ResearchPad - type-1-diabetes Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SAT-685 Euglycemic Diabetic Ketoacidosis in T1d: The Era of SGLT-2 Inhibitors and Keto-Diet]]> Introduction Euglycemic diabetic ketoacidosis (DKA) is a challenging diagnosis since near normal blood sugar levels can be misleading. In the present case, we describe a patient with Type 1 Diabetes (T1D) on SGLT2 who underwent a strict low carb diet. Case Report A 70-year-old female with past medical history of unspecified diabetes mellitus and primary hypothyroidism presented to emergency room complaining of nausea and dizziness of four days with decreased oral intake. She was alert and oriented, normal weight (52 kg, BMI 20 kg/m2) with stable vital signs, except for mild tachypnea (22/min). Initial labs showed serum glucose 136 mg/dL, bicarbonate 10 mmol/L (normal 20-31), anion gap of 27, venous blood gas pH 7.1, B-hydroxybutyrate 8.8 mmol/L (normal 0.02-0.27), glucosuria > 500 mg/dL, and moderate ketonuria. Screening for ethyl alcohol and ethylene glycol was negative. Lactic acid, cardiac enzymes, renal and liver function tests were normal. She was diagnosed with diabetes mellitus at age 37, on insulin since then. No alcohol use. Her new primary care physician found an A1C of 9.0% for which metformin 1000mg oral twice a day and empagliflozin 12.5 mg oral daily were added and aspart insulin was discontinued. Daily glargine remained at 20 units daily. She was advised to lose weight for which she started a keto-diet 4 weeks prior to this presentation. She had lost 15 pounds since then accompanied by polyuria and polydipsia. Upon admission, she received IV insulin and IV fluids. An endocrinology consultation was requested for euglycemic DKA secondary to SGLT2 complicated by starvation ketosis. Antibodies against glutamic acid decarboxylase were positive at 250 IU/mL (normal < 5). She was discharged on glargine, aspart insulins and oral medications were discontinued. Conclusion This case shows the importance of identifying the specific type of diabetes for appropriate individualization of therapy. Following a keto-diet in unrecognized T1D can trigger ketoacidosis in the setting of SGLT2 inhibitors leading to euglycemic diabetes ketoacidosis.

<![CDATA[SAT-668 Liver Function Test in Type 1 Diabetes Mellitus and Prevalence of Other Autoimmune Disease in Type 1 Diabetes Mellitus]]> Background

Recent studies suggest that non-alcoholic fatty liver disease (NAFLD) may be more common in type 1 diabetes. The pathogenesis of NAFLD has been hypothesized that, hepatic fat accumulation may be due to hyperglycemia induced activation of the transcription factors.

Type 1 DM inducing autoimmune process can also affect other organs. So screening for celiac disease, Hashimoto’s thyroiditis and other autoimmune disorders is necessary.



To evaluate the prevalence of NAFLD in type 1 DM. And to correlate glycosylated hemoglobin (HbA1c) with aspartate transaminase (AST) and alanine transaminase (ALT).


To determine the prevalence of autoimmune disease like hypothyroidism, celiac disease, vitamin B12 deficiency and Vitiligo in type 1 DM.


To study the prevalence of microvascular complications and correlate it with HBA1c.

Study design

Cross sectional study


Eighty patients with type 1 DM were taken, liver function test, HbA1c and TSH was sent. BMI was calculated. We calculated prevalence of elevated AST and ALT in all patients and correlated with HbA1c.

All patients were screened for other autoimmune disorders. Screening for celiac disease was done by celiac antibodies and antibodies positive patients underwent duodenal biopsy. Thyroid screening was done by TSH and anti TPO antibodies. Vitamin B12 levels were also measured.

Patients also underwent screening for microvascular complications to see its prevalence.

Statistical Analysis

Categorical data was represented in the form of frequencies and proportions. Chi square test was used as test of significance for qualitative data. Continuous data was represented as mean and standard deviation.

Pearson correlation or Spearman’s correlation was done to find the correlation between two quantitative variables and qualitative variables and quantitative variables respectively.


Mean age of subjects was 21.38 ± 6.16 years, 57.6% were females and 42.4% were males, mean HBA1c was 10.45 ± 2.54, mean AST was 24.71 ± 15.85 and mean ALT was 22.08 ± 15.13. In the study significant positive correlation was observed between HbA1c and ALT, i.e. With increase in HbA1c there was increase in ALT and vice versa. There was no significant correlation between HbA1c and AST.

In the study 21.2% were hypothyroid, 29.4%had Celiac disease, 1.2% had Vitiligo and 23.5% had B12 deficiency. In the study there was no significant association between Micro vascular complications and HbA1c.

In the study 3.5% had neuropathy, 7% had retinopathy, 4.7% had nephropathy.


Elevated ALT can be associated with NAFLD related risk factors. Type 1 diabetics with elevated ALT should be evaluated. And patients with type 1 DM should undergo screening for other autoimmune disease.

<![CDATA[SAT-670 The Perfect Storm for Diabetic Ketoacidosis]]> Background

Diabetic Ketoacidosis (DKA) is a life-threatening endocrine emergency characterized by metabolic acidosis occurring in the setting of hyperglycemia due to relative insulin deficiency leading to lipolysis and production of serum ketones. Clinical circumstances can potentiate this process, such as acute infection or insulin discontinuation. Additionally, patients on SGLT2-inhibitors are at risk for euglycemic DKA. In people with type 2 diabetes, DKA is uncommon; however, a combination of precipitating factors in these patients can lead to a greater risk of DKA, particularly in the setting of SGLT2-inhibitor use.

Clinical Case

A 63 year old male with past medical history significant for uncontrolled type 2 diabetes (10 year duration, HgA1c=11.2%, on insulins detemir and aspart, metformin, and empagliflozin), coronary artery disease, and treatment refractory antibody-negative polymyositis (baseline CPK levels ~1000-2000, on a burst of prednisone for flare) presented with fever (101.2F), fatigue, myalgias, and nausea with poor oral intake and insulin cessation after recent IV zoledronic acid infusion for prevention of steroid-induced osteoporosis. He was found to be acidemic with bicarbonate=16, AG=18, Cr=1.6 (baseline 1.1), lactic acid=2.9, glucose=245, glucosuria/ketonuria, serum osmolality=295, and CPK=3613. No infectious etiology was found. Differential diagnosis of precipitating factors of DKA includes: steroid-induced hyperglycemia with lipolysis and insulin resistance; starvation ketosis from poor oral intake due to bisphosphonate-induced flu-like illness; metformin-associated lactic acidosis in setting of acute kidney injury; ketone production secondary to insulin cessation in setting of febrile illness; and SGLT2-inhibitor use with dehydration secondary to decompensated hyperglycemia. He was treated for DKA with insulin and volume resuscitation. He was discharged with discontinuation of empagliflozin.


In people with type 2 diabetes and multiple medical problems, a collusion of clinical factors leading to acidemia can occur simultaneously and lead to a drastically increased risk of DKA, especially in the setting of SGLT2-inhibitor use. Clinicians should have heightened awareness of minor predisposing factors that in combination can increase risk of DKA in a patient with type 2 diabetes.

<![CDATA[SAT-686 Type 1 Diabetes Diagnosed in an 83 Year Old Man After Nivolumab Therapy]]> BACKGROUND

Immune checkpoint inhibitors are increasingly being used for a variety of cancers and are a promising treatment option. Immune related adverse effects are their major side effects, most common being hypophysitis and hypothyroidism. While diabetes and adrenalitis have only been rarely reported, these too are becoming more common. We present a case of type 1 diabetes associated with Nivolumab therapy diagnosed in an 83-year-old man.


An 83 year old male with past medical history of emphysema, coronary artery disease, hypertension, non-small cell lung cancer treated with lobectomy, hepatitis C cirrhosis with hepatocellular carcinoma with metastasis to lungs, who completed 10 cycles of Nivolumab presented to oncology clinic with complains of polyuria, polydipsia and a weight loss of 10 pounds over the last one week. Lab work showed a blood glucose of 743 with an anion gap of 18 and bicarb of 18. B-hydroxy butyrate was 3.19. He was admitted to our ICU for diabetic ketoacidosis. He did not have a history of diabetes mellitus. No family history of diabetes was reported. His Hemoglobin A1c was found to be 10.1. He had normal blood sugars before starting Nivolumab therapy. His C-peptide was found to be low at 0.61. Insulin antibody, Islet cell antibody, Zinc transporter antibody and GAD antibodies were negative. He was discharged on basal bolus Insulin regimen. He is being followed in our endocrinology clinic and continues to be insulin dependent.


Nivolumab is PD-1 (programmed cell death) inhibitor, which is used as cancer immunotherapy in multiple advanced cancers including hepatocellular carcinoma. Clinically significant endocrinopathies are documented in <5% of patients treated with PD-1 inhibitors. The cause of Diabetes by PD-1 inhibitors is not well defined but believed to be caused by destruction of pancreatic beta cells due to inhibition of autoimmunity by autoreactive T cells. Literature review showed only 42 published cases of PD-1 inhibitor induced type 1 diabetes. Average age at presentation was 62 years and about 69% patients were in DKA at diagnosis. In a recently published study involving 1163 patients who received PD-1 inhibitors, only 21 cases of diabetes were identified, 12 of those were with new onset DM and only 1 case was due to Nivolumab use.

Since this type of endocrinopathy is mainly reported in case reports, we will need more research for further understanding of the pathology so that we can keep a watch out for this adverse effect and prevent life- threatening complications.

<![CDATA[Life expectancy and survival analysis of patients with diabetes compared to the non diabetic population in Bulgaria]]> To evaluate the expected life expectancy in patients with diabetes in Bulgaria and to compare it to the expected life expectancy of the non-diabetic population in the country.MethodsIt is a retrospective observational population study on individuals diagnosed with diabetes, compared to the non-diabetic population in Bulgaria for the period 2012–2015. Data from the national diabetes register and national statistical institute were used to construct life-tables with probability of survival with t-test and Chi Square test. Confounder analysis was done by age, sex, and type of diabetes. All-cause mortality and deaths in diabetic patients were analyzed. Kaplan-Meier survival curves were constructed for each age group and a log-rank analysis was conducted.ResultsAverage life expectancy in the non-diabetic population, patients with Type 1 DM and with Type 2 DM is 74.8; 70.96 and 75.19 years, respectively. For 2012–2015 the mortality in the non-diabetic population remained constant and lower (average—1.48%) compared to type-1 DM (5.25%) and Type-2 (4.27%). Relative risk of death in diabetics was higher overall (12%), after the age of 70 before which the relative risk was higher for the non-diabetic population. This was observed as a trend in all analyzed years.ConclusionPatients with type 2 DM have a longer life-expectancy than patients with type-1 DM and overall Diabetics life expectancy equals that of the non-diabetic population, which could suggest improved disease control and its associated complications in Bulgaria. Male diabetics show slightly longer life expectancy than their counterparts in the non-diabetic population, by a marginal gain of 0.6 years for the entire observed period. Life expectancy in diabetic women increased by 1.3 years, which was not observed in the non-diabetic population. Prevalence of diabetes was higher for women. Improved diabetes control may explain this gain in life; however other studies are needed to confirm this. ]]> <![CDATA[SAT-662 Effects of SGLT Inhibitors or GLP1 Analogues on Glucose Homeostasis and Body Weight in Patients with Type 1 Diabetes: A Network Meta-Analysis]]> Objective: Despite intensive insulin treatment in patients with type 1 diabetes (T1D), many of them do not reach the glycemic target goal. We performed a network meta-analysis to evaluate the efficacy and safety of additional therapy to insulin in patients with T1D. Methods: We searched CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded from January 1970 until September 2019 to identify randomized controlled trials (RCTs) in T1D patients treated with insulin and metformin, sodium-glucose cotransporter (SGLT) inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). We performed direct and indirect network meta-analysis using Bayesian models and generated rankings of the different hypoglycemia agents by generating mixed treatment comparison. Results: With 23 RCTs (n = 5,151), we performed the network meta-analysis using eight groups; 1) insulin alone, 2) insulin and metformin, 3) insulin and canagliflozin, 4) insulin and dapagliflozin, 5) insulin and empagliflozin, 6) insulin and sotagliflozin, 7) insulin and liraglutide, and 8) insulin and exenatide. Compared with insulin alone, HbA1c was significantly lower in the group treated with insulin and sotagliflozin (mean difference: -0.43%; 95% credible intervals: -0.62 to -0.23). Total daily insulin dose was significantly lower in the insulin and sotagliflozin group by 6.3 U/day than in insulin alone group. Compared with insulin alone, body weight was significantly decreased in the group treated with canagliflozin by 4.5kg, sotagliflozin by 2.8kg, and exenatide by 5.1 kg, respectively. Severe hypoglycemic episodes did not differ between the groups. Conclusions: In patients with T1D, sotagliflozin add-on to insulin decreased HbA1c levels, daily insulin dose, and body weight without hypoglycemia compared to insulin monotherapy. Combined treatment of canagliflozin or exenatide with insulin was effective in weight loss compared with insulin alone in these patients.

<![CDATA[SAT-663 The Impact of Anxiety on the Successful Management of a Type I Diabetic Patient]]> Background: Patients with both type 1 diabetes mellitus (T1DM) and generalized anxiety disorder (GAD) are known to be at increased risk for hypoglycemic events, long-term hyperglycemia, weight gain and vascular disease. However, little research has been conducted regarding management of anxiety in patients with T1DM.

Clinical case: A 27 year old female with T1DM (controlled on an insulin pump), GAD, PTSD, and history of benzodiazepine abuse presented to the emergency department after experiencing multiple panic attacks the day of admission. Recently, patient had multiple bouts of emesis in addition to decreased oral intake. On admission, blood sugar was 54, which increased to 164 after administration of 1 amp of dextrose-50. Patient was obtunded and unable to provide much history. Overnight, insulin was not given due to patient’s poor oral intake. The following morning, patient had one cup of juice for breakfast. Accu-check shortly after revealed a blood glucose level over 500 and patient developed diabetic ketoacidosis (DKA) and was admitted to the ICU on our hospital DKA protocol. Once anion gap closed, patient was transferred out of the ICU for continued management of her diabetes. Patient went on to have multiple panic attacks for the duration of her hospitalization which were controlled with scheduled diazepam, valproic acid, lorazepam and quetiapine. Psychiatry was consulted and found that a major contributing factor to her developing recurrent DKA was her struggle with anxiety surrounding the responsibilities of managing her diabetes and its associated complications including gastroparesis and neuropathy. Further conversation revealed that her psychiatrist had passed away a few months prior to admission and that she had not established care with a new psychiatrist yet.

Discussion: Given the life changing nature of T1DM, it is not uncommon for these patients to have difficulty coping with the daily challenges required to optimally treat their condition. It can be frustrating when the slightest shift in caloric intake or exogenous insulin leads to life-threatening situations such as DKA. The above case sheds light on the profound medical consequences and setbacks that poorly controlled anxiety can have on diabetic patients. Therefore, recognizing the impact of anxiety on our patients with diabetes is critical in preventing further complications, especially microvascular, macrovascular and potentially other life-threatening events.

<![CDATA[SAT-684 A Deadly Triad: Coexistence of Acute Pancreatitis, Hypertryglyceridemia and Diabetic Ketoacidosis]]> The coexistence of diabetic ketoacidosis (DKA), hypertriglyceridemia and acute pancreatitis (AP) represent a complex phenomenon described as the enigmatic triad. The exact initial culprit and pathophysiologic mechanism of this chain of events are still unclear posing a challenge in management. DKA may lead to glucose and lipid metabolism dysregulation which can result in hypertriglyceridemia leading to AP. On the other hand, hypertriglyceridemia may induce AP which may decompensate diabetes and lead to DKA. In both scenarios, this triad results in an uncommon clinical presentation with up to 80% mortality rate. Most frequently reported in children, this entity accounts for only a handful of cases reported in the literature.

Case of an obese, non alcoholic 57 year old male without history of systemic illness who visits the emergency room due to mid-upper abdominal pain for the past day. Pain radiates to the back, worsens upon laying flat, and is associated with bloating and nausea. He denies previous similar episodes, vomiting, fever or bowel habit changes. Laboratory workup revealed lipidemic sample with hyperglycemia, metabolic acidosis, positive serum ketones, and normal amylase and lipase. Lipid panel revealed hypertriglyceridemia at 6,260 mg/dL (35-150). Glycated hemoglobin at 14.7%. Abdominal computed tomography showed peripancreatic inflammation consistent with pancreatitis. Given clinical and imaging criteria the diagnosis of severe hypertriglyceridemia induced AP and DKA were made. The patient was admitted to ICU and treated with intravenous insulin drip and supportive management. Resolution of DKA and successful decrease in triglycerides to less than 500 mg/dL was achieved by the third day of admission. After six days, the patient was discharged home with insulin and lipid lowering regimens.

This case demonstrates an extremely rare initial presentation of diabetes mellitus. This triad is the result of a toxic chain of events that may be lethal if not promptly identified. This case makes an exemplary lesson as to always take under consideration atypical etiologies to potentially life threatening conditions and also remarks that while uncommon, pancreatitis with normal pancreatic enzymes is a possible phenomenon. Even though false negative amylase has been associated with hypertriglyceridemia induced AP, only a few cases with negative lipase have been described. While no definite explanation has been yet discovered, negative lipase may be explained by early acinar cell apoptosis in AP. More research efforts are necessary in order to improve early diagnosis, treatment, and mortality rate for this rare but potentially deadly triad and to better understand the mechanisms underlying AP and the role that digestive enzymes play.

<![CDATA[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.

<![CDATA[SAT-667 Partial Beta-Cell Destruction: An Atypical Case of Immune Checkpoint Inhibitor Diabetes Mellitus]]> Background: Autoimmune diabetes mellitus (CPI-DM) caused by immune checkpoint inhibitors (CPIs) is rare- occurring in approximately one percent of patients exposed to this form of cancer immunotherapy. Typically, this immune related adverse event occurs after treatment with PD-1/PD-L1 inhibitors. It is characterized by abrupt insulinopenia leading to acute hyperglycemia. Beta cell autoantibodies are positive in approximately half the cases. DKA is common at the time of diagnosis. Recovery of beta cell function has been reported in only two case reports. In one case, spontaneous resolution occurred following cessation of CPI therapy and in the other the patient was treated with infliximab for concurrent inflammatory arthritis prior to resolution of CPI-DM.

Clinical Case: A 50-year-old woman was started on adjuvant pembrolizumab for stage IIIC melanoma following surgery. She had no prior history of diabetes mellitus, thyroid disease, or other autoimmune disease. Pre-infusion random blood glucoses (RBG) were 84 - 105 mg/dL. After 36 weeks, she developed hypothyroidism (TSH 17.5 (0.5-4.1 mIU/L), FT4 6 (10-18 ug/dL)) and started levothyroxine. Pembrolizumab was continued. For nine weeks following her diagnosis with CPI- hypothyroidism, her pre-infusion RBG ranged from 102-133. At 45 weeks (15 cycles) after initiating pembrolizumab, her RBG was 260. She was not on glucocorticoids and had no other signs of inflammation or stress. Pembrolizumab was continued. Just prior to her 17th cycle, 48 weeks after initiating adjuvant pembrolizumab, her RBG was 482 with a normal anion gap and HCO3, and her A1c was 8.9%. Her last dose of pembrolizumab was held. She started metformin and liraglutide. In just three weeks, a random c-peptide was inadequate at 1.7 (0.8-3.5 ng/mL) with a recent RBG of 220 and A1c of 10.3%, showing the acuity and extremity of her hyperglycemia. Over the course of the year, she has achieved excellent glucose control (A1c 6.3-7.1) on this regimen with preservation of insulin production (c-peptides 1.4-1.8 with matched RBG 92-129). She never required insulin. Her beta cell autoantibodies are negative.

Clinical Lessons: This is a case of CPI-DM in which the patient did not have complete loss of beta-cell function. The acuity of her hyperglycemia is not consistent with new onset type 2 diabetes. At diagnosis, her c-peptide was inadequate suggesting insufficient insulin production rather than insulin resistance. Therefore, her hyperglycemia is more consistent with CPI-DM than type 2 diabetes. Atypically, she did not progress to fulminant beta cell failure, which could have been due to cessation of pembrolizumab (which is not unique to this case), initiation of liraglutide and metformin, or other unknown immunologic responses that inhibited full beta cell loss. This case raises the possibility of preventing fully insulin dependent CPI-DM if hyperglycemia is caught and treated early.

<![CDATA[SAT-681 Transient Neonatal Diabetes Mellitus Triggered by EIF2AK3 and PTF1A Mutation]]> Background: Neonatal diabetes mellitus (NDM) occurs within the first 6 months of life. Advances in molecular genetics have identified various causatives genes. Mutations in EIF2AK3 causes Wolcott-Rallison syndrome characterized by NDM, multiple epiphyseal dysphasia and growth retardation. PTF1A is associated with the development of pancreas and cerebellum. Both EIF2AK3 and PTF1A mutations are causative genes for permanent NDM with spontaneous and autosomal recessive inheritance. We report a neonate with transient NDM with both EIF2AK3 and PTF1A variants confirmed by Sanger sequencing where each parent found to be a heterozygous carrier of each mutation. Case presentation: A two-day old boy was transferred from a local hospital due to hyperglycemia (blood glucose of 385 mg/dL) and glycosuria. Serum c-peptide (0.06 ng/mL) and insulin (0.64 μU/mL) were low. The patient did not present sings of ketoacidosis and was screened negative for pancreatic autoantibodies. The patient did not have any family history of diabetes. Molecular genetic analysis was performed and continuous infusion of intravenous insulin with pre-prandial bolus was started. Oral sulfonylurea therapy was attempted to prevent adverse neurocognitive outcome however, it showed no response and unable to stabilize blood glucose level. Targeted panel sequencing identified two different novel variants: a heterozygous missense mutation (c.3272G>T) in exon 17 of EIF2AK3 gene and heterozygous missense mutation (c.53C > T) in exon 1 of PTF1A gene; both of which have not been previously reported and were no likely pathogenic variants. The patient’s father confirmed to be heterozygous carriers of the EIF2AK3 mutation while mother being heterozygous carriers of the PTF1A mutation. Blood glucose level gradually began to stabilize with insulin therapy, and upon discharge the patient switched to continuous subcutaneous insulin infusion (pump) with continuous glucose monitoring. Conclusions: NDM caused by in combination of EIF2AK3 and PTF1A gene mutation is a rare condition and could resemble the disease progress of transient form of NDM. Although hyperglycemia might not be an issue of lifelong period, early genetic screening and prompt insulin initiation with consistent glucose monitoring are able to prevent further diabetic complications. In addition, the result of genetic testing in our patient raises the possibility of NDM as polygenic form of diabetes.

<![CDATA[SAT-676 Pembrolizumab Induced Worsening Glycemic Control and DKA in Type 2 Diabetes Mellitus]]> INTRODUCTION Pembrolizumab(Keytruda) is a humanized IgG4 anti-programmed cell death-1 (PD-1) antibody serving as an immune-checkpoint inhibitor, now approved by FDA to treat several types of cancer.

Although there are few reported cases of pembrolizumab induced new onset DKA in a non diabetic patients due to its autoimmune nature, its association in worsening glycemic control and DKA in pre-existing type 2 Diabetes mellitus is not well established.

CASE 79 years old female with past medical hx of DM type 2 (Hba1c 7.4 was started on metformin), COPD(on chronic steroids and trilogy machine at home), recently diagnosed with poorly differentiated adenocarcinoma of the left lung, metastasis to liver, PDL 1 positive at 99%, started on palliative chemotherapy with Keytruda, 2 weeks after the third cycle of keytruda presented to the ED for AMS. Patient noted to be very dehydrated, somnolescent and tachypnea. Labs consistent with sugars > 600, potassium 6.8, Bicarb 5, Anion gap 33, beta hydroxybutyrate 11.5 (on 7/15/19 0.6), HbA1c 9.7,(On 12/15/16 7.3, 9/25/18 6.7, 1/22/19 7.4). PH 7.31, lactate 2.4. WBC count 21.5- no infectious source identified (CXR, CT brain, UA clean). Patient was admitted for DKA and treated with IV insulin and IV fluids. After medically stable patient was discharged with Insulin regimen. Within 5 days after being discharged, patient presented to ED again with DKA with PH 7.27, Bicarb 8, anion gap 22, sugars>600, beta hydroxybuterate 13.70. Patient was Rx for DKA- after a week of hospitalization was discharged to Hospice(due to metastatic cancer) and few weeks later expired.To summarize, pt with well controlled type 2 DM on metformin presented with frequent DKA 2 weeks after treatment with third cycle of keytruda leading to worsening glycemic control in-turn making patient Insulin dependent.

CONCLUSION Incidence of Type 1 DM with pembrolizumab treatment is being increasingly recognized and reported, and DKA is a common initial presentation. However we need further studies to establish the mechanism of worsening glycemic control leading to Insulin dependent and DKA in patients with pre-existing type 2 diabetes.

Also, physicians should counsel patients about this potential immune related adverse effect and educate them about the symptoms of hyperglycemia and DKA.

REFERENCES Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review Jeroen M K de Filette1, Joeri J Pen2, Lore Decoster3, Thomas Vissers4, Bert Bravenboer1, Bart J Van der Auwera5, Frans K Gorus5, Bart O Roep6,7, Sandrine Aspeslagh3, Bart Neyns3, Brigitte Velkeniers1 and Aan V Kharagjitsingh1,2,5,8

Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes. Anupam Kotwal1, Candace Haddox2, Matthew Block3, Yogish C Kudva1. BMJ open Diabetes and research, Vol 7, issue1.

<![CDATA[SAT-683 A Case of Autoimmune Polyglandular Syndrome Type 2 and Guillain-Barré Syndrome]]> Background: Autoimmune polyglandular syndrome type 2 (APS2) is defined by the occurrence of two or more autoimmune diseases, with Addison’s disease being most prevalent, and autoimmune thyroid disease and type 1 diabetes mellitus also being common. Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculopathy that is also autoimmune in nature, resulting in ascending muscle weakness or paralysis.

Clinical Case: A 49 year old female with past medical history of vitiligo, subclinical hyperthyroidism, and Guillain-Barré syndrome (GBS) presented to our institution with fatigue, nausea, vomiting, polyuria, and polydipsia. She had no history of diabetes. Her history was also significant for GBS, diagnosed 5 months prior to her current admission. She was treated with intravenous immunoglobulin (IVIG) and had partial improvement of motor impairment. On exam, she was noted to have dry mucous membranes, epigastric tenderness, and patches of hyopigmented skin. Laboratory studies were consistent with diabetic ketoacidosis, and she was admitted to the ICU for management.

Labs from 5 months prior were significant for a HbA1c of 6.4% (4.0-5.6%), TSH <0.002 mIU/L (0.350-4.7 mIU/L), total T3 154.9 ng/dL (79-149 ng/dL), and free T4 1.7 ng/dL (0.7-1.9 ng/dL), and elevated thyroid stimulating immunoglobulin.

During the current admission, HbA1c had risen to 13.6%, C-Peptide 0.6 ng/mL (1.1-4.4 ng/mL) and GAD-65 antibody >250 IU/mL (<5 IU/mL), consistent with a diagnosis of late-onset type 1 diabetes. Repeat thyroid function tests (TSH <0.002 mIU/L, total T3 74 ng/dL, and free T4 1.2 ng/dL), were consistent with subclinical hyperthyroidism. A 21-hydoxylase antibody level was 13 U/mL (<1 U/mL), but cortisol rose appropriately in response to cosyntropin. Based on the patient’s constellation of vitiligo, autoimmune thyroid disease, type 1 diabetes, and elevated 21-hydroxylase antibodies, she was diagnosed with APS2.

Conclusion: We present an unusual case of a patient with APS2, who was diagnosed with type 1 diabetes 5 months after developing GBS and being treated with IVIG. Prior reports demonstrate an association between GBS and other autoimmune diseases, including one case report of GBS in a patient with APS2. HLA DR3 has been associated with APS2, type 1 diabetes, Addison’s disease and Grave’s disease. Its association with GBS is less clear, although HLA DR3 was increased in one Mexican cohort with GBS. This case report adds to the literature suggesting an association with GBS and other autoimmune diseases, specifically, with APS2.


Jin PP, Sun LL, Ding BJ, Qin N, Zhou B, et al. (2015) Human Leukocyte Antigen DQB1 (HLA-DQB1) Polymorphisms and the Risk for Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis. PLOS ONE 10(7): e0131374

Melmed, S., Polonsky, K. S., Larsen, P. R., & Kronenberg, H. (2016). Williams textbook of endocrinology. Philadelphia, PA: Elsevier

<![CDATA[SAT-665 A Case of Hyperglycemia in Post Pancreas Transplant Patient-Is It Insulin Deficiency or Insulin Resistance]]> Introduction

Pancreatic transplant (PTx) is a less commonly utilized option for patients with Type 1 Diabetes (DM1), usually with co-morbid end stage renal disease. Hyperglycemia in the post-PTx population can be multifactorial. We report a case of hyperglycemia with ketosis in a post-PTx patient due to insulin resistance and relative insulin deficiency.

Case Presentation

55-year-old male patient with DM1 who underwent simultaneous kidney-PTx. His immunosuppressant (IS) medications were tacrolimus, mycophenolate and prednisone. Tacrolimus levels were therapeutic and his transplant course was benign. He did not require insulin or other glucose-lowering medications post-PTx for 29 years. However, during evaluation for subacute illness with his PCP, he was found to have HbA1c of 12.6%, plasma glucose (PG) 776 mg/dl, and positive urine ketones. He was started on insulin degludec 24 units daily, which was quickly tapered to 8 units daily due to hypoglycemia. OGTT showed fasting PG of 93 mg/dl, 2-hour PG of 115 mg/dl, and stimulated C-peptide of 7.5 ng/ml. HbA1c improved to 7.4% after being on insulin for 1 month. Insulin degludec was tapered and discontinued within 2 months due to hypoglycemia despite low doses and robust PTx function. Home blood glucoses (BG) were controlled and HbA1c stable at 6% off insulin therapy. Eighteen months later, he was hospitalized for hyperglycemia with ketosis, without acidosis, during an upper respiratory infection. He was restarted on insulin (glargine, aspart). Once the acute stress resolved, his insulin dose needs reduced significantly, tapering down to insulin glargine 5 units daily. Along with daily home BG monitoring, HbA1c and C-peptide are performed every 3 months, with recent HbA1c 5.2% and C-peptide 3.0 ng/ml (simultaneous PG of 103 mg/dl).


Causes of post-PTx hyperglycemia include graft failure due to acute or chronic rejection, insulin resistance, beta cell dysfunction due to IS medications, pancreatitis, or, rarely, recurrence of autoimmunity. Factors predicting hyperglycemia are pre-PTx insulin dose, BMI and acute rejection. New onset type 2 diabetes can occur due to insulin resistance from IS medications and genetic predisposition. Measurement of C-peptide after OGTT can help determine the cause. Insulin is the standard treatment even with detectable C-peptide, though oral glucose-lowering medications have been used in the setting of insulin resistance. In this patient, severe hyperglycemia occurred during stress. He had very low insulin dose requirements when the stress and hyperglycemia resolved and reasonable C-peptide values. This scenario was most consistent with hyperglycemia due to insulin resistance and subsequent relative insulin deficiency during stress, with continued PTx function. This illustrates the importance of detailed assessment and personalized treatment in patients with post-PTx hyperglycemia.

<![CDATA[SAT-671 Glycogenic Hepatopathy. A Rare and Dramatic Manifestation of Poorly Controlled Type 1 Diabetes]]> Background: Glycogenic hepatopathy (GH) is a well described, yet underdiagnosed disorder in type 1 diabetes. Erratic blood glucose values and high insulin levels promote the excessive deposition of glucose storage in the liver as glycogen, resulting in hepatomegaly, right upper quadrant pain and abnormal liver function. GH was first described with the introduction of insulin as a therapy to treat type 1 diabetes in the early 20th century. As our ability to effectively treat type 1 diabetes mellitus has improved, GH is seen much less commonly. Today, GH generally effects adolescent or young adult patients with poorly controlled type 1 diabetes mellitus and DKA. It is reversible with successful treatment of hyperglycemia.

Clinical Case: An 18 year old woman with a history of poorly controlled type 1 diabetes mellitus and frequent admissions for DKA was admitted for DKA and pyelonephritis. On admission, the patient complained of significant right upper quadrant pain and was found to have elevated transaminase values of: AST 1199 U/L (<37 U/L), ALT 371 U/L (56 U/L), an elevated alkaline-phosphatase of 319 IU/L (<135 IL/L) and normal indices of biosynthetic function (INR/PT). After inpatient treatment of DKA and pyelonephritis, the right upper quadrant pain persisted and required pharmacologic analgesia. Radiographic evaluation demonstrated severe hepatomegaly (24 cm in maximum length) without focal lesions. Laboratory evaluation for viral hepatitis, autoimmune hepatitis, Celiac Disease, Wilson’s Disease and hemochromatosis were unremarkable. Given the patient’s persistent symptoms and severity of hepatomegaly, hepatic biopsy was performed.Biopsy findings were consistent with glycogenic hepatopathy demonstrating steatosis and glycogen deposition with nucleic glycogenation and mega mitochondria.Our patient had higher than usual insulin requirements for type 1 diabetes (~1 unit/kg/day). Abdominal pain, hepatomegaly and elevated LFTs resolved over a 2 month duration with improvement in her blood glucose control. Conclusions: GH is an established yet rare complication of poorly controlled type 1 diabetes. Glycogen deposition in the liver leads to painful hepatomegaly due to stretching of the liver capsule. GH has a female predominance (77%) and is characterized by elevated AST >>ALT with preserved liver biosynthetic function.It is postulated that GH is a result of elevated blood glucose levels and elevated insulin levels. The patient we describe has long standing poorly controlled type 1 diabetes mellitus, frequent admissions for DKA and high insulin requirements. To our knowledge, insulin requirements have not been investigated or previously reported as a potential risk factor for this condition.

<![CDATA[SAT-689 Amantadine Induced Severe Hypoglycemia in a Patient With Type 1 Diabetes and Multiple Sclerosis]]> Introduction: Amantadine is one of the few options commonly used to treat fatigue associated with multiple sclerosis. However, in a previous trial investigating the effect of amantadine on oral glucose tolerance test results, amantadine caused a reduction in plasma glucose and glucagon levels while increasing insulin levels in healthy volunteers [1]. If amantadine can reduce glucagon levels, we hypothesized that it might also cause hypoglycemia in patients with type 1 diabetes.

Case presentation: The patient is a 34-year-old African American male who has a past medical history of type 1 diabetes and multiple sclerosis. His baseline hemoglobin A1c values ranged from 6.9% to 7.6% and his weight was 88 Kg. His insulin glargine dose was 28 units daily while his insulin lispro was 10 units before meals. For almost one year he was followed in clinic and had no episodes of severe hypoglycemia (defined as hypoglycemia requiring assistance from another person).

The patient complained about gait imbalance and fatigue from multiple sclerosis for which he was followed by a neurologist. To treat these symptoms, he was prescribed amantadine 100 mg twice daily. A couple of hours following his first dose of amantadine after eating his usual breakfast (with his sister), the patient was found unconscious by his sister. Emergency Medical Services (EMS) was called and he was found to have a blood glucose of 22 mg/dL. He was admitted to the hospital. During that admission, amantadine was discontinued, and he was discharged on insulin glargine 24 units daily and insulin lispro 10 units with meals.

Discussion: We present a case of suspected amantadine induced severe hypoglycemia. In patients with type 1 diabetes, there is a loss of the pancreatic β-cells while the α-cells are preserved [2, 3]. We hypothesize that if amantadine reduces glucagon production from the α-cells, patients would be prone to severe hypoglycemia, presumably because of the unopposed insulin action. Although it is unlikely that the severe hypoglycemia was secondary to insulin since the patient was on stable doses, it cannot be completely excluded. We recommend caution when prescribing amantadine to patients on insulin therapy particularly within the first two hours after rapid acting insulin administration. More research is needed to explore this possibility.

References: [1] Diabetes Metab Syndr Obes 2009; 2: 203. [2] Br J Diabetes Vasc Dis 2014; 14: 45. [3] Peptides 2018; 10: 54.

<![CDATA[SAT-680 Diabetes Mellitus Induced by Programmed Cell Death-1 (PD-1) Inhibitors: A Case Report]]> Introduction:

Immune checkpoint blockade has revealed a remarkable success in the treatment of a range of cancer types. Immune-related adverse events on the endocrine system may be permanent and carry high morbidity and mortality.


A 35-year-old black male presented to the ED with acute onset diffuse abdominal pain, along with nausea and vomiting. Review of systems was positive for polyuria and polydipsia. The examination was unremarkable apart from a sizeable fungating lesion of the left lower extremity by the ankle measuring 12 x 8 cm. Investigations indicated blood sugars around 600, serum bicarbonate of 19 mEq/L, an anion gap of 19 mEq/L, serum BHB was elevated, and lactate within normal. The patient was diagnosed with DKA, started on an insulin drip, and admitted to the ICU.

Our patient had no known personal or family history of diabetes. A few years ago, he had suffered from a non-healing chronic ulcer in his left ankle secondary to a motor vehicle accident. Three months ago, he had been diagnosed with a well-differentiated squamous cell carcinoma, arising from his chronic non-healing ulcer. One month ago, He had started Pembrolizumab 200mg Intravenously, and he had received a total of two cycles, the last cycle was one week ago. Shortly after he presented to the ED with the above chief complaint.

He made a complete recovery and further investigations revealed HbA1c of 7.2%, C-peptide levels of <0.1 ng/mL, which supports the diagnosis of T1-DM. He was discharged home, and Pembrolizumab was continued.


Autoimmune T1-DM has been reported after receiving anti-PD-1 therapy. In a recent study included 27 patients with a variety of solid-organ cancers, and all had received anti–PD-1 antibodies treatment, autoimmune, T1-DM diabetes occurred in close to 1% of patients (1). A systematic review and meta-analysis were conducted recently showed that people developed T1-DM within three months of the initial PD-1 inhibitor exposure. Since patients treated with anti–PD-1 antibodies can present with life-threatening DKA, a high index of suspicion is crucial as early detection is the key to successful treatment and prevention of morbidity and mortality. It remains unclear if it is safe to restart the checkpoint inhibitor after an immune-related adverse event, and further studies are necessary in order to resolve this dilemma. A recent retrospective study included patients with melanoma showed that anti–PD-1 therapy could be safely resumed after severe adverse event requiring immunosuppression (2).


1. Stamatouli, A. M. et al. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes 67, 1471–1480 (2018).

2. Menzies, A. M. et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann. Oncol. 28, 368–376 (2017).

<![CDATA[SAT-678 New Onset Type 1 Diabetes and Immune Thrombocytopenic Purpura in an Adolescent Male: A Case Report]]> INTRODUCTION:

Type 1 diabetes mellitus (T1D) is an autoimmune condition caused by anti-pancreatic antibodies which attack and destroy the insulin-producing beta cells. Similarly, in immune thrombocytopenic purpura (ITP), anti-platelet antibodies destroy platelets, causing low platelet counts which can lead to petechiae and bleeding. Common autoimmune conditions seen in children with T1D include thyroid and celiac disease. Previous case reports discussed ITP in children with known T1D. Our patient presented with new onset T1D and diabetic ketoacidosis (DKA) in addition to new onset ITP.


The patient is a 12 year old previously healthy male with a several week history of polyuria, polydipsia and nocturia, in addition to fatigue and lack of weight gain in the previous two years. Initial labs confirmed diagnosis of T1D with hemoglobin A1c of 12.9% and serum glucose of 460 mg/dL, in addition to DKA, with bicarbonate of 13 mmol/L, pH of 7.30, elevated anion gap and beta-hydroxybutyrate. Due to the presence of DKA, the patient was started on an insulin drip. Thyroid labs showed hyperthyroidism, with TSH- <0.02 (0.5-4.5 mIU/L) and free T4- 2.84 (0.7-1.68 ng/dL), so he was started on methimazole 20 mg daily. Confirmatory pancreatic antibodies and thyroid antibodies were sent. CBC showed thrombocytopenia with initial platelet count of 41,000, hemoglobin of 16.9 g/dL, and white blood cells of 5.05. Follow up platelets continued low at 37,000, so he was seen by a hematologist, which confirmed the Diagnosisx of ITP. Patient had a history of easy bruising in arms and legs, one episode of epistaxis and minimal bleeding after brushing teeth, with negative history of hematuria. Follow up labs resulted in negative thyroid antibodies (TPO Ab, TSI and thyroglobulin Ab) with normalization of labsthyroid function tests, so the methimazole was discontinued. Patient is being followed by Hematologya hematologist, and pancreatic antibodies were done, which were negative. Hematology concurred with diagnosis of ITP despite negative antibodies due to diagnosis of T1D. First line therapy for ITP is IVIG and steroids, however due to national shortage of IVIG and risk for worsening hyperglycemia with steroids, these were avoided. Instead, patient was started on Eltrombopag daily for treatment of his ITP. Platelet count has improved on eltrombopag, with latest range of 126-146,000. Latest hemoglobin A1c is of 6.2%.


In the case of new onset type 1 diabetes mellitusT1D, it is’s important to keep in mind that ITP is another autoimmune condition that can present in these patientspresent. In addition to IVIG and steroids, Eltrombopag is a good ttreatment option that does not interfere with glycemic control. More research is needed to measure the frequency of ITP among patients with type 1 diabetes.

<![CDATA[Historical and new insights into pathogenesis of type 1 diabetes]]>


In recent years, there have been exciting new insights into pathogenesis of type 1 diabetes in a number of areas of immunology. In this edition, a collection of four review articles are presented, which encompass new findings presented at the Immunology of Diabetes Society meeting in London 2018. The articles are focused particularly in 4 related areas of investigation, which include autoantibodies in type 1 diabetes, new autoantigenic targets for CD4 T cells, trafficking of immune cells to the pancreas and islet‐immune interactions in the pancreas.

<![CDATA[Birth and coming of age of islet autoantibodies]]>


This review takes the reader through 45 years of islet autoantibody research, from the discovery of islet‐cell antibodies in 1974 to today’s population‐based screening for presymptomatic early‐stage type 1 diabetes. The review emphasizes the current practical value of, and factors to be considered in, the measurement of islet autoantibodies.