Association of Real-time Continuous Glucose Monitoring With Glycemic Control and Acute Metabolic Events Among Patients With Insulin-Treated Diabetes.

Importance: Continuous glucose monitoring (CGM) is recommended for patients with type 1 diabetes; observational evidence for CGM in patients with insulin-treated type 2 diabetes is lacking. Objective: To estimate clinical outcomes of real-time CGM initiation. Design, Setting, and Participants: Exploratory retrospective cohort study of changes in outcomes associated with real-time CGM initiation, estimated using a difference-in-differences analysis. A total of 41 753 participants with insulin-treated diabetes (5673 type 1; 36 080 type 2) receiving care from a Northern California integrated health care delivery system (2014-2019), being treated with insulin, self-monitoring their blood glucose levels, and having no prior CGM use were included. Exposures: Initiation vs noninitiation of real-time CGM (reference group). Main Outcomes and Measures: Ten end points measured during the 12 months before and 12 months after baseline: hemoglobin A1c (HbA1c); hypoglycemia (emergency department or hospital utilization); hyperglycemia (emergency department or hospital utilization); HbA1c levels lower than 7%, lower than 8%, and higher than 9%; 1 emergency department encounter or more for any reason; 1 hospitalization or more for any reason; and number of outpatient visits and telephone visits. Results: The real-time CGM initiators included 3806 patients (mean age, 42.4 years [SD, 19.9 years]; 51% female; 91% type 1, 9% type 2); the noninitiators included 37 947 patients (mean age, 63.4 years [SD, 13.4 years]; 49% female; 6% type 1, 94% type 2). The prebaseline mean HbA1c was lower among real-time CGM initiators than among noninitiators, but real-time CGM initiators had higher prebaseline rates of hypoglycemia and hyperglycemia. Mean HbA1c declined among real-time CGM initiators from 8.17% to 7.76% and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, -0.40%; 95% CI, -0.48% to -0.32%; P < .001). Hypoglycemia rates declined among real-time CGM initiators from 5.1% to 3.0% and increased among noninitiators from 1.9% to 2.3% (difference-in-differences estimate, -2.7%; 95% CI, -4.4% to -1.1%; P = .001). There were also statistically significant differences in the adjusted net changes in the proportion of patients with HbA1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; P < .001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2% to 16.1%; P < .001), and higher than 9% (adjusted difference-in-differences estimate, -7.1%; 95% CI, -9.5% to -4.6%; P < .001) and in the number of outpatient visits (adjusted difference-in-differences estimate, -0.4; 95% CI, -0.6 to -0.2; P < .001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; P < .001). Initiation of real-time CGM was not associated with statistically significant changes in rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason. Conclusions and Relevance: In this retrospective cohort study, insulin-treated patients with diabetes selected by physicians for real-time continuous glucose monitoring compared with noninitiators had significant improvements in hemoglobin A1c and reductions in emergency department visits and hospitalizations for hypoglycemia, but no significant change in emergency department visits or hospitalizations for hyperglycemia or for any reason. Because of the observational study design, findings may have been susceptible to selection bias.

Intervention by clinical pharmacists can improve blood glucose fluctuation in patients with diabetes and acute myocardial infarction: A propensity score-matched analysis.

Acute phase hyperglycemia and exaggerated glucose fluctuation may be associated with poor outcomes in diabetic patients after acute myocardial infarction (AMI). This study aimed to determine whether intervention by clinical pharmacists can mitigate blood glucose and glucose fluctuations in these fragile patients. This retrospective study enrolled patients with diabetes and AMI, from 1 January 2019 to 30 June 2020 in our institution. Blood glucose and glucose fluctuations were calculated before and after the pharmacist's intervention and between patients who underwent intervention and those who did not. Propensity score matching (PSM) was used to reduce the impact of patient characteristics on the results. A total of 170 patients were included in our primary analysis, including 29 patients who received the pharmacist intervention and 141 patients who did not. After the pharmacist's intervention, blood glucose (fasting blood glucose-FBG, from 11.9 to 9.8; postprandial blood glucose-PBG, from 15.3 to 13.2; mean blood glucose-BG, 14.5 to 12.3 mmol/L; p < .001), and glucose fluctuations (standard deviation of blood glucose-SDBG, from 3.8 to 3.0, mmol/L, p = .005) were significantly improved. Before PSM, no clear effects were found in intervention versus nonintervention patients, in terms of blood glucose and glucose fluctuation indicators, except for FBG (9.3 vs. 8.0. mmol/L, p = .005). Further analysis indicated a high incidence of FBG <7.8 mmol/L in nonintervention versus intervention patients (51.5% vs. 27.6%, p = .003). After PSM, a significant reduction in blood glucose fluctuation (SDBG, 3.0 vs. 4.1, p = .031; PBGE, 2.1 vs. 4.1, p = .017; LAGE, 4.7 vs. 7.2, mmol/L, p = .004), and PBG (11.1 vs. 13.0, mmol/L, p = .048) was observed in the intervention group than in the nonintervention group. The clinical pharmacist intervention contributed to improved outcomes, specifically, in reducing blood glucose fluctuations and potential hypoglycemia risk.

Immediate postoperative hyperglycemia after peripheral arterial bypass is associated with short-term and long-term poor outcomes.

OBJECTIVE: Although the impact of poorly controlled diabetes on surgical outcomes of patients undergoing lower extremity revascularization is well-known, it is not clear if immediate postoperative hyperglycemia (IPH) itself can be used as a surrogate for poor outcomes after peripheral arterial bypass. We sought to examine the effect of IPH in this patient population with its impact on short-term and long-term outcomes. METHODS: Retrospective review was completed for 505 patients who underwent either suprainguinal bypass surgery or infrainguinal bypass surgery between July 2002 and April 2018 for the treatment of peripheral arterial disease. All patients were undergoing first-time open bypass grafting. Patients were stratified into those who were normoglycemic or hyperglycemic (glucose ≥ 140 mg/dL) within 24 hours after surgery. A comparative analysis was performed on comorbidities and outcomes. RESULTS: Of 505 patients who underwent bypass grafting, 255 patients (50.5%) were hyperglycemic. The mean age of patients was 63.5 ± 14.1 years. The median follow-up was 5.2 years (range, 0.0-15.2 years). The distribution of procedures was as follows: femoral to popliteal bypasses (29%), femoral to femoral bypasses (17%), femoral to tibial bypasses (12%), aortobifemoral bypasses (10%), iliofemoral bypasses (9%), and axillofemoral bypasses (7%). At 30 days, hyperglycemic patients had an increased incidence of limb loss (8.3% vs 4.0%) and myocardial infarction (4.8% vs 0.8%) and incurred higher costs of hospital stay ($27,701 vs $22,990) (all P < .05). At 10 years, these patients had a higher incidence of needing major amputations (15.4% vs 9.4%; P = .025). Hyperglycemia after infrainguinal bypass was associated with nearly twice the risk of limb loss at 5 years (hazard ratio, 1.91; P = .034). Among the cohort of patients who required major amputations, the time duration between index revascularization and amputation was significantly shorter as compared with normoglycemic patients (P = .003). CONCLUSIONS: In this single-institution study with long-term follow-up, IPH was associated with increased rates of 30-day amputation and myocardial infarction, as well as an increased cost of hospital stay. In the long term, postoperative hyperglycemia was associated with greater major limb loss. Among the cohort of patients who required major amputations, the time period between revascularization and amputation was shorter for those patients who had IPH. IPH is an independent marker for poor outcomes after lower extremity revascularization procedures.

Gender differences in the impact of metabolic syndrome components on mortality in older people: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The influence of metabolic syndrome (MetS) on mortality may be influenced by age- and gender-related changes affecting the impact of individual MetS components. We investigated gender differences in the association between MetS components and mortality in community-dwelling older adults. METHODS AND RESULTS: Prospective studies were identified through a systematic literature review up to June 2019. Random-effect meta-analyses were run to estimate the pooled relative risk (RR) and 95% confidence intervals (95% CI) of all-cause and cardiovascular (CV) mortality associated with the presence of MetS components (abdominal obesity, high triglycerides, low HDL cholesterol, high fasting glycemia, and high blood pressure) in older men and women. Meta-analyses considering all-cause (103,859 individuals, 48,830 men, 55,029 women; 10 studies) and CV mortality (94,965 individuals, 44,699 men, 50,266 women; 8 studies) did not reveal any significant association for abdominal obesity and high triglycerides in either gender. Low HDL was associated with increased all-cause (RR = 1.16, 95% CI: 1.02-1.32) and CV mortality (RR = 1.34, 95% CI: 1.03-1.74) among women, while weaker results were found for men. High fasting glycemia was associated with higher all-cause mortality in older women (RR = 1.35, 95% CI: 1.22-1.50) more than in older men (RR = 1.21, 95% CI: 1.13-1.30), and CV mortality only in the former (RR = 1.36, 95% CI: 1.04-1.78). Elevated blood pressure was associated with increased all-cause mortality (RR = 1.16, 95% CI: 1.03-1.32) and showed marginal significant results for CV death only among women. CONCLUSIONS: The impact of MetS components on mortality in older people present some gender differences, with low HDL cholesterol, hyperglycemia, and elevated blood pressure being more strongly associated to all-cause and CV mortality in women.

Diabetes Technology in the Inpatient Setting for Management of Hyperglycemia.

In past decades, a rapid evolution of diabetes technology led to increased popularity and use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) in the ambulatory setting for diabetes management, and recently, the artificial pancreas became available. Efforts to translate this technology to the hospital setting have shown accuracy and reliability of CGM, safety of CSII in appropriate populations, improvement of inpatient glycemic control with computerized glycemic management systems, and feasibility of inpatient CGM-CSII closed-loop systems. Several ongoing studies are focusing on continued translation of this technology to improve glycemic control and outcomes in hospitalized patients.

Quality of Life and Glucose Control After 1 Year of Nationwide Reimbursement of Intermittently Scanned Continuous Glucose Monitoring in Adults Living With Type 1 Diabetes (FUTURE): A Prospective Observational Real-World Cohort Study.

OBJECTIVE: In 2016, nationwide reimbursement of intermittently scanned continuous glucose monitoring (isCGM) for people living with type 1 diabetes treated in specialist diabetes centers was introduced in Belgium. We undertook a 12-month prospective observational multicenter real-world study to investigate impact of isCGM on quality of life and glycemic control. RESEARCH DESIGN AND METHODS: Between July 2016 and July 2018, 1,913 adults with type 1 diabetes were consecutively recruited in three specialist diabetes centers. Demographic, metabolic, and quality of life data were collected at baseline, 6 months, and 12 months of standardized clinical follow-up. The primary end point was evolution of quality of life from baseline to 12 months. Secondary outcome measures were, among others, change in HbA1c, time spent in different glycemic ranges, occurrence of acute diabetes complications, and work absenteeism. RESULTS: General and diabetes-specific quality of life was high at baseline and remained stable, whereas treatment satisfaction improved (P < 0.0001). Admissions for severe hypoglycemia and/or ketoacidosis were rare in the year before study (n = 63 out of 1,913; 3.3%), but decreased further to 2.2% (n = 37 out of 1,711; P = 0.031). During the study, fewer people reported severe hypoglycemic events (n = 280 out of 1,913 [14.6%] vs. n = 134 out of 1,711 [7.8%]; P < 0.0001) or hypoglycemic comas (n = 52 out of 1,913 [2.7%] vs. n = 18 out of 1,711 [1.1%]; P = 0.001) while maintaining HbA1c levels. Fewer people were absent from work (n = 111 out of 1,913 [5.8%] vs. n = 49 out of 1,711 [2.9%]; P < 0.0001). Time spent in hypoglycemia significantly decreased in parallel with less time in range and more time in hyperglycemia. Eleven percent (n = 210) of participants experienced skin reactions, leading to stopping of isCGM in 22 participants (1%). CONCLUSIONS: Nationwide unrestricted reimbursement of isCGM in people with type 1 diabetes treated in specialist diabetes centers results in higher treatment satisfaction, less severe hypoglycemia, and less work absenteeism, while maintaining quality of life and HbA1c.

Disparities in glycaemic control, monitoring, and treatment of type 2 diabetes in England: A retrospective cohort analysis.

BACKGROUND: Disparities in type 2 diabetes (T2D) care provision and clinical outcomes have been reported in the last 2 decades in the UK. Since then, a number of initiatives have attempted to address this imbalance. The aim was to evaluate contemporary data as to whether disparities exist in glycaemic control, monitoring, and prescribing in people with T2D. METHODS AND FINDINGS: A T2D cohort was identified from the Royal College of General Practitioners Research and Surveillance Centre dataset: a nationally representative sample of 164 primary care practices (general practices) across England. Diabetes healthcare provision and glucose-lowering medication use between 1 January 2012 and 31 December 2016 were studied. Healthcare provision included annual HbA1c, renal function (estimated glomerular filtration rate [eGFR]), blood pressure (BP), retinopathy, and neuropathy testing. Variables potentially associated with disparity outcomes were assessed using mixed effects logistic and linear regression, adjusted for age, sex, ethnicity, and socioeconomic status (SES) using the Index of Multiple Deprivation (IMD), and nested using random effects within general practices. Ethnicity was defined using the Office for National Statistics ethnicity categories: White, Mixed, Asian, Black, and Other (including Arab people and other groups not classified elsewhere). From the primary care adult population (n = 1,238,909), we identified a cohort of 84,452 (5.29%) adults with T2D. The mean age of people with T2D in the included cohort at 31 December 2016 was 68.7 ± 12.6 years; 21,656 (43.9%) were female. The mean body mass index was 30.7 ± SD 6.4 kg/m2. The most deprived groups (IMD quintiles 1 and 2) showed poorer HbA1c than the least deprived (IMD quintile 5). People of Black ethnicity had worse HbA1c than those of White ethnicity. Asian individuals were less likely than White individuals to be prescribed insulin (odds ratio [OR] 0.86, 95% CI 0.79-0.95; p < 0.01), sodium-glucose cotransporter-2 (SGLT2) inhibitors (OR 0.68, 95% CI 0.58-0.79; p < 0.001), and glucagon-like peptide-1 (GLP-1) agonists (OR 0.37, 95% CI 0.31-0.44; p < 0.001). Black individuals were less likely than White individuals to be prescribed SGLT2 inhibitors (OR 0.50, 95% CI 0.39-0.65; p < 0.001) and GLP-1 agonists (OR 0.45, 95% CI 0.35-0.57; p < 0.001). Individuals in IMD quintile 5 were more likely than those in the other IMD quintiles to have annual testing for HbA1c, BP, eGFR, retinopathy, and neuropathy. Black individuals were less likely than White individuals to have annual testing for HbA1c (OR 0.89, 95% CI 0.79-0.99; p = 0.04) and retinopathy (OR 0.82, 95% CI 0.70-0.96; p = 0.011). Asian individuals were more likely than White individuals to have monitoring for HbA1c (OR 1.10, 95% CI 1.01-1.20; p = 0.023) and eGFR (OR 1.09, 95% CI 1.00-1.19; p = 0.048), but less likely for retinopathy (OR 0.88, 95% CI 0.79-0.97; p = 0.01) and neuropathy (OR 0.88, 95% CI 0.80-0.97; p = 0.01). The study is limited by the nature of being observational and defined using retrospectively collected data. Disparities in diabetes care may show regional variation, which was not part of this evaluation. CONCLUSIONS: Our findings suggest that disparity in glycaemic control, diabetes-related monitoring, and prescription of newer therapies remains a challenge in diabetes care. Both SES and ethnicity were important determinants of inequality. Disparities in glycaemic control and other areas of care may lead to higher rates of complications and adverse outcomes for some groups.

Comparison of clinical pharmacy specialists and usual care in outpatient management of hyperglycemia in Veterans Affairs medical centers.

PURPOSE: The results of a study to assess the effectiveness and safety of hyperglycemia management provided by clinical pharmacy specialists (CPSs) versus usual care in outpatients with diabetes from 53 Veterans Affairs (VA) medical centers are reported. METHODS: An historical cohort study of outpatients with baseline glycosylated hemoglobin (HbA1c) values of >9% who were referred to a CPS for management of hyperglycemia and primary care patients who were not referred to a CPS was conducted. The primary outcomes were change in HbA1c over time and time to reach an HbA1c value of <8%. Secondary outcomes included the number of visits to achieve an HbA1c value of <8%, proportion of patients with an HbA1c value of <6% who were receiving secretagogues, and proportion of patients with serious hypoglycemia. RESULTS: After propensity score matching by baseline characteristics, there were 12,327 patients in each group. The mean ± S.D. number of visits to reach an HbA1c value of <8% was 2.46 ± 1.58 in the pharmacist-managed group and 1.82 ± 1.27 with usual care (p < 0.001). The proportion of patients with an HbA1c value of <6% who were receiving secretagogues was 39.9% with pharmacist-managed care and 38.6% with usual care (p = 0.73). Serious hypoglycemia was noted in 4.3% of pharmacist-managed patients and 3.1% of usual care patients (p < 0.001). CONCLUSION: Data from 53 VA medical centers revealed that CPSs managed the care of ambulatory care patients with hyperglycemia as well as primary care providers.

Inequalities in glycemic control in childhood onset type 2 diabetes in England and Wales-A national population-based longitudinal study.

BACKGROUND: Not much is known about glycaemic-control trajectories in childhood-onset type 2 diabetes (T2D). We investigated characteristics of children and young people (CYP) with T2D and inequalities in glycemic control. METHODS: We studied 747 CYP with T2D, <19 years of age in 2009-2016 (from the total population-based National Pediatric Diabetes Audit [>95% diabetes cases in England/Wales]). Linear mixed-effects modeling was used to assess socioeconomic and ethnic differences in longitudinal glycated hemoglobin (HbA1c ) trajectories during 4 years post-diagnosis (3326 HbA1c data points, mean 4.5 data points/subject). Self-identified ethnicity was grouped into six categories. Index of Multiple Deprivation (a small geographical area-level deprivation measure) was grouped into SES quintiles for analysis. RESULTS: Fifty-eight percent were non-White, 66% were female, and 41% were in the most disadvantaged SES quintile. Mean age and HbA1c at diagnosis were 13.4 years and 68 mmol/mol, respectively. Following an initial decrease between diagnosis and end of year 1 (-15.2 mmol/mol 95%CI, -19.2, -11.2), HbA1c trajectories increased between years 1 and 3 (10 mmol/mol, 7.6, 12.4), followed by slight gradual decrease subsequently (-1.6 mmol/mol, -2, -1.1). Compared to White CYP, Pakistani children had higher HbA1c at diagnosis (13.2 mmol/mol, 5.6-20.9). During follow-up, mixed-ethnicity and Pakistani CYP had poorer glycemic control. Compared to children in the most disadvantaged quintile, those in the most advantaged had lower HbA1c at diagnosis (-6.3 mmol, -12.6, -0.1). Differences by SES remained during follow-up. Mutual adjustment for SES and ethnicity did not substantially alter the above estimates. CONCLUSIONS: About two-thirds of children with childhood-onset T2D were non-White, female adolescents, just under half of whom live in the most disadvantaged areas of England and Wales. Additionally, there are substantial socioeconomic and ethnic inequalities in diabetes control.

Amelioration of diabetic nephropathy using pomegranate peel extract-stabilized gold nanoparticles: assessment of NF-κB and Nrf2 signaling system.

BACKGROUND: Diabetic nephropathy (DN), an end-stage renal disorder, has posed a menace to humankind globally, because of its complex nature and poorly understandable intricate mechanism. In recent times, functional foods as potential health benefits have been gaining attention of consumers and researchers alike. Rich in antioxidants, the peel and seed of pomegranate have previously demonstrated protection against oxidative-stress-related diseases, including cardiovascular disorders, diabetes, and cancer. PURPOSE: This study was designed to investigate the ameliorative role of pomegranate peel extract-stabilized gold nanoparticle (PPE-AuNP) on streptozotocin (STZ)-induced DN in an experimental murine model. METHODS: Following the reduction methods, AuNP was prepared using the pomegranate peel ellagitannins and characterized by particle size, physical appearance, and morphological architecture. Modulatory potential of PPE-AuNP was examined through the plethora of biochemical and high throughput techniques, flow cytometry, immunoblotting, and immunofluorescence. RESULTS: The animals treated with PPE-AuNP markedly reduced the fasting blood glucose, renal toxicity indices, and serum TC and TG in a hyperglycemic condition. As evident from an increased level of plasma insulin level, PPE-AuNP normalized the STZ-induced pancreatic ß-cell dysfunction. The STZ-mediated suppression of endogenous antioxidant response was restored by the PPE-AuNP treatment, which reduced the generation of LPO as well as iROS. Furthermore, the hyperglycemia-mediated augmentation of protein glycation, followed by the NOX4/p-47phox activation, diminished with the application of PPE-AuNP. The histological and immunohistochemical findings showed the protective efficacy of PPE-AuNP in reducing STZ-induced glomerular sclerosis and renal fibrosis. In addition, it reduced proinflammatory burden through the modulation of the MAPK/NF-κB/STAT3/cytokine axis. Simultaneously, PI3K/AKT-guided Nrf2 activation was evident upon the PPE-AuNP application, which enhanced the antioxidant response and maintained hyperglycemic homeostasis. CONCLUSION: The findings indicate that the use of PPE-AuNPs might act as an economic therapeutic remedy for alleviating DN.

Assessment of pulsatile insulin secretion derived from peripheral plasma C-peptide concentrations by nonparametric stochastic deconvolution.

The characteristics of pulsatile insulin secretion are important determinants of type 2 diabetes pathophysiology, but they are understudied due to the difficulties in measuring pulsatile insulin secretion noninvasively. Deconvolution of either peripheral C-peptide or insulin concentrations offers an appealing alternative to hepatic vein catheterization. However, to do so, there are a series of methodological challenges to overcome. C-peptide has a relatively long half-life and accumulates in the circulation. On the other hand, peripheral insulin concentrations reflect relatively fast clearance and hepatic extraction as it leaves the portal circulation to enter the systemic circulation. We propose a method based on nonparametric stochastic deconvolution of C-peptide concentrations, using individually determined C-peptide kinetics, to overcome these limitations. The use of C-peptide (instead of insulin) concentrations allows estimation of portal (and not post-hepatic) insulin pulses, whereas nonparametric stochastic deconvolution allows evaluation of pulsatile signals without any a priori assumptions of pulse shape and occurrence. The only assumption required is the degree of smoothness of the (unknown) secretion rate. We tested this method first on simulated data and then on 29 nondiabetic subjects studied during euglycemia and hyperglycemia and compared our estimates with the profiles obtained from hepatic vein insulin concentrations. This method produced satisfactory results both in the ability to fit the data and in providing reliable estimates of pulsatile secretion, in agreement with hepatic vein measurements. In conclusion, the proposed method enables reliable and noninvasive measurement of pulsatile insulin secretion. Future studies will be needed to validate this method in people with type 2 diabetes.

Diabetes Technology: Monitoring, Analytics, and Optimal Control.

Over the past 50 years, the diabetes technology field progressed remarkably through self-monitoring of blood glucose (SMBG), continuous subcutaneous insulin infusion (CSII), risk and variability analysis, mathematical models and computer simulation of the human metabolic system, real-time continuous glucose monitoring (CGM), and control algorithms driving closed-loop control systems known as the "artificial pancreas" (AP). This review follows these developments, beginning with an overview of the functioning of the human metabolic system in health and in diabetes and of its detailed quantitative network modeling. The review continues with a brief account of the first AP studies that used intravenous glucose monitoring and insulin infusion, and with notes about CSII and CGM-the technologies that made possible the development of contemporary AP systems. In conclusion, engineering lessons learned from AP research, and the clinical need for AP systems to prove their safety and efficacy in large-scale clinical trials, are outlined.

The application of simple metrics in the assessment of glycaemic variability.

The assessment of glycaemic variability (GV) remains a subject of debate with many indices proposed to represent either short- (acute glucose fluctuations) or long-term GV (variations of HbA1c). For the assessment of short-term within-day GV, the coefficient of variation for glucose (%CV) defined as the standard deviation adjusted on the 24-h mean glucose concentration is easy to perform and with a threshold of 36%, recently adopted by the international consensus on use of continuous glucose monitoring, separating stable from labile glycaemic states. More complex metrics such as the Low Blood Glucose Index (LBGI) or High Blood Glucose Index (HBGI) allow the risk of hypo or hyperglycaemic episodes, respectively to be assessed although in clinical practice its application is limited due to the need for more complex computation. This also applies to other indices of short-term intraday GV including the mean amplitude of glycemic excursions (MAGE), Shlichtkrull's M-value and CONGA. GV is important clinically as exaggerated glucose fluctuations are associated with an enhanced risk of adverse cardiovascular outcomes due primarily to hypoglycaemia. In contrast, there is at present no compelling evidence that elevated short-term GV is an independent risk factor of microvascular complications of diabetes. Concerning long-term GV there are numerous studies supporting its association with an enhanced risk of cardiovascular events. However, this association raises the question as to whether the impact of long-term variability is not simply the consequence of repeated exposure to short-term GV or ambient chronic hyperglycaemia. The renewed emphasis on glucose monitoring with the introduction of continuous glucose monitoring technologies can benefit from the introduction and application of simple metrics for describing GV along with supporting recommendations.

[Cardiometabolic index as a predictor of cardiovascular risk factors in adolescents]. / Indice cardiometabólico como predictor de factores de riesgo cardiovascular en adolescentes.

OBJECTIVE: To evaluate the ability of the Cardiometabolic Index (CMI) to predict alterations in fasting glucose concentrations, dyslipidemia and hypertension in adolescents. MATERIALS AND METHODS: Descriptive, correlational and cross-sectional study. 278 adolescents aged between 12 and 15 years were evaluated. Serum glucose, triglycerides and HDL-C were determined and the TG/HD-C ratio was estimated. Weight, height and waist circumference were measured and body mass index, conicity index and waist-to-height ratio (WHtR) were determined. The product of WHtR and TG/HDL-C was the Cardiometabolic Index (CMI). Blood pressure was determined. RESULTS: The area under the ROC curve of the CMI as a predictor of dyslipidemia, hypertension (AHT) and impaired fasting glucose (IFG) was 0.777 (CI 95% = 0.712 to 0.842), 0.710 (CI 95% = 0.559 to 0.853) and 0.564 (CI 95% = 0.447 to 0.682), respectively. CONCLUSION: In the studied sample, CMI showed ability to predict dyslipidemia and hypertension, but not IFG.

OBJETIVO: Evaluar la capacidad del Índice Cardiometabólico (ICM) para predecir alteraciones en las concentraciones en ayuno de glucosa, dislipidemia e hipertensión en adolescentes. MÉTODOS: El estudio fue descriptivo, correlacional y transversal. Se evaluaron 278 adolescentes de entre 12 y 15 años. Se determinó las concentraciones de glicemia, triglicéridos, HDL-c y se calculó el índice TG/HDL-c. Se midió el peso, talla y circunferencia de cintura y se determinó el Índice de Masa Corporal, el de conicidad y la relación cintura talla (Rel. CC-T). El producto de la Rel. CC-T y TG/HDL-C constituyó el índice cardiometabólico (ICM). Se determinó la presión arterial. RESULTADOS: El área bajo la curva ROC del ICM como predictor de dislipidemia, hipertensión (HTA) y glucosa alterada en ayunas (GAA) fue de 0,777 (IC 95%=0,712-0,842), 0,710 (IC 95%=0,559-0,853) y 0,564 (IC 95%=0,447-0,682), respectivamente. CONCLUSIÓN: En la muestra estudiada el ICM mostró capacidad de predecir dislipidemia e HTA, pero no para GAA.

Spike in glucose levels after reperfusion during aortic surgery: assessment by continuous blood glucose monitoring using artificial endocrine pancreas.

OBJECTIVES: Although strict blood glucose control during cardiovascular surgery is essential to avoid postoperative complications, the various changes in glucose levels that occur during surgery have not been investigated in detail. In this study, we continuously monitored blood glucose changes during aortic surgery using the STG-55Ⓡ artificial endocrine pancreas (Nikkiso Inc., Tokyo). METHODS: Between December 2015 and 2016, we performed continuous blood glucose monitoring in 22 patients (14 men and 8 women, 72 ± 11 years old), who required hypothermic circulatory arrest during an ascending/aortic arch surgery, at the Jichi Medical University Hospital. Ascending aorta replacements were performed in two patients and partial/total arch replacement, in 20. All the patients required selective cerebral perfusion and hypothermic circulatory arrest (bladder temperature at 25-26 °C) during distal anastomosis. Closed-loop continuous blood glucose monitoring was performed during cardiopulmonary bypass using the STG-55Ⓡ artificial endocrine pancreas (Nikkiso Co., LTD, Tokyo). RESULTS: Blood glucose concentrations did not increase significantly from the time of the commencement of cardiopulmonary bypass to lower body ischemia. However, they dramatically increased immediately after reperfusion following lower body ischemia, and this hyperglycemia was sustained until the end of cardiopulmonary bypass. CONCLUSION: The current study clarified the peak glucose concentration during aortic surgery. These data may contribute to the management of blood glucose levels during aortic surgery.

Assessment of ß Cell Mass and Function by AIRmax and Intravenous Glucose in High-Risk Subjects for Type 1 Diabetes.

Context: There is little information regarding ß cell mass in individuals at early stages of type 1 diabetes (T1D). Objective: To investigate both acute insulin response to arginine at hyperglycemia (AIRmax), as a correlate of ß cell mass, and ß cell function by the intravenous glucose tolerance test (IVGTT) in subjects at early stages of T1D. Design/Setting/Participants: Forty subjects were enrolled: (1) low-risk group: relatives of patients with T1D with 0 to 1 antibody (n = 21) and (2) high-risk group: relatives with ≥2 antibodies (n = 19). Main Outcome Measure: Acute insulin and C-peptide responses to IVGTT and to AIRmax. Participants underwent two IVGTT and AIRmax procedures on different days. Results: AIRmax was reproducible, well tolerated, and correlated to first-phase insulin response (FPIR) from IVGTT (r = 0.779). The high-risk group had greater impaired ß cell function compared with the low-risk group, determined both by lower mean FPIR and a greater number of subjects below an established threshold for abnormal function [10 of 19 (52.6%) versus 4 of 21 (19%)]. There was a heterogeneous AIRmax response in these subjects with low FPIR, ranging from 38 to 250 µU/mL. Conclusions: There is significant variation in insulin secretory reserve as assessed by AIRmax in family members with low ß cell function assessed by FPIR. As AIRmax is a functional measure of ß cell mass, these data suggest heterogeneity in disease pathogenesis in which mass is preserved in relation to function in some individuals. The tolerability and reproducibility of AIRmax suggest it could be a useful stratification measure in clinical trials of disease-modifying therapy.

External national validation of the Leicester Self-Assessment score for Type 2 diabetes using data from the English Longitudinal Study of Ageing.

AIMS: To validate the Leicester Self-Assessment score using a representative English dataset for detecting prevalent non-diabetic hyperglycaemia or undiagnosed Type 2 diabetes (defined as HbA1c ≥6.0%) and for identifying those who may go on to develop Type 2 diabetes within 10 years. METHODS: Data were taken from the English Longitudinal Study of Ageing, a nationally representative dataset of people aged ≥50 years. The area under the receiver-operator curve and performance metrics for the score at the recommended score threshold (≥16), were calculated for the outcomes of HbA1c ≥42 mmol/mol (6.0%) at baseline and self-reported Type 2 diabetes within 10 years in those aged 50-75 years at baseline. RESULTS: A total of 3203 individuals had a baseline HbA1c measurement, of whom 247 (7.7%) had an HbA1c concentration ≥42 mmol/mol (6.0%). The area under the receiver-operator curve was 69.4% (95% CI 66.0-72.9) for baseline HbA1c ≥42 mmol/mol. A total of 3550 individuals had diabetes status recorded at 10 years, of whom 324 (9.1%) were diagnosed with Type 2 diabetes within this time; the area under the receiver-operator curve for this outcome was 74.9% (95% CI 72.4-77.5). The score threshold of ≥16 had a sensitivity of 89.2% (95% CI 85.3-92.4) and a specificity of 42.3% (95% CI 40.5-44.0) for Type 2 diabetes within 10 years. CONCLUSIONS: The Leicester Self-Assessment score is validated for use across England to identify people with non-diabetic hyperglycaemia or undiagnosed Type 2 diabetes. Those with a high score are at high risk of developing diabetes in the future.

Assessment of Glycemic Control in Nursing Home Residents with Diabetes.

OBJECTIVE: To describe glycemic control in nursing home residents with diabetes and to evaluate the relevance of HbA1c in the detection of hypoglycemia risk. DESIGN AND METHODS: Diabetes treatment, geriatric assessment, blood capillary glucose (n= 24,682), and HbA1c were collected from medical charts of 236 southern France nursing home residents during a 4-month period. Glycemic control was divided into four categories: tight, fair, and moderate or severe chronic hyperglycemia using the High Blood Glucose Index or the analysis of blood glucose frequency distribution. Hypoglycemia episodes were identified by medical or biological records. RESULTS: Glucose control was tight in 59.3 % and fair in 19.1 % of the residents. Chronic exposure to hyperglycemia was observed in 21.6 % of the residents (severe in 9.7 % and moderate in 11.9 %). Hypoglycemia was noticed in 42/236 (17.8%), in all categories of glycemic control. Relative hypoglycemia risk was significantly (P = 0.0095) higher in residents with moderate chronic hyperglycemia compared with those with tight control. The majority of residents with hypoglycemia (39/42) or chronic hyperglycemia (45/51) were insulin-treated. The relative risk of hypoglycemia was not significantly associated with HbA1c values. CONCLUSION: Hypoglycemia risk in nursing home residents is observed in all categories of glycemic control. In tight control, the potency of antidiabetic treatment should be reduced. In chronic hyperglycemia, diet and treatment should be reevaluated in order to reduce glucose variability. HbA1c is not sufficient for hypoglycemia risk detection; capillary blood glucose monitoring is warranted for nursing homes residents with diabetes.

Association of depressive symptomology and psychological trauma with diabetes control among older American Indian women: Does social support matter?

AIMS: Among older American Indian women with type 2 diabetes (T2DM), we examined the association between mental health and T2DM control and if social support modifies the association. METHODS: Survey data were linked to T2DM medical record information. Mental health measures were the Center for Epidemiologic Studies - Depression Scale and the National Anxiety Disorders Screening Day instrument. T2DM control was all HbA1c values taken post mental health measures. RESULTS: There was not a significant association between depressive symptomatology and higher HbA1c although increased depressive symptomatology was associated with higher HbA1c values among participants with low social support. There was a significant association between psychological trauma and higher HbA1c values 12months [mean 7.5, 95% CI 7.0-8.0 for no trauma vs. mean 7.0, 95% CI 6.3-7.6 for trauma with no symptoms vs. mean 8.4, 95% CI 7.7-9.1 for trauma with ≥1 symptom(s)] and 6months later [mean 7.2, 95% CI 6.7-7.7 for no trauma vs. mean HbA1c 6.8, 95% CI 6.2-7.4 for trauma with no symptoms vs. mean 8.4, 95% CI 7.6-9.2 for trauma with ≥1 symptom(s)]. High social support attenuated the association between psychological trauma and HbA1c values. CONCLUSIONS: T2DM programs may consider activities that would strengthen participants' social support and thereby building on an intrinsic community strength.

Assessment of response rates and yields for Two opportunistic Tools for Early detection of Non-diabetic hyperglycaemia and Diabetes (ATTEND). A randomised controlled trial and cost-effectiveness analysis.

AIMS: To assess the opportunistic use in primary care of a computer risk score versus a self-assessment risk score for undiagnosed type 2 diabetes. METHODS: We conducted a randomised controlled trial in 11 primary care practices in the UK. 577 patients aged 40-75years with no current diagnosis of type 2 diabetes were recruited to a computer based risk score (Leicester Practice Computer Risk Score (LPCRS)) or a patient self-assessment score (Leicester Self-Assessment Score (LSAS)). RESULTS: The rate of self-referral blood tests was significantly higher for the LPCRS compared to the LSAS, 118.98 (95% CI: 102.85, 137.64) per 1000 high-risk patient years of follow-up compared to 92.14 (95% CI: 78.25, 108.49), p=0.022. Combined rate of diagnosis of type 2 diabetes and those at risk of developing the disease (i.e. impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)) was similar between the two arms, 15.12 (95% CI: 9.11, 25.08) per 1000 high-risk patient years for LPCRS compared to 14.72 (95% CI: 9.59, 22.57) for the LSAS, p=0.699. For the base case scenario the cost per new case of type 2 diabetes diagnosed was lower for the LPCRS compared to the LSAS, £168 (95% Credible Interval (CrI): 76, 364), and £352 (95% CrI: 109, 1148), respectively. CONCLUSIONS: Compared to a self-assessment risk score, a computer based risk score resulted in greater attendance to an initial blood test and is potentially more cost-effective.