Small steps forward: Adjunctive therapy for T1D

In a 6-year follow-up of the Diabetes Complications and Control Trial (DCCT), among those initially randomized to intensive glycemic management, approximately 10% had a positive family history of T2D, with final triglyceride level 92 versus 76, low-density lipoprotein cholesterol 118 versus 111, and apolipoprotein B 90 versus 82 mg/dl among those not having such a history, and these individuals gained more weight during the trial, with final body mass index (BMI) 27.8 versus 26.4 kg/m2, respectively. Furthermore, those in the highest weight gain quartile had higher HbA1c, insulin dose, and levels of triglyceride, non–high-density lipoprotein cholesterol, and blood pressure, with this degree of weight gain showing significant association with carotid intima-medial thickness, a marker of atherosclerotic cardiovascular disease (ASCVD). Using the waist circumference, HbA1c, and blood pressure to derive an estimate of the glucose disposition rate (eGDR), several groups have shown lower eGDR to be associated with ASCVD and mortality, and using such an approach to estimate the change in insulin sensitivity over time in 1375 participants in the DCCT at entry and at 18.5-year follow-up, those with lower insulin sensitivity at both time points had greater likelihood of development of CVD events. A meta-analysis of 18 placebo-controlled trials of SGLT2i in T1D including 7396 participants over a mean duration of 19 weeks showed a 2.81-fold increased risk of DKA, affecting 1%–4% of treated patients, with greatest risk of DKA in trials of persons with lower insulin sensitivity and higher body weight, particularly in association with excessive insulin dose reduction, so that caution in use of these agents is appropriate.