ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Pediatr 2018;196:208-216.e2

Insulin deficiency or resistance activates intracellular hormone-sensitive lipase; this increases the release of non-esterified fatty acids from triglycerides stored in centrally distributed adipose tissue. High circulating levels of non-esterified fatty acids increase hepatic triglyceride synthesis, which in turn increases secretion of apolipoprotein B (apoB). Indeed, dyslipidemia is a common feature in T2DM. The risk of cardiovascular disease is greater at any given level of serum cholesterol in patients with diabetes, and its association with hypertriglyceridemia is stronger than in the general population. Cardio-metabolic disease risk is further increased both by poor glycemic control and by systemic inflammation, specifically hs-CRP.

Among T2DM adults, diabetic dyslipidemia can be partly corrected by insulin treatment and improved blood glucose control. The aim of the current study was to determine the impact of insulin therapy on lipid profiles and inflammatory markers in adolescents with T2DM and poor glycemic control. The mean HbA1c prior to initiation of insulin treatment was 9.7±1.7%. After 6 months of insulin therapy, the decrease in HbA1c was approximately −0.11± 2.1%. Prior to initiation of insulin treatment, lipid and inflammatory markers were rising steadily. After insulin therapy, lipid markers for total cholesterol, LDL-C, apoB, and triglycerides continued to rise, but at a slower rate. Those with the greatest reduction in HbA1c had the greatest reduction in total cholesterol, LDL-C, and apoB. Triglyceride level was independent of HbA1c level. Nevertheless, the small dense, more atherogenic LDL particles did not decline. Furthermore, the inflammatory markers: IL-6 and hs-CRP continued to rise steadily after insulin therapy. BMI remained stable over time.

The authors raised concern that starting insulin therapy in youth with T2DM may not protect against premature atherosclerosis. In a recent study that assessed barriers to taking glucose-lowering oral medications, about 70% and 80% of TODAY participants reported missing one or more doses in the two- or three-month interval since their last visit at 6 and 24 months, respectively.¹⁶ It is possible that these patients did not comply with insulin treatment as well, and that this might explain the lack of improvement in their metabolic profile.

16. Venditti EM, Tan K, Chang N, Laffel L, McGinley G, Miranda N et al. Barriers and strategies for oral medication adherence among children and adolescents with Type 2 diabetes. Diabetes Research and Clinical Practice 2018; 139: 24-31.