Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes

BACKGROUND: Obesity and type 2 diabetes (T2DM) are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM. METHODOLOGY/PRINCIPAL FINDINGS: Lipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD)-induced reduction in lysophosphatidylcholine (LPC) levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients. CONCLUSION: Irrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile

A case of serendipity*

An account is given of how a sensitive bioassay system for measurement of the neurotransmitter acetylcholine serendipitously led to the identification of adenosine triphosphate (ATP) released in vitro from active skeletal muscle. Subsequent application of the identification procedures to exercising human muscle in vivo, cardiac muscle cells in vitro, and human erythrocytes exposed to hypoxia gave rise to the general concept of ATP as a molecule that could influence cell function from the extracellular direction. Mechanisms of ATP release from cells in terms of “trigger” events such as mechanical distortion of the membrane, depolarization of the membrane, and exposure to hypoxia are discussed. Potential therapeutic uses of extracellular ATP in cancer therapy, radiation therapy, and a possible influence upon aging are discussed. Possible roles (distant and local) of extracellular ATP released from muscle during whole body exercise are discussed

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Neurocognitive therapeutic exercise improves pain and function in patients with shoulder impingement syndrome: A single-blind randomized controlled clinical trial

Background: Traditional rehabilitation improves pain and function in patients with shoulder impingement syndrome. Neurocognitive rehabilitation has shown to be highly effective after surgical reconstruction of the anterior cruciate ligament. However, its effects in patients with shoulder impingement syndrome have not yet been established. Aim: The aim of the study was to compare the effects of neurocognitive therapeutic exercise, based on proprioception and neuromuscular control, on pain and function in comparison to traditional therapeutic exercise in patients with shoulder impingement syndrome. Design: Single-blind randomized, non-inferiority clinical trial. Setting: Outpatient clinic of Geriatrics and Physiatrics, University Hospital. Population: Forty-eight patients with shoulder impingement syndrome (Neer stage I) and pain lasting for at least three months. Methods: Participants were randomly allocated (1:1) to either neurocognitive therapeutic exercise or traditional therapeutic exercise. Both treatments were provided one-hour session, three times a week for five weeks. The primary outcome measure was the short form of the Disability of the Arm, Shoulder and Hand Questionnaire (Quick-DASH questionnaire) for the assessment of physical ability and symptoms of the upper extremity. Secondary outcome measures: Constant-Murley shoulder outcome score for the determination of range of motion, pain and strength; American Shoulder and Elbow Surgeons Society standardized shoulder assessment form for the evaluation of physical ability in daily-living tasks; a visual analogue scale for pain assessment at rest and during movements; Likert score for the estimation of participant satisfaction. Endpoints: before treatment, end of treatment, 12 and 24 weeks after the completion of each intervention for all outcome measures, except for the Likert score that was evaluated only at the end of treatment. Follow-up: 24 weeks. Results: At the end of treatment and at follow-up, both treatment groups experienced improvements in all outcomes measures relative to baseline values, except for the visual analogue scale at rest that was unaffected by traditional therapeutic exercise. For all outcome measures, changes over time were greater in the neurocognitive therapeutic exercise group relative to the traditional therapeutic exercise group. The level of satisfaction with treatment was higher for participants in the neurocognitive therapeutic exercise group. Conclusion: Neurocognitive rehabilitation is effective in reducing pain and improving function in patients with shoulder impingement syndrome, with benefits maintained for at least 24 weeks. Clinical Rehabilitation Impact. In patients affected by shoulder impingement syndrome, pain, range of motion, skills and function of the shoulder can greatly benefit from neurocognitive rehabilitation