Diabetes Technology Meeting 2023.

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

SITAgliptin for Depressive Symptoms in Type 2 Diabetes: A Feasibility Randomized Controlled Trial.

OBJECTIVE: We tested the feasibility of using sitagliptin-a dipeptidyl peptidase-IV inhibitor-for depressive symptoms in type 2 diabetes (T2D). METHODS: In a feasibility, double-blind, randomized controlled trial, we recruited people aged 18 to 75 years with T2D (glycated hemoglobin A1c levels ≥53 and ≤86 mmol/mol prescribed oral hypoglycemic therapy) and comorbid depressive symptoms (Patient Health Questionnaire-9 score ≥10) from family practices in South London. Eligible patients were randomized to sitagliptin 100 mg per day or matched placebo for 12 weeks. The primary feasibility outcomes were participation rates, attrition rates, and adverse events. The primary clinical outcomes were depressive symptoms (Patient Health Questionnaire-9 and 16-item Quick Inventory of Depressive Symptomatology scores) at 12 weeks as assessed using analyses of covariance. Ranges of treatment effects were estimated using Cohen d and associated 95% confidence intervals, where negative values favored sitagliptin over placebo. RESULTS: Of 153 people screened across 32 practices, 44 were randomized (22 to each arm). The mean (standard deviation) age was 58.8 (8.3) years, 46% were female, and 52% were of non-white ethnicity. Of those treated, 1 patient (4.5%) in each arm withdrew, and there were no group differences in adverse events. Despite improving 12-week glycated hemoglobin A1c (d = -1.19 [95% confidence interval = -1.90 to -0.48), improvement in 12-week Quick Inventory of Depressive Symptomatology score with sitagliptin was inferior to placebo across the range of estimated treatment effects (d = 0.71 [0.13 to 1.30]). Effects of sitagliptin on inflammation were inconsistent (d = -0.32 [-0.81 to 0.17] for high-sensitivity C-reactive protein). CONCLUSIONS: Repositioning of oral hypoglycemic therapy for depressive symptoms in T2D is feasible. However, in this unpowered feasibility study, we did not detect evidence of superiority of sitagliptin over placebo. The results are cautioned by the small sample size and limited treatment duration.Trial Registration: EudraCT: 2015-004527-32.

Advances in technology for management of type 1 diabetes.

Technological advances have had a major effect on the management of type 1 diabetes. In addition to blood glucose meters, devices used by people with type 1 diabetes include insulin pumps, continuous glucose monitors, and, most recently, systems that combine both a pump and a monitor for algorithm-driven automation of insulin delivery. In the next 5 years, as many advances are expected in technology for the management of diabetes as there have been in the past 5 years, with improvements in continuous glucose monitoring and more available choices of systems that automate insulin delivery. Expansion of the use of technology will be needed beyond endocrinology practices to primary-care settings and broader populations of patients. Tools to support decision making will also need to be developed to help patients and health-care providers to use the output of these devices to optimise diabetes management.

The Prospective Association Between Inflammation and Depressive Symptoms in Type 2 Diabetes Stratified by Sex.

OBJECTIVE: We tested whether inflammation is associated with worsening depressive symptoms in type 2 diabetes and examined whether sex moderated this association. RESEARCH DESIGN AND METHODS: In a prospective cohort study of people with newly diagnosed type 2 diabetes, we measured depressive symptoms over a 2-year follow-up using the Patient Health Questionnaire-9 (PHQ-9). The independent variable was a composite inflammation burden score at diagnosis of diabetes, derived from hs-CRP, white cell count, interleukin (IL)-1ß, IL-1 receptor antagonist, monocyte chemotactic protein-1, and vascular endothelial growth factor concentrations. General linear models assessed 1) the association between overall inflammation burden and estimated marginal mean PHQ-9 score (ln transformed) at 2 years and 2) whether sex interacted with elevated inflammation burden (above-median score) in predicting change in PHQ-9 score. Models were adjusted for age, ethnicity, BMI, blood pressure, cholesterol, HbA1c, antidepressants, anti-inflammatory medications, and baseline ln PHQ-9 score. RESULTS: Of 1,174 people with complete inflammation data, mean (SD) age was 56.7 (11.0) years and 46.1% were of nonwhite ethnicity and 44.1% female. After full adjustment, inflammation burden was not associated with worsening ln PHQ-9 score (P = 0.65). However, female sex interacted with elevated inflammation in predicting higher 2-year ln PHQ-9 score (ß = 0.32, P = 0.005), showing that the difference by inflammation burden in females was 0.32 larger than in males. In post hoc comparisons, ln PHQ-9 score was higher in females than males with elevated inflammation (P = 0.003) but not with low inflammation (P = 0.34) burden. CONCLUSIONS: In type 2 diabetes, female sex confers specific vulnerability to the effects of inflammation on depressive symptoms.

The association of depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years in newly diagnosed type 2 diabetes: a prospective cohort study.

AIMS/HYPOTHESIS: We examined the associations between depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years, after diagnosis of type 2 diabetes. METHODS: In a multi-ethnic, primary care cohort (n = 1735) of adults, all with recent (<6 months) diagnosis of type 2 diabetes, we measured the associations between depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) and diabetes distress (Problem Areas in Diabetes [PAID] score ≥40), with change in 2 year HbA1c as the primary outcome and with incident rates of diabetes complications as secondary outcomes. Multivariate models were used to account for potential confounders. RESULTS: Of the 1651 participants (95.2%) of the total primary care cohort with available baseline PHQ-9 and PAID scores, mean ± SD age was 56.2 ± 11.1 years, 55.1% were men and 49.1% were of non-white ethnicity; 232 (14.1%) and 111 (6.7%) had depressive symptoms and diabetes distress, respectively. After adjustment for confounders, depressive symptoms were not associated with worsening HbA1c. After adjustment for age, sex, ethnicity, vascular risk factors and diabetes treatments, depressive symptoms were associated with increased risk of incident macrovascular complications (OR 2.78 [95% CI 1.19, 6.49], p = 0.018) but not microvascular complications. This was attenuated (p = 0.09) after adjustment for IL-1 receptor antagonist concentration. Diabetes distress was not associated with worsening HbA1c or incident complications. CONCLUSIONS/INTERPRETATION: In the first 2 years of type 2 diabetes, the effect of depressive symptoms and diabetes distress on glycaemic control is minimal. There was, however, an association between depressive symptoms and incidence of macrovascular complications. Elevated innate inflammation may be common to both depression and macrovascular diabetes complications, but these findings require replication.

Glycemic Control During Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Insulin Injections in Type 2 Diabetes: Individual Patient Data Meta-analysis and Meta-regression of Randomized Controlled Trials.

OBJECTIVE: To compare glycemic control during continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) in people with type 2 diabetes to identify patient characteristics that determine those best treated by CSII. RESEARCH DESIGN AND METHODS: Randomized controlled trials were selected comparing HbA1c during CSII versus MDI in people with type 2 diabetes. Data sources included Cochrane database and Ovid Medline. We explored patient-level determinants of final HbA1c level and insulin dose using Bayesian meta-regression models of individual patient data and summary effects using two-step meta-analysis. Hypoglycemia data were unavailable. RESULTS: Five trials were identified, with 287 patients randomized to receive MDI and 303 to receive CSII. Baseline HbA1c was the best determinant of final HbA1c: HbA1c difference (%) = 1.575 - (0.216 [95% credible interval 0.371-0.043] × baseline HbA1c) for all trials, but with largest effect in the trial with prerandomization optimization of control. Baseline insulin dose was best predictor of final insulin dose: insulin dose difference (units/kg) = 0.1245 - (0.382 [0.510-0.254] × baseline insulin dose). Overall HbA1c difference was -0.40% (-0.86 to 0.05 [-4.4 mmol/mol (-9.4 to 0.6)]). Overall insulin dose was reduced by -0.25 units/kg (-0.31 to -0.19) (26% reduction on CSII), and by -24.0 units/day (-30.6 to -17.5). Mean weight did not differ between treatments (0.08 kg [-0.33 to 0.48]). CONCLUSIONS: CSII achieves better glycemic control than MDI in people with poorly controlled type 2 diabetes, with ∼26% reduction in insulin requirements and no weight change. The best effect is in those worst controlled and with the highest insulin dose at baseline.

Long-term health economic benefits of sensor-augmented pump therapy vs continuous subcutaneous insulin infusion alone in type 1 diabetes: a U.K. perspective.

AIMS/HYPOTHESIS: Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP + LGS vs. CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP + LGS in type 1 diabetes patients using CSII in the U.K. METHODS: Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP + LGS was associated with a projected HbA1c reduction of -1.49% vs. -0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively. RESULTS: Projected outcomes showed that SAP + LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs. 14.9 quality-adjusted life years [QALYs], SAP + LGS vs. CSII), and higher life expectancy (23.8 vs. 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs. GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP + LGS vs. CSII. Findings of the base-case analysis remained robust in sensitivity analyses. CONCLUSIONS/INTERPRETATION: For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP + LGS is likely to be cost-effective compared with CSII plus SMBG.

The link between depression and diabetes: the search for shared mechanisms.

Depression is twice as common in people with type 1 or type 2 diabetes as in the general population, and is associated with poor outcomes. Evidence is growing that depression and type 2 diabetes share biological origins, particularly overactivation of innate immunity leading to a cytokine-mediated inflammatory response, and potentially through dysregulation of the hypothalamic-pituitary-adrenal axis. Throughout the life course, these pathways can lead to insulin resistance, cardiovascular disease, depression, increased risk of type 2 diabetes, and increased mortality. Proinflammatory cytokines might directly affect the brain, causing depressive symptoms. In type 1 diabetes, mediators of depression are not well studied, with research hindered by inconsistent definitions of depression and scarcity of observational, mechanistic, and interventional research along the life course. Despite few studies, evidence suggests that familial relationships and burden of a lifelong disorder with an onset early in personality development might contribute to increased vulnerability to depression. Overall, longitudinal research is needed to identify risk factors and mechanisms for depression in patients with diabetes, particularly early in the life course. Ultimately, improved understanding of shared origins of depression and diabetes could provide the potential to treat and improve outcomes of both disorders simultaneously. These shared origins are targets for primary prevention of type 2 diabetes.

Real-time continuous glucose monitoring in type 1 diabetes: a qualitative framework analysis of patient narratives.

OBJECTIVE: This study analyzed narratives about experiences of real-time continuous glucose monitoring (CGM) in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: People with type 1 diabetes using CGM and caregivers completed an online survey. Questions included duration of CGM, frequency of sensor wear, funding, and a free narrative about experiences or views about CGM. We used qualitative framework analysis to analyze 100 responses; 50% of participants were aged ≥ 18 years. RESULTS: Most participants (87%) used CGM with insulin pump therapy, 71% used sensors ≥ 75% of the time, and 66% received funding for CGM from the National Health Service. Four themes were identified: 1) metabolic control, 2) living with CGM (work and school, sleep, exercise, nutrition, frequency of self-monitoring of blood glucose [SMBG]), 3) psychological issues and patient/caregiver attitudes, and 4) barriers to CGM use (technical issues, financial issues, attitudes of healthcare professionals toward CGM). Despite some hassles, experiences were overwhelmingly positive, with improved glycemic control, diet and exercise management, quality of life, and physical and psychological well-being, as well as reduced frequency of SMBG. Technical problems included sensor inaccuracy and unreliability, and "alarm fatigue." The advantages of CGM used with an insulin pump with automatic suspension of insulin delivery during hypoglycemia were recorded by several participants, noting reduced hypoglycemia frequency and fear of nocturnal hypoglycemia. CONCLUSIONS: Patient and caregiver narratives indicate that CGM is a valuable addition to diabetes care for many with type 1 diabetes.

A novel fluorescent sensor protein for detecting changes in airway surface liquid glucose concentration.

Both lung disease and elevation of blood glucose are associated with increased glucose concentration (from 0.4 to ~4.0 mM) in the airway surface liquid (ASL). This perturbation of ASL glucose makes the airway more susceptible to infection by respiratory pathogens. ASL is minute (~1 µl/cm(2)) and the measurement of glucose concentration in the small volume ASL is extremely difficult. Therefore, we sought to develop a fluorescent biosensor with sufficient sensitivity to determine glucose concentrations in ASL in situ. We coupled a range of environmentally sensitive fluorophores to mutated forms of a glucose/galactose-binding protein (GBP) including H152C and H152C/A213R and determined their equilibrium binding properties. Of these, GBP H152C/A213R-BADAN (Kd 0.86 ± 0.01 mM, Fmax/F0 3.6) was optimal for glucose sensing and in ASL increased fluorescence when basolateral glucose concentration was raised from 1 to 20 mM. Moreover, interpolation of the data showed that the glucose concentration in ASL was increased, with results similar to that using glucose oxidase analysis. The fluorescence of GBP H152C/A213R-BADAN in native ASL from human airway epithelial cultures in situ was significantly increased over time when basolateral glucose was increased from 5 to 20 mM. Overall our data indicate that this GBP is a useful tool to monitor glucose homoeostasis in the lung.

Diabetes: insulin pump therapy for type 2 diabetes mellitus.

The evidence base for the efficacy of insulin pump therapy in type 2 diabetes mellitus (T2DM) has been inconsistent to date. However, a recent large-scale randomized controlled trial comparing pump treatment with multiple daily insulin injections in patients with poorly controlled T2DM has shown substantial improvement in glycaemic control with pump therapy.

The association between depressive symptoms and systemic inflammation in people with type 2 diabetes: findings from the South London Diabetes Study.

OBJECTIVE: The prevalence of depression and depressive symptoms is increased twofold in people with type 2 diabetes compared with the general population and is associated with worse biomedical outcomes and increased mortality. Type 2 diabetes, cardiovascular disease, and depression in nondiabetes subjects are independently associated with raised concentrations of circulating inflammatory markers, but it is not known if a similar association is observed in type 2 diabetes. We tested the hypothesis that higher depressive symptom scores in newly diagnosed type 2 diabetes patients were associated with higher concentrations of inflammatory markers. RESEARCH DESIGN AND METHODS: Depressive symptoms in adults with newly diagnosed type 2 diabetes recruited from primary care were assessed using the Patient Health Questionnaire-9. Twelve markers of inflammation (C-reactive protein [hs-CRP], interleukin-4 [IL-4], IL-6, IL-10, vascular endothelial growth factor [VEGF], tumor necrosis factor-α [TNF-α], IL-1ß, IL-1 receptor antagonist [IL-1RA], monocyte chemotactic protein-1 [MCP-1], white blood cell count [WBC], adiponectin, and triglyceride [TG]) were measured. Covariates included sociodemographic factors, adiposity, macrovascular disease, HbA1c, and prescribed medication. The association between each inflammatory marker and depressive symptom score was estimated by multiple linear regression. RESULTS: The baseline cohort consisted of 1,790 participants. After adjusting for covariates, CRP (B = 0.13, P < 0.001), IL-1ß (B = 0.06, P = 0.047), IL-1RA (B = 0.13, P < 0.001), MCP-1 (B = 0.11, P = 0.001), WBC (B = 0.13, P < 0.001), and TG (B = 0.10, P < 0.001) were associated with depressive symptoms. CONCLUSIONS: Increased inflammation may be involved in the pathogenesis of depressive symptoms in type 2 diabetes and contribute to the increased risk of complications and mortality in this group.

Nanolayer encapsulation of insulin-chitosan complexes improves efficiency of oral insulin delivery.

Current oral insulin formulations reported in the literature are often associated with an unpredictable burst release of insulin in the intestine, which may increase the risk for problematic hypoglycemia. The aim of the study was to develop a solution based on a nanolayer encapsulation of insulin-chitosan complexes to afford sustained release after oral administration. Chitosan/heparin multilayer coatings were deposited onto insulin-chitosan microparticulate cores in the presence of poly(ethylene) glycol (PEG) in the precipitating and coating solutions. The addition of PEG improved insulin loading and minimized an undesirable loss of the protein resulting from redissolution. Nanolayer encapsulation and the formation of complexes enabled a superior loading capacity of insulin (>90%), as well as enhanced stability and 74% decreased solubility at acid pH in vitro, compared with nonencapsulated insulin. The capsulated insulin administered by oral gavage lowered fasting blood glucose levels by up to 50% in a sustained and dose-dependent manner and reduced postprandial glycemia in streptozotocin-induced diabetic mice without causing hypoglycemia. Nanolayer encapsulation reduced the possibility of rapid and erratic falls of blood glucose levels in animals. This technique represents a promising strategy to promote the intestinal absorption efficiency and release behavior of the hormone, potentially enabling an efficient and safe route for oral insulin delivery of insulin in diabetes management.

Nonmetabolic complications of continuous subcutaneous insulin infusion: a patient survey.

BACKGROUND: Little is known about the frequencies and types of nonmetabolic complications occurring in type 1 diabetes patients being treated by modern insulin pump therapy (continuous subcutaneous insulin infusion [CSII]), when recorded by standardized questionnaire rather than clinical experience. SUBJECTS AND METHODS: A self-report questionnaire was completed by successive subjects with type 1 diabetes attending an insulin pump clinic, and those with a duration of CSII of ≥6 months were selected for analysis (n=92). Questions included pump manufacturer, insulin, infusion set type and duration of use, frequency of infusion set and site problems, pump malfunctions, and patient-related problems such as weight change since starting CSII. RESULTS: Median (range) duration of CSII was 3.3 (0.5-32.0) years, and mean ± SD duration of infusion set use was 3.2 ± 0.7 (range 2-6) days. The commonest infusion set problems were kinking (64.1% of subjects) and blockage (54.3%). Blockage was associated with >3 days of use of infusion sets plus lispro insulin in the pump (relative risk [95% confidence interval], 1.71 [1.03-2.85]; P=0.07). The commonest infusion site problem was lipohypertrophy (26.1%), which occurred more often in those with long duration of CSII (4.8 [2.38-9.45] vs. 3.0 [1.50-4.25] years; P=0.01). Pump malfunction had occurred in 48% of subjects (43% in the first year of CSII), with "no delivery," keypad, and battery problems commonly occurring. Although some patients reported weight gain (34%) and some weight loss (15%) on CSII, most patients (51%) reported no change in weight. CONCLUSIONS: Pump, infusion set, and infusion site problems remain common with CSII, even with contemporary technology.

The evidence base for diabetes technology: appropriate and inappropriate meta-analysis.

When we are interested in making decisions about best use, comparative therapeutic efficacy, or cost-effectiveness of diabetes technologies such as insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] or continuous glucose monitoring, meta-analysis for the purpose of literature summary is inappropriate and may be misleading. Instead, "decision-making meta-analysis" is more appropriate and should involve either preselection of trials based on intended use [e.g., elevated baseline hemoglobin A1c or hypoglycemia rate for trials of multiple daily injections (MDI) versus CSII] or metaregression of summary effect sizes in different trials against potential effect-modifying covariates such as baseline risk, or models of the covariates that determine effect size using individual patient data. Appropriate meta-analysis should also only include trials that are of sufficient duration to accurately measure outcomes such as severe hypoglycemia, and they should not use obsolete technology that is of proven inferiority to current technology. The use of appropriate decision-making meta-analysis is illustrated by the change in the rate ratio for severe hypoglycemia in randomized controlled trials of MDI versus CSII in type 1 diabetes from 1.56 (95% confidence interval 0.96-2.55; p = .074) for literature-summary meta-analysis to 2.0 (1.08-3.69; p = .027) for decision-making meta-analysis of all patients and 3.91 (1.35-11.36; p = .01) for trials in children.