Diabetes Glucose Control Research Articles

Development and implementation of ambulatory care pharmacy services at an internal medicine clinic.

This report describes the step-by-step process that led to expansion of ambulatory care pharmacy services at a newly established internal medicine clinic within a patient-centered medical home in North Carolina. Implementation of clinical pharmacist services at the clinic was led by a postgraduate year 2 (PGY2) pharmacy resident and guided by the 9 steps described in the book Building a Successful Ambulatory Care Practice: A Complete Guide for Pharmacists. After a needs assessment and review of the demographics and insurance status of the clinic's target population, it was determined that pharmacist services would focus on quality measures including diabetes nephropathy screening, diabetes eye examination, blood glucose control in diabetes, discharge medication reconciliation, annual wellness visits, and medication adherence in diabetes, hypercholesterolemia, and hypertension. Clinic appointments were conducted under 3 models: a pharmacist-physician covisit model, a "floor model" of pharmacist consultation on drug information or medication management issues during medical resident sign-out sessions with supervising physicians (medical residents could also see patients along with the pharmacist at a covisit appointment), and a covisit model of stacked physician and pharmacist appointments. The pharmacist's services were expanded from 2 half-day clinic sessions per week initially to 5 or 6 half-day clinic sessions by the end of the residency year. By the fourth quarter of the first PGY2 residency year in which ambulatory care pharmacy services were provided in the clinic, the clinical and financial impact of those services justified the addition of a second full-time pharmacist to the clinic team.

Mathematical model for assessing glycemic control in type 2 diabetes mellitus.

Glycated hemoglobin (HbA1c) and glycated albumin (GA) are vital markers for assessing glucose control in diabetes. This cross-sectional study involving 901 diagnosed type 2 diabetics aimed to compare calculated HbA1c, using the formula HbA1c = 2.6 + 0.03 x FBS (mg/dL), with directly measured HbA1c. Simultaneously, the study assessed the agreement between the two methods through regression analysis and explored correlations with various measures of glycemic control. The non-parametric Kolmogorov-Smirnov test indicated a non-normal data distribution, prompting appropriate statistical tests. Spearman's correlation coefficient revealed a strong correlation of calculated HbA1c, calculated GA, and estimated average glucose with measured parameters. Wilcoxon rank sum test indicated a significant difference between directly measured and calculated HbA1c (Z -9.487033, p < 0.0001). Passing Bablok regression analysis showed a significant deviation from linearity. Despite the potential cost benefits in resource-poor settings, caution is advised regarding interchangeable use of calculated and directly measured HbA1c in clinical decision-making. Data shows the importance of robust analytical methods in glycemic control assessment, offering insights for managing type 2 diabetes mellitus.

Body composition and sexual hormones for the glucose control of autoimmune diabetes in males: are they necessary to predict diabetes-related complications?

Glucose control in diabetes is essential for avoiding diabetes-related complications. To determine the impact of body composition and sexual hormones in glucose control and diabetes-related complications, in males with autoimmune diabetes. Thirty-nine patients with autoimmune diabetes and flash glucose monitoring were included. A morphofunctional nutritional evaluation with bioelectrical impedance vector analysis (BIVA), abdominal adipose tissue ultrasound, rectus femoris ultrasound and biochemical parameters, was performed. Strong, positive correlations were observed between body composition parameters, biochemical variables and sexual hormones (p<0.05). Adipose tissue measured by BIVA and ultrasound was more significantly associated with glucose control (including time in range >70%, glucose variability <36% determined by flash glucose monitoring; p<0.05) and the presence of microvascular/macrovascular complications (p<0.05) than lean mass. After adjusting by the duration of diabetes, BMI, abdominal circumference, fat mass and phase angle increased the risk for microvascular complications (OR 1.32(1.00 - 1.73), OR 1.06(1.00 - 1.12), OR 1.14(1.01 - 1.20), 0R 0.3(0.10 - 0.91) respectively; for macrovascular complications: BMI OR 1.38(1.04 - 1.84) and fat mass OR 1.26(1.00 - 1.58)]. Sexual hormone levels did not influence on glucose control or the development of diabetes-related complications. Anthrpometric parameters, especially adipose tissue, were associated with glucose control and variability determined by flash glucose monitoring. Furthermore, changes in fat and lean mass were associated with the presence of microvascular and macrovascular complications. Thus, a comprehensive nutritional evaluation might be useful for the evaluation of males with autoimmune diabetes, in order to identify patients with increased risk of complications.

Nighttime blood pressure and glucose control impacts on left ventricular hypertrophy: The Japan Morning Surge Home Blood Pressure (J-HOP) Study.

Several studies investigated the association between nighttime blood pressure (BP) and left ventricular hypertrophy (LVH) in diabetes, but since most of these studies were conducted in diabetes populations only, they did not compare differences in the impact of nighttime BP on LVH in subjects without diabetes. Moreover, data about the impact of glucose control in diabetes on the relationship between nighttime BP and LVH are sparse. We classified 1277 adults (age 64.7 ± 11.8 years) performing ambulatory BP monitoring while enrolled as part of the Japan Morning Surge Home Blood Pressure (J-HOP) study into groups according to the control status of daytime BP (systolic BP [SBP] < 135 mmHg or ≥135 mmHg), nighttime BP (SBP < 120 mmHg or ≥120 mmHg), and diabetes (HbA1c < 7.0% or ≥7.0%). LVH was assessed by echocardiography. LVH according to echocardiographic criteria was identified in 33.7% of the participants. The group with poorly controlled diabetes plus uncontrolled nighttime BP (n = 90) had a 2.1-fold higher risk of LVH compared to the group with controlled nighttime BP and non-diabetes (n = 505) (odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.29-3.44). No association was observed between uncontrolled daytime BP and diabetes for LVH. In the participants with poorly controlled diabetes (n = 146), uncontrolled nighttime BP posed a 3.1-fold higher risk of LVH compared to controlled nighttime BP (OR 3.12, 95%CI: 1.47-6.62). This association was not found in controlled diabetes. Uncontrolled nighttime BP was associated with a risk of LVH, especially among individuals with poorly controlled diabetes.

1400-P: Low Blood Oxygen Saturation Is Associated with Impaired Glucose Control in Diabetes

Low Blood Oxygen Saturation (BOS) is associated with increased overall morbidity / mortality and prevalence of diabetes is known to increase with altitude (lower 02 partial pressure). Individuals with complicated diabetes commonly have low blood oxygen saturation compared with nondiabetic patients. To unravel the link between low BOS and glucose metabolism, we investigated the correlation between BOS and glucose, BOS and HbA1c levels, BOS and VO2 consumption (Resting Energy Expenditure) in a cohort of adults with diabetes mellitus. The study included 1362 adults with diabetes (616 F, 746 M; 66.4 ± 14.2 years, range 18-85 years; BMI 27.6 ± 5.0 kg/m2, range 18-49.6 kg/m2; SpO2 97.2 ± 1.4%, range 88-100%; glucose 137.7 ± 45.0 mg/dl, range 50.0-323.0 mg/dl). A significant inverse correlation (Pearson) between the glucose (glucometer) and the BOS (pulsoximeter) (p&amp;lt;0.0001*; r = -0.1530). An inverse correlation (Pearson correlation) between the HbA1c levels and the BOS (n=1295; 568 F, 727 M; 67.5 ± 13.1 years, range 18-85 years; BMI 27.8 ± 5.2 kg/m2, range 18-49.8 kg/m2; HbA1c 52.9 ± 13.0, range 25-152 mmol/mol; p&amp;lt;0.0001*; r = -0.1351). In summary, we showed an inverse relationship between oxygen saturation and both glucose and glycosylated hemoglobin levels. Although the exact mechanisms behind lower blood oxygen saturation in diabetes are unknown, we speculate that a reduced pulmonary diffusion capacity as a consequence of pulmonary microvascular damage could play an important role. In conclusion, present preliminary data indicate the routine measurement of BOS along with glucose and glycosylated hemoglobin in the outpatient visit setting of diabetic patients as a biomarker of seriousness of disease. Disclosure L. Luzi: Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gelesis. Advisory Panel; Medtronic. Speaker's Bureau; Novo Nordisk, Novartis. C. Macrì: None. A. Ferrulli: None. C.C. Berra: None. C. Romano: None. S. Massarini: None. Funding IRCCS MultiMedica (Ricerca Corrente)

Mitotic CDK1 and 4E-BP1 II: A single phosphomimetic mutation in 4E-BP1 induces glucose intolerance in mice.

Cyclin-dependent kinase 1 (CDK1)/cyclin B1 phosphorylates many of the same substrates as mTORC1 (a key regulator of glucose metabolism), including the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Only mitotic CDK1 phosphorylates 4E-BP1 at residue S82 in mice (S83 in humans), in addition to the common 4E-BP1 phospho-acceptor sites phosphorylated by both CDK1 and mTORC1. We examined glucose metabolism in mice having a single aspartate phosphomimetic amino acid knock in substitution at the 4E-BP1 serine 82 (4E-BP1S82D) mimicking constitutive CDK1 phosphorylation. Knock-in homozygous 4E-BP1S82D and 4E-BP1S82A C57Bl/6N mice were assessed for glucose tolerance testing (GTT) and metabolic cage analysis on regular and on high-fat chow diets. Gastrocnemius tissues from 4E-BP1S82D and WT mice were subject to Reverse Phase Protein Array analysis. Since the bone marrow is one of the few tissues typically having cycling cells that transit mitosis, reciprocal bone-marrow transplants were performed between male 4E-BP1S82D and WT mice, followed by metabolic assessment, to determine the role of actively cycling cells on glucose homeostasis. Homozygous knock-in 4E-BP1S82D mice showed glucose intolerance that was markedly accentuated with a diabetogenic high-fat diet (p = 0.004). In contrast, homozygous mice with the unphosphorylatable alanine substitution (4E-BP1S82A) had normal glucose tolerance. Protein profiling of lean muscle tissues, largely arrested in G0, did not show protein expression or signaling changes that could account for these results. Reciprocal bone-marrow transplantation between 4E-BP1S82D and wild-type littermates revealed a trend for wild-type mice with 4E-BP1S82D marrow engraftment on high-fat diets to become hyperglycemic after glucose challenge. 4E-BP1S82D is a single amino acid substitution that induces glucose intolerance in mice. These findings indicate that glucose metabolism may be regulated by CDK1 4E-BP1 phosphorylation independent from mTOR and point towards an unexpected role for cycling cells that transit mitosis in diabetic glucose control.

Given According to Knowledge, Motivation and Behavioral Skills (IMB Model) The Effect of Diabetes Education on Self-Care

Aim: It has been determined that the education given according to the information, motivation, and behaviour model is effective in AIDS, chronic diseases, glucose control in diabetes, and self-care behaviours such as diet and exercise. The aim of this study, which is planned from this point of view, is to evaluate the effect of education given according to the information, motivation, and behaviour model on diabetic self-care management. Material and Methods: This study was conducted as an experimental study with a nonrandomized control group that included 90 diabetes mellitus individuals, with 45 in the intervention group and 45 in the control group. The control group were given formal diabetes mellitus education. In contrast, the intervention group received an education based on the information, motivation, and behaviour model and diabetes mellitus cases were followed for six months. Data were collected with a questionnaire on the essential characteristics of the patients, an evaluation form on the level of knowledge about diabetes, an evaluation form on their motivation about diabetes, and a diabetes self-care activities questionnaire. An Independent Sample-t test was used to analyze the data, and Paired Sample-test statistics were used to compare two dependent groups. Mann-Whitney U test was used to compare the measurement values of two independent groups that did not have a normal distribution. Wilcoxon test statistics were used to compare two dependent groups. Results: At the end of the study, it was determined that while HbA1c in the intervention group decreased for 6 months, knowledge scores, motivation levels and self-care skill scores increased (t=7.067, p

Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control.

Antioxidant intervention is considered to inhibit reactive oxygen species (ROS) and alleviate hyperglycemia. Paradoxically, moderate exercise can produce ROS to improve diabetes. The exact redox mechanism of these two different approaches remains largely unclear. Here, by comparing exercise and antioxidant intervention on type 2 diabetic rats, we found moderate exercise upregulated compensatory antioxidant capability and reached a higher level of redox balance in the liver. In contrast, antioxidant intervention achieved a low-level redox balance by inhibiting oxidative stress. Both of these two interventions could promote glucose catabolism and inhibit gluconeogenesis through activation of hepatic AMP-activated protein kinase (AMPK) signaling; therefore, ameliorating diabetes. During exercise, different levels of ROS generated by exercise have differential regulations on the activity and expression of hepatic AMPK. Moderate exercise-derived ROS promoted hepatic AMPK glutathionylation activation. However, excessive exercise increased oxidative damage and inhibited the activity and expression of AMPK. Overall, our results illustrate that both exercise and antioxidant intervention improve blood glucose control in diabetes by promoting redox balance, despite different levels of redox state(s). These results indicate that the AMPK signaling activation, combined with oxidative damage markers, could act as sentinel biomarkers, reflecting the threshold of redox balance that is linked to effective glucose control in diabetes. These findings provide theoretical evidence for the precise management of diabetes by antioxidants and exercise.

Recurrent Hypoglycemia Impaired Vascular Function in Advanced T2DM Rats by Inducing Pyroptosis.

Background Hypoglycemia is a dangerous side effect of intensive glucose control in diabetes. Even though it leads to adverse cardiovascular events, the effects of hypoglycemia on vascular biology in diabetes have not been adequately studied. Methods Aged Sprague-Dawley rats were fed a high-fat diet and given streptozotocin to induce type 2 diabetes mellitus (T2DM). Acute and recurrent hypoglycemia were then induced by glucose via insulin administration. Vascular function, oxidative stress, and pyroptosis levels in aortic tissue were assessed by physiological and biochemical methods. Results Hypoglycemia was associated with a marked decrease in vascular function, elevated oxidative stress, and elevated pyroptosis levels in the thoracic aorta. The changes in oxidative stress and pyroptosis were greater in rats with recurrent hypoglycemia than in those with acute hypoglycemia. Conclusions Hypoglycemia impaired vascular function in aged rats with T2DM by inducing pyroptosis. The extent of injury increased with the duration of blood glucose fluctuation.

Type 1 Diabetes Hypoglycemia Prediction Algorithms: Systematic Review.

BackgroundDiabetes is a chronic condition that necessitates regular monitoring and self-management of the patient’s blood glucose levels. People with type 1 diabetes (T1D) can live a productive life if they receive proper diabetes care. Nonetheless, a loose glycemic control might increase the risk of developing hypoglycemia. This incident can occur because of a variety of causes, such as taking additional doses of insulin, skipping meals, or overexercising. Mainly, the symptoms of hypoglycemia range from mild dysphoria to more severe conditions, if not detected in a timely manner.ObjectiveIn this review, we aimed to report on innovative detection techniques and tactics for identifying and preventing hypoglycemic episodes, focusing on T1D.MethodsA systematic literature search following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed focusing on the PubMed, Google Scholar, IEEE Xplore, and ACM Digital Library to find articles on technologies related to hypoglycemia detection in patients with T1D.ResultsThe presented approaches have been used or devised to enhance blood glucose monitoring and boost its efficacy in forecasting future glucose levels, which could aid the prediction of future episodes of hypoglycemia. We detected 19 predictive models for hypoglycemia, specifically on T1D, using a wide range of algorithmic methodologies, spanning from statistics (1.9/19, 10%) to machine learning (9.88/19, 52%) and deep learning (7.22/19, 38%). The algorithms used most were the Kalman filtering and classification models (support vector machine, k-nearest neighbors, and random forests). The performance of the predictive models was found to be satisfactory overall, reaching accuracies between 70% and 99%, which proves that such technologies are capable of facilitating the prediction of T1D hypoglycemia.ConclusionsIt is evident that continuous glucose monitoring can improve glucose control in diabetes; however, predictive models for hypo- and hyperglycemia using only mainstream noninvasive sensors such as wristbands and smartwatches are foreseen to be the next step for mobile health in T1D. Prospective studies are required to demonstrate the value of such models in real-life mobile health interventions.

102-LB: Retrospective Comparison of A1C between Hybrid Closed Loop Technology—Is There a Difference in Insulin Pump Type?

Background: Insulin pumps with and without hybrid closed loop technology (HCL) are now mainstream in the treatment of type 1 diabetes (T1D) . These technologies are well known to improve diabetes glucose control, safety, and quality of life. Objective: To determine if there is a difference in overall glucose control between the current FDA approved brands of pumps including those with HCL. Methods: A retrospective chart review was performed at Children’s Hospital Orange County to assess subjects with T1D who upgraded a device during the study period of Jan. 2021 to Dec. 2021. Subjects were divided by brand of pump (Omnipod, Medtronic 670G and Tandem Control IQ) and further categorized by upgrade device type. A1c was documented at baseline and within 3 to 6 months after pump upgrade. Statistics performed with the sign test (exact method) for paired data and Wilcoxon rank sum test comparing difference in A1c at baseline and after upgrade. Results: 125 subjects upgraded pumps in the study period. 84 subjects were included in the A1c analysis due to data availability. Subjects ranged in age from 5 to 24 years, 48% were female, and 83% used HCL. Most subjects chose to upgrade to Tandem Control IQ (73%) vs. Omnipod (16%) or Medtronic 770G (11%) . Difference in pre-A1c to post-A1c of subjects who upgraded from Medtronic 670G [ A1c 7.9% (7.2-8.7) ] to Tandem Control IQ [A1c 7.3% (6.95-7.7) ] was statistically significant (p&amp;lt;0.0003) . Although other groups had mild changes in A1c, they did not reach statistical significance. Conclusions: The majority of subjects preferred Tandem Control IQ HCL technology to other FDA approved devices. Tandem Control IQ showed significant improvement in A1c compared to Medtronic 670G in clinical practice. Further research is needed to determine if changes in A1c are sustained overtime. Disclosure C. S. Reh: None. S. Thompson: Other Relationship; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc.

Mitofusin 1 and 2 regulation of mitochondrial DNA content is a critical determinant of glucose homeostasis

The dynamin-like GTPases Mitofusin 1 and 2 (Mfn1 and Mfn2) are essential for mitochondrial function, which has been principally attributed to their regulation of fission/fusion dynamics. Here, we report that Mfn1 and 2 are critical for glucose-stimulated insulin secretion (GSIS) primarily through control of mitochondrial DNA (mtDNA) content. Whereas Mfn1 and Mfn2 individually were dispensable for glucose homeostasis, combined Mfn1/2 deletion in β-cells reduced mtDNA content, impaired mitochondrial morphology and networking, and decreased respiratory function, ultimately resulting in severe glucose intolerance. Importantly, gene dosage studies unexpectedly revealed that Mfn1/2 control of glucose homeostasis was dependent on maintenance of mtDNA content, rather than mitochondrial structure. Mfn1/2 maintain mtDNA content by regulating the expression of the crucial mitochondrial transcription factor Tfam, as Tfam overexpression ameliorated the reduction in mtDNA content and GSIS in Mfn1/2-deficient β-cells. Thus, the primary physiologic role of Mfn1 and 2 in β-cells is coupled to the preservation of mtDNA content rather than mitochondrial architecture, and Mfn1 and 2 may be promising targets to overcome mitochondrial dysfunction and restore glucose control in diabetes.

A Multitask Learning Approach to Personalized Blood Glucose Prediction.

Blood glucose prediction algorithms are key tools in the development of decision support systems and closed-loop insulin delivery systems for blood glucose control in diabetes. Deep learning models have provided leading results among machine learning algorithms to date in glucose prediction. However these models typically require large amounts of data to obtain best personalised glucose prediction results. Multitask learning facilitates an approach for leveraging data from multiple subjects while still learning accurate personalised models. In this work we present results comparing the effectiveness of multitask learning over sequential transfer learning, and learning only on subject-specific data with neural network and support vector regression. The multitask learning approach shows consistent leading performance in predictive metrics at both short-term and long-term prediction horizons. We obtain a predictive accuracy (RMSE) of 18.8 ±2.3, 25.3 ±2.9, 31.8 ±3.9, 41.2 ±4.5, 47.2 ±4.6mg/dL at 30, 45, 60, 90, and 120min prediction horizons respectively, with at least 93% clinically acceptable predictions using the Clarke Error Grid (EGA) at each prediction horizon. We also identify relevant prior information such as glycaemic variability that can be incorporated to improve predictive performance at long-term prediction horizons. Furthermore, we show consistent performance - ≤ 5% change in both RMSE and EGA (Zone A) - in rare cases of adverse glycaemic events with 1-6 weeks of training data. In conclusion, a multitask approach can allow for deploying personalised models even with significantly less subject-specific data without compromising performance.

Glucose control in diabetes during home confinement for the first pandemic wave of COVID-19: a meta-analysis of observational studies

AimTo assess the effect on glycaemic control of confinement due to lockdown measures, during COVID-19 pandemic, in people with type 1 (T1DM) and type 2 (T2DM) diabetes.MethodsMeta-analysis of observational studies reporting measures of glucose control and variability before and during and/or after periods of confinement caused by COVID-19 in 2020 and/or 2021.ResultsWe included 27 studies on T1DM. No significant change in Hba1c was observed after lockdown (WMD − 1.474 [− 3.26; 0.31] mmol/mol, I2 = 93.9). TIR significantly increased during and after lockdown (WMD: 2.73 1.47; 4.23 %, I2 = 81% and 3.73 [1.13; 5.33] %, I2 = 85%, respectively).We retrieved nine studies on T2DM patients. No significant variation in HbA1c was detected (WMD − 1.257 − 3.91; 1.39 mmol/mol, I2 = 98.3%). HbA1c had a more favourable trend in studies performed in Asia than in Europe (p = 0.022 between groups).ConclusionLockdown showed no significant detrimental effect on HbA1c in either T1DM or T2DM. Conversely, home confinement led to a reduction in mean glucose and glucose variability in T1DM, although with a high heterogeneity of results.

The effects and acceptability of different exercise modes on glycemic control in type 2 diabetes mellitus: A protocol for systematic review and network meta-analysis.

Introduction:Exercise has been believed to have positive effects on blood glucose control in patients with type 2 diabetes mellitus. However, few medical evidences have been found to ascertain which type of exercise has the best effect on blood glucose control in diabetes and which type of exercise is more acceptable. The purpose of this study is to compare the effects and acceptability of different exercise modes on glycemic control in type 2 diabetes patients by using systematic review and network meta-analysis.Methods and analysis:Relevant randomized controlled trial studies will be searched from PubMed, EMbase, CochraneCENTRAL, CNKI, VIP, and Chinese medical paper libraries. Primary outcome indicators: glycosylated hemoglobin and dropout rate of the research (number of dropouts/numbers of initially enrolled subjects). Secondary outcome measures: fasting blood glucose, body weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol, triglycerides (TG), diastolic pressure, systolic pressure (SBP). Two reviewers are arranged to screen Title, , and then review full text to further extract data. Standard meta-analysis and network meta-analysis of the data are performed afterward. Methodological quality assessment is planned to be conducted using Cochrane risk of bias tool. The outcome will be analyzed statistically according to Bayesian analysis methods. After that, subgroup analysis is conducted on the duration of intervention, whether there is supervision of intervention, frequency of intervention per week, age, gender, and medication use.Trial registration number:PROSPERO CRD42020175181Discussion:The systematic review and network meta-analysis include evidence of the impact of different exercise modes on blood glucose control in type 2 diabetes mellitus. There are 2 innovative points in this study. One is to conduct a classified study on exercise in as much detail as possible, and the other is to study the acceptability of different exercise modes. The network meta-analysis will reduce the uncertainty of intervention and enable clinicians, sports practitioners, and patients to choose more effective and suitable exercise methods.Ethics and dissemination:The findings of the study will be disseminated through publications in peer-reviewed journals and scientific conferences and symposia. Further, no ethical approval is required in this study.

Inspiratory Muscle Training on Glucose Control in Diabetes: A Randomized Clinical Trial.

This study evaluated the effects of inspiratory muscle training (IMT) in glucose control and respiratory muscle function in patients with diabetes. It was a randomized clinical trial conducted at the Physiopathology Laboratory of the Hospital de Clínicas de Porto Alegre. Patients with Type 2 diabetes were randomly assigned to IMT or placebo-IMT (P-IMT), performed at 30% and 2% of maximal inspiratory pressure, respectively, every day for 12 weeks. The main outcome measures were HbA1c, glycemia, and respiratory muscle function. Thirty patients were included: 73.3% women, 59.6 ± 10.7 years old, HbA1c 8.7 ± 0.9% (71.6 ± 9.8mmol/mol), and glycemia 181.8 ± 57.8mg/dl (10.5 ± 3.2mmol/L). At the end of the training, HbA1c was 8.2 ±0.3% (66.1 ± 3.3mmol/mol) and 8.7 ± 0.3% (71.6 ± 3.3mmol/mol) for the IMT and P-IMT groups, respectively (p = .8). Fasting glycemia decreased in both groups with no difference after training although it was lower in IMT at 8 weeks: 170.0 ± 11.4 mg/dl(9.4 ± 0.6 mmol/L) and 184.4 ± 15.0mg/dl (10.2 ± 0.8mmol/L) for IMT and P-IMT, respectively (p < .05). Respiratory endurance time improved in the IMT group (baseline = 325.9 ± 51.1s and 305.0 ± 37.8s; after 12 weeks = 441.1 ± 61.7s and 250.7 ± 39.0s for the IMT and P-IMT groups, respectively; p < .05). Considering that glucose control did not improve, IMT should not be used as an alternative to other types of exercise in diabetes. Higher exercise intensities or longer training periods might produce better results. The clinical trials identifier is NCT03191435.

Sub-clinical thickening of the fovea in diabetes and its relationship to glycaemic control: a study using swept-source optical coherence tomography

BackgroundAccumulation of multiple pockets of fluid at the fovea, as a complication of poor blood glucose control in diabetes, causes impairment of central vision. A new ability to demonstrate a pre-clinical phase of this maculopathy could be valuable, enabling diabetic individuals to be alerted to the need to improve their glycaemic control. This study aimed to use swept-source optical coherence tomography (SS-OCT) to measure foveal thickness and macular volume in diabetic individuals without cystoid macular oedema, and in non-diabetic individuals, and relate these measures to participants’ glycaemic control.MethodsCentre point thickness (CPT) and total macular volume (TMV) were measured using SS-OCT (DRI OCT Triton™, Topcon, Tokyo, Japan). Participants’ glycosylated haemoglobin (HbA1c) level was also assessed (A1cNow®+ System, PTS Diagnostics, Indianapolis, IN, USA). The diabetic (n = 27) and non-diabetic (n = 27) groups were matched for age (p = 0.100) and sex (p = 0.414), and HbA1c level differed between diabetic and non-diabetic groups (p < 0.0005). The diabetic group comprised type 1 (n = 7) and type 2 (n = 20) diabetic individuals who were matched for duration of diabetes (p = 0.617) and whose glycaemic control was similar (p = 0.814).ResultsDiabetic individuals had significantly higher CPT (t(37) = 3.859, p < 0.0005) than non-diabetic individuals. In the diabetic group, multiple linear regression analysis revealed a conspicuous relationship between CPT and HbA1c level (β = 0.501, t(21) = 3.139, p = 0.005): there was a 19-μm increase in CPT for each 1% increase in HbA1c level. This relationship was not present in the non-diabetic group (β = − 0.068, t(23) = − 0.373, p = 0.712).ConclusionsSS-OCT is the only way to measure macular thickness in vivo. Diabetic individuals en bloc had higher CPT compared with non-diabetic individuals. Moreover, in the diabetic group, HbA1c level significantly predicted CPT. Our results suggest that, in diabetes, sub-clinical thickening may occur at the fovea before cystoid macular oedema becomes clinically evident. This could provide diabetic individuals with an early warning of disease progression and motivate them to improve control of their diabetes, with a view to avoiding the need of intra-vitreal injections with their attendant risks.

Assisted 3D printing of microneedle patches for minimally invasive glucose control in diabetes.

Recently, microneedle systems have become an attractive solution for drug delivery. Traditionally, microneedle systems were fabricated via template molding methods. In this study, we present a novel method for the fabrication of a microneedle patch system. We used extrusion-based 3D printing and post stretching to fabricate a microneedle patch system for minimally invasive and glucose-responsive insulin delivery for diabetes treatment. First, we investigated the printability of various bioinks composed of alginate with hydroxyapatite as an additive. After printing the substrate and a cylindrical array of the patch, we stretched the top surface of the cylindrical array to form needle-like tips. The prepared microneedle patch contained 6×6 microneedles, and only the microneedles performed glucose-responsive release of insulin. Each microneedle was conical in shape, with a base diameter of 601μm, a tip diameter of 24μm, and a height of 643μm. The fabricated microneedles exhibited sufficient mechanical strength to penetrate the skin of mice and responsively released insulin according to the glucose levels both in glucose solution and in type 1 diabetic mice. When transdermal application was performed only once on the skin of mice, the microneedle patches regulated the blood glucose levels of diabetic mice in normoglycemic ranges for up to 40h and alleviated the diabetic symptoms of the mice. Our study proposed a method for the fabrication of microneedle patch systems, which can be potentially applied for transdermal drug delivery.

Relationship between loneliness and blood glucose control in diabetes

BackgroundThe data of the International Diabetes Federation show that about 463 million people have diabetes. Better understanding of psychosocial aspects of life with this disease has become one of healthcare priorities in this group of patients. The aim of this study was to assess the relationships between loneliness and blood glucose control in diabetic patients.MethodsThe study included 250 hospitalized patients with type 1 and 2 diabetes. The patients included in the study were those who had had diabetes for at least 1 year and received pharmacotherapy. Standardized Revised UCLA Loneliness Scale (R-UCLA) and an analysis of patient test results including 10 indicators of blood glucose control were used for data collection. Correlation analysis, i.e. Pearson’s linear correlation coefficient (r, parametric method), was used for hypothesis verification.ResultsLess than one-fifth (16%) of the patients included in the study had higher loneliness index (based on the R-UCLA scale), and this loneliness index (total result) was significantly correlated with higher blood pressure. No significant correlations were demonstrated between loneliness and the other 9 indicators of blood glucose control.ConclusionsSystolic blood pressure was significantly correlated with loneliness in patients with diabetes. Further studies are needed to confirm these findings.

7-LB: Insulin and Glucagon Coadministration in Type 1 Diabetes Prevents Hypoglycemia without Worsening Hyperglycemia

Despite pharmacological and technical advances, risk of hypoglycemia remains the greatest impediment to optimal glycemia in type 1 diabetes (T1D) and there is increasing interest in how the opposing actions of insulin and glucagon (Gn) may be harnessed to optimize glycemic control. We studied T1D subjects (n=11; age 36±4y, gender M:F 5:6, BMI 25.0±0.7 kg/m2, disease duration 23±3y, A1C 7.0±0.3%, daily insulin dose 43±3u) on two occasions, under meal challenge conditions (liquid mixed meal, 100g carbohydrate) during a phased 6h IV regular insulin infusion with (+Gn) and without (-Gn) IV glucagon. On both occasions, subjects were treated overnight with low dose IV insulin prior to the morning meal to prevent antecedent nocturnal hypoglycemia and to attain near-normal fasting glycemia. Insulin dosing was designed to control the early rise in plasma glucose (PG) but also to elicit hypoglycemia in the later phase. During +Gn, glucagon was co-administered with insulin at a fixed molar ratio. At the two visits, fasting PG was similar (-Gn 121±5, +Gn 119±6 mg/dl) and the initial meal-induced PG elevation (0-3h) was indistinguishable whether glucagon was present or not (peak PG -Gn 224±18, +Gn 228±15 mg/dl; ΔPG 0-180AUC -Gn 10501±3014, +Gn 11537±1778 mg.min/dl). During the latter phase (3-6h), 7/11 -Gn subjects experienced an excessive fall in PG to &amp;lt;80mg/dl with 5/11 dropping to 50mg/dl requiring IV glucose rescue (by protocol). During +Gn, the fall in PG was attenuated in all cases with a significant difference observed in PG nadir (-Gn 51.1±4.0, +Gn100.5±11.0 mg/dl; p=0.007). Appropriate elevations in plasma insulin and glucagon were observed in keeping with study design. To conclude, it is feasible that insulin and glucagon can be co-administered under specific conditions allowing protection against insulin-induced hypoglycemia without impeding hyperglycemic control. This unique observation offers insight into novel approaches to glucose control in diabetes. Disclosure B.W. Bode: Advisory Panel; Self; Medtronic, Novo Nordisk A/S. Consultant; Self; Eli Lilly and Company, Medtronic, Novo Nordisk A/S. Research Support; Self; Abbott, Advance, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, National Institutes of Health, Nova Biomedical, Novo Nordisk A/S, Provention Bio, Inc., Sanofi, Senseonics. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Senseonics. Stock/Shareholder; Self; Aseko. J. Boyd: None. A. Shah: Consultant; Self; Abvance Therapeutics. Stock/Shareholder; Spouse/Partner; Fractyl Laboratories, Inc. D. Parkes: Consultant; Self; Abvance Therapeutics, Fractyl Laboratories, Inc., Prolynx, ProSciento. S. Ghosh: Consultant; Self; Abvance Therapeutics, Fractyl Laboratories, Inc., Takeda Pharmaceutical Company Limited. A.D. Cherrington: Advisory Panel; Self; Biocon, Fractyl Laboratories, Inc., Metavention, Sekkei Bio, Sensulin, LLC., vTv Therapeutics, Zafgen, Inc. Consultant; Self; Thetis Pharmaceuticals LLC. Research Support; Self; Diasome Pharmaceuticals, Inc. Other Relationship; Self; Abvance Therapeutics, Novo Nordisk Inc.