Insulin resistance, role of metformin and other non-insulin therapies in pediatric type 1 diabetes

Abstract

Type 1 diabetes mellitus (T1DM) in youth is a challenging chronic medical condition. Its management should address not only the glycemic control but also insulin resistance and cardiovascular disease risk factors which are increasingly recognized to be present in youth with TID. Current knowledge on the mechanisms of insulin resistance in T1DM is reviewed. The use of adjunctive therapies that are beneficial to achieve adequate glycemic control while mitigating the effects of insulin resistance are discussed with a focus on metformin therapy and an overview of other new pharmacologic agents.

Comparison of adjunctive therapy with metformin and acarbose in patients with Type-1 diabetes mellitus

“…Our metformin group result was similar to some reported studies 4,5,7. For instance, a meaningful decrease in TG and PPG or a significant reduction in fasting blood glucose level have been reported in metformin group compared with placebo based on different studies 4,5.…”

“…For instance, a meaningful decrease in TG and PPG or a significant reduction in fasting blood glucose level have been reported in metformin group compared with placebo based on different studies 4,5. However, there are some controversial aspects about metformin consequences on regular insulin intake, HbA1C or BMI index.…”

“…Insulin is the core treatment of T1DM. Achieving stable blood glucose levels and adequate hemoglobin A1c (HbA1c)and preventing the development of micro vascular and macro vascular complications are the main goals of treatment in T1DM 5,6. The Diabetes Control and Complications Trial has shown that intensive insulin regimens to reduce glucose to near-normal levels are associated with delays in incidence and progression of diabetes-related complications 3,4,7…”

Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity

“…A substantial enrichment of differentially variable CpG positions was observed in these three different cell types from T1D twins, 126 suggesting the contribution of DNA methylation of B cells to T1D development. Although there is little evidence showing the association of epigenetic modifications in B cells with the pathogenesis of T1D, epigenetic drugs such as 5-Aza, 127 HDACs 128,129 and HDAC inhibitors 130,131 may exert their therapeutic effects on T1D via modifying B-cell activation and differentiation. Thus further studies on the potential link between abnormal epigenetic regulation of B cells and T1D may broaden our understanding of T1D pathogenesis (Table 1).…”

Type 1 Diabetes: Disease Stratification

“…With the advent of improved insulins and delivery systems such as insulin pumps, technology to measure glucose levels in real time such as continuous glucose monitors (CGMs), approval of the first automated hybrid closed loop systems (USA), emerging data from the use of adjunct therapies such as GLP1 analogs, SGLT inhibitors, and fixed dose and fixed ratio combinations of therapeutics with or without insulin, it behooves the research and clinical communities to exploit all options to understand the benefit/burden profiles of treatments and optimize care of patients [130][131][132] . This calls for deep phenotyping of individuals, including assessment of critical markers of disease onset and progression, such as age at onset, disease duration, body weight, insulin sensitivity, C-peptide level, adiposity, metabolic syndrome parameters, time in and out of desirable glucose range, glycemic variability, and plasma and urine markers suggestive of vascular diseases.…”