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Introduction: The Ketogenic “Keto” or “Carnivore” has come into mainstream focus for patients trying to lose weight. The aim is to induce “ketosis” by catabolizing fat into ketone bodies. Using these as fuel rather than carbohydrates. This shift can occur over the course of several days when carbohydrate intake is restricted to 20-50 g daily. This is effective for short-term weight loss but may lead to life-threatening euglycemic diabetic (eDKA) ketoacidosis in those with diabetes mellitus (DM) on SGLT2 inhibitors. Case 1: 71 year-old woman with controlled type 2 DM on sitagliptin, metformin and canagliflozin was admitted for eDKA after she presenting with worsening symptoms of shortness of breath for 3 days. Three days prior to admission, she had been experiencing shortness of breath and was started on prednisone for a presumed COPD exacerbation. On presentation, her anion gap was measured to be 31 with a serum bicarbonate level of <5 mmol/L. Beta hydroxybutyrate was critically elevated 118mg/dl (ref. 0.2-2.8). Serum glucose level is 265 mg/dl. She was also noted to have pre-renal acute kidney injury. Upon questioning, she recently started a “carnivore diet” in which she cut her carbohydrate intake to near zero. eDKA was treated with an IV insulin DKA protocol. She was discharged home on sitagliptin and metformin. Canagliflozin was discontinued and moderate carbohydrate intake was recommended with her diet. Upon follow up at our endocrinology clinic, her hemoglobin A1c remained stable at 7.1%. Case 2: 51 year-old woman with uncontrolled Type 1 DM on continuous subcutaneous insulin infusion treatment and dapagliflozin was admitted for eDKA. She also utilized a continuous glucose monitor. She had started a Keto diet 4 months prior, restricting her carb intake to 30 g daily. She progressively became fatigued, anorexic with short of breath. Upon evaluation at an urgent care, she was found to be dyspneic with a blood glucose of 276 mg/dl and anion gap of 32 and serum bicarbonate of <5 mmol/L, beta hydroxybutyrate was found to be 138 mg/dl. Her hemoglobin A1c on admission to ICU was 8.1%. She was treated as per DKA treatment protocol. She responded well and discharged with increase in her basal doses. Conclusions: These cases demonstrate serious negative consequences that can occur with carbohydrate restriction with SGLT2 inhibitor use. Prior to this, one case has been reported of eDKA associated with Dapagliflozin[1], as well as two other a cases of eDKA associated with T1DM.[2] We postulate the common thread of carbohydrate restriction was essential in tipping the balance to DKA without the cardinal feature of hyperglycemia seen in the classical presentations of DKA. Here, we present our case series in efforts to raise awareness regarding risk of low carbohydrate diets in patient’s prescribed SGLT2. A detailed history regarding patient’s dietary habits and appropriate discuss on risks of new therapy is necessa...

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Intorduction: Breast cancer is estimated to be the third leading cause of cancer-related death in women. A commonly mutated pathway in breast cancer is the phosphoinositide-3-kinase (PI3K) pathway. Newer agents inhibiting PI3K are now available for the treatment of advanced cancers. Metabolic complications of new onset diabetes/hyperglycemia and hyperlipidemia are commonly seen. The precise mechanism through which PI3K inhibitors cause hyperglycemia is unknown. We present a patient who developed hyperglycemia within 2 weeks of starting alpelisib. Clinical Case: A 68 y.o female with history of metastatic invasive lobular carcinoma of the right breast HR-positive, HER-2 negative who presents for evaluation of hyperglycemia. She was diagnosed with metastatic breast carcinoma and failed multiple treatment options. She was started on alpelisib 2 weeks prior and had no history of glucose intolerance. Her pretreatment HbA1c was 5.5% (n &lt;5.7%). After initiation of alpelisib, fasting blood glucose ranged between 100-140 mg/dL (n 100-125 mg/dL), while post-prandial blood glucose ranged between 150-300 mg/dL (n &lt;140 mg/dl). Her HbA1c rose to 7% (n &lt;5.7%). She did not manifest any macrovascular or microvascular complications, but did have a family history of type 2 diabetes mellitus. After initially being started on metformin, the dose increased to 1500 mg daily with the addition of glimepiride 1 mg. She eventually achieved stable euglycemia on metformin alone. Conclusion: Hyperglycemia has been reported to commonly occur with PI3K inhibitor therapy, the mechanism of which is poorly understood. One purposed mechanism is the effect on AMP kinase pathway which may also affect the efficacy of metformin. Here, we present a case of new onset T2DM in the setting of HR-positive, HER-2 negative breast cancer effectively treated with metformin. Future studies are needed to establish the prevalence and incidence of drug-induced hyperglycemia in patients administered PI3K inhibitors, as well as the best management approach to ensuing hyperglycemia. Reference: André F, Ciruelos EM, Rubovszky G, et.al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940. Guena, E, Roda, D, Rafii, S. Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on phase I clinical trials. Br J Cancer. 2015;113:1541-1547 Busaidy, NL, Farooki, A, Dowlati, A. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol. 2012;30:2919-2928.