Continuous Glucose Monitoring in Older Adults: What We Know and What We Have Yet to Learn.

OBJECTIVE: To assess the growing use of continuous glucose monitoring (CGM) systems by older adults and explore additional areas integration that could benefit adults with frailty. BACKGROUND: The use of CGM devices has expanded rapidly in the last decade. This has been supported by substantial data showing significant benefit in glycemic metrics: hemoglobin A1c improvements, less hypoglycemia, and improved quality of life. However, sub-populations, such as older persons, exist where available data are limited. Furthermore, frail older adults represent a heterogeneous population with their own unique challenges to the management of diabetes. This group has some of the poorest outcomes related to the sequela of diabetes. For example, hypoglycemia resulting in significant morbidity and mortality is more frequent in older person with diabetes than in younger persons with diabetes. METHOD: We present a concise literature review on CGM use in the older adult as well as expand upon glycemic and nonglycemic benefits of CGM for patients, caregivers, and providers. Retrospective analysis of inpatient glycemic data of 16,935 older adults with Type 2 diabetes mellitus at Atrium Health Wake Forest Baptist indicated those with fraility managed with insulin or sulfonylurea had the highest rates of delirium (4.8%), hypoglycemia (3.5%), cardiovascular complications (20.2%) and ED visits/hospitalizatoins (49%). In addition, we address special consideration of specific situations including inpatient, palliative and long term care settings. CONCLUSION: This review article summarizes the available data for CGM use in older adults, discusses the benefits and obstacles with CGM use in this population, and identifies areas of future research needed for improved delivery of care to older persons with diabetes.

Primary Adrenal Insufficiency due to Cryptococcus With Persistent Adrenal Enlargement and Insufficiency.

Background/Objective: Infiltrative fungal infections are an unusual cause of primary adrenal insufficiency (AI). Our objective is to present a long-term follow-up of a patient with AI due to cryptococcal adrenalitis. Case Report: A 47-year-old woman presented in January 2004, with 50-lb weight loss, nausea, emesis, and headache with diplopia. During the 6 months prior to her presentation the patient had multiple admissions for evaluation of recurrent nausea and emesis. Prior to the most recent of these admissions, the patient developed a headache; evaluation of her cerebrospinal fluid revealed the presence of Cryptococcus, and she was treated with a 2-week course of amphotericin B. Physical examination demonstrated a temperature of 101.1 °F, heart rate of 110 bpm, and blood pressure of 94/65 mm Hg. She appeared ill and was underweight with dry mucous membranes and photophobia. Laboratory tests revealed random cortisol of 0.5 µg per dL. CT imaging showed bilateral adrenal gland enlargement and fine needle aspiration of the adrenal gland revealed encapsulated budding yeast. Stress dose intravenous glucocorticoids were administered and switched to oral hydrocortisone and fludrocortisone because the patient clinically improved with a second course of amphotericin B. Further evaluation in 2017 revealed persistently enlarged adrenal glands, positive cryptococcus antigen, and low IgG levels. Discussion: Our literature review noted few publications of AI caused by disseminated cryptococcus with no long-term follow-up of these cases beyond a 1- to 4-year time frame. Conclusion: Patients with AI due to disseminated fungal infection need long-term follow-up to assess for resolution of adrenal enlargement and evaluation of immunocompromised status.

Precision nephrotoxicity testing using 3D in vitro models.

Nephrotoxicity is a significant concern during the development of new drugs or when assessing the safety of chemicals in consumer products. Traditional methods for testing nephrotoxicity involve animal models or 2D in vitro cell cultures, the latter of which lack the complexity and functionality of the human kidney. 3D in vitro models are created by culturing human primary kidney cells derived from urine in a 3D microenvironment that mimics the fluid shear stresses of the kidney. Thus, 3D in vitro models provide more accurate and reliable predictions of human nephrotoxicity compared to existing 2D models. In this review, we focus on precision nephrotoxicity testing using 3D in vitro models with human autologous urine-derived kidney cells as a promising approach for evaluating drug safety.

A Consensus Statement for Continuous Glucose Monitoring Metrics for Inpatient Clinical Trials.

Diabetes Technology Society organized an expert consensus panel to develop metrics for research in the use of continuous glucose monitors (CGMs) in a hospital setting. The experts met virtually in small groups both before and after an April 13, 2023 virtual meeting of the entire panel. The goal of the panel was to develop consensus definitions in anticipation of greater use of CGMs in hospital settings in the future. Establishment of consensus definitions of inpatient analytical metrics will be easier to compare outcomes between studies. Panelists defined terms related to 10 dimensions of measurements related to the use of CGMs including (1) hospital hypoglycemia, (2) hospital hyperglycemia, (3) hospital time in range, (4) hospital glycemic variability, (5) hospital glycemia risk index, (6) accuracy of CGM devices and reference methods for CGMs in the hospital, (7) meaningful time blocks for hospital glycemic goals, (8) hospital CGM data sufficiency, (9) using CGM data for insulin dosing, and (10) miscellaneous factors. The panelists voted on 51 proposed recommendations. Based on the panel vote, 51 recommendations were classified as either strong (43) or mild (8). Additional research is needed on CGM performance in the hospital. This consensus report is intended to support that type of research intended to improve outcomes for hospitalized people with diabetes.

Feasibility of intraoperative continuous glucose monitoring: An observational study in general surgery patients.

BACKGROUND: Perioperative hyperglycemia is associated with adverse outcomes in surgical patients, and major societies recommend intraoperative monitoring and treatment targeting glucose <180-200 mg/dL. However, compliance with these recommendations is poor, in part due to fear of unrecognized hypoglycemia. Continuous Glucose Monitors (CGMs) measure interstitial glucose with a subcutaneous electrode and can display the results on a receiver or smartphone. Historically CGMs have not been utilized for surgical patients. We investigated the use of CGM in the perioperative setting compared to current standard practices. METHOD: This study evaluated the use of Abbott Freestyle Libre 2.0 and/or Dexcom G6 CGMs in a prospective cohort of 94 participants with diabetes mellitus undergoing surgery of ≥3 h duration. CGMs were placed preoperatively and compared to point of care (POC) BG checks obtained by capillary samples analyzed with a NOVA glucometer. Frequency of intraoperative blood glucose measurement was at the discretion of the anesthesia care team, with a recommendation of once per hour targeting BG of 140-180 mg/dL. Of those consented, 18 were excluded due to lost sensor data, surgery cancellation, or rescheduling to a satellite campus resulting in 76 enrolled subjects. There were zero occurrences of failure with sensor application. Paired POC BG and contemporaneous CGM readings were compared with Pearson product-moment correlation coefficients, and Bland-Altman plots. RESULTS: Data for use of CGM in perioperative period was analyzed for 50 participants with Freestyle Libre 2.0, 20 participants with Dexcom G6, and 6 participants with both devices worn simultaneously. Lost sensor data occurred in 3 participants (15%) wearing Dexcom G6, 10 participants wearing Freestyle Libre 2.0 (20%) and 2 of the participants wearing both devices simultaneously. The overall agreement of the two CGM's utilized had a Pearson correlation coefficient of 0.731 in combined groups with 0.573 in Dexcom arm evaluating 84 matched pairs and 0.771 in Libre arm with 239 matched pairs. Modified Bland-Altman plot of the difference of CGM and POC BG indicated for the overall dataset a bias of -18.27 (SD 32.10). CONCLUSIONS: Both Dexcom G6 and Freestyle Libre 2.0 CGMs were able to be utilized and functioned well if no sensor error occurred at time of initial warmup. CGM provided more glycemic data and further characterized glycemic trends more than individual BG readings. Required time of CGM warm up was a barrier for intraoperative use as well as unexplained sensor failure. CGMs had a fixed warm of time, 1 h for Libre 2.0 and 2 h for Dexcom G6 CGM, before glycemic data obtainable. Sensor application issues did not occur. It is anticipated that this technology could be used to improve glycemic control in the perioperative setting. Additional studies are needed to evaluate use intraoperatively and assess further if any interference from electrocautery or grounding devices may contribute to initial sensor failure. It may be beneficial in future studies to place CGM during preoperative clinic evaluation the week prior to surgery. Use of CGMs in these settings is feasible and warrants further evaluation of this technology on perioperative glycemic management.

Efficacy of Control-IQ Technology in a General Endocrine Clinic.

OBJECTIVE: Recent advances in technology have allowed for the expanded use of hybrid closed-loop insulin pump therapy and automated insulin delivery systems for the management of diabetes mellitus. We assessed the outcomes of introducing Tandem t:slim X2 with the Control-IQ technology in a general endocrine clinic. METHODS: Data from 66 adults with type 1 (n = 61) and type 2 (n = 5) diabetes mellitus were aggregated for analysis. Patients were either transitioned from traditional insulin pump therapy or multiple daily injection therapy to Tandem t:slim X2 with the Control-IQ technology from January 2020 to June 2021. The assessed clinical end points included changes in time below range, time above range, and time in target range. Changes in hemoglobin A1C before and after Control-IQ technology implementation were noted. The primary outcome was a change in time in target range with the Control-IQ technology. RESULTS: There was a significant increase in time in target range when comparing pre- and post-Control-IQ technology (49.5% vs 63.3%, P < .0003) values. There was a reduction in time above range (46.8% vs 34.9%, P < .0013), a decrease in time below range (4.0% vs 1.7%, P = .017), and a decrease in hemoglobin A1C after transitioning to the Control-IQ technology (7.7% [61 mmol/mol] vs 7.1% [54 mmol/mol], P < .017). The patient dropout rate was low (7%). CONCLUSION: The Control-IQ technology system was effective in reducing hyperglycemia while increasing time in target range and decreasing hypoglycemia. This technology is a useful and effective addition to the growing number of automated insulin delivery systems. The clinical outcomes mirror the results found in the key adult pivotal trials.

Telehealth Technologies and Their Benefits to People With Diabetes.

This article reviews the current diabetes technology landscape and how recent advancements are being used to help overcome barriers in the management of diabetes. The authors offer case examples of how digital tools and platforms can facilitate diabetes care via telehealth and remote patient monitoring for individuals in special populations. They also provide tips to ensure success in implementing diabetes technology to provide the best possible care for people with diabetes in outpatient settings.

Real-World Efficacy of the Hybrid Closed-Loop System.

BACKGROUND: Hybrid closed-loop (HCL) insulin pump therapy (Medtronic 670G) is an emerging technology that is growing in use worldwide. Initial clinical trials demonstrated the effectiveness of HCL in reducing hypoglycemia and improving glucose control; however, these subjects were intensely monitored and supervised. There has been concern regarding the ability of patients to remain in auto mode. We aimed to assess HCL when used in a typical outpatient endocrine clinic. METHODS: We initially analyzed data from 80 individuals with type 1 diabetes managed in an endocrine clinic by a single certified diabetes educator (CDE). We then included our other providers and had 230 subjects by the end of the study. Patients were either transitioned from traditional insulin pump or multiple daily insulin injection therapy (MDI) to HCL. Patients initiated to HCL pump therapy from July 2017 through February 2020 were studied. Endpoints of change in time in hypoglycemic/hyperglycemic range and time in target range were analyzed. The primary outcome was a change in percent time in the target range during manual mode compared with auto mode. RESULTS: There was an 18.2% increase in average time in target range when comparing manual mode to auto mode (59.3% vs 70.1%, P < .0001). Average time in hyperglycemic range was significantly reduced by 26.7% (39.0% vs 28.6%, P < .0001) but without increasing average time in hypoglycemic range (1.7% vs 1.3%, P = 0.95). CONCLUSIONS: HCL was effective in reducing hyperglycemia and increasing time in the target range but did not increase hypoglycemia. These data suggest HCL will improve the metrics of glucose control.

Characteristics and Attitudes of Men Using Anabolic Androgenic Steroids (AAS): A Survey of 2385 Men.

Additional characterization of patients using anabolic androgenic steroids (AAS) is needed to improve harm reduction and cessation resources for patients. Our group sought to expand upon the currently limited data regarding AAS use by performing a web-based survey assessing experiences of males using AAS. Participants included men over the age of 18 with history of AAS use within the past 5 years. Data were collected between August 2019 and April 2020. Primary outcome measures included age when starting AAS, dose of AAS, motivations for use, experiences with health-care professionals, and rate of successful cessation. The survey was accessed 3640 times, resulting in 2385 completed surveys meeting the inclusion criteria (68.93% participation rate).Average participant age was 31.69 ± 10.09 years. Over half of respondents were from the United States (n = 1271, 53.3%). Motives to use AAS included improving appearance (n = 1959, 82.2%), strength gain (n = 1192, 50%), and self-esteem/body image issues (n = 712, 29.87%). Participants rated physicians poorly, regarding knowledge of AAS (4.08 ± 2.23). Most participants did not reveal AAS use to their health-care providers (n = 1338, 56.1%); of those that did, 55.30% (n = 579) reported feeling discriminated against for their use. Of 46.16% (n = 1101) attempting AAS cessation, 60.22% (n = 663) were unsuccessful. Challenges in the management of AAS use include early onset of use, supraphysiologic doses used, and frequently present body image disorders stress. Distrust of health-care providers, poor cessation rates, and lack of physician training further exacerbate this. These findings should serve to reinforce previous calls to action for further research on the treatment of AAS use disorder.

Subcutaneous Insulin Dosing Calculators for Inpatient Glucose Control.

PURPOSE OF REVIEW: The goal of this review is to summarize information about insulin dosing software and calculators used as computerized decision support systems or electronic glucose management systems (eGMS). These are used for hospitalized, insulin-treated patients with diabetes. We describe the advantages and disadvantages and the rationale for their use. RECENT FINDINGS: We compared commercially available insulin dosing software, namely, Glucommander™, EndoTool®, GlucoStabilizer®, and GlucoTab®, in addition to computerized order entry systems that are available in electronic health records. The common feature among these eGMS is their ability to limit occurrences of hypoglycemia while achieving and maintaining patients at target blood glucose level. More research needs to be done examining the efficacy of eGMS in disease-specific states and their benefits and utility in preventing adverse outcomes. Their long-term benefits to health care systems are beginning to emerge in cost-saving benefits and prevention of readmissions.

Impaired Regeneration Potential in Urinary Stem Cells Diagnosed from the Patients with Diabetic Nephropathy.

Stem cells present in urine possess regenerative capacity to repair kidney injury. However, the unique characteristics of urinary stem cells (USC) from patients with diabetic nephropathy (d-USC) are unknown. The goal of this study was to investigate stemness properties in cell phenotype and regenerative potential of d-USC, compared to USC from healthy individuals. Methods: Thirty-six urine samples collected from patients (n=12, age range 60-75 years) with diabetic nephropathy (stages 3-4 stage chronic kidney disease [CKD]) were compared with 30 urine samples from healthy age-matched donors (n=10, age range 60-74 years). Results: There were approximately six times as many cells in urine samples from patients with diabetic nephropathy, including twice as many USC clones as healthy donors. However, approximately 70% of d-USC had weaker regenerative capacity as assessed by cell proliferation, less secretion of paracrine factors, weaker telomerase activity, and lower renal tubular epithelial differentiation potential compared to healthy controls. In addition, the levels of inflammatory factors (IL-1ß and Cx43) and apoptotic markers (Caspase-3, and TUNEL) were significantly increased in d-USC compared to USC (p<0.01). Protein levels of autophagy marker (LC3-II) and mTOR signaling molecules (p-mTOR/mTOR, p-Raptor/Raptor and p-S6K1) were significantly lower in patient with diabetic nephropathy (p<0.01). Nevertheless, up to 30% of d-USC possessed similar regenerative capacity as USC from healthy donors. Conclusions: Regenerative performance of most d-USC was significantly lower than normal controls. Understanding the specific changes in d-USC regeneration capability will help elucidate the pathobiology of diabetic nephropathy and lead to prevent USC from diabetic insults, recover the stemness function and also identify novel biomarkers to predict progression of this chronic kidney disease.

Comparison of Computer-Guided Versus Standard Insulin Infusion Regimens in Patients With Diabetic Ketoacidosis.

BACKGROUND: This study was performed to investigate the efficacy of Glucommander (GM) (Glytec®), a computer-based algorithm versus standard (paper form-based) continuous insulin infusion (CII) in the treatment of patients with diabetic ketoacidosis (DKA). METHODS: This was a retrospective multicenter study involving 2665 patients with DKA treated with either GM (n = 1750) or standard protocols (n = 915) across 34 institutions in the United States. GM estimates the rate of CII using an insulin sensitivity factor referred to as a "multiplier" that ranges between 0.01 and 0.03. Outcomes of interest were differences in time to resolve DKA (blood glucose [BG] <200 mg/dL and bicarbonate < 18 mmol/L) and number of hypoglycemic events defined as a BG <70 mg/dl. RESULTS: Treatment with GM was associated with lower rates of hypoglycemia during the time of the insulin drip (12.9% vs 35%, P = .001), faster time to normalization of blood glucose (9.7 ± 8.9 vs 10.97 ± 10.2 hours, P = .0001) and resolution of metabolic acidosis (13.6 ± 11.8 vs 17.3 ± 19.6 hours, P = .0001), and shorter hospital length of stay (3.2 ± 2.9 vs 4.5 ± 4.8 days, P = .01) compared to standard care. Best treatment outcomes were achieved with an initial multiplier of 0.01 and a glucose target range between 120 and 180 mg/dl. CONCLUSION: The GM algorithm in DKA treatment resulted in lower rates of hypoglycemia and faster DKA resolution over standard paper-based algorithms. Prospective randomized clinical trials comparing the efficacy and cost of computer-based algorithms versus standard CII regimens are warranted.

Improvement in inpatient glycemic care: pathways to quality.

The management of inpatient hyperglycemia is a focus of quality improvement projects across many hospital systems while remaining a point of controversy among clinicians. The association of inpatient hyperglycemia with suboptimal hospital outcomes is accepted by clinical care teams; however, the clear benefits of targeting hyperglycemia as a mechanism to improve hospital outcomes remain contentious. Glycemic management is also frequently confused with efforts aimed at intensive glucose control, further adding to the confusion. Nonetheless, several regulatory agencies assign quality rankings based on attaining specified glycemic targets for selected groups of patients (Surgical Care Improvement Project (SCIP) measures). The current paper reviews the data supporting the benefits associated with inpatient glycemic control projects, the components of a successful glycemic control intervention, and utilization of the electronic medical record in implementing an inpatient glycemic control project.

Tides of change: improving glucometrics in a large multihospital health care system.

BACKGROUND: This study explores the relationship between education for inpatient diabetes providers and the utilization of insulin order sets, inpatient glucometrics, and length of stay in a large health care system. METHODS: The study included patients with and without the diagnosis of diabetes. An education campaign included provider-directed diabetes education administered via online learning modules and in-person presentations by trained individuals. Relationships among provider-attended diabetes education, order set usage, and inpatient glucometrics (hypo- and hyperglycemia) were analyzed, as well as length of stay. RESULTS: Insulin use knowledge scores for all providers averaged 52%, and improved significantly to 93% (P < .001) by the end of the education intervention period. Likewise utilization of electronic basal-bolus order sets increased from a baseline of 20% for patients receiving insulin to 86% within 6 weeks (P < .01) of introduction of order sets. During the study, the incidence of hypoglycemia and hyperglycemia declined from 1.47% to 1.27% and from 23.21% to 17.80%, respectively. However, these improvements were not sustained beyond the completion of the education campaign. CONCLUSIONS: Education of diabetes health care providers was provided in a large, multihospital system through the use of online learning modules. Adoption of standardized insulin order sets was associated with an improvement in glucometrics. This educational and quality initiative resulted in overall improvements in insulin knowledge, adherence to recommended order sets, inpatient glucometrics, and patient length of stay. These improvements were not sustained, reinforcing the need for repeated educational interventions for those involved in providing inpatient diabetes care.

Recombinant human parathyroid hormone therapy (1-34) in an adult patient with a gain-of-function mutation in the calcium-sensing receptor-a case report.

OBJECTIVE: To describe a case of hypocalcemia in a patient with a gain-of-function mutation in the calcium-sensing receptor that was undetected until adulthood and successfully treated with recombinant parathyroid hormone. METHODS: The clinical findings, laboratory data, and a review of the pertinent literature are presented. RESULTS: A 55-year-old woman was hospitalized and seen by the endocrinology consult service for hypocalcemia that was refractory to repeated doses of intravenous calcium gluconate. She expressed concern about chronic leg muscle cramps and paresthesias of the lips and fingertips. In addition, she had no history of neck surgery, neck irradiation, or any autoimmune disease. She was a well-appearing female with no dysmorphic features or skin changes. Laboratory tests revealed hypocalcemia, hyperphosphatemia, hypomagnesemia, and hypovitaminosis D. Her parathyroid hormone concentration (PTH) was low at 14.2 pg/mL. Her PTH and calcium concentrations remained low despite repletion of magnesium and treatment with calcitriol and oral calcium replacement. A 24-hour collection for urinary calcium showed inappropriate hypercalciuria. Medical records showed her hypocalcemia to be chronic. Additionally, several family members had also complained of muscle cramps. A congenital cause of her hypoparathyroidism was considered, and genetic testing confirmed heterozygosity for a gain-of-function mutation in the calcium-sensing receptor gene associated with autosomal dominant familial isolated hypoparathyroidism (ADH). Treatment with subcutaneous recombinant human parathyroid hormone teriparatide (rhPTH [1-34]) 20 mcg twice daily for three days normalized her calcium and phosphorus concentrations. CONCLUSION: rhPTH (1-34) is an effective treatment for patients with hypoparathyroidism due to gain-of-function mutations in the calcium-sensing receptor. ADH can be insidious in presentation and the diagnosis can be missed unless there is a high index of suspicion.