The streetlight effect

‘The streetlight effect in type 1 diabetes’ is an intriguing article published earlier this year in the journal ‘Diabetes’. http://diabetes.diabetesjournals.org/content/64/4/1081.full

 

The authors explain the ‘streetlight effect’ using the following narrative: A police officer is patrolling a neighbourhood when he sees a man, dishevelled and reeking of alcohol, crawling around underneath a streetlight. The officer walks over to the man and asks if there is a problem. The drunkard turns to the officer and conveys that he dropped a quarter and was trying to find it. The officer peruses the area and after observing nothing in the light emanating from the streetlight, he asks the man where exactly he dropped it. With this, the drunken man replies that he dropped it two blocks away. When the police officer asks him why he is looking for his money all the way over here, the man replies, “Because the light is better here.”

 

So, what does this have to do with type 1 diabetes (T1DM)? The authors argue that the painfully slow progress in finding the underlying cause of this condition, let alone any cure may be because researchers have been looking in the wrong place. They then go on to examine eight truisms about T1DM, highlighting that the evidence upon which they are based may be less solid than is generally thought. These include the following ‘facts” (these all resonated with me as I have previously expounded these to both patients and students):

 

T1DM is a disease with specificity for pancreatic beta-cells. The authors point out that studies dating back to the 1940’s clearly show that patients with T1DM also have abnormal pancreatic exocrine function and that they have autoantibodies to exocrine antigens (such as lactoferrin and carbonic anhydrase).

 

‘Insulitis’ is the Hallmark Lesion of T1DM. Histological examination of the pancreas in T1DM is relatively uncommon and much of the current knowledge is based on a seminal study by Gepts in 1965 and data from animal models of T1DM (such as the NOD mouse). However, nearly one third of the subjects reported by Gepts had no evidence of insulitis and even in the mouse model; its presence can be minimal.

 

T1DM develops when 85–95% of beta-cells are lost. The evidence for this is surprisingly limited with highly variable patterns of beta-cell loss at the time of symptom onset.Over time, people with T1DM have
a complete loss of C-peptide, reflecting a complete loss of beta-cells. The authors point out that the majority of patients retain the ability to produce C-peptide long after disease onset and that preservation of this phenomenon could be an important therapeutic target.

 

T1DM and type 2 diabetes (T2DM) are two completely different diseases. The authors list several lines of evidence that suggests a marked overlap between the two conditions including; markers of autoimmunity, links with obesity, insulin resistance, amyloid deposition in T1DM and beta-cell destruction in T2DM.

 

The authors give other examples and suggest that by ‘thinking outside the box’; research may eventually make progress in this frustrating arena. Food for thought…..

 

Professor Steve Bain