Pleiotropic Effects of Cocaine Abuse in Hyperglycemic Crisis: Main Culprit or Accomplice but Never an Innocent Bystander

Abstract

Hyperglycemic crises, including diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS), significantly affect clinical outcomes and impose a heavy economic burden. Among the steadily increased recreational drug abuse, cocaine has become the most frequently misused substance. However, there is limited understanding of the relationship between cocaine use and hyperglycemic crises. We report 4 cases retrospectively to examine the relationship between cocaine abuse and DKA/HHS. In Case 1, a patient with Type 1 diabetes mellitus (T1DM) presented with altered mental status and a combination of DKA and HHS, where cocaine use led to missed insulin doses, resulting in the crisis. Case 2 involved the same patient who later developed DKA due to cavitary pneumonia and sepsis, requiring mechanical ventilation, vasopressors, and renal replacement therapy. Cocaine inhalation caused pulmonary damage that triggered DKA. Case 3 involved a patient with Type 2 diabetes mellitus (T2DM) who abused cocaine intravenously, leading to DKA-HHS and necrotizing fasciitis that required emergency surgery. Case 4 was a patient with obesity, insulin resistance, and T2DM on oral medications, where cocaine likely exacerbated insulin resistance and triggered DKA. In all 4 cases, treatment focused on aggressive rehydration, insulin infusion, electrolyte correction, and addressing underlying causes. The hyperglycemic crises resolved within 12 to 24 hours. However, managing cocaine-related complications proved difficult, leading to high morbidity and mortality rates, including altered mental status with airway issues, kidney failure, rhabdomyolysis, and infections that could result in septic shock or death. In Case 4, cocaine use significantly worsened insulin resistance and T2DM, contributing to DKA. In conclusion, cocaine abuse has multiple effects and can act as an unusual trigger for hyperglycemic crises by causing missed insulin doses, dehydration, infections, and chronic worsening of insulin resistance. Cocaine abuse can trigger and/or worsen hyperglycemic crises through various mechanisms, such as damage to the cardiopulmonary and renal systems, psychosocial changes, weakened immunity and infections, and alterations in hormones and metabolism (Figure 3). We suggest incorporating questions about substance abuse into routine patient history assessment and performing toxicology screenings, particularly for individuals who have frequent admissions for DKA/HHS. Additionally, we share our expertise in managing this specific group of patients.

Plain language summary

Hyperglycemic crises, including diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS), significantly impact clinical outcomes and impose a substantial economic burden. Cocaine has emerged as the most frequently misused substance; however, it remains unclear whether cocaine abuse can lead to hyperglycemic crises. Our objective is to investigate the relationship between cocaine abuse and hyperglycemic crises. We conducted a retrospective analysis of four cases to explore this association.We shared our experience in managing these complex clinical scenarios and recommend incorporating drug toxicology screening into patient history assessment and laboratory tests.

Introduction

The hyperglycemic crisis is a serious metabolic complication of diabetes, which includes diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS), affecting both type 1 (T1DM) and type 2 diabetes (T2DM). The US Centers for Disease Control and Prevention reports a steady increase in DKA cases, with hospitalizations rising from 140 000 in 2009 to 220 340 in 2017, ¹ marking a 54.9% increase per 1000 patient years between 2009 and 2014. ² The cost of treating DKA in the US was $5.1 billion in 2014, with an average cost of $26 566 per episode, ³ which rose to $6.76 billion in 2017, averaging about $31 000 per hospitalization. ² The incidence of HHS was reported at 16.5% for T1DM and 3.9% for T2DM per 10 000 person-years. ⁴ While the mortality rate for DKA is below 1%, ⁵ it can reach up to 20% for HHS, depending on comorbidities and the severity of the case, with the highest mortality seen in patients with both DKA and HHS. ⁶

Identifying the triggers for DKA and HHS is crucial for early prevention, diagnosis, and management, which can improve outcomes and reduce healthcare costs. Noncompliance with treatment is the most prevalent factor, occurring in 45% to 50% of cases, followed by infections, which account for approximately 26%. ⁷ Other contributing factors include pancreatitis, acute myocardial infarction, and strokes. ⁷ Furthermore, a study found that 20.6% of patients experiencing a hyperglycemic crisis had a history of active substance abuse, with cocaine being the most commonly used substance, followed by cannabis and alcohol. ⁸ Research also indicates that 13% of adult DKA patients and 9% of patients with HHS reported cocaine use, which may be relate to missed insulin therapy and alterations in counter-regulatory hormones.^9,10 Additionally, cocaine use is associated with an increased risk of heart attacks, strokes, and arrhythmias, and an independent risk factor for recurrent DKA.^9-11 Nevertheless, evidence linking cocaine abuse to hyperglycemic complications remains limited.

Patients with cocaine intoxication and DKA/HHS have high mortality rates. Managing these conditions is challenging, and there is limited data on effective treatment strategies. A case study showed that a patient with DKA and cocaine intoxication had severe hypothermia; and was successfully treated using a cardiac arrest rewarming protocol and a rigorous DKA management protocol. ¹² The consensus report regarding hyperglycemic crises in adults with diabetes pointed out that low socioeconomic and psychological factors are related to hyperglycemic crises; but failed to demonstrate the causative link of substance abuse with hyperglycemic crises and their management. ¹³

In this article, we present 4 cases involving 3 patients who were cocaine users and were admitted for DKA, HHS, or both. This study aims to identify a potential link between cocaine abuse and hyperglycemic crises, such as DKA and HHS. We also share our experience in managing this group of patients.

Case Description

Case 1

A 49-year-old man with a medical history of hypertension, T1DM, and cocaine use presented to the emergency department (ED) due to altered mental status (AMS). He was taking 30 units of insulin glargine and 15 units of insulin lispro before meals, with no other significant health issues. He was found unconscious in his vomit, with a crack pipe nearby. At the scene, his blood pressure was 86/40 mmHg and heart rate was 89 beats per minute. He was administered Narcan and a 1-L normal saline infusion. Upon arrival at the ED, he was only able to recognize his name, scoring 13 on the Glasgow Coma Scale (GCS; E3 V4 M6). His vital signs included a temperature of 95.0°F, heart rate of 97 beats per minute, respiratory rate of 24 breaths per minute, blood pressure of 80/47 mmHg, and oxygen saturation of 94% on room air, with a body mass index (BMI) of 18.8 (Table 1). He exhibited Kussmaul respirations and appeared severely dehydrated, with clear lung sounds and no heart murmurs. Laboratory results showed a glucose level of 1.515 mg/dL, anion gap of 39.1 mmol/L, bicarbonate of 7.9 mmol/L, potassium of 7.6 mmol/L, blood urea nitrogen (BUN) of 98 mg/dL, creatinine of 4.4 mg/dL, and an estimated glomerular filtration rate (eGFR) of 17.4 ml/min/1.73 m². Serum acetone was positive, serum osmolality was 379 mOsm/kg, hemoglobin A1C (HbA1c) was 14%, and arterial blood gas (ABG) results indicated a pH of 7.12, O₂ of 113 mmHg, CO₂ of 20 mmHg, and bicarbonate of 6 mmol/L. His white blood cell count (WBC) was 24.9 × 10⁹/L, urinalysis showed hyaline casts with positive glucose, ketones, and 1 + protein, and a urine drug screen (UDS) was positive for cocaine (Table 2). A CT scan of the head was normal. He was diagnosed with combined DKA and HHS due to cocaine use, along with acute renal failure (ARF), volume depletion, and hypothermia. He was admitted to the intensive care unit (ICU) for rewarming, lactated Ringer’s infusion, and an insulin drip as per protocol. His hypotension improved with fluid administration, and ampicillin/sulbactam was added for suspected aspiration pneumonia, although cultures returned negative. Within 12 hours, his DKA-HHS resolved, and he was downgraded for further supportive care. His creatinine level decreased to 1.5 mg/dL (eGFR 48), and he was discharged home on day 4 with instructions to continue his insulin regimen.

Table 1.

Clinical characteristics.

	Case 1	Case 2	Case 3	Case 4
Age (y)	49	51	67	46
Gender (M/F)	M	M	F	M
BMI (kg/m2)	23	22	41	33.5
Cocaine use	Smoking	Smoking	Injection	Smoking
Marijuana use	Yes	Yes	No	No
Alcohol use	Yes	Yes	Yes	No
Opioid use	No	No	No	No
Current smoker	Yes	Yes	Yes	Yes
Diabetic medications	Insulin	Insulin	Oral medications	Oral medications
Family history of diabetes	No	No	No	Yes
Infection	No	Cavitary pneumonia	Necrotizing fasciitis	No
Comorbidities	HTN, depression	CKD stage II, HTN	HTN, CKD stage II	HTN, PE on Eliquis
Temperature (°F)	95	97.7	96.2	97.7
BP (mmHg)	80/47	90/50	103/64	147/93
HR (beats per min)	97	148	106	125
RR (breaths per min)	24	26	34	18
SaO2 (%) on room air	94%	80%	90%	96%
DKA/HHS	DKA-HHS	DKA	DKA-HHS	DKA
Mechanical ventilation	No	Yes	Yes	No
Vasopressors	No	Yes	Yes	No
Mortality	No	Yes	No	No

Abbreviations: CKD, chronic kidney disease; DKA, diabetic ketoacidosis; HTN, hypertension; T1DM, type 1 diabetes; T2DM, type 2 diabetes.

Table 2.

Laboratory data at time of arrival and 24 hours.

	Reference range	Case 1		Case 2		Case 3		Case 4
		Arrival	24 h	Arrival	24 h	Arrival	24 h	Arrival	24 h
Chemistry
Sodium (mmol/L)	136-145	130	152	135	141	130	140	132	137
Potassium (mmol/L)	3.5-5.3	7.6	3.9	4.1	5.0	6.8	5.2	3.8	4.1
Chloride (mmol/L)	98-110	83	112	101	110	95	110	101	106
Calcium (mg/dL)	8.6-10.4	8.7	8.5	9.1	8.9	9.2	9.4	9.0	8.5
Magnesium (mg/dL)	1.5-2.5	3.2	2.6	2.0	2.1	2.5	2.0	1.8	2.1
Bicarbonate (mmol/L)	20-16	7.9	29.9	17.1	27.5	8.6	21.6	13.3	22.1
Anion gap (mmol/L)	6-12	39.1	4.9	14.9	3.5	26.4	9.7	17.7	10.9
Glucose (mg/dL)	70-140	1515	250	483	174	1393	376	396	232
Hemoglobin A1c (%)	4-5.6	13	/	11.3	/	10.5	/	11.4	/
Serum ketones	-	+	-	+	-	+	-	+	-
BUN (mg/dL)	6-24	98	65	30.0	42	105	108	22	14
Creatinine (mg/dL)	0.6-1.2	4.4	1.9	4.2	4.1	2.49	2.67	1.65	1.09
GFR (ml/min/1.73 m2)	>90	17.4	45.9	13.0	13.5	30.5	25.7	65.0	84.4
Liver function
AST (U/L)	10-36	130	/	39	/	15	/	42	/
ALT (U/L)	9-46	54	/	18	/	22	/	41	/
AKP (U/L)	40-115	126	/	130	/	152	/	82	/
Albumin (g/dL)	3.6-5.1	2.3	/	2.5	/	2.1	/	4.3	/
Others
Lactic acid (mmol/L)	0-2.1	2.1	/	3.83	5.40	2.9	3.1	-	/
Troponin (ng/L)	<54	30	/	38	/	29	/	31	/
Lipase (U/L)	12-53	75	/	50	/	44	/	45	/
CK (U/L)	52-336	510	/	280	/	488	480	230	/
Urinalysis
Ketones	-	1+	/	1+	/	+	/	+	/
Protein	-	1+	/	4+	/	2+	/	-	/
Hyaline casts	-	+	/	+	/	+	/	-	/
Leukocyte esterase	-	-	/	-	/	-	/	-	/
Nitrates	-	-	/	-	/	-	/	-	/
Lipid panel
Triglyceride (mg/dL)	0-150	110	/	115	/	135	/	139	/
HDL (mg/dL)	>40	80	/	75	/	80	/	57	/
LDL-c (mg/dL)	<100	105	/	110	/	125	/	99	/
Blood count
WBC (× 103/µL)	3.5-10.5	24.9	11.3	6.8	6.9	27.8	18.8	9.8	8.5
RBC (× 106/µL)	4.32-5.72	3.02	3.44	3.96	3.97	5.24	5.2	5.0	5.1
Hemoglobin (g/dL)	13.5-17.5	10.3	11.5	13.0	12.6	11.5	11.2	14.3	14.6
Platelets (× 103/µL)	150-450	332	272	212	202	441	352	280	231
Blood coagulation
PT (s)	9.4-12.4	12.6	/	12.9	/	12.5	/	10.7	/
APTT (s)	23-32	30.8	/	35.7	/	30.2	/	25.5	/
INR	0.83-1.17	1.12	/	1.16	/	1.19	/	0.96	/
Auto-antibodies
Anti-islet cell	-	/	/	/	/	-	/	-	/
Anti-GAD	-	/	/	/	/	-	/	-	/

Abbreviations: AKP, alkaline phosphatase; APTT, activated partial thromboplastin time; BUN, blood urea nitrogen; GAD, anti-glutamic acid decarboxylate antibody; INR, International normalized ratio; PT, prothrombine time; −: negative; +: positive; /: missing data.

Case 2

Two years later, the patient was readmitted to the ICU due to a cough and worsening shortness of breath that had persisted for 3 days. He was in respiratory distress but remained fully conscious. His vital signs included a temperature of 97.7°F, heart rate of 148, respiratory rate of 26, blood pressure of 90/50, and oxygen saturation of 80%, requiring bi-level positive airway pressure support (Table 1). He exhibited rapid breathing, dullness on percussion, and inspiratory crackles, but there were no signs of jugular vein distention or heart murmurs. Laboratory results showed a blood glucose level of 483 mg/dL, an anion gap of 14.9 mmol/L, bicarbonate at 17.1 mmol/L, positive acetone in both serum and urine, BUN of 105 mg/dL, creatinine of 4.1 mg/dL, eGFR of 13.2 ml/min/1.73 m², HbA1c of 10.6%, and normal coagulation tests. A venous blood gas (VBG) indicated a pH of 7.27 and bicarbonate of 15 mmol/L. Urinalysis revealed 4 + protein, hyaline casts, and a urine drug screen positive for cocaine (Table 2). Tests for COVID-19, influenza, and respiratory syncytial virus were negative. Troponin levels were negative, B-type natriuretic peptide was normal, and left ventricular ejection fraction (LVEF) was decreased at 35% (compared to 55% during the previous admission). A CT scan of the chest showed multifocal cavitary pneumonia (Figure 1). He was diagnosed with acute hypoxemic respiratory failure (AHRF) due to necrotizing pneumonia, sepsis, DKA, and heart failure with reduced ejection fraction (HFrEF). Treatment included empirical administration of ceftriaxone, azithromycin, and metronidazole, along with an insulin drip and careful fluid management due to HFrEF. The tuberculosis QuantiFeron test was negative, and acid-fast bacilli cultures were pending. His respiratory condition worsened, leading to intubation and mechanical ventilation, and his blood pressure dropped, requiring vasopressors a few hours later. Blood cultures confirmed methicillin-susceptible Staphylococcus aureus (MSSA), prompting a change in antibiotics to cefazolin. A transesophageal echocardiogram ruled out endocarditis. Bronchoscopy revealed secretions but negative microbiology and cytology results, with no signs of hemorrhage. He remained oliguric, and hemodialysis was started on day 3. The following day, he was transferred to a tertiary hospital for continuous renal replacement therapy (CRRT) due to ongoing low blood pressure requiring vasopressors. After tapering off the vasopressors, he received a tunneled hemodialysis catheter for hemodialysis (HD) and was extubated to room air on day 9. On day 11, he underwent placement of a percutaneous endoscopic gastrostomy tube due to oropharyngeal dysphagia and was being prepared for discharge to a rehabilitation facility. However, the next day, he experienced an in-hospital pulseless electrical activity arrest (PEA) and died despite resuscitation efforts.

Figure 1.

CT chest showing multifocal cavitary pneumonia for case 2. There are multiple patchy foci of airspace opacities within both lungs, some of them are cavitary in nature, suggesting cavitary pneumonia as pointed by the arrows.

Case 3

A 67-year-old woman with a medical history of stage II chronic kidney disease, intravenous cocaine use, and poorly managed T2DM on oral medications was brought to the ED due to confusion. She lived alone, and her son had spoken to her 3 days prior, noting she had a cold and was taking over-the-counter cough medicine. Upon arrival, she was lethargic, with a Glasgow Coma Scale score of 7/15 (E1V2M4). Her initial vital signs were a temperature of 96.2°F, heart rate of 106, respiratory rate of 34, blood pressure of 103/64, and oxygen saturation of 90% (Table 1). A physical examination of her heart and lungs showed no significant issues, but she exhibited rapid breathing and an increased heart rate. She was intubated for airway protection. An examination revealed an ulcer on her left gluteus, and a CT scan indicated significant soft tissue swelling and subcutaneous air in the left gluteus, raising suspicion for necrotizing fasciitis, along with a small abscess in the right gluteus (Figure 2). Laboratory tests showed a blood glucose level of 1393 mg/dL, an anion gap of 26.4 mmol/L, bicarbonate at 8.6 mmol/L, BUN at 30 mg/dL, creatinine at 2.1 mg/dL, eGFR at 36.2 ml/min/1.73 m², serum osmolality at 375 mOsm/kg, A1c at 11.1%, and WBC at 27.8 × 10⁹/L (Table 2). An arterial blood gas analysis indicated a pH of 7.12 and bicarbonate at 15.7 mmol/L. Urinalysis was positive for ketones and coarse granular casts, and a urine drug screen was positive for cocaine. She was diagnosed with combined DKA and HHS, sepsis, necrotizing fasciitis, acute cocaine intoxication, acute toxic metabolic encephalopathy, acute hypoxic respiratory failure, and acute renal failure. Treatment included fluids, an insulin infusion, and empirical antibiotics (vancomycin, cefepime, and metronidazole). She underwent emergency incision and drainage of the left gluteal area and perineum, along with excisional debridement of skin and soft tissue, followed by another sharp debridement on day 3 and a transverse loop diverting colostomy on day 5 to prevent fecal contamination. Tissue cultures identified Enterococcus species and E. coli, leading to a change in antibiotics to ampicillin/sulbactam. The DKA-HHS resolved within 12 hours. She was weaned off vasopressors and extubated on day 6. Her non-oliguric acute renal failure gradually improved, returning to a baseline creatinine level of 1.2 mg/dL. The wound showed signs of healing. She was discharged to a rehabilitation facility on day 10 with a regimen of 40 units of daily basal and postprandial insulin, along with a 10-day course of amoxicillin/clavulanic acid and doxycycline. During her follow-up visit, her C-peptide level was 2.5 (reference range 0.5 to 2.7 ng/mL), and she tested negative for auto-antibodies related to islet cells and glutamic acid decarboxylase (GAD; Table 2). Her insulin regimen was adjusted to oral hypoglycemic agents such as empagliflozin and sitagliptin/metformin.

Figure 2.

CT scan showing extensive soft tissue swelling and subcutaneous air in the left gluteus suspicious for necrotizing fasciitis and small abscess in the right gluteus for case 3. CT scan of pelvis: Extensive subcutaneous air and soft tissue swelling within the medial left gluteal region tracking anterior (L, thin arrow) as well as within the medial right gluteal region inferiorly (thick arrow) correlating with necrotizing fasciitis. There is a 2.2 × 1.3 × 2.0 cm superficial fluid collection in the medial left gluteal area in the superficial soft tissue, posterior to the inferior coccyx (thin arrow). This finding represents abscess formation. Air is also seen extending into the inferior posterior peritoneum on the left with no intra-abdominal fluid collection.

Case 4

A 46-year-old man with a medical history of hypertension, a 6-year history of well-managed T2DM treated with metformin, a pulmonary embolism on Apixaban, and a history of cocaine abuse was admitted to the ED from a cocaine rehabilitation facility due to experiencing 5 hours of widespread abdominal pain. Upon arrival, his vital signs were: temperature 97.7°F, heart rate 125, respiratory rate 18, blood pressure 147/93, and oxygen saturation 98% on room air (Table 1). He was fully alert and oriented. A physical examination of his heart and lungs showed no abnormalities, while his abdomen was soft with mild tenderness throughout. Laboratory results indicated a glucose level of 396 mg/dL, bicarbonate of 13.3 mmol/L, an anion gap of 17.7 mmol/L, positive serum acetone, a BUN of 22 mg/dL, creatinine of 1.51 mg/dL, an eGFR of 51.5 ml/min/1.73 m², and an A1c of 11.4% (Table 2). Troponin levels were negative, and white blood cell counts were normal. Urinalysis showed ketones but no signs of infection, but a urine drug screen was positive for cocaine. An arterial blood gas analysis revealed a pH of 7.28 and bicarbonate of 14 mmol/L (Table 2). A CT scan of the abdomen showed no intra-abdominal issues, and cultures were negative for infection. He was diagnosed with diabetic ketoacidosis (DKA) due to acute cocaine intoxication and poorly controlled T2DM. He received 2 L of lactated Ringer’s solution and 2 intravenous pushes of 10 units of regular insulin, spaced 2 hours apart. Follow-up lab results after 6 hours indicated that the DKA had resolved. He was able to eat and was switched to subcutaneous basal insulin and metformin before discharge. His body mass index was 34 kg/m², C-peptide level was 2.9 ng/mL, and he tested negative for islet cell and glutamic acid decarboxylase auto-antibodies, but exhibited significant insulin resistance as shown by elevated values of Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), triglyceride-glucose index (TyG), and the ratio of triglycerides (TG) to high-density lipoprotein (HDL; Table 3). He was transitioned to a regimen of metformin, empagliflozin, and sitagliptin.

Table 3.

Lipid profile and insulin resistance markers for case 4.

Lipid profile	Reference range	Values	IR markers	Reference range	Values
Glucose (mg/dL)	70-140	372
HDL (mg/dL)	⩾40	32.2	HOMA-IR	0.5-1.4	18.5
LDL (mg/dL)	⩽100	99	TyG	<4.5	6.04
Triglyceride (mg/dL)	0-150	476	TG/HDL-c	<6.0	14.78

Abbreviations: HOMA-IR, homeostasis model assessment for insulin resistance; TG/HDL-c, the ratio of triglycerides (TG) to high-density lipoprotein (HDL); TyG, triglyceride-glucose index.

Discussion

We documented 4 cases of poorly managed diabetes that resulted in hyperglycemic crises (DKA/HHS or both) in conjunction with cocaine use or intoxication. The first 2 patients (cases 1 and 2) had T1DM, while the other 2 (cases 3 and 4) had T2DM. All 4 cases successfully resolved their hyperglycemic crises. Research indicates that active cocaine use was present in 13% of adult DKA patients and acted as an independent risk factor for recurrent DKA.^10,11 Another study found that cocaine use was reported in approximately 17% of patients experiencing hyperglycemic crises; however it lacked sufficient statistical power to establish a strong link between cocaine use and hyperglycemic crises. ¹⁴ This discrepancy may be attributed to a significantly larger control group compared to the case group, which could skew the estimated odds ratio. ¹⁴ Our case series provides compelling evidence that cocaine serves as an unusual trigger or contributing factor to hyperglycemic crises in both T1DM and T2DM patients, highlighting the novelty of this study.

Case 1 involved a patient with T1DM who likely missed insulin doses, resulting in severe hyperglycemia and hypovolemia, which subsequently lead to DKA and HHS. The hypovolemia was exacerbated by acute cocaine intoxication, which caused hyperthermia, vasoconstriction, and a state of euphoria. The literature indicates that cocaine users are more likely to miss insulin doses compared to non-users the day before hospitalization (45.1% vs 24.7%). ¹¹ Additionally, cocaine mimics the effects of an overactive sympathetic nervous system by disrupting monoamine reuptake, leading to increased levels of norepinephrine, dopamine, and serotonin, ¹⁵ which prolong their effects on their respective receptors. Cocaine toxicity can further impair renal and cardiac functions, potentially resulting in hypotension and hypothermia if hypovolemia persists. In severe cases, cocaine intoxication can lead to encephalopathy, seizures, arrhythmias, apnea, and cardiac arrest. This patient exhibited acute kidney injury (AKI) and rhabdomyolysis, ultimately developing encephalopathy and hypothermia. In this case, cocaine abuse contributed to the patient’s failure to administer insulin, which collectively precipitated his hyperglycemic crisis.

Case 2 involved a patient with a history of chronic cocaine abuse who experienced recurrent DKA, septic shock, cavitary pneumonia, and acute renal failure, necessitating CRRT or hemodialysis. Cocaine addiction increases the risk of infections and can lead to more severe and rapid progression of certain infectious diseases due to compromised cellular immunity.^16,17 There have been reports of cocaine use resulting in severe complications, such as Staphylococcus sepsis. ¹⁸ In our case, the patient developed methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia, which correlated with his cavitary lung lesions, suggesting a Staphylococcus aureus infection likely related to cocaine use or possible aspiration pneumonia due to cocaine-induced encephalopathy. The presence of bacteremia rendered other potential causes of cavitary lung lesions, such as fungal, mycobacterial, or parasitic infections, or vasculitis like Wegener’s granulomatosis,^19,20 less probable. A chest CT scan ruled out pulmonary embolism with infarction, and a negative bronchoalveolar lavage made pulmonary hemorrhage or malignancy unlikely. In this case, cocaine inhalation contributed to pulmonary injury and exacerbated infection-related DKA.

Case 3 involved a patient with T2DM who was on oral glycemic medications and developed a combination of DKA and HHS triggered by intravenous cocaine use and NF. The occurrence of NF in intravenous cocaine users has been documented in the literature. ²¹ In diabetic patients, NF should be suspected as it can mimic non-purulent cellulitis. Signs such as tenderness extending beyond the erythematous area, crepitus, skin changes like ecchymosis or bullae, and paresthesia should raise concerns for NF.^22,23 A CT scan is typically the first imaging choice, ²² but magnetic resonance imaging is considered the gold standard in uncertain cases. NF usually involves polymicrobial infections and can be life-threatening, necessitating urgent surgical debridement, with intraoperative tissue cultures being crucial. ²⁴ Similar to Case 2, cocaine use in Case 3 was closely associated with the exacerbation of infection-related DKA.

Case 4 involved a patient with T2DM who was being treated with oral glycemic medications and presented with obesity and insulin resistance (IR). The only identified factor that triggered the development of DKA was cocaine use. Frequent cocaine consumption may disrupt lipid metabolism, body composition, and plasma leptin levels, all of which are closely associated with IR. Another study indicated that cocaine reduces levels of glucagon-like peptide-1, insulin, and amylin, hormones that are crucial for regulating metabolism and IR. ²⁵ Furthermore, repeated cocaine use activates the signaling pathways of norepinephrine, dopamine, and serotonin, which can affect insulin secretion in response to glucose and alter the structure of pancreatic islets. ²⁶ Cocaine use also diminishes the cortisol response from the hypothalamic-pituitary-adrenal (HPA) axis, leading to lower testosterone levels, which is another risk factor for adrenal insufficiency and exacerbated IR. ²⁷ In this case, the patient’s preserved C-peptide levels and negative autoantibodies ruled out T1DM. Laboratory results indicated dyslipidemia and significant IR. The DKA was mild and resolved quickly with treatment. It is likely that cocaine abuse significantly contributed to the patient’s worsening IR and T2DM, ultimately leading to the onset of DKA.

The primary treatment for cocaine-related hyperglycemic crises involves intensive rehydration, insulin administration, electrolyte balance, and addressing underlying causes. Currently, there are no established guidelines for managing combined DKA and HHS. In our 4 cases, the hyperglycemic crisis was resolved within 12 to 24 hours by adhering to an institutional DKA care protocol. However, addressing cocaine-related comorbidities is challenging yet essential for achieving better outcomes. One major concern is acute toxic metabolic encephalopathy, which may require urgent airway management and mechanical ventilation for protection, particularly in cases of combined DKA-HHS. Caution is advised when using benzodiazepines due to their potential for respiratory depression, even though they are typically the first choice for reducing cocaine-induced sympathetic over-activity. Two of our 4 patients required intubation and mechanical ventilation due to encephalopathy and the need for airway protection. Another issue was cocaine-induced kidney damage complicated by rhabdomyolysis. This kidney injury results from damage to the renal glomeruli, tubules, vasculature, and interstitial tissues due to endothelial dysfunction, oxidative stress, and platelet aggregation. Additionally, conditions such as renal infarction, vasculitis, thrombotic microangiopathy, malignant hypertension, or ischemic acute tubular necrosis can exacerbate kidney damage, leading to acute renal failure that may require renal replacement therapy. All 4 of our cases experienced renal injury, with 2 developing rhabdomyolysis and 1 needing CRRT and then hemodialysis. The third concern is infections and sepsis related to cocaine use, which require appropriate antibiotics and possibly emergency surgery. Case 2 had necrotizing pneumonia with septic shock, which was treated with medication. After a complicated hospital stay, he was eventually able to discontinue vasopressors and mechanical ventilation. Case 3 underwent urgent surgical debridement followed by a diverting colostomy and ultimately recovered well. Lastly, cocaine can lead to heart-related issues such as myocarditis, arrhythmias, hypertensive emergencies, strokes, liver enzyme elevation, or pancreatitis. Case 2 presented with heart failure with reduced ejection fraction, likely due to chronic cocaine-induced hypertension and cardiomyopathy. His initial negative troponin test ruled out acute myocarditis, but he ultimately succumbed to a pulseless electrical activity cardiac arrest during hospitalization. In our cases, cocaine-related hyperglycemic crises were associated with significant morbidity and mortality.

Conclusion

Cocaine abuse can trigger and/or worsen hyperglycemic crises through various mechanisms, such as damage to the cardiopulmonary and renal systems, psychosocial changes, weakened immunity and infections, and alterations in hormones and metabolism (Figure 3). We suggest incorporating questions about substance abuse into routine patient history assessment and performing toxicology screenings, particularly for individuals who have frequent admissions for DKA/HHS. Additionally, we share our expertise in managing this specific group of patients.

Figure 3.

Pleiotropic effects of cocaine abuse in hyperglycemic crisis. Cocaine abuse has pleiotropic acute and chronic toxic effects in causing or precipitating hyperglycemic crisis.

Abbreviations: AI, adrenal insufficiency; AKI, acute kidney injury; NR, necrotizing fasciitis: PE, pulmonary embolism; PNA, pneumonia.