Adaptive Biobehavioral Control: A Pilot Analysis of Human-Machine Coadaptation in Type 1 Diabetes.

Background: While it is well recognized that an automated insulin delivery (AID) algorithm should adapt to changes in physiology, it is less understood that the individual would also have to adapt to the AID system. The adaptive biobehavioral control (ABC) method presented here attempts to compensate for this deficiency by including AID into an information cloud-based ecosystem. Methods: The Web Information Tool (WIT) implements the ABC concept via the following: (1) a Physiological Adaptation Module (PAM) that tracks metabolic changes and adapts AID parameters accordingly and (2) a Behavioral Adaptation Module (BAM) that provides information feedback. The safety of WIT (primary outcome) was assessed in an 8-week randomized, two-arm parallel pilot study. All participants used the Control-IQ® AID system enhanced with PAM, but only those in the Experimental group had access to BAM. Secondary glycemic outcomes were computed using the 2-week baseline period and the last 2 weeks of treatment. Results: Thirty participants with type 1 diabetes (T1D) completed all study procedures (17 female/13 male; age: 40 ± 14 years; HbA1c: 6.6% ± 0.5%). No severe hypoglycemia, DKA, or other serious adverse events were reported. Comparing the Experimental and Control groups, no significant difference was observed in time in range (70-180 mg/dL): 74.6% vs 73.8%, adjusted mean difference: 2.65%, 95% CI (-1.12%,6.41%), P = 0.161. Time in 70-140 mg/dL was significantly higher in the Experimental group: 50.7% vs 49.2%, 5.71% (0.44%,10.97%), P = 0.035, without increased time below range: 0.54% (-0.09%,1.17%), P = 0.089. Conclusion: The results demonstrate that it is safe to integrate an AID system into the WIT ecosystem. Validation in a full-scale study is ongoing.

Intensive, telemedicine-based, self-management program for rural, underserved patients with diabetes mellitus: Re-entry of retired endocrinologists into practice.

INTRODUCTION: Endocrinology workforce data demonstrate a substantial gap in the number of practicing endocrinologists, a phenomenon particularly affecting patients with diabetes in rural, financially challenged, underserved areas. We evaluated the concept that retired endocrinologists could re-enter practice part time and utilize telemedicine in collaboration with personnel in Federally Qualified Community Health Center clinics to conduct an intensive self-management program and provide 6-month concurrent care for patients with diabetes. METHODS: The program involved intensive glucose control measures and education in diabetes, nutrition, and lifestyle changes over a 6-month period. Key elements included comprehensive initial telehealth evaluations, frequent phone calls, and collaboration with certified diabetes care and education specialists, referring providers, referring-clinic staff, and the University of Virginia Telehealth Center. RESULTS: The mean A1C in the 139 patients completing the 6-month self-management program decreased from 10.3 ± 1.94% to 7.78 ± 1.51% p < 0.0001. The number of treatment modalities per patient ranged from one to five with several different regimens utilized. The majority of patients maintained the reduction in A1C levels without recidivism over a mean follow-up of 16 months after discharge. Strategies using meal replacements are being implemented to facilitate weight loss. DISCUSSION: This program resulted in improved A1C levels of patients with diabetes in rural, financially challenged, underserved areas; met recidivism goals; and provided a practical template to reduce the workforce gap of endocrinologists in those areas.

Evaluation of a Web-Based Simulation Tool for Self-Management Support in Type 1 Diabetes: A Pilot Study.

OBJECTIVE: To develop and evaluate a novel Web-based Simulation Tool (WST) that brings simulation technologies to people with Type 1 Diabetes (T1D), enabling unique patient-data interactions seamlessly on a daily basis. METHODS: A pilot clinical trial was conducted to assess system usability. The study consisted of one week of observation (Phase 1) and four weeks of interaction with WST (Phase 2). Responses to Technology Acceptance (TA) and Diabetes Distress Scale (DDS) questionnaires were collected, and follow-up interviews were conducted after Phase 2. RESULTS: Fifteen participants with T1D using Control-IQ technology (age: 36 ± 13 years, HbA1c: 6.5% ± 0.7%) completed all study procedures. Generated simulation models achieved a median Mean Absolute Relative Difference (MARD) of 6.8% [interquartile range, IQR: 5.1%, 9.1%]. A decrease in expected benefits (likely explained by issues with the third-party data collection system) and an increase in expected burdens were observed. On a 1-5 scale, ease of use, trust, and usefulness scores were 3 [3,4], 4 [3,4], and 4 [3,4], respectively. Time below 70 mg/dL decreased between Phases 1 and 2 (1.6% [0.7%,3.7%] vs 0.8% [0.5%,3.0%]). A reduction in mean emotional burden was also observed (2.5 ± 1.1 vs 2.1 ± 0.8). CONCLUSIONS: Results indicate that there was a learning curve to WST, but also that most participants trusted the system and found it useful in their diabetes care. SIGNIFICANCE: Simulation technologies like WST could be used by educators and patients to facilitate diabetes self-management, leading to better diabetes literacy and reducing associated distress.

Automated Insulin Delivery with SGLT2i Combination Therapy in Type 1 Diabetes.

Background: Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as adjunct therapy to insulin in type 1 diabetes (T1D) has been previously studied. In this study, we present data from the first free-living trial combining low-dose SGLT2i with commercial automated insulin delivery (AID) or predictive low glucose suspend (PLGS) systems. Methods: In an 8-week, randomized, controlled crossover trial, adults with T1D received 5 mg/day empagliflozin (EMPA) or no drug (NOEMPA) as adjunct to insulin therapy. Participants were also randomized to sequential orders of AID (Control-IQ) and PLGS (Basal-IQ) systems for 4 and 2 weeks, respectively. The primary endpoint was percent time-in-range (TIR) 70-180 mg/dL during daytime (7:00-23:00 h) while on AID (NCT04201496). Findings: A total of 39 subjects were enrolled, 35 were randomized, 34 (EMPA; n = 18 and NOEMPA n = 16) were analyzed according to the intention-to-treat principle, and 32 (EMPA; n = 16 and NOEMPA n = 16) completed the trial. On AID, EMPA versus NOEMPA had higher daytime TIR 81% versus 71% with a mean estimated difference of +9.9% (confidence interval [95% CI] 0.6-19.1); p = 0.04. On PLGS, the EMPA versus NOEMPA daytime TIR was 80% versus 63%, mean estimated difference of +16.5% (95% CI 7.3-25.7); p < 0.001. One subject on SGLT2i and AID had one episode of diabetic ketoacidosis with nonfunctioning insulin pump infusion site occlusion contributory. Interpretation: In an 8-week outpatient study, addition of 5 mg daily empagliflozin to commercially available AID or PLGS systems significantly improved daytime glucose control in individuals with T1D, without increased hypoglycemia risk. However, the risk of ketosis and ketoacidosis remains. Therefore, future studies with SGLT2i will need modifications to closed-loop control algorithms to enhance safety.

ECTOPIC THYROID TISSUE MASQUERADING AS A FUNCTIONAL CAROTID BODY PARAGANGLIOMA.

OBJECTIVE: Ectopic thyroid tissue (ETT) is a rare entity resulting from thyroid gland dysembryogenesis. We present a case of ETT confirmed by histopathology that was misdiagnosed clinically as a carotid body tumor. METHODS: A 34-year-old female with a history of thyroidectomy for a goiter presented with 1 year of worsening tachycardia (heart rate ranging from 82 to 111 beats per minute), anxiety, hot flashes, and intolerance to heat. For further evaluation, we obtained imaging of her neck, including a thyroid ultrasound, a computed tomography (CT) scan, and an octreotide scan. We also performed laboratory studies including fractionated 24-hour urine meta-nephrines and thyroid function tests. RESULTS: Her thyroid ultrasound showed a mass at the right carotid bifurcation, which was confirmed on CT as well as on an octreotide scan. Her free thyroxine was 0.6 ng/dL (normal, 0.7 to 1.5 ng/dL) and her thyroid-stimulating hormone was 4.51 mIU/L (normal, 0.45 to 4.5 mIU/L). Her fractionated 24-hour total urine metanephrines were 1,502 mcg/24-hour (normal, 149 to 535 mcg/24-hour). She underwent resection of a vascular mass from the carotid bifurcation. Histologic examination revealed ETT with dilated follicles filled with colloid with no evidence of paraganglioma/carotid body tumor. CONCLUSION: The somatostatin receptor is typically present in paragangliomas; however, there are reports of octreotide uptake within thyroid goiters. It has been demonstrated that psychoactive medications can increase urine metanephrines. Given the patient's psychiatric history and that no other tumors were identified on imaging, it was felt that the elevated urine normetanephrine in this case was most likely due to psychoactive medication use. This case demonstrates the preoperative imaging findings and postoperative pathologic confirmation of an unusual presentation of ETT.

The Use of a Smart Bolus Calculator Informed by Real-time Insulin Sensitivity Assessments Reduces Postprandial Hypoglycemia Following an Aerobic Exercise Session in Individuals With Type 1 Diabetes.

OBJECTIVE: Insulin dosing in type 1 diabetes (T1D) is oftentimes complicated by fluctuating insulin requirements driven by metabolic and psychobehavioral factors impacting individuals' insulin sensitivity (IS). In this context, smart bolus calculators that automatically tailor prandial insulin dosing to the metabolic state of a person can improve glucose management in T1D. RESEARCH DESIGN AND METHODS: Fifteen adults with T1D using continuous glucose monitors (CGMs) and insulin pumps completed two 24-h admissions in a hotel setting. During the admissions, participants engaged in an early afternoon 45-min aerobic exercise session, after which they received a standardized dinner meal. The dinner bolus was computed using a standard bolus calculator or smart bolus calculator informed by real-time IS estimates. Glucose control was assessed in the 4 h following dinner using CGMs and was compared between the two admissions. RESULTS: The IS-informed bolus calculator allowed for a reduction in postprandial hypoglycemia as quantified by the low blood glucose index (2.02 vs. 3.31, P = 0.006) and percent time <70 mg/dL (8.48% vs. 15.18%, P = 0.049), without increasing hyperglycemia (high blood glucose index: 3.13 vs. 2.09, P = 0.075; percent time >180 mg/dL: 13.24% vs. 10.42%, P = 0.5; percent time >250 mg/dL: 2.08% vs. 1.19%, P = 0.317). In addition, the number of hypoglycemia rescue treatments was reduced from 12 to 7 with the use of the system. CONCLUSIONS: The study shows that the proposed IS-informed bolus calculator is safe and feasible in adults with T1D, appropriately reducing postprandial hypoglycemia following an exercise-induced IS increase.

Recent Exposure to Hypoglycemia Increases Glucose Variability Following a Hyper/Hypoglycemic Metabolic Challenge in T1D.

AIMS: In type 1 diabetes (T1D), repeated hypoglycemic episodes may reduce hormonal defenses and increase the risk for severe hypoglycemia. In this work, we investigate the effect of a structured hyper/hypoglycemic metabolic challenge on the postintervention glucose variability in T1D subjects studied at home. METHODS: Thirty T1D subjects using insulin pump were monitored with blood glucose meters (SMBG) during a 1-month observation period. After 2 weeks of monitoring, participants were admitted at the University of Virginia Clinical Research Unit to undergo an 8-hour metabolic challenge. The intervention was designed to create hyperglycemia shortly followed by hypoglycemia, mimicking a real-life scenario of underbolused meal followed by overcorrection. After the intervention, subjects were monitored for 2 more weeks. Glycemic variability was assessed before and after the challenge using the low blood glucose index (LBGI). Glucagon counterregulation (GCR) response to induced hypoglycemia was also measured. LBGI variation and GCR were linked to prior exposure to hypoglycemia. RESULTS: Subjects significantly exposed to hypoglycemia in the 2 weeks before the intervention had a significant increase of postchallenge LBGI ( P < .001) and lower GCR response ( P < .05). Recent occurrence of hypoglycemia and number of years not using an insulin pump were identified as significant predictors of postchallenge LBGI ( P < .001). CONCLUSION: Glycemic swings, a common result of suboptimal insulin treatment, have a significant impact on future (days) glycemic control in T1D subjects with a recent history of hypoglycemia, as measured in the field. Choice of past insulin therapy may also mediate this effect.

Decrease of Serum IGF-I following Transsphenoidal Pituitary Surgery for Acromegaly.

BACKGROUND: In the immediate postoperative period following resection of growth hormone (GH)-secreting pituitary tumors, serum concentrations of GH have limited ability to predict remission of acromegaly. Since many actions of GH actions are mediated by insulin-like growth factor-1 (IGF-I), we aimed to determine the rates of fall of IGF-I during 72 h after surgical resection of pituitary tumors. METHODS: We studied patients who were undergoing pituitary surgery for acromegaly. IGF-I was measured by LC-MS and GH by immunoassay. Remission was defined by the combination of serum GH <0.4 ng/mL during oral glucose tolerance testing performed 8 weeks after the surgical procedure and normal IGF-I at ≥8 weeks. RESULTS: During the first 72 h after surgery, the mean (SD) rate of decline of IGF-I was 185 (61) ng/mL per 24 h in those who achieved remission (n = 23), with a mean (SD) apparent half-life of 55 (19) h. IGF-I had decreased to <65% of the preoperative IGF-I on postoperative day 2 in 20 of 23 remission patients (87%) vs none of 5 patients who did not achieve remission. GH was <2.7 ng/mL on day 2 in 21 of 23 remission patients (91%), but in none of the nonremission patients. The combination of IGF-I and GH on day 2 separated the remission and nonremission groups of patients. CONCLUSIONS: Rapid decline of serum IGF-I during the immediate postoperative period warrants further study as an analytically independent adjunct to GH measurement for early prediction of biochemical remission of acromegaly.

The level of circulating octanoate does not predict ghrelin O-acyl transferase (GOAT)-mediated acylation of ghrelin during fasting.

BACKGROUND: Acyl-ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin O-acyl transferase (GOAT) attaches an 8-carbon medium-chain fatty acid (MCFA) (octanoate) to serine 3 of ghrelin. This acylation is necessary for the activity of ghrelin. Animal data suggest that MCFAs provide substrate for GOAT and an increase in nutritional octanoate increases acyl-ghrelin. OBJECTIVES: To address the question of the source of substrate for acylation, we studied whether the decline in ghrelin acylation during fasting is associated with a decline in circulating MCFAs. METHODS: Eight healthy young men (aged 18-28 years, body mass index range, 20.6-26.2 kg/m(2)) had blood drawn every 10 minutes for acyl- and desacyl-ghrelin and every hour for free fatty acids (FFAs) during the last 24 hours of a 61.5-hour fast and during a fed day. FFAs were measured by a highly sensitive liquid chromatography-mass spectroscopy method. Acyl- and desacyl-ghrelin were measured in an in-house assay; the results were published previously. Ghrelin acylation was assessed by the ratio of acyl-ghrelin to total ghrelin. RESULTS: With the exception of MCFAs C8 and C10, all other FFAs, the MCFAs (C6 and C12), and the long-chain fatty acids (C14-C18) significantly increased with fasting (P < .05). There was no significant association between the fold change in ghrelin acylation and circulating FFAs. CONCLUSIONS: These results suggest that changes in circulating MCFAs are not linked to the decline in ghrelin acylation during fasting and support the hypothesis that acylation of ghrelin depends at least partially on the availability of gastroluminal MCFAs or the regulation of GOAT activity.

Four-hour infusion of hydrocortisone does not suppress the nocturnal increase of circulating acyl- or desacyl-ghrelin concentrations in healthy young adults.

BACKGROUND: Ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin is found in the circulation in two forms: acyl- and desacyl-ghrelin. Acyl- and desacyl-ghrelin concentrations increase at night, when cortisol concentrations are low. Acute ghrelin administration increases ACTH and cortisol concentrations and a feedback loop between the ghrelin and ACTH-cortisol axis has been postulated. A previous study showed that exogenously induced hypercortisolism for 5 days decreased plasma ghrelin concentrations. OBJECTIVE: The objective of the study was to determine whether a 4-hour infusion of hydrocortisone given at a time of low endogenous cortisol concentrations (11:00 pm to 3:00 am) acutely suppresses acyl- and desacyl-ghrelin. METHODS: Eight healthy young men aged (mean ± SD) 21.5 ± 2.7 years with a body mass index of 22.4 ± 2.5 kg/m(2) were studied in a single-blind, placebo-controlled study during two separate overnight admissions on the Clinical Research Unit. The volunteers received either a 4-hour (11:00 pm to 3:00 am) infusion of hydrocortisone or a saline infusion. The hydrocortisone infusion rate was 0.3 mg/kg·h for the initial 3 minutes, 0.24 mg/kg·h for 9 minutes, and then 0.135 mg/kg·h until the end of the infusion. Plasma acyl- and desacyl-ghrelin concentrations (in-house two site sandwich assay) and ACTH, cortisol, insulin, GH, and glucose levels were measured every 10 minutes for 16 hours (5:00 pm to 9:00 am). RESULTS: The mean differences (lower 95% limit; upper 95% limit) between the saline infusion and hydrocortisone infusion for acyl- and desacyl-ghrelin concentrations were not significantly different from zero. The infusion period (11:00 pm to 3:00 am) was as follows: acyl-ghrelin, 0.22 (-7.39; 7.83) (P = 1.00); desacyl-ghrelin, -3.36 (-17.66; 10.95) (P = 1.00). The postinfusion period (3:00-7:00 am) was as follows: acyl-ghrelin, 8.68 (1.07; 16.28); (P = .056); desacyl-ghrelin, 8.75 (-5.56; 23.05) (P = .403). CONCLUSIONS: A short-term increase in circulating cortisol concentrations by exogenous hydrocortisone infusion does not suppress circulating nocturnal acyl- or desacyl-ghrelin concentrations. Thus, it is likely that the diurnal pattern of ghrelin secretion is under circadian control and not directly regulated by cortisol.

Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults.

BACKGROUND: Acyl-ghrelin is thought to have both orexigenic effects and to stimulate GH release. A possible cause of the anorexia of aging is an age-dependent decrease in circulating acyl-ghrelin levels. OBJECTIVES: The purpose of the study was to compare acyl-ghrelin and GH concentrations between healthy old and young adults and to examine the relationship of acyl-ghrelin and GH secretion in both age groups. METHODS: Six healthy older adults (age 62-74 y, body mass index range 20.9-29 kg/m(2)) and eight healthy young men (aged 18-28 y, body mass index range 20.6-26.2 kg/m(2)) had frequent blood samples drawn for hormone measurements every 10 minutes for 24 hours. Ghrelin was measured in an in-house, two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in a sensitive assay (Immulite 2000), and GH peaks were determined by deconvolution analysis. The acyl-ghrelin/GH association was estimated from correlations between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-minute interval preceding each GH burst. RESULTS: Twenty-four-hour mean (±SEM) GH (0.48 ± 0.14 vs 2.2 ± 0.3 µg/L, P < .005) and acyl-ghrelin (14.7 ± 2.3 vs 27.8 ± 3.9 pg/mL, P < .05) levels were significantly lower in older adults compared with young adults. Twenty-four-hour cortisol concentrations were higher in the old than the young adults (15.1 ± 1.0 vs 10.6 ± 0.9 µg/dL, respectively, P < .01). The ghrelin/GH association was more than 3-fold lower in the older group compared with the young adults (0.16 ± 0.12 vs 0.69 ± 0.04, P < .001). CONCLUSIONS: These results provide further evidence of an age-dependent decline in circulating acyl-ghrelin levels, which might play a role both in the decline of GH and in the anorexia of aging. Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are less tightly linked to GH regulation.

Growth hormone axis and aging.

Growth hormone (GH) and/or ghrelin mimetics represent potential treatment and/or prevention options for musculoskeletal impairment associated with aging. Use of improvement in muscle function as an outcome in studies of GH and ghrelin mimetics is complicated by the lack of a standardized definition for clinically meaningful efficacy of this end point. Based on preliminary study results, the use of ghrelin mimetics may be more suitable for use in this age group than GH itself. There are still several unanswered questions related to the use of ghrelin mimetics in the elderly, which prevents recommendation for its use at the current time.

The role of ghrelin in GH secretion and GH disorders.

In humans, growth hormone (GH) is secreted from the anterior pituitary in a pulsatile pattern. The traditional view is that this secretory pattern is driven by two counter regulatory neurohormones, GHRH and somatostatin. Ghrelin, the natural ligand for the growth hormone (GH)-secretagogue receptor (GHS-R), is produced in the stomach. Ghrelin is the strongest GH secretagogue known to date, but the role of endogenous ghrelin in the regulation of circulating GH levels remains controversial. The following review examines the evidence suggesting that endogenous ghrelin may be a key regulator of GH peak amplitude and discusses studies of diseases with altered GH levels, where it is found that in these states GH and ghrelin levels change in a similar way.

The ghrelin axis in disease: potential therapeutic indications.

Ghrelin, the natural ligand for the growth hormone (GH)-secretagogue receptor (GHS-R), is produced predominantly in the stomach. It is present in the circulation in two major forms, an acylated and an unacylated form, both of which have reported activities. Some of the best understood actions of acylated ghrelin administration are its orexigenic effects, and the stimulation of GH secretion. Ghrelin also seems to play a role in glucose homeostasis, lipid metabolism and immune function. Based on its orexigenic and metabolic effects, ghrelin and ghrelin mimetics have potential benefit in antagonizing protein breakdown and weight loss in catabolic conditions such as cancer cachexia, renal, cardiac and pulmonary disease, and age-related frailty. Ghrelin also has potentially useful positive effects on cardiac function and gastric motility. Ghrelin antagonists may be of benefit to increase insulin sensitivity and potentiate weight loss. The following chapter presents some background on ghrelin and ghrelin assays and discusses some of the potential therapeutic approaches for the use of ghrelin, ghrelin mimetic compounds and ghrelin antagonists in clinical disease.

Intrarenal ghrelin infusion stimulates distal nephron-dependent sodium reabsorption in normal rats.

Ghrelin is a 28-amino acid peptide hormone that exerts powerful orexigenic effects. Ghrelin receptor expression has been reported in the kidney, but the role of ghrelin in the kidney is unknown. The present studies confirmed ghrelin receptor mRNA expression in the kidneys of normal Sprague Dawley rats (n=6) using reverse transcription polymerase chain reaction (PCR) and sequencing of the 588-bp PCR product. To test intrarenal ghrelin action, uninephrectomized rats received 3 cumulative 1-hour renal interstitial (RI) infusions of 5% dextrose in water (vehicle, n=21), ghrelin (n=10), ghrelin plus specific ghrelin receptor antagonist [D-Lys-3]-GHRP-6 (n=24), or [D-Lys-3]-GHRP-6 alone (n=32). Mean arterial pressure (MAP), urine sodium excretion rate (U(Na)V), glomerular filtration rate (GFR), fractional excretion of sodium (FE(Na)), and fractional excretion of lithium (FE(Li)) were calculated for each period. RI ghrelin infusion significantly decreased U(Na)V to 86 ± 4.9% (P<0.05), 74 ± 6.5% (P<0.01), and 62 ± 10% (P<0.01) of baseline during periods 1 to 3, respectively. Ghrelin also significantly decreased FE(Na) to 68 ± 11% (P<0.05), 57 ± 8.6% (P<0.001), and 59 ± 12% (P<0.01) of baseline, without changing GFR or FE(Li). Identical ghrelin infusions in the presence of [D-Lys-3]-GHRP-6 failed to permit reductions in U(Na)V or FE(Na). Following [D-Lys-3]-GHRP-6 infusion alone, U(Na)V increased from 0.06 ± 0.01 to 0.18 ± 0.03 µmol/min (P<0.0001). Concomitant increases in FE(Na) were also observed (0.23 ± 0.03% to 0.51 ± 0.06% [P<0.001]), without changes in MAP, GFR, or FE(Li). Together, these data introduce a novel intrarenal ghrelin-ghrelin receptor system, which, on activation, significantly increases Na(+) reabsorption at the level of the distal nephron.

The ghrelin O-acyltransferase-ghrelin system: a novel regulator of glucose metabolism.

PURPOSE OF REVIEW: Ghrelin, an orexigenic hormone secreted from the stomach, exists in the circulation in two isoforms: des-acyl and acyl ghrelin. Acylation by the enzyme ghrelin O-acyl-transferase (GOAT) enables ghrelin to activate the ghrelin receptor. This review discusses recent findings illustrating the role of acyl ghrelin, des-acyl ghrelin and GOAT in regulating glucose homeostasis. RECENT FINDINGS: Recent publications support a role of ghrelin in modulating glucose homeostasis. Novel cellular mechanisms have been proposed to explain these effects. Controversy on this topic continues to exist owing to inconsistent observations made in both rodents and humans. Many recent studies are uncovering a role of des-acyl ghrelin in glucose metabolism specifically in modulating insulin sensitivity and glucose uptake into adipocytes. A novel role of ghrelin acylation by the enzyme GOAT in regulating glucose metabolism during caloric deprivation has newly been discovered. SUMMARY: Ghrelin plays a role in regulating glucose homeostasis through the modulation of insulin secretion and insulin sensitivity. Acyl ghrelin and des-acyl ghrelin appear to have opposing glucoregulatory effects and regulation of acylation by the enzyme GOAT appears to play a role in mediating glucose metabolism. Modulation of GOAT or ghrelin signaling may be a clinically relevant strategy to treat metabolic diseases such as type II diabetes.

AutoDecon: a robust numerical method for the quantification of pulsatile events.

This work presents a new approach to the analysis of aperiodic pulsatile heteroscedastic time-series data, specifically hormone pulsatility. We have utilized growth hormone (GH) concentration time-series data as an example for the utilization of this new algorithm. While many previously published approaches used for the analysis of GH pulsatility are both subjective and cumbersome to use, AutoDecon is a nonsubjective, standardized, and completely automated algorithm. We have employed computer simulations to evaluate the true-positive, the false-positive, the false-negative, and the sensitivity percentages of several of the routinely employed algorithms when applied to GH concentration time-series data. Based on these simulations, it was concluded that this new algorithm provides a substantial improvement over the previous methods. This novel method has many direct applications in addition to hormone pulsatility, for example, to time-domain fluorescence lifetime measurements, as the mathematical forms that describe these experimental systems are both convolution integrals.

Does low-dose growth hormone therapy improve the body composition of patients infected with HIV?

Use of highly active antiretroviral therapy in patients infected with HIV can lead to lipodystrophy, a condition characterized by changes in body-fat distribution. In addition, infected individuals often exhibit relative growth hormone (GH) deficiency. Treatment with supraphysiological levels of GH improves body composition in these patients, but is associated with adverse effects. In this Practice Point commentary, we discuss an 18-month, randomized, double-blind, placebo-controlled study of low-dose GH therapy in 56 HIV-positive adults with lipodystrophy and relative GH deficiency. Lo et al. found that administration of low-dose GH (mean 0.33 mg daily) led to improvements in body composition (e.g. visceral adipose-tissue area), diastolic blood pressure and triglyceride levels. Furthermore, this treatment regimen was not associated with an increased incidence of adverse events compared with placebo. Here, we discuss the implications of the findings of Lo et al., and describe additional strategies that might be used to treat lipodystrophy in HIV-positive individuals.