The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Since activation of central K_ATP channels suppresses EGP in non-diabetic rodents and humans, this study examined whether type 2 diabetic humans and rodents retain central regulation of EGP. The K_ATP channel activator diazoxide was administered in a randomized, placebo-controlled crossover design to eight type 2 diabetes subjects and seven age- and BMI-matched healthy controls. Comprehensive measures of glucose turnover and insulin sensitivity were performed during euglycemic ‘pancreatic’ clamp studies following diazoxide and placebo administration. Complementary rodent clamp studies were performed in Zucker Diabetic Fatty rats. In type 2 diabetes subjects, extrapancreatic K_ATP channel activation with diazoxide under fixed hormonal conditions failed to suppress EGP, while matched controls demonstrated a 27% reduction in EGP (p=0.002) with diazoxide. Diazoxide also failed to suppress EGP in diabetic rats. These results suggest that suppression of EGP by central K_ATP channel activation may be lost in type 2 diabetes. Restoration of central regulation of glucose metabolism could be a promising therapeutic target to reduce hyperglycemia in type 2 diabetes.

Severe obesity increases the risk for negative outcomes in patients with coronavirus disease 2019 (COVID-19). Our objectives were to investigate the effect of BMI on in-hospital outcomes in our New York City Health and Hospitals’ ethnically diverse population, further explore this effect by age, sex, race/ethnicity, and timing of admission, and, given the relationship between COVID-19 and hyperinflammation, assess the concentrations of markers of systemic inflammation in different BMI groups. A retrospective study was conducted in hospitalized patients with COVID-19 in the public health care system of New York City from 1 March 2020 to 31 October 2020. A total of 8833 patients were included in this analysis (women: 3593, median age: 62 years). The median body mass index (BMI) was 27.9 kg/m². Both overweight and obesity were independently associated with in-hospital death. The association of overweight and obesity with death appeared to be stronger in men, younger patients, and individuals of Hispanic ethnicity. We did not observe higher concentrations of inflammatory markers in patients with obesity as compared to those without obesity. In conclusion, overweight and obesity were independently associated with in-hospital death. Obesity was not associated with higher concentrations of inflammatory markers.

Malignant struma ovarii diagnosis is challenging due to its benign histologic appearance and rarity. We present a case of struma ovarii determined malignant after pulmonary metastases were incidentally discovered. A 29-year-old female with a history of benign struma ovarii presented to the emergency room with right lower abdominal pain. Abdomen and pelvis computed tomography showed multiple bilateral pulmonary nodules, which demonstrated well-differentiated thyroid tissue on biopsy. Review of prior ovarian pathology identified features of highly differentiated thyroid carcinoma. Laboratory studies were negative for thyroglobulin (TG) antibodies, thyrotropin was 0.713 mIU/L, and TG was 169 ng/mL. The patient underwent total thyroidectomy, revealing a 0.3 cm follicular variant papillary thyroid microcarcinoma without lymphovascular invasion. An I-123 whole-body scan revealed bilateral metastases in the thigh muscles. I-123 whole-body scan after receiving I-131 therapy demonstrated uptake in the lungs, thyroid bed, and bilateral thighs. A computed tomography scan 5 months later revealed a decreased size of the pulmonary nodules. Careful histologic examination is key in making an early diagnosis of malignant struma ovarii. It requires a high index of suspicion and close histologic examination to identify malignant features, mainly the presence of cytologic overlapping ground-glass nuclei and mitotic activity or vascular invasion. Additionally, a thorough review of the imaging is needed to identify any abnormal findings suggestive of metastases. Our case demonstrates that this diagnosis may be made retrospectively after the discovery of metastases and patients can have excellent response to I-131 therapy despite a relatively low TG level.

Background: COVID-19 has been associated with a higher risk of death in patients with diabetes mellitus (DM). However, there is a dearth of data regarding the effects of diabetic ketoacidosis (DKA) in these patients. We explored the in-hospital outcomes of patients who presented with COVID-19 and DKA. Methods: A propensity score-matched observational retrospective cohort study was conducted in hospitalized patients with COVID-19 in the public healthcare system of New York City from 1 March 2020 to 31 October 2020. Patients were matched, and a subgroup analysis of patients with DKA and COVID-19 and patients without COVID-19 was conducted. Results: 13,333 (16.0%) patients with COVID-19 and 70,005 (84.0%) without COVID-19 were included in the analysis. The in-hospital mortality rate was seven-fold in patients with DKA and COVID-19 compared to patients with COVID-19 and without DKA (80 (36.5%) vs. 11 (5.4%), p < 0.001). Patients with COVID-19 and DKA had a two-fold higher likelihood for in-hospital death (OR: 1.95; 95% CI: 1.41–2.70; p < 0.001) after adjusting for multiple variables. Conclusions: DKA was associated with significantly higher in-hospital mortality in hospitalized patients with COVID-19.

Article published by the Endocrine Society Article published by the Endocrine Society