Peripheral focused ultrasound stimulation and its applications: From therapeutics to human-computer interaction.

Peripheral focused ultrasound stimulation (pFUS) has gained increasing attention in the past few decades, because it can be delivered to peripheral nerves, neural endings, or sub-organs. With different stimulation parameters, ultrasound stimulation could induce different modulation effects. Depending on the transmission medium, pFUS can be classified as body-coupled US stimulation, commonly used for therapeutics or neuromodulation, or as an air-coupled contactless US haptic system, which provides sensory inputs and allows distinct human-computer interaction paradigms. Despite growing interest in pFUS, the underlying working mechanisms remain only partially understood, and many applications are still in their infancy. This review focused on existing applications, working mechanisms, the latest progress, and future directions of pFUS. In terms of therapeutics, large-sample randomized clinical trials in humans are needed to translate these state of art techniques into treatments for specific diseases. The airborne US for human-computer interaction is still in its preliminary stage, but further efforts in task-oriented US applications might provide a promising interaction tool soon.

Accuracy of Continuous Glucose Monitors for Inpatient Diabetes Management.

INTRODUCTION: In hospitalized patients, continuous glucose monitoring (CGM) may improve glycemic control, prevent hypoglycemic events, and reduce staff workload compared with point-of-care (POC) capillary glucose monitoring. METHODS: To evaluate CGM accuracy and safety of use in the inpatient setting, two versions of CGM sensors were placed on 43 and 34 adult patients with diabetes admitted to non-intensive care unit (ICU) medical wards, respectively. CGM accuracy relative to POC and safety of use were measured by calculating mean absolute relative difference (MARD) and by Clarke Error Grid (CEG) analysis. RESULTS: CGM version 2 had improved accuracy compared with CGM version 1 with MARD 17.7 compared with 21.4%. CGM accuracy did not change with POC value or with time of sensor wear. On CEG, 98.8% of paired values fell within acceptable zones A and B. CONCLUSION: Despite reduced accuracy compared with the outpatient setting, both versions of CGMs had acceptable safety profiles in the inpatient setting.

Can Transcranial Electrical Stimulation Facilitate Post-stroke Cognitive Rehabilitation? A Systematic Review and Meta-Analysis.

Background: Non-invasive brain stimulation methods have been widely utilized in research settings to manipulate and understand the functioning of the human brain. In the last two decades, transcranial electrical stimulation (tES) has opened new doors for treating impairments caused by various neurological disorders. However, tES studies have shown inconsistent results in post-stroke cognitive rehabilitation, and there is no consensus on the effectiveness of tES devices in improving cognitive skills after the onset of stroke. Objectives: We aim to systematically investigate the efficacy of tES in improving post-stroke global cognition, attention, working memory, executive functions, visual neglect, and verbal fluency. Furthermore, we aim to provide a pathway to an effective use of stimulation paradigms in future studies. Methods: Preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed. Randomized controlled trials (RCTs) were systematically searched in four different databases, including Medline, Embase, Pubmed, and PsychInfo. Studies utilizing any tES methods published in English were considered for inclusion. Standardized mean difference (SMD) for each cognitive domain was used as the primary outcome measure. Results: The meta-analysis includes 19 studies assessing at least one of the six cognitive domains. Five RCTs studying global cognition, three assessing visual neglect, five evaluating working memory, three assessing attention, and nine studies focusing on aphasia were included for meta-analysis. As informed by the quantitative analysis of the included studies, the results favor the efficacy of tES in acute improvement in aphasic deficits (SMD = 0.34, CI = 0.02-0.67, p = 0.04) and attention deficits (SMD = 0.59, CI = -0.05-1.22, p = 0.07), however, no improvement was observed in any other cognitive domains. Conclusion: The results favor the efficacy of tES in an improvement in aphasia and attentive deficits in stroke patients in acute, subacute, and chronic stages. However, the outcome of tES cannot be generalized across cognitive domains. The difference in the stimulation montages and parameters, diverse cognitive batteries, and variable number of training sessions may have contributed to the inconsistency in the outcome. We suggest that in future studies, experimental designs should be further refined, and standardized stimulation protocols should be utilized to better understand the therapeutic effect of stimulation.

Effectiveness of Continuous Glucose Monitoring in Older Adults with Type 2 Diabetes Treated with Basal Insulin.

Objective: To evaluate the effectiveness and safety of real-time continuous glucose monitoring (CGM) in adults 65 years old and older with type 2 diabetes (T2D) using basal without bolus insulin. Research Design and Methods: Using data from the MOBILE randomized trial comparing CGM versus blood glucose meter (BGM) monitoring for T2D treated with basal insulin, the treatment effect in participants ≥65 years (range: 65-79 years, N = 42) was compared with the treatment effect in participants <65 years (range: 33-64 years, N = 133). Results: For participants ≥65 years old, mean change in hemoglobin A1c (HbA1c) was -1.08% in the CGM group and -0.38% in the BGM group (adjusted mean difference = -0.65% [95% confidence interval (CI) -1.49 to 0.19]). In contrast, the adjusted mean difference in HbA1c between treatment groups was -0.35% [95% CI -0.77 to 0.07] in the <65 years age group. For time in range 70-180 mg/dL (TIR), mean adjusted treatment group difference was 19% (95% CI 4 to 35, P = 0.01) in ≥65 years old participants and 12% (95% CI 4 to 19, P = 0.003) in those <65 years old. Comparable treatment group differences favoring the CGM group were observed in both the ≥65 and <65 years age groups for mean glucose and less time >180, 250, and 300 mg/dL. Hypoglycemia was low in both groups with little difference between treatment groups in both age groups. Conclusions: In this study of adults with T2D treated with basal insulin without bolus insulin, participants ≥65 years old using CGM had a greater increase in TIR and a reduction in hyperglycemia than those using BGM and the benefit appeared to be at least as great as that observed in younger adults.

Disrupted cortico-peripheral interactions in motor disorders.

Motor disorders may arise from neurological damage or diseases at different levels of the hierarchical motor control system and side-loops. Altered cortico-peripheral interactions might be essential characteristics indicating motor dysfunctions. By integrating cortical and peripheral responses, top-down and bottom-up cortico-peripheral coupling measures could provide new insights into the motor control and recovery process. This review first discusses the neural bases of cortico-peripheral interactions, and corticomuscular coupling and corticokinematic coupling measures are addressed. Subsequently, methodological efforts are summarized to enhance the modeling reliability of neural coupling measures, both linear and nonlinear approaches are introduced. The latest progress, limitations, and future directions are discussed. Finally, we emphasize clinical applications of cortico-peripheral interactions in different motor disorders, including stroke, neurodegenerative diseases, tremor, and other motor-related disorders. The modified interaction patterns and potential changes following rehabilitation interventions are illustrated. Altered coupling strength, modified coupling directionality, and reorganized cortico-peripheral activation patterns are pivotal attributes after motor dysfunction. More robust coupling estimation methodologies and combination with other neurophysiological modalities might more efficiently shed light on motor control and recovery mechanisms. Future studies with large sample sizes might be necessary to determine the reliabilities of cortico-peripheral interaction measures in clinical practice.

Cortico-muscular interaction to monitor the effects of neuromuscular electrical stimulation pedaling training in chronic stroke.

Neuromuscular electrical stimulation (NMES) has been widely utilized in post-stroke motor restoration. However, its impact on the closed-loop sensorimotor control process remains largely unclear. This is the first study to investigate the directional changes in cortico-muscular interactions after repetitive rehabilitation training by measuring the noninvasive electroencephalogram (EEG) and electromyography (EMG) signals. In this study, 10 subjects with chronic stroke received 20 sessions of NMES-pedaling interventions, and each training session included three 10-min NMES-driven pedaling trials. In addition, pre- and post-intervention assessments of lower limb isometric contraction were conducted before and after the whole NMES-pedaling interventions. The EEG (128 channels) and EMG (3 bilateral lower limb sensors) signals were collected during the isometric contraction tasks for the paretic and non-paretic lower limbs. Both the cortico-muscular coherence (CMC) and generalized partial directed coherence (GPDC) values were analyzed between eight selected EEG channels in the central primary motor cortex and EMG channels. The results revealed significant clinical improvements. Additionally, rehabilitation training facilitated cortico-muscular interaction of the ipsilesional brain and paretic lower limbs (p = 0.004). Moreover, both the descending and ascending cortico-muscular pathways were altered after NMES-training (p = 0.001, p < 0.001). Therefore, the results implied potential applications of EEG-EMG in understanding neuromuscular changes during the post-stroke motor rehabilitation process.

The Effect of Discontinuing Continuous Glucose Monitoring in Adults With Type 2 Diabetes Treated With Basal Insulin.

OBJECTIVE: To explore the effect of discontinuing continuous glucose monitoring (CGM) after 8 months of CGM use in adults with type 2 diabetes treated with basal without bolus insulin. RESEARCH DESIGN AND METHODS: This multicenter trial had an initial randomization to either real-time CGM or blood glucose monitoring (BGM) for 8 months followed by 6 months in which the BGM group continued to use BGM (n = 57) and the CGM group was randomly reassigned either to continue CGM (n = 53) or discontinue CGM with resumption of BGM for glucose monitoring (n = 53). RESULTS: In the group that discontinued CGM, mean time in range (TIR) 70-180 mg/dL, which improved from 38% before initiating CGM to 62% after 8 months of CGM, decreased after discontinuing CGM to 50% at 14 months (mean change from 8 to 14 months -12% [95% CI -21% to -3%], P = 0.01). In the group that continued CGM use, little change was found in TIR from 8 to 14 months (baseline 44%, 8 months 56%, 14 months 57%, mean change from 8 to 14 months 1% [95% CI -11% to 12%], P = 0.89). Comparing the two groups at 14 months, the adjusted treatment group difference in mean TIR was -6% (95% CI -16% to 4%, P = 0.20). CONCLUSIONS: In adults with type 2 diabetes treated with basal insulin who had been using real-time CGM for 8 months, discontinuing CGM resulted in a loss of about one-half of the initial gain in TIR that had been achieved during CGM use.

Effect of Continuous Glucose Monitoring on Glycemic Control in Patients With Type 2 Diabetes Treated With Basal Insulin: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied. Objective: To determine the effectiveness of CGM in adults with type 2 diabetes treated with basal insulin without prandial insulin in primary care practices. Design, Setting, and Participants: This randomized clinical trial was conducted at 15 centers in the US (enrollment from July 30, 2018, to October 30, 2019; follow-up completed July 7, 2020) and included adults with type 2 diabetes receiving their diabetes care from a primary care clinician and treated with 1 or 2 daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without noninsulin glucose-lowering medications. Interventions: Random assignment 2:1 to CGM (n = 116) or traditional blood glucose meter (BGM) monitoring (n = 59). Main Outcomes and Measures: The primary outcome was hemoglobin A1c (HbA1c) level at 8 months. Key secondary outcomes were CGM-measured time in target glucose range of 70 to 180 mg/dL, time with glucose level at greater than 250 mg/dL, and mean glucose level at 8 months. Results: Among 175 randomized participants (mean [SD] age, 57 [9] years; 88 women [50%]; 92 racial/ethnic minority individuals [53%]; mean [SD] baseline HbA1c level, 9.1% [0.9%]), 165 (94%) completed the trial. Mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months in the CGM group and from 9.0% to 8.4% in the BGM group (adjusted difference, -0.4% [95% CI, -0.8% to -0.1%]; P = .02). In the CGM group, compared with the BGM group, the mean percentage of CGM-measured time in the target glucose range of 70 to 180 mg/dL was 59% vs 43% (adjusted difference, 15% [95% CI, 8% to 23%]; P < .001), the mean percentage of time at greater than 250 mg/dL was 11% vs 27% (adjusted difference, -16% [95% CI, -21% to -11%]; P < .001), and the means of the mean glucose values were 179 mg/dL vs 206 mg/dL (adjusted difference, -26 mg/dL [95% CI, -41 to -12]; P < .001). Severe hypoglycemic events occurred in 1 participant (1%) in the CGM group and in 1 (2%) in the BGM group. Conclusions and Relevance: Among adults with poorly controlled type 2 diabetes treated with basal insulin without prandial insulin, continuous glucose monitoring, as compared with blood glucose meter monitoring, resulted in significantly lower HbA1c levels at 8 months. Trial Registration: ClinicalTrials.gov Identifier: NCT03566693.

Glycaemic profiles of diverse patients with type 2 diabetes using basal insulin: MOBILE study baseline data.

Basal insulin is often prescribed to patients with suboptimally controlled type 2 diabetes (T2D); however, its therapeutic efficacy is inadequate in many. During the MOBILE study's baseline phase, we evaluated 173 participants' continuous glucose monitoring (CGM) data (mean ± SD age 57 ± 9 years; 50% female; HbA1c 9.1% [range 7.1%-11.6%]; 40% using sulphonylureas; 19% using NPH; reported self-monitored blood glucose [SMBG] frequency median 1.0 checks/day) who were using basal, but not prandial insulin. Blinded CGM data were recorded for 10 days prior to randomization. The mean glucose value was 208 ± 47 mg/dL and it was lowest in the early morning. Mean time in the 70-180 mg/dL range was 9.6 ± 6.1 hours/day (40% ± 25%). Hyperglycaemia was extensive with medians of 14.7 (61%) and 5.0 (20.9%) hours/day with glucose greater than 180 and 250 mg/dL, respectively. Hypoglycaemia was infrequent (median [IQR] 0 [0, 4.3] minutes/day [0.0% {0.0%, 0.3%}] with glucose less than 70 mg/dL). Blinded CGM highlights the limitations of infrequent SMBG in basal insulin users with T2D and allows characterization of hyperglycaemia and hypoglycaemia in basal insulin users with suboptimal control. The MOBILE study randomized phase will define the benefits of using real-time CGM compared with SMBG in this population.

ROBOTIC PARAGANGLIOMA RESECTION IN A PREGNANT PATIENT.

OBJECTIVE: Functional paragangliomas in pregnancy are rare; however, if not recognized and treated early, they can be life-threatening. New treatment approaches with robotic resection are promising. METHODS: We present a case of a pregnant female with a paraganglioma which was successfully resected during the second trimester using Da Vinci Xi robotic system. Paraganglioma was diagnosed with plasma and urinary catecholamines and metanephrines, a contrast computed tomography (CT) scan, and confirmed with surgical pathology. RESULTS: The patient was initially seen in the emergency room prior to the index pregnancy for nausea, vomiting, and intermittent, left lower quadrant abdominal pain, episodic sweating, palpitations, and anxiety. CT scan of the abdomen and pelvis showed a 4.8 × 4.3 cm heterogeneously enhancing mass in the left retroperitoneum adjacent to the aorta just below the left adrenal gland. She had normal plasma metanephrines but elevated plasma normetanephrines of 7.12 nmol/L (normal, <0.89 nmol/L). Twenty-four-hour urine norepinephrine and catecholamines were elevated to 604 µg (normal, <90 µg/24 hours) and 610 µg (normal, <115 µg/24 hours), respectively. Chromogranin A was elevated to 940 ng/mL (normal, 0 to 95 ng/mL). Paraganglioma was suspected. Doxazosin was started for blood pressure control. The patient became pregnant unexpectedly shortly after. She was managed by a multidisciplinary team. At 18 weeks of pregnancy, she underwent a transabdominal robotic resection of the left retroperitoneal paraganglioma with an excellent outcome. CONCLUSION: Functional paragangliomas in pregnancy are rare but must be recognized and treated early to reduce maternal and fetal complications. An innovative robotic approach should be considered and explored.

Rewiring the Lesioned Brain: Electrical Stimulation for Post-Stroke Motor Restoration.

Electrical stimulation has been extensively applied in post-stroke motor restoration, but its treatment mechanisms are not fully understood. Stimulation of neuromotor control system at multiple levels manipulates the corresponding neuronal circuits and results in neuroplasticity changes of stroke survivors. This rewires the lesioned brain and advances functional improvement. This review addresses the therapeutic mechanisms of different stimulation modalities, such as noninvasive brain stimulation, peripheral electrical stimulation, and other emerging techniques. The existing applications, the latest progress, and future directions are discussed. The use of electrical stimulation to facilitate post-stroke motor recovery presents great opportunities in terms of targeted intervention and easy applicability. Further technical improvements and clinical studies are required to reveal the neuromodulatory mechanisms and to enhance rehabilitation therapy efficiency in stroke survivors and people with other movement disorders.

Pathway-specific modulatory effects of neuromuscular electrical stimulation during pedaling in chronic stroke survivors.

BACKGROUND: Neuromuscular electrical stimulation (NMES) is extensively used in stroke motor rehabilitation. How it promotes motor recovery remains only partially understood. NMES could change muscular properties, produce altered sensory inputs, and modulate fluctuations of cortical activities; but the potential contribution from cortico-muscular couplings during NMES synchronized with dynamic movement has rarely been discussed. METHOD: We investigated cortico-muscular interactions during passive, active, and NMES rhythmic pedaling in healthy subjects and chronic stroke survivors. EEG (128 channels), EMG (4 unilateral lower limb muscles) and movement parameters were measured during 3 sessions of constant-speed pedaling. Sensory-level NMES (20 mA) was applied to the muscles, and cyclic stimulation patterns were synchronized with the EMG during pedaling cycles. Adaptive mixture independent component analysis was utilized to determine the movement-related electro-cortical sources and the source dipole clusters. A directed cortico-muscular coupling analysis was conducted between representative source clusters and the EMGs using generalized partial directed coherence (GPDC). The bidirectional GPDC was compared across muscles and pedaling sessions for post-stroke and healthy subjects. RESULTS: Directed cortico-muscular coupling of NMES cycling was more similar to that of active pedaling than to that of passive pedaling for the tested muscles. For healthy subjects, sensory-level NMES could modulate GPDC of both ascending and descending pathways. Whereas for stroke survivors, NMES could modulate GPDC of only the ascending pathways. CONCLUSIONS: By clarifying how NMES influences neuromuscular control during pedaling in healthy and post-stroke subjects, our results indicate the potential limitation of sensory-level NMES in promoting sensorimotor recovery in chronic stroke survivors.

Cortico-Muscular Coherence Modulated by High-Definition Transcranial Direct Current Stimulation in People With Chronic Stroke.

High-definition transcranial direct current stimulation (HD-tDCS) is a potential neuromodulation apparatus for stroke rehabilitation. However, its modulatory effects in stroke subjects is still not well understood. In this paper, the offline modulatory effects of HD-tDCS on the ipsilesional primary motor cortex were investigated by performing wrist isometric contraction tasks before and after HD-tDCS in eleven unilateral chronic stroke subjects using a synchronized HD-tDCS and electroencephalogram/electromyography measurement system. This paper is a randomized, single blinded, and sham-controlled crossover study. Each subject randomly received three HD-tDCS (anode, cathode, and sham) with at least one-week washout period. Online feedback-guided medium-level wrist isometric contraction tasks were conducted for the affected upper limbs before stimulation and 10, 30, and 50 min after the end of 10-min 1-mA HD-tDCS. The characteristics of corticomuscular coherence (CMC), cortical oscillation power spectral density, and power spectral entropy were analyzed during tasks and compared across all sessions and stimulation conditions. Anode HD-tDCS induced significant CMC changes in stroke subjects, while cathode and sham stimulation did not induce significant CMC changes. The largest neuromodulation effects were observed at 10 min immediately after anodal HD-tDCS.

Excitation Comparison between Multi-site Stimulation using Network-based tDCS and Focal Stimulation using High-definition tDCS.

Transcranial direct current stimulation (tDCS) has been developed rapidly in recent years and derived various forms which serve as therapeutic tools for neurological disorders. However, differences of stimulation effect among these stimulation strategies have not been fully explored. In this pilot study, we compared the stimulation effect between High-definition tDCS (HD-tDCS) and Network-based tDCS (NB-tDCS) on a healthy subject. HD-tDCS mainly stimulated primary motor cortex with 2mA current and NB-tDCS was designed to stimulate main motor-related areas including primary motor cortex, premotor cortex and supplementary motor area with the same amount of current in total. Cortico-muscular coherence (CMC) derived from EEG/EMG, which measures the synchrony between cortical neural activity and muscles, was collected from isometric wrist extension tasks. The results demonstrated more motor-related regions excited and longer high-level lasting effect after NB-tDCS compared with HD-tDCS, which indicated the potential power of multi-site stimulation. This study might provide some guidance and hints for transcranial stimulation strategies in the future.

USE OF CONTINUOUS GLUCOSE MONITORING LEADS TO DIAGNOSIS OF HEMOGLOBIN C TRAIT IN A PATIENT WITH DISCREPANT HEMOGLOBIN A1C AND SELF-MONITORED BLOOD GLUCOSE.

OBJECTIVE: Hemoglobin A1c (HbA1c) is a useful tool for the diagnosis and management of diabetes mellitus and generally an excellent marker of overall glycemic control for the preceding 8 to 12 weeks; however, the test is not without its pitfalls. A suspicion of falsely high or low HbA1c should prompt clinicians to evaluate for possible causes. Here, we present the novel use of continuous glucose monitoring (CGM) in a case of a 49-year-old African American woman with discrepant HbA1c and self-monitored blood glucose (SMBG). CGM data suggested that the HbA1c values were falsely elevated, and subsequent evaluation led to a diagnosis of hemoglobin C (HbC) trait. METHODS: Case identified is described. Point-of-care (POC) and central laboratory HbA1c were measured on the Bayer DCA 2000 and Bio-Rad Variant II Turbo ion-exchange high-performance liquid chromatography platforms, respectively. RESULTS: The patient had an elevated POC HbA1c of 10.8% (95 mmol/mol) and a central laboratory HbA1c of 9.2% (77 mmol/mol). The patient's glucose meter measured an average glucose of 138 mg/dL. The Freestyle LibrePro professional CGM was used to investigate the reliability of the patient's SMBG and showed an average glucose of 165 mg/dL. An investigation into potential causes for falsely elevated HbA1c revealed a previously undiagnosed HbC trait. CONCLUSION: CGM is a valuable tool to assess HbA1c and SMBG discordance and to guide subsequent diabetes management. Our results suggest that the HbA1c may have been overestimated in our patient due to HbC trait; therefore, results must be interpreted with caution.

Low Gamma Band Cortico-muscular Coherence Inter-Hemisphere Difference following Chronic Stroke.

Brain oscillation and motor control process would change due to chronic stroke. Inter-hemisphere brain activation patterns may relate to motor related recovery. This study employed cortico-muscular coherence to explore cortical motor control process during wrist isometric contraction experiments of both affected and unaffected hands from chronic stroke subjects. Eleven chronic stroke subjects with moderate hand function involved in the experiments and each subject took three visits. Multitaper coherence estimation with bias-correction was performed to acquire cortico-muscular coherence, neuronal coherence source Localization was conducted to determine typical scalp motivation area during isometric contraction. Non-parametric permutation based multiple frequency bin statistics was utilized to compare the difference between two sides. The results demonstrated significant typical low gamma band inter-hemisphere disparity in cortico-muscular coherence between two sides after chronic stroke. The spatial topographical pattern and source Localization outcomes also supported these findings.

A Case of Cushing's Syndrome due to Ectopic Adrenocorticotropic Hormone Secretion from Esthesioneuroblastoma with Long Term Follow-Up after Resection.

We present a case of a 52-year-old male who developed Cushing's Syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion from a large esthesioneuroblastoma (ENB) of the nasal sinuses. The patient initially presented with polyuria, polydipsia, weakness, and confusion. Computed tomography scan of the head and magnetic resonance imaging showed a 7 cm skull base mass centered in the right cribriform plate without sella involvement. Work-up revealed ACTH-dependent hypercortisolemia, which did not suppress appropriately after high-dose dexamethasone. Subsequent imaging of the chest, abdomen, and pelvis did not reveal other possible ectopic sources of ACTH secretion besides the ENB. His hospital course was complicated by severe hypokalemia and hyperglycemia before successful surgical resection of the tumor, the biopsy of which showed ENB. Postoperatively, his ACTH level dropped below the limit of detection. In the ensuing 4 months, he underwent adjuvant chemoradiation with carboplatin and docetaxel with good response and resolution of hypokalemia and hyperglycemia, with no sign of recurrence as of 30 months postoperatively. His endogenous cortisol production is rising but has not completely recovered.

Effects of differing antecedent increases of plasma cortisol on counterregulatory responses during subsequent exercise in type 1 diabetes.

OBJECTIVE: Antecedent hypoglycemia can blunt neuroendocrine and autonomic nervous system responses to next-day exercise in type 1 diabetes. The aim of this study was to determine whether antecedent increase of plasma cortisol is a mechanism responsible for this finding. RESEARCH DESIGN AND METHODS: For this study, 22 type 1 diabetic subjects (11 men and 11 women, age 27 +/- 2 years, BMI 24 +/- 1 kg/m(2), A1C 7.9 +/- 0.2%) underwent four separate randomized 2-day protocols, with overnight normalization of blood glucose. Day 1 consisted of morning and afternoon 2-h hyperinsulinemic- (9 pmol x kg(-1) x min(-1)) euglycemic clamps (5.1 mmol/l), hypoglycemic clamps (2.9 mmol/l), or euglycemic clamps with a physiologic low-dose intravenous infusion of cortisol to reproduce levels found during hypoglycemia or a high-dose infusion, which resulted in further twofold greater elevations of plasma cortisol. Day 2 consisted of 90-min euglycemic cycling exercise at 50% Vo(2max). RESULTS: During exercise, glucose levels were equivalently clamped at 5.1 +/- 0.1 mmol/l and insulin was allowed to fall to similar levels. Glucagon, growth hormone, epinephrine, norepinephrine, and pancreatic polypeptide responses during day 2 exercise were significantly blunted following antecedent hypoglycemia, low- and high-dose cortisol, compared with antecedent euglycemia. Endogenous glucose production and lipolysis were also significantly reduced following day 1 low- and high-dose cortisol. CONCLUSIONS: Antecedent physiologic increases in cortisol (equivalent to levels occurring during hypoglycemia) resulted in blunted neuroendocrine, autonomic nervous system, and metabolic counterregulatory responses during subsequent exercise in subjects with type 1 diabetes. These data suggest that prior elevations of cortisol may play a role in the development of exercise-related counterregulatory failure in those with type 1 diabetes.

Stimulation of both type I and type II corticosteroid receptors blunts counterregulatory responses to subsequent hypoglycemia in healthy man.

Antecedent increases of corticosteroids can blunt counterregulatory responses to subsequent stress. Our aim was to determine whether prior activation of type I corticosteroid (mineralocorticoid) or type II corticosteroid (glucocorticoid) receptors blunts counterregulatory responses to subsequent hypoglycemia. Healthy volunteers participated in five randomized 2-day protocols. Day 1 involved morning and afternoon 2-h hyperinsulinemic (9 pmol.kg(-1).min(-1)) euglycemic clamps (PE; n = 14), hypoglycemic clamps (PH; n = 14), or euglycemic clamps with oral fludrocortisone (PE + F; type I agonist, 0.2 mg, n = 14), oral dexamethasone (PE + D; type II agonist, 0.75 mg, n = 13), or both (PE + F + D; n = 14). Day 2 was identical in all protocols and consisted of a 2-h hyperinsulinemic hypoglycemic clamp. Day 2 insulin (625 +/- 40 pmol/l) and glucose (2.9 +/- 0.1 mmol/l) levels were similar among groups. Levels of epinephrine, norepinephrine, glucagon, growth hormone, and MSNA were significantly blunted by prior activation of both type I and type II corticosteroid receptors to PE. Prior activation of both corticosteroid receptors also significantly blunted NEFA during subsequent hypoglycemia. Thus, levels of a wide spectrum of key counterregulatory mechanisms (neuroendocrine, ANS, and metabolic) were blunted by antecedent pharmacological stimulation of either type I or type II corticosteroid receptors in healthy man. These data suggest that activation of type I corticosteroid receptors in man can have acute and profound regulating effects on physiological stress in man. Both type I and type II corticosteroid receptors may be involved in the multiple mechanisms controlling counterregulatory responses to hypoglycemia in healthy man.

Type B insulin resistance syndrome associated with systemic lupus erythematosus.

OBJECTIVE: To document a case of type B insulin resistance syndrome associated with systemic lupus erythematosus. METHODS: We present the clinical course of a female patient with type B insulin resistance syndrome, from the onset, diagnosis, and empiric treatment until remission of her disease. RESULTS: A 40-year-old African American woman with systemic lupus erythematosus presented with a relatively acute onset of severe hyperglycemia in January 2004. Her hyperglycemia was resistant to treatment with high doses of insulin (up to an equivalent dose of regular insulin of 4,500 units daily). The diagnosis of type B insulin resistance syndrome was confirmed after her insulin receptor antibody was found to be strongly positive. The patient's hemoglobin Ale level improved substantially after she had been treated with azathioprine for 3 months. By November 2004, she was able to discontinue insulin therapy. Repeated insulin receptor antibody testing in February 2005 revealed that her insulin receptor antibody had become negative. The patient's fasting glucose level became normal, and only occasional mild postprandial hyperglycemic episodes have been noted. CONCLUSION: Immunosuppressive therapy with azathioprine seems to be responsible for our patient's remission of type B insulin resistance, although the possibility of the occurrence of a spontaneous remission cannot be completely excluded.