Historical aspects of type 2 diabetes

Diabetes was rare before the twentieth century. Early Sanskrit physicians linked it to affluence and over-eating, and nineteenth century clinicians distinguished between diabetes in the young and thin as against the middle aged and overweight. Insulin was soon seen not to be essential for the survival of many (though not all) late onset patients after its introduction in 1922, and diabetes was long classified into insulin-dependent and non-insulin dependent varieties on this basis. The distinction between insulin sensitive and insulin resistant diabetes was made in the 1930s, but the terms type 1 and type 2 diabetes (first proposed in 1950) were not adopted until the 1970s. Diet remained the mainstay of treatment until the introduction of tolbutamide and other oral therapies from the 1950s onward transformed the approach to therapy, now extended to many with asymptomatic hyperglycaemia. Type 2 diabetes first appeared among the affluent classes of modern societies, spreading down the social scale as living conditions improved. It reached epidemic proportions by the end of the century and was recognised as a major cardiovascular risk factor. The value of early detection and treatment of hyperglycaemia (as against other risk factors) in cardiovascular risk reduction remains controversial.

Early Origins

The Sanscrit oral tradition, which extends back over thousands of years, attributes the following description to Susruta, almost always cited in the translation of Chandra Bose (1907):

“Madhumeha (honey urine) is a disease which the rich principally suffer from, and is brought on by their overindulgence in rice, flour and sugar. The patient feels weak and emaciated and complains of frequent urination, thirst and prostration. Ants flock around his urine. Boils and tuberculosis are frequent complications”.

This sounds like a clear description of type 2 diabetes. Aretaeus of Cappadocia (c 100-200 AD) describes diabetes as a chronic disease with a slow prodrome and rapid final decompensation, but makes no link with obesity or overindulgence. Thomas Willis (1621-75), in contrast, writes that:

"Diabetes was so rare among the ancients that many famous physicians did not mention it but in our age given over to good fellowship and guzzling down of unallayed wine, we meet with examples enough, I may say daily, of this disease" [1]

The Nineteenth Century

Clinicians began to distinguish between two types of diabetes in the second half of the nineteenth century, and the association between diabetes and obesity became more obvious, although the frequently cited comment that Apollinaire Bouchardat(1806-86) observed an improvement in his patients because of enforced starvation during the siege of Paris may turn out to be a legend. He did however advise his patients to "mangez le moins possible". Therapy before and for some time after the introduction of insulin was based around a variety of unpalatable diets which may have worked by discouraging the patient from eating at all.

Obesity and diabetes

Elliot Joslin (1870-1962) was one of the first to apply statistical methods to diabetes, drawing upon his own extensive case records as well as life insurance and mortality data[2]. Kelly West (1925-1980), often called the "father of diabetes epidemiology", credits Joslin with the first systematic examination of diabetes in terms of obesity, and the first use of the term "epidemic" in relation to diabetes in 1921[3].

The impact of insulin

Insulin transformed the lives of children and young adults with diabetes, but had limited impact upon the survival of those diagnosed at the age of 50 [4]. This was probably because insulin had little effect upon the high cardiovascular mortality associated with late onset diabetes.

Insulin sensitive and insensitive diabetes

Clinicians soon noted that higher doses of insulin were needed to control glucose levels in older or fatter patients, and this was established on a more formal footing when Sir Harold Himsworth MD, FRS (1905-1993) (1905-93) tested the ability of injected insulin to clear an oral glucose load from the circulation. From this he deduced that there were insulin sensitive patients whose diabetes was due to insulin deficiency and insulin insensitive patients whose diabetes was due to resistance to insulin. He also noted the existence of an intermediate type of patient who did not fit into either category.

Body composition and diabetes

Anthropometrists who set out to define the diabetic phenotype in the 1940s soon noted that patients attending a New York diabetic clinic were slender if young and more adipose when the disease presented in later life. John Lister in London combined anthropometry with Himsworth's insulin sensitivity test, and noted the distinctive phenotype of the older insulin-insensitive patients, whom he referred to as type 2, incontrast to the less distinctive type 1 patients. The terminology did not catch on until the 1970s.

Diabetes becomes a risk factor

For the first half of the twentieth century, diabetes meant symptoms plus glycosuria. Borderline diabetes - raised blood glucose without obvious symptoms - was well recognised, but generally not considered worth treating. One reason for this is that the renal threshold for glucose rises with age, and older people can therefore run higher blood glucose before this spills over into the urine. Consequently they experience fewer symptoms of thirst and polyuria.

Two developments changed this relaxed attitude. One was that prospective studies such as Framingham identified hyperglycaemia as a risk factor for cardiovascular disease in parallel with hypertension and hyperlipidaemia. The other was the introduction of tolbutamide in 1957, which greatly simplified the management of the condition[5]. The combination of risk factor and effective therapy provided a great stimulus to wider population screening and intervention.

Finally recognised!

The discovery of type 1 diabetes led to greater recognition of type 2 diabetes as a distinct variant of diabetes[6]. The older terms "maturity onset diabetes" and "non-insulin-dependent diabetes" (NIDDM) were abandoned in favour of the newer terminology between 1980 and the 1990s.

When should we intervene?

The recognition of hyperglycaemia as a cardiovascular risk factor resulted in a long-running and still unfinished discussion as to the level of glycaemic exposure (and ways of defining that level) that would justify intervention. Since cardiovascular risk begins to rise within the normal range of glucose in the population, and the impact of glucose-lowering therapies upon cardiovascular risk is small, the controversy is not likely to end soon.

There has however been a clear trend toward earlier and more aggressive intervention, which has translated into lower diagnostic thresholds and the reintroduction of the concept of prediabetes. These issues are discussed elsewhere in Diapedia.

Diabesity

This term appears to have first been introduced in 1980[7]. The subsequent epidemic of diabesity may be attributed to rising affluence in many parts of the globe, reduced physical activity, and increasing lifespan (type 2 diabetes favours the over-60s). Lower diagnostic thresholds, simpler screening methods and increased awareness of condition have also contributed to the increase. The major adverse consequence is an increased risk of cardiovascular disease although, mercifully, overall mortality from this is falling in the population as a whole, and this may be reflected in the risk for those with diabetes.

What's in a name?

Type 2 diabetes is essentially diagnosed by default, i.e. by the presence of hyperglycaemia for which no other cause is apparent. The glycaemic threshold for diagnosis is settled (and periodically revised) by expert committee, and there are no non-glycaemic hallmark features, whether genetic or metabolic. Many think that the condition is heterogeneous: in other words, we may be in the same situation as our predecessors who tried to understand "diabetes" without appreciating that this was a heterogeneous condition. Attempts to subdivide type 2 diabetes have to date helped to identify a number of monogenic subtypes of diabetes, but the common form of the condition still eludes precise definition. Better understanding of the heterogeneity of type 2 diabetes might well help us to manage it more effectively.

References

  1. ^ Tattersall RB. Diabetes. The biography. Oxford University Press, 2009

  2. ^ Joslin EP. Treatment of Diabetes Mellitus. Second Edition, Lea and Febiger, Philadelphia and New York, 1917

  3. ^ West KM. Epidemiology of diabetes and its vascular lesions. Elsevier, New York, 1978

  4. ^ Dublin LI. The facts of life from birth to death. Macmillan, New York, 1951

  5. ^ Greene JA. Prescribing by numbers. Drugs and the definition of disease. Johns Hopkins University Press 2007

  6. ^ Gale EAM. The discovery of type 1 diabetes. Diabetes 2001;50:217–26

  7. ^ [No authors listed]. From the NIH: Successful diet and exercise therapy is conducted in Vermont for "diabesity". JAMA 1980;243:519-20

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