Identifying Ontarians with Type 2 Diabetes Mellitus in Administrative Data: A Comparison of Two Case Definitions.

INTRODUCTION: This study compared two previously validated sensitive and specific diabetes case definitions to explore the impact of different classification methods in Ontario ICES administrative data. METHODS: This study included patients captured by the Ontario Diabetes Database with type 2 diabetes using either the sensitive cohort definition (≥ 2 physician visits for diabetes within 1 year or ≥ 1 drug claim for diabetes or ≥ 1 hospitalization with diabetes), or the specific cohort definition (≥ 3 physician visits for diabetes within 1 year), between October 1, 2013 to September 30, 2015. Each cohort's demographic and clinical features were described using descriptive analysis. RESULTS: Using sensitive and specific definitions, 1,093,812 and 783,228 patients with type 2 diabetes were identified, respectively. Overall, the demographic and clinical characteristics were similar between cohorts. Patients in the sensitive cohort had mean age of 64.1 years and were 52.4% male, compared to 64.8 years and 53.6% male in the specific cohort. In the sensitive and specific cohorts respectively, 64.4% and 55.7% of patients reported one-year mean HbA1c of < 7% (53 mmol/mol) and 25.3% and 31.5% reported levels between 7.0-8.5% (53-69 mmol/mol). CONCLUSIONS: Although sample sizes were different between sensitive and specific cohorts, demographic and clinical characteristics were similar.

Determining the Associations Between Glucocorticoid Use During Hematologic Chemotherapy Treatment and New-onset Diabetes and Hyperglycemia and Mortality: A Population-based Cohort Study.

OBJECTIVES: The aim of this study was to determine the associations between glucocorticoid administration during chemotherapy for hematologic malignancy and hyperglycemia, new-onset diabetes, and mortality in Ontario, Canada. Hospitalization and emergency room utilization during the chemotherapy treatment period were also described. METHODS: We conducted a retrospective cohort study using health administrative data from ICES, Ontario, to assess risk of new-onset diabetes, new-onset hyperglycemia, and hyperglycemia for individuals with leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) receiving glucocorticoids during chemotherapy between 2006 and 2016. Using multivariable regression models, we determined the associations between glucocorticoid exposure and our outcomes of interest, controlling for age, sex, marginalization, and comorbidities. RESULTS: Our cohort included 19,530 individuals; 71.1% (n=13,893) received a glucocorticoid. The highest proportion of hyperglycemia occurred with leukemia (25.4%, n=1,301). Of the 15,580 individuals with no history of diabetes, those with leukemia had the highest rate of new-onset diabetes (7.1%, n=279) and new-onset hyperglycemia (18.1%, n=641), and glucocorticoid exposure increased the risk of new-onset diabetes (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p=0.04) and new-onset hyperglycemia (HR 1.28, 95% CI 1.09 to 1.5, p=0.003). Hyperglycemia during chemotherapy increased the risk of all-cause mortality for the combined (HR 1.18, 95% CI 1.09 to 1.27, p<0.0001) and NHL (HR 1.16, 95% CI 1.04 to 1.28, p=0.007) cohorts. CONCLUSIONS: Hyperglycemia is common during hematologic chemotherapy treatment and is associated with a modest increased risk of all-cause mortality. Routine screening, monitoring, and management of hyperglycemia should be an integral part of treatment plans for leukemia, NHL, or HL, with or without glucocorticoid administration.

Screening and Management Recommendations for Type 2 Diabetes in Women With Breast Cancer.

Breast cancer increases the risk of type 2 diabetes 1.07- to 4.27-fold, depending on patient and treatment characteristics, such as postmenopausal status, hormone therapy, and treatment with adjuvant chemotherapy. We evaluated the current evidence and considered the role of increased screening for type 2 diabetes in this at-risk population. This narrative review was conducted using Embase and MEDLINE databases. Keywords including diabetes and breast cancer were used. Articles were limited to those published in English between 2000 and 2022. It appears that the increased risk of diabetes begins at or just after breast cancer diagnosis, and remains elevated for at least 10 to 15 years, with greatest risk in the first 2 years after diagnosis. Subsets of patients with breast cancer appear to be at higher risk of developing type 2 diabetes, including those who were treated with adjuvant chemotherapy or hormone therapy. Further investigation is needed to develop specific screening recommendations for this population. If screening is performed with a glycated hemoglobin test during breast cancer treatment, then hemoglobin should be measured at the same time given the association of breast cancer therapy with anemia. Presence of breast cancer should not be a major factor when choosing among available antihyperglycemic agents. Overall, patients with breast cancer appear to be at an increased risk of developing type 2 diabetes. This increased risk suggests the need for further investigation to develop specific screening recommendations for this at-risk population.

Sparsely Granulated Corticotroph Pituitary Macroadenoma Presenting With Pituitary Apoplexy Resulting in Remission of Hypercortisolism.

Objective: Pituitary corticotroph macroadenomas, which account for 7% to 23% of corticotroph adenomas, rarely present with apoplexy. This report aimed to describe a patient with a sparsely granulated corticotroph tumor (SGCT) presenting with apoplexy and remission of hypercortisolism. Case Report: A 33-year-old male patient presented via ambulance with sudden onset of severe headache and nausea/vomiting. Physical examination revealed bitemporal hemianopsia, diplopia from right-sided third cranial nerve palsy, abdominal striae, facial plethora, and dorsal and supraclavicular fat pads. Magnetic resonance imaging demonstrated a 3.2-cm mass arising from the sella turcica with hemorrhage compressing the optic chiasm, extension into the sphenoid sinus and cavernous sinus. Initial investigations revealed a plasma cortisol level of 64.08 (reference range [RR], 2.36-17.05) mcg/dL. He underwent emergent transsphenoidal surgery. Pathology was diagnostic of SGCT. Postoperatively, the following laboratory findings were found: (1) cortisol level, <1.8 ug/dL (RR, 2.4-17); (2) adrenocorticotropic hormone level, 36 pg/mL (RR, 0-81); (3) thyroid-stimulating hormone level, 0.07 uIU/mL (RR, 0.36-3.74); (4) free thyroxine level, 1 ng/dL (RR, 0.8-1.5); (5) luteinizing hormone level, <1 mIU/mL (RR, 1-12); (6) follicle-stimulating hormone level, 1 mIU/mL (RR, 1-12); and (7) testosterone level, 28.8 ng/dL (RR, 219.2-905.6), with ongoing requirement for hydrocortisone, levothyroxine, testosterone replacement, and continued follow-up. Discussion: Corticotroph adenomas are divided into densely granulated, sparsely granulated, and Crooke cell tumors. Sparsely granulated pattern is associated with a larger tumor size and decreased remission rate after surgery. Conclusion: This report illustrates a rare case of hypercortisolism remission due to apoplexy of an SGCT with subsequent central adrenal insufficiency, hypothyroidism, and hypogonadism.

Suggested Canadian Standards for Perioperative/Periprocedure Glycemic Management in Patients With Type 1 and Type 2 Diabetes.

OBJECTIVES: The goal of this quality initiative was to develop consensus standards for glycemic management of patients with diabetes who undergo surgical procedures in Canada. METHODS: A modified Delphi method was used to gather broad stakeholder input and arrive at a consensus for perioperative/periprocedure diabetes management. RESULTS: Glycemic management standards were developed for the following categories: Organization of Care; Preoperative Assessment; Immediate Preoperative and Intraoperative; Postanesthesia Care Unit or Recovery Room; Postoperative Period; and Transition to Outpatient Care. CONCLUSIONS: It is anticipated these standards will serve as a basis to develop clinical tools to support the recommendations.

KIT Mutation in Gastric Gastrointestinal Stromal Tumor in a Patient With Familial Paraganglioma Syndrome Type 4.

OBJECTIVE: Familial paraganglioma syndrome type 4 is associated with mutations in the succinate dehydrogenase complex subunit B (SDHB) gene. We report the case of a patient with familial paraganglioma syndrome type 4 with the mutation c.600G>T; p.Trp200Cys who developed a gastric gastrointestinal stromal tumor (GIST) with a KIT mutation. METHODS: Clinical, radiographic, and genetic data have been presented. RESULTS: A 40-year-old man with familial paraganglioma syndrome type 4 and recurrent paraganglioma presented with epigastric pain. He had undergone resection of a paraganglioma superior to the right adrenal gland at 19 years of age, resection of two para-aortic paragangliomas at 39 years, and resection of a paraganglioma in the interatrial septum at 40 years. Computed tomography scan showed a 3.2 × 3.8-cm gastric body intraluminal polypoid mass. A partial gastrectomy was performed, which revealed a GIST with a KIT mutation (NM_000222.2[KIT]:c.2466T>A[p.Asn822Lys]). CONCLUSION: This case provides further evidence that mutations in SDHB and KIT are not mutually exclusive with GISTs. It also identifies the need for endoscopic evaluation for GIST in patients with familial paraganglioma syndrome type 4 with unexplained gastrointestinal symptoms.

Integrating Exercise Counseling Into the Medical School Curriculum: A Workshop-Based Approach Using Behavior Change Techniques.

Objective. Physician physical activity (PA) counseling remains low due partly to lack of knowledge, emphasizing the importance of providing learning opportunities to develop competency, given the strong associations between PA and health. This study aimed to describe the behavior change techniques (BCTs) used in an "Exercise Expo" workshop and examine the workshop's effectiveness for improving social cognitions to discuss exercise with patients. Methods. Second-year medical students (N = 54; Mage ± SD = 25.4 ± 2.95 years) completed questionnaires assessing attitudes, perceived behavior control (PBC), subjective norms, and intentions to provide PA counseling pre- and postworkshop. Repeated-measures analyses of variance evaluated changes in these theory of planned behavior constructs. Results. The most used BCTs included presenting information from credible sources, with opportunities for practicing the behavior and receiving feedback. Significant increases in attitudes, PBC and intentions to discuss PA were observed from pre-post Exercise Expo (P ≤ .01). No statistically significant differences in subjective norms were observed (P = .06). Conclusions. The Exercise Expo significantly improved social cognitions for PA counseling among medical students. Future interventions should target improvements in subjective norms to increase the likelihood the workshop improves PA counseling behavior. The evidence supports the usefulness of a workshop-based educational strategy to enhance medical students' social cognitions for PA counseling.

Survey of perceptions and educational needs of primary care providers regarding management of patients with class II and III obesity in Ontario, Canada.

BACKGROUND: Primary care providers (PCPs) are typically the primary contact for patients with obesity seeking medical and surgical weight loss interventions; however, previous studies suggest that fewer than 7% of eligible adult patients are referred to publically funded medical and surgical weight loss interventions (MSWLI). METHODS: We performed an anonymous survey study between October 2017 and June 2018 to explore the knowledge, experiences, perceptions, and educational needs of PCPs in Southeastern Ontario in managing patients with class II and III obesity. RESULTS: Surveys were distributed to 591 PCPs (n = 538 family physicians; n = 53 nurse practitioners) identified as practicing in the Southeastern Ontario and 92 (15.6%) participated. PCPs serving a rural population estimated that 14.2 ± 10.9% of patients would qualify for MSWLI compared to 9.9 ± 8.5% of patients of PCPs serving an urban population (p = .049). Overall, 57.5% of respondents did not feel competent prescribing MSWLI to patients with class II/III obesity, while 69.8% stated they had 'good' knowledge of the referral criteria for MSWLI. 22.2% of respondents were hesitant to refer patients for bariatric surgery (BS) due to concerns about postoperative surgical complications and risks associated with surgery. Only 25% of respondents were comfortable providing long-term follow up after BS, and only 39.1% had participated in continuing education on management of patients with class II/III obesity in the past 5 years. CONCLUSION: The majority of PCPs believe there is a need for additional education about MSWLI for patients with class II/III obesity. Future studies are needed to develop and compare the effectiveness of additional education and professional development around risks of contemporary BS, indications to consider referral for MSWLI, management and long-term follow-up of patients after BS.

Patients eligible and referred for bariatric surgery in southeastern Ontario: Retrospective cohort study.

OBJECTIVE: To evaluate the proportion of eligible individuals, within one health region in Ontario, who were referred for publicly funded medical and surgical weight-loss interventions (MSWLI). DESIGN: A retrospective cohort study that used primary care data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) and referral data from the Ontario Bariatric Network (OBN). SETTING: Primary care practices within southeastern Ontario that contribute data to CPCSSN. PARTICIPANTS: Patients with class II (body mass index [BMI] 35.0 to 39.9 kg/m2) or III (BMI ≥ 40 kg/m2) obesity who were eligible for referral to the OBN for MSWLI. MAIN OUTCOME MEASURES: Primary care data about patients within the CPCSSN database were linked to referral records within the OBN database using 3 indirect identifiers to determine the proportion of patients with class II and III obesity who were referred to the OBN for MSWLI. An adjusted multivariate logistic regression model was used to determine the most significant predictors of referral. RESULTS: Of the 87 276 patients within one health region in Ontario, 15 526 (17.8%) patients had class II or III obesity and were eligible for referral for MSWLI. Only 966 out of those 15 526 (6.2%) patients were actually referred for MSWLI. In the multivariate regression analysis, BMI had the strongest association with referral in terms of adjusted odds ratio (AOR), varying from 2.50 (95% CI 2.04 to 3.06) for a BMI of 40.0 to 44.9 kg/m2, to 5.15 (95% CI 4.21 to 6.30) for a BMI of 50.0 kg/m2 or greater. Referral was more likely for female than male patients (AOR = 2.18; 95% CI 1.86 to 2.57), those living rurally than for urban dwellers (AOR = 1.39; 95% CI 1.20 to 1.60), and those aged 30 to 39 (AOR = 1.61; 95% CI 1.24 to 2.09) and 40 to 49 (AOR = 1.53; 95% CI 1.18 to 1.98) compared with other age groups. CONCLUSION: Within one health region in Ontario, the referral rate of patients with class II and III obesity for MSWLI was low. Our findings highlight the need for further research to understand and address the barriers to referral of patients with class II and III obesity for MSWLI.

Prevalence and Clinical Characteristics of Adults Presenting With Sodium-Glucose Cotransporter-2 Inhibitor-Associated Diabetic Ketoacidosis at a Canadian Academic Tertiary Care Hospital.

OBJECTIVES: In this study, we examined the prevalence and clinical characteristics of sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated diabetes ketoacidosis (DKA). METHODS: A retrospective chart review of patients admitted for DKA over 4 years. Patients with SGLT2i-associated DKA were invited for pancreatic autoantibody testing. A subset of patients were invited for an interview to identify clinical characteristics suggestive of undiagnosed latent autoimmune diabetes in adults (LADA). RESULTS: Of 647 DKA admissions, 6.6% were associated with SGLT2i use. Time from SGLT2i initiation and DKA ranged from 2 weeks to 3.25 years; 69.8% had euglycemic DKA. Pancreatic autoantibody testing on 20 patients identified 5 originally diagnosed with type 2 as having LADA. Four were interviewed and had a LADA clinical risk score predictive of this diagnosis. CONCLUSIONS: A larger study is needed to qualify the role of the LADA clinical risk score with confirmatory pancreatic autoantibody testing before SGLT2i initiation to reduce DKA risk.

Variability of Clinical Practice Management of Type 1 and Type 2 Diabetes During Surgery Across Canada.

OBJECTIVE: As part of a larger project to develop quality standards in perioperative diabetes management, the goal of this project was to assess self-reported management of surgical patients with diabetes across healthcare institutions and specialties in Canada. METHODS: Current practice of perioperative management of patients with diabetes was assessed using multiple-choice questions based on commonly encountered clinical scenarios involving patients with type 1 and type 2 diabetes. The survey was sent to a broad stakeholder group of individuals involved in perioperative medicine in academic and community settings across Canada. RESULTS: Responses to clinical case scenarios demonstrated more consistent approaches for patients with type 1 diabetes undergoing cardiac surgery, possibly reflecting more robust evidence. There was more variability in the management of noninsulin antihyperglycemic agents and hyperglycemia in patients with type 2 diabetes undergoing noncardiac surgery. CONCLUSIONS: Given the variability in clinical practice, standards and clinical tools are required for perioperative and periprocedural glycemic management in Canada to inform practice, improve the experience and outcomes for people with diabetes and provide a foundation for quality improvement initiatives and benchmarking.

LONG TERM FOLLOW-UP OF ONE OF THE FIRST PATIENTS TO RECEIVE HUMAN GROWTH HORMONE THERAPY.

OBJECTIVE: Treatment of growth hormone (GH) deficiency with GH extracts from human pituitary glands was introduced by Dr. Maurice Raben at Tufts New England Medical Center in 1956. We report long term follow-up of one of the first patients treated with GH. METHODS: Clinical, radiographic, and genetic data are presented. RESULTS: A 78-year-old man presented for follow-up. He was one of the first patients to receive GH therapy from Raben in 1958. Growth was reported as normal until age 3 and then decelerated. At age 17 years, he was 129.5 cm with absent sexual development and bone age of 7 years. Treatment was initiated with desiccated thyroid and cortisone acetate for 8 months. Human GH extract was then initiated with 2 mg 3 times/week for 2 years, then 3 mg 3 times/week for 6 months, resulting in a final height of 168.9 cm. Testosterone intramuscularly every 2 weeks was added with sexual maturation over 2 years. He remained on testosterone injections until the age of 40 years, and on transdermal testosterone until the age of 50 years. At age 27 years, he was treated by Raben with human chorionic gonadotropin and menotropins for spermatogenesis restoration with successful conception by his wife. At age 78 years, pituitary MRI revealed a tiny amount of pituitary tissue within normal-sized sella turcica with absent pituitary infundibulum. A combined pituitary hormone deficiency genetic panel did not reveal any mutations. CONCLUSION: Sixty-two years later, the patient remains in good health and grateful to a pioneer in Endocrinology for groundbreaking therapy of short stature. The cause of his hypopituitarism remains unknown.

RAPID DESENSITIZATION WITH INTRAVENOUS INSULIN IN A PATIENT WITH DIABETIC KETOACIDOSIS AND INSULIN ALLERGY.

OBJECTIVE: We report a case of insulin desensitization in a patient with known allergy to multiple insulin preparations who presented with diabetic ketoacidosis (DKA). METHODS: Clinical and laboratory data, and desensitization protocols are presented. RESULTS: A 65-year-old woman with type 2 diabetes and a documented insulin allergy presented with severe DKA. She was managed initially with intravenous (IV) fluids, sodium bicarbonate, and hemodialysis. An intradermal skin test was positive for 0.01 units/mL of human regular insulin. A rapid desensitization protocol for IV human regular insulin was initiated after pretreatment with methylprednisolone, ranitidine, montelukast, and cetirizine. An initial dilution of 1 unit of insulin in 100,000 mL of 0.9% sodium chloride was started at 5 mL/hour IV. The dilution was increased at 60-minute intervals to 1 unit/10,000 mL, 1 unit/1,000 mL, 1 unit/100 mL, 1 unit/10 mL, then 1 unit/1 mL. The dose was then increased from 1 to 7 units/hour (0.1 units/kg body weight/hour). The anion gap closed after 24 hours, and overlapping desensitization was started for subcutaneous (SC) human regular insulin starting with 0.00001 units with a gradual increase to 7 units before meals and 6 units at bedtime over 5 days. There were no anaphylactic reactions to IV or SC insulin. She was discharged with human regular insulin SC 4 times daily, oral montelukast, cetirizine, diphenhydramine as needed, and an epinephrine pen. No allergic reactions were reported at follow-up visits. CONCLUSION: Rapid insulin desensitization is possible to allow treatment of DKA with human regular insulin IV in patients with known insulin allergy.

BILATERAL ADRENAL HEMORRHAGE WITH ADRENAL INSUFFICIENCY AFTER DALTEPARIN USE POST HIP ATHROPLASTIES.

OBJECTIVE: Multiple case reports have implicated the use of heparin for deep vein thrombosis (DVT) prophylaxis with bilateral adrenal hemorrhage. Only 1 previous report has described this with the low molecular weight product, dalteparin. We report a case following bilateral hip arthroplasties. METHODS: Clinical and laboratory data are presented. RESULTS: A 69-year-old woman underwent bilateral total hip arthroplasties with dalteparin 5,000 international units subcutaneously daily for 30 days postoperatively. The patient's past medical history was unremarkable. She was discharged 5 days post-surgery and required readmission 1 day later for epigastric pain, nausea, and vomiting. Her platelet count was 91 × 109/L (normal, 150 to 400 × 109/L). She was discharged after 4 days with pain resolution. She presented 4 weeks later with nausea and vomiting for several days. Serum sodium was 123 mmol/L (normal, 133 to 145 mmol/L), potassium was 6.0 mmol/L (normal, 3.7 to 5.3 mmol/L), total calcium was 3.37 mmol/L (normal, 2.25 to 2.80 mmol/L), creatinine was 404 µmol/L (normal, 0 to 85 µmol/L), and her platelet count was normal. On short adrenocorticotropic hormone stimulation test, baseline plasma cortisol was 123 nmol/L and the peak was 129 nmol/L. She was treated with hydrocortisone, fludrocortisone, and 0.9% saline with resolution of symptoms and normalization of electrolytes, calcium, and renal function. Computed tomography showed bilateral adrenal masses. Core needle biopsy was consistent with necrosis. There were no bleeding disorders on hematologic work 3 months later. The most likely etiology of bilateral adrenal hemorrhage was heparin-induced thrombocytopenia from dalteparin. CONCLUSION: This case highlights the importance of vigilance for the complication of bilateral adrenal hemorrhage with adrenal insufficiency in patients receiving dalteparin for DVT prophylaxis.

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.