The impact of diabetic autonomic neuropathy on the incretin effect

BACKGROUND: The aim of this study was to determine the effect of diabetic autonomic neuropathy (AN) on the incretin effect in patients with type 2 diabetes mellitus (DM2). MATERIAL/METHODS: Forty patients with DM2 (20 with and 20 without AN) and 10 healthy controls were studied. The subjects underwent an oral glucose tolerance test (OGTT) and 7-14 days later an intravenous infusion of 25 g glucose. Blood samples were drawn for glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) determination during the tests. The incretin effect was calculated from the total integrated amount of insulin or C-peptide during OGTT (A) and intravenous glucose infusion (B) according to the formula (A-B)/Ax100. RESULTS: Total insulin and C-peptide responses during OGTT were significantly higher than those after IV glucose infusion in the group of normal subjects, but not in the groups of diabetic patients. After the oral glucose load, GIP levels presented a significant increase in normal subjects and patients without AN, whereas GLP-1 levels increased only in normal subjects. Calculated either with the insulin or C-peptide responses, the incretin effect presented no significant difference between the two diabetic groups. However, using insulin responses, only the patients with AN had significantly lower incretin effect than controls, whereas when using C-peptide responses, both diabetic groups did. CONCLUSIONS: The incretin effect was impaired in both groups of diabetic patients. Autonomic neuropathy may further impair the incretin effect in DM2 through interference with GIP secretion or hepatic insulin extraction.     

Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

OBJECTIVE

To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations.

RESEARCH DESIGN AND METHODS

Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period.

RESULTS

Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 ± 8.8 vs. 295.6 ± 10.7 and 281.6 ± 9.8 kcal, P < 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P < 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P < 0.001) in all groups at 12 h in an intensity-dependent manner (P < 0.05). REE reached baseline after 48 h in the low- and moderate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P < 0.001) and remained elevated (P < 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 h and remained elevated for 24 h only in the high-intensity group (P < 0.001).

CONCLUSIONS

Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals.Aging is characterized by progressive impairment of carbohydrate intolerance and is usually accompanied by physical inactivity and obesity, which may induce hyperinsulinemia, insulin resistance, and cardiovascular disease (1). Obesity, a growing health concern, is characterized by low-grade inflammation, which is associated with insulin resistance and metabolic diseases such as diabetes (2).Leptin and adiponectin, adipose tissue–derived cytokine proteins, are involved in insulin resistance and inflammation (3). Leptin improves fatty acid oxidation in muscle, regulates short-term carbohydrate intake, mediates energy balance and body weight, and upregulates resting energy expenditure (REE) (3). Adiponectin is inversely related to body fatness and type 2 diabetes risk in healthy adults (4), has an anti-inflammatory action, and is involved in substrate metabolism (5,6). Aging increases body fat and leptin levels probably owing to an upregulation of leptin gene expression and is characterized by a negative association between adiponectin and body fat distribution (4).Exercise is believed to extend life-span by reducing the incidence of cardiovascular and other degenerative diseases and increases functional performance in older individuals (7). Regular exercise seems to create energy deficits that help to regulate body weight and fat on a long-term basis in older individuals (1). Chronic resistance exercise increases muscle tissue, reduces aging-related sarcopenia (8), and alters adipokine responses in elderly individuals (7). Acute resistance exercise may elevate lipid mobilization in subcutaneous adipose tissue, energy expenditure, and neuroendocrine responses of obese subjects (9). Although the American Diabetes Association endorses resistance exercise as a means of improving body composition and metabolic control in obesity and diabetes (2), limited information exists regarding the acute effects of resistance exercise on adipokine and REE responses in aging. Therefore, the purpose of the present investigation was to explore 1) the time course of leptin, adiponectin, and REE responses after a single resistance exercise bout in elderly individuals and 2) whether resistance exercise intensity represents an important factor in adipokine and REE responses in elderly individuals.     

A Case of Fatal Agranulocytosis That Developed in a Patient with β-Thalassemia Major Treated with Deferiprone

A 29-year-old male with transfusion-dependent β-thalassemia major (β-TM), splenectomized and on chelation therapy with deferiprone (DFP or L1) due to heart and liver hemosiderosis, presented with high fever and agranulocytosis. Deferiprone was discontinued and a broad spectrum antibiotic therapy was started intravenously. The patient remained febrile and showed no recovery of neutrophil count even after the initiation of granulocyte colony-stimulation factor (G-CSF). After 12 days at the hospital, he developed respiratory failure and was transferred to the intensive care unit (ICU) where he developed multi-organ failure and died 3 days later. To investigate the mechanism of agranulocytosis, bone marrow mononuclear cells of a healthy volunteer were plated on culture dishes, with or without the patient’s serum. The observation of colony forming units of progenitor cells in dishes that contained the patient’s serum, provided inconclusive explanation of the possible mechanism of DFP-induced agranulocytosis. This is a case of fatal agranulocytosis developing in a patient being treated with DFP, a well recognized but rare complication of this drug. Further studies are required in order to elucidate the possible pathogenic mechanism of agranulocytosis due to DFP and to provide clear guidelines in order to best care for the patient.     

New exposure technique for management of giant internal carotid artery aneurysm

We are presenting a case of giant internal carotid artery aneurysm (ICAA) managed by a new exposure technique. Following double mandibular osteotomy, the exposure of the entire aneurysm was achieved by mandible mobilization. The aneurysm repair was performed by resection and graft interposition. Mandible bone reconstruction was succeeded via mini plate osteosynthesis. No adverse events were noticed during the 24-month follow-up period. The surgical ICAA management is necessary to prevent severe complications. In cases of aneurysm extension to the skull base, double mandibular osteotomy is a safe technique that facilitates aneurysm exposure and control.     

Aseptic femoral head necrosis in a patient receiving long term courses of inhaled and intranasal corticosteroids

Aseptic (avascular) necrosis of the femoral head in adults has been associated with a variety of disease entities. It is also recognized as a potential complication of systemic corticosteroid therapy. Inhaled corticosteroids are the first line anti-inflammatory agents for the long term treatment of asthma. However, long term treatment of asthma with inhaled corticosteroids has been accompanied by concern about both systemic and topical side effects. The most worrying potential systemic effects are adrenal insufficiency, growth suppression, glaucoma and osteoporosis. Fluticasone proprionate may be prescribed at higher doses to relieve respiratory symptoms in the belief that it generates fewer side effects than other inhaled steroids. Studies have shown that fluticasone is safer than beclomethasone or budesonide, with limited oral absorption and extensive hepatic first pass metabolism leading to a lower systemic bioavailability. However growth retardation and asymptomatic adrenal suppression in children receiving high-dose fluticasone have been reported. We report a rare case of avascular osteonecrosis of the femoral head associated with the use of long term inhaled fluticasone propionate along with the intranasal application of triamcinolone acetonide.     

Genetic alterations of glutathione S-transferases in asthma: do they modulate lung growth and response to environmental stimuli?

Glutathione S-transferases (GSTs) constitute a super family of dimeric phase II metabolic enzymes that catalyze the conjugation of reduced glutathione with various electrophilic compounds and reactive oxygen species (ROS). Failure to detoxify ROS, as a sequel of altered GST genotype is able to aggravate the inflammatory cascade, promote bronchoconstrictor mechanisms, activate asthma-like symptomatology, and hamper lung development. Intriguingly, the same GST genotype can aggravate or improve physiological traits and maturation of respiratory system, from gestation to late adulthood. This article attempts to unravel the complex interaction of GST's genetic variations with "inner" and "outer", polymorphic and erratic, human environment (tobacco smoke, urban pollution, workplaces, and in utero status). Considering that these variations are very frequent among ethnicities and that GSTs play a part in respiratory system formation and maturation, they appear to be of great interest for the clinician and the researcher in this field.     

Bioabsorbable magnesium versus standard titanium compression screws for fixation of distal metatarsal osteotomies – 3 year results of a randomized clinical trial

Background

For the treatment of hallux valgus commonly distal metatarsal osteotomies are performed. Persistent problems due to the hardware and the necessity of hardware removal has led to the development of absorbable implants. To overcome the limitations of formerly used materials for biodegradable implants, recently magnesium has been introduced as a novel implant material. This is the first study showing mid-term clinical and radiological (MRI) data after using magnesium implants for fixation of distal metatarsal osteotomies.