Reduced Hypoglycemia and Increased Time in Target Using Closed-Loop Insulin Delivery During Nights With or Without Antecedent Afternoon Exercise in Type 1 Diabetes

OBJECTIVE

Afternoon exercise increases the risk of nocturnal hypoglycemia (NH) in subjects with type 1 diabetes. We hypothesized that automated feedback-controlled closed-loop (CL) insulin delivery would be superior to open-loop (OL) control in preventing NH and maintaining a higher proportion of blood glucose levels within the target blood glucose range on nights with and without antecedent afternoon exercise.

RESEARCH DESIGN AND METHODS

Subjects completed two 48-h inpatient study periods in random order: usual OL control and CL control using a proportional-integrative-derivative plus insulin feedback algorithm. Each admission included a sedentary day and an exercise day, with a standardized protocol of 60 min of brisk treadmill walking to 65–70% maximum heart rate at 3:00 p.m.

RESULTS

Among 12 subjects (age 12–26 years, A1C 7.4 ± 0.6%), antecedent exercise increased the frequency of NH (reference blood glucose <60 mg/dL) during OL control from six to eight events. In contrast, there was only one NH event each on nights with and without antecedent exercise during CL control (P = 0.04 vs. OL nights). Overnight, the percentage of glucose values in target range was increased with CL control (P < 0.0001). Insulin delivery was lower between 10:00 p.m. and 2:00 a.m. on nights after exercise on CL versus OL, P = 0.008.

CONCLUSIONS

CL insulin delivery provides an effective means to reduce the risk of NH while increasing the percentage of time spent in target range, regardless of activity level in the mid-afternoon. These data suggest that CL control could be of benefit to patients with type 1 diabetes even if it is limited to the overnight period.While exercise has a myriad of benefits including improvements in cardiovascular health, body composition, and psychological well-being, it often is a double-edged sword for patients with type 1 diabetes. In patients with diabetes, the benefits of exercise are offset, in part, by the inadequacy of current methods of insulin replacement to respond to changing metabolic demands both during and after exercise, leading to an increased risk of hypoglycemia. Most severe hypoglycemic events occur during sleep, and the frequency of biochemical hypoglycemia is increased on nights after afternoon exercise. Indeed, in a study of 50 well-controlled children and adolescents with type 1 diabetes, the Diabetes Research in Children Network (DirecNet) showed that the percentage of nights during which blood glucose levels fell to ≤60 mg/dL nearly doubled (from 28 to 48%) for nights with compared with nights without antecedent afternoon exercise (1).A number of pathophysiologic factors contribute to the increased vulnerability of youth with type 1 diabetes to nocturnal hypoglycemia (NH) after sedentary or physically active days. Using the hypoglycemic clamp technique, Jones and colleagues demonstrated that plasma epinephrine responses to hypoglycemia are markedly blunted in children and adolescents with and without diabetes during deep sleep at night (2). These findings were extended by Banarer and Cryer, who also demonstrated decreased epinephrine responses to hypoglycemia during sleep in adults with type 1 diabetes (3). Using the euglycemic clamp technique to maintain stable plasma glucose and insulin levels during the night, McMahon and colleagues have more recently shown that the rate of exogenous glucose infusion had to be sharply increased 7–11 h after afternoon exercise, even in the face of unchanged plasma insulin concentrations (4). In patients who receive fixed basal insulin doses given by insulin pump or injections of long-acting insulin analogs, the increased metabolic demands that occur on nights after afternoon exercise combined with the impaired ability of falling glucose levels to stimulate an adequate epinephrine response during sleep put patients with type 1 diabetes at increased jeopardy for NH (5).Continuous glucose monitoring (CGM) systems provide a means to optimize overnight glucose control in patients with type 1 diabetes by more fully exploiting the variable basal infusion rate capability of insulin pumps based on retrospective analysis of overnight glucose profiles. However, even optimized overnight basal rates in generally sedentary children can lead to NH on nights after unexpected antecedent afternoon exercise. While the JDRF CGM randomized clinical trial demonstrated that CGM is effective in lowering A1C levels in patients with type 1 diabetes who use the devices frequently, the risk of severe hypoglycemic events was not reduced and prolonged episodes of NH were common in children and in adults (6,7). Recently, use of sensor augmented pump (SAP) therapy has been demonstrated to decrease time spent in hypoglycemia compared with pump therapy alone; yet, episodes of hypoglycemia could not be eliminated (8). Additionally, while SAP therapy may be the best possible treatment modality currently commercially available, its use by patients has been limited, with data from the Type 1 Diabetes Exchange estimating usage of CGM to 6% of study participants (9). These data support the contention that no treatment of type 1 diabetes will be optimal until there is feedback control of insulin-delivery rates based on real-time changes in sensor glucose levels.Steil and colleagues carried out the “first in man” studies of a closed-loop (CL) system using an external insulin pump, external glucose sensor, and a proportional-integrative-derivative (PID) algorithm in 10 adult patients with type 1 diabetes in a clinical research center setting (10). While delays in insulin absorption resulting from the use of the subcutaneous route of insulin administration contributed to early postprandial hyperglycemia and late postmeal hypoglycemia, overnight glucose control was outstanding. Subsequent studies have demonstrated the ability of CL systems to regulate glucose levels during the overnight period (11–17), but physical activity of study subjects was restricted in most of these inpatient investigations. In this study, we used the same exercise paradigm that doubled the rate of NH in the DirecNet study (1) to examine and compare the frequency of NH during open-loop (OL) and CL insulin delivery on nights with and without antecedent exercise in the afternoon in a group of adolescents and young adults with well-controlled type 1 diabetes.     

A comparison of bilevel and continuous positive airway pressure noninvasive ventilation in acute cardiogenic pulmonary edema

Background

Whether bilevel positive airway pressure (BiPAP) is advantageous compared with continuous positive airway pressure (CPAP) in acute cardiogenic pulmonary edema (ACPO) remains uncertain. The aim of the meta-analysis was to assess potential beneficial and adverse effects of CPAP compared with BiPAP in patients with ACPO.

Methods

Randomized controlled trials comparing the treatment effects of BiPAP with CPAP were identified from electronic databases and reference lists from January 1966 to December 2012. Two reviewers independently assessed study quality. In trials that fulfilled inclusion criteria, we critically evaluate the evidence for the use of noninvasive ventilation on rates of hospital mortality, endotracheal intubation, myocardial infarction, and the length of hospital stay. Data were combined using Review Manager 4.3 (The Cochrane Collaboration, Oxford, UK). Both pooled effects and 95% confidence intervals (CIs) were calculated.

Results

Twelve randomized controlled trials with a total of 1433 patients with ACPO were included. The hospital mortality (relative risk [RR], 0.86; 95% CI, 0.65-1.14; P = .46; I² = 0%) and need for requiring invasive ventilation (RR, 0.89; 95% CI, 0.57-1.38; P = .64; I² = 0%) were not significantly different between patients treated with CPAP and those treated with BiPAP. The occurrence of new cases of myocardial infarction (RR, 0.95; 95% CI, 0.77-1.17; P = .53, I² = 0%) and length of hospital stay (RR, 1.01; 95% CI, − 0.40 to 2.41; P = .98; I² = 0%) were also not significantly different between the 2 groups.

Conclusions

There are no significant differences in clinical outcomes when comparing CPAP vs BiPAP. Based on the limited data available, our results suggest that there are no significant differences in clinical outcomes when comparing CPAP with BiPAP.     

Plant species used in dental diseases: Ethnopharmacology aspects and antimicrobial activity evaluation

Ethnopharmacological relevance: Ethnopharmacological surveys show that several plant species are used empirically by the population, in oral diseases. However, it is necessary to check the properties of these plant species.     

Study on the correlation between false-positive filling defect in LAA CT and LAA structure in patients with atrial fibrillation based on TEE

Objective

This study aims to explore the actual meaning of “false positive filling defect” in left atrial appendage (LAA) computed tomography (CT) in patients with atrial fibrillation (AF), with transesophageal echocardiography (TEE) as the gold standard.

Methods

Patients with AF undergoing cardiac CT angiography and TEE examinations for proposed radiofrequency catheter ablation between October 2020 and October 2021 were selected as the study subjects. Transesophageal echocardiography was taken as the “gold standard,” and spontaneous echocardiographic contrast (SEC) and thrombus events were defined as positive events. The CT manifestations were classified into three groups (true positive, false positive, and true negative) to evaluate the differences in left atrium (LA) anterior–posterior diameter (LAAP), LA anterior wall thickness, and LAA orifice long diameter and short diameter, area, and depth between the three groups.

Results

(1) There was no statistical difference in LA anterior wall thickness between the three groups (p > .05); there was a statistical difference in LAAP (only) between the true-positive group and the true-negative group (p < .05). (2) There was a statistical difference in LAA orifice long diameter, short diameter, and area between the true-positive group and the true-negative group as well as between the false-positive group and the true-negative group (p < .05). (3) There was a statistical difference in LAA depth between the true-positive group and the false-positive group as well as between the true-positive group and the true-negative group (p < .05). (4) The area under the receiver operator characteristic curve (AUC) of LAA depth affecting the LAA thrombus and SEC was 0.863 (confidence interval = 0.718–1.000), the sensitivity was 77.8%, and the specificity was 90.6% for predicting the occurrence of LAA thrombus and SEC in patients with nonvalvular AF (NVAF) and an LAA depth of ≥50.84 mm.

Conclusions

There was a difference in LAA diameter between the TEE-based CT false-positive group and the other groups. A “CT false positive” is an objectively existing state, and CT might be able to identify the LAA hemodynamic disorder earlier than TEE. Furthermore, a CT + TEE combined application could more accurately evaluate LAA hemodynamics in patients with AF.     

Efficacy and safety of community-based moxibustion for primary hypertension: A randomized controlled trial with patient preference arms

Moxibustion has been shown to have a potential antihypertensive effect, but its applicability for the primary care of hypertension is unclear. The authors conducted a multicenter randomized controlled trial (RCT) with patient preference arms to investigate the effect, safety, cost-effectiveness, and compliance of moxibustion in community patients with hypertension. Patients with primary hypertension were enrolled from seven communities randomly or nonrandomly assigned to receive self-administered moxibustion + the original hypertensive regimen or the original hypertensive regimen alone for 6 months. The authors mainly evaluated the effects of moxibustion on hypertensive outcomes and adverse events. As a result, a total of 160 and 240 patients were recruited into the randomized and nonrandomized arms, respectively, with 87.5% completing the follow-up. At month 6, there was a significantly greater reduction in systolic blood pressure (SBP) (difference: −10.57 mmHg), a higher proportion of responders (82.2% vs. 53.7%; odds ratio 4.00), and better improvements in hypertensive symptoms and quality of life (QoL) in the moxibustion group than in the control group in the randomized population, but there was no significant between-group difference in diastolic blood pressure (DBP). The nonrandomized findings showed the same effect direction for all outcomes, except for DBP. All moxibustion-related adverse events were mild. In conclusion, moxibustion can reduce SBP and improve hypertensive symptoms and QoL in community patients with hypertension, with good safety and low cost, although its effect on DBP remains uncertain. The findings suggest that moxibustion may be an appropriate technique for community primary care of hypertension.     

Meta-analysis of blood parameters related to lipid and glucose metabolism between two subtypes of primary aldosteronism

It remains unclear whether metabolic profiles differ within the subtypes of primary aldosteronism (PA). This meta-analysis aimed to compare the blood parameters related to lipid and glucose metabolism at baseline between unilateral PA and bilateral PA. A search was performed using PubMed, Web of Science, and Sciencedirect databases, supplemented by hand-searching of related references. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for each parameter. Twenty-one studies involving 4197 patients with PA were included. Compared with bilateral PA groups, unilateral PA groups demonstrated significantly lower low-density lipoprotein cholesterol (LDL-C, SMD: −.14 mmol/L, 95% CI: −.20, −.07), total cholesterol (TC, SMD: −.16 mmol/L, 95% CI: −.23, −.09), triglyceride (TG, SMD: −.22 mmol/L, 95% CI: −.29, −.16), fasting blood glucose (FBG, SMD: −.11 mmol/L, 95% CI: −.18, −.04), hemoglobin A1c (HbA1c, SMD: −.21%, 95% CI: −.30, −.13), and homeostasis model assessment-insulin resistance (HOMA-IR, SMD: −.40, 95% CI: −.58, −.23). No significant difference was found in high-density lipoprotein cholesterol (HDL-C) level between the two groups (SMD: .40 mmol/L, 95% CI: −.02, .11). To sum up, comparison of several blood metabolic parameters between the two subtypes suggested that the bilateral PA may associate with a higher prevalence of impaired glucose and lipid metabolism than unilateral PA; however, results should be treated with caution. Additional well-designed studies are needed to prove the present results and better elucidate the link between metabolic abnormalities and etiologies of each PA subtype.     

Hydroplaners' Doctors Keep A Full Kit — and Crossed Fingers

A Forum for Our Readers

Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Forum, THE PHYSICIAN AND SPORTSMEDICINE, 4530 W 77th St, Minneapolis, MN 55435.     

Sudden Death and Jogging

Meticulous necropsy studies might help unravel the puzzle of deaths in seemingly healthy individuals; exercise stress testing is a useful screening device.