Recurrent Episodes Of Hypoglycemia Research Articles

Documentation of a novel FBP1 gene mutation in the Arabian ethnicity: a case report

BackgroundFructose-1,6-bisphosphatase deficiency is a rare autosomal recessive disorder characterized by impaired gluconeogenesis. Fructose-1,6-bisphosphatase 1 (FBP1) mutations demonstrate ethnic patterns. For instance, Turkish populations commonly harbor exon 2 deletions. We present a case report of whole exon 2 deletion in a Syrian Arabian child as the first recording of this mutation among Arabian ethnicity and the first report of FBP1 gene mutation in Syria.Case presentationWe present the case of a 2.5-year-old Syrian Arab child with recurrent hypoglycemic episodes, accompanied by nausea and lethargy. The patient’s history, physical examination, and laboratory findings raised suspicion of fructose-1,6-bisphosphatase deficiency. Whole exome sequencing was performed, revealing a homozygous deletion of exon 2 in the FBP1 gene, confirming the diagnosis.ConclusionThis case highlights a potential novel mutation in the Arab population; this mutation is well described in the Turkish population, which suggests potential shared mutations due to ancestral relationships between the two ethnicities. Further studies are needed to confirm this finding.

Addressing recurrent hypoglycaemia through thoracic surgical intervention: understanding Doege-Potter syndrome, a rarity in syndromes

Doege-Potter syndrome (DPS), a rare paraneoplastic phenomenon characterised by non-islet cell tumour hypoglycaemia (NICTH), presents clinicians with intricate diagnostic and therapeutic challenges. This comprehensive review consolidates current understanding, clinical presentations, diagnostic modalities, therapeutic interventions, and emerging trends in managing DPS. The pathophysiology of DPS revolves around dysregulated insulin-like growth factors (IGF), particularly IGF-2, produced by mesenchymal tumours, notably solitary fibrous tumours (SFT). Clinical manifestations encompass recurrent hypoglycaemic episodes, often distinct from typical hypoglycaemia, with implications for insulin and counterregulatory hormone levels. Diagnosis necessitates a multidisciplinary approach integrating biochemical assays, imaging studies, and histopathological confirmation of the underlying neoplasm. Surgical resection remains the cornerstone of treatment, complemented by adjunctive therapies to manage persistent hypoglycaemia. Prognosis is influenced by successful tumour resection and long-term surveillance for recurrence. A patient-centred approach, incorporating supportive services and multidisciplinary care, is essential for optimal outcomes in individuals affected by DPS.

Insulin autoimmunity associated with vitiligo: a rare case presentation.

Insulin autoantibody syndrome (IAS) or Hirata's disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes. Insulin autoantibodies are diagnostic for the condition. Hirata's disease has been seen to be associated with other autoimmune conditions. Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology. Although autoimmunity plays a role in the pathogenesis of both the diseases, association between the two has not been reported till date. In our case, a 72-year-old Indian woman with vitiligo for the past 30 years presented with recurrent episodes of fasting hypoglycaemia. She was found to have very high levels of fasting insulin, C-peptide, and insulin antibody and was diagnosed with IAS. Thus, we conclude that the clinical spectrum of Hirata's disease has to be taken as more heterogenous than previously assumed. Insulin autoantibody syndrome (IAS) or Hirata's disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes in which insulin plays a major role. Insulin autoantibodies are diagnostic for IAS. The endocrine insulin and its autoantibodies play a major role in the pathogenesis of the disease. Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology. IAS and vitiligo are two diseases with autoimmune aetiology which has been seen to be associated with each other (the first case to be reported). The clinical spectrum of Hirata's disease has to be taken as more heterogenous than previously assumed. On dealing with autoimmune diseases, we should also keep in mind about other diseases with autoimmune pathogenesis.

Focal congenital hyperinsulinism

In congenital hyperinsulinemic hypoglycemia - the most common cause of persistent hypoglycemia in infancy - a focal lesion can be identified in 50% of the cases. With appropriate medical care based upon early diagnosis, these patients can be cured by the resection of the lesion rendering unnecessary long time medical care, and avoiding serious brain damage from recurrent hypoglycemic episodes. Genetic testing and 18F-fluoro-dihydroxyphenylalanine PET/CT imaging are essential for determining the best possible treatment. We report 2 cases of focal congenital hyperinsulinism - both male infants: 22 and 2 months of age - treated successfully with enucleation of the pancreas lesion (Semmelweis University, Budapest). Both patients had the pathognomonic mutation of the ABCC8 gene of the ATP-sensitive potassium channel. Radiologic imaging and histology confirmed the diagnosis, and after the operation, pharmacological treatment was terminated in both cases. During the follow-up period (5 and 1.5 years, respectively) they are euglycemic, with no morbidities attributed to the operation. We believe that these two operations for focal hyperinsulinism - diagnosed and localised by the above detailed genetic and specific radiological testing - were the first of their kind in Hungary. Based on the acquired experience, every necessary examination can be achieved in our country to improve patient care, reduce morbidity and medical costs. Orv Hetil. 2023; 164(47): 1877-1884.

Glucose Transport and Utilization in the Hippocampus: From Neurophysiology to Diabetes-Related Development of Dementia.

The association of diabetes with cognitive dysfunction has at least 60 years of history, which started with the observation that children with type 1 diabetes mellitus (T1D), who had recurrent episodes of hypoglycemia and consequently low glucose supply to the brain, showed a deficit of cognitive capacity. Later, the growing incidence of type 2 diabetes mellitus (T2D) and dementia in aged populations revealed their high association, in which a reduced neuronal glucose supply has also been considered as a key mechanism, despite hyperglycemia. Here, we discuss the role of glucose in neuronal functioning/preservation, and how peripheral blood glucose accesses the neuronal intracellular compartment, including the exquisite glucose flux across the blood-brain barrier (BBB) and the complex network of glucose transporters, in dementia-related areas such as the hippocampus. In addition, insulin resistance-induced abnormalities in the hippocampus of obese/T2D patients, such as inflammatory stress, oxidative stress, and mitochondrial stress, increased generation of advanced glycated end products and BBB dysfunction, as well as their association with dementia/Alzheimer's disease, are addressed. Finally, we discuss how these abnormalities are accompained by the reduction in the expression and translocation of the high capacity insulin-sensitive glucose transporter GLUT4 in hippocampal neurons, which leads to neurocytoglycopenia and eventually to cognitive dysfunction. This knowledge should further encourage investigations into the beneficial effects of promising therapeutic approaches which could improve central insulin sensitivity and GLUT4 expression, to fight diabetes-related cognitive dysfunctions.

Clopidogrel-induced non-diabetic hypoglycemia reported from Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a case report

BackgroundRecurrent episodes of hypoglycemia may be caused by several factors, including drugs, critical illnesses, hormonal deficiency, non-islet cell tumor endogenous hyperinsulinism, and accidental, surreptitious, or malicious hypoglycemia. Multiple drugs have been previously reported as causes of hypoglycemia, with moderate and low-quality evidence. However, Clopidogrel as a cause of non-diabetic hypoglycemia is rarely reported. Here we describe a single non-diabetic patient who experienced recurrent episodes of hypoglycemia after initiation of clopidogrel for clinical suspicion of acute coronary syndrome.Case presentationThe patient, a 33-year-old Ethiopian male with documented hypertension on antihypertensive medication, has started receiving treatment for acute coronary syndrome after experiencing angina symptoms. He experienced hypoglycemia following the start of Clopidogrel, but it subsided once it was stopped. Currently, he has a follow-up at the cardiac clinic with a normal measurement of his serum blood glucose level.ConclusionNon-diabetic hypoglycemia is a rare illness characterized by low blood glucose levels in people who do not have diabetes. Patients with severe hypoglycemia may become unconscious or have seizures as a result of low blood sugar. Severe hypoglycemia is fatal and must be treated as soon as possible. Therefore, if non-diabetic hypoglycemia occurs, a thorough evaluation of the causes is essential, particularly any potential drug as a cause of hypoglycemia should be evaluated.

Current and future therapies to treat impaired awareness of hypoglycemia.

In order to achieve optimal glycemic control, intensive insulin regimes are needed for individuals with Type 1 Diabetes (T1D) and insulin-dependent Type 2 Diabetes (T2D). Unfortunately, intensive glycemic control often results in insulin-induced hypoglycemia. Moreover, recurrent episodes of hypoglycemia result in both the loss of the characteristic warning symptoms associated with hypoglycemia and an attenuated counterregulatory hormone responses. The blunting of warning symptoms is known as impaired awareness of hypoglycemia (IAH). Together, IAH and the loss of the hormonal response is termed hypoglycemia associated autonomic failure (HAAF). IAH is prevalent in up to 25% in people with T1D and up to 10% in people with T2D. IAH and HAAF increase the risk of severe hypoglycemia 6-fold and 25-fold, respectively. To reduce this risk for severe hypoglycemia, multiple different therapeutic approaches are being explored that could improve awareness of hypoglycemia. Current therapies to improve awareness of hypoglycemia include patient education and psychoeducation, the use of novel glycemic control technology, pancreas/islet transplantation, and drug therapy. This review examines both existing therapies and potential therapies that are in pre-clinical testing. Novel treatments that improve awareness of hypoglycemia, via improving the counterregulatory hormone responses or improving hypoglycemic symptom recognition, would also shed light on the possible neurological mechanisms that lead to the development of IAH. To reduce the risk of severe hypoglycemia in people with diabetes, elucidating the mechanism behind IAH, as well as developing targeted therapies is currently an unmet need for those that suffer from IAH.

SAT154 Insulin Autoimmune Syndrome In The Setting Of Metastatic Colon Cancer: Case Report

Abstract Disclosure: M. Bernal: None. J. Suarez: None. K.M. Tuna: None. F. Amer: None. M. Lamas: None. Insulin Autoinmune Syndrome is a rare cause of hypoglycemia. Its incidence is higher among Asians, Japanese patients. Also known as Hirata’s disease, it is characterized by the presence of a hyperinsulinemic state, hypoglycemia, elevated insulin antibodies titers without prior exposure to exogenous insulin, and no pathological abnormalities of the pancreatic islets cells. Some commonly used drugs and viruses have been identified as triggers. We present the case of 65-year-old male Caucasian patient who presented with recurrent episodes of hypoglycemia, that started after surgical resection of a metastatic liver lesion, in the context of metastatic colon cancer. During the workup, it was confirmed that patient had hyperinsulinemia, hypoglycemia, and positive auto-insulin antibodies without previous exposure to exogenous insulin and no imaging findings suggestive of a pancreatic abnormality. The relevance of this case is not only related to the rarity of this entity in the Western World, but also the possibility of being associated with a paraneoplastic syndrome in the setting of metastatic colon cancer, which to the best our knowledge, has not yet been described in the literature as a possible trigger of Insulin Autoimmune Syndrome. Presentation: Saturday, June 17, 2023

Recurrent Hypoglycaemia in A Diabetic Patient: The Unexpected Diagnosis

Hypoglycaemia is a common complication seen in diabetic patients receiving insulin. However, insulin is not the risk factor for hypoglycaemia attack as patient with underlying liver problem is also at risk. Thus, as an attending physician, a high index of suspicion is required in dealing with hypoglycaemia patient. We report a 60-year-old woman with underlying diabetes mellitus who presented with recurrent hypoglycaemic episodes and noted to have multiple benign liver cysts that progressed into hepatic failure secondary to hepatocellular carcinoma.

An unusual presentation of severe preeclampsia presenting with maternal collapse in the post-cesarean section secondary to drug toxicity associated with pituitary hemorrhage: a case report

BackgroundSevere preeclampsia presenting with maternal collapse post-cesarean section secondary to drug toxicity associated with pituitary hemorrhage is rare.Case presentationA 24-year-old primigravida 27 weeks of gestation presented with severe preeclampsia, and underwent emergency cesarean section; postoperatively, she had a sudden maternal collapse and cardiac arrest while on labetalol and magnesium infusion. Following the return of spontaneous circulation (ROSC), the patient was found to have severe bradycardia with prolonged QTc interval and recurrent hypoglycemic episodes. Investigations had revealed low serum cortisol with the brain showing pituitary hemorrhage with features of atypical Sheehan’s syndrome without lactation failure.ConclusionsDrug toxicity is an important cause of maternal collapse and cardiac arrest. Pituitary hemorrhage needs to be suspected in maternal patients with recurrent hypoglycemic episodes with or without postpartum hemorrhage (PPH). Continuous monitoring, use of maternal early warning scoring systems (MEWS), and prudence in the perioperative period/labor room will help in reducing the complications.

Doege-Potter Syndrome Secondary to a Solitary Fibrous Tumor of the Abdominopelvic Cavity: A Case Report

Solitary fibrous tumors (SFTs) are rare neoplasms initially identified as "localized fibrous mesothelioma" predominantly found in the pleural cavity. Common clinical manifestations include pain, the presence of a palpablemass, as well as neurological or vascular symptoms. Tumors located in the abdomen or pelvis can exert pressure on adjacent structures, leading to symptoms such as urinary obstruction or retention, bowel obstruction or constipation, and abdominal distention. Doege-Potter syndrome is characterized by hypoglycemia resulting from excessive production of insulin-like growth factors by the tumor. We report the case of a 54-year-old male patient, diagnosed with type II diabetes 8 years ago, currently not undergoing any treatment, Admitted for investigation of recurrent episodes of hypoglycemia.

Long-term follow-up of methimazole-associated insulin autoimmune syndrome: a rare case report

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of long-term follow-up of IAS in China is limited. We herein report a case of drug-induced IAS in a 44-year-old Chinese woman. She had been taking methimazole for Graves’ disease and had subsequently presented with recurrent hypoglycemic episodes. Laboratory assessments on admission revealed that her serum insulin level was significantly elevated (>1000 µIU/mL) and that she was positive for serum insulin autoantibody, leading to a diagnosis of IAS. Human leukocyte antigen DNA typing identified *04:06/*09:01:02, an immunogenetic determinant associated with IAS. After treatment with prednisone for 2 months, the hypoglycemic episodes disappeared, her serum insulin level gradually declined, and her insulin antibody levels became negative. Clinicians should be aware of the potential for methimazole to trigger autoimmune hypoglycemia in people with a genetic predisposition.

Abstract #1404146: The Ups and Downs of Diagnosing Insulinoma

Insulinomas are rare neuroendocrine tumors of the pancreas. The diagnosis of an insulinoma may be delayed in the geriatric population, as older individuals often have comorbid conditions making evaluation more difficult. The case described here involves an exceptionally rare presentation of insulinoma in a 78-year-old male with underlying type 2 diabetes mellitus and heart failure. A 78-year-old man with a past medical history of type 2 diabetes, heart failure, and chronic kidney disease presented to the hospital with bilateral lower extremity edema and shortness of breath. He had been hospitalized four times during the previous six months for acute heart failure exacerbations accompanied by recurrent episodes of hypoglycemia. Of note, his diabetes was well-controlled with glimepiride and dapagliflozin only. The patient reported symptomatic hypoglycemia, primarily during fasting episodes, with nadir serum glucose values between 40 and 50 mg/dL. During hospitalizations, total insulin (range 22-68 uU/mL), and C peptide (range 6.9-16.4 ng/mL) concentrations were inappropriately elevated when glucose was low, indicative of endogenous hyperinsulinemia. However, this hypoglycemia was thought to be secondary to recent sulfonylurea use in the setting of poor diet and acute renal insufficiency related to heart failure. Both glimepiride and dapagliflozin were held, though he inadvertently continued to take glimepiride until his fourth hospitalization. During his fourth admission, the patient continued to have symptomatic hypoglycemia. As his sulfonylurea screen was negative, he underwent an Octreoscan that revealed radiotracer uptake in the distal pancreas. An endoscopic ultrasound with biopsy revealed a well-differentiated neuroendocrine tumor of the pancreas. His heart failure made agents such as diazoxide, verapamil, and phenytoin undesirable, and he was discharged on subcutaneous octreotide three times daily with a plan to follow up in the surgery clinic. The presentation of insulinomas in the geriatric population can be variable and nonspecific, increasing the risk of misdiagnosis or delay of diagnosis. Missing the diagnosis can lead to increased morbidity and mortality via cognitive impairment and falls. Our patient experienced a delay in diagnosis of insulinoma of over one year despite satisfying the criteria of Whipple’s triad during his first admission. The patient had been asked to stop all anti-diabetic medications during his third admission. However, he misunderstood and continued glimepiride. Further, his acute renal insufficiency, heart failure, and decreased appetite provided alternative causes for his hypoglycemia. Insulinomas are extremely rare pancreatic neuroendocrine tumors that typically present in patients between 40 and 60 years of age. However, there have been reports of these rare tumors in older individuals, who often have comorbid conditions making their diagnosis more difficult. This case report highlights the importance of including insulinoma as a cause of persistent endogenous hypoglycemia among the geriatric population.

Recurrent hypoglycemia in a patient with hepatocellular carcinoma

Hypoglycemia is a common complication of diabetes mellitus. Patients may present with any kind of symptoms, either autonomic or neuroglycopenic. Here, we report a case of a 70-year-old man with type 2 diabetes mellitus with a newly diagnosed hepatocellular carcinoma presenting with recurrent episodes of hypoglycemia. The insulin treatment was withheld initially. However, the patient's diabetic control worsened after starting treatment for his hepatocellular carcinoma. Hence, the insulin treatment was resumed. This case highlighted the challenge in balancing the management of hypoglycaemia and poor diabetic control in a patient who has diabetes mellitus and hepatocellular carcinoma. Primary care practitioners need to have high clinical suspicion to monitor these patients to prevent hypoglycemia and manage them accordingly.

Abstract #1404669: Diazoxide in the Treatment of Asymptomatic Refractory Hypoglycemia in End Stage Renal Disease

Diabetic patients with end-stage renal disease (ESRD) treated with insulin or any other diabetic agent show high variations in their glucose metabolism, lower insulin clearance level, and uncertain accuracy of glycemic control measurements. Therefore, these patients are at a greater risk of developing hypoglycemia. Diazoxide use in the treatment of spontaneous and refractory hypoglycemia in this population has not been well documented. We report a case of a young diabetic male that has been successfully treated with diazoxide for his asymptomatic refractory hypoglycemic episodes. A young man with type 2 diabetes mellitus complicated by diabetic nephropathy, on hemodialysis for ESRD, presented with shortness of breath due to COVID pneumonia. After resolution of his infection, he was noted to have recurrent asymptomatic hypoglycemic episodes, although he has been off his diabetes medications for the past few years due to worsening of his kidney function. His oral intake was adequate and there was no concern for malnutrition, or any substance use. From the testing performed, we were able to exclude exogenous insulin or insulin secretagogues use and the presence of insulin antibodies. Insulin and noninsulin (insulin-like growth factor) mediated mechanisms were also ruled out. Since he was having recurrent and refractory asymptomatic hypoglycemic episodes and to minimize the need for supplemental dextrose containing fluids, he was started on diazoxide at 3 mg/kg/day. Knowing the risk of fluid retention with diazoxide, this patient on hemodialysis tolerated it well. Diazoxide helped reduce his episodes of hypoglycemia and he was then safely discharged on it. In ESRD, hypoglycemia can be explained by the impaired contribution of the kidneys to gluconeogenesis and glucose release, as well as the higher insulin levels caused by insulin resistance and decrease in insulin clearance. When his hypoglycemia persisted even after the resolution of his infection, further testing and work-up was done and other causes of hypoglycemia were ruled out. Generally, diazoxide is used as a treatment to manage the symptoms of hypoglycemia in congenital hyperinsulinism, insulinomas and post bariatric surgery cases of hyperinsulinemic hypoglycemia. However, it has not been the optimal treatment when it comes to treating hypoglycemia in ESRD patients because of its side effects; specifically, fluid retention, and electrolyte imbalances. In our case, the patient was treated with diazoxide as a last resort, despite its known side effects and the limited documentation of its use in ESRD patients. Actually, a few other case reports, have also shown promising results with the use of diazoxide for that purpose with no or minimal side effects. However, there are not enough studies that have shown the benefits or risks of long-term treatment of diazoxide in ESRD patients, an area of growing interest.

Abstract #1402832: Doege-Potter Syndrome Due to Solitary Fibrous Tumor of the Kidney

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor which can be benign or malignant. A small subset (<5%) of patients with SFT present with refractory hypoglycemia, known as Doege-Potter syndrome. This is due to increased production of insulin-like growth factor (IGF-2), its precursor pro-IGF-2, and is associated with large tumor size or aggressive clinical behavior. A 77-year-old female was brought to the ER after was found down at home with hypoglycemia down to 20 mg/dL during a wellness check. She had slurred speech and right-sided weakness. MRI of the brain and MRA of head and neck were unremarkable. She was found to have a urinary tract infection which was treated with antibiotics. Due to concern for stroke, aspirin was started. Subsequently she developed hematuria. A CT abdomen and pelvis was performed that revealed a large 17 x 12 x 11 cm heterogenous exophytic mass from the anterior margin of the right kidney. Patient's encephalopathy and focal weakness resolved with glucose administration, but she continued to have recurrent hypoglycemic episodes. A repeat MRI of the brain showed no evidence of metastatic disease and no evidence of CVA. Thyroid, adrenal and liver function tests were within normal range, and insulin and C-peptide levels were grossly suppressed during hypoglycemic episodes. IGF-1 and IGF-2 levels were normal. In the absence of any underlying endocrine pathology or the administration of any hypoglycemic agent, clinically Whipple’s triad was positive (symptoms attributable to hypoglycemia, plasma hypoglycemia at time of symptoms and resolution of symptoms with treatment of hypoglycemia). Tumor induced hypoglycemia was suspected and she underwent right radical nephrectomy. Pathology demonstrated a fully resected large (21 x 11.5 x 11 cm) spindle cell neoplasm, positive for CD34 and STAT6, consistent with solitary fibrous tumor. Post-surgically her hypoglycemia resolved. Our case highlights the importance of early diagnosis and intervention in Doege-Potter syndrome. Hypoglycemia with low levels of serum insulin, C-peptide, and beta-hydroxybutyrate in a healthy-appearing person should prompt evaluation for a tumor with cross-sectional imaging of the chest, abdomen, and pelvis. Although our patient had normal IGF-2 levels, pro-IGF-2 levels were not checked. In SFT the hypoglycemia may be due to elevated IGF-2 or pro-IGF-2 levels which leads to inappropriate activation of systemic insulin receptors and inhibition of glucose release from the liver leading to fatal hypoglycemia. Tumor induced hypoglycemia should be considered as the primary differential diagnosis when hypoglycemia is without an alternative cause.

Automatic inference of hypoglycemia causes in type 1 diabetes: a feasibility study.

Hypoglycemia is the most common adverse consequence of treating diabetes, and is often due to suboptimal patient self-care. Behavioral interventions by health professionals and self-care education helps avoid recurrent hypoglycemic episodes by targeting problematic patient behaviors. This relies on time-consuming investigation of reasons behind the observed episodes, which involves manual interpretation of personal diabetes diaries and communication with patients. Therefore, there is a clear motivation to automate this process using a supervised machine learning paradigm. This manuscript presents a feasibility study of automatic identification of hypoglycemia causes. Reasons for 1885 hypoglycemia events were labeled by 54 participants with type 1 diabetes over a 21 months period. A broad range of possible predictors were extracted describing a hypoglycemic episode and the subject's general self-care from participants' routinely collected data on the Glucollector, their diabetes management platform. Thereafter, the possible hypoglycemia reasons were categorized for two major analysis sections - statistical analysis of relationships between the data features of self-care and hypoglycemia reasons, and classification analysis investigating the design of an automated system to determine the reason for hypoglycemia. Physical activity contributed to 45% of hypoglycemia reasons on the real world collected data. The statistical analysis provided a number of interpretable predictors of different hypoglycemia reasons based on self-care behaviors. The classification analysis showed the performance of a reasoning system in practical settings with different objectives under F1-score, recall and precision metrics. The data acquisition characterized the incidence distribution of the various hypoglycemia reasons. The analyses highlighted many interpretable predictors of the various hypoglycemia types. Also, the feasibility study presented a number of concerns valuable in the design of the decision support system for automatic hypoglycemia reason classification. Therefore, automating the identification of the causes of hypoglycemia may help objectively to target behavioral and therapeutic changes in patients' care.

Diabetes and cognitive function: An evidence-based current perspective.

Several epidemiological studies have clearly identified diabetes mellitus (DM) as a major risk factor for cognitive dysfunction, and it is going to be a major public health issue in the coming years because of the alarming rise in diabetes prevalence across the world. Brain and neural tissues predominantly depend on glucose as energy substrate and hence, any alterations in carbohydrate meta-bolism can directly impact on cerebral functional output including cognition, executive capacity, and memory. DM affects neuronal function and mental capacity in several ways, some of which include hypoperfusion of the brain tissues from cerebrovascular disease, diabetes-related alterations of glucose transporters causing abnormalities in neuronal glucose uptake and metabolism, local hyper- and hypometabolism of brain areas from insulin resistance, and recurrent hypoglycemic episodes inherent to pharmacotherapy of diabetes resulting in neuronal damage. Cognitive decline can further worsen diabetes care as DM is a disease largely self-managed by patients. Therefore, it is crucial to understand the pathobiology of cognitive dysfunction in relation to DM and its management for optimal long-term care plan for patients. A thorough appraisal of normal metabolic characteristics of the brain, how alterations in neural metabolism affects cognition, the diagnostic algorithm for patients with diabetes and dementia, and the management and prognosis of patients when they have this dangerous combination of illnesses is imperative in this context. This evidence-based narrative with the back-up of latest clinical trial reviews elaborates the current understanding on diabetes and cognitive function to empower physicians to manage their patients in day-to-day clinical practice.

Hypoglycemia in Patients With LAMA2-CMD

BackgroundHypoglycemia has been reported in patients with LAMA2-CMD, but the frequency, risk factors, and correlation to genotype/phenotype have not been systematically assessed to date. MethodsA retrospective cohort study was performed on 48 patients with LAMA2-CMD. Patients were divided into two groups: a hypoglycemic group, with at least one episode of hypoglycemia, and a nonhypoglycemic group. The groups were compared according to gait function, epilepsy, intellectual disability, constipation, gastroesophageal reflux, gastrostomy, weight percentile, scoliosis, the use of a ventilator device, the use of a feeding device, neuromuscular disease swallowing status scale, and type of mutation. ResultsFifteen patients (31.2%) presented with at least one episode of symptomatic hypoglycemia and eight (16.6% of the cohort) had two or more episodes. All patients who had hypoglycemia were in the nonambulant group. We observed a correlation between gait, the use of ventilator and feeding devices, and swallow function with hypoglycemia. Patients with extremely low weight were five times more likely to have recurrent episodes of hypoglycemia. The presence of at least one missense variant appears to be associated with a lower risk of hypoglycemia. ConclusionPatients with LAMA2-CMD are at risk of hypoglycemia. The risk is more relevant in patients with severe phenotype and patients with loss-of-function variants. For patients with extremely low weight, the risk is higher. Blood glucose should be actively measured in patients who are fasting or have infections, and health care providers should be prepared to identify and treat these patients.

A case of metabolic encephalopathy due to recurrent hypoglycemia caused by insulin: A case report

Abstract A metabolic encephalopathy brought on by dangerously low blood glucose levels is called hypoglycemic encephalopathy. Transient hypoglycemic episodes are frequent, particularly in diabetic patients. This complication is seen in diabetes patients who are taking insulin/insulin secretagogues. Severe persistent hypoglycemia can result in seizures, a protracted state of coma, and a wide range of other global and focal neurologic impairments. The main pathological alterations in hypoglycemic encephalopathy include widespread denaturation and necrosis of the neurons as a result of a lack of energy, which is accompanied by a significant number of glial cells entering the brain. In our case, the patient had recurrent hypoglycemic episodes, which led to the development of hypoglycemic encephalopathy caused by insulin. It is important for clinicians to be aware of this potential complication and to closely monitor patients with diabetes who are being treated with insulin.