Optimizing Glycemic Outcomes for Minoritized and Medically Underserved Adults Living with Type 1 Diabetes.

Individuals living with type 1 diabetes (T1D) from medically underserved communities have poorer health outcomes. Efforts to improve outcomes include a focus on team-based care, activation of behavior change, and enhancing self-management skills and practices. Advanced diabetes technologies are part of the standard of care for adults with T1D. However, health care providers often carry implicit biases and may be uncomfortable with recommending technologies to patients who have traditionally been excluded from efficacy trials or have limited real-world exposure to devices. We review the literature on this topic and provide an approach to address these issues in clinical practice.

Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease.

The Kidney Precision Medicine Project (KPMP) aims to create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies through molecular investigation of human kidney biopsies obtained from participants with acute kidney injury (AKI) or chronic kidney disease (CKD). We present the case of a 66-year-old woman with diabetic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included diabetes mellitus complicated by neuropathy and eye disease, increased insulin resistance, hypertension, albuminuria, and relatively preserved glomerular filtration rate (early CKD stage 3a). The patient's histopathology was consistent with diabetic nephropathy and arterial and arteriolar sclerosis. Three-dimensional, immunofluorescence imaging of the kidney biopsy specimen revealed extensive peri-glomerular neovascularization that was underestimated by standard histopathologic approaches. Spatial transcriptomics was performed to obtain gene expression signatures at discrete areas of the kidney biopsy. Gene expression in the areas of glomerular neovascularization revealed increased expression of genes involved in angiogenic signaling, proliferation and survival of endothelial cells, as well as new vessel maturation and stability. This molecular correlation provides additional insights into the development of kidney disease in patients with diabetes and spotlights how novel molecular techniques employed by the KPMP can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.

Proof-of-concept Application of Continuous Glucose Monitoring Data Analytics to Identify Diabetes Glucotypes.

Background: In this proof-of-concept study, we evaluated if monogenic diabetes resulting from mutations of the HNF-1α gene (HNF1A-MODY) has a distinctive continuous glucose monitoring (CGM) glucotype, in comparison to type 1 diabetes (T1D). Methods: Using CGM data from 5 subjects with HNF1A-MODY and 115 subjects with T1D, we calculated multiple glucose metrics, including measures of within- and between-day variability (such as coefficient variation for each hour [CVb_1h]). Results: The MODY and T1D cohorts had minimum CVb_1h of 11.3 ± 4.4 and 18.0 ± 4.9, respectively (P = .02) and maximum CVb_1h of 33.9 ± 5.0 and 50.3 ± 10, respectively (P < .001). All subjects with HNF1A-MODY had a minimum %CVb_1h ≤ 17.3% and maximum %CVb_1h ≤ 37.1%. In contrast, only 12 of 115 subjects with T1D had both a minimum and maximum %CVb_1h below these thresholds (P < .001). Conclusion: HNF1A- MODY is characterized by a low hourly, between-day glucose variability. CGM-derived glucose metrics may have potential applicability for screening for atypical diabetes phenotypes in the T1D population.

An Opportunity for Improvement: Evaluation of Diabetes Technology Education Among Adult Endocrinology Training Programs.

BACKGROUND: Despite increases in continuous glucose monitor (CGM) and insulin pump use in adults with diabetes, there is room for expansion. Technology adoption may be influenced by the training environment and fellowship education. However, little is known about adult endocrinology trainee comfort with, understanding of, or methods by which trainees receive education about diabetes technology. METHODS: Mixed methods, sequential explanatory evaluation using survey and semi-structured interviews of endocrinology trainees and fellowship leadership in Accreditation Council for Graduate Medical Education (ACGME)-accredited adult endocrinology fellowship programs to assess trainee and leadership comfort with, perceived knowledge of, and current methods for diabetes technology education. RESULTS: Seventy-seven respondents completed the survey. The majority of training programs have curricula for training on insulin pumps (74%) and CGM (75.3%); 52% of fellows felt curricula are adequate. First- and second-year fellows were more comfortable with CGM than insulin pump use. Only half of third-year fellows felt comfortable with starting insulin pump therapy or recommending insulin dose adjustments based on CGM rate of change arrows. Qualitative interviews identified the importance of both direct instruction and experiential learning in diabetes technology education. CONCLUSIONS: Almost half of trainees feel that curricula for learning to use and manage insulin pumps and CGM are inadequate and feel uncomfortable with critical aspects of technology use, demonstrating the need for increased attention to trainee education in the use of diabetes technology. Based on a better understanding of current and preferred methods for instruction, this study provides direction for future development of initiatives to improve fellow education in this field.

Delays in Continuous Glucose Monitoring Device Initiation: A Single Center Experience and a Call to Change.

Background: Continuous glucose monitoring (CGM) has been increasingly shown to be beneficial in patients with both types 1 and 2 diabetes using insulin. Despite this, challenges remain in obtaining coverage for these devices. We sought to define the process of initiation of CGM and better understand factors associated with successful initiation. Methods: A single-center retrospective cohort study of 271 patients seen over a 3-year period from 2017 to 2020 in the adult endocrinology clinic at Boston Medical Center who were prescribed CGM was performed. The primary outcome was time to CGM initiation. Secondary outcomes included factors associated with initiation and continued use of CGMs and glycemic control. Results: Obtaining CGM through pharmacy benefit was significantly faster than through durable medical equipment companies (78 days vs. 152 days, P < 0.0001). Factors associated with initiation of CGM were younger age, private insurance, and education with a clinical diabetes educator. Identifying as black or Hispanic was significantly associated with decreased initiation of CGM. Glycemic control as represented by hemoglobin A1c improved in patients initiated on CGM from 9.06% to 8.22% (P < 0.001). Conclusion: Prescribing CGM as a pharmacy benefit significantly reduces the time to initiation, but on average, still takes several months, delaying potentially life-saving care for patients living with diabetes. Barriers to CGM initiation must be addressed to ensure timely delivery of optimal care to our patients.

The use of vitamin D in preventing post-thyroidectomy hypocalcemia: An endocrinologist survey study.

OBJECTIVE: To evaluate the use of preoperative vitamin D levels and postoperative vitamin D supplementation among endocrinologists for the prevention of post-thyroidectomy hypocalcaemia. METHODS: Endocrinologist members of the American Thyroid Association (ATA) were contacted via email to complete a 21-question survey, which included both questions about demographic information, and preventing and managing postoperative hypocalcaemia after thyroidectomy. Univariate and multivariate analysis was performed to determine the respondents' use of preoperative vitamin D levels, dose and duration of preoperative vitamin D repletion, decision to delay surgery for low vitamin D levels in the case of a benign or malignant disease, and routine prescription of postoperative calcium or vitamin D supplementation. RESULTS: 225 endocrinologists who were ATA members responded to the questionnaire. When compared to endocrinologists practicing in other countries, those that practice in the United States were 2.5 times more likely to check preoperative vitamin D levels (95% CI[1.404, 4.535], P = .002), significantly more likely to replete vitamin D deficient patients with high-dose vitamin D (ie ≥50K IU/week), 4.458 times more likely to prescribe prophylactic supplemental calcium (95% CI[2.446, 8.126]; P < .0001) and 3.48 more likely to prescribe supplemental vitamin D (95% CI [1.906, 6.355]; P < .0001). Endocrinologists who have been in practice for >10 years were also 1.915 times more likely to prescribe supplemental vitamin D (95% CI (1.080, 3.395); P = .0263). Physicians that treat >50 thyroidectomy cases/year were 2.083 more likely to recommend a vitamin D repletion duration of >1 month than those that treat ≤50 cases/year ([1.036, 4.190], P = .0395). Lastly, if the patient has low preoperative vitamin D levels, 47.05% of respondents chose to delay surgery in a benign disease, while only 11.61% of respondents would do so in a case of malignant disease. CONCLUSIONS: Approximately one-half of surveyed endocrinologists reported using preoperative vitamin D levels to assess a patient's risk for post-thyroidectomy hypocalcaemia. Endocrinologists practicing in the United States, compared to those practicing in other countries, were more likely to both test for preoperative vitamin D levels and to recommend prophylactic post-thyroidectomy calcium and vitamin D supplementation.

Optimal Glycemic Control in a Patient With HNF1A MODY With GLP-1 RA Monotherapy: Implications for Future Therapy.

We present the case of a 27-year-old woman with inadequately controlled HNF1A maturity-onset diabetes of the young (MODY) who was successfully transitioned from sulfonylurea therapy to once-weekly monotherapy with dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA). More than a decade from diabetes diagnosis, she has maintained optimal glycemic control without hypoglycemia for >12 months while receiving GLP-1 RA therapy alone. This case illustrates the potential for successful use of GLP-1 RA monotherapy in patients with HNF1A MODY.

Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study.

AIMS: Increased proinsulin (PI) compared to C-peptide (CP) concentrations have been reported, both prior to type 1 diabetes mellitus (T1D) onset, as well as early in disease. In this pilot study, we sought to define the normal PI secretion in a healthy cohort and compare this to a local T1D cohort and a separate well-defined nationally representative T1D cohort with measurable CP. METHODS: Thirteen healthy subjects and 12 T1D subjects with T1D >3 years from the local T1D cohort completed mixed meal tolerance tests (MMTT) with PI and CP measured over 90 and 240 minutes. The change in CP (maximum versus baseline, ΔCP) during MMTT in the T1D Exchange T1D cohort was stratified according to non-fasting PI concentrations, based on a fasting PI threshold, as defined by the healthy control group. RESULTS: The maximum fasting PI in the control group was 6 pmol/L. Individuals from the T1D Exchange with a non-fasting PI ≥ 6 pmol/L had a lower ΔCP during a MMTT, compared to those with a PI < 6 pmol/L. While only three individuals from the local T1D cohort had measurable CP and PI during the MMTT, those with a greater ΔCP had lower PI secretion. CONCLUSION: While all T1D subjects from the T1D Exchange secreted measurable non-fasting PI, those with a greater non-fasting PI demonstrated a decrease in ΔCP during the MMTT. PI may be preferentially secreted compared to CP in some individuals with long standing T1D.

Rethinking the Endpoints of mHealth Intervention Research in Diabetes Care.

Mobile health (mHealth) is an emerging branch of medicine that utilizes technology to impact health care. With increasing access to smartphones and mobile devices, there has been an increase in both the availability and use of mHealth resources, including the use of text messages, apps, and web portals. In diabetes, there is particular interest as technology has long been a mainstay of management through glucometers, insulin pumps and continuous glucose monitors, which are increasingly interconnected. Although there is high demand for mHealth interventions in diabetes, there is no clear consensus on the best way to monitor these interventions. While randomized controlled trials are considered the gold standard for most medical research, we propose that alternative trial designs may be more applicable in the ever-changing mHealth landscape.

PRESERVED PROINSULIN SECRETION IN LONG-STANDING TYPE 1 DIABETES.

OBJECTIVE: Recent literature has reported preserved residual beta-cell function (C-peptide "microsecretion") in many individuals with long-standing type 1 diabetes (T1D). However, the concentrations of detectable insulin/C-peptide in the serum are usually very low, and beta-cell mass is typically negligible. Proinsulin is measurable in the early years after diagnosis, consistent with the presence of residual functioning beta cells. However, individuals are not expected to secrete significant amounts of proinsulin beyond the early years after diagnosis. Our primary objective was to measure the prohormone, proinsulin, in a heterogeneous cohort of individuals with long-standing T1D. We also sought to assess whether proinsulin secretion might occur in certain individuals despite the absence of measurable C-peptide. METHODS: Random postmeal proinsulin concentrations were measured in 97 subjects with T1D (disease duration >3 years) recruited from within the T1D Exchange Clinic Network participants who took part in the Residual C-peptide Study. RESULTS: Forty-nine of these subjects had undetectable baseline and stimulated C-peptide (C-peptide [-]), and 48 of them had detectable C-peptide concentrations (C-peptide [+]). All the C-peptide (+) subjects had detectable serum proinsulin. Eight (16%) of the C-peptide (-) subjects had detectable serum proinsulin. CONCLUSION: We report the observation that proinsulin secretion persists in a proportion of individuals with long-standing T1D, even in the absence of measurable C-peptide. It is not yet clear why certain patients with T1D retain the ability to secrete proinsulin many years after diagnosis. ABBREVIATIONS: CP = C-peptide CV = coefficient of variation ELISA = enzyme-linked immunosorbent assay IQR = inter-quartile range MMTT = mixed-meal tolerance test NIBSC = National Institute for Biological Standards and Control PI = proinsulin T1D = type 1 diabetes.

Active cocaine use does not increase the likelihood of hyperglycemic crisis.

OBJECTIVE: Hyperglycemic crisis encompasses a group of diabetes emergencies characterized by insulin deficiency with high morbidity and mortality. Cocaine use is increasingly prevalent in the United States and may be associated with increased risk of diabetic ketoacidosis. The objective was to determine if active cocaine use at hospital admission could be considered a risk factor for development of hyperglycemic crisis. METHODS: A retrospective case-control analysis was performed on 950 inpatients with hyperglycemia at an urban academic hospital. Patients admitted with non-emergent hyperglycemia were compared to patients who met criteria for diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hyperosmolar ketoacidosis (HK), based on the absence or presence of cocaine metabolites on urine toxicology screen. Outcomes included frequency of cocaine use in patients with DKA, HHS, HK, and non-emergent hyperglycemia; phenotypic characteristics of cocaine users vs. non-users with hyperglycemia; phenotypic characteristics of patients with hyperglycemic crisis vs. non-emergent hyperglycemia. RESULTS: 950 patients were admitted with hyperglycemia, 133 of which met criteria for hyperglycemic crisis. There was no significant difference in the frequency of cocaine use in individuals with non-emergent hyperglycemia compared to individuals with hyperglycemic crisis (16.9% vs. 17.2%, p = 0.90). 16.9% of patients with DKA, 16.4% of patients with HHS, and 6.4% of patients with HK were cocaine users. CONCLUSIONS: We found no association between active cocaine use at the time of hospital admission and development of hyperglycemic crisis, when compared to non-emergent hyperglycemia. The role of routine screening for cocaine use in patients with hyperglycemic crisis is unclear.

Mediastinal parathyroid adenoma with osteitis fibrosis cystica: robot-assisted thoracic surgical resection.

Mediastinal parathyroid adenomas can be resected by sternotomy or video-assisted thoracoscopic surgery. Robot-assisted thoracic surgical approaches have recently been described. We report robot-assisted thoracic surgical resection of a mediastinal parathyroid in a morbidly obese patient. Additional comorbidities included multiple pathological fractures related to hypercalcemia. Intraoperative parathyroid hormone levels confirmed successful removal of the adenoma. Hungry bone syndrome developed after surgery but eventually resolved. Robot-assisted thoracic surgery avoided the need for sternotomy and associated concerns related to poor bone healing. Robot-assisted thoracic surgery has potential advantages over video-assisted thoracoscopic surgery in patients with obesity because of easier instrument articulation within the thoracic cavity rather than at the chest wall.

Metformin may be associated with false-negative cancer detection in the gastrointestinal tract on PET/CT.

OBJECTIVE: Concurrent therapy with the antihyperglycemic drug metformin can hinder the detection of malignancy in the abdominal and pelvic portions of 18F-fluordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging performed for the diagnosis or staging of malignancy, as well as for treatment response and radiation therapy planning. This is due to the metformin-induced increase in intestinal FDG radiotracer uptake. We aim to bring this potentially important interaction to the attention of clinicians who care for cancer patients with diabetes. METHODS: We searched MEDLINE (from 1970 to January 2014) and Google Scholar for relevant English-language articles using the following search terms: "metformin and FDG/PET, metformin and bowel uptake, metformin, and cancer, metformin and the intestine, metformin pharmacokinetics, hyperglycemia and FDG/PET." We reviewed the reference lists of pertinent articles with respect to metformin gut physiology, impact on FDG uptake and the effect on diagnostic accuracy of abdominalpelvic PET/CT scans with concurrent metformin therapy. RESULTS: We reviewed the action of metformin in the intestine, with particular emphasis on the role of metformin in PET/CT imaging and include a discussion of clinical studies on the topic to help refine knowledge and inform practice. Finally, we discuss aspects pertinent to the management of type 2 diabetes (T2D) patients on metformin undergoing PET/CT. CONCLUSIONS: Metformin leads to intense, diffusely increased FDG uptake in the colon, and to a lesser degree, the small intestine, which limits the diagnostic capabilities of FDG PET/CT scanning and may mask gastrointestinal malignancies. We suggest that metformin be discontinued 48 hours before FDG PET/CT scanning is performed in oncology patients. More rigorous data are needed to support the widespread generalizability of this recommendation.

The syndrome of hypoparathyroidism, deafness, and renal anomalies.

OBJECTIVE: We review the syndrome of hypoparathyroidism, deafness, and renal anomalies (HDR syndrome). METHODS: The current understanding and relevant literature pertaining to the background, genetic considerations, clinical features, prognosis, and treatment of HDR syndrome are reviewed. RESULTS: The combination of hypoparathyroidism, deafness, and renal anomalies constitutes an unusual syndrome associated most commonly with haploinsufficiency in GATA3, which encodes a transcription factor that binds to the (A/T) GATA (A/G) consensus DNA sequence. Sensorineural hearing loss is the most consistently expressed clinical feature, being present in almost all affected individuals, and the combination of hypoparathyroidism and hearing impairment occurs in well over 90% of those affected, with various renal anomalies being the most heterogeneous feature of the classic triad. We characterize, in tabular form, the individual cases described in the literature and propose a classification scheme based on the presence or absence of renal anomalies. We also include the specific genetic abnormality and renal anomaly associated with each individual case. CONCLUSION: HDR syndrome is a heterogeneous syndrome most commonly associated with GATA3 haploinsufficiency.