BackgroundHypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature.Case presentationA 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411–1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient’s IGF-2 levels normalized and hypoglycemic symptoms resolved.ConclusionDue to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as “big IGF” also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.

Highlights• Hypoglycemia is frequent in patients with type 1 and type 2 diabetes who are treated with insulin and/or insulin secretagogues. • Hypoglycemia can be fatal and appears to increase the risk of cardiovascular disease and subsequent mortality. • Clinicians must make efforts to reduce hypoglycemia while maintaining optimal control. These efforts include patient education, use of continuous glucose monitoring, and the use of medications with a lower risk of hypoglycemia. AbstractHypoglycemia is a frequent occurrence in patients with diabetes who are treated with insulin and insulin secretagogues. Hypoglycemia is the limiting factor that prevents patients from achieving the glycemic control known to reduce the microvascular complications of diabetes. Recurrent episodes of hypoglycemia can lead to impaired awareness of hypoglycemia where the first symptom of a low blood sugar is unconsciousness. The fear of hypoglycemia has a significant effect on the quality of life of patients and their families. In the acute setting, hypoglycemia can kill, and clinical trials have demonstrated that a single episode of severe hypoglycemia increases the risk of subsequent mortality and cardiovascular events. Clinicians must make efforts to recognize and prevent hypoglycemia in order to prevent the adverse events associated with this event. Patient education is central to these efforts. Recent developments in glucose monitoring and drug development have provided more approaches that can be used to reduce the risk of hypoglycemia in patients with diabetes. K E Y W O R D S cardiovascular disease, diabetes, hypoglycemia, insulin, mortality

Aims Diabetic ketoacidosis (DKA) is an emergency with high morbidity and mortality. This study examined patient factors associated with hospitalization for recurrent DKA. Methods Characteristics of 265 subjects admitted for DKA at Hennepin County Medical Center between January 2017 and January 2019 were retrospectively analyzed. Differences between subjects with a single admission versus multiple were reviewed. Results Forty-eight out of 265 patients had recurrent DKA. Risk factors included African American race (adjusted odds ratio (aOR) versus white non-Hispanic = 4.6, 95% CI 1.8–13, p = 0.001) or other race/ethnicity (aOR = 8.6, 2.9–28, p < 0.0001), younger age (aOR 37-52y versus 18-36y = 0.48, 0.19–1.16, p = 0.10; aOR 53-99y versus 18-36y = 0.37, 0.12–0.99, p = 0.05), type 1 diabetes mellitus (aOR = 2.4, 1.1–5.5, p = 0.04), ever homeless (aOR = 2.5, 1.1–5.4, p = 0.03), and drug abuse (aOR = 3.2, 1.3–7.8, p = 0.009). DKA cost a median of $29,981 per admission. Conclusions Recurrent DKA is costly, and social determinants are strong predictors of recurrence. This study highlights the need for targeted preventative care programs.

Objective: We report a new, life-threatening adverse effect of zoledronic acid. One of the adverse effects of zoledronic acid is acute phase reaction (APR). Mild APR is characterized by arthralgia, myalgia, headache, and fever, which are usually self-limiting. Here, we present a case of severe systemic inflammatory response syndrome (SIRS) following zoledronic acid infusion, leading to multi-organ failure. Methods: A 63-year-old female presented to the emergency department with fever, headache, and myalgia within hours after zoledronic acid infusion. Approximately 24 hours later, she developed progressive weakness and confusion. She was febrile, tachycardic, and tachypneic on presentation. Subsequently, she developed acute respiratory distress syndrome, stress or Takotsubo cardiomyopathy, shock with hypotension, and acute tubular necrosis with acute kidney failure. Results: All infectious work-up was unrevealing. She was diagnosed with severe SIRS leading to multiorgan failure. She needed aggressive supportive therapies, including mechanical ventilation, multiple vasopressors, and renal replacement therapy. She was treated with systemic steroids. She gradually improved over the next 4 weeks. Conclusion: Mild APRs are common with administration of nitrogen-based bisphosphonates. However, to date, severe life-threatening APR as seen in the above-mentioned case has not been reported. It is important for clinicians to be aware of the possibility of such adverse effects. This case highlights the need for further investigation related to underlying mechanisms of APR by bisphosphonates and identification of patients at risk so that alternative treatments may be considered. (AACE Clinical Case Rep. 2018;4:e26-e29) Abbreviations: APR = acute phase reaction; FPPS = farnesyl pyrophosphate synthase; IPP = isopentenyl pyrophosphate; IV = intravenous; UTI = urinary tract infection

Objective In this secondary analysis of the Rural Engagement in Primary Care for Optimizing Weight Reduction (RE‐POWER) randomized trial, the authors determined the effectiveness of weight‐loss interventions in people with diabetes compared with those without diabetes living in rural areas. Methods The RE‐POWER study was a randomized trial designed to determine the effectiveness of nonpharmacological behavioral weight‐loss interventions in rural participants with obesity, comparing the individual in‐clinic visit model to in‐person group sessions and phone group sessions over 24 months. In this secondary analysis, weight loss was compared in participants with and without diabetes. The effects of factors such as medications, insulin, and behavioral factors were compared. Results Participants with diabetes were less likely to lose weight during the study compared with those without diabetes up to 18 months (4.12% vs. 5.31%; net difference = 1.46%; 95% CI: 0.63%‐2.28%). Participants with diabetes on insulin lost less weight than patients with diabetes not on insulin at 6 months (4.52% vs. 6.88%; net difference = 2.35%; 95% CI: 0.55%‐4.16%). The group with diabetes had significantly lower changes in blood pressure and lipid parameters versus the group without diabetes. Conclusions Patients with diabetes in rural areas were less likely to lose weight, and metabolic parameters were less responsive to weight loss, compared with patients without diabetes.