Use of amniotic membrane in hard-to-heal wounds: a multicentre retrospective study.

OBJECTIVE: Hard-to-heal (chronic) wounds negatively impact patients and are a source of significant strain on the healthcare system and economy. These wounds are often resistant to standard of care (SoC) wound healing approaches due to a diversity of underlying pathologies. Cellular, acellular, and matrix-like products, such as amniotic membranes (AM), are a potential solution to these challenges. A growing body of evidence suggests that AM may be useful for treatment-resistant wounds; however, limited information is available regarding the efficacy of dehydrated amniotic membrane (DHAM) on multi-aetiology, hard-to-heal wounds. Therefore, we analysed the efficacy of DHAM treatment in reducing the size of hard-to-heal diabetic and venous leg ulcers (VLUs) that had failed to improve after SoC-based treatments. METHOD: In this multicentre retrospective study, we analysed wound size during clinic visits for patients being treated for either diabetic or VLUs. During each visit, the treatment consisted of debridement followed by application of DHAM. Each wound was measured after debridement and prior to DHAM application, and wound volumes over time or number of DHAM applications were compared. RESULTS: A total of 18 wounds in 11 patients were analysed as part of this study. Wounds showed a significant reduction in volume after a single DHAM application, and a 50% reduction in wound size was observed after approximately two DHAM applications. These findings are consistent with reports investigating DHAM treatment of diabetic ulcers that were not necessarily resistant to treatment. CONCLUSION: To our knowledge, this study is the first to directly compare the efficacy of standalone DHAM application to hard-to-heal diabetic and venous leg ulcers, and our findings indicate that DHAM is an effective intervention for resolving these types of wounds. This suggests that implementing this approach could lead to fewer clinic visits, cost savings and improved patient quality of life. DECLARATION OF INTEREST: This research was supported in part by Merakris Therapeutics, US, and facilitated access to deidentified patient datasets, which may represent a perceived conflict of interest; however, the primary data analysis was performed by FSB who is unaffiliated with Merakris Therapeutics. TCB is a founder, employee of and shareholder in Merakris Therapeutics; WSF is a co-founder of, consultant for, and shareholder in Merakris Therapeutics, and was also supported by the National Institutes of Health National Center for Advancing Translational Sciences Clinical and Translational Science Awards Grant KL2 Scholars Program (KL2TR001441). The research was also supported through endowments to WSF from the University of Texas Medical Branch Mimmie and Hallie Smith Endowed Chair of Transplant Research and the John L Hern University Chair in Transplant Surgery.

Safety and efficacy of acellular human amniotic fluid and membrane in the treatment of non-healing wounds in a patient with chronic venous insufficiency.

Chronic, non-healing venous ulcers of the lower extremity are often limb-threatening conditions. Their management is characterized by a prolonged and frequently frustrating clinical course that represents an economic burden to both the patient and healthcare system. During the last two decades, thermal ablation of underlying incompetent venous systems has been extensively utilized to treat chronic venous insufficiency. Despite successful correction of venous hypertension, a substantial subgroup of patients remain affected by non-healing venous ulcers, thus posing a significant clinical challenge. In this case report, we detail quantitative and qualitative wound treatment course in a patient refractory to standard interventions, by treatment with a combination of cell-free amniotic fluid and dehydrated amniotic membrane following successful thermal ablation of refluxing veins.

Chatbots to Support Mental Wellbeing of People Living in Rural Areas: Can User Groups Contribute to Co-design?

Digital technologies such as chatbots can be used in the field of mental health. In particular, chatbots can be used to support citizens living in sparsely populated areas who face problems such as poor access to mental health services, lack of 24/7 support, barriers to engagement, lack of age appropriate support and reductions in health budgets. The aim of this study was to establish if user groups can design content for a chatbot to support the mental wellbeing of individuals in rural areas. University students and staff, mental health professionals and mental health service users (N = 78 total) were recruited to workshops across Northern Ireland, Ireland, Scotland, Finland and Sweden. The findings revealed that participants wanted a positive chatbot that was able to listen, support, inform and build a rapport with users. Gamification could be used within the chatbot to increase user engagement and retention. Content within the chatbot could include validated mental health scales and appropriate response triggers, such as signposting to external resources should the user disclose potentially harmful information or suicidal intent. Overall, the workshop participants identified user needs which can be transformed into chatbot requirements. Responsible design of mental healthcare chatbots should consider what users want or need, but also what chatbot features artificial intelligence can competently facilitate and which features mental health professionals would endorse.

Genistein and exercise do not improve cardiovascular risk factors in the ovariectomized rat.

OBJECTIVE: To investigate the effect of either genistein, or exercise, or both, on parameters that are indicators of cardiovascular health. METHODS: We investigated the effect of genistein treatment (300 mg genisten/kg body weight/day), or exercise training, or combined genistein and exercise training, for a period of 6 weeks on physical characteristics, cardiovascular plasma markers, blood pressure, aortic morphology, cardiac structure and oxidative stress in the ovariectomized (OVX) Sprague-Dawley rat. Comparisons were made with intact rats. RESULTS: Ovariectomy (compared to intact) resulted in significant decreases in uterine weight (6-fold, p < 0.0001), insulin levels (4-fold, p = 0.0214), insulin/glucose ratio (3-fold, p = 0.0029), and tumor necrosis factor-α plasma levels (2-fold, p < 0.0001). Similarly, aortic blood pressure was significantly increased (by 8%, p < 0.0033) in OVX rats, without changes in aortic luminal or wall dimensions. Heart surface area was significantly increased (by 16%, p = 0.0160) in OVX rats and this was without changes in non-protein thiol levels (a marker of oxidative stress). Physical characteristics were not altered by treatment with genistein, or genistein with exercise, with the exception of increased uterine weight in OVX rats treated under these same conditions. There were no effects of genistein or exercise on indices of blood pressure and aortic morphology in the OVX rat. However, right ventricular nuclei count was reduced in sedentary genistein-treated rats compared to non-treated control OVX rats. CONCLUSION: Our results indicate that administration of genistein at this dose, treadmill running, or the combination of both, are not associated with any improvement in cardiovascular function and structure, and risk factors in an ovariectomy model of postmenopause.

Protection against L-NAME-induced reduction in cardiac output persists even after cessation of angiotensin-converting enzyme inhibitor treatment.

AIM: We have demonstrated that short-term angiotensin-converting enzyme (ACE) inhibition in adult spontaneously hypertensive rats produces cardiac changes that persist following cessation of treatment that result in a reduced inflammatory, proliferative and fibrotic response to the nitric oxide synthase inhibitor N(ω) -Nitro-l-arginine methyl ester (L-NAME). The present study examines whether prior ACE inhibition with enalapril also protects against L-NAME-induced cardiac dysfunction. METHODS: Rats were treated with enalapril (Enal + L) or tap water (Con, Con + L) for 2 weeks followed by a 2-week washout period. At this point, Con + L and Enal + L rats were treated with L-NAME for 10 days. Hearts were perfused in the working mode, mean arterial pressure (MAP) was assessed via radiotelemetry, and myocardial injury was evaluated in hematoxylin and eosin-stained sections. RESULTS: L-NAME increased MAP by a similar magnitude in Con + L and Enal + L. L-NAME-induced statistically significant decreases in flow-mediated functional parameters in Con + L rats including cardiac output, stroke volume and coronary flow. This was prevented by prior enalapril treatment. Prior enalapril did not prevent L-NAME-induced myocardial injury, but may have lessened the degree of it. Regardless of treatment, changes in cardiac function did not correlate with myocardial injury. CONCLUSION: Despite equivalent impact on MAP and incidence of myocardial infarction, prior enalapril treatment resulted in the preservation of cardiac function following L-NAME. Understanding the mechanisms by which transient ACE inhibition protects against reductions in cardiac function in the absence of ongoing treatment may reveal novel targets for heart failure treatment.

The soy isoflavone genistein inhibits the reduction in Achilles tendon collagen content induced by ovariectomy in rats.

The objective of this study was to evaluate the effects of genistein and moderate intensity exercise on Achilles tendon collagen and cross-linking in intact and ovariectomized (OVX) female Sprague-Dawley rats. Rats were separated into eight groups (n = 9/group): intact or OVX, treadmill exercised or sedentary, genistein-treated (300 mg/kg/day) or vehicle. After 6 weeks, tendons were assayed for the collagen-specific amino acid hydroxyproline and hydroxylyslpyridinoline (HP). Collagen content was not influenced by exercise (P = 0.40) but was lower (P < 0.001) in OVX-vehicle rats compared with intact vehicle rats (OVX: 894 ± 35 µg collagen/mg dry weight; intact: 1185 ± 72 µg collagen/mg dry weight). In contrast, collagen content in OVX rats treated with genistein was greater (P = 0.010, 1198 ± 121 µg collagen/mg dry weight) when compared with untreated rats and was not different from intact rats (P = 0.89). HP content was lower in OVX genistein-treated rats when compared with intact genistein-treated rats, but only within the sedentary animals (P = 0.05, intact-treated: 232 ± 39 mmol/mol collagen; OVX-treated: 144 ± 21 mmol/mol collagen). Our findings suggest that ovariectomy leads to a reduction in tendon collagen, which is prevented by genistein. HP content, however, may not have increased in proportion to the addition of collagen. Genistein may be useful for improving tendon collagen content in conditions of estrogen deficiency.

Downregulation of oxytocin receptors in right ventricle of rats with monocrotaline-induced pulmonary hypertension.

AIM: pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1ß, IL-6 and tumour necrosis factor-α in the hypertrophied RV in a model of PH. METHODS: RV hypertrophy was induced in male Sprague-Dawley rats with monocrotaline (MCT; 60 mg kg(-1) ) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio. RESULTS: in the RV of MCT-treated rats, a approximately 40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1ß and IL-6. CONCLUSION: our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1ß and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH.

Impact of fasting and postprandial state on plasma carnitine concentrations during aerobic exercise in type 2 diabetes.

The effects of metabolic states of fasting and post-absorption on plasma concentrations of free carnitine (FC), acylcarnitine (AC) and total carnitine (TC) were compared during submaximal exercise in subjects with type 2 diabetes mellitus. Ten sedentary men (54+/-5 years) treated with oral hypoglycaemic agents were tested on two separate occasions: following an overnight fast and 2 h after a 395-kcal standardised breakfast. Exercise was performed at 60% of [Formula: see text]O(2peak) on a cycle ergometer for 60 min. Blood samples were drawn at rest for baseline values and following 60 min of exercise and 30 min of recovery. Our results show that: (1) baseline levels of TC, FC and AC were similar in fasted and postprandial groups, (2) TC and AC levels were increased during exercise in the fasted group only, (3) FC levels were decreased during exercise in both fasted and postprandial state and (4) the AC/FC ratio increased during exercise in the fasted group. Our results indicate that the metabolic state of the diabetic patient is associated with a different plasma carnitine status. These patterns may reflect differences in energy metabolism associated with fasting and postprandial hyperglycaemia.

A newly synthesised molybdenum/ascorbic acid complex alleviates some effects of cardiomyopathy in streptozocin-induced diabetic rats.

BACKGROUND: Exogenous insulin does not prevent cardiac failure in patients with type 1 diabetes mellitus and a cardioprotective insulin mimic is greatly needed. Certain transition metals are known to act as insulin mimics and may be cardio- protective. In this study, the ability of a newly synthesised molybdenum/ascorbic acid complex to strengthen cardiac function was investigated. METHODS AND DESIGN: Male CD rats were assigned to one of five groups: non-diabetic control, non-diabetic control treated with molybdenum/ascorbic acid complex, diabetic treated with sodium ascorbate, diabetic treated with molybdenum/ascorbic acid complex and untreated diabetics. Type 1 diabetes was induced by streptozocin injection. Once diabetes was confirmed, treatment was initiated by adding either the molybdenum/ascorbic acid complex or sodium ascorbate to the drinking water and continued for 6 weeks. Following the treatment period, the animals were terminated, and their hearts were excised and mounted in a working heart perfusion apparatus. Blood samples were taken for plasma glucose and plasma lipid level determination. Cardiac function was evaluated using 1 hour of low-flow ischaemic stress followed by 30 minutes of reperfusion. RESULTS: Hearts from the animals treated with the molybdenum/ascorbic acid complex displayed the best aerobic performance of all the diabetic animals. Blood glucose levels and blood lipid levels were significantly lower in animals treated with the complex than in other diabetic animals. The group treated with the complex also had a lower drinking rate than the other diabetic groups. Furthermore, hearts from animals treated with the molybdenum/ascorbic acid complex showed a greater degree of recovery from low-flow ischaemia than any other group. CONCLUSIONS: The molybdenum/ascorbic acid complex showed some significant insulin-mimic and cardioprotective effects. Further development of this complex could provide a drug useful for alleviating some of the cardiovascular problems associated with diabetes mellitus.

Gut transport of a molybdenum/ascorbic acid complex.

BACKGROUND: Relatively little work has been done on the absorption of trace elements in the mammalian small intestine. Recently, studies have demonstrated that a molybdenum/ascorbic acid complex has shown some promise as a potentially orally administered insulin-mimetic agent. However, the transport mechanism of the molybdenum/ascorbic acid complex is unknown. In this study we examine some aspects of the movement of the complex across the intestinal wall using measurements of elemental molybdenum as an indicator because it is not possible to measure the complex directly. METHODS: Everted rat small intestine sacs were used to determine some aspects of the transport of the complex across the intestine. Intestinal sacs from five rats were incubated in a medium containing 1 g/L of the molybdenum complex. Sacs from a further five rats had 1 mmol/L of 2,4-dinitrophenol, a known inhibitor of oxidative phosphorylation, added to the incubation medium. In a second experiment, everted sacs from five rats were also incubated in media containing one of six concentrations of the molybdenum complex (0.5, 1, 2, 4, 8 or 10 g/L). RESULTS: There was no significant difference between transport rates of groups with or without 2,4-dinitrophenol in the incubation medium, suggesting that the predominant mechanism of molybdenum transport is energy-independent. There was a significant positive, linear increase in the transport rate with increasing concentration of the molybdenum complex. CONCLUSION: These data suggest that the predominant mechanism of this molybdenum/ascorbic acid complex transport in the small intestine is non-saturable and therefore not protein-mediated.

Cardiac function and ischaemic tolerance during acute loss of metabolic control in the diabetic BB Wor rat.

The effect of loss of metabolic control, by with-holding insulin treatment, on reperfusion recovery of cardiac function following ischaemia was studied in the spontaneously diabetic "BB" Wor rat. The study involved a group of insulin-treated diabetic BB rats (insulin-treated) and diabetic BB rats in which insulin treatment was withheld 24 h prior to study (insulin-withdrawn). Hearts were isolated and perfused at a constant left atrial filling pressure of 15 cm H(2)O and aortic afterload resistances of 100 and 140 cm H(2)O. Hearts were then subjected to 20 min of ischaemia followed by 30 min of reperfusion. Withdrawing insulin treatment from the BB Wor rat resulted in a dramatic increase in the levels of plasma glucose and free fatty acids. Hearts from these rats perfused under aerobic conditions demonstrated reductions in heart rate, positive and negative dP/dt, cardiac output and left ventricular minute work, whereas diastolic pressure was elevated. Following ischaemia, recovery of cardiac function in the insulin-treated BB Wor rat returned to preischaemic levels, whereas hearts from insulin-withdrawn rats displayed impaired recovery. Throughout reperfusion, heart rate, positive dP/dt, cardiac output and left ventricular minute work remained significantly lower in hearts from insulin-withdrawn rats compared to treated rats. Our results indicate that acute loss of metabolic control increases the sensitivity of the heart to ischaemia, even in the acutely diabetic BB Wor rat.

Benign metastasizing leiomyoma.

Benign metastasizing leiomyoma is a rare clinical entity that has been described in several previous reports. Although the exact pathophysiology of the disease is unknown, two predominant theories exist: (1) metastasis from an existing leiomyoma (commonly seen with uterine leiomyoma) or (2) multicentric leiomyomatous growths rather than actual metastases. We present an interesting case in which several elements of the patient's history complicated the differential diagnosis.

Short-term carnitine deficiency does not alter aerobic rat heart function but depresses reperfusion recovery after ischemia.

Clinical and experimental studies have shown that long-term carnitine deficiency is often associated with cardiomyopathy and ischemic failure. The present study was designed to determine whether cardiac dysfunction is seen in an experimental model of short-terrm carnitine deficiency. Carnitine deficiency was induced in Sprague-Dawley rats by supplementing the drinking water with sodium pivalate for a period of 2 weeks. This resulted in a 25% depletion of total myocardial carnitine content. When isolated working hearts from these animals were paced and subjected to increments in left atrial filling pressure, there were no differences in mechanical function compared with control hearts. Following no-flow ischemia, however, recovery of cardiac output and relaxation parameters was depressed in hearts from pivalate-treated animals. Under these conditions, L-carnitine prevented the depressions of function from occurring. Our results show that short-term carnitine deficiency is not associated with cardiac dysfunction under normoxic conditions. However, hearts from pivalate-treated animals are more susceptible to ischemic injury and thus may prove to be useful for the study of metabolic and functional aspects of carnitine deficiency.

Leukocyte-platelet aggregation, platelet surface P-selectin, and platelet surface glycoprotein IIIa after percutaneous coronary intervention: Effects of dalteparin or unfractionated heparin in combination with abciximab.

BACKGROUND: Plaque disruption with resultant platelet activation and leukocyte-platelet aggregation is a pathophysiologic process common to both acute coronary syndromes and percutaneous coronary interventions. Unfractionated heparin is a standard antithrombotic therapy in patients with both acute coronary syndromes and in those undergoing percutaneous coronary interventions. Low-molecular-weight heparins have been reported to cause less platelet activation than unfractionated heparin. METHODS: Monocyte-platelet aggregates, neutrophil-platelet aggregates, platelet surface P-selectin, and platelet surface glycoprotein (GP) IIIa were measured serially by whole blood flow cytometry in 40 patients with unstable angina (randomly assigned to either unfractionated heparin 70 U/kg or the low-molecular-weight heparin dalteparin 60 IU/kg) undergoing coronary intervention with planned abciximab administration (in 2, one-half-dose boluses). Assays were performed at baseline, 5 minutes after administration of either type of heparin, 10 minutes after the first bolus of abciximab, 10 minutes after second bolus of abciximab, and 8 to 10 and 16 to 24 hours after administration of either heparin. RESULTS: No significant differences in clinical outcomes were observed between patients receiving either unfractionated heparin or dalteparin. The number of circulating P-selectin-positive platelets was increased by unfractionated heparin but not dalteparin, and abciximab reversed this increase. The number of circulating P-selectin-positive platelets was reduced below baseline levels in both treatment groups 8 to 10 and 16 to 24 hours after study drug administration. At 8 to 10 and 16 to 24 hours after administration of study drug, platelet degranulation in response to iso-thrombin receptor agonist peptide 1.5 mmol/L was significantly reduced by almost 50% (compared with immediately after study drug administration). Both unfractionated heparin and dalteparin significantly increased the numbers of circulating monocyte-platelet and neutrophil-platelet aggregates, which were subsequently reduced to baseline levels after administration of the second abciximab bolus and to below baseline at both 8 to 10 and 16 to 24 hours in all patients. After both unfractionated heparin and dalteparin administration, platelet surface GP IIIa expression was significantly increased compared with baseline at both 8 to 10 and 16 to 24 hours. CONCLUSIONS: Dalteparin in combination with abciximab in patients with unstable angina undergoing coronary intervention appears to be safe. Unfractionated heparin, but not dalteparin, degranulates platelets in patients with unstable angina. Both heparins increase the number of circulating monocyte-platelet and neutrophil-platelet aggregates. Abciximab therapy during coronary interventions rapidly reduces the number of degranulated platelets and leukocyte-platelet aggregates.

Laparoscopic telescope with alpha port and aesop to view open surgical procedures.

Laparoscopy has advanced surgery by allowing the surgeon to operate within a patient's abdominal and pelvic cavity with minimal trauma and scarring. The coupling of a video camera to the laparoscopic telescope has had the secondary effect of allowing others to view the surgical field either on color video monitors or by watching the video feed over the Internet at a remote location. These advancements have allowed better teaching and mentoring of operations. Open procedures can benefit from this technology as well but have suffered in the past from inadequate methods to depict the open surgical field. We used the Alpha Port and Aesop robot to position a sterile laparoscopic telescope near the surgical field to view open cholecystectomies performed on five pigs and to send the video feed over the Internet to remote physicians. Viewing the video on the monitor, the surgeons performed the operation in a comfortable ergonomic upright position. Both the surgeons and the remote physicians found the quality of the video to be excellent, and the remote physicians felt comfortable learning and mentoring surgical procedures using this technique.

Real-time Internet connections: implications for surgical decision making in laparoscopy.

OBJECTIVE: To determine whether a low-bandwidth Internet connection can provide adequate image quality to support remote real-time surgical consultation. SUMMARY BACKGROUND DATA: Telemedicine has been used to support care at a distance through the use of expensive equipment and broadband communication links. In the past, the operating room has been an isolated environment that has been relatively inaccessible for real-time consultation. Recent technological advances have permitted videoconferencing over low-bandwidth, inexpensive Internet connections. If these connections are shown to provide adequate video quality for surgical applications, low-bandwidth telemedicine will open the operating room environment to remote real-time surgical consultation. METHODS: Surgeons performing a laparoscopic cholecystectomy in Ecuador or the Dominican Republic shared real-time laparoscopic images with a panel of surgeons at the parent university through a dial-up Internet account. The connection permitted video and audio teleconferencing to support real-time consultation as well as the transmission of real-time images and store-and-forward images for observation by the consultant panel. A total of six live consultations were analyzed. In addition, paired local and remote images were "grabbed" from the video feed during these laparoscopic cholecystectomies. Nine of these paired images were then placed into a Web-based tool designed to evaluate the effect of transmission on image quality. RESULTS: The authors showed for the first time the ability to identify critical anatomic structures in laparoscopy over a low-bandwidth connection via the Internet. The consultant panel of surgeons correctly remotely identified biliary and arterial anatomy during six laparoscopic cholecystectomies. Within the Web-based questionnaire, 15 surgeons could not blindly distinguish the quality of local and remote laparoscopic images. CONCLUSIONS: Low-bandwidth, Internet-based telemedicine is inexpensive, effective, and almost ubiquitous. Use of these inexpensive, portable technologies will allow sharing of surgical procedures and decisions regardless of location. Internet telemedicine consistently supported real-time intraoperative consultation in laparoscopic surgery. The implications are broad with respect to quality improvement and diffusion of knowledge as well as for basic consultation.

Prior meal enhances the plasma glucose lowering effect of exercise in type 2 diabetes.

PURPOSE: To compare the changes in plasma glucose and insulin levels in response to 1 h of exercise performed at 60% of VO(2peak) either in the fasted state or 2 h after a standardized breakfast in subjects with type 2 diabetes. METHODS: Ten sedentary men with type 2 diabetes treated with oral agents and not under strict metabolic control were tested on two occasions (fasted and fed state) in a random order at a 1-wk interval. RESULTS: Plasma glucose was slightly but not significantly higher at the beginning of exercise performed in the fed state versus the fasted state (12.4 +/- 1.3 vs 11.1 +/- 1.1 mmol x L(-1) respectively; mean +/- SE, P = 0.06). However, after exercise, plasma glucose levels were much lower in the fed state (7.6 +/- 1.1 mmol x L(-1)) compared with the fasted state (10.0 +/- 1.0 mmol x L(-1); P = 0.009). Insulin levels were higher at the beginning of the exercise bout performed in the fed state (177 +/- 26 vs 108 +/- 19 pmol x L(-1); P < 0.05) and during exercise. Similar respiratory exchange ratio at identical workload indicated that the difference in glycemic response was not due to differences in whole body substrate utilization. Plasma concentrations of free fatty acids, glucagon, epinephrine, and norepinephrine were also similar during both experiments. CONCLUSIONS: One hour of aerobic exercise has a minimal impact on plasma glucose level when performed in fasted moderately hyperglycemic men with type 2 diabetes but induces an important decrease in plasma glucose level when performed 2 h after breakfast. Because glucose utilization increased similarly during exercise in both conditions, the higher insulin levels after the meal might have blunted glucose production, creating an imbalance between total glucose production and total peripheral utilization in the fed state in contrast to the fasted state.