DCCT/EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) – studies of type 1 diabetes – do not naturally represent what we understand as “diabesity”, but this paper describes insulin-induced metabolic syndrome with weight gain and the fascinatingly controversial topic of the risks versus benefits of insulin. Insulin has saved countless lives, but has considerable faults; almost 100 years after its introduction, there is a veiled suggestion that alternatives might be preferable.
The DCCT/EDIC research team churns out high quality papers at a spectacular rate, recently on the genetics of erectile dysfunction (Hotaling et al, 2012), and on cardiac autonomic neuropathy (Pop-Busui et al, 2013), but this one is more engaging and clinically useful. David Nathan, Harvard Professor, described the importance of DCCT: “More than 99% of the patients stayed with it for an average of 6.5 years. I’d suggest that’s a world record. We were looking to reduce complications by about 30% and we ended up with a reduction that was more than double that (Watts, 2012).” At the time of the setting up of DCCT, there was controversy about benefits of tight glucose control; some thought that complications had more to do with genetic susceptibility or other factors.
What DCCT originally revealed seems obvious in hindsight precisely because of the wisdom of DCCT and its like which illustrated the evolution of diabetes. DCCT studied insulin use in type 1 diabetes, but its message is relevant to type 2 diabetes: optimising glycaemic control by responsibly intensifying treatment reduces the risk of complications (DCCT Study Group, 1993). On the negative side, however, risks of hypoglycaemia and severe hypoglycaemia alongside weight gain increased. In 1993, when DCCT ended, the same cohort of patients were recruited for the EDIC study, which showed that intensive diabetes therapy had long-term beneficial effects on the risk of cardiovascular disease (Nathan et al, 2005).
However, as shown in the present study, the quartile from the intensive treatment group with the highest weight gain moved on average from a normal BMI 24 kg/m2 to an obese 31 kg/m2, displaying metabolic syndrome including worsening waist circumference. The study sheds light on the effects of insulin-induced weight gain on cardiometabolic health: those who gained most weight suffered the worst deterioration in HbA1c. Total cholesterol was higher in weight gainers, as was LDL, with a reduced quality of the LDL particle, alongside raised blood pressure, significantly increasing percentage of patients achieving metabolic syndrome eligibility. Furthermore, intima-media thickness was greater in high-gainers, with coronary artery calcium also trending higher.
Finally, in a fascinating dénouement, comes a suggestion that complications are actually caused by genetic susceptibility, not HbA1c at all! We live and learn.
To view the summaries of each paper, please download the PDF.
