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ADMA (asymmetric dimethylarginine), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations in plasma glucose and insulin on plasma ADMA levels in young people with T1D (Type 1 diabetes). Fifteen young patients (ten males) with T1D, median age 18.3 (13.2–24.4) years, HbA1c (glycated haemoglobin) 9% (6.4–13.6%), underwent an overnight (18:00–08:00 hours) variable insulin infusion for euglycaemia, followed by a hyperinsulinaemic–euglycaemic clamp (08:00–12:00 hours). Blood samples were collected every 15 min for determination of ADMA, SDMA (symmetric dimethylarginine), valine, phenylalanine, arginine, creatinine and glucose. Insulin levels were assessed every 30 min. During the overnight period, glucose levels increased following the evening meal. In response to the protein intake there was a significant increase in ADMA, arginine, valine, phenylalanine and creatinine. For the remaining part of the night, glucose levels progressively decreased reaching 5 mmol/l by 04:00 hours. ADMA and SDMA did not change significantly. During the hyperinsulinaemic clamp, a significant fall in ADMA was observed, from 0.468±0.056 to 0.364±0.050 μmol/l (P<0.001). A significant fall was also found in SDMA, valine, phenylalanine, arginine and the ADMA/SDMA ratio (all P<0.001), but not in creatinine levels. No correlation was found between insulin sensitivity and ADMA. We conclude that acute changes in glycaemia do not significantly affect plasma ADMA levels whereas infusion of insulin significantly reduces ADMA, suggesting an important role for insulin in the regulation of this cardiovascular risk factor. [ABSTRACT FROM AUTHOR]

AbstractBackground:This study examined parental attitudes towards overnight closed-loop (CL) glucose control in children and young people with type 1 diabetes (T1D).Methods:Twelve families recruited by the INsulin PUmp Therapy group (INPUT), a U.K. patient/carer-led support group for people with T1D, attended a focus meeting on CL. The concept of CL was explained, and clinical results and plans regarding the Artificial Pancreas Project at Cambridge were presented. Participants completed a questionnaire to evaluate parental feelings about T1D management and attitudes towards overnight CL insulin delivery.Results:Nineteen parents (12 mothers and seven fathers) anonymously completed the questionnaire. Main concerns about diabetes were related to long-term complications (84%) and hypoglycemia (16%). Achieving good glucose control represented major challenge for carers (83%) with nighttime being the most difficult period to manage (56%), worrying most parents (71%) particularly because of fear of hypoglycemia (33%). The development of CL to manage diabetes was welcomed by all parents (100%) with 95% happy for their child to wear a continuous glucose monitor together with an insulin pump. All parents were ready to respond to additional alarms at night with 90% parents not worried about their child's overnight insulin delivery being controlled by a computer.Conclusions:Selected parents of children with T1D who are already insulin pump users express implied trust in the technology for overnight CL insulin delivery. Nighttime blood glucose control is the biggest challenge and concern for parents, and the development of a commercially available overnight CL system may be an important goal. [ABSTRACT FROM AUTHOR]

Increased levels of IMCL (intramyocellular lipid) have been shown to be associated with reduced steady-state glucose infusion rates during a hyperinsulinaemic–euglycaemic clamp (M-value). The aim of the present study was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production [hepatic SI (insulin sensitivity)] and increase in glucose disposal (peripheral SI). In the present study, 11 healthy young adults (7 male, 4 female; aged 21–31 years) undertook, in random order, an hyperinsulinaemic–euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic SI, a 1H-MRS (proton-magnetic resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X-ray absorptiometry) scan to assess body composition. IMCL levels (range, 3.2–10.7) were associated with whole-body fat mass (r=0.787, P=0.004), fat mass corrected for height (r=0.822, P=0.002) and percentage of central fat mass (r=0.694, P=0.02), but were not related to whole-body FFM (fat-free mass; r=−0.472, P=0.1). IMCL levels correlated closely with the M-value (r=−0.727, P=0.01) and FFM-corrected peripheral SI (r=−0.675, P=0.02), but were not related to hepatic SI adjusted for body weight (r=0.08, P=0.8). The results of the present study suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral, but not hepatic, SI in normal populations. Given the close relationship of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in SI. [ABSTRACT FROM AUTHOR]