Feasibility and Performance of Continuous Glucose Monitoring to Guide Computerized Insulin Infusion Therapy in Cardiovascular Intensive Care Unit.

BACKGROUND: We evaluated the feasibility of real-time continuous glucose monitoring (CGM) for titrating continuous intravenous insulin infusion (CII) to manage hyperglycemia in postoperative individuals in the cardiovascular intensive care unit and assessed their accuracy, nursing acceptance, and postoperative individual satisfaction. METHODS: Dexcom G6 CGM devices were applied to 59 postsurgical patients with hyperglycemia receiving CII. A hybrid approach combining CGM with periodic point-of-care blood glucose (POC-BG) tests with two phases (initial-ongoing) of validation was used to determine CGM accuracy. Mean and median absolute relative differences and Clarke Error Grid were plotted to evaluate the CGM accuracy. Surveys of nurses and patients on the use of CGMs experience were conducted and results were analyzed. RESULTS: In this cohort (mean age 64, 32% female, 32% with diabetes) with 864 paired POC-BG and CGM values analyzed, mean and median absolute relative difference between POC-BG and CGM values were 13.2% and 9.8%, respectively. 99.7% of paired CGM and POC-BG were in Zones A and B of the Clarke Error Grid. Responses from nurses reported CGMs being very or quite convenient (n = 28; 93%) and it was favored over POC-BG testing (n = 28; 93%). Majority of patients (n = 42; 93%) reported their care process using CGM as being good or very good. CONCLUSION: This pilot study demonstrates the feasibility, accuracy, and nursing convenience of adopting CGM via a hybrid approach for insulin titration in postoperative settings. These findings provide robust rationale for larger confirmatory studies to evaluate the benefit of CGM in postoperative care to improve workflow, enhance health outcomes, and cost-effectiveness.

Measurement of cognition and profiling early learning environments in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: Childhood stunting is associated with poorer child health, growth and development including diminished cognitive abilities. Mapping out the links between child stunting and Early Childhood Education and Development is critical to increasing understanding of the causes and effects of childhood stunting, and for programme and policy development. The aim of this study is to investigate and compare the development and educational environments across India, Indonesia and Senegal, and to identify the multifactorial drivers and impacts of childhood stunting to inform a new typology. METHODS AND ANALYSIS: This current study is part of an interdisciplinary observational research study, where women are recruited during pregnancy and mother-infant pairs followed prospectively, up to 24 months after birth. Eight measures will be used to profile children's early development and learning environments in two sample cohorts: (A) children aged 12 and 24 months born to the women recruited during pregnancy (ie, 500 pregnant mothers per country) and (B) a preschool case-control cohort of siblings from the main cohort aged between 3:6 and 5:6 years of age where anthropomorphic measures will be collected to assess degrees of stunting. Profiling of the development and learning environments in the countries will include both parent/caregiver self-reported and local staff (enumerators) direct assessments of children and settings. ETHICS AND DISSEMINATION: This study was approved by the institutional ethics committees of all partner institutions. In India, Indian Council of Medical Research-National Institute of Nutrition, Hyderabad; In Indonesia, Ethics Committee of the Faculty of Medicine, University of Indonesia; and in Senegal, National Ethics Committee for Scientific Research in Senegal.The findings of the study will be disseminated in national and international meetings, seminars, conferences and peer-reviewed journals.

Spectrum of Diabetic Neuropathy: New Insights in Diagnosis and Treatment.

Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.

Cardiovascular Autonomic Neuropathy and Risk of Kidney Function Decline in Type 1 and Type 2 Diabetes: Findings From the PERL and ACCORD Cohorts.

Results of previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among people with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N = 469) and with type 2 diabetes (T2D) from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (N = 7,973). Baseline CAN was ascertained with electrocardiogram-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss of ≥5 mL/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed-effects, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 mL/min/1.73 m2/year (95% CI -1.93 to -0.37; P = 4.0 × 10-3) in PERL and 0.34 mL/min/1.73 m2/year (95% CI -0.49 to -0.19; P = 6.3 × 10-6) in ACCORD. This translated to 2.11 (95% CI 1.23-3.63; P = 6.9 × 10-3) and 1.39 (95% CI 1.20-1.61; P = 1.1 × 10-5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (hazard ratio 2.60 [95% CI 1.15-5.45], P = 0.02, in PERL and hazard ratio 1.54 [95% CI 1.28-1.84], P = 3.8 × 10-6, in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help with development of new therapies to prevent kidney function decline in patients with diabetes.

A Novel Receivership Model for Transition of Young Adults With Diabetes: Experience From a Single-center Academic Transition Program.

OBJECTIVE: The transition from pediatric to adult care for young adults with diabetes represents an important but often challenging time characterized by a shift from a family-centered care model of pediatrics to a patient-centered care model of adult medicine. We developed a structured transition program based on an adult receivership model at a large academic medical center to improve care coordination and patient satisfaction with the transition process. METHODS: From 2016 to 2020, we implemented a series of quality improvement efforts for young adults aged 18 to 23 years with diabetes by incorporating best practices from the American Diabetes Association guidelines on care for emerging adults. We measured transition orientation attendance, patient satisfaction, hemoglobin A1c (HbA1c) pre- and post-transfer, and care gaps to determine the impact of the program. RESULTS: In this study, 307 individuals with type 1 diabetes and 16 individuals with type 2 diabetes were taken care of by the adult endocrinology department at the University of Michigan between January 1, 2016 and October 31, 2020. We observed high attendance rates (86% among internal transfers) and favorable patient satisfaction scores for the transition orientation session. Despite the glycemic challenges posed during the transition, HbA1c modestly yet significantly improved 1-year after transfer (-0.4%, P < .01). CONCLUSION: We successfully established and maintained a young adult diabetes transition program using a quality improvement approach. Future work will focus on reducing care gaps at the time of transfer, assessing long-term retention rates, and enhancing care coordination for patients referred from outside the health network.

Cost and utilization of healthcare services for persons with diabetes.

AIMS: Describe and compare healthcare costs and utilization for insured persons with type 1 diabetes (T1D), type 2 diabetes (T2D), and without diabetes in the United States. METHODS: Using a nationally representative healthcare claims database, we identified matched persons with T1D, T2D, and without diabetes using a propensity score quasi-randomization technique. In each year between 2009 and 2018, we report costs (total and out-of-pocket) and utilization for all healthcare services and those specific to medications, diabetes-related supplies, visits to providers, hospitalizations, and emergency department visits. RESULTS: In 2018, we found out-of-pocket costs and total costs were highest for persons with T1D (out-of-pocket: $2,037.2, total: $25,652.0), followed by T2D (out-of-pocket: $1,543.3, total: $22,408.1), and without diabetes (out-of-pocket: $1,122.7, total: $14,220.6). From 2009 to 2018, out-of-pocket costs were increasing for persons with T1D(+6.5 %) but decreasing for T2D (-7.5 %) and without diabetes (-2.3 %). Medication costs made up the largest proportion of out-of-pocket costs regardless of diabetes status (T1D: 51.4 %, T2D: 55.4 %,without diabetes: 51.1 %). CONCLUSIONS: Given the substantial out-of-pocket costs for people with diabetes, especially for those with T1D, providers should screen all persons with diabetes for financial toxicity (i.e., wide-ranging problems stemming from healthcare costs). In addition, policies that aim to lower out-of-pocket costs of cost-effective diabetes related healthcare are needed with a particular focus on medications.

Urinary epidermal growth factor levels correlate with cardiovascular autonomic neuropathy indices in adults with type 1 diabetes.

The relationship between urinary endothelial growth factor (uEGF) and cardiovascular autonomic neuropathy (CAN) in adults with type 1 diabetes was evaluated. uEGF levels at baseline and standardized CAN measures were collected at baseline and annually for 3 years for type 1 diabetes adults. Linear regression analysis and linear mixed effects model were used for analysis. In this cohort (n = 44, 59% women, mean ± standard deviation age 34 ± 13 years and diabetes duration 14 ± 6 years), lower baseline uEGF levels correlated with lower baseline expiration : inspiration ratios (P = 0.03) and greater annual declines in Valsalva ratios (P = 0.02) in the unadjusted model, and correlated with lower low-frequency power : high-frequency power ratios (P = 0.01) and greater annual changes in low-frequency power : high-frequency power ratios (P = 0.01) after adjustment for age, sex, body mass index, and hemoglobin A1C. In conclusion, baseline uEGF levels correlate to baseline and longitudinal changes in CAN indices. A large-scale, long-term study is needed to validate uEGF as a reliable CAN biomarker.

On diabetic foot ulcer knowledge gaps, innovation, evaluation, prediction markers, and clinical needs.

Diabetic foot ulcers (DFUs) remain a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Despite major advances in diabetes treatment in general, there is a paucity of FDA approved technologies and therapies to promote successful healing. Furthermore, accurate biomarkers to identify patients at risk of non-healing and monitor response-to-therapy are significantly lacking. To date, research has been slowed by a lack of coordinated efforts among basic scientists and clinical researchers and confounded by non-standardized heterogenous collection of biospecimen and patient associated data. Novel technologies, especially those in the single and 'multiomics' arena, are being used to advance the study of diabetic foot ulcers but require pragmatic study design to ensure broad adoption following validation. These high throughput analyses offer promise to investigate potential biomarkers across wound trajectories and may support information on wound healing and pathophysiology not previously well understood. Additionally, these biomarkers may be used at the point-of-care. In combination with national scalable research efforts, which seek to address the limitations and better inform clinical practice, coordinated and integrative insights may lead to improved limb salvage rates.

The conundrum of diabetic neuropathies-Past, present, and future.

Diabetic neuropathy (DN) remains arguably the most prevalent chronic complication in people with both type 1 and type 2 diabetes, including in youth, despite changes in the current standards of clinical care. Additionally, emerging evidence demonstrates that neuropathy affects a large proportion of people with undiagnosed diabetes and/or prediabetes, as well as those with obesity. Here we summarize the latest epidemiology of DN, recent findings regarding the pathophysiology of the disease, as well as current outcome measures for screening and diagnosis, in research and clinical settings. The authors discuss novel perspectives on the impact of social determinants of health in DN development and management, and the latest evidence on effective therapies, including pharmacological and nonpharmacological therapies for neuropathic pain. Throughout the publication, we identify knowledge gaps and the need for future funding to address these gaps, as well as needs to advocate for a personalized care approach to reduce the burden of DN and optimize quality of life for all affected individuals.

Urologic complications in diabetes.

Urologic complications such as bladder and sexual dysfunction among men and women with diabetes have received relatively little attention. This is despite emerging evidence that demonstrates that urologic complications increase with age in the general population and are more common in individuals with diabetes compared to those without diabetes. Here we summarize the latest information about the epidemiology of urologic complications in the setting of diabetes and the most recent findings regarding pathophysiology. In addition, we identify knowledge gaps and need for future funding to address these gaps that will reduce the burden of urologic complications in diabetes and optimize quality of life for all individuals affected by it.

Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange.

AIMS: We aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry. METHODS: DAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010-2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed. RESULTS: Of the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004). CONCLUSIONS: DAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further.

Benefit of Continuous Glucose Monitoring in Reducing Hypoglycemia Is Sustained Through 12 Months of Use Among Older Adults with Type 1 Diabetes.

Objective: To evaluate glycemic outcomes in the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) randomized clinical trial (RCT) participants during an observational extension phase. Research Design and Methods: WISDM RCT was a 26-week RCT comparing continuous glucose monitoring (CGM) with blood glucose monitoring (BGM) in 203 adults aged ≥60 years with type 1 diabetes. Of the 198 participants who completed the RCT, 100 (98%) CGM group participants continued CGM (CGM-CGM cohort) and 94 (98%) BGM group participants initiated CGM (BGM-CGM cohort) for an additional 26 weeks. Results: CGM was used a median of >90% of the time at 52 weeks in both cohorts. In the CGM-CGM cohort, median time <70 mg/dL decreased from 5.0% at baseline to 2.6% at 26 weeks and remained stable with a median of 2.8% at 52 weeks (P < 0.001 baseline to 52 weeks). Participants spent more time in range 70-180 mg/dL (TIR) (mean 56% vs. 64%; P < 0.001) and had lower hemoglobin A1c (HbA1c) (mean 7.6% [59 mmol/mol] vs. 7.4% [57 mmol/mol]; P = 0.01) from baseline to 52 weeks. In BGM-CGM, from 26 to 52 weeks median time <70 mg/dL decreased from 3.9% to 1.9% (P < 0.001), TIR increased from 56% to 60% (P = 0.006) and HbA1c decreased from 7.5% (58 mmol/mol) to 7.3% (57 mmol/mol) (P = 0.025). In BGM-CGM, a severe hypoglycemic event was reported for nine participants while using BGM during the RCT and for two participants during the extension phase with CGM (P = 0.02). Conclusions: CGM use reduced hypoglycemia without increasing hyperglycemia in older adults with type 1 diabetes. These data provide further evidence for fully integrating CGM into clinical practice. Clinicaltrials.gov (NCT03240432).

Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.

OBJECTIVE: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

Association Between Management of Continuous Subcutaneous Basal Insulin Administration and HbA1C.

BACKGROUND: While we expect that patients who adjust their insulin delivery algorithms between clinic visits to have better glucose control compared to those who do not, this effect has not been quantified. METHOD: This is a single-center retrospective cohort study including pediatric and adult patients with type 1 diabetes evaluating insulin pump self-management behaviors. Basal insulin dose information was obtained from the Glooko-Diasend database, and used to quantify the frequency and magnitude of basal insulin daily dose adjustments within the 90-day window preceding HbA1c measurement. We use a linear mixed-effects model to analyze associations between frequency/magnitude of daily basal insulin changes and HbA1c. RESULTS: We present data on 114 adult (44 ± 17 years, 60% female) and 212 pediatric (12 ± 4 years, 50% female) patients. Individuals changed their basal insulin dose on 72%-94% (interquartile range [IQR]) of observed days relative to the previous day. These changes varied 0.6%-2.4% IQR from the previous day's value. In pediatric patients, lower HbA1c was associated with more frequent daily profile adjustments, while controlling for rate of hypoglycemia (z = -3.2, P = .001). In adults, there was no relationship between HbA1c and magnitude or frequency of basal profile adjustments. CONCLUSIONS: Pediatric patients who frequently modify their basal insulin exhibit somewhat better clinical outcomes, although the magnitude by which their basal amount is changed does not contribute to this effect.

Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D).

AIMS: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D. METHODS: Pilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period. RESULTS: Forty-five T2D participants on metformin monotherapy (mean age 57 ±â€¯8 years, duration 7 ±â€¯6 years, HbA1c 7.8 ±â€¯1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride. CONCLUSIONS: Short term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN. CLINICAL TRIAL REGISTRATION: NCT02973477.

The Prevalence of Diabetic Microvascular Complications in China and the USA.

PURPOSE OF REVIEW: Diabetes can lead to development of devastating microvascular complications, such as nephropathy, retinopathy, and peripheral sensory and autonomic neuropathy. While China and the USA both face the threat of this major public health challenge, the literature is limited in describing similarities and differences in the prevalence, and risk factors for the development, of diabetic microvascular complications between these two countries. RECENT FINDINGS: The current review discusses the following: (1) the most recent evidence on prevalence of diabetic microvascular complications in China and the USA (including downtrends of diabetes retinopathy and neuropathy in the USA); (2) differences in patient risk factors of these complications; (3) challenges and current knowledge gaps (such as lacking national epidemiological data of diabetic complications in China); and (4) potential future clinical and research opportunities (including needs in diabetes evaluation and management in remote areas and standardization of methods in evaluating diabetic complications across countries). Diabetic microvascular complications remain to be health threats in both China and the USA. Further investigations are needed for comprehensive understanding and effect prevention and management of these complications.

Managing Hyperglycemia in the COVID-19 Inflammatory Storm.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) is now at global pandemic levels causing significant morbidity and mortality. Patients with diabetes are particularly vulnerable and more likely to get severe complications when infected with this virus. Although the information continues to emerge, here we provide our perspective on initial outcomes observed in hospitalized patients with diabetes and the potential role played by the proinflammatory metabolic state in these patients that promotes fertile ground for the virus' inflammatory surge, resulting in severe insulin resistance and severe hyperglycemia. The rapidly evolving renal failure, hypotension, pressor and steroid use, and variable nutritional support further complicates their management. Thus, timely implementation of glucose management protocols addressing these complex scenarios while also following COVID-19-related trajectories in inflammatory biomarkers and being cognizant of the health care provider exposure may substantially affect morbidity and mortality.

Commercially Available Insulin Products Demonstrate Stability Throughout the Cold Supply Chain Across the U.S.

OBJECTIVE: A recent publication questioned the integrity of insulin purchased from U.S. retail pharmacies. We sought to independently validate the method used, isotope dilution solid-phase extraction (SPE) liquid chromatography mass spectrometry (LC-MS), and expand analysis to two U.S. Pharmacopeia (USP) methods (high-performance LC with ultraviolet detection and LC-MS). RESEARCH DESIGN AND METHODS: Each method was used to evaluate nine insulin formulations, purchased at four pharmacies, within five geographic locations in the U.S. RESULTS: All human and analog insulins measured by the USP methods (n = 174) contained the expected quantity of active insulin (100 ± 5 units/mL). When using isotope dilution SPE-LC-MS, units-per-milliliter values were well below product labeling due to unequal recovery of the internal standard compared with target insulin. CONCLUSIONS: Insulin purchased from U.S. pharmacies is consistent with product labeling.