Objective: Achieving and maintaining recommended glycemic targets, including those for glycated hemoglobin A1c (A1C), is key to improving outcomes in patients with type 2 diabetes (T2D). As fasting plasma glucose and postprandial glucose contribute to overall A1C, targeting both is essential for sustaining glycemic control. Methods: This review examines the complementary mechanisms of action of glucagon-like peptide 1 (GLP-1) receptor agonists and basal insulin; they both enhance glucose-stimulated insulin release and suppress glucagon secretion. GLP-1 receptor agonists also slow gastric emptying and increase satiety. Results: Adding a GLP-1 receptor agonist to therapy with a basal insulin analog has been associated with improved overall glycemic control, with comparable risk of hypoglycemia and no weight gain. Titratable fixed-ratio co-formulations of basal insulin and a GLP-1 receptor agonist have been shown to improve glycemic control, with less complex dosing schedules, possibly increasing treatment adherence. The slow titration of fixed-ratio co-formulations has been shown to reduce the occurrence and severity of gastrointestinal adverse events associated with the use of a separate GLP-1 receptor agonist. Titratable fixed-ratio co-formulations also mitigate insulin-associated weight gain, and show a comparable risk of hypoglycemia to basal insulin use alone. Conclusions: The efficacy and safety of titratable fixed-ratio co-formulations have been demonstrated for insulin degludec/liraglutide and insulin glargine/lixisenatide in the DUAL and LixiLan trials, respectively, in both insulin-naive and -experienced patients. Titratable fixed-ratio co-formulations represent an attractive treatment option for many patients with T2D. ARTICLE HISTORY

Many people with diabetes do not achieve individualized treatment targets. Therapeutic inertia, the underuse of effective therapies in preventing serious clinical end points, is a frequent, important contributor to this failure. Clinicians, patients, health systems, payors, and producers of medications, devices, and other products for those with diabetes all play a role in the development of therapeutic inertia and can all help to reduce it.

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Diamond-Blackfan anemia (DBA) is a rare genetic condition that presents due to bone marrow failure caused by a dysfunction in ribosomal biogenesis and function. The patients would often require chronic transfusions as treatment, which puts them at high risk for the development of secondary hemochromatosis. This secondary hemochromatosis results in endocrinopathies due to iron deposition into the endocrine glands. We present an interesting case report of a female patient with multiple endocrinopathies due to secondary hemochromatosis resulting from chronic transfusion therapy. Her endocrinopathies included hypothyroidism complicated by myxedema coma and, interestingly, hypoparathyroidism, which has seldom been reported in DBA patients. Early diagnosis and precise treatment of life-threatening conditions like myxedema coma in DBA patients can avoid morbidity and mortality.

Introduction: Maturity Onset Diabetes of the Young (MODY) is a relatively uncommon, but increasingly recognized cause of diabetes. Many MODY patients are misdiagnosed as type 1 or type 2 diabetes mellitus (DM) and may be treated suboptimally for many years before they are recognized. We present one such patient who went 49 years before accurate diagnosis. Case: A 59 year-old female with a history of type 2 DM presented with complaints of difficulty controlling her blood sugar. She was being treated with metformin, and had been recently started on low dose glimepiride due to persistently elevated hemoglobin A1c (HbA1c). She was diagnosed as type 2 DM at 10 years of age. Her weight was normal at the time of diagnosis, and she did not require insulin. Family history included many family members diagnosed as type 2 DM, including her maternal grandmother, mother, brother, sister, son, and two nieces. All were diagnosed in their teens, and only her son currently requires insulin. On exam, she was not obese (BMI 26 kg/m2) with no signs of insulin resistance. Antibodies to glutamic acid decarboxylase (GAD Ab) were undetectable, and C-peptide was elevated to 4.04 ng/mL in response to mild hyperglycemia. Genetic testing revealed a defect in the Hepatocyte Nuclear Factor 4 Alpha (HNF4A) gene, consistent with MODY subtype 1. The dose of glimepiride was increased, and her HbA1c improved from 8.1% to 6.1% after two months. Discussion: MODY is a form of diabetes caused by single gene mutations related to beta cell development, regulation, and function. These defects lead to impaired glucose sensing and insulin release. MODY should be suspected in patients with a strong family history of diabetes, lack of signs of insulin resistance, onset at young age, and absence of features of type 1 DM (i.e., negative GAD Ab and detectable C-peptide). MODY subtype 1 patients are typically sensitive to sulfonylurea therapy, and this is considered first-line treatment. However, some patients may develop progressive beta cell dysfunction as they age and will ultimately require insulin therapy. Disclosure D. Englert: None. J. Dendy: None.

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Hypoglycemia secondary to sulfonylureas and clopidogrel have been independently described in the literature. However, there has been minimal investigation into the risk of clopidogrel-induced hypoglycemia in the setting of long-term or concomitant sulfonylurea use in patients with Type 2 diabetes mellitus. We present a case of a patient with diabetes well managed on glimepiride (second-generation sulfonylurea) for more than 10 years who presented with an episode of hypoglycemia shortly after initiation of clopidogrel for peripheral vascular disease.

Background: A pheochromocytoma diagnosed during pregnancy is an extremely rare condition with an incidence of 0.002% of all pregnancies. If untreated, consequences are devastating including a maternal and fetal mortality as high as 50%. There is no consensus in the literature regarding the management of this condition during pregnancy. Clinical Case: A 25-year-old woman G4P1021 presented at 15 weeks of gestation with shortness of breath, palpitations and chest pain. Vitals revealed hypertension and tachycardia. A CT angiogram of the chest was obtained which ruled out a pulmonary embolism but detected a 5.5-cm left adrenal mass. Biochemical work up revealed elevated plasma and urine normetanephrines. A dexamethasone suppression test was normal. A plasma aldosterone to renin ratio was normal. An MRI of the abdomen confirmed the presence of a large heterogeneous 6-cm left adrenal mass. A multi-disciplinary team discussion including an obstetrician, endocrinologist, endocrine surgeon and anesthesiologist led to the decision to perform an adrenalectomy during the second trimester. Doxazosin was started at a dose of 2 mg daily, which was later titrated up to 2 mg BID with excellent blood pressure control. Metoprolol was added 4 days prior to surgery for heart rate control. A laparoscopic left adrenalectomy was performed at 19 weeks of gestation. Intra-operatively, the patient had a brief period of hypotension which resolved with IV fluids and a short course of vasopressors. Patient did not have any post-operative complications and is currently normotensive and with a normal heart rate without the use of any anti-hypertensive medications. Repeat plasma metanephrines and normetanephrines were within the reference range. Her latest obstetric ultrasound at 20 weeks of gestation revealed a live fetus without anatomical abnormalities. The fetus is within the normal weight and size percentiles. Conclusion: A pheochromocytoma is a rare event during pregnancy and is associated with high maternal and fetal mortality rates. Timely diagnosis and proper treatment are of utmost importance to reduce mortality. The optimal time for surgical tumor removal has not been established but the second trimester appears to be safest period given the risk for spontaneous abortion during the first trimester and that the enlarged uterus diminishes tumor accessibility during the third trimester. Pre-operative medical management is crucial similar to non-pregnant patients. The treatment of these patients should include a dedicated team including an obstetrician, anesthesiologist, surgeon and endocrinologist.