Evolution of Diabetes?

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As a medical student and health care professional, if there is one disease that continually comes up in daily discussion, it’s diabetes.  As a disease, diabetes is one that I would not wish on anyone, not that I ever wish disease on anybody to begin, but I wouldn’t wish it on my worst enemy.  As a disease diabetes my initially seem fairly tame, but it has the potential to eventually affect just about every organ system in the body.

As I begin to plan my career as a future Family Medicine Physician, I know that I will be dealing with diabetes on a regular basis.  Any opportunity I have to learn more about the risk factors to look out for in order to help people avoid it, or to better manage it is one I need to take.  So I am following up on a previous post regarding the frequency of the 230Cys allele found in Native American groups as a potential adaptation to feast or famine and storage of energy in the form of fat to hold out during harsh conditions.

How is this relevant to diabetes?  Well, first of all, a little background.  Diabetes is a disease that has a huge global burden. Currently, around 285 million people worldwide are affected and that number could potentially climb to 430 million by the year 2030.  Diabetes also accounts for 12% of all health care expenditure.  It is also a highly genetically associated disease, at least Type 2 Diabetes.  Now, in type 2 diabetes the individual will have high levels of circulating insulin.  Insulin is a key regulator of fat storage.  It is released following meals in response to glucose from the meal and stimulates the uptake of that glucose into liver, muscle and fat.  It also acts to antagonize other hormones that would breakdown and use the stored glucose as energy.  So, this is where I got to thinking, if there is a gene that is linked evolutionarily to helping survive famine, is there a potential link between such genes and diabetes.

I ended up discovering a wonderful review article that addressed a number of the questions that I had.  First of all, the fact remains that Type 2 Diabetes is a highly multifactorial disorder.  Just a few of the factors that come in to play include: gender, race, age, diet, and body type.  Numerous studies have tried to determine just how big a factor genetics plays in development of the disease.  Through genome wide association studies at least 40 loci have been associated with development of diabetes.  Prevalence of any one of these genes varied among ethnic groups, however, the combined effect of multiple loci (dependent on ethnicity) seemed to be similar, about a 10-20% risk.  One thing that the various loci did seem to have in common was the fact that the majority of them related to Beta cell function (cells in the pancreas that secrete insulin).  Other studies seemed to conclude that by taking the sum of these loci and calculating a genetic risk score that individuals with low genetic risk scores were not affected by consumption of a western diet and development of diabetes.

Tying this back to the beginning, the paper also discussed a theory regarding the prevalence of Type 2 Diabetes and feast/famine cycles.  The theory is called the Thrifty Genotype and the Thrifty Phenotype.  It states that obesity and Type 2 Diabetes are likely caused by positive selection of genotypes for efficiency of metabolism and energy/fat storage.  This partially explains the increased prevalence of Type 2 Diabetes in indigenous populations that were subject to feast and famine cycles compared to lower prevalence in Europeans who were not subjected to those conditions.  However, despite this, there is no clear over representation of alleles in those groups.  Alternatively, the Thrifty Phenotype postulates that infants who experienced poor conditions in utero adapted to those conditions in such a way as to make it detrimental when they become adults in a nutrient rich environment.  This has been shown in several studies where children born during times of famine were later found to be at higher risk of Type 2 Diabetes when they later consumed a western diet as adults than those who were not exposed to famine in utero.  However, this theory runs into problems as infants born to obese and diabetic mothers (high nutrient in utero environment) also have increased risk of diabetes as adults.

All this just goes to show how complex Type 2 Diabetes is.  While there may be some adaptive component that is no longer necessary in a society where resources are not scarce, it is hardly the complete picture.  However, knowing the various components of what can potentially contribute to Type 2 Diabetes is essential to my future practice as a Family Medicine Physician as it gives me more clues about things to look out for in my patients.

Reference

Hu, F. (2011). Globalization of diabetes: the role of diet, lifestyle, and genes.. Diabetes Care, 34(6), 1249-1257. DOI: 10.2337/dc11-0442.

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4 comments on “Evolution of Diabetes?

  1. Yoder says:

    Great post, Jon! One point isn’t quite clear to me, though: when you say that gene variants (alleles) shown to be associated with diabetes are associated with 10-20% risk of diabetes, is that 10-20% greater risk than the population average, or an absolute 1-in-10 to 2-in-10 risk?

    • yoderjb says:

      Sorry about that confusion. Generally, in medical studies it tends to be more common that any risk discussed is an increased or greater risk than the population average or control population. So yes, that’s a 10-20% greater risk not absolute risk.

  2. I read a article a couple days ago how if you do a blood test it is possible to catch type two diabetic in its early stage before it will take control of your body. My questions is it possible to catch type 2 diabetics at its early stages or signs of this disease? I read that people who have high levels of SFRP4, a protein with inflammatory properties that is found in the blood, are five times more likely to develop type 2 diabetes within a few years.

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