Collateral status affects the onset-to-reperfusion time window for good outcome.

OBJECTIVE: To characterise the time window in which endovascular thrombectomy (EVT) is associated with good outcome, and to test the differential relationship between functional outcome and onset-to-reperfusion time (ORT), depending on collateral status. METHODS: This was a retrospective analysis of clinical and imaging data of 554 consecutive patients, who had recanalisation success by EVT for anterior circulation large artery occlusion, from the prospectively maintained registries of 16 comprehensive stroke centres between September 2010 and December 2015. The patients were dichotomised into good and poor collateral groups, based on CT angiography. We tested whether the likelihood of good outcome (modified Rankin Scale, 0-2) by ORT was different between two groups. RESULTS: ORT was 298 min±113 min (range, 81-665 min), and 84.5% of patients had good collaterals. Age, diabetes mellitus, previous infarction, National Institutes of Health Stroke Scale, good collaterals (OR 40.766; 95% CI 10.668 to 155.78; p<0.001) and ORT (OR 0.926 every 30 min delay; 95% CI 0.862 to 0.995; p=0.037) were independently associated with good outcome. The drop in likelihood of good outcome associated with longer ORT was significantly faster in poor collateral group (OR 0.305 for every 30 min; 95% CI 0.113 to 0.822) than in good collateral group (OR 0.926 for every 30 min; 95% CI 0.875 to 0.980). CONCLUSIONS: Earlier successful recanalisation was strongly associated with good outcome in poor collateral group; however, this association was weak during the tested time window in good collateral group. This suggests that the ORT window for good outcome can be adjusted according to collateral status.

Pyroelectric and Piezoelectric Properties of (1-x)Na0.5K0.5NbO3-xBiScO3 Lead-Free Ceramics.

In this research, the pyroelectric and piezoelectric properties of (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were investigated and analyzed. (Na, K)NbO3 based (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were prepared by a conventional mixed oxide method. As the substituent, BiScO3 material enhanced the sintering mechanism of NKN ceramic, which improved the density, pyroelectric and piezoelectric properties, without any structural distortion. In this study, the structural dependent improved piezoelectric properties of (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were investigated with various sintering temperatures. Also, the pyroelectric properties of (1 - x)Na0.5K0.5NbO3-xBiScO3 ceramics were observed up to 200 °C for the devices applications. The crystalline structures of the (1-x)Na0.5K0.5NbO3-x BiScO3 ceramics were measured by X-ray diffraction (XRD). The microstructure was examined by field emission scanning electron microscopy (FE-SEM). In addition, piezo-electric charge coefficient d33 and pyroelectric coefficient will be discussed.

Adjusting patients streaming initiated by a wait time threshold in emergency department for minimizing opportunity cost.

Purpose Two different systems for streaming patients were considered to improve efficiency measures such as waiting times (WTs) and length of stay (LOS) for a current emergency department (ED). A typical fast track area (FTA) and a fast track with a wait time threshold (FTW) were designed and compared effectiveness measures from the perspective of total opportunity cost of all patients' WTs in the ED. The paper aims to discuss these issues. Design/methodology/approach This retrospective case study used computerized ED patient arrival to discharge time logs (between July 1, 2009 and June 30, 2010) to build computer simulation models for the FTA and fast track with wait time threshold systems. Various wait time thresholds were applied to stream different acuity-level patients. National average wait time for each acuity level was considered as a threshold to stream patients. Findings The fast track with a wait time threshold (FTW) showed a statistically significant shorter total wait time than the current system or a typical FTA system. The patient streaming management would improve the service quality of the ED as well as patients' opportunity costs by reducing the total LOS in the ED. Research limitations/implications The results of this study were based on computer simulation models with some assumptions such as no transfer times between processes, an arrival distribution of patients, and no deviation of flow pattern. Practical implications When the streaming of patient flow can be managed based on the wait time before being seen by a physician, it is possible for patients to see a physician within a tolerable wait time, which would result in less crowded in the ED. Originality/value A new streaming scheme of patients' flow may improve the performance of fast track system.

Improving process quality for pediatric emergency department.

PURPOSE: Overcrowding in emergency departments (EDs) leads to longer waiting times and results in higher number of patients leaving the ED without being seen by a physician. EDs need to improve quality for patients' waiting time and length of stay (LoS) from the perspective of process and flow control management. The paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: The retrospective case study was performed using the computerized ED patient time logs from arrival to discharge between July 1, 2009 and June 30, 2010. Patients were divided into two groups either adult or pediatric with a cutoff age of 18. Patients' characteristics were measured by arrival time periods, waiting times before being seen by a physician, total LoS and acuity levels. A discrete event simulation was applied to the comparison of quality performance measures. FINDINGS: Statistically significant differences were found between the two groups in terms of arrival times, acuity levels, waiting time stratified for various arrival times and acuity levels. The process quality for pediatric patients could be improved by redesign of patient flow management and medical resource. RESEARCH LIMITATIONS/IMPLICATIONS: The results are limited to a case of one community and ED. This study did not analyze the characteristic of leaving the ED without being seen by a physician. PRACTICAL IMPLICATIONS: Separation of pediatric patients from adult patients in an ED can reduce the waiting time before being seen by a physician and the total staying time in the ED for pediatric patients. It can also lessen the chances for pediatric patients to leave the ED without being seen by a physician. ORIGINALITY/VALUE: A process and flow control management scheme based on patient group characteristics may improve service quality and lead to a better patient satisfaction in ED.

Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion: A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Analysis of the layering pattern of the apparent diffusion coefficient (ADC) for differentiation of radiation necrosis from tumour progression.

OBJECTIVES: To evaluate the added value of diffusion-weighted imaging (DWI) to perfusion-weighted imaging (PWI) for differentiating tumour progression from radiation necrosis. METHODS: Sixteen consecutive patients who underwent removal of a metastatic brain tumour that increased in size after stereotactic radiosurgery were retrospectively reviewed. The layering of the ADC was categorised into three patterns. ADC values were measured on each layer, and the maximum rCBV was measured. rCBV and the layering pattern of the ADC of radiation necrosis and tumour progression were compared. RESULTS: Nine cases of radiation necrosis and seven cases of tumour progression were pathologically confirmed. Radiation necrosis (88.9 % vs. 14.3 %) showed a three-layer pattern of ADC with a middle layer of minimum ADC more frequently. If rCBV larger than 2.6 was used to differentiate radiation necrosis and tumour progression, the sensitivity was 100 % but specificity was 56 %. If the lesions with the three-layer pattern of ADC with moderately increased rCBV (2.6-4.1) were excluded from tumour progression, the sensitivity and specificity increased to 100 %. CONCLUSIONS: The three-layer pattern of ADC shows high specificity in diagnosing radiation necrosis; therefore, combined analysis of the ADC pattern with rCBV may have added value in the correct differentiation of tumour progression from radiation necrosis.

Exendin-4 protects against sulfonylurea-induced ß-cell apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from ß-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by ß-cell exhaustion and apoptosis. ER stress induced by Ca(2+) depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear. Glucagon like peptide-1 (GLP-1) has anti-apoptotic effects in ß-cells after the induction of oxidative and ER stress. In this study, we examined the anti-apoptotic action of a GLP-1 analogue in ß-cell lines and islets against ER stress induced by chronic treatment of sulfonylurea. HIT-T15 and dispersed islet cells were exposed to glibenclamide for 48 h, and apoptosis was evaluated using Annexin/PI flow cytometry. Expression of the ER stress-related molecules and sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca(2+) concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca(2+) replenishing by SERCA restoration. These findings will further the understanding of one cause of glibenclamide-induced ß-cell loss and therapeutic availability of GLP-1-based drugs in secondary failure by sulfonylurea during treatment of diabetes.

Exendin-4 Protects Against Sulfonylurea-Induced ß-Cell Apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from ß-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by ß-cell exhaustion and apoptosis. ER stress induced by Ca2+ depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear. Glucagon like peptide-1 (GLP-1) has anti-apoptotic effects in ß-cells after the induction of oxidative and ER stress. In this study, we examined the antiapoptotic action of a GLP-1 analogue in ß-cell lines and islets against ER stress induced by chronic treatment of sulfonylurea. HIT-T15 and dispersed islet cells were exposed to glibenclamide for 48 h, and apoptosis was evaluated using Annexin/PI flow cytometry. Expression of the ER stress-related molecules and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca2+ concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca2+ replenishing by SERCA restoration. These findings will further the understanding of one cause of glibenclamide-induced ß-cell loss and therapeutic availability of GLP-1-based drugs in secondary failure by sulfonylurea during treatment of diabetes.

Effect of ergonomic design changes in hand tools on physiological cost and subjective ratings.

Users of hand tools expect that tools after ergonomic changes in design will require less muscular activity and cause fewer musculoskeletal disorders than conventional tools. Reports on evaluation of ergonomic design changes in hand tools are controversial. In this study, we measured the effect of changes in tool design with physiological cost of performance and subjective ratings in a simulated setting. We determined physiological cost of performance by measuring muscle activity of the right and left forearm (flexor carpi ulnaris) with electromyography. We collected a questionnaire with subjective ratings before and after each experimental task. Before the tests, ergonomically reconfigured hacksaws received better rating scores than original hacksaws. However, we found no differences in subjective ratings of the hacksaws after the tests. In addition, electromyographic activity did not show any significant differences between the original and modified tools.

Chronic administration of ezetimibe increases active glucagon-like peptide-1 and improves glycemic control and pancreatic beta cell mass in a rat model of type 2 diabetes.

Ezetimibe is a cholesterol-lowering agent targeting Niemann-Pick C1-like 1, an intestinal cholesterol transporter. Inhibition of intestinal cholesterol absorption with ezetimibe may ameliorate several metabolic disorders including hepatic steatosis and insulin resistance. In this study, we investigated whether chronic ezetimibe treatment improves glycemic control and pancreatic beta cell mass, and alters levels of glucagon-like peptide-1 (GLP-1), an incretin hormone involved in glucose homeostasis. Male LETO and OLETF rats were treated with vehicle or ezetimibe (10 mg kg(-1)day(-1)) for 20 weeks via stomach gavage. OLETF rats were diabetic with hyperglycemia and significant decreases in pancreatic size and beta cell mass compared with LETO lean controls. Chronic treatment of OLETF rats with ezetimibe improved glycemic control during oral glucose tolerance test compared with OLETF controls. Moreover, ezetimibe treatment rescued the reduced pancreatic size and beta cell mass in OLETF rats. Interestingly, ezetimibe significantly decreased serum dipeptidyl peptidase-4 activity and increased serum active GLP-1 in OLETF rats without altering serum total GLP-1. These findings demonstrated that chronic administration of ezetimibe improves glycemic control and pancreatic beta cell mass, and increases serum active GLP-1 levels, suggesting possible involvement of GLP-1 in the ezetimibe-mediated beneficial effects on glycemic control.

Notch1 Has an Important Role in ß-Cell Mass Determination and Development of Diabetes.

BACKGROUND: Notch signaling pathway plays an important role in regulating pancreatic endocrine and exocrine cell fate during pancreas development. Notch signaling is also expressed in adult pancreas. There are few studies on the effect of Notch on adult pancreas. Here, we investigated the role of Notch in islet mass and glucose homeostasis in adult pancreas using Notch1 antisense transgenic (NAS). METHODS: Western blot analysis was performed for the liver of 8-week-old male NAS mice. We also conducted an intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test in 8-week-old male NAS mice and male C57BL/6 mice (control). Morphologic observation of pancreatic islet and ß-cell was conducted in two groups. Insulin secretion capacity in islets was measured by glucose-stimulated insulin secretion (GSIS) and perifusion. RESULTS: NAS mice showed higher glucose levels and lower insulin secretion in IPGTT than the control mice. There was no significant difference in insulin resistance. Total islet and ß-cell masses were decreased in NAS mice. The number of large islets (≥250 µm) decreased while that of small islets (<250 µm) increased. Reduced insulin secretion was observed in GSIS and perifusion. Neurogenin3, neurogenic differentiation, and MAF bZIP transcription factor A levels increased in NAS mice. CONCLUSION: Our study provides that Notch1 inhibition decreased insulin secretion and decreased islet and ß-cell masses. It is thought that Notch1 inhibition suppresses islet proliferation and induces differentiation of small islets. In conclusion, Notch signaling pathway may play an important role in ß-cell mass determination and diabetes.

Notch signaling in pancreatic endocrine cell and diabetes.

Recent studies have improved our understanding of the physiological function of Notch signaling pathway and now there is compelling evidence demonstrating that Notch is a key regulator of embryonic development and tissue homeostasis. Although further extensive studies are necessary to illustrate the molecular mechanisms, new insights into the role of Notch signaling in pancreas development and diabetes have been achieved. Importantly, the ability to regulate Notch signaling intensity both positively and negatively may have therapeutic relevance for diabetes. Thus, this paper reviews the current knowledge of the roles of Notch signaling in the pancreatic endocrine cell system.

Transferrin fusion technology: a novel approach to prolonging biological half-life of insulinotropic peptides.

Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to 2 min for native GLP-1. GLP-1-Tf retained the acute, glucose-dependent insulin-secretory properties of native GLP-1 in diabetic animals and had a profound effect on proliferation of pancreatic beta-cells. In addition, Tf and the fusion proteins did not cross the blood-brain-barrier but still reduced food intake after peripheral administration. EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides.

Exendin-4 protects oxidative stress-induced ß-cell apoptosis through reduced JNK and GSK3ß activity.

Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of ß-cell mass through ß-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of ß-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from ß-cell and differentiation to ß-cell from progenitor cells. Also, it probably has an antiapoptotic effect on ß-cell, but detailed mechanisms are not proven. Therefore, we examined the protective mechanism of GLP-1 in ß-cell after induction of oxidative stress. The cell apoptosis decreased to ~50% when cells were treated with 100 µM H(2)O(2) for up to 2 hr. After pretreatment of Ex-4, GLP-1 receptor agonist, flow cytometric analysis shows 41.7% reduction of ß-cell apoptosis. This data suggested that pretreatment of Ex-4 protect from oxidative stress-induced apoptosis. Also, Ex-4 treatment decreased GSK3ß activation, JNK phosphorylation and caspase-9, -3 activation and recovered the expression of insulin2 mRNA in ß-cell lines and secretion of insulin in human islet. These results suggest that Ex-4 may protect ß-cell apoptosis by blocking the JNK and GSK3ß mediated apoptotic pathway.

Adaptation of perturbation to postural control in individuals with diabetic peripheral neuropathy.

Loss of sensation in the feet due to diabetic peripheral neuropathy can cause deterioration of postural control and result in higher risk of trips, slips or falls. In the literature, many studies have reported that people with diabetic peripheral neuropathy tend to show greater displacement of body sway than normal people when the base of support is disrupted. But not much is known about postural characteristics of diabetics with peripheral neuropathy at the moment of postural stability disruptions and during the time span for recovering stability. The objective of this study was to analyze differences of postural characteristics between diabetics with peripheral neuropathy and diabetics without peripheral neuropathy. A learning effect of perturbation was found for the diabetic peripheral neuropathy group in the posterior direction of perturbation during the first phase, which may indicate that it could be possible to design a postural control program for those people.

Comparison of the Effects of Liraglutide on Islet Graft Survival Between Local and Systemic Delivery.

Islet transplantation has emerged as a promising treatment for type 1 diabetes mellitus. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, protects beta cells after islet transplantation by improving glycemic control through several mechanisms. In this study, we compared the effects of local pretreatment and systemic treatment with liraglutide on islet transplantation in a diabetic mouse model. Streptozotocin (STZ)-induced diabetic C57BL/6 mice were transplanted with syngeneic islets under the kidney capsule. Isolated islets were either locally treated with liraglutide before transplantation or mice were treated systemically by intraperitoneal injection after islet transplantation. Local pretreatment of islets with liraglutide was more effective in increasing body weight, decreasing hemoglobin A1c levels, and lowering blood glucose levels in STZ-diabetic mice transplanted with islets. Local pretreatment was also more effective in increasing insulin secretion and islet survival in STZ-diabetic mice. Histological analysis of the transplantation site revealed fewer apoptotic cells following local pretreatment compared with systemic injection of liraglutide. These findings indicate that liraglutide administered once locally before transplantation might have superior effects on islet preservation than systemic administration.

Melatonin attenuates lipopolysaccharide-induced acute lung inflammation in sleep-deprived mice.

Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia. Recent studies have shown an association between sleep deprivation (SD) and inflammation, however, the underlying mechanisms remain unclear. In the present study, we investigated whether melatonin protects against acute lung inflammation in SD. Male ICR mice were deprived sleep using modified multiplatform water bath for 3 days. Acute lung inflammation was induced by lipopolysaccharide (LPS; 5 mg/kg). Melatonin (5 mg/kg) and LPS was administered in SD mice at day 2. Mice were divided into five groups as control, SD, LPS, LPS + SD, and LPS + SD + melatonin (each group, n = 11). Mice were killed on day 3 after treatment of melatonin and LPS for 24 hr. Lung tissues were collected for histological examination and protein analysis. The malondialdehyde (MDA) level was determined for the effect of oxidative stress. Melatonin restored weight loss in LPS + SD. Histological findings revealed alveolar damages with inflammatory cell infiltration in LPS + SD. Melatonin remarkably attenuated the alveolar damages. In western blot analysis, LPS reduced the levels of Bcl-XL and procaspase-3 in SD mice. After treatment with melatonin, the levels of Bcl-XL and procaspase-3 increased when compared with LPS + SD. LPS treatment showed an increase of TUNEL-positive cells, whereas melatonin prevented the increase of cell death in LPS + SD animals. In lipid peroxidation assay, melatonin significantly reduced the elevated MDA level in LPS + SD. Our results suggest that melatonin attenuates acute lung inflammation during SD via anti-apoptotic and anti-oxidative actions.

Factors influencing insulin sensitivity during hyperinsulinemic-euglycemic clamp in healthy Korean male subjects.

Background and objective: The effects of age and related factors on insulin sensitivity have not been definitively evaluated in East Asian populations. We proposed a reference range for the glucose disposal rate (M-value) on hyperinsulinemic-euglycemic study and its association with other parameters. Methods: Healthy, non-diabetic young (n=10) and elderly (n=13) male subjects with normal body mass index were eligible for this study. Subjects who passed the oral glucose tolerance test (OGTT) underwent hyperinsulinemic-euglycemic clamp with high-dose (80 mU/m2·min) insulin infusion. Results: M-values were normalized to body weight (MBW) and fat-free mass (MFFM). Neither M-value was significantly different between age groups (P=0.458 and P=0.900, respectively). An inverse correlation was observed between MFFM and baseline insulin (r=-0.418; P=0.047), baseline C-peptide (r=-0.426; P=0.043) and OGTT 2-hour glucose (r=-0.452; P=0.030). Regarding correlations with other insulin sensitivity indices, M-values were positively associated with the Matsuda index but not with homeostasis model assessment of insulin resistance. Conclusion: Our results suggest that age is not a critical determinant of insulin sensitivity, while fasting insulin and C-peptide levels, OGTT 2-hour glucose level, and Matsuda index are predictable markers of insulin sensitivity in healthy Koreans.

Long-acting FC-fusion rhGH (GX-H9) shows potential for up to twice-monthly administration in GH-deficient adults.

OBJECTIVE: Hybrid Fc-fused rhGH (GX-H9) is a long-acting recombinant human growth hormone (GH) under clinical development for both adults and children with GH deficiency (GHD). We compared the safety, pharmacokinetics and pharmacodynamics of weekly and every other week (EOW) dosages of GX-H9 with those of daily GH administration in adult GHD (AGHD) patients. DESIGN: This was a randomized, open-label, active-controlled and dose-escalation study conducted in 16 endocrinology centers in Europe and Korea. METHODS: Forty-five AGHD patients with or without prior GH treatment were enrolled. Patients with prior GH treatments were required to have received the last GH administration at least 1 month prior to randomization. Subjects were sequentially assigned to treatment groups. Fifteen subjects were enrolled to each treatment group and randomly assigned to receive either GX-H9 or Genotropin (4:1 ratio). GX-H9 dosage regimens for Groups 1, 2 and 3 were 0.1 mg/kg weekly, 0.3 mg/kg EOW and 0.2 mg/kg EOW, respectively. All Genotropin-assigned subjects received 6 µg/kg Genotropin, regardless of treatment group. Main outcome analyses included measurements of serum insulin-like growth factor 1 (IGF-I), safety, pharmacokinetics, pharmacodynamics and immunogenicity. RESULTS: Mean GX-H9 peak and total exposure increased with an increase in dose after a single-dose administration. The mean IGF-I response was sustained above baseline over the intended dose interval of 168 h for the weekly and 336 h for the EOW GX-H9 groups. Safety profiles and immunogenicity were not different across the treatment groups and with Genotropin. CONCLUSIONS: GX-H9 has the potential for up to twice-monthly administration.

Contribution of nonesterified fatty acids to insulin resistance in the elderly with normal fasting but diabetic 2-hour postchallenge plasma glucose levels: the Baltimore Longitudinal Study of Aging.

Isolated postchallenge hyperglycemia (IPH) with normal fasting plasma glucose <100 mg/dL and plasma glucose with diabetic 2-hour plasma glucose >or=200 mg/dL after an oral glucose tolerance test (OGTT) is a common occurrence in the elderly. We sought to understand what unique characteristics this population might have that puts it at risk for this particular metabolic finding. We therefore conducted a longitudinal study of volunteers in the Baltimore Longitudinal Study of Aging (BLSA). All volunteers had an OGTT performed (75 g) on 2 or more occasions. We measured plasma levels of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, leptin, adiponectin, resistin, C-reactive protein, cytokines, and their soluble receptors, as well as nonesterified free fatty acids (NEFAs). We determined that 22 subjects in BLSA had IPH, accounting for 2.1% of the BLSA population. All 22 were older than 65 years. They were then matched by age, sex, and body mass index to 12 subjects who had isolated impaired glucose tolerance (IGT) and 15 subjects with normal glucose tolerance (NGT). All subjects had normal fasting glucose levels <100 mg/dL in accordance with the American Diabetes Association Expert Committee on the Classification and Diagnosis of Diabetes Mellitus criteria (2003). We found that subjects with IPH had similar plasma insulin levels to the other 2 groups, except at the 2-hour time when their insulin levels were higher than NGT (P < .05). Although there was a clear trend for differences in the insulinogenic index, the areas under the curves for insulin, systolic blood pressure, adiponectin, and C-reactive protein across the glucose tolerance categories revealed no statistical significance. Cytokines and their soluble receptors, gut hormones, and adipokines were similar in all 3 groups. The NEFA levels were significantly elevated in the fasting state (P < .05) in the IPH compared with NGT, with IGT intermediate between the other 2 groups. The rate of clearance of NEFAs after the OGTT decreased progressively from the NGT to the IPH group (in micromoles per liter per minute: NGT, 11.9 vs IGT, 7.6 vs IPH, 3.0). We conclude that the rate of suppression of lipolysis in the elderly determines the sensitivity of glucose uptake to insulin after OGTT.