Approach to the Patient With Type 2 Diabetes Requiring Add-On Medication.

In the last 20 years, the number of approved agents and agent classes for management of type 2 diabetes has expanded significantly. This more robust armamentarium affords us the opportunity to utilize drugs with complementary modes of action to address progressive hyperglycemia as insulin secretion declines over time. Furthermore, some of these agents provide additional benefits, such as weight loss, prevention of major adverse cardiac events (MACE), and protection against declining renal function. This dramatic increase of treatment options has led to complex published treatment advice which may be challenging for the busy clinician. A critical element in medication selection is awareness of the hemoglobin A1c (HbA1c)-lowering potency of the agent being considered, and the distance of the patient's HbA1c level from the individualized goal. Other important factors in choosing medication as diabetes progresses include the recognition that there is a diminishing return of glucose-lowering efficacy as add-on agents are introduced, and that the extent of benefit for cardiac and renal protection is not fully understood. In addition, the availability of newer non-insulin agents may distract the clinician from utilizing insulin, the most potent agent available. The goal of this article is to provide a straightforward approach to add-on medication in the treatment of type 2 diabetes, recognizing the limits of polypharmacy and the importance of employing agents best suited to achieving treatment targets. Proposed is a practical tool which provides stepwise guidance, utilizing available data on medication efficacy, while allowing flexibility based on clinician and patient preference.

Multisystem Progeroid Syndrome With Lipodystrophy, Cardiomyopathy, and Nephropathy Due to an LMNA p.R349W Variant.

BACKGROUND: Pathogenic variants in lamin A/C (LMNA) cause a variety of progeroid disorders including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome. Six families with 11 patients harboring a pathogenic heterozygous LMNA c.1045C>T; p.R349W variant have been previously reported to have partial lipodystrophy, cardiomyopathy, and focal segmental glomerulosclerosis (FSGS), suggesting a distinct progeroid syndrome. METHODS: We report 6 new patients with a heterozygous LMNA p.R349W variant and review the phenotype of previously reported patients to define their unique characteristics. We also performed functional studies on the skin fibroblasts of a patient to seek the underlying mechanisms of various clinical manifestations. RESULTS: Of the total 17 patients, all 14 adults with the heterozygous LMNA p.R349W variant had peculiar lipodystrophy affecting the face, extremities, palms, and soles with variable gain of subcutaneous truncal fat. All of them had proteinuric nephropathy with FSGS documented in 7 of them. Ten developed cardiomyopathy, and 2 of them died early at ages 33 and 45 years. Other common features included premature graying, alopecia, high-pitched voice, micrognathia, hearing loss, and scoliosis. Metabolic complications, including diabetes mellitus, hypertriglyceridemia, and hepatomegaly, were highly prevalent. This variant did not show any abnormal splicing, and no abnormal nuclear morphology was noted in the affected fibroblasts. CONCLUSIONS: The heterozygous LMNA p.R349W variant in affected individuals has several distinct phenotypic features, and these patients should be classified as having multisystem progeroid syndrome (MSPS). MSPS patients should undergo careful assessment at symptom onset and yearly metabolic, renal, and cardiac evaluation because hyperglycemia, hypertriglyceridemia, FSGS, and cardiomyopathy cause major morbidity and mortality.

Everyday objects and spaces: How they afford resilience in diabetes routines.

Thirty million Americans currently have diabetes, and a substantial portion do not reach the goals of clinical treatment. This is in part due to the complex barriers to effective self-care faced by people with diabetes. This study uses a patient work perspective, focusing on the everyday, lived experience of managing diabetes. Our primary research goal was to explore how the work of self-care is embedded in the other routines of everyday living. We found that everyday objects and spaces were instrumental in the incorporation of diabetes work into daily routines. Objects anchored diabetes tasks by linking illness-specific artifacts to space and time (e.g. a morning routine), and by enabling the performance on diabetes tasks while on the move in either planned or unplanned ways.

Approach to the Patient With Thyrotoxicosis Using Telemedicine.

CONTEXT: The potential for endocrine care via telemedicine has been recognized since the early 2000s when clinical outcome data demonstrated improvements in glycemic control with telemedicine. The widespread use of telemedicine during the COVID-19 pandemic has pushed telemedicine beyond diabetes care and into clinical areas with a paucity of published data. The evaluation and treatment of thyrotoxicosis heavily relies on laboratory assessment and imaging with physical exam playing a role to help differentiate the etiology and assess the severity of thyrotoxicosis. CASE DESCRIPTION: We describe a patient presenting for evaluation of new thyrotoxicosis via telemedicine, and describe modifications to consider for thorough, safe evaluation via telemedicine. CONCLUSION: Telemedicine may be an ideal way to assess and treat patients with thyrotoxicosis who are not able to physically attend a visit with an endocrinologist but still have access to a laboratory for blood draws. Potential challenges include access to imaging and high-volume surgeons if needed. Clinical and economic outcomes of telemedicine care of thyrotoxicosis should be studied so that standards of care for endocrine telemedicine can be established.

Clinical Excellence in Endocrinology.

CONTEXT: Clinical endocrinology is a field driven largely by numerical parameters. To achieve outstanding patient care, however, the clinical endocrinologist must employ a range of skills which can collectively be called "clinical excellence." While there is extensive published guidance regarding appropriate medical management and outcomes for endocrine patients, there has been no consensus definition of excellence in the field, nor any recommendation as to how excellence can be achieved. EVIDENCE ACQUISITION: Literature review, review of websites of professional societies, clinical organizations, and government agencies. EVIDENCE SYNTHESIS AND RECOMMENDATIONS: After review of endocrine clinical outcomes guidelines and published descriptions of clinical excellence generally, key aspects of clinical excellence in endocrinology were derived: the ability to work in teams, communication and interpersonal skills, skillful negotiation of the health care system, and a strong knowledge base and scholarly approach. Examples of how these skills drive superior outcomes for patients are discussed. CONCLUSIONS: Clinical excellence in endocrinology is necessary to optimize care for endocrine patients. A definition of clinical excellence should be adopted by professional societies and medical institutions and its importance in patient care recognized and emphasized. Efforts should be undertaken in the context of endocrine fellowship training and faculty development to foster the skills inherent in clinical excellence.

Ectopic ACTH Production Leading to Diagnosis of Underlying Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) has been described as a source of ectopic ACTH secretion in patients with Cushing's syndrome. This is an infrequent association, occurring in less than 1% of MTC cases. Among these, it is even more unusual for an initial diagnosis of hypercortisolism to lead to the discovery of underlying MTC. Here we present a case of a patient with weakness, diarrhea, and hypokalemia who was found first to have Cushing's syndrome and later diagnosed with metastatic MTC. The patient was treated initially with oral agents to control his hypercortisolism, then with an etomidate infusion after experiencing intestinal perforation. He also received vandetanib therapy targeting his underlying malignancy, as this has been shown to reverse clinical signs of Cushing's syndrome in patients with MTC and subsequent ectopic ACTH secretion. Bilateral adrenalectomy was ultimately required. Medullary thyroid carcinoma should be considered in patients presenting with Cushing's syndrome due to ectopic ACTH secretion, and a multimodality treatment approach is often required.

Continuing improvement in type 2 diabetes care through performance-based evaluations.

AIMS: The timely evidence-based care of type 2 diabetes mellitus (T2DM) is imperative for achieving and maintaining glycemic control, reducing complications, and changing the paradigm of this epidemic. Based largely on results from earlier performance improvement (PI) activities, we conducted a continuing medical education (CME)-certified PI activity to foster improved adherence to guideline recommendations and current evidence for the care of patients with T2DM. METHODS: Participants engaged in a 3-stage process of self-assessment, goal setting, and reassessment. RESULTS: A total of 64 clinicians completed the entire PI process, abstracting data from 1600 patient charts before and after a period of self-improvement. After the intervention, clinicians were more likely to assess patients for disease-related complications and provide counseling on proper nutrition, exercise, and smoking cessation. Patients with A1C, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) values above goal (defined as A1C ≥7, BP ≥130/80 mm Hg, and LDL-C >100 g/dL) were more likely to receive treatment modifications compared with baseline clinician performance. Significant changes observed in patient outcomes included improved mean A1C values (baseline 7.5% vs postintervention 7.3%; P = .027), decreased likelihood of BP at or above 130/80 mm Hg (baseline 37% vs postintervention 30%; P < .001), and decreased likelihood of LDL-C above 100 g/dL (baseline 33% vs postintervention, 27%; P < .001). CONCLUSIONS: Significant changes in clinician performance of key quality measures were reported in patients with T2DM after a PI CME activity improved adherence to evidence-based recommendations of care.

Growth hormone (GH) replacement therapy in adult-onset gh deficiency: effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial.

Adult GH deficiency (AGHD) is characterized by an altered body composition, an atherogenic lipid profile, decreased exercise capacity, and diminished quality of life. We performed a randomized, double-blind, placebo-controlled, multicenter study in 166 subjects with AGHD to assess the effects of GH on these outcomes. GH was initiated at 0.0125 mg/kg.d, increased to 0.025 mg/kg.d as tolerated, or decreased to 0.00625 mg/kg.d for 12 months. Primary measures of efficacy included body composition, strength and endurance, and quality of life. Additional parameters included serum IGF-I concentrations, serum lipids, and bone mineral density. After 12 months, 79% of subjects remained on GH 0.0125 mg/kg.d, whereas 21% received 0.00625 mg/kg.d. GH-treated men and women demonstrated significant decreases in total body and trunk fat and increases in lean body mass over baseline. In GH-treated men, mean IGF-I SD scores exceeded age-adjusted normal ranges, whereas similar doses produced a smaller response in women. GH treatment was associated with significant improvements in total cholesterol and low-density lipoprotein (P < 0.05 for all). No significant treatment effects were observed in strength and endurance, quality of life, or bone mineral density. GH treatment was generally well tolerated. Subjects with AGHD should receive individualized GH therapy to maintain IGF-I between the mean value and +2 SD and improve body composition and cardiovascular risk factors.