ResearchPad - type-2-diabetes-mellitus Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-692 Comprehensive and Structured Care Program for Patients with Type 2 Diabetes Mellitus: A Preliminary Report from Raipur, Chhattisgarh State of India]]> Aim: To assess the glycemic outcomes of T2DM patients enrolled in comprehensive structured care program at the outpatient clinic of Apollo Sugar at Raipur, India. Methods: This is a preliminary, prospective, single-center, observational study on T2DM patients from Jan 2018 to December 2018. Uncontrolled diabetes or patients with comorbid conditions with the duration of disease for more than one year and age ≥18 years and who gave consent to enroll in the program were included in the study. The structured care program is a 6 months program where patients were continuously engaged by counseling them on diabetes management- diet and exercise, self-monitoring of blood glucose, health interactions with the remote health coach through a mobile app. Baseline demographics and clinical data were collected at the time of enrollment and were followed up for 6 months. HbA1c reduction is the target measurement of this program. Descriptive statistics were used to analyze and report the data. A paired t-test is used to check the significant reduction in HbA1c from baseline to follow up Results: Total 102 patients were included in this study. Mean (SD) age was 50.7 (10.5) years, males were 78 (76%) and females were 24 (24%). The mean (SD) duration of diabetes and BMI were 7.9 (7.0) years and 27.5 (4.5) kg/m2 respectively. At the time of enrollment, patients were at mean HbA1c of 9.0(2.1)%, fasting (F) and post-prandial (PP) blood (BG) glucose was 194(68) mg/dL and 247(94) mg/dL respectively. Among these patients 38% had neuropathy and 15% had retinopathy as their complications. These patients were regularly followed up over the phone call to counsel on diabetes management with a healthy diet, exercise, self-monitoring of blood glucose, and medication compliance. After 6 months followup the HbA1c, FBG, and PPBG were 7.6 (1.5) %, 139 (50) mg/dL, and 196 (75) mg/dL, respectively with a significant mean reduction of 1.4%, 56 mg/dL, and 51 mg/dL (p <0.001). Further analysis of glycemic outcomes between these patients on oral hypoglycemic agents (OHAs) and OHAs+insulin, the reduction in HbA1c (1.5%) was not significant. Conclusion: Our study demonstrates that a structured care program might bring a clinically significant glycemic control through tight adherence to SMBG, diet, exercise, and medication. To establish these results a study in large sample is in progress.

<![CDATA[SUN-684 The Dance of Diabetes]]> Nonketotic hyperglycemic chorea-ballism (NKHCB) is a rare movement disorder typically associated with uncontrolled type 2 diabetes. It is often the result of a focal lesion of the contralateral basal ganglia. Here we present a case of a patient who presented with hyperglycemic chorea as the initial manifestation of their diabetes. A 73 year old caucasian female with no known past medical history was brought to the emergency room with involuntary movements of the left face, arm and leg. These movements were sudden in onset and not suppressible. Her vitals were stable on arrival and exam was benign apart from choreiform movements of the left arm, left leg and left perioral muscles. Her labs were significant for a random blood glucose level of 418 mg/dl and HbA1c of 12%. As part of her workup she underwent a CT head which showed an asymmetric hyperdensity involving the right putamen. She underwent additional workup of chorea to exclude infection, vitamin deficiencies, heavy metal poisoning, electrolyte imbalances, liver dysfunction, all of which returned negative. She eventually underwent an MRI of the brain which showed symmetric, mildly bright T1 signal within both putamen suggestive of mild bilateral calcium deposition bilaterally. The patient was further evaluated by neurology who felt that her overall clinical presentation and imaging findings were consistent with a diagnosis of NKHCB. She was placed on an insulin regimen with significant improvement in blood glucose levels. Her symptoms resolved within two weeks as noted on outpatient follow up. NKHCB is a rare condition that manifests in the setting of uncontrolled nonketotic diabetes mellitus. The exact underlying pathophysiology of changes seen on imaging of patients with NKHCB is not fully understood. The diagnosis is based on typical clinical and radiological features including the presence of ballistic or choreiform movements in the setting of marked hyperglycemia and the absence of ketoacidosis. This case is unusual as her chorea was the presenting symptom of her diabetes which was previously undiagnosed. The characteristic radiological feature is a high signal intensity basal ganglia lesion on the T1-weighted brain MRI. The mainstay of treatment includes normalization of the blood glucose, although in some cases antipsychotic use has been described. In most cases, complete resolution of symptoms has been reported within 10 months. Given the excellent prognosis with management of blood glucose, non ketotic hyperglycemia is an important differential to consider in a patient presenting with chorea-hemiballismus.

<![CDATA[SUN-682 Type Two Diabetes Patient in Remission After Twelve Years of Diagnosis]]> Introduction

Type 2 diabetes (T2D) has been defined as a lifelong condition which is inevitably progressive.1 The idea that beta cell function certainly declines with time in diabetic people who have developed T2D has been definitively disproven.2 It has been recognised that the processes that cause T2D can be reversed and T2D remission can be achieved.2

Many studies show that, by changing life style dramatically, controlling diabetes can improve significantly and a significant proportion of patients can also reduce or come off their glucose-lowering therapies.3 This has been formally proven in DIRECT, with clear evidence of gradual continuing improvement in beta cell functional capacity over at least 12 months.4 Remission was linked to weight loss, as two third of those who lost more than 10kg were in remission after two years.4


A case study was done on a 66 years old male, who is diabetic for the last 12 years, with other comorbidities: hypertension and hypercholesterolemia.

He presented with Hemoglobin A1C (HbA1c) of 7.4% with BMI of 37.7 kg/m2 on four oral hypoglycaemic agents and basal insulin of 20 units per day.

His treatment was changed by adding Glucagon-like peptide-1 receptor agonists (GLP-1 RA) for better glycemic control and weight reduction in a setting of a multidisciplinary team approach, including endocrinologist, diabetes educator, dietitian and physical trainer.


Over the last one year and two months, patient was able to stop all his diabetes medication including GLP-1 RA. Over three years follow ups patient achieved weight reduction of 17.3% with HbA1c of 6.5% and additional other metabolic factor benefits.


Even with 12 years of diabetes, reversibility of T2D can still be achieved with weight reduction of over 15%. We will wait for another 10 months to reconfirm our data for two years remission.


1. Steven S, Taylor R. Restoring normoglycaemia by use of a very low calorie diet in long‐and short‐duration Type 2 diabetes. Diabetic Medicine. 2015 Sep;32(9):1149-55.

2. Nagi D, Hambling C, Taylor R. Remission of type 2 diabetes: a position statement from the Association of British Clinical Diabetologists (ABCD) and the Primary Care Diabetes Society (PCDS). British Journal of Diabetes. 2019 Jun 27;19(1):73-6.

3. Wing RR, Blair E, Marcus M, Epstein LH, Harvey J. Year-long weight loss treatment for obese patients with type II diabetes: does including an intermittent very-low-calorie diet improve outcome?. The American journal of medicine. 1994 Oct 1;97(4):354-62.

4. Taylor R, Al-Mrabeh A, Zhyzhneuskaya S, Peters C, Barnes AC, Aribisala BS, Hollingsworth KG, Mathers JC, Sattar N, Lean ME. Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for β cell recovery. Cell metabolism. 2018 Oct 2;28(4):547-56.

<![CDATA[SUN-695 Should Vitamin B12 Status Monitoring Be Implemented for Patients Taking Metformin?]]> Introduction: Cobalamin (vitamin B12) is used in multiple metabolic processes, functioning primarily as a coenzyme with Methylmalonyl-CoA mutase and Methionine synthase in humans. Without functioning enzyme, substrate levels build up which are neurotoxic, leading to neurological debilitation. Lack of enzyme also halts cellular replication processes causing severe anemia. Since numerous studies have found decreased cobalamin levels in patients who regularly take metformin1, then could regular monitoring of cobalamin levels in such patients prevent these outcomes?

Case Presentation: We present a 50-year-old female who reported to the ED with general weakness and shortness of breath after having a seizure. Her medical history included type 2 diabetes mellitus being treated with metformin and a history of seizures controlled by carbamazepine since childhood.

Neurological exam abnormalities consisted of DTRs that were 1/4 on all proximal and distal upper and lower extremities and absent fine sensory and vibratory sensation on ankles and feet bilaterally. Patient was also ataxic. Hgb A1c was 14%. Head CT, chest x-ray, EKG, and cardiac markers found no abnormalities. CBC found a profound pancytopenia with WBC 1.6, RBC 1.27, Hgb 5.2, MCV 119, MCH 40.9, MCHC 34.3, RDW 18.2, and platelets 113. Blood smear was normal. Bone marrow sample showed normochromic macrocytic cells with no other abnormalities. Folate level was normal and cobalamin was found to be low (61.5 pmol/L). Intrinsic factor antibodies were negative. Extensive autoimmune workup was also negative.

Discussion: Our patient’s neurological symptoms and pancytopenia were found to be due to multiple factors. R. Pawlak, found that metformin use had a 2.45 (p < 0.0001) times higher odds of developing B12 deficiency in comparison to non-metformin users1. This was also supported by a systemic review of the impact of metformin

Carbamazepine is known for its effects on decreasing the absorption of folate and has statistically been found to decrease cobalamin significantly as well.

There are several B12 assessment methods available to providers, including serum/plasma B12, Mean Corpuscular Volume (MCV), Homocysteine (Hcy), Holotranscobalamin II (holoTCII), and serum and urinary Methylmalonic Acid (MMA). Urinary MMA has been found to be the most specific and sensitive of these markers when adjusted by kidney function (through serum creatinine levels) and while fasting

Conclusion: Currently, there are no screening guidelines by the U.S.P.S.T.F or American Diabetes Association for cobalamin deficiency. However, neurologic deficits and macrocytic anemia could be prevented through monitoring cobalamin levels in diabetics receiving metformin treatment. This monitoring might be needed more in patients with seizure disorderon Carbamazebin.

<![CDATA[SUN-690 HNF4A Mutation in Siblings with Diazoxide Responsive Congenital Hyperinsulinism]]> Background: Congenital hyperinsulinism (HI) is the leading cause of severe, persistent hypoglycemia in infants. Transient HI seen at risk neonates due to prenatal stress and some of the congenital HI cases due to mutations in K-ATPase channel are responsive to diazoxide. It is not a common practice to obtain genetic evaluation for diazoxide responsive HI. However, children with dominant inactivating variants in HNF4A gene may present with diazoxide-responsive HI and mimic transient HI in infancy.

Objective: To describe two siblings with diazoxide responsive HI with HNF4A mutation associated with maturity onset diabetes of youth type 1 (MODY1).

Clinical Case: Case 1, term female with macrosomia and Case 2, preterm male appropriate for gestational age were born to same mother without gestational diabetes and with no perinatal stress. Siblings were non-dysmorphic and both presented with hypoglycemia during first week of life. Diagnosis of HI is confirmed based on inappropriately suppressed β-hydroxybutyrate at the time of hypoglycemia and inappropriate glycemic response to glucagon consistent with increased insulin action. Both siblings responded to diazoxide therapy. Family history was significant for late-onset diabetes in paternal extended family. Case 1 required very low dose diazoxide (2 mg/kg/day) during first year of life to sustain normoglycemia. She came off of diazoxide at 19 months of age. Case 2 is normoglycemic on 5mg/kg/day diazoxide at 4 months of age. Genetic evaluation through whole exome sequencing pursued upon diagnosis of Case 2 revealed paternally inherited heterozygous pathogenic start loss variant in HNF4A gene (c.3G>T) in both siblings. Father was completely asymptomatic without any history of hypo- or hyperglycemia.

Conclusion: HNF4A gene encodes hepatocyte nuclear factor-4-alpha that regulates hepatic gluconeogenesis and lipid metabolism. Dominant inactivating variants in HNF4A gene associated with familial HI, are typically associated with increased size for gestational age, mild diazoxide-responsive hypoglycemia (which may be transient) and monogenic diabetes during adolescence. HNF4A mutations were described as one of the most common genetic cause of diazoxide-responsive congenital hyperinsulinism and are associated with MODY1. It is important to consider genetic evaluation in diazoxide responsive HI cases. Identifying children with HNF4A variant early on will impact their long-term follow-up leading to earlier diagnosis and treatment of MODY-1 and potentially improve long-term outcomes.

<![CDATA[SUN-683 Was Metformin the Culprit for This Lactic Acidosis?]]> Introduction

Metformin is the first-line drug for treatment of Type 2 diabetes. A meta-analysis of 70,490 patient-years of metformin use reported no lactic acidosis. We present a case of a patient who developed lactic acidosis while on Metformin; with other contributing factors.

Case Description

A 72-year old male with dementia, diabetes, hypertension, hypothyroidism and “muscular dystrophy” was admitted with encephalopathy. Medications included levothyroxine, donepezil, insulin glargine and metformin. A Brain CT scan revealed frontal lobe atrophy and lacunar infarcts. Admission blood work revealed lactic acidosis of 5.6. Sepsis workup was negative. Metformin was discontinued, and the patient improved with intravenous hydration. Upon discharge, Metformin was restarted. Follow-up lactic acid was normal. After a subsequent hospitalization with similar presentation and peak lactic acid of 4.7, metformin was stopped altogether. The patient was referred to a neuromuscular specialist and a diagnosis of Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) was made. The “muscular dystrophy” was likely mitochondrial disease. A third hospitalization (while not on Metformin) saw a peak lactic acid of 2.8. We concluded that the lactic acidosis was secondary to MELAS, but Metformin had caused the significant spikes seen during the first two hospitalizations.


Mitochondrial disorders must be in the differential diagnosis for patients diagnosed with muscular dystrophy. The hallmark of MELAS syndrome is stroke-like episodes that result in hemiparesis, hemianopia, or cortical blindness. Other features include seizures, recurrent headaches, vomiting, short stature, and muscle weakness. Patients with mitochondrial diseases also have a high incidence of diabetes. Lactic acidosis occurs during stress. DNA testing is the gold standard for diagnosis.


Metformin is contraindicated in patients with mitochondrial disease and diabetes due to the predisposition for lactic acidosis. This is not part of the current package inserts for prescribers and patients- and we strongly recommend inclusion of this language.

<![CDATA[SUN-678 Telediabetes Improves A1C and Patient Satisfaction: A Pilot Study in a VA Institution]]> Introduction: Rural Americans experience significant health disparities and have poorer health outcomes compared to their urban counterparts. Access to health care services in rural areas remains an ongoing challenge. Telehealth services can efficiently and effectively improve access to healthcare for people living in rural and remote areas. However, it is unclear if telemedicine services would be effective in the veteran population. Therefore, we have initiated a pilot studyto verify the effectiveness and satisfaction of diabetes care delivered through telehealth (Telediabetes) in a Phoenix VA community-based outpatient clinic (CBOC).

Methods: The Southeast CBOC is a remote VA clinic in Phoenix with the largest volume of patients with diabetes. Inclusion criteria were patients with type 2 diabetes that have been seen at least one time in the endocrinology clinic at the Phoenix VA and were willing toparticipate in telemedicine. Of the 36 patients that qualified for the study, 20 (55%) were scheduled, 11 (31%) were unreached, and only 5 (14 %) declined. Interventions included optimizing use of newer diabetes medications such as GLP-1 agonists and SGLT2 inhibitors andefforts to improve adherence to treatment regimens. Methods to improve adherence included offering home self-monitoring of blood glucose, increased frequency of visits, including home video conferencing and recommending referrals to nutrition and clinical pharmacists for amultidisciplinary approach. Patient satisfaction was assessed through a validated 5-question survey using a Likert scale 1-5 immediately after each visit. The primary outcomes were change in A1c and patient satisfaction.

Results: 95% (17/18) of the participants were males, the mean age was 62.5±.14.0 years-old, and the mean BMI was 34.4±6.8 kg/m2. Median follow-up time was 189 days (range: 89-417). During follow-up, A1c decreased by 0.8% (baseline: 9.5±2.2 vs. post-visit: 8.7±2.0%, p=0.017).Overall, all patients were fully satisfied (Likert score of 5) with the telediabetes visits and 94% of the patients would choose telehealth over face-to-face appointments. Up to now 37% of patients have had at least a second visit with telediabetes.

Conclusion: Telediabetes is an effective alternative to face-to-face visits for rural veterans, as demonstrated in other communities. The high patient satisfaction and decrease in A1c in this study showed that the program can be expanded to increase access to diabetes care in remoteareas.

<![CDATA[SUN-699 Canagliflozin Induced Severe Hyponatremia- a Rare Life Threatening and Poorly Understood Complication- a Case Report]]> Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load. This can occasionally lead to severe dehydration, hypotension and in some cases, severe hyponatremia. The effects of SGLT2 inhibitors on sodium and water handling by the renal tubules is not well studied.

Clinical Case: A 49-year-old male with history of type 2 diabetes mellitus on canagliflozin, an SGLT2 inhibitor, who was brought to the Emergency Room following a motor vehicle accident from acute onset of confusion and altered mental status. Initial trauma workup was negative. He was found to have severe hyponatremia to 118 mEq/ L (n 135–145 mEq/ L) and was also noted to be in euglycemic ketoacidosis with positive serum ketones (qualitative assessment) along with acute onset urinary retention. Urine toxicology was negative including negative blood alcohol level. Thyroid function was normal 1.080 mIU/ L (n 0.47- 6.90mIU/L). His total urine osmolar excretion was ~ 2400 mOsm in 12h (n 500–800 mOsm/kg of water/ 24 hours), confirming the diagnosis of his ongoing massive osmotic diuresis. On admission, his antidiuretic hormone (ADH) level was noted to be elevated to 9.1 pg/mL (n <4.3pg/ mL). This severe degree of hyponatremia was postulated to be secondary to canagliflozin causing massive osmotic diuresis resulting in severe intravascular volume depletion with reflex increase in antidiuretic hormone (ADH) compounded by increased free water intake by the patient.

Conclusion: With more widespread use of this relatively new hypoglycemic medication with protective metabolic and cardiovascular benefits that include weight loss and reduction of BP in T2DM patients, it is equally important to understand the physiology of potentially life-threatening adverse effects associated with severe volume depletion by massive osmotic diuresis and electrolyte abnormalities that include hypernatremia (even hyponatremia), and the timely recognition of euglycemic ketoacidosis.

<![CDATA[SUN-694 Case Study of Nonalcoholic Steatohepatitis Reversibility in Type Two Diabetic Patient with Weight Loss Using Liraglutide]]> Introduction Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease.1 NAFLD prevalence is likely to be between 75- 100% in the morbidity obese. Where Nonalcoholic steatohepatitis (NASH) in turns develops in 30% of patients with NAFLD. Obesity prevalence in Kuwait is estimated to be 39% for adults male and 52% for adults females.2 No pharmacotherapy is approved for NAFLD treatment, and the basis treatment is lifestyle modifications focusing on body fat loss.3 A study showed that may take 10% or more weight loss to have an impact on NASH Activity Scores as assessed by liver biopsy. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are approved for the treatment of T2D and obesity and have also been shown to reduce liver inflammation and fibrosis.3

Methods A 54 years old male presented to our clinic with a history of hypothyroidism, diabetes with Hemoglobin A1C (HbA1c) of 7%, hypercholesterolemia and overweight with Body Mass Index (BMI) of 27.6 kg/m2

Patient’s investigations showed high Gamma-glutamyl transferase (GGT) and ferritin level, and due to his abnormal liver function test patient was referred for abdominal ultra sound that showed fatty liver disease. With a high NAFLD score, he was referred for Fibroscan that showed fibrosis score of F3; which indicates a sever liver scarring.

GLP-1 RA was started for weight management and a better glycemic control in a setting of multidisciplinary team, including endocrinologist, diabetes educator, dietitian and a physical trainer.

Results In a six months’ period of time, patient was able to lose 15.3% of his total body weight, with better glycemic control of HbA1c of 5.6% from 7% and his repeated Fibroscan showed improvement in his score from F3 to F0 with other clinically important outcomes.

Conclusion GLP-1 RA seems to be safe to use for patients with NASH, and it might have benefits of reversing fibrosis in addition to other benefits such as weight reduction and HbA1c improvement.

References 1- Babusik P, Bilal M, Duris I. Nonalcoholic fatty liver disease of two ethnic groups in Kuwait: comparison of prevalence and risk factors. Medical Principles and Practice. 2012;21(1):56-62.

2- Jamal MH. The Status of Organ Transplantation in Kuwait.

3- Seghieri M, Christensen AS, Andersen A, Solini A, Knop FK, Vilsbøll T. Future Perspectives on GLP-1 Receptor Agonists and GLP-1/glucagon Receptor Co-agonists in the Treatment of NAFLD. Frontiers in endocrinology. 2018;9.

<![CDATA[SUN-677 The Warburg Effect: A Case of Persistent Hypoglycemia and Lactic Acidosis]]> Background: It is well established that malignant cells are able to metabolize glucose to lactate in the presence of oxygen, known as the Warburg effect (WE) - a rare metabolic complication of malignancies, presenting with lactic acidosis & hypoglycemia. It signifies a poor prognosis with high mortality rates. We present the case of a woman with malignancy who presented with persistent hypoglycemia requiring a dextrose drip and type B lactic acidosis. Clinical case: A 63-year-old female was referred to our institution for persistent hypoglycemia and lactic acidosis after being admitted to another hospital for a urinary tract infection. Her history was notable for generalized fatigue & weight loss. She had lactic acidosis (18-25mEq/L; Normal: 0.5–2.2mEq/L) despite stable hemodynamics that did not improve with resuscitation & antibiotics. Her hospital course was complicated by worsening mental status & non- hypoxic respiratory distress due to profound acidosis, requiring intubation. She required a dextrose infusion of up to 40g/hour to maintain normoglycemia and with the infusion, an increase in lactate level was noted. Workup to rule out insulin-dependent hypoglycemia, adrenal insufficiency, GH deficiency, MELAS, mesenteric ischemia & drug-related lactic acidosis was unremarkable. EEG was not suggestive of seizure activity. Initial labs were notable for elevated levels of CA-19-9 408U/mL (normal: 0–34), & CA 125 430U/mL (normal: 0–34) which were attributed to her newly diagnosed cirrhosis. However, the degree of her liver dysfunction was felt to be not severe enough to cause hypoglycemia. Imaging studies looking for tumors were unrevealing. A bone marrow biopsy done to rule out occult malignancy showed metastatic carcinoma with neuroendocrine features. Further treatment was not pursued by her family. Based on the diagnosis of metastatic cancer, it was felt that her persistent hypoglycemia was due to the Warburg effect. Conclusion: The Warburg effect (WE) is observed in cancers when the malignant cells utilize glycolysis over oxidative phosphorylation, regardless of oxygen content, for energy production. This involves aerobic glycolysis & lactic acid is its by-product. Cancer cells use more glucose via the glycolysis pathway to meet their demands leading to hypoglycemia & concurrent lactic acidosis despite normal oxygen levels. WE is a rare but severe complication of malignancies that signifies a poor prognosis. Patients with this complication need to be monitored closely until definitive treatment can be implemented. This case highlights the importance of maintaining a high clinical index of suspicion for diagnosing WE. Reference Elhomsy G. C., Eranki V., Albert S. G., et al. “Hyper-warburgism,” a cause of asymptomatic hypoglycemia with lactic acidosis in a patient with non-Hodgkin’s lymphoma. The Journal of Clinical Endocrinology & Metabolism. 2012;97(12):4311–4316.

<![CDATA[SUN-688 Pancreatic Cancer in Longstanding Diabetes]]> Background

Pancreatic Cancer carries one of the highest mortality rates in the US and it is established that there is a relationship between Pancreatic Cancer and Type 2 Diabetes Mellitus. We present a case of a woman with longstanding T2DM who developed Pancreatic Cancer and worsening of her T2DM.

Case Presentation

86 year old female was brought to the ER by her family due to jaundice and scleral icterus. Additionally, her blood glucose levels had been uncontrolled in the previous month despite good control for years. Her AST was 871 and ALT was 827, Alkaline Phosphatase was 591, and Total Bilirubin was 13.9, mainly direct with a value of 11.11. The patient had a CT Abdomen and was found to have a mass in the head of her pancreas. She underwent an Endoscopic Ultrasound and FNA biopsy. Cytology results were consistent with Pancreatic Adenocarcinoma. The mass was unresectable and it was recommended she transition to hospice. Regarding her T2DM, she was diagnosed 15 years ago and prior to the last month, her glucose had been well controlled on Metformin and Glipizide, never requiring Insulin. HbA1C 1 year prior was 6.7 and HbA1C during the admission was 8.5. During the month preceding her pancreatic cancer diagnosis, her family noticed her blood glucose levels were running higher than usual. During her admission, her glucose continued to range from 178-315 even though she was on Lantus 12 units nightly and an Insulin Sliding Scale before meals.


Although a relationship between Pancreatic Cancer and T2DM has been found, recent studies have shown that this relationship is bidirectional and complex. Several reports have shown that there is a risk association that the shorter the duration of T2DM the higher the average risk association between Pancreatic Cancer and T2DM. Several cohort and case-control studies of patients diagnosed with Pancreatic Cancer show that 25-50% of patients will have developed T2DM within 1-3 years before their diagnosis of Pancreatic Cancer and 85% of patients diagnosed with Pancreatic cancer have impaired glucose tolerance. The mechanism of action of T2DM causing Pancreatic Cancer includes insulin resistance, hyperinsulinemia, hyperglycemia, and chronic inflammation and it is proposed that this pathogenesis is more of a humoral process rather than local tumor destruction of the gland. A factor supporting this is that insulin and C-Peptide levels are reported to be higher in patients with Pancreatic Cancer and T2DM.


Unexplained elevation in HA1C should prompt clinicians to run a differential diagnosis of factors that can induced hyperglycemia. This case highlights the importance of recognizing pancreatic malignancy as a possible cause of worsening hyperglycemia in T2DM.

<![CDATA[SUN-673 Development of Euglycemic Diabetic Ketoacidosis in a Patient with Well-Controlled Type 2 Diabetes Mellitus on a Sodium-Glucose Transporter 2 Inhibitor]]> Background: We describe the case of a patient with euglycemic diabetic ketoacidosis (euDKA), in the setting of sodium-glucose cotransporter-2 (SGLT2) inhibitor use, complicated by non-anion gap metabolic acidosis and low-carbohydrate diet leading to admission.

Presentation: A 43-year-old woman with a history of type 2 diabetes mellitus treated with Metformin, with no prior history of DKA, was admitted with progressive dizziness, nausea, vomiting, malaise, palpitations, and dyspnea starting 3 days prior to admission. Her other history includes anemia due to uterine fibroids, hypertension, and hyperlipidemia. Hemoglobin A1C was 6.7%, however in the setting of anemia. She denied polyuria and polydipsia, and alcohol and drug use. She was started on a low-dose SGLT2i and pioglitazone 1 week prior to admission.

Labs revealed mild hyperglycemia (blood glucose 145 mg/dL), with mixed anion-gap and non-anion-gap metabolic acidosis, and respiratory alkalosis [arterial pH 6.97 (rr7.35-7.45), PCO2 <13.0 mmHg (rr 32-45 mmHg), bicarbonate 5mm/dL (rr 24-33 mg/dL), anion gap 22, B-hydroxybutyrate 12.52 mmol/L (rr 0-0.3 mmol/L), and chloride 108 mEq/L (rr 98-109 mEq/L)], with normal renal function, hepatic function, and lactate. Infectious work-up was negative, including chest x-ray and urinalysis.

She was diagnosed with euDKA due to SGLT2i. The SGLT2i was stopped and she was treated with insulin drip, intravenous fluids, and temporary bicarbonate drip given combined acidoses and severely low bicarbonate level, until her acidosis cleared. The patient noted that she had lately been eating a very low-carbohydrate diet in order to improve her glycemic control and promote weight loss.

Discussion: In this case, DKA was likely precipitated by ketogenesis from low-carbohydrate diet for 1 week while taking a low-dose SGLT2i. Additionally, the dual anti-hyperglycemic therapy with Metformin and SGLT2i contributed to high anion-gap metabolic acidosis, along with the presence of a non-anion-gap metabolic acidosis. The patient was successfully transitioned to Metformin and pioglitazone upon discharge. As the use of SGLT2i is becoming widespread across multiple disciplines, recognizing euDKA in the setting of profound acidemia and very low carbohydrate diet in patients who are overall lower risk is particularly important.

<![CDATA[SUN-681 Does Short Term Intensive Insulin Therapy in Newly Diagnosed Type 2 Diabetes Mellitus Delay Eventual Insulin Dependence]]> In patients with type 2 diabetes mellitus (T2DM), dysfunction of β-cells starts years before the diagnosis of T2DM and rapidly worsens after overt hyperglycemia. Use of short-term intensive insulin therapy (STIIT) at the time of diagnosis of overt hyperglycemia has shown clinical recovery of β-cells for up to 2 years. A systematic literature review of studies looking for the effect of STIIT, used within two years of diagnosis of T2DM, on the duration from relapse of hyperglycemia to eventual insulin dependence is presented in this abstract.

The key phrases ‘type 2 diabetes mellitus’, ‘short-term insulin therapy’, ‘β-cell failure’, and ‘permanent insulin dependence’ were used to search English literature. For simplicity the duration of diabetes in these studies was divided into three periods: Period 1- Diagnosis of T2DM to initiation of STIIT, Period 2- End of STIIT until relapse of hyperglycemia i.e. total glycemic remission period, and Period 3- Relapse of hyperglycemia to permanent dependence on insulin therapy. Studies were excluded if all of their participants had diagnosis of T2DM for more than 2 years at the time of inclusion, i.e., if period 1 was more than 2 years.

Six clinical trials involving STIIT were identified (Period 2). No studies that examined the clinical course of T2DM in their patients beyond the relapse of hyperglycemia (Period 3) were identified.

This literature review identified a lack of data about this important clinical question- do ‘recovered’ β-cells from STIIT exhibit a better response to non-insulin therapies after the end of period 2 and, hence, delay the secondary β-cell failure in period 3? There is a need to conduct studies with longer follow up to characterize the differences in the disease course between patients treated with STIIT and patients treated with non-insulin therapies. This can help us understand scope of STIIT beyond the initial functional remission of β-cells.

<![CDATA[SUN-691 Type 2 Diabetes Management in the Context of Smith-Magenis Syndrome: Case Report]]> Background: Smith-Magenis syndrome (SMS) is a rare condition caused by microdeletion chromosome 17p11.2 via RAI1 gene mutations, causing disrupted circadian sleep-wake patterns. Characteristic behaviors include: sleep disturbance, anxiety, maladaptive habits with self-injury (biting, picking, self-hugging, page-flipping) and outbursts. Characteristic features include: craniofacial abnormalities, short stature, 2/3 toe syndactyly, scoliosis, cardiac and genitourinary defects, hypotonia, peripheral neuropathy, epilepsy, childhood-onset truncal obesity, toileting difficulties. Management of adults with SMS span multiple disciplines: otolaryngology, audiology, ophthalmology, assessments of scoliosis, seizures, familial psychosocial health, sleep and behavioral changes with each medication. Annual assessments include: fasting lipids, thyroid panel, screening urinalysis. Patients should receive standard treatment for comorbid endocrine conditions, classically: hypercholesterolemia, hypothyroidism, growth hormone deficiency.

Clinical Case: 49-year-old Hispanic female with history of SMS who presented to endocrinology for type 2 diabetes mellitus (T2DM) management. Past medical history includes T2DM with peripheral neuropathy, hypertension, hypercholesterolemia, intellectual disability, anxiety, recurrent genitourinary infections, sleep apnea. Physical exam is remarkable for macroglossia, truncal obesity, scoliosis, extremity excoriations evident of skin picking and xerosis, syndactyly of 2nd-3rd toes. Patient exhibited maladaptive behaviors like page-flipping, self-hugging, tantrums. Over the past 3 years, BMI remained in the obese range (>30 kg/m2) and A1c fluctuated from 7.0 to 10.6% averaging 8.8% (<5.7%). Patient is currently managed on insulin glargine, pioglitazone and liraglutide. She did not tolerate metformin due to dose-dependent diarrhea. Patient’s mother chose against SGLT2 inhibitors due to diminished genitourinary hygiene. T2DM management was complicated by patient behaviors, including nocturnal consumption of fructose-containing food and beverages, exercise intolerance, and associated caregiver fatigue.

Conclusion: This case describes a patient managed for metabolic dysfunction in conjunction with a rare microdeletion disorder causing neurobehavioral disturbance with disrupted circadian sleep-wake patterns. The most difficult aspects of diabetes management included difficulty implementing lifestyle modifications to control the patient’s hyperglycemia.

<![CDATA[SUN-686 Diabetic Retinopathy in Latinos with Type 2 Diabetes: Temperance Is Protective]]> Diabetic retinopathy (DR) is a duration-dependent complication of diabetes (DM). Yet some people with DM do not develop DR despite long disease duration. We evaluated such a group in search of novel factors that might signal protection from DR, using a large cohort of Latinos with type 2 DM and readable retinal images in the GOLDR study (n=614). Participants were phenotyped and 7-field retinal images were evaluated using Airlie House criteria. We identified 90 participants with DM>10y without evidence for DR (NoDR). We compared this group of patients with another group more susceptible to DR with evidence for earlier onset DR, in DM <10y duration (EoDR, n=103). Duration of diabetes in NoDR was [x+SEM] 14.2+ 0.6y, and in EoDR, 4.3+ 2.9 y (p<0.001), a 10-y spread. We found that most of the typical DR-associated risk factors could not explain DR protection in NoDR, including age, sex, age at DM onset, systolic blood pressure (SBP), percent insulin users, duration of hypertension, fasting plasma glucose, A1C, urine albumin/creatinine ratio and estimate glomerular filtration rate; these parameters were not significantly different in the two groups. Protective factors that did emerge were female sex (p=0.02), lower diastolic BP 69.1+0.9 vs. 72.5+0.9 (p<0.01) and lower alcohol intake 3.1+0.8 vs. 7.8+2 de/w (14g drink equivalents/week; p=0.025). In a sensitivity analysis to determine whether sex accounted for the apparent effect of alcohol on DR, we evaluated the men in the study, who were more likely to be drinkers. Alcohol consumption was compared in men with DR who reported drinking alcohol (n=93) compared to men without DR who also reported drinking (n=53). Men without DR reported significantly less alcohol intake, 14.8+2.4 vs. 25.9 +3.3 de/w in those with DR (P<0.01), suggesting that a possible protective benefit of lower alcohol consumption observed in NoDR was not likely to be mediated by the presence of fewer men in that cohort. In summary, type 2 diabetic patients with no evidence of DR after 10y were more likely to be women, have a lower diastolic BP, and who imbibed less alcohol when compared with a more accelerated DR subgroup with <10yrs duration of DM. We conclude that in type 2 DM Latino patients, a focus on alcohol intake may be a useful management strategy in addition to traditional medication-based BP control and renal protection, as well as a pathophysiological pathway for DR worthy of investigation.

<![CDATA[SUN-693 What Else Should Be Done in Patients with Uncontrolled Type 2 Diabetes and Severe Insulin Allergy?]]> 9.8%. The patient is still following up with us and plans for desensitization once the osteomyelitis of the foot is controlled. Discussion and conclusion: Insulin allergy is a rare but severe condition that calls for immediate work-up. It can be managed well in close cooperation between the endocrinologist and the immunologist. Our patient developed IgE-mediated symptoms occurring immediately after insulin injection and confirmed by intradermal skin testing. Specific immunotherapy has been reported in case reports in the literature and should be considered for these patients Following AACE guidelines for the management of T2DM with the addition of bromocriptine mesylate until desensitization was a beneficial option for our patient. ]]> <![CDATA[SUN-675 Breast Cancer Treatment Causes Diabetes]]> 500mg/dL. She has a history of ER, PR positive and HER2 negative invasive adenocarcinoma of right breast with bone metastases that has progressed on chemotherapy, radiation therapy and hormone therapy. Her PI3KCA gene mutation was positive and she was started on alpelisib a week prior to hospitalization. Physical examination revealed heart rate 98/min, blood pressure 160/74mmHg, BMI 21, dry oral mucosa and reduced skin turgor. Urinalysis showed >1000mg/dL glycosuria. Random plasma glucose was 354mg/dL. Creatinine was 1.07mg/dL (baseline 0.70mg/dL). She was resuscitated with IV saline and started on glimepiride 2mg oral twice daily, glargine 5 units at bedtime with correctional insulin regimen. Despite therapy, plasma glucose remained 180-350mg/dL. Discontinuation of alpelisib, rapidly improved her plasma glucose. Discussion: PI3K (phosphatidylinositol 3 kinase) activation by insulin is a key step in whole body glucose metabolism. PI3K inhibition leads to glycogen breakdown in liver and marked insulin resistance by reduced glucose uptake in skeletal muscle and adipose tissue. Treatment options using oral agents or insulin are limited in these patients. As more patients with cancer are approved for treatment with PI3K inhibitors, clinicians need to be more aware of the mechanism of hyperglycemia to effectively manage it. More evidence based consensus is needed on management of hyperglycemia with PI3K inhibition. ]]> <![CDATA[SUN-697 Importance of Immunosuppressive Therapy for Managing Insulin Resistance Type B]]> <![CDATA[SUN-685 Approach to a Potential Liver Transplant Candidate with Insulin Antibody-Mediated Severe Insulin Resistance]]>


Insulin antibody (IA)-mediated insulin resistance is a rare autoimmune condition resulting in uncontrolled hyperglycemia. High titers of IA are associated with increased mortality secondary to severe insulin resistance and labile blood sugars. There is a paucity of standardized treatment for these patients. Although there have been reported cases of success with immunosuppressants, none of these cases involved patients with liver cirrhosis. We present a case of IA-mediated severe insulin resistance which resulted in uncontrolled hyperglycemia and ultimately delayed liver transplantation.

A 61-year-old male with IA-positive type 2 diabetes, decompensated hepatitis B and NASH cirrhosis presented with several episodes of diabetic ketoacidosis (DKA) and worsening insulin resistance. His liver transplant listing had been placed on hold until glycemic control is achieved. The patient was diagnosed with type 2 diabetes mellitus in 1998. He has no prior autoimmune history. His disease was controlled on Levemir 100 units daily until March 2019 when he presented with his first episode of DKA. He subsequently required 200 units of insulin degludec daily and U-500 insulin 200 units with meals. The patient was readmitted to our hospital in August 2019 for a variceal bleed. His hospital course was complicated by a second occurrence of DKA requiring 100-150 units/hour on an insulin drip for resolution. Labs were significant for HbA1c 8.7% and IA >625 uU/mL (negative if <5.0 uU/mL). He required increasing amounts of basal and prandial insulin after discharge. The patient was again admitted within two months for abdominal pain concerning for spontaneous bacterial peritonitis, which was complicated by his third episode of DKA. Glucoses remained uncontrolled in the range of 170 to 300 mg/dL despite high insulin doses upon discharge. Metformin was contraindicated due to episode of lactic acidosis in the setting of his cirrhosis and concern for repeated episodes of DKA prevented use of SGLT-2 inhibitors. Extensive multidisciplinary discussions led to the decision for an upcoming trial of mycophenolate mofetil followed by plasmapheresis. The goal is to improve glycemic control while also minimizing infection risk to ultimately list him for a liver transplant.

This patient highlights a major therapeutic challenge related to uncontrolled hyperglycemia and insulin resistance from anti-insulin antibodies in a cirrhotic patient. This can place patients at high risk for infection, poor wound healing and most importantly prohibit liver transplantation. Immunosuppressant therapy and plasmapheresis may drastically lower insulin antibodies and improve glycemic control, however, it will increase the risk of infection.

<![CDATA[SUN-698 Management of Hyperglycemia in an Adult Patient with Glycogen Storage Disease Type 1b]]> 70 mg/dL and lactate <2mmol/L during the night. We report a case of an adult patient with GSD1b admitted with inability to tolerate oral intake and found to have persistent hyperglycemia on admission requiring insulin therapy.Clinical Case: A 31 year old female with a history of GSD1b complicated by hypoglycemia, Crohn’s disease, chronic pancreatitis and neutropenia was admitted for abdominal pain, emesis and inability to tolerate CS. She was made NPO and was started on a dextrose drip to avoid hypoglycemia and hyperlactatemia. The rate of dextrose infusion was adjusted to maintain lactate levels <2 mmol/L. She developed persistent hyperglycemia with glucose values of 250–350 mg/dL. Laboratory evaluation revealed an HbA1c of 7.6% (reference [ref] 4.3–5.6%), C-peptide of 1.3 ng/mL (ref 0.8–3.9 ng/mL), lactate of 2.3–3.1 mmol/L (ref 0.5–2.2 mmol/L). BHB levels were normal (WNL). Anti-GAD, insulin and islet cell antibodies were negative. The main goal was to avoid hypoglycemia while keeping ketone and lactate levels WNL. The decision was made to start a regular insulin infusion at a constant rate of 1 u/hr to keep BG <180 mg/dL while on the dextrose infusion with close monitoring of lactate and BHB. Insulin and dextrose drip rates were adjusted based on BG. The ultimate goal was to determine total daily insulin requirements while ingesting her home CS doses and to transition to long acting insulin. Short acting insulin boluses were not used given risk of hypoglycemia. The patient’s unpredictable tolerance to CS made determining a fixed insulin dose challenging. She eventually managed to tolerate CS and was transitioned to 10 units of insulin Detemir twice daily. She was discharged with plans to get a CGM and a ketone meter. BG readings at home were between 140–170 mg/dL.Conclusion: We report a rare case of GSD1b and diabetes. The pathogenesis may be related to effects of chronic pancreatitis or metabolic syndrome. Treatment of hyperglycemia in patients with GSD1b is challenging given the heightened risk of fasting hypoglycemia. Treatment options are limited, and there are no data regarding the safe use of insulin in this patient population. ]]>