of insulin on the kidney 9 or transient hyperaldosteronism . 4 Others have suggested that similar to pathophysiology of anorexia nervosa leading to re-feeding syndrome , intensive fluid resuscitation during an insulin insufficiency state ( like DKA in our patient ) may lead to extravasation of fluid to the subcutaneous tissue . This leads to peripheral edema , which is exaggerated with hyperglycemia-related increase in capillary permeability . 10 Genetic susceptibility for this condition was noted by Suzuki et al when they reported four patients with insulin-induced edema after insulin initiation , who all had the 3243 mitochondrial tRNA mutation suggesting role of mitochondrial function . 11
Before the diagnosis of insulin edema is made , other common causes of edema – from cardiac , renal , or liver-related causes as well as related to chronic urticaria , certain medications ( including Thiazolidinediones 12 ) – need to be ruled out , especially if the patient presents with generalized swelling . 13 Localized swelling , especially in the leg , could be due to deep-vein thrombosis , cellulitis , compartment syndrome , lymphedema , or thyroid disease and needs to be assessed for . 13
Once other causes are excluded , clinicians need to reassure patients and their families of its transient nature . 1 , 2 The majority of cases are asymptomatic within two weeks . 14 It is important , however , for the physician to be cautious in patients with pre-existing hepatic , cardiac , or renal disease and to monitor them closely . The mainstay of treatment is by-fluid restriction and a low salt diet (< 2g sodium / day ). 4 The use of diuretics in treatment has been debated due to the self-limited course and should be reserved for severe causes of insulin edema that do not respond to non-pharmacologic options . 4 Rarely , cases in literature describe the role of ephedrine in such cases , especially those that relate to diabetic autonomic neuropathy . 15 This medication causes a decrease in renin production and a decrease in sodium and water resorption due to pressor effect on the afferent glomerular arterioles and allows for total body fluid levels to decrease and help reduce the effects of the edema .
Our patient was non-compliant with her insulin treatment in the past , and now had features of insulin edema within the expected time frame following “ restart ” of insulin therapy . She was appropriately assessed for other causes of her swelling before the diagnosis was made and did well without much intervention .
1 . Bas VN , Cetinkaya S , Agladioglu SY , et al . Insulin oedema in newly diagnosed type 1 diabetes mellitus . J Clin Res Pediatr Endocrinol . 2010 ; 2 ( 1 ): 46-48 .
2 . Aravamudhan A , Gardner C , Smith C , Senniappan S . Insulin oedema in a child with newly diagnosed diabetes mellitus . European journal of pediatrics . 2014 ; 173 ( 5 ): 685-687 .
3 . Leifer A . A CASE OF INSULIN EDEMA . Journal of the American Medical Association . 1928 ; 90 ( 8 ): 610-611 .
4 . Kalambokis GN , Tsatsoulis AA , Tsianos EV . The edematogenic properties of insulin . American journal of kidney diseases : the official journal of the National Kidney Foundation . 2004 ; 44 ( 4 ): 575-590 .
5 . Lee P , Kinsella J , Borkman M , Carter J . Bilateral pleural effusions , ascites , and facial and peripheral oedema in a 19-year-old woman 2 weeks following commencement of insulin lispro and detemir--an unusual presentation of insulin oedema . Diabetic medicine : a journal of the British Diabetic Association . 2007 ; 24 ( 11 ): 1282-1285 .
6 . Kan Y , Anno T , Kawasaki F , et al . Bilateral lower limb edema induced by rapid improvement of glycemic control with insulin therapy in a subject with poorly controlled type 2 diabetes . Acta diabetologica . 2017 ; 54 ( 6 ): 611-613 .
7 . O ’ Neal KS , Francis BA , Condren ME , Chalmers LJ . Insulin edema in a patient with cystic fibrosis-related diabetes . Diabetes Care . 2012 ; 35 ( 2 ): e6 .
8 . Evans DJ , Pritchard-Jones K , Trotman-Dickenson B . Insulin oedema . Postgraduate Medical Journal . 1986 ; 62 ( 729 ): 665-668 .
9 . DeFronzo RA , Cooke CR , Andres R , Faloona GR , Davis PJ . The effect of insulin on renal handling of sodium , potassium , calcium , and phosphate in man . The Journal of clinical investigation . 1975 ; 55 ( 4 ): 845-855 .
10 . Ehrlich S , Querfeld U , Pfeiffer E . Refeeding oedema : an important complication in the treatment of anorexia nervosa . European child & adolescent psychiatry . 2006 ; 15 ( 4 ): 241-243 .
11 . Suzuki Y , Kadowaki H , Taniyama M , et al . Insulin edema in diabetes mellitus associated with the 3243 mitochondrial tRNA ( Leu ( UUR )) mutation ; case reports . Diabetes research and clinical practice . 1995 ; 29 ( 2 ): 137-142 .
12 . Huang A , Raskin P . Thiazolidinediones and Insulin . Treatments in Endocrinology . 2005 ; 4 ( 4 ): 205-220 .
13 . Trayes KP , Studdiford JS , Pickle S , Tully AS . Edema : diagnosis and management . American family physician . 2013 ; 88 ( 2 ): 102-110 .
14 . Mamoulakis D , Bitsori M , Galanakis E , Raissaki M , Kalmanti M . Insulin-induced oedema in children and adolescents . Journal of paediatrics and child health . 2006 ; 42 ( 10 ): 655-657 .
15 . Hopkins DF , Cotton SJ , Williams G . Effective treatment of insulin-induced edema using ephedrine . Diabetes Care . 1993 ; 16 ( 7 ): 1026-1028 .
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Volume 117 • Number 9 March 2021 • 203