Monday, 18 June 2012

Hyperinsulinaemia and Insulin Resistance - An Engineer's Perspective.

Another techie post.
There's been some arguing discussion over whether Hyperinsulinaemia (HI) causes Insulin Resistance (IR). My answer is...Yes and No.

HI increases IR, long-term. See Downregulation and upregulation: The Insulin Receptor and Insulin oscillation.

HI doesn't increase IR, short-term. How can I claim this? The above diagram represents a Negative Feedback (NFB) control system, which is how Blood Glucose is regulated.

"Input" represents Glucose from digested sugars and starches. The arrow pointing at AOL represents Blood Glucose (BG). The triangle containing AOL represents pancreatic beta cells. "Output" represents Insulin Secretion (ISec). More BG = More ISec.

The box containing ß represents three things that work in parallel to reduce Blood Glucose.
1) The Liver. More ISec = Hepatic Glucose Production rate decreased.
2) Muscle mass. More ISec = Glucose intake to Muscle mass rate increased, via Glu-T4.
3) Fat mass. More ISec = Glucose intake to Fat mass rate increased, via Glu-T4.
The three things aren't of equal strength, but they provide overall negative feedback.

If overall negative feedback is halved due to doubling of overall IR in the above three paths, ISec doubles. If you don't believe me, see Idealised Negative Feedback Inverting Amplifier using an idealised op amp on WolframAlpha. Double the value of resistance 2 (the negative feedback resistor R2). and the output voltage on the inverting amplifier doubles from -10V to -20V.

The idealised Negative Feedback Inverting Amplifier using an idealised op amp on WolframAlpha is interesting in that an idealised op amp (the triangle with + and - inputs) has infinity gain and ±infinity voltage on its power supplies. As a result, there is zero volts (output voltage divided by infinity) between the idealised op amp's + terminal and its - terminal. If the idealised op amp's + terminal is connected to 0V (a.k.a. "Earth"), its - terminal is at 0V (a.k.a. "Virtual Earth") and has zero variation, whatever the input voltage. An actual op amp has a voltage gain of ~140dB (~10,000,000), so an output voltage of -10V can be achieved with a voltage of 1uV (one millionth of a Volt) on its - terminal.

If pancreatic beta cells had a zero threshold and infinity gain like an idealised op amp, BG would be zero and have zero variation with varying Glucose input. Pancreatic beta cells actually have a positive threshold and low gain, so BG is positive and varies slightly with varying Glucose input.

If ISec becomes zero (as in type 1 diabetes), there is zero negative feedback and BG increases. The same thing happens to the voltage on the idealised op amp's - terminal if its power supplies are 0V instead of ±infinity.

If ISec becomes insufficient (as in type 2 diabetes), there is insufficient negative feedback and BG increases. The same thing happens to the voltage on the idealised op amp's - terminal if its power supplies are limited to ±5V.

Having established that ISec is proportional to overall IR, what would happen if overall IR was proportional to ISec? If ISec doubled, overall IR would double, which would double ISec, which would double overall IR, ad infinitum. ISec would increase to maximum instantly. THIS DOESN'T HAPPEN. Therefore, IR doesn't increase in proportion to ISec, short term.

Long-term, increased ISec increases IR for a variety of reasons, one of them being that increased ISec increases the rate at which cells fill with glycogen. Once full of glycogen, cells must down-regulate their intake by down-regulating Glu-T4 and Glu-T2 (fat and liver cells also up-regulate their output of stuff) or burst.

Reduce your IR by addressing all of the factors in Insulin Resistance: Solutions to problems.

Chris Highcock emailed me a link to Muscular strength and markers of insulin resistance in European adolescents: the HELENA Study.


Simon Carter said...

Hi Nigel,
I greatly enjoy reading your blog and I am learning a lot from it. Thank you for the effort you put into it. In the last paragraph above you wrote, " eating a diet that results in you unconsciously eating less and moving more." Can you expand on what you specifically would include and exclude in such a diet?

Nigel Kinbrum said...

Everybody is different, so what works for me may not work for you. That said, I restrict my intake of refined carbohydrates as they cause some sluggishness, even though my insulin sensitivity is better than it was years ago.

Unknown said...

What about a high unrefined carbohydrate diet? Primarily loads of vegetables, whole grains and legumes. Would you experience similar levels of sluggishness on such an approach?

Nigel Kinbrum said...

Non-starchy vegetables don't make me feel sluggish (but they do make me blow!). Starchy vegetables may or may not make me feel sluggish, depending on how they're cooked. Potatoes & parsnips roasted in animal fat until they're crispy are very moreish, so I over-eat them and feel sluggish. Plain boiled salad potatoes are not a problem, especially when eaten cold (as cooling converts some of the amylopectin into amylose a.k.a. resistant starch).

Whole grains: It depends.

1) Wholemeal flour contains everything that's in a whole grain, but the grain is not intact. I find that stuff made out of flour is too easy to over-eat (which makes me sluggish) and it also causes a rapid build-up of dental plaque. I'm currently having only one slice of toasted Burgen Soya & Linseed bread underneath one fried middle rasher + 3 medium eggs for breakfast without feeling sluggish.

2) Rolled, puffed & boiled grains e.g. rolled wheat/oats, puffed wheat/corn/rice & boiled rice are not a problem (unless accompanied by loads of sugar, which encourages over-eating). Cold boiled rice contains some resistant starch.

Unknown said...

I see. Interesting.

By the way, I am thankful that I wasn't completely asleep during physics class in college because otherwise, I would've clubbed myself over the head from reading this post. Good analogy.