Recurrent Episodes Of Hypoglycemia Research Articles

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.

Abstract 136

Introduction: Insulin autoimmune syndrome (Hirata’s disease) is a rare cause of hypoglycemia characterised by recurrent hypoglycemic episodes due to insulin autoantibodies, without any prior exposure to insulin. Method: Retrospective review of patients with hyperinsulinemichypoglycemiawas done. 10 patients (8 females), aged between 7 to 60 years (mean 42.9 years), from year 2005 to 2021 were assessed. Results: Four patients presented with fasting hypoglycemia, while all of them had post-absorptive hypoglycemic episodes. Four (40%) patients had evidence of other autoimmune conditions (three Hashimoto’s thyroiditis &amp; one autoimmune cholangiopathy). Mean insulin was 2782uIU/mL (61-14,332), and mean C-peptide was 12.9 ng/dL (3.6-37.6). Mean anti insulin antibody level was 77.8% (13.6-98.82) in samples evaluated by RIA (till 2015), and 84.7 u/mL by ELISA (2016 onwards). Three (30%) patients had positive history of offending drug usage (clopidpgrel, torsemide and pantoprazole). One of the patients had history of Covid-19 infection three months prior. Treatment with low carbohydrate diet, alpha glucosidase inhibitor &amp;/or prednisolone was effective in all symptomatically. Conclusion: In hyperinsulinemichypoglycemia, when insulin is markedly elevated, but C-peptide is only moderately elevated, insulin autoimmune syndrome should be suspected and insulin in dilution and anti-insulin antibody should be checked. Also, history of other autoimmune conditions, and history of any offending drug usage should be diligently investigated in these patients.

PSUN280 A Rare Genetic Disorder With Recurrent Hypoglycemic Episodes and Ketonemia Requiring Multidisciplinary Team Management During Pregnancy

Abstract Introduction Beckwith-Wiedemann syndrome (BWS; OMIM 130650) is a multisystem human genomic imprinting disorder of chromosome 11p15.5. It is characterized by overgrowth and cancer susceptibility and is known to have a highly variable clinical spectrum. The main features include lateralized overgrowth and hypoglycemia due to prolonged hyperinsulinism. Most case reports on BWS are focused on the pediatric population with very scarce data in adults. Clinical case A 29-year-old, paralympic swimmer and genetically diagnosed female with BWS had recurrent episodes of hypoglycemia during her second pregnancy. She had a history of six previous first trimester miscarriages, anti-phospholipid syndrome, hypoglycaemic seizures, asthma, and migraines. Pre-pregnancy, she was investigated for a neurological cause of her seizures and an electroencephalogram and brain imaging were unremarkable. She underwent extensive investigations for evaluation of hypoglycemia and was diagnosed as having hyperinsulinemia secondary to pancreatic hypertrophy. Factitious hypoglycemia was also ruled out. Tumor localization studies were all negative. A supervised fast could not be conducted due to the inability of the patient to tolerate the test. Her first viable pregnancy was 2 years back, during which she required a prolonged hospital (including the intensive care unit) admission with multiple in-hospital complications and requiring enteral feeding. During her current pregnancy, she experienced recurrent episodes of severe disabling hypoglycemia resulting in seizures. She was commenced on diazoxide, however, despite that, she continued to have hypoglycemic episodes for which she had to self-inject Glucagon several times. She also had unexplained weight loss with ketonemia undeterred by a high-caloric diet. She refused to be on naso-jejunal feeding or enteral feeding. She self funded a flash glucose monitor which recorded her blood glucose levels between 2.0 to 3.4 mmol/L during the episodes of hypoglycemia. Dietitians were continually involved in her care to provide nutritional support and to optimize blood glucose control through dietary manipulation. Conclusion This was a very interesting and complicated case of a genetic disorder that presented multiple challenges during pregnancy. Management focused on psychological concerns, the severe catabolic state leading to rapid weight loss, recurrent hypoglycemic episodes, ketonemia, nutritional support, and fetal well-being monitoring. A multi-disciplinary team approach to management involved the obstetrics, endocrinology, dietetics, and gastroenterology teams. This resulted in a successful outcome for her pregnancy. Very limited data is available on health issues associated with BWS in adulthood and there is no data available on the obstetric management of women with BWS. Additionally, the unexplained weight loss and ketonemia associated with hypoglycemia make this case unique. Further studies are warranted and national guidelines are required to ensure that women with BWS achieve optimum pregnancy outcomes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT277 Glucocorticoid Therapy for Management of Hypoglycemia in the context of Non-Islet Cell Tumor-Induced Hypoglycemia

Abstract Background Non-islet cell tumor-induced hypoglycemia (NICTH) is a rare paraneoplastic syndrome which can cause recurrent hypoglycemia. There is no clear standard of care for management of hypoglycemia. Often, these patients have high morbidity and therefore surgical tumor resection is not always possible. Clinical case: This is the case of a 69 year-old male presenting with altered mental status in the context of hypoglycemia without clear etiology with an initial serum glucose level of 32 mg/dL (normal range 60-100 mg/dL) which quickly corrected after administration of intravenous glucose. He was found to have a large bowel obstruction with CT abdomen revealing an underlying neoplasm. Biopsy of suspected lesion on colonoscopy revealed colorectal adenocarcinoma. Repeated episodes of hypoglycemia complicated by seizures required inpatient management. Workup included serum insulin level which resulted in suppressed level (&amp;lt;1. 0 uU/mL, normal range 1.9-23. 0 uU/mL), low c-peptide level (0.1 ng/mL, normal range 1.1-4.4 ng/mL), low beta hydroxybutyrate level (0. 07 mmol/L, normal level &amp;lt;0.3 mmol/L), cortisol level of 43.7 mcg/dL, undetectable insulin like growth factor-1 (IGF-1) level (&amp;lt;10 ng/mL, normal range 59-230 ng/mL) and low insulin like growth factor-2 (IGF-2) level (66 ng/mL, normal range 333 - 967 ng/mL). IGF2: IGF1 ratio was 66 (ratio &amp;gt;10 is indicative for diagnosis of non-islet cell tumor hypoglycemia). Due to extremely poor oral intake and recurrent episodes of hypoglycemia despite continuous dextrose infusion, the patient was started on 20 mg prednisone daily. Eventually, 40 mg of intravenous methylprednisolone in addition to dextrose infusion was needed as maintenance therapy effectively preventing hypoglycemia. Given his poor functional status, the surgical and oncology team decided he was no longer a surgical or chemotherapy candidate. Eventually, palliative medicine was consulted and the patient was transitioned to comfort care with a plan for outpatient hospice. Conclusion NICTH should be suspected in any patient with hypoglycemia without clear etiology, especially if there are suggestions to NICTH such as known malignancy or newly diagnosed mass. Once NICTH is identified and a primary tumor is found, complete tumor resection represents ideal management, however, not always attainable. In such cases, dextrose infusion might be insufficient to prevent hypoglycemia and is not always the preferred option given the required long-term venous access. In these circumstances, early high dose glucocorticoids are safe and appear to successfully prevent hypoglycemic events. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP219 Laparoscopic Gastrostomy tube (LGT) Placement for Management of Post Bariatric Surgery Hypoglycemia Syndrome (PBSHS).

Abstract Introduction Bariatric surgery is currently the most effective long term management for morbid obesity. Laparoscopic bariatric surgery whether gastric banding (LGB), sleeve gastrectomy (LSG) or gastric bypass (LRYGB) are now more commonly done. One major complication that can follow these procedures are the hypoglycemic syndromes; post bariatric surgery hypoglycemia syndrome (PBSHS). PBSHS is a spectrum ranging from mild reactive hypoglycemia to hypoglycemia with dumping syndrome to the most severe being post bariatric surgery nesidioblastosis (PBSN). Clinical case; The patient is a 33 yr old Caucasian lady with past history of morbid obesity who had LSG in 2012 with poor weight loss response. This was converted to LRYGB in 2016 with much better weight loss response. Within 1.5 yrs of the LRYGB however she started having recurrent hypoglycemic episodes which were initially mild and mostly postprandial (PP) but rapidly escalated to both fasting and PP states. Work up revealed that she had both reactive and fasting hypoglycemia and despite dietary interventions the episodes escalated and with "defensive eating" she progressively gained weight. Her hypoglycemic spells were confirmed as insulin mediated and consistent with PBSN. Medical therapy escalated to maximum dose acarbose, octreotide and high dose diazoxide. The frequency and severity of the hypoglycemic spells worsened and in 2021 she had over 7 hospital admissions from severe hypoglycemia with additional ED visits despite medication use including emergent glucagon use and CGMS monitoring with a DEXCOM device. She had hypoglycemia unawareness with progressively declining quality of life. Rather than possible attempted reversal of the LRYGB a LGT was placed to see if this would ameliorate her symptoms. She now drinks only non-caloric fluids per oral and all caloric intake is via the LGT. The clinical response has been swift and dramatic. Since LGT placement over 3 mths now she has had no symptomatic hypoglycemic episode and no ED nor hospital admissions. Post LGT placement CGMS profile demonstrated marked improvements in glycemic profile and post LGT mixed meal tests (MMT). A dichotomy was demonstrated between her glycemic profile on MMT for oral vs LGT caloric intake providing confirmation of the therapeutic effect of the LGT placement. Discussion With the increasing utilization of bariatric surgery for management of obesity and diabetes, the prevalence of PBSHS is expected to increase. This complication can be difficult and expensive to manage while negatively impacting weight loss and quality of life. Our case provides proof of principle evidence to suggest LGT placement as a management consideration in severe cases of PBSN. Conclusions LGT placement should be considered as an option in patients with severe PBSN that is poorly controlled with maximal medical and lifestyle interventions. Presentation: No date and time listed

Autonomic dysfunction and risk of severe hypoglycemia among individuals with type 2 diabetes.

There are limited data on the link between cardiac autonomic neuropathy (CAN) and severe hypoglycemia in type 2 diabetes. Here, we evaluated the associations of CAN with severe hypoglycemia among 7,421 adults with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes study. CAN was defined using ECG-derived measures. Cox's and Andersen-Gill regression models were used to generate HRs (HRs) for the first and recurrent severe hypoglycemic episodes, respectively. Over 4.7 years, there were 558 first and 811 recurrent hypoglycemic events. Participants with CAN had increased risks of a first episode or recurrent episodes of severe hypoglycemia. The intensity of glycemic management modified the CAN association with hypoglycemia. In the standard glycemic management group, compared with those of participants without CAN, HRs for a first severe hypoglycemia event and recurrent hypoglycemia were 1.58 and 1.96, respectively. In the intensive glycemic management group, HRs for a first severe hypoglycemia event and recurrent hypoglycemia were 1.10 and 1.24, respectively. In summary, CAN was independently associated with higher risks of a first hypoglycemia event and recurrent hypoglycemia among adults with type 2 diabetes, with the highest risk observed among those on standard glycemic management.

PSUN254 Hirata's Disease - An Unexpected Surprise

Abstract The diagnosis of hypoglycemia in adults without diabetes mellitus is a medical challenge. Insulin autoimmune syndrome (IAS), also known as Hirata's Disease, is a rare condition characterized by episodes of spontaneous hypoglycemia secondary to hyperinsulinemia in the setting of positive insulin autoantibodies. 380 cases of IAS have been reported worldwide between 1970 and 2009 with majority of cases seen in patients of Asian descent. Here we present a case of a patient who presented with episodes of recurrent hypoglycemia secondary to IAS.85 year old Asian female presented to the endocrinology office for recurrent episodes of presyncope which were associated with presumed hypoglycemia. Patient denied a history of gastric bypass surgery, diabetes, use of oral hypoglycemic agents, change in eating habits, fevers, weight loss, or night sweats. A continuous glucose monitor was placed during the visit due to patient having difficulties using a glucometer and on follow-up, multiple episodes of hypoglycemia were noted, dropping down to 50mg/dL throughout the day. Due to recurrent symptomatic hypoglycemic episodes, she was admitted to the hospital for a workup. Point of care (POC) glucose on presentation to the ED was 166 mg/dL. 4 hours later in the ED, POC glucose was 42 mg/dL with serum confirmation of 44 mg/dL. Last meal was about 6 hours prior to this event and no dextrose containing solutions were used in the ER. Prior to correction of hypoglycemia, blood specimen sent for the following: c-peptide 3.4 ng/mL, beta-hydroxybutyrate 0.12 mmol/L, insulin level 285 µIU/mL, and proinsulin 93.7 pmol/L. Sulfonylurea screen was negative. CT pancreas with IV contrast showed no evidence of pancreatic mass suggestive of insulinoma. Due to recurrent episodes of hypoglycemia in the hospital, the patient was started on Diazoxide 50 mg every eight hours. An insulin antibody level sent from the initial specimen, eventually resulted and was elevated to above 50 U/mL. A comprehensive review of the patient's medications was performed; none were new or were associated with autoantibody formation. Patient denied recent symptoms of viral illness or family history of hypoglycemia. Literature review revealed the possible benefits of acarbose over diazoxide in management of IAS; diazoxide was switched to acarbose 50 mg three times a day before meals. Outpatient follow-up showed drastic reduced frequency of hypoglycemia while on Acarbose.IAS is a rare but important etiology of hypoglycemia in adults without diabetes mellitus. IAS involves the formation of insulin autoantibody complexes, which binds to the insulin receptors and prevents insulin from binding to its receptors in the postprandial phase. Insulin is then released from the complexes irrespective of blood glucose concentrations, therefore inducing postprandial hypoglycemia. Prompt recognition and diagnosis of IAS can allow for appropriate treatment and avoidance of performing unnecessary imaging and invasive procedures. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP202 Geriatric Type 1 Diabetes- unique management challenge

Abstract Case Presentation A 87 year old female with a past medical history of Type 1 Diabetes Mellitus (DM), Parkinson's disease and osteoporosis was sent from an assisted living facility to the emergency department for evaluation of elevated blood glucose levels. She had a long standing history of type 1 DM and further review revealed that she had extremely labile (brittle) blood sugars, with multiple prior hospitalizations for both hypoglycemia and hyperglycemia. Assisted living facility staff reported that her blood sugars were persistently elevated despite receiving scheduled insulin doses. On presentation, she did not have any specific complaints except for polydipsia and polyuria. She was hemodynamically stable, alert and oriented to time, place and person. Initial lab work included serum glucose 754 (70-79 mg/dL), bicarbonate 25 (21-31 mmol/L), anion gap 10 (6-14 mmol/L), ketone 0.9 (&amp;lt; 0.6 mmol/L), leukocyte count 4.7 (4-11 k/mm u) and creatinine 1. 06 (0.6-1.2 mg/dL). Urinalysis showed glycosuria and proteinuria but no evidence of infection. IVF and insulin were started. Extensive infectious work-up was negative. Her blood glucose levels stabilized with basal-bolus regimen and correctional doses of insulin. Tight glycemic control was avoided due to her history of hypoglycemic unawareness and multiple previous episodes for severe and recurrent hypoglycemia. Discussion Brittle diabetes is a disorder commonly seen in patients with Type 1 DM and is characterized by extreme swings in blood glucose levels (severe recurrent hypoglycemic and hyperglycemic episodes) without a clear cut precipitating cause requiring hospitalizations. It has been linked to autonomic dysfunction, hormonal imbalance, psychological issues, nutrient malabsorption and autoimmune conditions. Geriatric Type 1 DM presents great challenges in management as it combines micro and macro vascular complications of long standing DM with geriatric syndrome - concurrent comorbidities, cognitive losses of various degrees, vision and hearing loss, loss autonomic and hormonal counter-regulation, and progressive frailty leading to severe glycemic instability makes self management of DM near impossible. Our patient was an elderly female with osteoporosis, Parkinson's and hypoglycemic unawareness. Great care was taken to maintain her blood glucose levels in the optimal range both during and after hospitalization. Daily insulin was being administered by staff after checking blood glucose levels, avoiding the possibility of dose omission or errors. Detailed instructions on administration of the correct dose of insulin according to caloric consumption and physical activity were provided. With this case, we wish to highlight the unique challenge Brittle Diabetes in geriatric presents, and as this sector of population is growing owing to better treatment options for diabetics and longer life expectancy, there is a growing need to recognize this entity, adopt a multi-disciplinary patient centered approach and prioritize prevention of both hypoglycemia and extreme hyperglycemia over tight glycemic control. Presentation: No date and time listed

Postbariatric hypoglycemia in symptomatic versus asymptomatic patients: proposals for clinical assessments

IntroductionRecurrent hypoglycemia due to postbariatric hypoglycemia (PBH) is a postoperative complication after Roux-en-Y gastric bypass (RYGBP). The historic term is late dumping syndrome or reactive hypoglycemia. The aim of this...

Diabetic ketoacidosis as first presentation of latent autoimmune diabetes in adults in a patient with hashitoxicosis as first presentation of Hashimoto’s thyroiditis: a case report

BackgroundLatent autoimmune diabetes in adults is an infrequent form of autoimmune diabetes mellitus, while Hashimoto’s thyroiditis, the most common thyroid disease in adults, rarely manifests as thyrotoxicosis. The concurrent initial presentation of these two autoimmune disorders is extremely rare.Case presentationA 29-year-old male of Albanian descent presented after being hospitalized owing to diabetic ketoacidosis. The diagnosis of type 1 diabetes mellitus was placed, and intensified insulin therapy was initiated. Medical history was not of significance except a 5 kg weight loss within 2 months. The patient presented with recurrent episodes of hypoglycemia, and the doses of preprandial and basal insulin were reduced. The differential diagnosis included type 1 diabetes mellitus “honeymoon” period or another type of diabetes mellitus. His serological tests only revealed positive autoantibodies against glutamic acid decarboxylase 65 and C-peptide. The diagnosis leaned toward latent autoimmune diabetes in adults, and the therapeutic approach involved cessation of preprandial insulin therapy, regulation, and subsequent discontinuation of basal insulin and introduction of metformin. Two years later, basal insulin was reintroduced along with a glucagon-like peptide-receptor agonist and metformin. Further physical examination during the initial visit disclosed upper limb tremor, lid lag, excessive sweating, increased sensitivity to heat, and tachycardia. Laboratory tests were indicative of hashitoxicosis (suppressed level of thyroid-stimulating hormone, high levels of total and free thyroid hormones, positive anti-thyroglobulin and anti-thyroid peroxidase, and negative anti-thyroid-stimulating hormone receptor). Thyroid-stimulating hormone level was spontaneously restored, but an increase was observed during follow-up. Levothyroxine was administrated for 2 years until the patient had normal thyroid function.ConclusionsThe prevalence of thyroid autoantibodies in patients with latent autoimmune diabetes in adults ranges from 20% to 30%. This correlation can be attributed to genetic involvement as well as disorders of immune tolerance to autoantigens. Hence, this report gives prominence to the holistic approach and consideration of comorbidities in patients with diabetes mellitus.

Minimizing Hypoglycemia with Insulin Therapy

Iatrogenic hypoglycemia is the most feared and common complication of insulin therapy. Hypoglycemia can have serious consequences and can be potentially life-threatening. In addition to the neurological manifestations of severe hypoglycemia, hypoglycemia may be associated with cognitive dysfunction, cardiovascular events, arrhythmias, and increased mortality. Recurrent episodes of hypoglycemia may lead to hypoglycemia unawareness, which increases the risk of severe hypoglycemia. Therefore, prevention of hypoglycemia remains a priority in persons with diabetes on insulin therapy. The “THINK” strategy provides a comprehensive approach for diabetes care providers to minimize the risk of hypoglycemia related to insulin therapy by mitigating factors that increase the risk. This requires setting reasonable glycemic Targets keeping in mind a person's risk of hypoglycemia; choosing the right Tools such as insulin formulation and regimen with lower risk and adequate glucose monitoring; judicious Titration of insulin doses; use of modern Technology such as continuous glucose monitoring, continuous subcutaneous insulin infusion, and sensor augmented pumps in patients at high risk; maintaining Harmony between insulin dose, diet, physical activity, and changes in lifestyle; Individualization of diabetes therapy; ensuring there are No errors in insulin administration; and empowering patients with Knowledge about hypoglycemia. The THINK strategy offers a handy tool for tailoring insulin therapy to minimize hypoglycemia risk.

Mitchell-Riley Syndrome: Improving Clinical Outcomes and Searching for Functional Impact of RFX-6 Mutations.

Aims/HypothesisCaused by biallelic mutations of the gene encoding the transcription factor RFX6, the rare Mitchell–Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, duodenal atresia, and severe chronic diarrhea. So far, sixteen cases have been reported, all with a poor prognosis. This study discusses the multidisciplinary intensive clinical management of 4 new cases of MRS that survived over the first 2 years of life. Moreover, it demonstrates how the mutations impair the RFX6 function.MethodsClinical records were analyzed and described in detail. The functional impact of two RFX6R181W and RFX6V506G variants was assessed by measuring their ability to transactivate insulin transcription and genes that encode the L-type calcium channels required for normal pancreatic beta-cell function.ResultsAll four patients were small for gestational age (SGA) and prenatally diagnosed with duodenal atresia. They presented with neonatal diabetes early in life and were treated with intravenous insulin therapy before switching to subcutaneous insulin pump therapy. All patients faced recurrent hypoglycemic episodes, exacerbated when parenteral nutrition (PN) was disconnected. A sensor-augmented insulin pump therapy with a predictive low-glucose suspension system was installed with good results. One patient had a homozygous c.1517T>G (p.Val506Gly) mutation, two patients had a homozygous p.Arg181Trp mutation, and one patient presented with new compound heterozygosity. The RFX6V506G and RFX6R181W mutations failed to transactivate the expression of insulin and genes that encode L-type calcium channel subunits required for normal pancreatic beta-cell function.Conclusions/InterpretationMultidisciplinary and intensive disease management improved the clinical outcomes in four patients with MRS, including adjustment of parenteral/oral nutrition progression and advanced diabetes technologies. A better understanding of RFX6 function, in both intestine and pancreas cells, may break ground in new therapies, particularly regarding the use of drugs that modulate the enteroendocrine system.

Case Report: Jejunoileal Atresia With Persistent Poor Bowel Function Can Occur After Surgical Correction for Hirschsprung Disease

Jejunoileal atresia (JIA) is one of the common etiologies of intestinal obtrusion in neonates. However, cases of concomitant ileal atresia and Hirschsprung disease (HD) rarely occur. We report the case of a male infant who had JIA concomitantly with HD that was re-anastomosed. The patient underwent an exploratory laparotomy to resect the dilated terminal ileum. Subsequently, owing to a significantly dilated proximal bowel, he underwent a second exploratory laparotomy. However, he continued to have feeding intolerance postoperatively. He had colonic aganglionosis and was diagnosed with HD. A third laparotomy was then performed. Additionally, he had recurrent episodes of gram-negative bacteremia, especially candida parapsilosis fungemia, despite receiving antibiotics and antifungal, and there were no identifiable underlying genetic or immunological causes. Finally, the patient had recurrent episodes of hypoglycemia, central hypothyroidism, and multiple organ failure and died at the age of 7 months. The concomitant ileal atresia and HD was thought to be due to a common intrauterine vascular accident, together with loss of bowel, thereby acting as a barrier for the caudal migration of neuromeric cells and leading to colonic aganglionosis. In this case, ileal atresia was associated with colonic aganglionosis, central hypothyroidism, and persistent bacteremia, which is a unique finding. In cases of JIA, persistent poor bowel function after surgical correction of concomitant HD should be considered.

Factitious Disorder: A Paradox Case with Recurrent Symptomatic Hypoglycemia

A 57-year-old woman with a past medical history of diabetes mellitus (A1C 4.5%) and depression presented to the hospital for evaluation of recurrent episodes of hypoglycemia. She complained of lightheadedness, diaphoresis, and measured blood glucoses in the 40s at home.

The phenotypic spectrum of dihydrolipoamide dehydrogenase deficiency in Saudi Arabia

BackgroundDihydrolipoamide dehydrogenase deficiency (DLDD) is a rare metabolic disorder inherited in an autosomal recessive manner. This heterogeneous disease has a variable clinical presentation, onset, and biochemical markers. Materials and methodsWe retrospectively reviewed the clinical and molecular diagnosis of eight cases with DLDD from four referral centers in Saudi Arabia. ResultsRemarkably, we found hepatic involvement ranging from acute hepatic failure to chronic hepatitis in five patients. In addition, neurological disorders in the form of seizures, developmental delay, ataxia, hypotonia and psychomotor symptoms were found in five patients, two of them with a combination of hepatic and neurological symptoms. In addition, only one patient had recurrent episodes of hypoglycemia. While most patients had the hepatic form of homozygous variant c.685G > T in the DLD gene, one patient was found to have a novel variant c.623C > T that had neurological and hepatic symptoms. ConclusionsWe describe the largest reported DLDD cohort in the Saudi population. Clinical, biochemical, radiological, and molecular characterization was reviewed and no clear genotype-phenotype correlation was found in this cohort.