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

Case Descriptions

Case 1

A 14-year-old African American male presented with diabetic ketoacidosis (DKA) and new-onset T1D with initial HbA1c>14% (>130 mmol/mol). With multiple daily injection (MDI) insulin therapy, his HbA1c declined to 5.6% (38 mmol/mol) after 3 months. Simultaneously, burning and allodynia developed in his chest, abdomen, and lower extremities as well as early satiety with a 4 kg weight loss. Evaluation for weight loss demonstrated normal adrenal, thyroid, liver, and renal function, and was negative for inflammatory bowel disease. Over the next few months, his appetite normalized, and he regained 8 kg. His pain was discussed with rheumatology and neurology, and presentation was deemed consistent with TIND. Low-dose gabapentin was offered, but not pursued. His symptoms resolved over 4 months without treatment or worsening glycemic control.

Case 2

A 16-year-old Caucasian female presented with DKA and new-onset T1D with HbA1c >14% (>130 mmol/mol). MDI insulin therapy was initiated. Generalized insulin edema with pleural effusions developed within 1 week, marked by an 18 kg weight gain that improved with diuretics. Over 4 weeks, her HbA1c improved to 9.9% (85 mmol/mol), at which time she developed pain and paresthesia of her chest, abdomen, back, hands, and feet. She reported early satiety with an 11 kg weight loss over 3 months and palpitations. Bilateral, moderate nonproliferative retinopathy, macular edema, and cataracts were also noted at T1D diagnosis. Additional screening for microvascular complications revealed microalbuminuria. Her evaluation was negative for pancreatitis, urinary tract infection, nephrolithiasis, and celiac disease. She had normal iron studies and inflammatory markers, and no vitamin deficiencies. A gastric emptying study revealed gastroparesis. Her electrocardiogram was notable for sinus tachycardia and echocardiogram was normal. She had normal muscle strength, deep tendon reflexes, and sensation to touch, temperature, vibration, and proprioception. Neurology diagnosed her with TIND and initiated gabapentin. Situational tachycardia was suspected, but over the next several months she experienced palpitations that awakened her from sleep and occurred at rest. Due to concerns for dysautonomia she was referred back for cardiologic consultation, but she did not follow up. With improved glycemic control over the next 6 months her neuropathy, autonomic symptoms, and microvascular manifestations subsided, and medications were tapered off.

Case 3

A 19-year-old Caucasian male with a five-year history of poorly controlled T1D was motivated to improve glycemic control. In 1 month, his HbA1c declined from 12.1% (109 mmol/mol) to 8.6% (70 mmol/mol). He developed burning pain in his feet and early satiety with a 3 kg weight loss. His exam was notable for normal muscle strength, deep tendon reflexes, and sensation to light touch and proprioception. He had mildly decreased vibration sensation in his feet with tenderness of the plantar surfaces. Neurology diagnosed him with TIND and started gabapentin along with cognitive behavioral therapy. His pain was refractory to treatment and he was subsequently lost to follow-up. One year later, he returned to the endocrine clinic with HbA1c 6.5% (48 mmol/mol) and no complaints of pain or early satiety off medication.

Case 4

A 22-year-old African American male with a 3-year history of poorly controlled T1D with HbA1c >14% (>130 mmol/mol) was transitioned to insulin pump therapy. Over 2 months, his HbA1c improved to 10.5% (91 mmol/mol). Pain in his lower extremities and genitalia developed without associated impotence or urinary symptoms. Evaluation was performed by urology, pain team, and neurology. A computed tomography scan of abdomen and pelvis, testicular ultrasound, and infectious and lymphoproliferative disease workup was unremarkable. Deep tendon reflexes were symmetrically depressed at his knees and ankles. His pain was refractory to gabapentin, but improved modestly with acupuncture. He experienced a 4.5 kg weight loss attributed to decreased appetite and intermittent emesis in setting of severe pain. Given the unremitting pain, he developed depression and was started on duloxetine. Over 5 months, his HbA1c rose to 13.5% (124 mmol/mol) and symptoms resolved. His glycemic control gradually improved, and he has maintained a HbA1c near 10% (86 mmol/mol) without return of symptoms.

Case 5

A 19-year-old Caucasian male with a 3-year history of poorly controlled T1D reinitiated consistent MDI insulin therapy. Over 2 months, his HbA1c decreased from >14% (>130 mmol/mol) to 8.3% (67 mmol/mol). He developed burning pain in his extremities, torso, and perineum, and profuse diarrhea with emesis. He lost 8 kg over 5.5 months, resulting in admission. Evaluation demonstrated normal esophagogastroduodenoscopy, colonoscopy, gastric emptying scan, and magnetic resonance imaging (MRI) of abdomen and pelvis. He had a negative celiac screen, nonelevated secretory diarrhea hormones, negative bacterial overgrowth test, negative infectious workup, normal inflammatory markers, normal thyroid testing, and negative rheumatologic markers. He was diagnosed with diabetic enteric neuropathy and TIND, and started on medical therapy (Table 1). He developed restrictive eating behaviors given concern for worsening diarrhea and body image issues, and he was later diagnosed with anorexia nervosa. Within 3 months of his neuropathic symptoms, he also developed microalbuminuria, which is ongoing. He has continued medications for symptom management since initiation 2 years prior. His HbA1c remains between 6% and 8.5% (42–69 mmol/mol).

Case 6

A 9-year-old Caucasian female was admitted with severe DKA and in a coma due to medical neglect 1 month post-T1D diagnosis. Her HbA1c was >14% (>130 mmol/mol). She reinitiated MDI insulin therapy upon discharge with her foster family. Over 1 month, her glycemic control improved to HbA1c 6% (42 mmol/mol), she developed paresthesia of her lower extremities, incontinence, and reported difficulties in walking as well as a 14 kg weight loss. Her exam was remarkable for pain to palpation of right lower extremity, decreased strength of right dorsiflexor and plantar flexor, and right foot drop. Deep tendon reflexes were intact. Spine MRI was normal. She was diagnosed with TIND and referred to physical medicine and rehabilitation, but did not follow up. All symptoms resolved without intervention over 3 months. Her HbA1c has ranged from 6% to 6.2% (42–44 mmol/mol).

Case 7

A 17-year-old Caucasian male with new-onset, antibody-negative T1D was started on MDI insulin therapy. His glycemic control improved from HbA1c >14% (>130 mmol/mol) to 10.7% (93 mmol/mol) over 4 weeks. He developed allodynia and paresthesia in his lower extremities and scrotum, and a decreased appetite with 10 kg weight loss. Microalbuminuria and mild, nonproliferative retinopathy developed. He had a normal spine MRI and a delayed gastric emptying scan. His presentation was consistent with TIND, and he was started on gabapentin and self-initiated cannabis. His symptoms persisted, so treatment was modified (Table 1). He had gradual resolution of all symptoms over 10 months, aside from unchanged retinopathy, and he discontinued all noninsulin medications. His HbA1c remains <6% (<42 mmol/mol).