Recurrent Hypoglycemia Research Articles

The Effect of Insulin Degludec Versus Insulin Glargine U100 on Glucose Metrics Recorded During Continuous Glucose Monitoring in People With Type 1 Diabetes and Recurrent Nocturnal Severe Hypoglycemia.

Comparing continuous glucose monitoring (CGM)-recorded metrics during treatment with insulin degludec (IDeg) versus insulin glargine U100 (IGlar-100) in people with type 1 diabetes (T1D) and recurrent nocturnal severe hypoglycemia. This is a multicenter, two-year, randomized, crossover trial, including 149 adults with T1D and minimum one episode of nocturnal severe hypoglycemia within the last two years. Participants were randomized 1:1 to treatment with IDeg or IGlar-100 and given the option of six days of blinded CGM twice during each treatment. CGM traces were reviewed for the percentage of time-within-target glucose range (TIR), time-below-range (TBR), time-above-range (TAR), and coefficient of variation (CV). Seventy-four participants were included in the analysis. Differences between treatments were greatest during the night (23:00-06:59). Treatment with IGlar-100 resulted in 54.0% vs 49.0% with IDeg TIR (70-180 mg/dL) (estimated treatment difference [ETD]: -4.6%, 95% confidence interval [CI]: -9.1, -0.0, P = .049). TBR was lower with IDeg at level 1 (54-69 mg/dL) (ETD: -1.7% [95% CI: -2.9, -0.5], P < .05) and level 2 (<54 mg/dL) (ETD: -1.3% [95% CI: -2.1, -0.5], P = .001). TAR was higher with IDeg compared with IGlar-100 at level 1 (181-250 mg/dL) (ETD: 4.0% [95% CI: 0.8, 7.3], P < .05) and level 2 (> 250 mg/dL) (ETD: 4.0% [95% CI: 0.8, 7.2], P < .05). The mean CV was lower with IDeg than that with IGlar-100 (ETD: -3.4% [95% CI: -5.6, -1.2], P < .05). For people with T1D suffering from recurrent nocturnal severe hypoglycemia, treatment with IDeg, compared with IGlar-100, results in a lower TBR and CV during the night at the expense of more TAR.

Cognition in patients with post-bariatric hypoglycemia.

Bariatric surgery, a highly effective treatment for obesity and associated comorbidities, may improve cognition and brain volume in parallel with cardiometabolic function. However, some post-bariatric individuals develop post-bariatric hypoglycemia (PBH), which can be frequent and severe. The impact of recurrent hypoglycemia on cognition in PBH is unknown. The objective of this study was to determine whether individuals with PBH display reduced cognitive function compared with postsurgical counterparts without hypoglycemia. Fourteen adults with a history of Roux-en-Y gastric bypass with hypoglycemia (PBH+, n = 7) or without PBH (PBH-, n = 7) completed assessments of memory, executive function, attention, and psychomotor speed. PBH+ individuals displayed significantly decreased performance in category fluency (p < 0.01), category switching (p < 0.01), and category switching accuracy (p < 0.01), compared with PBH- individuals. Performance in the first (p = 0.03) and third intervals (p = 0.045) of verbal fluency was significantly lower in PBH+ individuals versus PBH- individuals. All other assessments did not differ. PBH+ individuals may be at greater risk for cognitive impairment compared with PBH- individuals, as suggested by impaired semantic processing and cognitive flexibility, as well as greater difficulty initiating and sustaining word retrieval.

Development and clinical application of a stability-indicating chromatography technique for the quantification of diazoxide

Diazoxide is a potential candidate for the treatment of transitional hypoglycaemia in infants. A clinical trial is currently underway to investigate whether low-dose oral diazoxide is beneficial for severe or recurrent transitional neonatal hypoglycaemia (the NeoGluCO Study, registration ANZCTR12620000129987). The present study aimed to develop and validate the parameters for quantifying diazoxide from neonatal plasma samples, and to assess the stability of extemporaneously prepared diazoxide suspensions to support the NeoGluCO Study. To determine the plasma concentration of diazoxide, a protein precipitation mediated extraction protocol was developed, which demonstrated >94% diazoxide extraction recoveries from all samples. The method was linear over the range of 0.2–40 μg/mL (R2 > 0.9994) with a limit of quantification of 0.2 μg/mL. Accuracy of the method was within 97–106% with relative standard deviation < 6% for all samples. Diazoxide-plasma samples were stable for up to three months at −20 °C and up to 48 h when stored in the auto-sampler. Samples were stable for up to two freeze-thaw cycles, with further cycles compromising stability of diazoxide in plasma. The developed method was applied to determine chemical stability of the extemporaneously prepared diazoxide suspensions. These were stable at both 2–8 °C and 25 °C/60% RH, with 98% of diazoxide remaining after 35 days in both storage conditions. Diazoxide was successfully quantified from plasma collected from six neonates enrolled in the NeoGluCO Study, using the developed protocol. Overall, an efficient and reproducible extraction protocol was developed and validated for the estimation of diazoxide from human plasma.

The Antinarcolepsy Drug Modafinil Reverses Hypoglycemia Unawareness and Normalizes Glucose Sensing of Orexin Neurons in Male Mice.

Perifornical hypothalamus (PFH) orexin glucose-inhibited (GI) neurons that facilitate arousal have been implicated in hypoglycemia awareness. Mice lacking orexin exhibit narcolepsy, and orexin mediates the effect of the antinarcolepsy drug modafinil. Thus, hypoglycemia awareness may require a certain level of arousal for awareness of the sympathetic symptoms of hypoglycemia (e.g., tremors, anxiety). Recurrent hypoglycemia (RH) causes hypoglycemia unawareness. We hypothesize that RH impairs the glucose sensitivity of PFH orexin GI neurons and that modafinil normalizes glucose sensitivity of these neurons and restores hypoglycemia awareness after RH. Using patch-clamp recording, we found that RH enhanced glucose inhibition of PFH orexin GI neurons in male mice, thereby blunting activation of these neurons in low-glucose conditions. We then used a modified conditioned place preference behavioral test to demonstrate that modafinil reversed hypoglycemia unawareness in male mice after RH. Similarly, modafinil restored normal glucose sensitivity to PFH orexin GI neurons. We conclude that impaired glucose sensitivity of PFH orexin GI neurons plays a role in hypoglycemia unawareness and that normalizing their glucose sensitivity after RH is associated with restoration of hypoglycemia awareness. This suggests that the glucose sensitivity of PFH orexin GI neurons is a therapeutic target for preventing hypoglycemia unawareness.

Effectiveness of flash glucose monitoring in patients with type 1 diabetes and recurrent hypoglycemia between early and late stages after flash glucose monitoring initiation

AimsEvaluate the effectiveness of reimbursed flash glucose monitoring with optional alarms (FGM) in preventing severe hypoglycemia (SH) and reducing hypoglycemia exposure in T1D patients prone to hypoglycemia. MethodsAmbispective study in T1D patients treated with multiple daily injections (MDI) and prone to hypoglycemia, initiating reimbursed FGM (FreeStyle Libre 2). The primary outcome was the number of SH events (requiring third party assistance) and main secondary outcomes were time below range < 70 (TBR < 70) and < 54 mg/dL (TBR < 54), impaired awareness of hypoglycemia (IAH) and quality of life (QoL). Logistic regression models were constructed to explore variables associated with success of the intervention. ResultsWe included 110 patients (52.7 % women, mean age 47.8 ± 17.0 years). SH events at 1-year follow-up decreased from 0.3 ± 0.6 to 0.03 ± 0.2 (p < 0.001). Significant reductions in patients presenting an SH (26.4 % vs. 2.9 %, p < 0.001) and IAH (47.1 % vs. 25.9 %, p = 0.002) were observed, as well as improvements in QoL. TBR < 70 and TBR < 54 were not significantly reduced. Baseline GMI was inversely associated with a decrease in TBR < 70 [OR 0.37 (0.15–0.93)] and directly with an increase in time in range 70–180 mg/dL [OR 2.10 (1.03–4.28)]. ConclusionsFGM decreased SH and improved hypoglycemia awareness and QoL. Initial tight glycemic control was associated with a decrease in hypoglycemia, while patients with suboptimal control reduced hyperglycemia.

Successful laparoscopic resection of a rare focal form of congenital hyperinsulinism: Case report and literature review

Congenital hyperinsulinism is a severe disease that causes irreversible damage to the cerebral cortex. This article presents a clinical observation of successful surgical treatment for a child with an extremely rare form of hyperinsulinism accompanied by two foci in the opposite ends of the pancreas. The child was in extremely critical condition from birth due to recurrent hypoglycemia and was diagnosed with hyperinsulinism at the age of two weeks. Specific therapy with diazoxide and octreotide was initiated but proven to be ineffective (parenteral glucose administration was still needed, and octreotide only provided partial results). When the child was one month old, positron emission tomography-computed tomography with 18F-DOPA was performed and revealed the focal hyperfixation of the radiopharmaceutical in the tail and head of the pancreas. This finding indicated the presence of two pathological foci or a focus in the tail and the physiological accumulation of the radiopharmaceutical in the head. At the age of one month and 20 days, the child underwent laparoscopic revision of the pancreas to visualize a focus in the tail that was confirmed by express biopsy. The resection of the tail (15%) was performed with confirmation of clear resection margins. During further revision, a focus was detected in the head. Resection was again performed with histological confirmation of complete resection. On the 12th day after the operation, the child was discharged without therapy with clinical recovery. The child is currently being monitored (for over six months), growing and developing according to age. A fasting test was performed, and the recurrence of hyperinsulinism was ruled out. This article presents a detailed description of the clinical and radiological examination results, the patients history, the surgical techniques, and the intervention results. As part of the discussion, a literature review on the behavior of laparoscopic resections of the pancreas in children with congenital hyperinsulinism was carried out.

146-OR: Causative Role of Hypothalamic Ventromedial Glucose-Inhibited Neurons in Impaired Counterregulatory Responses to Hypoglycemia

The development of impaired counterregulatory responses (CRR) after recurrent hypoglycemia (RH) is one of the most life-threatening and debilitating aspects of Type 1 Diabetes (T1D). Numerous scientific evidence points to the ventromedial nucleus of the hypothalamus (VMH) glucose-inhibited (GI) neurons as major players in the development of impaired CRR. However, there is no current evidence of a causative role of VMH GI neurons in impaired CRR. In this study, we used a protocol in which mice were injected with insulin (2.5 U/kg, i.p.) for 4 consecutive days. These mice displayed impaired CRR after 2-deoxy-D-glucose (2-DG) administration (200 mg/kg, i.p. injected on the 5th day) with blunted levels of circulating glucose, corticosterone, and epinephrine in comparison to mice with intact CRR after 2-DG administration. Using a TRAP2:tdTomato mouse model, we labeled (tdTomato) GI neurons by injecting 4-hydroxytamoxifen after 2-DG administration. Four weeks later, the mice were injected with either insulin or vehicle for 4 days followed by 2-DG administration, of which the brains were then immunostained and analyzed for cFos in the VMH. We observed a significant decrease in double-labeled tdTomato/cFos cells in mice with impaired CRR compared to the controls, thus suggesting an altered VMH GI neuronal activation following insulin-induced RH. In support of this, chemogenetic activation of VMH GI neurons in mice with impaired CRR significantly increased blood glucose levels following 2-DG administration compared to mice with impaired CRR. Overall, our data provide evidence for a direct and causal involvement of VMH GI neurons in the development of impaired CRR following RH. Disclosure F.Copperi: None. X.Shen: None. S.Diano: None. Funding Naomi Berrie Diabetes Center; National Institute of Diabetes and Digestive and Kidney Diseases (DK107293)

147-OR: Revisiting the Impact of Opioid Receptor Blockade on Hypoglycemia-Associated Autonomic Failure (HAAF)

HAAF, which has been defined as &amp;gt;20% reduction in average epinephrine (Epi) levels following recurrent hypoglycemia (PMID: 28911152), complicates insulin therapy in T1D. We previously showed that activation of opioid receptors induces HAAF, while intravenous (IV) administration of the opioid receptor antagonist naloxone prevents HAAF. Because of its wide clinical use and possible direct CNS effects, we examined the effects of intranasal naloxone (IN) on hypoglycemia and HAAF. Seventeen (15M, age 43.8±8.7) healthy adults were enrolled in a randomized, placebo-controlled, cross-over, double-blinded study in which they underwent three hyperinsulinemic hypoglycemic clamp studies (duration 2h, glucose nadir 54 mg/dL), with administration of IN (4mg) or placebo during the first two clamps. Two subjects were excluded for lack of Epi response to hypoglycemia. Nine of the remaining 15 subjects developed HAAF, confirming inter-individual variability in susceptibility to HAAF (PMID: 32915987, 35475026). Among the 15 subjects included in the analysis, Epi levels trended downward between the 1st and 3rd clamps in placebo studies (mean ± SEM: 677 ± 114 vs. 512 ± 78 pg/mL, p=0.054), whereas Epi levels remained stable in IN studies (1st vs. 3rd: 519 ± 70 vs. 487 ± 77 pg/mL, p= 0.69). Among the 9 subjects who developed HAAF, Epi levels during the 1st clamp were significantly lower with IN vs. placebo (493 ± 102 vs. 858 ± 161 pg/mL, p=0.03), but there was no further reduction in Epi with IN (1st vs. 3rd: 493±102 vs. 539±101 pg/ml, p=0.67). In summary, these studies suggest differential effects of intranasal naloxone on initial vs. repeated hypoglycemic episodes. Specifically, IN may be effective in preventing Epi blunting during repeated exposure to hypoglycemia. In subjects susceptible to HAAF, IN may paradoxically blunt the Epi response to initial hypoglycemic exposure. Future studies should investigate the clinical significance of initial vs. ongoing epinephrine responses to hypoglycemia. Disclosure C.E.Boyle: None. M.Hawkins: None. E.Lontchi yimagou: Employee; Sanofi. S.Aleksic: None. P.M.Mathias: None. M.Nogueira cordeiro: None. A.Manavalan: None. M.Carey: None. N.Jiang: None. O.Sandu: None. I.Gabriely: None. K.Zhang: None. Funding National Institutes of Health (R01DK079974)

1072-P: Incidence of Inpatient Hypoglycemia by Specialty Area—A Case for Targeted Inpatient CGM

Inpatient hypoglycemia is traumatic for people with diabetes and increases length of stay, hospital costs and subsequent mortality (at least in the elderly). We report inpatient hypoglycemia by specialty ward in an 800-bed, acute hospital serving a largely deprived population (350,000) with diabetes prevalence 8%. Over 1 year, 21,089 inpatients with diabetes had 176,603 point of care (POC) tests (median 8.4, ward range 1.1-29.2, POC tests/person/stay); and 9.2 (ward range 2.1-24.7)% of subjects experienced hypoglycemia (CBG &amp;lt;72 mg/dl). Patients who experienced hypoglycemia had 2.6 (range 1.2-5.8) episodes of hypoglycemia either from early persistence (failure of protocol-driven hypoglycemia treatment) or late recurrence. There was a strong correlation between POC testing frequency and detection of hypoglycemia (Chi-square, Yates’ correction = 8.4374, p=0.004). Compared with the whole hospital (index 1.0), specialty wards hypo index ranged 10-fold from 0.2 to 5.1. A recent RCT demonstrated CGM superiority over POC testing in preventing recurrent inpatient hypoglycemia. Consistent with this RCT, our data suggest that increased POC testing is associated with increased hypoglycemia detection and our approach might guide initial targeting of CGM to highest risk specialty wards for hospitals unable to deploy CGM simultaneously in every inpatient specialty ward area. Disclosure G.A.Lewis: None. J.Cardwell: None. S.Bujawansa: Stock/Shareholder; Merck &amp; Co., Inc., GlaxoSmithKline plc. K.J.Hardy: Other Relationship; Sanofi, Speaker's Bureau; Napp Pharmaceuticals Limited.

145-OR: Counterregulatory Response to Hypoglycemia Is Improved with Serotonin and Norepinephrine Reuptake Inhibitors

We previously reported that serotonin and norepinephrine reuptake inhibitors, amitriptyline (AMT) and imipramine (IMP), restored hypoglycemia awareness in rodents. To test the hypothesis that AMT and IMP could prevent the development of an impaired counterregulatory response (CRR) to hypoglycemia, Sprague-Dawley rats (250-350 g) with pre-implanted arterial and jugular cannulae were randomly assigned to one of four treatment groups: 1) recurrent saline controls (RS, n=8); 2) recurrent insulin-induced hypoglycemia (RH, 30-50 mg/dl, n=8); 3) RH + AMT (10 mg/kg IP, n=8); or 4) RH + IMP (5 mg/kg IP, n=8). Following 3-days of RS/RH treatment, all groups underwent 90-minute hyperinsulinemic (50 mU.kg-1.min-1) hypoglycemic (40-45 mg/dL) clamps. Blood glucose was similar for all groups during the clamp. Glucose infusion rates during the last 30-minutes were significantly reduced for both RH+AMT (23.7 mg/kg/min) and RH+IMP (24.8 mg/kg/min) as compared to RH (40.4 mg/kg/min), indicating that both drugs improved the glucoregulatory response to hypoglycemia. In conclusion, these studies identify 1) the involvement of serotonin and norepinephrine neurotransmitter pathways in the development of blunted counterregulatory responses to hypoglycemia, 2) in subjects with blunted CRR, these drugs may be useful therapeutic agents to improve the glucoregulatory response to hypoglycemia. Disclosure E.L.Macon: None. M.H.Devore: None. A.Iles: None. L.A.Schoeder: None. B.Patel: None. M.B.Music: None. S.Fisher: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK118082)

396-P: The Humanistic Burden of Type 1 Diabetes in U.S. Adults With or Without Recurrent Severe Hypoglycemic Events—A Qualitative Interview Study

Introduction: Despite advances in technology, many people with type 1 diabetes (T1D) still experience severe hypoglycemic events (SHEs). This study explored the perceived humanistic burden of T1D in adults using continuous glucose monitor (CGM) in the US with or without recurrent SHEs. Methods: In 60-minute semi-structured interviews, adult CGM users with self-reported T1D diagnosis (≥5 yrs.) described the burden of TID on quality of life (QoL). Participants ranked the ‘top 3’ negative impacts of T1D on QoL. Subgroup analyses were conducted in participants with recurrent SHE (rSHE; ≥2 SHEs last yr.) and without recurrent SHE (nSHE; ≤1 SHEs last yr.). Results: Participants (N=31; 42% rSHEs, 58% nSHEs) were 74% female and 81% were married. Mean age of T1D diagnosis was 28 yrs. Median SHEs in the past year in the rSHE group were 3 and in the nSHE group were 0. Both groups had mean HbA1c of 7.1%. rSHE and nSHE participants used hybrid closed loop systems (hCLS) (53.8% vs. 44.4%), multiple daily injections (23.1% vs. 33.3%) and continuous subcutaneous insulin infusion pump without hCLS (23.1% vs. 22.2%), respectively. All participants reported negative impacts on physical health, mental health, sleep, relationships, leisure activities, work/studies, and sex life. The ‘top 3’ ranked impacts for the rSHE cohort were physical health and sleep (tied at first) followed by leisure activities. Impacts to physical health, mental health, and relationships were ‘top 3’ for the nSHE cohort. Conclusions: Recurrent severe hypoglycemia is observed to persist despite use of advanced diabetes technology. Negative impacts on physical health ranked as the primary concern in both rSHE and nSHE cohorts. However, moderate variability in ranked negative impact order was observed between the cohorts. Disclosure A.Boateng-kuffour: None. P.Callahan: Consultant; Rhythm Pharmaceuticals, Inc., Abbott Diabetes, HealthCore Inc., BMS, Employee; Vertex Pharmaceuticals Incorporated, Genesis Research. K.Chandarana: Employee; Vertex Pharmaceuticals Incorporated, Stock/Shareholder; Vertex Pharmaceuticals Incorporated. J.L.Gaglia: Advisory Panel; Dompé, Consultant; Vertex Pharmaceuticals Incorporated, Abata Therapeutics, Avotres Inc., Current Health, Research Support; Avotres Inc., Dompé, Imcyse, Stock/Shareholder; Vertex Pharmaceuticals Incorporated. M.Phinney: None. E.Guzman ortega: Research Support; Vertex Pharmaceuticals Incorporated. R.N.Krupnick: Consultant; Vertex Pharmaceuticals Incorporated. M.Reaney: None. W.H.Polonsky: Consultant; Abbott Diabetes, Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Insulet Corporation, Intuity Medical, Inc., MannKind Corporation, Provention Bio, Inc., Sanofi-Aventis U.S., Vertex Pharmaceuticals Incorporated.

Ghrelin does not impact the blunted counterregulatory response to recurrent hypoglycemia in mice.

Recurrent episodes of insulin-induced hypoglycemia in patients with diabetes mellitus can result in hypoglycemia-associated autonomic failure (HAAF), which is characterized by a compromised response to hypoglycemia by counterregulatory hormones (counterregulatory response; CRR) and hypoglycemia unawareness. HAAF is a leading cause of morbidity in diabetes and often hinders optimal regulation of blood glucose levels. Yet, the molecular pathways underlying HAAF remain incompletely described. We previously reported that in mice, ghrelin is permissive for the usual CRR to insulin-induced hypoglycemia. Here, we tested the hypothesis that attenuated release of ghrelin both results from HAAF and contributes to HAAF. C57BL/6N mice, ghrelin-knockout (KO) + control mice, and GhIRKO (ghrelin cell-selective insulin receptor knockout) + control mice were randomized to one of three treatment groups: a "Euglycemia" group was injected with saline and remained euglycemic; a 1X hypoglycemia ("1X Hypo") group underwent a single episode of insulin-induced hypoglycemia; a recurrent hypoglycemia ("Recurrent Hypo") group underwent repeated episodes of insulin-induced hypoglycemia over five successive days. Recurrent hypoglycemia exaggerated the reduction in blood glucose (by ~30%) and attenuated the elevations in plasma levels of the CRR hormones glucagon (by 64.5%) and epinephrine (by 52.9%) in C57BL/6N mice compared to a single hypoglycemic episode. Yet, plasma ghrelin was equivalently reduced in "1X Hypo" and "Recurrent Hypo" C57BL/6N mice. Ghrelin-KO mice exhibited neither exaggerated hypoglycemia in response to recurrent hypoglycemia, nor any additional attenuation in CRR hormone levels compared to wild-type littermates. Also, in response to recurrent hypoglycemia, GhIRKO mice exhibited nearly identical blood glucose and plasma CRR hormone levels as littermates with intact insulin receptor expression (floxed-IR mice), despite higher plasma ghrelin in GhIRKO mice. These data suggest that the usual reduction of plasma ghrelin due to insulin-induced hypoglycemia is unaltered by recurrent hypoglycemia and that ghrelin does not impact blood glucose or the blunted CRR hormone responses during recurrent hypoglycemia.

Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes

IntroductionHypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to...

Astrocyte Glycogen Is a Major Source of Hypothalamic Lactate in Rats With Recurrent Hypoglycemia.

Astrocytic glycogen serves as the major source of elevated lactate levels in the ventromedial hypothalamus (VMH) of animals exposed to recurring episodes of hypoglycemia. Antecedent hypoglycemia alters VMH glycogen turnover. Antecedent exposure to hypoglycemia enhances glycogen shunt activity in the VMH during subsequent bouts of hypoglycemia. In the immediate hours following a bout of hypoglycemia, sustained elevations in glycogen phosphorylase activity in the VMH of recurrently hypoglycemic animals contribute to sustained elevations in local lactate levels.

Brief Review: Pancreatic Islet Transplantation for Type 1 Diabetes in Humans

Pancreatic islet transplantation (ITx) has moved from the experimental phase of development to a position of an accepted and appropriate procedure to apply in clinical medicine. The primary indication for use of ITx is for management of dangerous and recurrent hypoglycemia secondary to use of exogenous insulin for management of hyperglycemia in people with type 1 diabetes. ITx involves procurement of a pancreas donated by a person who has died. The organ is taken to a specialized laboratory for isolation of islets that will be infused into the liver via a cannula put into the hepatic portal vein of an awake recipient by a radiologist. Success rates of maintaining normal blood glucose after the ITx are very high and almost as effective as transplanting an entire pancreas via surgery. Often more than one procedure is required to achieve success. One major attraction to the procedure is that it avoids the more dangerous and complicated procedure of surgical transplantation of the entire pancreas. However, in both instances recipients must undergo and maintain immunosuppressive drugs to avoid rejection of the islets. ITx is also used for management of patients with chronic, painful pancreatitis who undergo pancreatectomy. In this instance the patient’s own islets are returned by infusion into the liver as is done with type 1 diabetes patients. No immunosuppression is required. Success rates of autoislet transplantations are also quite high if a sufficiently mass of islets can be recovered from the resected pancreas.

Patient with Recurrent Hypoglycemia Caused by Malignant Giant Insulinoma

Insulinoma is a functional endocrine tumor in the pancreas and the most common cause of hypoglycemia due to endogenic hyperinsulinism. Insulinoma is a rare case, with an incidence of 1-4 cases per million people each year. Malignant insulinoma is an insulinoma that is proven to metastasize to other tissues and only happens in 5-10% of insulinoma cases. Insulinoma with a size &gt;9 cm is classified as giant insulinoma. Since 1927, fewer than 40 cases of giant insulinoma have been reported. 56 years old female was referred from a private hospital with the chief complaint of decreased consciousness due to recurrent hypoglycemia. On physical examination, palpable ±12x4 cm solid mass with an uneven surface in the epigastric region. Laboratory tests found an increase in c-peptide, fasting insulin, and liver function tests. A contrast CT scan found a heterogeneous solid mass 7.6x8.6x13.6 cm in cauda of the pancreas and hepatomegaly with multiple metastatic nodules. Results of pancreas and liver biopsy showed poorly differentiated carcinoma that metastasizes to the liver. In this case, based on patient history, physical and other examinations, it can be concluded that the patient was diagnosed with an observation of recurrent hypoglycemia caused by giant insulinoma with liver metastases.

A Rare Case of recurrent Hypoglycaemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A potential role for GPR107 in hypoglycemia unawareness

Hypoglycemia unawareness (HU) is a major barrier to achieving glycemic control in diabetic patients and remains a severe complication for type 1 and many type 2 diabetics. Due to the limited availability of animal models and significant variations between existing models, our understanding is limited regarding the cellular mechanisms and neural pathways responsible for this loss of metabolic control in the setting of recurrent hypoglycemia. Our group has recently identified GPR107 as a receptor for neuronostatin (NST), a 13 amino acid peptide derived from the somatostatin prepro-hormone. In our novel rat model of HU, we show that GPR107 expression is dramatically increased in the hypothalamus of rats exhibiting loss of hypoglycemia-induced food intake. Using a GPR107-flox rat model, we evaluated the effect of loss of GPR107 in the hypothalamus on the development of HU. Our preliminary data indicate that knockdown of hypothalamic GPR107 protects rats against HU induced by exposure to recurrent hypoglycemia. Future work will focus on the mechanisms underlying the role of GPR107 in the development of this dangerous clinical entity. National Institute of Health (NIH) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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 #1412446: Pseudohypoglycemia in a Patient with Scleroderma with Minimal Skin Involvement

Point-of-care (POC) glucose monitor is often used in hospitalized patients and is a valuable tool for deciding therapy in cases of abnormal glucose levels. However, it has limitations in conditions such as Raynaud’s phenomenon, monoclonal gammopathies, leukemia, and peripheral hypoperfusion. (1). Here, we describe a patient whose results of POC were unreliable, resulting in overtreatment of hypoglycemia. A 76-year-old African American woman with a history of scleroderma, diagnosed after a skin biopsy was admitted for hypoglycemia. Her symptoms of scleroderma include significant esophageal dysmotility but minimal skin involvement. She was initially treated with hydroxychloroquine which improved her symptoms but discontinued after a few months when it was suspected of causing hypoglycemia. While in rehab for a pubic rami fracture, she was diagnosed with recurrent hypoglycemia and started on Diazoxide. She was transferred to our facility because of persistent hypoglycemia requiring a dextrose drip and multiple infusions of 25g of 50 percent glucose. Despite being on Diazoxide, she had remained hypoglycemic with POC blood glucose readings as low as 30-50 mg/dl. A 72-hour fast was initiated, and Diazoxide was stopped. A fasting blood sugar test off Diazoxide for four days showed discordant fingerstick and plasma blood glucose levels of 59 mg/dl and 138 mg/dl, respectively. Plasma levels of insulin (<1 uU/ml), proinsulin (1.6 pmol/L), and C-peptide (0.4 ng/ml) were appropriately low in the setting of a fast. Records from inpatient rehab showed three episodes of hypoglycemia measured by POC. However, all values of low glucose seen on POC testing had a corresponding normal plasma glucose level. We could not find an episode of hypoglycemia confirmed by a plasma glucose test. She had insulin and C-peptide levels checked several times, and none of them elevated in the setting of normal plasma glucose. Insulin levels ranged from 2.2-13.0 [2.6-24.9 uU/ml], and C-peptide levels ranged from 1.2-2.0 [1.1-4.4 ng/ml], all within normal limits. Additional workup for other etiologies of hypoglycemia showed normal cortisol stimulation test, low IGF-2, and elevated chromogranin A. This patient was diagnosed with hypoglycemia based on POC glucose levels only. If plasma glucose had been used to confirm hypoglycemia this patient could have been diagnosed with pseudohypoglycemia sooner and avoided unnecessary testing and medications. She was also treated for hypoglycemia with dextrose-containing intravenous fluids and Diazoxide. Treating hypoglycemia reflexively is understandable, given the significant risks of withholding treatment. However, Diazoxide likely contributed to this patient’s symptoms of nausea and anorexia already caused by her esophageal dysmotility. It is likely that the minimal skin involvement of her disease minimized the suspicion of psudohypoglycemia. It is worth mentioning that hydroxychloroquine, used for scleroderma management, was stopped for the presumed hypoglycemia. This case highlights the importance of confirming POC testing and evaluating for potential causes of discordant results.