But what really interested me is that not everyone has the mutation. Natural selection has kept the Inuit’s options open. Should the population meet conditions under which the mutation is a handicap, the race will continue. And there is something very human about this. I doubt you will see a comparable variation in bowerbirds, for example. Humans are the acme of long-term survivalists, retaining a diversity of metabolic variations rather than developing a single, fiendishly clever, niche specialisation. There are humans that make vitamin D from very little sunshine (but are highly vulnerable to burning solar radiation), and humans that make D slowly (but are largely immune to sunburn). Our ancient and modern population movements and interbreeding have increased this diversity in any given place, but the Inuit demonstrate that there is something innate about it. It gives us what Nassim Nicholas Taleb memorably calls “antifragility”.
Now consider the genetic propensity to insulin resistance and type 2 diabetes. At the genome level this is expressed in more than one way (as are the carnitine mutations of the Inuit type). The result of becoming insulin resistant is the glucagon dominance of hepatic metabolism. Glucagon wants to rip fat and protein into ketone bodies and glucose. In type 1 diabetes this gives you diabetic ketoacidosis (systemic acidosis triggered by a toxic brew of hyperglycaemia and hyperketonaemia) and the wasting of fat and protein reserves, but when dietary carbohydrate, or perhaps any food, is unavailable this glucagon dominance is the means of survival. Those individuals who become keto-adapted easily – those who become insulin resistant quickly – have an advantage. These are the strong ones in lean times (and as humans are social animals, they can help the others survive). But in the interests of anti-fragility, human evolution also favours some individuals with extra amylase gene copies (just a copy, the low-hanging fruit of evolution) and insulin sensitivity. These individuals can become strong when starchy foods are plentiful, and will survive longer when animal foods are unavailable.
Let’s say you’ve descended from the insulin-resistant line (perhaps also exposed to accidental insults I haven’t mentioned, such as toxins or pathogens colliding with your metabolism, or unlucky micronutrient scarcity). The diabetician tells you that your high FPG and HbA1c are down to your genes. This has two meanings – the good news is that your personal behaviour didn’t result in your diagnosis (although in fact the odds are it has had some bearing on it), the bad news is that there is little you can do to prevent what is a progressively deteriorating condition (although we will prescribe a high-carb, high-fibre, low-fat diet that will make it worse, and drugs that won’t cure it).
Whereas what this diagnosis should mean is this; you have glucagon dominance. You have a genetic adaptation to a diet low in carbohydrate but high in fat and protein, with periods of fasting. If you go with the flow of glucagon dominance, if you feed yourself on the foods that are glucagon metabolism substrates and avoid the insulin metabolism substrates, and if you go hungry some of the time, you will likely get better. At any rate, you won’t have a deteriorating condition that will eventually take a ton of drugs to control poorly.
Links - Hyperlipid on Inuit
Unger and Cherrington on Glucagon
UKPDS. Failure of low-fat diet and drug treatment of T2D
Westman and Vernon. Success of low-carbohydrate treatment of T2D
Lim and Taylor. Success of fasting treatment of T2D