Summary of a guest lecture given today by Dr P Costanzo an Interventional radiologist working in the UK. You can find him on pubmed here and on twitter here:
Increasing BMI has been shown to increase all cause mortality in this NEJM study in 1.46 million white patients. Further extrapolation showed this was mainly due to cardiovascular death.
Furthermore obesity levels are on the rise. So too are the levels of type 2 diabetes. However, the mortality levels for patients with type 2 diabetes has not shown the same rise infact it has been petty stable for many years.
A large cohort of type 2 diabetic patients (T2DM) was taken by Costanzo et al. and divided into categories of weight and then following up over 10 years for mortality. The kaplan meier survival curve was interesting, displaying the so called obesity paradox. Patients who were underweight with a low BMI (less than 20 or 18.5) had the highest mortality. Increasing BMI showed a protective effect with the highest BMI values having the lowest mortality. A paradox indeed.
Further extrapolation of the data by cause of death showed a protective effect of obesity in T2DM in sepsis and cancer (again paradoxical, considering cancers relationship with obesity).
Dr Costanzo went on to explain possible mechanisms of this, citing the important relationship between low birth weight and increased lifetime risk of T2DM. And how this may be part of the so called evolutionary Thifty phenotype, a phenotype in which high blood sugar can be maintained in starvation providing a survival advantage. It is well known that subsaharan populations (and also indian populations) who move to say the UK (or anywhere) and start a western diet are likely to develop diabetes. He mentions the lipgenic model of T2DM and how subcutaneous fat is neutral to us but visceral fat is the fat that as it accumulates increases cardiovascular mortality. There is a kind of tipping point where when lets say SC fat is full, visceral fat begins to accumulate (where is the level?).
The last part of Dr Costanzos talk was incredibly interesting. HB1AC levels documented across all values of BMI is more or less the same in his cohort (unreleased data unfortunately, paper release in 2017), except for the underweight BMI values in which it generally higher. You can postulate that HB1AC is therefore not linked to mortality, and infact other studies confirm this. My notes run out at this point, I guess I was trying to concentrate, but the final part of this section he shows that good BP control in T2DM can reduce mortality in T2DM and perhaps glycemic control has little to do with cardiovascular mortality.
In fact a nice point was that two new anti-diabetic drugs being studied at the moment; Liraglutide and Empagliflozin, are the only drugs that have been shown to reduce cardiovasuclar mortality in T2DM. These two drugs also have a blood pressure lowering effect.
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