Many different things can go wrong in that normal course of events, and so the term “diabetes mellitus” covers a wide variety of underlying problems linked by shared symptoms arising from high levels of blood sugar. That diversity can be crudely partitioned into two groups of diseases: so-called Type-2 or non-insulin-dependent diabetes mellitus (also known as “adult-onset diabetes”), and the much less common Type-1 or insulin-dependent diabetes mellitus (also known as “juvenile-onset diabetes”). The latter is an autoimmune disease in which a person’s antibodies destroy the person’s own pancreatic cells that secrete insulin. Type-1 diabetics tend to be thin, to produce no insulin, and to require multiple daily injections of insulin. Many of them carry certain genes (certain so-called HLA alleles) that code for elements of the immune system. Type-2 diabetes instead involves increased resistance of body cells to the person’s own insulin, so that cells fail to take up glucose at normal rates. As long as the pancreas can respond by releasing more insulin, the cells’ resistance can be overcome, and blood glucose remains within a normal range. But eventually the pancreas becomes exhausted, it may no longer be able to produce enough insulin to overcome that resistance, blood glucose levels rise, and the patient develops diabetes. Type-2 diabetes patients tend to be obese. In early stages of the disease they can often control their symptoms by dieting, exercising, and losing weight, without requiring tablets or insulin injections.
However, distinguishing Type-2 and Type-1 diabetes can be difficult, because Type-2 diabetes is now increasingly appearing already in teen-agers, while Type-1 diabetes may not first appear until in adulthood. Even Type-2 diabetes (as defined by insulin resistance) is associated with many different genes and manifests itself by varied symptoms. All of my subsequent discussion in this chapter will concern the much more common (about 10 times commoner) Type-2 diabetes, which I shall henceforth refer to simply as “diabetes.”
Genes, environment, and diabetes
More than 2,000 years ago, Hindu physicians noting cases of “honey urine” commented that such cases “passed from generation to generation in the seed” and also were influenced by “injudicious diet.” Physicians today have rediscovered those deadly insights, which we now rephrase by saying that diabetes involves both genetic and environmental factors, and possibly also intra-uterine factors affecting the fetus during pregnancy. Evidence for a role of genes includes the 10-times-higher risk of getting diabetes if you have a diabetic first-degree relative (a parent or a sibling) than if you don’t. But diabetes, like hypertension, is not one of those simple genetic diseases (as is sickle-cell anemia) in which a mutation in the same gene is responsible for the disease in every patient. Instead, dozens and dozens of different genetic susceptibility factors for diabetes have been identified, many of them united only by their common feature that a mutation in any of those genes may result in high blood-glucose levels due to insulin resistance. (I mention again that these comments apply to Type-2 diabetes; Type-1 diabetes involves its own separate set of genetic susceptibility factors.)
In addition to those genetic factors in diabetes, diabetes also depends upon environmental and lifestyle factors. Even if you are genetically predisposed to diabetes, you won’t necessarily get the disease, as would be the case if you carried a pair of genes for muscular dystrophy or Tay-Sachs disease. The risk of developing diabetes increases with age, and with having diabetic first-degree relatives, and with being born of a diabetic mother, which you yourself can’t do anything about. But other risk factors that predict diabetes are factors under our control, including especially being overweight, not exercising, eating a high-calorie diet, and consuming much sugar and fat. Most diabetics (I emphasize again, most Type-2 diabetics) can reduce their symptoms by reducing those risk factors. For example, the prevalence of diabetes is 5 to 10 times higher in obese people than in those of normal weight, so that diabetes patients can often regain health by dieting, exercising, and losing weight, and those same measures can protect people predisposed to diabetes against getting the disease.
Many types of natural experiments, including ones that I mentioned at the beginning of this chapter as demonstrating the relation between the Western lifestyle and non-communicable diseases in general, specifically illustrate the role of environmental factors in diabetes. The worldwide rise in those factors underlies the current worldwide diabetes epidemic. One such type of natural experiment involves the rise and fall of diabetes prevalences accompanying the rise and fall of Western lifestyle and affluence in the same population. In Japan, graphs against time of diabetes prevalence and economic indicators are parallel, down to details of year-to-year wiggles. That’s because people eat more, hence they risk developing more diabetes symptoms, when they have more money. Diabetes and its symptoms decline or disappear in populations under starvation conditions, such as French diabetes patients under the severe food rationing imposed during the 1870–1871 siege of Paris. Groups of Aboriginal Australians who temporarily abandoned their acquired sedentary Western lifestyle and resumed their traditional vigorous foraging reversed their symptoms of diabetes; one such group lost an average of 18 pounds of body weight within seven weeks. (Remember that obesity is one of the leading risk factors for diabetes.) Decreases in diabetes symptoms and in waist circumference were also noted for Swedes who for three months abandoned their very un-Mediterranean Swedish diet (over 70% of calories from sugar, margarine, dairy products, alcohol, oil, and cereals) and adopted instead a Mediterranean diet typical of slim Italians. Swedes who adopted a “Paleolithic diet” designed to resemble that of hunter-gatherers became even healthier and developed even slimmer waists.
Another natural experiment is provided by the sky-high explosions of diabetes among groups that emigrated and thereby gave up a vigorous Spartan lifestyle to adopt sedentary high-calorie low-exercise living based on abundant supermarket food. A dramatic example involved the Yemenite Jews who were airlifted to Israel by Operation Magic Carpet in 1949 and 1950, and were thereby plunged abruptly into the 20th century from formerly medieval conditions. Although Yemenite Jews were almost free of diabetes upon reaching Israel, 13% of them then became diabetic within two decades. Other migrants who sought opportunity and instead found diabetes included Ethiopian Jews moving to Israel, Mexicans and Japanese moving to the U.S., Polynesians moving to New Zealand, Chinese moving to Mauritius and Singapore, and Asian Indians moving to Mauritius, Singapore, Fiji, South Africa, the U.S., and Britain.
Developing countries that have recently been growing more affluent and Westernized have correspondingly been growing more diabetic. In first place stand the eight Arab oil-producers and newly affluent island nations that now lead the world in national diabetes prevalences (all of them above 15%). All Latin American and Caribbean countries now have prevalences above 5%. All East and South Asian countries have prevalences above 4% except for five of the poorest countries, where prevalences remain as low as 1.6%. The high prevalences of the more rapidly developing countries are a recent phenomenon: India’s prevalence was still below 1% as recently as 1959 but is now 8%. Conversely, most sub-Saharan African countries are still poor and still have prevalences below 5%.
Those national averages conceal large internal differences that constitute further natural experiments. Around the world, urbanization results in less exercise and more supermarket food, obesity, and diabetes. Individual urban populations that thereby achieved notably high diabetes prevalences include the already mentioned Wanigela people of Papua New Guinea’s capital city (37% prevalence) and several groups of urban Aboriginal Australians (up to 33%). Both of those cases are all the more striking because diabetes was unknown among New Guineans and Australians under traditional conditions.
Thus, the Western lifestyle somehow increases the risk that those enjoying it will become diabetic. But the Western lifestyle consists of many interlinked components: which components contribute most to the risk of diabetes? While it isn’t easy to tease apart the effects of correlated influences, it ap
pears that the three strongest risk factors are obesity and sedentary lifestyle (which you can do something about) and family history of diabetes (which you can’t do anything about). Other risk factors that you can’t control are either high or low birth weight. While diet composition surely acts at least in part by its relation to obesity, it also seems to have some independent influence: among people matched for obesity, those consuming a Mediterranean diet appear to be at lower risk than those with high intakes of sugar, saturated fatty acids, cholesterol, and triglycerides. Not exercising may create risks mainly through predisposing towards obesity, while smoking, inflammation, and high alcohol consumption appear to be independent risk factors. In short, Type-2 diabetes originates with genetic factors and possibly intra-uterine factors, which may become unmasked later in life by lifestyle factors resulting in disease symptoms.
Pima Indians and Nauru Islanders
These proofs of an environmental role in diabetes are illustrated by the tragedies of the two peoples with the highest rates of diabetes in the world: Pima Indians and Nauru Islanders. To consider the Pimas first, they survived for more than 2,000 years in the deserts of southern Arizona, using agricultural methods based on elaborate irrigation systems, supplemented by hunting and gathering. Because rainfall in the desert varies greatly from year to year, crops failed about one year in every five, forcing the Pimas then to subsist entirely on wild foods, especially wild jackrabbits and mesquite beans. Many of their preferred wild plants were high in fiber, low in fat, and released glucose only slowly, thereby constituting an ideal antidiabetic diet. After this long history of periodic but brief bouts of starvation, the Pimas experienced a more prolonged bout of starvation in the late 19th century, when white settlers diverted the headwaters of the rivers on which the Pimas depended for irrigation water. The result was crop failures and widespread starvation. Today the Pimas eat store-bought food. Observers who visited the Pimas in the early 1900s reported obesity to be rare and diabetes almost non-existent. Since the 1960s, obesity has become widespread among the Pimas, some of whom now weigh more than 300 pounds. Half of them exceed the U.S. 90th percentile for weight in relation to height. Pima women consume about 3,160 calories per day (50% over the U.S. average), 40% of which is fat. Associated with this obesity, Pimas have achieved notoriety in the diabetes literature by now having the highest frequency of diabetes in the world. Half of all Pimas over age 35, and 70% of those at ages 55 to 64, are diabetic, leading to tragically high occurrences of blindness, limb amputations, and kidney failure.
My second example is Nauru Island, a small remote tropical Pacific island colonized by Micronesians in prehistoric times. Nauru was annexed by Germany in 1888, was occupied by Australia in 1914, and eventually achieved independence in 1968 as the world’s smallest republic. However, Nauru also has a less welcome distinction as the grimly instructive site of a rarely documented phenomenon: an epidemic of a genetic disease. Our familiar epidemics of infectious diseases flare up when transmission of the infectious agent increases, and then wane when the number of susceptible potential victims falls, due both to acquired immunity of the survivors and to differential mortality of those who are genetically susceptible. An epidemic of a genetic disease flares up instead because of a rise in environmental risk factors, and then wanes when the number of susceptible potential victims falls (but only because of the preferential deaths of those who are genetically more susceptible, not because of acquired immunity; one doesn’t acquire immunity to diabetes).
The traditional lifestyle of Nauruans was based on agriculture and fishing and involved frequent episodes of starvation because of droughts and the island’s poor soils. Early European visitors nevertheless noted that Nauruans were plump, and that they admired big fat people and put girls on a diet to fatten them and so make them more attractive in their eyes. In 1906 it was discovered that most of Nauru underlying those poor soils consists of rock with the world’s highest concentration of phosphate, an essential ingredient of fertilizer. In 1922 the mining company extracting the rock finally began to pay royalties to the islanders. As a result of this new wealth, average sugar consumption by Nauruans reached a pound per day in 1927, and laborers were imported because Nauruans disliked working as miners.
During the Second World War Nauru was occupied by Japanese military forces, who imposed forced labor, reduced food rations to half a pound of pumpkin per day, and then deported most of the population to Truk, where half of them died of starvation. When the survivors returned to Nauru after the war, they regained their phosphate royalties, abandoned agriculture almost completely, and resumed shopping in supermarkets, heaping their shopping carts with big bags of sugar and eating double their recommended calorie intake. They became sedentary and came to rely on motor vehicles to travel around their little island (averaging one and a half miles in radius). Following independence in 1968, per-capita annual phosphate royalties rose to $23,000, making Nauruans among the world’s richest people. Today they are the most obese Pacific Island population, and the one with the highest average blood pressure. Their average body weight is 50% greater than that of white Australians of the same height.
Although colonial European physicians on Nauru knew how to recognize diabetes and diagnosed it there in non-Nauruan laborers, the first case in a Nauruan was not noted until 1925. The second case was recorded in 1934. After 1954, however, the disease’s prevalence rose steeply, and it became the commonest cause of non-accidental death. One-third of all Nauruans over the age of 20, two-thirds of those over age 55, and 70% of those few who survive to the age of 70 are diabetics. Within the past decade the disease’s prevalence has begun to fall, not because of mitigation of environmental risk factors (obesity and the sedentary lifestyle are as common as ever), but presumably because those who are genetically most susceptible have died. If this interpretation should prove correct, then Nauru would provide the most rapid case known to me of natural selection in a human population: an occurrence of detectable population-wide selection within less than 40 years.
Diabetes in India
Table 11.1 summarizes for comparison some prevalences of diabetes around the world. It’s obvious that there are big differences among countries in their national average prevalences, ranging from low values of 1.6% in Mongolia and Rwanda up to high values of 19% in the United Arab Emirates and 31% in Nauru. But Table 11.1 also illustrates that these national averages conceal equally big differences within any given country related to differences in lifestyle: at least in developing countries, wealthy or Westernized or urban populations tend to have much higher prevalences than do poor or traditional or rural populations.
India provides excellent examples of those subnational differences. (For this information I am grateful to Professor V. Mohan, of the Madras Diabetes Research Foundation.) The average prevalence in India as of the year 2010 was 8%. But there was little diabetes in India until just a few decades ago. Surveys in 1938 and 1959, in large cities (Calcutta and Mumbai) that are today strongholds of diabetes, yielded prevalences of only 1% or less. Only in the 1980s did those numbers start to rise, first slowly and now explosively, to the point where India today harbors more diabetics (over 40,000,000) than any other nation. The reasons are essentially the same as those behind the diabetes epidemic around the world: urbanization, rise in standard of living, the spread of calorie-rich sweet and fatty fast foods cheaply available in cities to rich and poor people alike, and increased sedentariness associated with replacement of manual labor by service jobs, and with video games and television and computers that keep children (and adults) seated lethargically watching screens for hours every day. Although the specific role of TV has not been quantified in India, a study in Australia found that each hour per day spent watching TV is associated with an 18% increase in cardiovascular mortality (much of it related to diabetes), even after controlling for other risk factors such as waist circumference, smoking, alcohol intake, and diet. But those factors notoriously increase with TV watching time,
so the true figure must be even larger than that 18% estimate.
Table 11.1. Prevalences of Type-2 diabetes around the world
POPULATION PERCENTAGE PREVALENCES
European and Middle Eastern “Whites”
41 Western European countries 6 (range, 2–10)
4 overseas Western European countries (Australia, Canada, New Zealand, U.S.) 8 (range, 5–10)
1 very poor Arab country (Yemen) 3
2 poor Arab countries (Jordan, Syria) 10
6 wealthy Arab countries 16 (range, 13–19)
Yemenite Jews, traditional ~0
Yemenite Jews, Westernized 13
Africans
rural Tanzania 1
Rwanda 2
urban South Africa 8
U.S. African-Americans 13
Asian Indians
urban India, 1938–1959 ~1
rural India today 0.7
urban Singapore 17
urban Mauritius 17
urban Kerala 20
urban Fiji 22
Chinese
rural China ~0
urban Hong Kong 9
urban Singapore 10
urban Taiwan 12
urban Mauritius 13
Pacific Islanders
Nauru, 1952 0
Nauru, 2002 41
Nauru, 2010 31
Papua New Guinea, traditional ~0
The World Until Yesterday: What Can We Learn From Traditional Societies? Page 53