Treatment-induced Neuropathy of Diabetes in Youth: Case Series of a Heterogeneous and Challenging Complication

Case Series of a Heterogeneous and Challenging Complication

Eirene G. Alexandrou; Sarah D. Corathers; Amit Lahoti; Jacob Redel; Siobhan Tellez; Nana-Hawa Yayah Jones; Ahlee Kim


J Endo Soc. 2020;4(12) 

In This Article

Abstract and Introduction


Treatment-induced neuropathy of diabetes (TIND) is a small fiber neuropathy precipitated by rapid correction of hyperglycemia. Literature on TIND in pediatric diabetes is scarce. We present 7 cases of TIND in children and young adults, increasing awareness of this condition in pediatric diabetes and broadening the scope of published knowledge.


Treatment-induced neuropathy of diabetes (TIND), first described in 1933, is a painful somatosensory and autonomic neuropathy occurring with rapid improvement in glycemic control (>2% decline in glycosylated hemoglobin A1c [HbA1c] over 3 months) achieved by insulin, oral hypoglycemic agents, or severe dietary restriction in patients with recent or remote type 1 (T1D) and type 2 diabetes (T2D).[1–3] Neuropathic symptoms are described as either burning, freezing, tingling, stinging, or allodynia, follow a symmetric distribution, and are worse distally. Risk factors include higher baseline HbA1c (>10% or 86 mmol/mol), diabetic anorexia or weight loss, and female gender.[3,4] TIND is distinct from diabetic polyneuropathy (DPN), given its acute onset and often reversible nature. TIND is also associated with autonomic dysfunction and microvascular complications, underscoring the importance of an interdisciplinary approach to care.[4,5] Current management, including gabapentinoids, tricyclics, or serotonin reuptake inhibitors, is limited by our understanding of TIND pathophysiology,[4–6] of which there are a few postulated mechanisms. One theory relates to hyperglycemia-induced microcirculatory changes that cannot remodel at the same rate of decline in serum glucose, leading to ischemic conditions within the endoneurium. Another thought is that acute glucose deprivation leads to cellular apoptosis and, once a normoglycemic state is achieved, the subsequent firing of regenerating axons results in the development of neuropathic symptoms.[4] Treatment response in TIND is variable with a gradual (but sometimes incomplete) resolution of symptoms over 3 to 24 months.[4–6] Cases of TIND are well described in adult literature, and a recent report has shown that 11% of patients (n = 954) referred to a diabetic neuropathy clinic had presentations consistent with TIND.[3] The prevalence in children remains unclear, as pediatric literature is scarce, with only 2 cases reported.[4,7]

In this series, we describe 7 cases of TIND in children and young adults treated at 2 pediatric centers (Cincinnati Children's Hospital Medical Center and Le Bonheur Children's Hospital). We aim to promote recognition of this condition, especially within the pediatric community. Additionally, we look to broaden the scope of published knowledge regarding TIND, highlight its varied course and treatment challenges, and inspire continued research in the area to better define TIND so that novel prevention and treatment strategies can be developed.