었습니다. 증가된칼로리가 비만을 유발하지 않았고, 감소된 칼로리도 체중을 줄이지 못했습니다. 운동은 작동하지 않았습니다. 그래서, 비만의 진짜 병인은 무엇입니까? 인슐린.

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 favorite 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.

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환자가 인슐린을 과다 복용하면 어떻게 됩니까? 체중이 증가합니다. 인슐린을 많이 복용할수록 체중이 증가됩니다. 얼마나 먹느냐 또는 얼마나 운동을 하느냐는 중요하지 않습니다. 체중은 계속 유지됩니다. 이 정확한 원리를 보여주는흥미로운 실험은 당뇨병 환자의 집중 치료와 연관이 있습니다.
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.

제2형 당뇨병 환자에 대한 집중 전통적인 인슐린 치료법
Intensive Conventional Insulin Therapy for Type II Diabetes

Diabetes Care 16:23-31 Henry RR

연구원들은 당이 거의 정상이 될 때까지 14명의 당뇨병 환자에게 인슐린 공급을 늘렸습니다. 처음에, 그들은 약만먹었습니다. 6개월간, 하루에 평균 100단위를 복용할 때까지 인슐린을 늘렸습니다.
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.

체중이 8.7kg(19파운드)로 늘었습니다. 환자의 하루 칼로리 섭취량은, 평균 300칼로리가 감소되었습니다! 즉, 적게 먹는환자의 체중이 엄청나게 늘었습니다. 이것은 체중증가의 원인은 칼로리가 아니라는 것을 의미합니다. 인슐린이었습니다! 이런 식으로 생각해봅시다. 인슐린은 체중을 증가시키는 신체의 호르몬 신호 - 체중설정기(Body Set Weight, BSW) 입니다. 인슐린이 증가하면, BSW를 높입니다. 체중을 늘리려면, 더 먹거나 총에너지소비(TEE)를줄여야 합니다. 그러면 인슐린이 몸을 살찌게 만듭니다. 살찌려면 더 먹거나 TEE를 줄일 수 있습니다. 더 먹는 행위는살찌기 위한 호르몬 신호에 대한 응답입니다. 이 연구에서는 인슐린 투여량을 대폭 늘렸습니다. 이 호르몬 신호에 따라, 몸은 체중을 늘리려고 합니다(BSW를 높게 설정). 체중이 늘면, 환자는 칼로리를 제한하려고 노력합니다. 더 먹지 않았기때문에, 체중을 늘리기 위한 에너지를 절약하기 위해서 몸이 강제로 '종료' 됩니다. TEE가 저하됩니다. 몸이 피곤하고, 춥고, 배고파집니다. 그리고 체중은 계속해서 증가됩니다. 대부분의 기존의 저칼로리 저지방 다이어트와 유사한 것같습니다. 다이어트, 운동, 우울한 기분 그리고 여전히 체중을 줄일 수 없습니다.
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.

실제로 인슐린 투여량과 체중증가 사이에는 직접적인 상관관계가 있습니다. 인슐린을 많이 복용하면 체중이증가됩니다. 인슐린 레벨이 높을수록 체중이 더 늘었습니다. 인슐린이 비만이 일으킵니다.
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.

최근의 연구(N Engl J Med 2007;357:1716-30 Holman RR)는 이것과 정확히 같은 효과를 보여주었습니다.
A more recent study (N Engl J Med 2007;357:1716-30 Holman RR) showed this exact same effect.

제2형 당뇨병에서 경구 치료에 대한 Biphasic, Prandial 또는 Basal Insulin의 추가
Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes

이 연구에서는 경구 약으로 치료 중인 708명의 당뇨병 환자에게 인슐린을 추가하였습니다. 체중은 어떻게 되었습니까? 늘었습니다. 놀라운 일이 아닙니다 - 모든 임상의사들은 인슐린이 체중을 늘린다는 사실을 이미 알고 있습니다.
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.

 

인슐린을 가장 많이 복용한 사람들의 체중이 제일 많이 늘었습니다. 가장 적게 복용한 사람들의 체중이 제일 적게늘었습니다. 인슐린은 일반적 비만을 야기할 뿐만 아니라, 부분적 비만도 야기합니다. 정기적으로 인슐린을 주사맞는사람들은 가끔 지방비후증(lipohypertrophy)을 경험할 수 있습니다. 이것은 인슐린이 살이 찌는 신호라는 개념을확실하게 해줍니다. 그것을 단순히 체중증가를 유발하는 당뇨 치료라고 주장하는 사람들도 있을 수 있습니다. 혈당을줄이면, 그 당은 혈액에서 나와서 지방 형태로 체내에 들어갑니다. 이것이 사실이라면, 어떤 당뇨병 치료도 동등한체중증가를 일으켜야 합니다. 제2형 당뇨병 치료를 다른 에이전트와 비교할 수 있습니다. 다행히도, 이미 완료된 큰UKPDS (영국 전향적 당뇨병 연구)가 있었습니다. 
여기서 설명하겠습니다. 당뇨병에는 여러 약(경구용 혈당강하제)이 있습니다. Sulphonylureas(SU)은 인슐린을 더 많이생성하도록 췌장을 자극하는 종류의 약물입니다. 인슐린이 비만을 야기한다면, 호르몬 비만 이론 때문에 이런 종류의약물은 실제로 체중을 증가시킬 것입니다. Metformin은 다른 종류의 약물입니다. Metformin은 전적으로 다른 약입니다. Metformin은 인슐린 증감제(sensitizer)로 취급됩니다. 즉, 인슐린이 몸에서 보다 효율적으로 활동하게 도와줍니다. Metformin은 혈청 인슐린 레벨을 높이지 않습니다.
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.

이것은 훌륭합니다. 이제 3가지 타입의 약(인슐린, SU, metformin)의 서로 다른 효과를 비교할 수 있습니다. 이들 모두혈당 감소 효과가 있지만, 체내에서 인슐린 레벨에 대한 효과는 완전히 다릅니다. 인슐린이 혈중 인슐린 레벨을 최대한올릴 것이고, SU는 올리지만 인슐린만큼은 아니고, metformin은 전혀 올리지 않습니다. 
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.

체중에 미치는 영향은 무엇인가? What are the effects on weight?

예상대로, 인슐린 그룹이 체중을 제일 많이 증가시킵니다. Chlorpropamide와 glyburide(sulphonyureas)도 체중을늘리지만 인슐린만큼은 아닙니다. metformin 그룹은 체중 중립입니다. 이 그룹은 어떤 단독 식단보다 체중을 더 늘리지않았습니다.
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. The metformin group was weight neutral. This group did not gain any more weight than those on diet alone.

그래서 인슐린과 글리부리드(인슐린 레벨을 높이는) 모두 체중을 늘립니다. 혈당은 치료하지만 인슐린 레벨을 높이지않는 메트포르민은 체중을 늘리지 않습니다. UKPDS출판 이후 당뇨병을 치료하는 새로운 종류의 약물이도입되었습니다. 이들은 DPP4 종류의 약물입니다. 이들 약물의 작동 메커니즘은 식사에 응답하여 인슐린 농도를증가시키는 것이다. 이는 인슐린 레벨의 지속적인 상승을 초래하지 않습니다. 기대한 대로 DPP4는 체중 중립적입니다. 이 연구에서, 글리피지드(인슐린 레벨을 높이는 설포닐우레아)는 체중을 증가시킵니다. 인슐린 레벨을 지속적으로높이지 않는 자누비아는 체중을 늘리지 않습니다. 당이 동일한 레벨로 처리된다는 사실에도 불구하고 말입니다. 결과는매우 일치합니다. 인슐린 레벨을 높이면 체중이 증가됩니다. 인슐린 레벨을 낮추면 체중이 줍니다. 우리는 점차 비만에대한 호르몬 요인의 중요성을 인식하고 있습니다. 최근 "인슐린 저항과 염증이 키네틱 체중 변화를 예측한다 (Insulin resistance and inflammation predict kinetic body weight changes)" 라는 제목의 연구는 체중 재증가의 가장 강력한예측자는 인슐린 저항(insulin resistance, IR) 이라고 말했습니다. 

의지도 아니고, 칼로리 섭취도 아니고, 개별적 지원도 아닙니다. 

인슐린. 인슐린. 인슐린. 인슐린이 가장 중요합니다. 

몸은 인슐린의 영향을 받아, "살찌기" 라는 지시를 받습니다. 그 응답으로 더 먹거나 및/또는 에너지 소비를 줄입니다. 그것은 자발적 행동이 아닙니다. 아래를 기억해야 합니다:
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. Under the influence of insulin, our body receives instructions to “gain fat”.  In response, we eat more and/ or decrease energy expenditure.  It is not a voluntary act.  Remember this:

문제는 칼로리 균형방법이 아니고, 호르몬 균형 방법입니다. 

대부분의 경우, 중요한 문제는 열량을 줄이는 방법이 아니고 인슐린을 줄이는 방법입니다.
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.

 

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