Elevated C-peptide Levels Research Articles

Other Diagnostic Tests for Young-Onset Type 2 Diabetes Mellitus

We have read with interest the article entitled “A Cross-sectional Study to Evaluate Beta Cell Function in Individuals with Newly Diagnosed Young-Onset Type 2 Diabetes Mellitus and its Complications,”1 elevated C-peptide levels are indicative of both insulin resistance and beta cell malfunction. These factors are directly linked to the development of complications associated with young-onset Type 2 Diabetes Mellitus (YO-T2DM), including obesity, hypertension, and diabetic kidney disease. The present letter aims to expand the current diagnostic testing options for early detection of YO-T2DM.

Future clinical prospects of C-peptide testing in the early diagnosis of gestational diabetes.

Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy. It is one of the most common metabolic disorders among expectant mothers, with potential serious short- and long-term complications for both maternal and offspring health. C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin. It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin. Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis. Inadequate compensation by islet beta-cells results in hyperglycemia. The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis. Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes. Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.

A Cross-sectional Study to Assess Beta-Cell Function in Individuals with Recently Diagnosed Young-Onset Type 2 Diabetes Mellitus and Its' Complications.

The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications. A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels. 113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C-peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C-peptide levels. Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Adipose-Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold.

Intra-portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose-derived stromal cells (ASCs) can potentially improve the islet micro-environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long-term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double-layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro-inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet-ASC scaffolds reach normoglycemia seven days post-transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet-ASC scaffolds stay normoglycemic and show elevated levels of C-peptide compared to mice transplanted with islet-only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro-environment.

Alterations of adipokines, pancreatic hormones and incretins in acute and convalescent COVID-19 children

BackgroundThe Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), accountable for Coronavirus disease 2019 (COVID-19), may cause hyperglycemia and additional systemic complexity in metabolic parameters. It is unsure even if the virus itself causes type 1 or type 2 diabetes mellitus (T1DM or T2DM). Furthermore, it is still unclear whether even recuperating COVID-19 individuals have an increased chance to develop new-onset diabetes.MethodsWe wanted to determine the impact of COVID-19 on the levels of adipokines, pancreatic hormones, incretins and cytokines in acute COVID-19, convalescent COVID-19 and control children through an observational study. We performed a multiplex immune assay analysis and compared the plasma levels of adipocytokines, pancreatic hormones, incretins and cytokines of children presenting with acute COVID-19 infection and convalescent COVID-19.ResultsAcute COVID-19 children had significantly elevated levels of adipsin, leptin, insulin, C-peptide, glucagon and ghrelin in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had elevated levels of adipsin, leptin, insulin, C-peptide, glucagon, ghrelin and Glucagon-like peptide-1 (GLP-1) in comparison to control children. On the other hand, acute COVID-19 children had significantly decreased levels of adiponectin and Gastric Inhibitory Peptide (GIP) in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had decreased levels of adiponectin and GIP in comparison to control children. Acute COVID-19 children had significantly elevated levels of cytokines, (Interferon (IFN)) IFNγ, Interleukins (IL)-2, TNFα, IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12, IL-17A and Granulocyte-Colony Stimulating Factors (G-CSF) in comparison to convalescent COVID-19 and controls. Convalescent COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IL-1β, IFNα, IFNβ, IL-6, IL-12, IL-17A and G-CSF in comparison to control children. Additionally, Principal component Analysis (PCA) analysis distinguishes acute COVID-19 from convalescent COVID-19 and controls. The adipokines exhibited a significant correlation with the levels of pro-inflammatory cytokines.ConclusionChildren with acute COVID-19 show significant glycometabolic impairment and exaggerated cytokine responses, which is different from convalescent COVID-19 infection and controls.

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

Основные принципы дифференциальной диагностики типов сахарного диабета у лиц молодого возраста

Aim: To study peculiarities of various types of diabetes mellitus (DM) in young patients. Key points. In patients with DM onset in young age, it is challenging to correctly identify the DM type, therefore, it is essential to know the peculiarities of the onset and progression of each type. DM1 patients present with severe pancreatic β-cell dysfunction. Slow immunemediated DM is diagnosed in the presence of glutamic acid decarboxylase antibodies, but without any need to use insulin for 1 year after the diagnosis. DM2 is characterised with normal or elevated C-peptide levels, absence of antibodies, and presence of some signs of metabolic syndrome. In young patients, DM with autosomal dominant inheritance can be verified, which is caused by pathogenic mutations in associated genes — MODY (Maturity Onset Diabetes of the Young). Conclusion. A review of literature demonstrates the need in thorough differential diagnosis of a DM type if young patients present with hyperglycaemia. Keywords: slow immune-mediated diabetes mellitus, MODY, diabetes mellitus, young patients.

ODP284 Hyperinsulinism-Hyperammonaemia syndrome: a dive into the rare presentation and diagnostic challenges encountered in adults

Abstract Background Hyperinsulinemic-hyperammonemia, a rare form of congenital hyperinsulinemia, can seldom present in adulthood if failed to be diagnosed during infancy, enabling it to be difficult to identify, and predisposing affected individuals to neurological complications. Case A 20-year-old female with intellectual disability, seizure disorder and ornithine transcarbamylase deficiency was admitted for recurrent episodes of asymptomatic hypoglycemia. Her medications included risperidone, fluoxetine, levetiracetam, lacosamide, ferrous sulphate and acetaminophen. Physical examination including vital signs was unremarkable. Relevant labs included a fasting glucose of 46mg/dl [70-99]. Further work up of hypoglycemia revealed an IGF-1 of 215ng/dl [85-350] and AM Cortisol of 6.5mcg/dl [5-25]. Given a low AM cortisol level under stress, an ACTH stimulation test was done with appropriate response of cortisol of 24 following cosyntropin administration, ruling out adrenal insufficiency. The patient continued to have h ypoglycemia noted on several glucometer checks every 4 hours where she remained asymptomatic. She was further evaluated with a mixed meal study where no hypoglycemia was noted. A 72 -hour fast was performed which was terminated based on a venous blood sample glucose reading of 50 mg/dl confirmed after hypoglycemia was noted on a glucometer check. The labs showed elevated C-peptide levels of 4ng/ml [0.4-2], insulin of 4mIU/L [<25] and proinsulin level of 2.3pmol/l [3-20]. Levels of insulin and proinsulin were noted to be inappropriately normal in the setting of hypoglycemia. Beta hydroxybutyrate was low at 0.1mmol/L [<0.5] and glucagon inappropriately normal at 36pg/ml [50-100]. Sulfonylurea, meglitinide and autoimmune antibody screen were negative. CT abdomen and pelvis was negative for pancreatic abnormality. In the absence of evidence for acquired causes of hyperinsulinemic hypoglycemia, congenital cases were investigated. Based on that, further labs were obtained including ammonia levels which was elevated at 177.2 u/dl [15-45]. Accordingly, GLUD-1 gene mutation was sent, given high suspicion for hyperinsulinemic hyperammonemia syndrome, which resulted positive and confirmed the diagnosis. She was started on a protein restricted diet and diazoxide which regulated her blood glucose levels effectively. Discussion Hyperinsulinism/hyperammonemia (HI/HA) syndrome is a form of congenital hyperinsulinism caused by activating mutations of the GLUD 1 gene which encodes Glutamate Dehydrogenase, a key enzyme in the beta cell pathway of amino acid-stimulated insulin secretion. The resultant syndrome is characterized by fasting and protein induced hypoglycemia, elevated serum ammonia levels without typical hyperammonemic symptoms. Management includes effective blood glucose control with an insulin inhibitor such as diazoxide and a protein restricted diet with consideration to predominantly include carbohydrates and fat. Conclusion Hyperinsulinemia hyperammonemia is a rare form of congenital hyperinsulinemia typically diagnosed during infancy and should be considered as a possible differential diagnosis in patients presenting with new onset hypoglycemia, as timely diagnosis and intervention can prevent forthcoming neurological complications. Presentation: No date and time listed

Study of serum C-peptide levels in newly diagnosed diabetic mellitus subjects of North Gujarat region of India

Background: Serum C-peptide has appeared as the chief clinical and practically adequate marker of β-cell function of pancreas. Serum insulin and C-peptide are concomitantly secreted into the blood circulation in equal amount. The aim of the study was to determine serum C-peptide levels in newly diagnosed diabetic mellitus subjects of North Gujarat region of India.Methods:The present cross-sectional study was done on 50 subjects of recently diagnosed Diabetes mellitus (T2DM) and non-diabetic healthy controls at Banas Medical College and our trust-based hospital. All diabetics patients were further classified into two groups; normal FC group consist of subjects with FC level 0.5-3.2 ng/ml (N=14) and high FC group included subjects with FC>3.2 ng/ml (N=36). The patients' demographic and anthropometric parameters were recorded; detailed history and clinical examination were performed in the entire cases. All biochemical parameters were analyzed. Results: Predominance of the T2DM subjects was in the age group of 41-50 years. Mean value for age (p<0.01), anthropometric (p<0.01), fasting plasma glucose (p<0.001), HbA1c (p<0.01), cholesterol (p<0.01), triglycerides (p<0.001) and C-peptide (p<0.001) were significantly higher in the T2DM subjects. The mean values of fasting plasma glucose (p<0.001) and HbA1c (p<0.01) are significantly higher in T2DM subject with high C-peptide level as compared to normal C-peptide level. Conclusions:In our study, we conclude that elevated levels of fasting C-peptide in newly diagnosed T2DM. Therefore, we suggested that serum C-peptide levels are valuable as marker of endogenous insulin production from β-cell of pancreas.

Congenital insulin resistance in the practice of the pediatrician and pediatric endocrinologist -path to diagnosis

Introduction. Hyperinsulinemic hypoglycemia in children is most commonly due to congenital hyperinsulinism. When hyperinsu-linemia is accompanied by fasting hypoglycemia and postprandial hyperglycemia, rare syndromes of severe insulin resistance, which include Rabson - Mendenhall syndrome, should be suspected. This article provides an analytical review of current data on this rare genetic pathology and presents a clinical case of a previously undescribed combination of Rabson-Mendenhall syndrome with mutations in the insulin receptor gene INSR in the compound heterozygous state with multiple congenital anomalies of other organs.Clinical case. Patient N, 5.5 months old boy, with suspected congenital hyperinsulinism due to episodes of frequent severe hypoglycemia from the first day of life. At the age of 5 months, an episode of hypoglycemia up to 2.2 mmol/L was registered at an appointment with a pediatric endocrinologist. An examination was ordered, which found that against a background decrease in blood glucose to 1.9 mmol/L, C-Peptide level >5000 ng/mL, insulin level >300 lU/mL, cortisol - 971 nmol/L, TSH -3.88 mlU/L, free T4 - 10.53 pmol/L (10-23.2).The importance of early diagnosis of severe insulin resistance to prevent developmental disorders in children is emphasized. The issue of organizing multiple effective monitoring of a patient’s glycemia required special attention in this clinical case. Due to the features of metabolism in young children, we abandoned flash glucose monitoring systems and used a modern glucose meter with an integration program with a mobile application and the ability to generate reports for subsequent analysis as a reliable means of glycemic control.Summary. Based on the results of the genetic study in association with the clinical phenotype, age of debut, the patient was clinically diagnosed with Rabson-Mendenhall syndrome.Discussion. The paradoxical nature of glycemic fluctuations (severe fasting hypoglycemia and postprandial diabetic hyperglycemia) is quite typical for syndromes of severe insulin resistance and should draw the attention of an informed primary care physician.Conclusion. Careful attention to the symptoms of hypoglycemia, especially with a debut in the neonatal period, recurrent episodes, and the severity of the decrease in blood glycemia. If normal or elevated levels of insulin and C-peptide are detected against the background of hypoglycemia, the first thing to think about is congenital hyperinsulinism.

Severe Hypoglycemia in a Non-Diabetic Patient

Introduction: Accidental ingestion of insulin secretagogue may result in severe life-threatening hypoglycemia. Patients in long-term care may be especially vulnerable if proper medication administration safety guidelines are not followed. Case: A 62-year-old woman who was staying at a residential living facility (RLF) for the homeless, presented to the emergency room with altered mental status. Her past medical history included hypertension, COPD, psoriasis, and alcohol abuse. Prior to arriving to the emergency room, she was drinking alcohol excessively. Head CT results were normal. Capillary blood glucose (FBG) level was noted to 38 on EMS arrival. Her FBG improved to 69 after glucagon and her mental status improved shortly afterwards. ED was planning on discharging her when she became unresponsive with tonic-clonic seizure-like activity. The FBG at that time was 17. She was given Ativan and 10% Dextrose IV followed by 5% Dextrose Normal Saline (D5NS) drip. She recovered consciousness and was admitted for further monitoring. Endocrinology was consulted for hypoglycemia (HG). The patient denied prior diagnosis of diabetes mellitus or access to diabetic medications. Her medications were dispensed to her daily by staff at RLF. We held D5NS in order to perform testing for HG. Within 30 minutes she developed symptoms of HG. Hypoglycemic profile labs including C-peptide, insulin, beta-hydroxybutyrate, pro-insulin, hypoglycemic agent screen, insulin antibodies were drawn prior to reversal of HG. Laboratory findings: Venous BG - 26 mg/dL. Beta-hydroxybutyrate level (BHB) - 0.02 mmol/L (n, 0.02–0.27). The insulin antibody - 6.9 ng/mL (n, <5). C-peptide - 8.5 uU/mL (n, 1.1–4.4), insulin level - 53.2 uIU/mL (n, 2.6–24.9). Proinsulin - 8.6 pmol/L (n, <10.0). She had normal GFR of 95.94 mL/min/1.73m2 (n, >60) and elevated liver enzymes. Abdominal ultrasound results were consisted with cirrhosis. HG resolved after 36 hours. HG drug screen performed at Mayo Clinic lab by highly sensitive LC/MS/MS assay was positive for Glimepiride. Discussion: This case illustrates importance of high degree of suspicion for drug-induced HG in a patient presenting with profound HG and no previous history of diabetes. Discharging this patient prematurely could have resulted in hypoglycemic coma and death. Severity of HG was not consistent with alcoholism and cirrhosis. Suppressed BHB level coupled with high-normal pro-insulin and markedly elevated C-peptide and insulin levels were consistent with endogenous hyperinsulinemia. Sulfonylureas are known to have a long half-life; hypoglycemic effect can last for 12 to 24 hours or longer, especially in patients with impaired kidney or hepatic dysfunction. Since results of HG work-up are typically not available for several days, clinical observation and avoidance of premature discharge following initial reversal of HG are very important.

Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population.

C-peptide measurement may represent a better index of pancreatic β-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and the development of type 2 diabetes independent of glucose and insulin levels and to examine potential effect-modification by variables related to kidney function. We included 5176 subjects of the Prevention of Renal and Vascular End-Stage Disease study without type 2 diabetes at baseline. C-peptide was measured in plasma with an electrochemiluminescent immunoassay. Cox proportional hazards regression was used to evaluate the association between C-peptide level and type 2 diabetes development. Median C-peptide was 722 (566–935) pmol/L. During a median follow-up of 7.2 (6.0–7.7) years, 289 individuals developed type 2 diabetes. In multivariable-adjusted Cox regression models, we observed a significant positive association of C-peptide with the risk of type 2 diabetes independent of glucose and insulin levels (hazard ratio (HR): 2.35; 95% confidence interval (CI): 1.49–3.70). Moreover, we found significant effect modification by hypertension and albuminuria (p < 0.001 and p = 0.001 for interaction, respectively), with a stronger association in normotensive and normo-albuminuric subjects and absence of an association in subjects with hypertension or albuminuria. In this population-based cohort, elevated C-peptide levels are associated with an increased risk of type 2 diabetes independent of glucose, insulin levels, and clinical risk factors. Elevated C-peptide level was not independently associated with an increased risk of type 2 diabetes in individuals with hypertension or albuminuria.

Microencapsulated islet allografts in diabetic NOD mice and nonhuman primates.

Our goal was to assess the efficacy of encapsulated allogeneic islets transplanted in diabetic NOD mice and streptozotocin (STZ)-diabetic nonhuman primates (NHPs). Murine or NHP islets were microencapsulated and transplanted in non-immunosuppressed mice or NHPs given clinically-acceptable immunosuppressive regimens, respectively. Two NHPs were treated with autologous mesenchymal stem cells (MSCs) and peri-transplant oxygen therapy. Different transplant sites (intraperitoneal [i.p.], omental pouch, omental surface, and bursa omentalis) were tested in separate NHPs. Graft function was monitored by exogenous insulin requirements, fasting blood glucose levels, glucose tolerance tests, percent hemoglobin A1c (% HbA1c), and C-peptide levels. In vitro assessment of grafts included histology, immunohistochemistry, and viability staining; host immune responses were characterized by flow cytometry and cytokine/chemokine multiplex ELISAS. Microencapsulated islet allografts functioned long-term i.p. in diabetic NOD mice without immunosuppression, but for a relatively short time in immunosuppressed NHPs. In the NHPs, encapsulated allo-islets initially reduced hyperglycemia, decreased exogenous insulin requirements, elevated C-peptide levels, and lowered % HbA1c in plasma, but graft function diminished with time, regardless of transplant site. At necropsy, microcapsules were intact and non-fibrotic, but many islets exhibited volume loss, central necrosis and endogenous markers of hypoxia. Animals receiving supplemental oxygen and autologous MSCs showed improved graft function for a longer post-transplant period. In diabetic NHPs and mice, cell-free microcapsules did not elicit a fibrotic response. The evidence suggested that hypoxia was a major factor for damage to encapsulated islets in vivo. To achieve long-term function, new approaches must be developed to increase the oxygen supply to microencapsulated islets and/or identify donor insulin-secreting cells which can tolerate hypoxia.

1786-P: The New Insulin Sensitizer MSDC-0602K Synergizes with the GLP-1 Receptor Agonist Liraglutide

First generation insulin sensitizers improve both hyperglycemia and hyperinsulinemia and can preserve beta cell mass and function. GLP-1 receptor agonists work by augmenting glucose-stimulated insulin secretion. Our objective was to assess potential additive effects of the new insulin sensitizer, MSDC-0602K (0602K) when combined with a GLP-1 receptor agonist in db/db mice. Mice were gavaged daily with 30 mg/kg 0602K or vehicle, injected subcutaneously every other day with 200 μg/kg Liraglutide (Lira) or vehicle, or received both drugs. Lira reduced glycemia and plasma fructosamine levels, while 0602K or 0602K+Lira normalized glycemia and fructosamine to lean db/+ mouse levels. Both drugs alone improved glucose tolerance compared to vehicle db/db, while the combination of 0602K+Lira further improved glucose tolerance even compared to lean db/+ mice. Vehicle treated db/db mice displayed elevated insulin and C-peptide levels, which were both reduced by 0602K treatment. C-peptide levels were lowered to a greater degree than insulin, indicating that 0602K treatment exerted a major effect on insulin secretion. In contrast, Lira increased the insulin and C-peptide levels in db/db mice, while the combination of 0602K+Lira displayed reduced levels of insulin and C-peptide similar to 0602K-alone treatment. Pancreas immunohistochemistry of vehicle treated db/db mice showed little islet insulin content, but islet insulin was significantly increased by 0602K or 0602K+Lira treatment. Isolated islets from lean, naïve mice showed no defect in glucose-stimulated insulin secretion with 0602K treatment, suggesting that the lowered insulinemia in vivo is due to corrected insulin resistance rather than direct inhibition of insulin secretion. In conclusion, the new insulin sensitizer MSDC-0602K improves insulinemia and helps to restore islet insulin content when used alone or in combination with Liraglutide. Glucose tolerance displayed additive effects with combined 0602K+Lira treatment. Disclosure K.D. Pyles: None. D. Kamm: None. J.R. Colca: Stock/Shareholder; Self; Cirius Therapeutics, Metabolic Solutions Development Company. K.S. McCommis: None. Funding National Institutes of Health (R01HL136658)

SAT-679 Autoimmune Hypoglycemia: A Treatment Challenge

Background: Upon evaluation of patients with recurrent hypoglycemia, both exogenous and endogenous causes should be excluded. Among endogenous hyperinsulinemic hypoglycemia (EHH) pathologies, Insulin Autoimmune Syndrome (IAS), even though extremely rare, must be considered. Most cases of IAS have been reported in the Oriental population, mostly Japanese. No gold standard of care for this condition has been established. Clinical Case: This is the case of an 82 year-old obese female patient with dyslipidemia, obstructive sleep apnea, and osteoarthritis that comes to the Endocrinology clinics for evaluation due to recurrent episodes of hypoglycemia. She refers that for the last three years she had been presenting with multiple episodes of symptomatic hypoglycemia, even levels as low as 30 mg/dL, requiring multiple hospitalizations. Consequently, she refers a 15-pound weight gain because of multiple daily snacks. Home medications were simvastatin and diclofenac. She denies using insulin, sulfonylureas, other hypoglycemic agents, alcohol, or illicit substances. Abdominal MRI and PET CT scan were remarkable only for an atrophic pancreas without focal masses. Patient was hospitalized for a supervised 72-hour fast, resulting in severe hypoglycemia within 14 hours with elevated insulin levels at 46.3 uIU/mL (1.7-31.0 uIU/mL), elevated C-peptide levels at 5.79 ng/mL (0.9-4.3 ng/mL) and elevated insulin antibodies 53µU/mL (<5µU/mL). Patient showed sufficient hepatic reserve after glucagon administration as well as intact cortisol and growth hormone axis upon severe hypoglycemia. With these results, a diagnosis of IAS was made; not associated with other autoimmune diseases, or with medications with sulfhydryl groups, such as the cases already reported on literature. This condition represents a therapeutic challenge because there is no gold standard of care. Literature recognizes diverse treatment options that range from diet modification to more aggressive therapies, including plasmapheresis and immunosupressants. Our patient was managed with diet modification including frequent snacks and Diazoxide with the goal of decreasing insulin levels and inducing hyperglycemia. Diazoxide therapy achieved a steady euglycemic state and decreased insulin antibodies. Patient developed intolerable bilateral lower extremity edema and treatment was modified to complex carbohydrates, frequent snacks in the daytime and Diazoxide only at bedtime, which is the longer fasting period. Patient has remained without episodes of hypoglycemia and diabetes has not been diagnosed since starting treatment two years ago. Conclusion: Early recognition of IAS is essential in order to avoid unnecessary studies and procedures which could delay management. Although no gold standard therapy has been identified for this condition, our case report identifies Diazoxide as a compelling medical treatment.

SUN-606 Identification of NASH Using Data from NHANES III

Nonalcoholic steatohepatitis (NASH) is a serious liver condition marked by hepatic steatosis (HS), cell damage and inflammation. Patients with NASH are at risk for developing cirrhosis and hepatic cancer. Currently, the definitive method of diagnosing NASH is by liver biopsy. To avoid the costs and risks associated with biopsy procedures, there has been considerable effort to develop a non-invasive method of identifying patients with NASH. However, none of these methods has become accepted as a “gold standard.” Our objective was to compare three non-invasive methods of identifying NASH by using data from NHANES III (1988-1994) to determine variables associated with published formulas to identify NASH. We used ultrasound data to identify subjects with moderate - severe HS. Among those with HS, we identified the NASH population using either the HAIR score, the NASH liver fat score, or the Gholam score. The HAIR score was developed in a sample of obese patients, is based on hypertension, insulin resistance and alanine transaminase (ALT) levels, and had an AUROC of 0.9, a sensitivity of 0.8, and a specificity of 0.89. The NASH liver fat score was developed in a Finnish population undergoing gastric bypass, and validated in an Italian population of liver biopsy patients. This score incorporates metabolic syndrome, type 2 diabetes, serum insulin, AST, and ALT. In the Finnish and Italian populations, respectively, it had AUROCs of 0.73 and 0.74, sensitivities of 59.5 and 92.9, and specificities of 79.7 and 32.7. The Gholam score was developed in a sample of obese patients and uses aspartate aminotransferase (AST) and type 2 diabetes diagnosis. It had an AUROC of 0.82, a sensitivity of 0.76, and a specificity of 0.66. We performed multinomial logistic regression to compare each NASH population to the normal population (those with no or only mild HS). We identified 1236 subjects as having NASH by at least one method. 18% of these were identified by all 3 methods, while 20% were identified by 2 methods. All three methods identified significant risk factors for NASH (p<0.05) as being overweight or obese, having elevated AST or ALT levels, and having elevated C-peptide, serum glucose, or serum triglyceride levels. However, the HAIR and Gholam methods also identified being Mexican-American as a significant risk factor, with the NASH liver fat score did not. Being a former alcohol drinker and not meeting guidelines for physical activity were significant risk factors when using the NASH liver fat score. Further refinement of a noninvasive method for identifying NASH is required. Considerable care must be taken in interpreting risk factors, because the results differ depending which method is used. This could have implications in clinical practice as well, where patients and their risk factors may be mis-identified if formulas are used and not liver biopsy.

An Unusual Presentation of Insulinoma: Confusion With Psychiatric Symptoms

Insulinoma is a rare but common functional neuroendocrine tumor that secretes an excess amount of insulin resulting in mostly fasting hypoglycemia but can also cause postprandial hypoglycemia. It usually presents with neuroglycopenic and autonomic sympathetic symptoms that resolve following the administration of dextrose. The patients may remain symptomatic from 1 week to as long as several decades before diagnosis. Insulinoma presenting with psychiatric symptoms has been documented in case/case series reports. Laboratory findings of elevated insulin and C-peptide level in the presence of hypoglycemia and absence of plasma sulfonylurea are suggestive of the diagnosis. Localization of the tumor is essential preoperatively. Surgery usually cures most of the patients, but a minority will have a recurrence especially with malignant insulinoma. The manuscript presents a case of insulinoma presenting with psychiatric symptoms without sympathetic symptoms that led to the delay of the diagnosis for 3 months as initially thought to be related to psychiatric problems. Pancreatic insulinoma was localized by computed tomography (CT) scan and confirmed with endoscopic ultrasound (EUS). The patient underwent successful resection of the tumor, and her symptoms were completely resolved. J Med Cases. 2020;11(5):142-144 doi: https://doi.org/10.14740/jmc3477

Elevated C-peptide Levels Are Associated With Acute Rejection in Kidney Pancreas Transplantation

BackgroundWe assessed whether allograft rejection or failure can be predicted by an acute increase in C-peptide production from the transplanted pancreas. MethodsPatients with a minimum of 5 years of follow-up post simultaneous pancreas-kidney transplant were identified. C-peptide levels were obtained during clinic visits routinely. Graft failure was defined as return to dependence on insulin therapy or return to dialysis for pancreas and kidney grafts, respectively. Protocol kidney allograft biopsies were performed at 3 and 12 months. For-cause biopsies were also performed. ResultsAcute rejections were detected in 11 patients on biopsy results of the renal allograft. C-peptide levels drawn prior to documented rejections were significantly higher in patients with acute rejection than patients with borderline or no rejection (P = .006). Receiver operating characteristics curves for C-peptide indicated greater accuracy in predicting rejection than simultaneously drawn serum creatinine or lipase. ConclusionsHigher C-peptide levels in simultaneous pancreas-kidney recipients is associated with acute rejection vs nonrejection.

Postprandial Metabolism is Impaired in Overweight Normoglycemic Young Adults without Family History of Diabetes

While the risk factors for Type 2 diabetes (T2DM) are known, early predictive markers of transition from normal to a prediabetes state are unidentified. We studied the basal metabolism and metabolic response to a mixed-meal challenge in 110 healthy subjects in the age group of 18 to 40 years (Male:Female = 1:1); grouped into first degree relatives of patients with T2DM (n = 30), those with a body mass index >23 kg/m2 but <30 kg/m2 (n = 30), those with prediabetes (n = 20) and normal controls (n = 30). We performed an untargeted metabolomics analysis of plasma and related that with clinical and biochemical parameters, markers of inflammation, and insulin sensitivity. Similar to prediabetes subjects, overweight subjects had insulin resistance and significantly elevated levels of C-peptide, adiponectin and glucagon and lower level of ghrelin. Metabolites such as MG(22:2(13Z, 16Z)/0:0/0:0) and LysoPC (15:0) were reduced in overweight and prediabetes subjects. Insulin sensitivity was significantly lower in men. Fasting levels of uric acid, xanthine, and glycochenodeoxycholic-3-glucuronide were elevated in men. However, both lysophospholipids and antioxidant defense metabolites were higher in women. Impaired postprandial metabolism and insulin sensitivity in overweight normoglycemic young adults indicates a risk of developing hyperglycemia. Our results also indicate a higher risk of diabetes in young men.

Pancreatic Insulinoma: Case Report of Rare Tumor

Insulinoma is a rare neuroendocrine tumor that causes inappropriate release of insulin, resulting in episodes of hypoglycemia. It classically present with neuroglycopenic and autonomic sympathetic symptoms. These symptoms resolve promptly following glucose administration. Demonstration of elevated C-peptide level in the presence of hypoglycemia and absence of plasma sulfonylurea is suggestive of the diagnosis. Pre-operative localization of the tumor is essential. Herein, we present the case of middle-aged man who had a 6-month history of recurrent episodes of irritability and fatigue that resolved after eating. Pancreatic insulinoma was localized by computed tomography scan. The patient underwent successful resection of the tumor, and his symptoms showed complete resolution.