What are the common causes of hypoglycemia in patients with renal failure. How does renal dysfunction contribute to low blood sugar levels. What are the key clinical considerations for managing hypoglycemia in kidney disease patients.

The Prevalence and Significance of Hypoglycemia in Renal Failure

Hypoglycemia occurs more frequently in patients with renal failure than is commonly recognized. Its presence often indicates multi-organ dysfunction and carries a poor prognosis. Understanding the complex pathophysiology and clinical implications of hypoglycemia in the context of kidney disease is crucial for proper management.

Common Triggers and Risk Factors for Hypoglycemia in Renal Patients

Several factors can precipitate or exacerbate hypoglycemia in individuals with kidney dysfunction:

• Medications: Insulin, oral hypoglycemic agents, propranolol, salicylates, disopyramide
• Alcohol consumption
• Sepsis
• Chronic malnutrition or acute caloric deprivation
• Concomitant liver disease
• Congestive heart failure
• Endocrine deficiencies

How do these factors interact with renal dysfunction to increase hypoglycemia risk? The impaired kidney function alters normal glucose homeostasis mechanisms, making patients more susceptible to the blood sugar-lowering effects of medications, infections, and metabolic stressors.

Pathophysiological Mechanisms of Spontaneous Uremic Hypoglycemia

When no obvious trigger is identified, hypoglycemia in renal failure patients is termed “spontaneous uremic hypoglycemia.” Several mechanisms contribute to this phenomenon:

1. Deficiency of gluconeogenesis precursors (e.g., alanine)
2. Impaired gluconeogenesis and glycogenolysis
3. Reduced renal gluconeogenesis
4. Decreased renal insulin degradation and clearance
5. Poor nutritional status
6. Deficiency in counterregulatory hormones (e.g., catecholamines, glucagon)

The relative contribution of these factors may vary between patients, highlighting the complex and individualized nature of hypoglycemia in renal failure.

The Impact of Dialysis on Blood Glucose Regulation

Dialysis treatment itself can influence blood glucose levels in patients with renal failure. Two main mechanisms are involved:

1. Chronic Malnutrition

Long-term dialysis often leads to a state of chronic malnutrition, which predisposes patients to hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis.

2. Post-Dialysis Hypoglycemia

The high glucose content in dialysate can induce hyperinsulinemia, potentially leading to a reactive hypoglycemic episode after the dialysis session concludes.

How can healthcare providers mitigate the risk of dialysis-related hypoglycemia? Careful monitoring of blood glucose levels before, during, and after dialysis sessions is essential. Adjusting dialysate glucose concentrations and providing appropriate nutritional support can help maintain glycemic stability.

Unique Clinical Presentation of Hypoglycemia in Renal Failure

Recognizing hypoglycemia in patients with renal failure can be challenging due to its atypical presentation:

• Predominance of neuroglycopenic symptoms
• Reduced autonomic nervous system response
• Lack of catecholamine release
• Variable severity and duration of episodes

Why do neuroglycopenic symptoms predominate in uremic hypoglycemia? The frequent dysfunction of the autonomic nervous system in renal failure patients, combined with impaired catecholamine release, diminishes the typical adrenergic symptoms of hypoglycemia (e.g., sweating, tremors, palpitations). This makes the neurological manifestations more prominent.

Diagnostic Approach to Hypoglycemia in Renal Failure

A systematic approach is crucial for accurately diagnosing hypoglycemia in patients with kidney disease:

1. Exclude obvious causes (medications, alcohol, recent dietary changes)
2. Assess for triggering events (infection, cardiac decompensation)
3. Evaluate nutritional status and recent caloric intake
4. Screen for concomitant endocrine disorders
5. Perform frequent and careful glucose determinations

Why is frequent glucose monitoring essential in renal failure patients? The atypical presentation and potentially rapid onset of hypoglycemia in this population necessitate vigilant monitoring, especially when changes in mental or neurological status occur.

Management Strategies for Hypoglycemia in Renal Failure

Effectively managing hypoglycemia in patients with renal failure requires a multifaceted approach:

1. Acute Management

• Prompt administration of glucose (oral or intravenous)
• Correction of underlying precipitating factors
• Close monitoring of blood glucose levels

2. Long-term Prevention

• Medication review and adjustment
• Optimization of nutritional status
• Regular blood glucose monitoring
• Patient and caregiver education

How can healthcare providers balance glycemic control with hypoglycemia prevention in renal patients? Individualizing treatment plans, using renal-adjusted medication dosing, and emphasizing the importance of regular glucose monitoring are key strategies.

The Role of Nutrition in Preventing Uremic Hypoglycemia

Proper nutrition plays a crucial role in preventing hypoglycemia in patients with renal failure:

• Adequate caloric intake
• Balanced macronutrient composition
• Regular meal timing
• Supplementation of gluconeogenic precursors

Why is nutritional management particularly challenging in renal failure patients? The dietary restrictions necessary for managing kidney disease (e.g., protein, potassium, and phosphorus limitations) can make it difficult to maintain adequate caloric intake and glucose homeostasis. Collaboration with a renal dietitian is often essential to strike the right balance.

Implications for Prognosis and Long-term Care

The occurrence of hypoglycemia in renal failure patients has significant prognostic implications:

• Marker of multi-system failure
• Associated with increased morbidity and mortality
• Potential contributor to cognitive decline

How does the recognition and management of hypoglycemia impact long-term outcomes in renal failure patients? Early identification and appropriate management of hypoglycemia can potentially improve overall prognosis, reduce complications, and enhance quality of life for patients with kidney disease.

Future Directions in Research and Clinical Practice

As our understanding of hypoglycemia in renal failure evolves, several areas warrant further investigation:

• Development of renal-specific glucose monitoring technologies
• Exploration of novel nutritional strategies to support glucose homeostasis
• Investigation of the long-term cognitive effects of recurrent hypoglycemia in renal patients
• Optimization of dialysis protocols to minimize hypoglycemia risk

How might advances in these areas improve the care of renal failure patients prone to hypoglycemia? Enhanced monitoring capabilities, targeted nutritional interventions, and refined dialysis techniques could significantly reduce the incidence and impact of hypoglycemia in this vulnerable population.

Addressing the Challenges of Hypoglycemia Management in Renal Failure

Managing hypoglycemia in patients with renal failure presents unique challenges:

1. Altered Drug Metabolism

Renal dysfunction affects the metabolism and clearance of many medications, including those used to treat diabetes. This altered pharmacokinetics can increase the risk of hypoglycemia and necessitates careful dosing adjustments.

2. Comorbid Conditions

Patients with renal failure often have multiple comorbidities, such as cardiovascular disease and neuropathy, which can mask or exacerbate hypoglycemic symptoms. How does this complex clinical picture impact hypoglycemia management? It requires a holistic approach that considers the interplay between various organ systems and tailors treatment to the individual patient’s needs.

3. Glycemic Variability

Renal failure patients often experience significant fluctuations in blood glucose levels due to factors such as altered insulin clearance, variable dietary intake, and the effects of dialysis. This glycemic variability increases the risk of both hyper- and hypoglycemia.

4. Cognitive Impairment

Chronic kidney disease and recurrent hypoglycemia can both contribute to cognitive decline. This may impact a patient’s ability to recognize and respond to hypoglycemic symptoms, as well as adhere to complex treatment regimens.

What strategies can healthcare providers employ to overcome these challenges? A multidisciplinary approach involving nephrologists, endocrinologists, dietitians, and diabetes educators is often necessary to provide comprehensive care and optimize glycemic control while minimizing hypoglycemia risk.

The Impact of Emerging Technologies on Hypoglycemia Management in Renal Failure

Advancements in diabetes management technology offer new opportunities for improving care in renal failure patients:

1. Continuous Glucose Monitoring (CGM)

CGM systems provide real-time glucose data and can alert patients and caregivers to impending hypoglycemia. How can CGM benefit renal failure patients specifically? By providing early warning of glucose trends, CGM can help prevent severe hypoglycemic episodes and guide more precise medication and diet adjustments.

2. Artificial Pancreas Systems

Closed-loop insulin delivery systems that automatically adjust insulin dosing based on CGM data show promise for improving glycemic control. While these systems are primarily designed for type 1 diabetes, their potential application in complex cases of type 2 diabetes with renal failure warrants exploration.

3. Telemedicine and Remote Monitoring

Digital health platforms enable closer monitoring and more frequent adjustments to treatment plans. This can be particularly beneficial for renal failure patients who require intensive management and may have mobility limitations.

What considerations are necessary when implementing these technologies in the renal failure population? Factors such as the impact of uremia on sensor accuracy, the need for renal-specific algorithms, and patient education on technology use must be addressed to maximize the benefits of these innovations.

Psychosocial Aspects of Hypoglycemia in Renal Failure

The psychological and social impacts of hypoglycemia in renal failure patients are significant but often overlooked:

1. Fear of Hypoglycemia

Recurrent hypoglycemia can lead to anxiety and fear, potentially causing patients to maintain higher blood glucose levels as a protective measure. How does this fear impact overall disease management? It may lead to suboptimal glycemic control and reduced quality of life.

2. Social Isolation

The unpredictability of hypoglycemic episodes can lead patients to limit their social activities and engagements, contributing to feelings of isolation and depression.

3. Caregiver Burden

Managing hypoglycemia in renal failure patients often requires significant support from family members or caregivers, which can lead to stress and burnout.

4. Impact on Employment and Independence

Frequent hypoglycemic episodes can affect a patient’s ability to work or live independently, leading to financial stress and loss of autonomy.

What strategies can healthcare providers employ to address these psychosocial challenges? Incorporating mental health screening, providing access to support groups, and offering education on coping strategies can help patients and caregivers better manage the emotional aspects of hypoglycemia in renal failure.

Ethical Considerations in Managing Hypoglycemia Risk in End-Stage Renal Disease

As renal failure progresses to end-stage disease, managing hypoglycemia risk becomes increasingly complex and raises several ethical considerations:

1. Quality of Life vs. Tight Glycemic Control

In patients with limited life expectancy, the balance between achieving glycemic targets and maintaining quality of life becomes more nuanced. How should clinicians approach this balance? Individualizing glycemic goals and involving patients in shared decision-making is crucial.

2. Resource Allocation

Advanced monitoring technologies and newer medications can improve hypoglycemia management but may be costly. How should healthcare systems balance the potential benefits of these interventions with their economic impact?

3. End-of-Life Care

As patients approach the end of life, the appropriateness of intensive glucose management and hypoglycemia prevention measures may need to be reevaluated. What factors should guide these decisions? Patient preferences, overall prognosis, and the potential for hypoglycemia to contribute to suffering should all be considered.

4. Research Ethics

Conducting clinical trials in this vulnerable population presents unique ethical challenges. How can researchers balance the need for evidence-based guidelines with the protection of patient well-being?

Addressing these ethical considerations requires open communication between healthcare providers, patients, families, and ethicists to ensure that management decisions align with patient values and best medical practices.

In conclusion, hypoglycemia in renal failure represents a complex clinical challenge that requires a nuanced understanding of its multifaceted pathophysiology, careful monitoring, and individualized management strategies. By addressing the unique aspects of glucose regulation in kidney disease, healthcare providers can improve outcomes and quality of life for this vulnerable patient population. Continued research and technological advancements hold promise for further refining our approach to this important aspect of renal patient care.

Hypoglycemia associated with renal failure

Review

. 1989 Mar;18(1):103-21.

R Arem 
¹

Affiliations

Affiliation

• ¹ Department of Medicine, Baylor College of Medicine, Houston, Texas.

• PMID:

  2645122

Review

R Arem.

Endocrinol Metab Clin North Am.

1989 Mar.

. 1989 Mar;18(1):103-21.

Author

R Arem 
¹

Affiliation

• ¹ Department of Medicine, Baylor College of Medicine, Houston, Texas.

• PMID:

  2645122

Abstract

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.

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Low Blood Sugar and Chronic Kidney Disease

Disclaimer: This article is for informational purposes only and is not intended to be a substitute for medical advice or diagnosis from a physician.

The most common cause of kidney disease is diabetes. The bodies of people with diabetes do not use the hormone insulin properly or does not make insulin at all, so insulin injections or other diabetes medications are required. Because insulin helps keep the amount of sugar in the blood at a normal level, people with diabetes are at risk for both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia), especially when there are changes in diet, activity or medications. Blood sugar below 70 mg/dL is considered low.

Kidney disease and the risk for low blood sugar

The greatest risk of low blood sugar occurs in someone who has both chronic kidney disease (CKD) and diabetes. Whether or not someone has diabetes, a person with CKD is at risk for low blood sugar because of changes in appetite and meal routine. When kidney function declines insulin and other diabetes medications remain in the system longer because of decreased kidney clearance. For a person with diabetes, insulin and other diabetes medications that lower blood sugar may require an adjustment to prevent low blood sugar.

Causes of low blood sugar

Common causes of low blood sugar include:

• Skipping meals or waiting too long to eat
• A decrease in usual food intake because of poor appetite
• Taking too much insulin or diabetes medicine
• Receiving insulin or diabetes medicine at the wrong time
• Increasing physical activity
• Drinking alcoholic beverages

People with chronic kidney disease sometimes experience a loss of appetite that can lead to skipping meals or not eating enough. This often causes a drop in blood sugar.

Symptoms of low blood sugar

Some of the symptoms of low blood sugar include the following:

• Headache
• Tiredness
• Weakness
• Sweating
• Feeling shaky
• Feeling hungry
• Feeling anxious or nervous
• Feeling cranky
• Confusion
• Blurry or double vision
• Rapid or pounding heartbeat

Some people with low blood sugar may not always experience these symptoms. If the sugar level falls too low, a person can sometimes faint, have a seizure or go into a coma.

Preventing low blood sugar

For people with diabetes, there are ways to help prevent low blood sugar.

• Eat on a regular basis and follow the meal plan prescribed by the doctor and renal dietitian.
• Follow a “sick day eating” guideline when you don’t feel like eating.
• Check blood sugar levels regularly.
• Take the recommended dosage of diabetes medicine at the recommended time.
• Contact the doctor if frequent low blood sugar levels occur. A medication adjustment may be needed.
• Don’t drink alcohol without eating food. Have no more than one or two drinks.
• When exercising, stop and check blood sugar. Snacks and medicines should be on-hand and taken as needed. Medications may sometimes need to be adjusted before rigorous exercise.
• Ask the healthcare team about eating a snack at bedtime to help keep blood sugar from dropping overnight.

The healthcare team will work customize the dose and timing of medications to go with the diabetes and CKD patient’s daily routine and meal plan. If a meal is skipped or a person exercises more or less than usual, the result can be low blood sugar. Also, if you plan to switch dialysis treatments, you may need to check your blood sugar more often.

Summary

A person with kidney disease is at risk for low blood sugar. It is important for patients to learn the symptoms of low blood sugar and develop ways to help prevent it. Patients with diabetes must work with their healthcare team and be vigilant about following the team’s recommended meal and exercise plans. The greatest risk of low blood sugar occurs in someone who has both kidney disease and diabetes, so it’s important to maintain a healthy lifestyle that helps prevent so blood sugar levels.

SPONTANEOUS HYPOGLYCEMIA IN CHRONIC RENAL INSUFFICIENCY | Bonapart I.E., Diderich Ph.P.N.M., Elte J.W.F., Rietveld A.P., op de Hoek C.T.

Key words: hypoglycemia, neuroglycopenic symptoms, renal gluconeogenesis, renal clearance of insulin, renal breakdown of insulin.

Spontaneous hypoglycemia in renal failure is more common than is commonly believed. The pathogenesis of this condition is complex. Understanding the underlying mechanism is of interest to all practitioners who manage patients with renal insufficiency. The proposed publication describes a case of “spontaneous” hypoglycemia in a patient with no other disease other than renal insufficiency. Various mechanisms causing hypoglycemia or participating in its development are considered.

Key words: hypoglycaemia; neuroglycopenic symptoms; renal gluconeogenesis; renal insulin clearance; renal insulin degradation.

Spontaneous hypoglycaemia in renal failure occurs more frequently than is considered generally. Its pathogenesis is complex. Understanding the underlying mechanisms is of interest to all practitioners attending patients with renal failure. A case report is presented describing a patient with ‘spontaneous’ hypoglycaemia, without any ilness other than renal failure.

The various mechanisms contributing to or causing hypoglycaemia are reviewed.

I.B. Bonapart, Ph. P.N.M. Diderich, J.W.F. Elte, A.P. Rietveld, C.T. op de Hoek*
*Corresponding author

Introduction

The phenomenon of spontaneous hypoglycemia in patients with renal insufficiency (RI) remained unrecognized until 1970 [1]. Since that time, it has become clear that spontaneous hypoglycemia can occur in PN [2,3]. Fisher et al. found that 26 out of 9Four patients hospitalized for 6 months for hypoglycemia had PN in the absence of diabetes mellitus [3]. The pathogenesis of this condition is often complex and may vary from patient to patient [3]. All practitioners who manage patients with PN are interested in understanding the mechanisms of development and prevention of hypoglycemia.
We present data from a survey of a patient with spontaneous hypoglycemia due to PN.

Clinical case

A 42-year-old man with PN caused by hypertension was admitted to the hospital for examination for spontaneous hypoglycemia on April 1994. For 4 years, on average 2 times a month, he experienced bouts of yawning, fatigue, dizziness, drowsiness and nausea with vomiting. The patient did not drink alcohol. He fasted approximately once a week for 24 hours. Medications included captopril (12.5 mg twice daily) from 1989, alfacalcidol, calcium carbonate, vitamin B complex, ascorbic acid, and aluminum hydroxide from 1991, and also ferrosulfate and erythropoietin since 1993. Since 1991, the patient has been hemodialyzed twice a week for end-stage renal failure. There were no visible abnormalities on physical examination. The patient’s body weight was constant and corresponded to his height (body mass index 21.2 kg/m2).
Up to this point, the patient had not been suspected of hypoglycemia and had not measured glucose levels. During a severe attack in April 1994, the patient again experienced yawning, fatigue, dizziness, drowsiness (neuroglycopenic symptoms) and nausea with vomiting, this time leading to coma. He was hospitalized for treatment. Blood samples were taken from him in order to find out if hypoglycemia could be the cause of this condition.
Immediately after intravenous administration of a 50% glucose solution, the patient came out of the coma, while the plasma glucose level returned to normal. The results of a biochemical blood test are presented in table. 1. Laboratory studies at the time of admission showed a decrease in plasma glucose to 2.7 mmol/l and an increase in the content of insulin and C-peptide, respectively, to 36 mU/l and 1460 pmol/l. Other parameters were normal, including serum pH, hepatic synthesis (antithrombin III, albumin, partial thromboplastin time – PTT), liver enzyme activity, and thyroid function. Insulin autoantibodies or ethanol were not detected.
Further studies, including imaging techniques (chest and abdominal radiography, thoracoabdominal computed tomography – CT, including contrast, ultrasound of the heart and abdomen), did not reveal abnormalities, with the exception of small cystic lesions of the kidneys.
Daily glucose profile, fasting test (96 h; glucose 4.4-7.7 mmol/l and insulin 7.3-8.7 mU/l), glucose tolerance test (oral administration of 75 g glucose with measurement of its blood levels immediately after administration and after 30, 60, 90 and 120 min), glucagon stimulation test (intravenous administration of 1 mg of glucagon with measurement of glucose and C-peptide immediately after administration and after 4 and 6 minutes), test with ACTH stimulation (intravenous administration of 0.25 mg of corticotropin with measurement of cortisol immediately after stimulation, after 30 and 60 minutes) were normal. The fasting insulin/glucose ratio (glucose level minus 1. 5 divided by insulin levels) ranged from 1.9 to 2.1.
Since the presence of insulinoma is suspected at values ​​of this ratio greater than 9, the result did not point to it.
Due to the fact that the patient needed hemodialysis, regular monitoring and appropriate studies were possible during subsequent attacks. The patient again had predominantly neuroglycopenic symptoms, but did not lead to coma. The patient took blood for research, the results of which are presented in table. 1. Plasma levels of glucose, insulin and C-peptide again exceeded the normal range.
The levels of other analyzed parameters, including serum glucagon, catecholamines, growth hormone and cortisol, were normal. The results point to hypoglycemia with elevated circulating insulin levels with no apparent cause other than PI.

Discussion

In PN, hypoglycemia can occur spontaneously, without any apparent reason (Table 2) [2,4-7]. Hypoglycemia in PN is characterized by neuroglycopenic symptoms rather than catecholamine-mediated manifestations, regardless of the underlying mechanism [3].
Neuroglycopenic manifestations include fatigue, dizziness, abnormal behavior, visual and focal neurological symptoms [3, 8]. These symptoms are most common in patients with chronic PN due to the fact that catecholamines are not released in response to hypoglycemia [3, 9]. It has been established that in chronic PI there is a decrease in the direct counterregulatory hormonal response.
A change in the blood glucose threshold for initiating hormonal secretion (as seen in patients with insulinoma, when more hypoglycemia is required to activate the hormonal response) may be the cause of this phenomenon. Another explanation is the inability to produce normal amounts of hormones in response to hypoglycemia, which is likely due to a reduced ability to secrete the hormone. It is suggested that the mechanism of the reduced catecholamine response is multifactorial [9]. In diabetic patients, the reduced counter-regulatory response is probably due to some extent to autonomic neuropathy. However, a reduced counter-regulatory response is also observed in the absence of signs of autonomic neuropathy. The appearance of a reduced counterregulatory response may be an early manifestation of autonomic neuropathy [9].
Criteria for hypoglycemia vary and are widely discussed. We defined hypoglycemia as a combination of symptoms suggestive of this condition, with a conditional threshold of 3.3 mmol/L and an immediate response to therapy.
The threshold level for counterregulatory hormonal secretion is a higher glucose level than for the initiation of symptoms of autonomic warming, which in turn requires a higher glucose level than that associated with the onset of acute neuroglycopenic symptoms and deterioration of cerebral function [10].
Central nervous system (CNS) symptoms were described by A. Garber [11] and M. Block [1] at plasma glucose levels of 3.1 and 2.9, respectively.mmol/l. Our patient developed a coma at a glucose level of 2.7 mmol/l.
CNS symptoms may appear at higher glucose levels than is commonly believed.
A possible explanation for this phenomenon is the decrease in the immediate counter-regulatory catecholamine response observed in PI.
An increase in the concentration of epinephrine in response to hypoglycemia can lead to an increase in cerebral blood flow in healthy people. Theoretically, this mechanism may be impaired in patients with PN, leading to early onset of CNS symptoms at relatively high glucose concentrations.
The kidneys influence glucose metabolism in several ways. They play a leading role in gluconeogenesis due to the presence of a significant amount of the enzyme glucose-6-phosphatase [5]. Destruction of the renal cortex can lead to a sharp decrease in glucose production [3]. The kidneys are the most important extrahepatic site of insulin degradation and are second only to the liver in terms of insulinase activity. In PI, there is a pronounced limitation of the metabolic level of insulin clearance [12-14] and a delay in the destruction of insulin [3, 15].
Impaired hepatic glycogen synthesis and release are also thought to be additional causes of hypoglycemia in PN [3]. Hemodialysis can lead to a deficiency in gluconeogenesis through the removal of products such as alanine [2, 3]. A high concentration of glucose in the dialysate is well known as a cause of reactive hypoglycemia [3]. Lactic acidosis is often observed in PN and has been described as the cause of reduced gluconeogenesis [4, 12].
Numerous studies were performed during various episodes in our patient in order to identify a possible cause of hypoglycemia (see Table 1).
The dialysate did not contain glucose, and therefore reactive hypoglycemia was excluded. Although patients with PN are usually underweight, in this particular case the body mass index and albumin levels were normal, indicating the absence of chronic malnutrition. Insulinoma was ruled out based on a negative 96-hour fast, a normal insulin/glucose ratio, and a normal abdominal CT scan, including contrast. Against the presence of liver disease, normal results of determining its function, data from ultrasound and CT scan testified.
Thyroid function results ruled out hypothyroidism, which is a rare cause of hypoglycemia. Insulin antibodies (a very rare cause) as well as ethanol (a well-known cause of hypoglycemia) were absent. There were no signs of the presence of tumors that could produce insulin-like peptides [15, 16]. Some additional studies have been conducted to rule out other possible causes of hypoglycemia. Thus, the analysis of the daily glucose profile showed normal fluctuations in its level. Glucose tolerance test results did not indicate reactive hypoglycemia or late onset hypoglycemia (latent diabetes). The glucagon stimulation test showed an adequate increase in glucose levels, indicating normal glycogenolysis. The results of the test with ACTH stimulation exclude the presence of adrenal insufficiency.
Neuroglycopenic symptoms predominated. This was confirmed by the results of analyzes of blood samples taken during bouts of hypoglycemia, which showed normal levels of glucagon, catecholamines, growth hormone and cortisol. Acute calorie deficiency caused by regular skipping of meals can lead to a decrease in hepatic glucose storage, which, in combination with reduced gluconeogenesis in the kidneys, contributes to the development of hypoglycemia. There appears to be a discrepancy between normal fasting test results and the patient’s history prior to hypoglycemia. There is no certainty that the hunger test was performed correctly. Again, symptoms of hypoglycemia were noted after the fasting period. The patient was advised to eat adequately, after which there was a reduction in the manifestations of hypoglycemia. Therefore, we can conclude that in this patient a certain role in the development of hypoglycemia was played by a lack of calories.

Reference values ​​ Values ​​at first admission in a coma Mean values ​​for the next three attacks (extreme) Glucose, mmol/l 3. 8-5.5 2.7 2.7 (2.6-2.8) Insulin, mU/l 1-20 36 44 (26-68) C-peptide, pmol/l 304-1380 1460 2473 (1409-3710) pH 7.35-7.42 7.41 7.41 (7.40-7.41) Glucagon, ng/l 0-80 Not measured 72*(59-92) Epinephrine, mmol/l 0-1 ” ” 1*(1-1) Norepinephrine mmol/L 0-3 “” 3*(3-3) Growth hormone, mU/l 0-15 ” ” 5. 7*(0.3-12) Cortisol, µmol/l 0.18-0.72 ” ” 0.49*(0.46-0.56) *Samples taken at the time of onset of symptoms of suspected hypoglycemia. After 10 and 15 minutes, the indicators were within the reference values ​​

In addition, hemodialysis is known to remove glyconeogenesis precursors. Elevated insulin levels support a mechanism for delaying insulin breakdown and reduced renal clearance.
We concluded that PN was the cause of hypoglycemia in this case. Since the presence of an insulinoma is ruled out, elevated insulin levels support this conclusion. An acute caloric deficit and hemodialysis may have contributed to the onset of hypoglycemia.

Table 2. Causes of spontaneous hypoglycemia in PI and factors that play a role in its development

1. Reduced renal glyconeogenesis 2. Reduced hepatic glucose production Enzymatic defect in the process of gluconeogenesis Glycogenolysis defect 3. Reduced calorie intake Chronic malnutrition Acute calorie loss Gastrointestinal malabsorption 4. Removal of gluconeogenesis precursors by hemodialysis 5. High glucose concentration in the dialysate: reactive hypoglycemia 6. Reduced breakdown and clearance of insulin by the kidneys 7. Reduced immediate counter-regulatory hormonal response (glucagon and catecholamines) 8. Medication b-Blockers Acetylsalicylic acid Angiotensin converting enzyme (ACE) inhibitors

The pathogenesis of spontaneous hypoglycemia is complex and varies from patient to patient. Hypoglycemia should be suspected in every patient with PN if there is any change in behavior or neurological status. This is especially important if the patient is being treated with β-blockers, acetylsalicylic acid, and possibly ACE inhibitors, which can also induce hypoglycemia [17-19]. Our patient developed severe hypertension and was treated with ACE inhibitors and high doses of calcium antagonists. Since the correction of nutrition was able to achieve a decrease in the frequency and severity of hypoglycemia, ACE inhibitors were not canceled.
To prevent hypoglycemia in patients with suspected hypoglycemia, it is necessary to ensure an adequate intake of calories and, if hypoglycemia does occur, the use of the above drugs should be avoided if possible.

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