The influence of synaptic activity on neuronal health

According to the theory of neuronal health, neurons exist in a spectrum of states ranging from highly resilient to vulnerable. An unhealthy neuron may be rendered dysfunctional or non-viable by an insult that would ordinarily be non-toxic to a healthy neuron. Over the years it has become clear that a neuron’s health is subject to dynamic regulation by electrical or synaptic activity. This review highlights recently identified activity dependent signalling events which boost neuronal health through the transcriptional control of pro- and anti-apoptotic genes, the enhancement of antioxidant defences, and the regulation of mitochondrial and neurotrophic factor availability. Furthermore, activity dependent signals have recently been shown to influence a variety of events specific to individual neurodegenerative diseases, which will also be highlighted

Specific effects of biliopancreatic diversion on the major components of metabolic syndrome: along-term follow-up study

OBJECTIVE: Gastric bypass and biliopancreatic diversion (BPD) are known to have a beneficial effect on glucose metabolism superior to that of the other bariatric operations. Thanks to its excellent weight loss results and to its specific actions, BPD has proven able to guarantee permanent normalization of serum glucose, triglyceride, and cholesterol levels in the vast majority, if not the totality, of operated patients. However, clinical studies on the duration of these effects in large patient populations are still lacking. RESEARCH DESIGN AND METHODS: The files of 312 BPD obese patients with type 2 diabetes operated on from June 1984 to January 1993 were examined. Pre- and postoperative serum glucose, triglyceride, and cholesterol levels, along with arterial pressure measurements, were considered. RESULTS: After BPD, fasting serum glucose concentration fell within normal values in all but two of the operated subjects and remained in the physiological range in all but six up until 10 years. Serum triglyceride and total cholesterol steadily normalized in all subjects with abnormally high preoperative values, and arterial hypertension disappeared in the vast majority of the preoperatively hypertensive patients. CONCLUSIONS: BPD proved able to reverse all the major components of the metabolic syndrome in nearly all the operated subjects, with results being strictly maintained over a 10-year follow-up period. This outcome, which far exceeds those following similar weight loss at short or long term obtained by any other means, confirms the existence of specific actions of BPD on the major components of metabolic syndrome

The long-term impact of biliopancreatic diversion on glycemic control in the severely obese with type 2 diabetes mellitus in relation to preoperative duration of diabetes.

Background: Bariatric surgery has been shown to beeffective in severely obese patients with type 2 diabetes mellitus(T2DM). Objective: Evaluate the long-term efficacy of biliopancreatic diversion (BPD) for the treatmentof T2DM depending on the preoperative duration of T2DM. Setting: University Hospital.Methods: Retrospective analysi sinvestigating 2 subsets of severely obese patients who had undergone BPD from1984 to1995.The first included 52 patients witha preoperative T2DM duration of 1 year (SD group \u2013 49 on orala gents and 3 oni nsulin),and thesecond included 68 patients who had been diabeticfor 4 5 years before BPD (LD group \u2013 52 on ora lagents and 16on insulin). Postoperatively, T2D T2DM was regarded as in remission when fasting serum glucose(FSG) was lower than100mg/dLon regular diet and without antidiabeti ctherapy. Results: In the SD patients ,the numbe ro findividuals without T2DM remission were lower both at 5\u201310 (0/31,0%of patients,versus 8/54,15 %of patients, p o .04) and at 4 15 years (1/28,3%of patients, versus10/41,24%ofpatients, p o .0012). Furthermore,afterBPD,thenumberofpatients with dyslipidemiastronglyreduced(p o .001) inbothgroups,valuesat5\u201310 years remaining very similar to those observedat 4 15 years. Conclusion: These reults indicate that severely obese patients with longer T2DMduration have a worse metabolic outcome maintained at long and very long term following BPD

Effects of Gastric Bypass on Type 2. Diabetes in Patients with BMI 30 to 35

BACKGROUND: This study aims to investigate if the benefits on glycemic control following Roux-en-Y gastric bypass (RYGB) in morbidly obese type 2 diabetes (T2DM) patients are maintained in the 30-35 kg/m2 BMI (body mass index) range, comparing results with those in literature. METHODS: The study participants were twenty T2DM patients aging 35-70 years, BMI 30.0-34.9 kg/m2, minimum diabetes duration 3 years, glycosylated haemoglobin (HbA1c) 657.5 % despite good clinical practice medical therapy, submitted to laparoscopic RYGB, and monitored during 36 months. Twenty-seven matched diabetic patients as controls. RESULTS: Five females, mean age 57 (42-69)\u2009years, weight 96.0 (70-111)\u2009kg, BMI 32.9 (30.3-34.9)\u2009kg/m2, waist circumference 112 (100-128)\u2009cm, diabetes duration 14 (3-28)\u2009years, HbA1c 9.5 (7.5-14.2)\u2009%, and C-peptide 3.2 (1,6-9.1)\u2009mcg/l. Ten patients were on insulin. There was no mortality, and there were two major late complications. BMI and waist decreased stabilizing around 25 kg/m2 and 92 cm. Fasting serum glucose and HbA1c reached values around 150 mg/dl and 7 %, which subsequently maintained. There was remission in 25 % of cases, control 45 %, and all the others improved. HOMA-IR and insulin sensitivity index normalized at 1 month, then maintained. AIR and insulinogenic index showed no postoperative changes. Diabetes remission correlated negatively with duration (p\u2009<\u20090.05; r 2\u2009=\u20090.61), while control positively with C-peptide (p\u2009<\u20090.05; r 2\u2009=\u20090.19). In the control group, FSG, HbA1c, serum triglyceride, and cholesterol significantly decreased with considerable progressive increase of antidiabetic/antihyperlipemic therapy. All patients had HbA1c >7 % at 2-3 years. CONCLUSIONS: Glycemic control obtained by RYGB in this study was less good than that reported by others, apparently due to different patient selection criteria. Our results do not support RYGB weight loss-independent effect on beta-cell function in the T2DM patients with BMI 30-35 kg/m2

Serum levels of osteopontin predict diabetes remission after bariatric surgery

AIM: Bariatric surgery has been shown to effectively improve glycaemic control in morbidly obese subjects. However, the molecular bases of this association are still elusive and may act independently of weight loss. Here, our retrospective study has investigated the inflammatory molecule osteopontin (OPN) as a potential predictor of type 2 diabetes mellitus (T2DM) remission. METHODS: Baseline serum levels of OPN were analyzed in 41 T2DM patients who underwent bariatric surgery. Anthropometric measures and biochemical variables, including insulin sensitivity indices (HOMA2), were assessed at baseline and at 1 and 3 years after surgery. RESULTS: At baseline, patients who experienced T2DM remission had increased waist circumference, body weight and BMI, and higher serum OPN, compared with non-remitters. Patients with and without T2DM remission improved their lipid and glucose profiles, although insulin-resistance indices were only improved in the T2DM remission group. In the overall cohort of both T2DM remission and non-remission patients, baseline circulating levels of OPN significantly correlated with reductions of body weight and BMI over time, and insulin sensitivity improved as well. However, only the HOMA2-%S remained independently associated with serum OPN on multivariate linear regression analysis (B: 0.227, 95% CI: 0.067-0.387, \u3b2\u2009=\u20090.831; P = 0.010). Baseline values of OPN predicted 3-year T2DM remission independently of body weight loss, lower BMI and duration of diabetes (OR: 1.046, 95% CI: 1.004-1.090; P\u2009=\u2009 0.033). CONCLUSION: Although larger studies are still needed to confirm our preliminary results, preoperative OPN serum levels might be useful for predicting 3-year T2DM remission independently of weight loss in patients undergoing bariatric surgery