Short-term Blood Glucose Control Research Articles

Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery.

The ongoing rise in diabetes incidence necessitates improved therapeutic strategies to enable precise blood glucose control with convenient device form factors. Microneedle patches are one such device platform capable of achieving therapeutic delivery through the skin. In recent years, polymeric microneedle arrays have been reported using methods of in situ polymerization and covalent crosslinking in microneedle molds. In spite of promising results, in situ polymerization carries a risk of exposure to toxic unreacted precursors remaining in the device. Here, a polymeric microneedle patch is demonstrated that uses dynamic-covalent phenylboronic acid (PBA)-diol bonds in a dual role affording both network crosslinking and glucose sensing. By this approach, a pre-synthesized and purified polymer bearing pendant PBA motifs is combined with a multivalent diol crosslinker to prepare dynamic-covalent hydrogel networks. The ability of these dynamic hydrogels to shear-thin and self-heal enables their loading to a microneedle mold by centrifugation. Subsequent drying then yields a patch of uniformly shaped microneedles with the requisite mechanical properties to penetrate skin. Insulin release from these materials is accelerated in the presence of glucose. Moreover, short-term blood glucose control in a diabetic rat model following application of the device to the skin confirms insulin activity and bioavailability. Accordingly, dynamic-covalent crosslinking facilitates a route for fabricating microneedle arrays circumventing the toxicity concerns of in situ polymerization, offering a convenient device form factor for therapeutic insulin delivery.

Effect of Leptin Levels of Type 2 Diabetes Mellitus and Diabetic Complications.

To investigate serum leptin levels in patients with type 2 diabetes mellitus (T2DM) and the relationship between leptin levels and T2DM complications and prevalence. A total of 355 patients, 282 cases with T2DM and 73 normal controls, were recruited at 1st Medical Centre, Chinese PLA General Hospital (Beijing, China) between November 2013 and July 2014. Levels of serum leptin, biochemical markers and sexual hormones were measured, and clinical characteristics were retrieved through the electronic medical record system. Leptin levels in females were higher than that in males. Leptin levels in T2MD patients were positively correlated with body mass index, percent body fat, triglyceride, cystatin C homocysteine and salivary acid, and negatively correlated with glycosylated serum protein and glycosylated albumin levels. Leptin levels in males were positively correlated with systolic pressure and estradiol, and negatively correlated with testosterone and high density lipoprotein cholesterol. Sex (female) was positively correlated with the duration of disease. Leptin levels in T2DM patients with complications such as hypertension, diabetic nephropathy, diabetic peripheral neuropathy and coronary heart disease were higher than that in patients without such complications. Leptin levels in females with diabetic retinopathy and diabetic macroangiopathy were higher than that in patients without such complications, but there was no difference in males. Leptin has significant gender differences. Leptin levels are related to body mass index, percent body fat and sex hormone level in T2DM patients and may affect short-term blood glucose control in T2DM patients. Leptin levels are related to complications in patients with T2DM and affect the prevalence rates of complications.

The Correlation between Time in Range and Diabetic Microvascular Complications Utilizing Information Management Platform.

Background In recent years, the time of blood glucose within the target range is a new research hotspot in blood glucose management. TIR is expected to be a novel indicator for evaluating the efficacy of glycemic control and predicting diabetic complications. However, its relationship with diabetic complications has not been fully elucidated. Objective To explore the relationship between time in range (TIR) and glycosylated hemoglobin (HbA1C) through the information big data management platform. Possible association between TIR and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) was investigated, attempting to provide theoretical basis for the clinical application of TIR and to explore the TIR control scope suitable for diabetic patients. Methods A total of 5,644 type 2 diabetic patients hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Nanchang University, were selected from April 2017 to June 2020. Fingertip capillary blood glucose monitoring (FCGM) was monitored for a total of 455,664 times, and patients who are nondiabetic, pregnant, or with diabetic ketosis were excluded. Patients with 7 blood glucose points monitored for at least three consecutive days were selected as subjects in the study. 1,895 males and 1,513 females with diabetes were included, with an average age of (59.74 ± 13.40) years old and an average course of disease of 8.28 ± 7.11 years. The proportion of time in range (TIR) (70∼180 mg/dl) within the target range and the correlation between TIR and HbA1C were analyzed, as well as the relationship between TIR and the risk of diabetic complications. Results (1) The average of TIR and HbA1C was 49.65 ± 23.36% and 8.92 ± 2.49%, respectively, and was linearly correlated. With the decrease of TIR, HbA1C increased significantly, and the difference was statistically significant (P < 0.01, R2 = 0.458). The correlation coefficient of mean TIR with mean HbA1C was −0.626. (2) There were 836 patients diagnosed with diabetic nephropathy (DN). The difference of TIR value between DN and non-DN was significant (T = 2.250, P < 0.05). Risk assessment showed the lower the TIR was, the higher the risk of DN was. TIR less than 40% was a risk factor for DN (OR = 1.249, 95% CI: 0.915–1.375). (3) There were 1,296 patients diagnosed with diabetic peripheral neuropathy (DPN). The difference of TIR value between DPN and non-DPN was significant (T = 3.844, P < 0.01). TIR value less than 70% was a risk factor for DPN (OR = 1.030, 95% CI: 0.769–1.379). (4) There were 2,077 patients diagnosed with diabetic retinopathy (DR). The difference of TIR value between DPN and non-DPN was significant (T = 3.608, P < 0.01). TIR value less than 50% was a risk factor for DR (OR = 1.092, 95% CI: 0.898–1.264). Summary. TIR may serve as a reference index for short-term blood glucose control, strongly reflecting the clinical blood glucose regulation and predicting the risk of diabetic microvascular complications.

Does delay in planned diabetes care influence outcomes for aboriginal Australians? A study of quality in health care

BackgroundTo examine the association between delay in planned diabetes care and quality of outcomes.MethodsA retrospective analysis of primary care and inpatient records for 2567 Aboriginal patients, with diabetes, living in 49 remote communities in the Northern Territory of Australia. Poisson regression was used to estimate the association between delay from diagnosis to documented diabetes care plan and three outcome measures: mean HbA1c level, most recent blood pressure and number of diabetes-related hospital admissions.ResultsCompared with no delay (< 60 days), patients with delay had increased risk of elevated mean HbA1c: 60 days to < 2 years, incidence rate ratio (IRR), 1.2 (95% CI:1.07–1.39); 2 years to < 4 years, incidence rate ratio (IRR), 1.2 (95% CI:1.04–1.45); 4 years and over, incidence rate ratio (IRR), 1.3 (95% CI:1.12–1.52). There was no evidence of association between delay and optimal blood pressure control. Risk of diabetes-related admission increased with increased delay. Compared with no delay the IRRs for delay were: 60 days to < 2 years, 1.2 (95% CI:1.07–1.42); 2 to < 4 years, 1.3 (95% CI: 1.15–1.58): and 4 years and over, 2.6 (95% CI,2.28–3.08).ConclusionThe study found that a timely diabetes care plan was associated with better short-term blood glucose control and fewer diabetes-related admissions but not with improved blood pressure control. Delays may be a result of both patient and service-related factors.

Insulin resistance and cardiovascular risk in older adult Nigerians with type 2 diabetes

Background: Insulin resistance (IR), which refers to decreased metabolic response to normal concentrations of insulin, has been associated with increasing age and is a trigger to the cascade of cardiometabolic abnormalities hence increasing cardiovascular disease (CVD) risk in elderly populations with type 2 diabetes (T2D). Strategies targeting IR may be key to mitigating excess CVD morbidities in elderly patients with T2D. Aim: The aim of this study is to evaluate the relationship between IR and CVD and also to identify cardiometabolic risk (CMR) factors as primary targets of CVD reduction in the older populations of Nigerians with T2D. Settings and Design: Lagos, Nigeria. Cross-sectional, analytical. Subjects and Methods: A total of 363 adult Nigerians with T2D aged between 40 and 100 years old were consecutively recruited for this study. T2D was defined according to the WHO criteria. Data were collected using a questionnaire and fasting blood samples were collected for analysis. Statistical Analysis Used: The data were analyzed using the IBM SPSS statistical package. Statistical significance was set at value of P Results: T2D patients in the age group of 60–80 years had significantly higher blood pressure than those in the younger age group, (P = 0.009). Fasting plasma glucose (FPG) and glycated hemoglobin were the highest in the age group of 40–60 years, (P = 0.016). IR was associated with older age in the T2D (P = 0.026). IR showed a significant correlation with CMR factors. Multivariate regression showed FPG to be independently associated with IR (P = 0.003). Conclusion: IR correlated with CMR factors and was independently associated with FPG, re-emphasizing focus on short-term blood glucose control in elderly diabetic populations.

The Assessment of Blood Glucose Distribution according to the Fasting State and Glycemic Control Indicators for Diabetes Screening

This study analyzed the distribution of the blood glucose level according to the fasting status. Moreover, a relationship was analyzed between fasting blood glucose level and glycemic control indicators. A total of 707 outpatients, who visited Dankook University Hospital, were included and classified into either the fasting group and the non-fasting group. The mean blood glucose level of each group was calculated and analyzed by sex, age, and clinic. In addition, blood glucose, HbA1c, fructosamine, and 1,5-AG were measured in 153 fasting health check-up patients, and the correlation between the blood glucose level and glycemic control indicators was evaluated. Blood glucose averages between the two groups (non-fasting 111.9 vs. fasting 103.6 mg/dL) were different (p＜0.05); and the mean difference was lower in women (4.8 mg/dL) than in men (12.2 mg/dL). A significant difference of the median glucose values among the age groups was only observed in the non-fasting group (Kruskal-Wallis test, p＜0.01), and not in the fasting group. A 1,5-Anhydroglucitol was estimated to be significantly correlated with the fast blood glucose level in the range of the criteria of impaired fasting glucose (IFG). We presented an assessment of the distribution of blood glucose level in accordance with the fasting status among outpatients, and estimated that 1,5-anhydroglucitol was well correlated with the fasting blood glucose than fructosamine and HbA1c, through the analysis of results of health screening subjects. It is suggested that the use of glycemic indicators that reflect short-term blood glucose control can be used together with the blood glucose measurement in the screening of diabetes mellitus.

Abstract TP208: 1,5-anhydro-d-glucitol as a Predictor of Cerebral Infarction in Patients With Glycated Hemoglobin A1c-based Good Diabetes Control

Introduction: Current guidelines set the goal of diabetes control to a glycated hemoglobin A1c (HbA1c) level of &lt;7% in order to prevent macrovascular events. However, we often experience diabetes patients with cerebral infarction (CI), even though their HbA1c level is well-controlled. A reason for this disparity between the diabetes control status and CI onset may be the limitation of HbA1c as a diabetes control indicator. HbA1c reflects the mean blood glucose level over the past 2-3 months. Therefore, with HbA1c, we cannot evaluate short-term blood glucose control and glycemic variability, which are reported as risk factors for CI. Measurement of 1,5-anhydro-D-glucitol (1,5AG) allows the evaluation of these factors. Hypothesis: 1,5AG can be used to evaluate the risk of CI in patients with well-controlled diabetes. Methods: We retrospectively reviewed the medical records of 1169 patients with diabetes who received treatment for CI at our hospital between 2009 and 2014. These patients were divided into the following two groups according to their HbA1c-based diabetes control status: a CI-low group (HbA1c &lt;7%, n=549) and a CI-high group (HbA1c ≧7%, n=620). We also included a non-CI group of 394 diabetes patients without CI (control group), and these patients were further divided into the following two groups in the same manner: a nonCI-low group (n=199) and a nonCI-high group (n=195). The 1,5AG levels were compared between the CI-low and nonCI-low groups, and the CI-high and nonCI-high groups. Results: There was no difference in the 1,5AG level between the CI-high and nonCI-high groups (8.8±7.3% vs. 8.9±7.1%, p=0.83). However, the 1,5AG level was significantly lower in the CI-low group than in the nonCI-low group (12.5±8.1% vs. 15.2±8.8%, p&lt;0.001). This difference remained significant after adjusting for age and sex. Conclusion: The results of this study show that short-term glycemic control and glycemic variability have a significant relationship with existing CI especially in patients with good diabetes control. The 1,5AG level may be a surrogate measure of the risk of CI in patients with HbA1c levels that indicate good diabetes control.

Glycaemic load versus carbohydrate counting for insulin bolus calculation in patients with type 1 diabetes on insulin pump.

To evaluate feasibility and effectiveness on short-term blood glucose control of using glycaemic load counting (GLC) versus carbohydrate counting (CC) for prandial insulin dosing in patients with type 1 diabetes (T1D). Nine T1D patients on insulin pump, aged 26-58 years, HbA1c 7.7 ± 0.8 % (61 ± 8.7 mmol/mol), participated in this real-life setting study. By a crossover design, patients were randomised to calculate their pre-meal insulin dose based on the insulin/glycaemic load ratio (GLC period) or the insulin/carbohydrate ratio (CC period) for 1 week, shifting to the alternate method for the next week, when participants duplicated their first week food plan. Over either week, a blind subcutaneous continuous glucose monitoring was performed, and a 7-day food record was filled in. Total daily insulin doses (45 ± 10 vs. 44 ± 9 I.U.; M ± SD, p = 0.386) and basal infusion (26 ± 7 vs. 26 ± 8 I.U., p = 0.516) were not different during GLC and CC periods, respectively. However, the range of insulin doses (difference between highest and lowest insulin dose) was wider during GLC, with statistical significance at dinner (8.4 ± 6.2 vs. 6.0 ± 3.9 I.U., p = 0.041). Blood glucose iAUC after lunch was lower, albeit not significantly, during GLC than CC period (0.6 ± 8.6 vs. 3.4 ± 8.2 mmol/l∙3 h, p = 0.059). Postprandial glucose variability, evaluated as the maximal amplitude after meal (highest minus lowest glucose value), was significantly lower during GLC than CC period at lunch (4.22 ± 0.28 vs. 5.47 ± 0.39 mmol/l, p = 0.002) and dinner (3.89 ± 0.33 vs. 4.89 ± 0.33, p = 0.026). Calculating prandial insulin bolus based on glycaemic load counting is feasible in a real-life setting and may improve postprandial glucose control in people with T1D.

Insulin delivery by injection in children and adolescents with diabetes

Type 1 diabetes is treated with insulin, which has traditionally been delivered by vial and syringe. However, for many patients, dosing inaccuracy, pain, anxiety, inconvenience, and social acceptability present barriers to this method of administration (1-5). This has contributed to the increased popularity of alternative insulin delivery systems, including pen delivery devices (4, 6). Evidence suggests that discreet devices, such as insulin pens, facilitate adherence to intensive insulin therapy regimens, help improve lifestyle flexibility, and reduce injection pain compared with the conventional syringe-based regimens, as shown in studies in adults and adolescents (7). In addition, compared with the vial and syringe method of insulin administration, pens may provide more accurate dosing - which is particularly important in children - thereby improving short-term blood glucose control and potentially improving long-term outcomes (5, 8). Children, in particular, may benefit from insulin pens that are simple to use as adherence issues may be more evident in this patient group (9). Pens for insulin delivery in children with type 1 diabetes have been used for a long time in Europe, and have recently gained in popularity in many other places around the world (4, 10). Furthermore, the conventional vial and syringe method of insulin delivery is beginning to be considered as obsolete (11). Moreover, there is a continued drive to improve insulin pen technology, to refine and enhance the functionality and usability of these pens. However, despite recent advances in pen design and function, the selection of pens available especially for children is limited.

Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats.

Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6-10 mmol/l or 10-20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10-15% following short- and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p = 0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p = 0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r = -0.60, p < 0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion.

Inhibition of glomerular glucosaminyl N-deacetylase in diabetic rats

The enzyme glucosaminyl N-deacetylase plays a key role in heparan sulphate biosynthesis since N-deacetylation is a prerequisite for N- and further O-sulphation of the carbohydrate polymer. Diabetes induced inhibition of this enzyme could be an important factor in the development of diabetic nephropathy. In this study glomerular glucosaminyl N-deacetylase activity and urinary albumin excretion were measured in insulin-treated streptozotocin-diabetic rats. Furthermore, in an attempt to provide evidence of genetically dependent differences in the vulnerability of the N-deacetylase enzyme, two closely related rat strains (H and U) were studied. A significant 10% inhibition in enzyme activity was found among rats with mean blood glucose values between 9 and 17 mmol/liter, P less than 0.05. There was a pronounced difference between the two rat strains in the vulnerability of the enzyme against blood glucose alterations. The U rat appeared highly sensitive to short-term blood glucose control judged by the correlation between blood glucose and N-deacetylase activity (r = -0.73, P = 0.005, N = 16), where no such correlation was found in the H rat (r = 0.02, P = 0.9, N = 14). Urinary albumin excretion was increased in diabetic H rats and significantly correlated to glomerular N-deacetylase activity (r = -0.62, P = 0.02, N = 14). The U rats developed a 10-fold rise in albumin excretion compared to H rats, but this albuminuria was apparently not related to the presence of diabetes or correlated to glomerular N-deacetylase activity. It is concluded that the diabetes induced inhibition of glucosaminyl N-deacetylase may play an important role in the pathogenesis of diabetic nephropathy.