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 Table of Contents  
Year : 2022  |  Volume : 19  |  Issue : 4  |  Page : 142-145

Rhabdomyolysis: A rare and often-missed complication of diabetic ketoacidosis

1 Department of Paediatrics, Lagos University Teaching Hospital, Lagos, Nigeria
2 Department of Paediatrics, Endocrinology and Metabolism Unit, College of Medicine, Lagos University Teaching Hospital, Lagos, Nigeria

Date of Submission12-Jun-2022
Date of Acceptance13-Oct-2022
Date of Web Publication09-Nov-2022

Correspondence Address:
Dr. Elizabeth Eberechi Oyenusi
Department of Paediatrics, Endocrinology and Metabolism Unit, College of Medicine, Lagos University Teaching Hospital, Lagos
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcls.jcls_46_22

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A 19-year-old male with type 1 diabetes mellitus (diagnosed at 12 years of age) was brought to the emergency room with fever and altered sensorium. His compliance with his insulin regimen was questionable. Examination revealed a Glasgow Coma Scale of 5/15, sluggishly-reacting pupils, severe dehydration, and fever (temperature 38.8°C). Vital signs at the upper limit of normal, urethral catheter drained dark red urine with output of 1–2 ml/kg/hr. Laboratory investigations showed hyperglycemia (250 mg/dL), ketonuria (+) hematuria (+++) and proteinuria (++), and glycated hemoglobin (HbA1C) – 9.6%. Full blood count showed leukopenia, neutrophilia, and thrombocytopenia. Deranged electrolytes included hypernatremia, metabolic acidosis, and hypophosphatemia with elevated urea and blood urea nitrogen. Serum creatinine kinase (CK) was elevated. A diagnosis of diabetic ketoacidosis (DKA) with rhabdomyolysis (RM) and raised intracranial pressure was made and he was managed with adequate fluid resuscitation, osmotic diuresis, glycemic control, platelet transfusion, and antibiotics with clinical improvement. Normal CK levels were documented 3 months later. RM is a rare complication of DKA. High index of suspicion should be maintained for prompt detection and management to prevent potential complications, especially acute kidney injury.

Keywords: Diabetic ketoacidosis, hypophosphatemia, rhabdomyolysis, type 1 diabetes

How to cite this article:
Oleolo-Ayodeji KO, Salako HO, Moronkola OA, Oyenusi EE, Oduwole AO. Rhabdomyolysis: A rare and often-missed complication of diabetic ketoacidosis. J Clin Sci 2022;19:142-5

How to cite this URL:
Oleolo-Ayodeji KO, Salako HO, Moronkola OA, Oyenusi EE, Oduwole AO. Rhabdomyolysis: A rare and often-missed complication of diabetic ketoacidosis. J Clin Sci [serial online] 2022 [cited 2023 Mar 20];19:142-5. Available from: https://www.jcsjournal.org/text.asp?2022/19/4/142/360621

  Introduction Top

Rhabdomyolysis (RM), a potentially life-threatening condition describes the rapid breakdown of striated muscle resulting in leakage of the intracellular contents into the circulation.[1],[2],[3],[4] It is characterized by the triad of muscle weakness, myalgia, and dark urine.[3.4] Causes are classified into three: traumatic, nontraumatic exertional, and nontraumatic nonexertional.[3] Some specific causes are trauma, drugs, infections, hyperthermia, and metabolic abnormalities including diabetic emergencies.[1],[3],[4],[5],[6] Historically, Casteels et al[5] cited a report of the first case of RM in diabetic ketoacidosis and several other reports have followed thereafter. Although RM may be asymptomatic, it can also be lethal by causing acute kidney injury and severe electrolyte derangements with attendant morbidity and mortality.[2],[3],[7] High index of suspicion is necessary for diagnosis, owing to its subtle presentation and need for early intervention to prevent associated complications, hence this case report.

  Case Report Top

A 19-year-old male adolescent, a known patient of the endocrinology unit with type 1 diabetes mellitus (T1DM) diagnosed 7 years prior was brought to the emergency room with complaints of fever and generalized body weakness of 4 days duration and unresponsiveness of a day's duration. The fever was high grade, intermittent and temporarily relieved by paracetamol with associated anorexia but no vomiting. The generalized weakness was associated with body pains. There was no prior history of trauma, physical exertion, or substance abuse. A day before presentation, he was said to be unresponsive to call and stimulation. There was no convulsive episode. He was taken to a private hospital where the random plasma glucose was 350 mg/dl (normal for his age in T1DM: 90–120 mg/dl). He was being given glargine (Lantus®) and Humalog Mix-25 insulins at 0.8 units/kg/day. He had been prescribed short-acting insulin previously but the parents erroneously procured a premixed insulin instead. Intravenous antibiotics (names unknown) were also administered. He was subsequently referred to our facility due to poor response.

He had been planned to be transitioned to the adult clinic at 18 years of age but defaulted due to the COVID-19 pandemic until he was brought into the emergency room. The patient's compliance with insulin regimen while in the hostel could not be totally ascertained. He had no previous abnormal renal function tests. He neither smokes cigarettes, marijuana, or any other substances nor takes alcohol. The patient's father is being managed for type 2 DM diagnosed about 25 years prior.

On examination, he was unconscious (Glasgow Coma Scale-5/15), severely dehydrated, and febrile (temperature – 38.8°C) with sluggishly reactive pupils. He had Kussmaul respiration with a rate of 30 cycles/min. His blood pressure was 130/80 mmHg and his pulse was 100 bpm and feeble. His breath sounds were normal in intensity with no added sounds. The first and second heart sounds were heard with no murmurs. Abdominal examination revealed no organomegaly. A urethral catheter inserted was draining dark red urine with output of 1–2 ml/kg/hr. His weight on admission was 85 kg (between 75th and 90th percentile according to the Centre for Disease Control growth charts).

Initial laboratory investigations showed hyperglycemia (250 mg/dL), urinary dipstick revealed: ketonuria (+) blood (+++) and proteinuria (++) while HbA1c was 9.6% (higher than the target for good glycemic control of <6.5%). Full blood count (FBC) showed leukopenia, neutrophilia, and thrombocytopenia. Results of serum electrolytes at admission showed hypernatremia, low bicarbonate, increased anion gap, and low phosphate. The serum urea and blood urea nitrogen (BUN) were mildly elevated. Other details of serial investigations are shown in [Table 1].
Table 1: Results of laboratory investigations

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In view of the dark red urine from the catheter, there were considerations of a possible traumatic catheterization or kidney conditions causing hematuria and also the possibility of myoglobinuria (the dipstick test for blood detects the peroxidase activity of erythrocytes but myoglobin and hemoglobin also will catalyze this reaction). Urine microscopy showed no red blood cells, red cell casts or granular casts, ruling out acute glomerulonephritis or actual hematuria secondary to trauma, and making myoglobinuria a likely cause of the positive dipstick reaction. A presumptive diagnosis of DKA complicated by RM (based on generalized body weakness, body pains, red urine, and associated hypophosphatemia) was made and serum creatine kinase (CK) was requested. The presence of sluggishly-reactive pupils and altered consciousness suggested increased intracranial pressure.

Management of the patient included correction of dehydration using an initial bolus of 20 ml/kg of normal saline over 1 h, thereafter the rest of the rehydration fluid (80 ml/kg) was given along with the maintenance fluid over 48 h. Soluble (short-acting) insulin infusion was started at 0.05u/kg/h (4.3u) due to the random plasma glucose of 250 mg/dl. His plasma glucose was monitored hourly using a bedside glucometer: If plasma glucose rose higher than 250 mg/dl, normal saline infusion and insulin rate of 0.1u/kg/hour, (8.5u) was instituted while with a plasma glucose of 250 mg dl and below, 5% dextrose saline and an insulin rate of 0.05u/kg/h were used. Potassium was replaced by adding 20 mmol of 15% potassium chloride to each 500 ml of fluid. Urinary ketones were checked two hourly. There were no facilities for checking blood ketones. Intravenous ceftriaxone was administered at the rate of 1 g twelve hourly for 5 days due to probable sepsis based on the FBC that was suggestive of sepsis and fever in the patient. He was also transfused with two pints of platelets. Increased intracranial pressure was managed with an infusion of mannitol at 0.5 g/kg given over 15 min.

DKA resolved with correction of electrolytes derangement and improvement in his clinical condition and the patient commenced on oral feeds and transitioned to subcutaneous insulin with long-acting glargine, (Lantus®) 27 units at night and short-acting insulin (Humulin R®) 13 units prebreakfast, 14 units prelunch and 12 units predinner. Insulin dosing was subsequently titrated with the results of his 8-point plasma glucose profile to achieve normoglycemia. Due to financial constraints, the serum creatine kinase could not be done till the 5th and incidentally the last day on admission and it was markedly increased as shown in [Table 1]. He was subsequently discharged since he was clinically stable and is being followed up with self-home plasma glucose monitoring and administration of subcutaneous insulin at home. Deranged electrolytes, urea, and BUN had reverted to normal at discharge while serum CK done at 3 months of follow-up had normalized as shown in [Table 1].

  Discussion Top

DKA is a nontraumatic nonexertional cause of RM as occurred in our patient.[1],[8],[9] In a study by Wang et al.,[6] 20% of patients admitted with diabetic emergencies developed RM with 13 out of 116 of those with DKA being affected. Among the significant differences between the patients, those with RM had significantly higher BUN than those without RM. Our patient had elevated BUN even though not markedly elevated.

With regard to the duration of diabetes and risk of RM, a significant association between increased mean T1DM duration (≥5 years) and DKA patients with RM has been reported[10] similar to our patient who had been diagnosed 7 years prior.

Not much is reported on the epidemiology of RM; however, a recent review[8] documented that annually, about 26,000 cases are reported in the United States. In addition, the incidence is noticed to be higher in African Americans, males, obese patients, and individuals aged ≤10 years and ≥60 years.

Other associated factors present in the index patient such as hypophosphatemia could also have contributed to the occurrence of RM as in other reports.[5],[7],[10],[11],[12] It is also noteworthy that increased BUN is documented as one of the reliable predictors for the occurrence of RM in patients with hypophosphatemia[12] making our patient doubly susceptible to RM.

Intracellular phosphate shifting in severe prolonged ketoacidosis and insulin infusions for correction of hyperglycemia can lead to reduced serum phosphate levels. In addition, there is an initial increase in urinary phosphate secretion as a reaction to an acidemia-induced inhibition of phosphate proximal tubular reabsorption. As a result, prolonged hypophosphatemia can cause RM from cellular injury secondary to decreased intracellular concentration of adenosine triphosphate and 2,3 diphosphoglycerate.[4],[7],[13] There are varied schools of thought on routine phosphate replacement in DKA.[14],[15]

In the study by Wang et al.[6] on “RM in diabetic emergencies,” most patients with RM were detected by muscle enzyme studies and had showed no clinical features of RM, and so were described as subclinical. This could be attributed to the extent of muscle injury.[6] Considering that subclinical RM is common in diabetic emergencies, routine screening of RM in diabetic emergencies is important in view of its high mortality rate and RM-associated acute renal failure.[6]

The management of RM includes fluid resuscitation and prevention of renal injury and specific treatment of the precipitating condition.[8]


Tests to demonstrate the elevation of serum myoglobin concentration could not be done due to the unavailability of the investigation in our facility and unaffordability outside the facility. However, since the elevation of serum myoglobin concentration can be seen in cardiac muscle injury as well, its presence alone is said not to be sensitive enough to diagnose RM. Many authors report that the elevation of CK above 1000 or 5-fold is usually enough to make a diagnosis of RM.[4],[6]

In conclusion, RM can complicate DKA, especially in patients with hypophosphatemia and increased BUN. Appropriate measures should be taken to prevent acute renal failure with attendant morbidity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Authors' Contributions

All authors were involved in management of the case. OKO and OEE drafted the manuscript. All authors read and approved the final manuscript for submission.


The authors would like to thank the patient and his parents for consent and permission to use the patient's information for the purpose of this report.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Sauret JM, Marinides G, Wang GK. Rhabdomyolysis. Am Fam Physician 2002;65:907-12.  Back to cited text no. 1
Grossman RA, Hamilton RW, Morse BM, Penn AS, Goldberg M. Nontraumatic rhabdomyolysis and acute renal failure. N Engl J Med 1974;291:807-11.  Back to cited text no. 2
Amin A, Gandhi B, Torre S, Amirpour A, Cheng J, Patel M, et al. Rhabdomyolysis-induced acute kidney injury in diabetic emergency: Underdiagnosed and an important association to be aware of. Case Reports in Medicine, 2018:Article ID 4132738. https://doi.org/10.1155/2018/4132738.  Back to cited text no. 3
Mannix R, Tan ML, Wright R, Baskin M. Acute pediatric rhabdomyolysis: Causes and rates of renal failure. Pediatrics 2006;118:2119-25.  Back to cited text no. 4
Casteels K, Beckers D, Wouters C, Van Geet C. Rhabdomyolysis in diabetic ketoacidosis. Pediatr Diabetes 2003;4:29-31.  Back to cited text no. 5
Wang LM, Tsai ST, Ho LT, Hu SC, Lee CH. Rhabdomyolysis in diabetic emergencies. Diabetes Res Clin Pract 1994;26:209-14.  Back to cited text no. 6
Al-Matrafi J, Vethamuthu J, Feber J. Severe acute renal failure in a patient with diabetic ketoacidosis. Saudi J Kidney Dis Transpl 2009;20:831-4.  Back to cited text no. 7
[PUBMED]  [Full text]  
Gupta A, Thorson P, Penmatsa KR, Gupta P. Rhabdomyolysis: Revisited. Ulster Med J 2021;90:61-9.  Back to cited text no. 8
Al-Azzawi OF, Razak MK, Al Hammady SJ. Rhabdomyolysis; is it an overlooked DKA complication. Diabetes Metab Syndr 2019;13:3047-52.  Back to cited text no. 9
Li W, Gong C, Wu D, Liu M. Two case reports of severe pediatric hyperosmolar hyperglycemia and diabetic ketoacidosis accompanied with rhabdomyolysis and acute renal failure. J Pediatr Endocrinol Metab 2014;27:1227-31.  Back to cited text no. 10
Kutlu AO, Kara C, Cetinkaya S. Rhabdomyolysis without detectable myoglobulinuria due to severe hypophosphatemia in diabetic ketoacidosis. Pediatr Emerg Care 2011;27:537-8.  Back to cited text no. 11
Singhal PC, Kumar A, Desroches L, Gibbons N, Mattana J. Prevalence and predictors of rhabdomyolysis in patients with hypophosphatemia. Am J Med 1992;92:458-64.  Back to cited text no. 12
Zierler KL. Increased muscle permeability to aldolase produced by depolarization and by metabolic inhibitors. Am J Physiol 1958;193:534-8.  Back to cited text no. 13
Amanzadeh J, Reilly RF Jr. Hypophosphatemia: An evidence-based approach to its clinical consequences and management. Nat Clin Pract Nephrol 2006;2:136-48.  Back to cited text no. 14
Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, et al. ISPAD Clinical practice consensus guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes 2018;19 Suppl 27:155-77.  Back to cited text no. 15


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