Mitigating micro-and macro-vascular complications of diabetes beginning in adolescence

Abstract

Diabetes is a chronic disorder, which manifests when insulin levels or resistance to insulin action becomes insufficient to control systemic glucose levels. Although the number of available agents to manage diabetes continues to expand rapidly, the maintenance of euglycemia by individuals with diabetes remains a substantial challenge. Unfortunately, many patients with type 1 and type 2 diabetes will ultimately experience diabetes complications. These complications result from the toxic effects of chronic hyperglycemia combined with other metabolic derangements that afflict persons with diabetes. This review will present a comprehensive look at the complications of diabetes, the risk factors for their progression, the mechanistic basis for their development, and the clinical approach to screening for, preventing, and treating these sequelae. In addition, since diabetes is commonly diagnosed in childhood, we will provide a special focus on the care of the adolescent patient.

Keywords: complications; diabetes; glycemia; macrovascular; microvascular; nephropathy; neuropathy; pediatric; retinopathy.

Figure 1

The Diabetes Control and Complications Trial: percent reduction of microvascular complication with intensive therapy. Patients age 13 to 39 with T1DM were divided into two cohorts, primary prevention cohort (no complications), and secondary intervention cohort (mild to moderate retinopathy, urine microalbumin <200 mg/24 h). The patients who underwent intensive therapy with insulin showed significant reduction of microvascular complications in both cohorts. Drawn from data of Skyler JS. Diabetic complications. The importance of glucose control. Endocrinol Metab Clin North Am. 1996;25(2):243–254.

Figure 2

The contributions of hyperglycemia to vascular endothelial dysfunction and atherogenesis are mediated through several processes, including increased production of advanced glycation end products, activation of protein kinase C and sorbitol. These factors serve to enhance inflammatory processes including the activation of NF-κβ and the production of pro-inflammatory cytokines. In turn, these factors cause injury to the vascular endothelium. This final common mechanism promotes atherogenesis and facilitates the vascular complications of diabetes. Abbreviations: AGEs, advanced glycation end products; DAG, diacylglycerol; PKC, protein kinase C; LDL, low-density lipoprotein; GSH, glutathione; NADPH, nicotinamide adenine dinucleotide phosphate; NF-κβ, nuclear factor-κβ.