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Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study cohort.
Mengozzi, A, Tricò, D, Nesti, L, Petrie, J, Højlund, K, Mitrakou, A, Krebs, M, Mari, A, Natali, A, ,
Metabolism: clinical and experimental. 2020;:154185
Abstract
BACKGROUND/AIMS: Uncertainty still exists on the earliest beta-cell defects at the bases of the type 2 diabetes. We assume that this depends on the inaccurate distinction between fasting and post-load glucose homeostasis and aim at providing a description of major beta-cell functions across the full physiologic spectrum of each condition. METHODS In 1320 non-diabetic individuals we performed an OGTT with insulin secretion modeling and a euglycemic insulin clamp, coupled in subgroups to glucose tracers and IVGTT; 1038 subjects underwent another OGTT after 3.5 years. Post-load glucose homeostasis was defined as mean plasma glucose above fasting levels (δOGTT). The analysis was performed by two-way ANCOVA. RESULTS Fasting plasma glucose (FPG) and δOGTT were weakly related variables (stβ = 0.12) as were their changes over time (r = -0.08). Disruption of FPG control was associated with an isolated and progressive decline (approaching 60%) of the sensitivity of the beta-cell to glucose values within the normal fasting range. Disruption of post-load glucose control was characterized by a progressive decline (approaching 60%) of the slope of the full beta-cell vs glucose dose-response curve and an early minor (30%) decline of potentiation. The acute dynamic beta-cell responses, neither per se nor in relation to the degree of insulin resistance appeared to play a relevant role in disruption of fasting or post-load homeostasis. Follow-up data qualitatively and quantitatively confirmed the results of the cross-sectional analysis. CONCLUSION In normal subjects fasting and post-load glucose homeostasis are largely independent, and their disruption is sustained by different and specific beta-cell defects.
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[Modern methods of energy homeostasis correction in elderly patients].
Rumiantseva, SA, Silina, EV, Tsukurova, LA, Stupin, VA, Chichanovskaia, LV, Nazarov, MV, Kovalenko, AL, Kabaeva, EN
Advances in gerontology = Uspekhi gerontologii. 2014;(4):746-52
Abstract
In the multicenter randomized clinical-instrumental prospective study 185 patients aged 55-75 years (mean age 68 years) with 94 men and 91 women with cerebral infarction were included. All the patients were hospitalized in the period from 6 to 24 hours from the time of the debut of clinical symptoms, 42,2% of patients scored 14 and above on NIH scale on admission. Patients were randomized into 3 groups: 1st group consisted of 64 patients treated as an antioxidant by 5% solution of ascorbic acid 2 times a day the recommended dose (20 ml/day) for 20 days; 2nd group consisted of 72 patients who received energy monitor Cytoflavin in a daily dose of 20 ml (10.0 ml/drip 2 times a day for 10 days); 3rd group consisted of 49 patients with Cytoflavin therapy extended to 20 days, moreover from 11th to 20th day the dose was 10 ml/day. Cytoflavin treatment was more efficient than ascorbic acid, which can be explained by different pharmacologic mechanisms. Treatment with Cytoflavin for 10 days resulted in a significant decrease of ischemia zone volume by 25% in average, treatment with Cytoflavin for 20 days--by 29%, which manifested in better outcomes in neurologic and functional status. Ascorbic acid demonstrated no effect on morphologic parameters. Patients having at the time of admission 18-20 points according to the NIH and treated with Cytoflavin for 20 days demonstrated significant trend towards improvement of the parameters of the neurological status.
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A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.
Wong, SC, Kumar, P, Galloway, PJ, Blair, JC, Didi, M, Dalzell, AM, Hassan, K, McGrogan, P, Ahmed, SF
Clinical endocrinology. 2011;(5):599-607
Abstract
BACKGROUND It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). AIMS To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. DESIGN AND SETTING Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. INTERVENTION Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. MAIN OUTCOME MEASURE Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. RESULTS Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. CONCLUSIONS Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.
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Insulin resistance in hypertensives: effect of salt sensitivity, renin status and sodium intake.
Raji, A, Williams, GH, Jeunemaitre, X, Hopkins, PN, Hunt, SC, Hollenberg, NK, Seely, EW
Journal of hypertension. 2001;(1):99-105
Abstract
OBJECTIVE Homeostasis Model Assessment (HOMA index) is predictive of insulin sensitivity in normal and diabetic patients. This study was designed to see if insulin resistance in hypertensives, measured using the HOMA index, differs, based on salt sensitivity, renin status and sodium intake. METHODS Fasting insulin and glucose were determined in subsets of 426 essential hypertensives, and normotensives. HOMA was calculated as fasting glucose (mmol) x fasting insulin (muU/ml)/22.5. RESULTS Four hundred and twenty-six essential hypertensives and normotensives from four HERMES centers form the basis of this report. There was no difference in the HOMA index between hypertensives and normotensives (P= 0.291) or between hypertensives grouped according to blood pressure salt sensitivity (P = 0.153). However, when essential hypertensives were subgrouped by renin status, the low-renin group had significantly lower (P< 0.01) HOMA index than the normal/high-renin group. When normal/high-renin group was divided into modulators and non-modulators, the nonmodulators had significantly higher HOMA index (P< 0.001) than other hypertensive subsets. The effect of sodium intake on the HOMA index was significant only for non-modulators (P< 0.002), with salt restriction increasing insulin resistance. CONCLUSION Insulin sensitivity differs among subsets of essential hypertension, non-modulators being most insulin resistant and the low-renin subset insulin sensitive. Salt restriction might have an adverse effect on insulin sensitivity in non-modulators. The reduction in cardiovascular risk seen in low-renin hypertensives may be related to their increased insulin sensitivity; in contrast, the clustering of cardiovascular risk factors seen in nonmodulators may be due to increased insulin resistance.
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Effect of propofol with and without EDTA on haemodynamics and calcium and magnesium homeostasis during and after cardiac surgery.
Wahr, J, Vender, J, Gilbert, HC, Spiess, B, Horrow, JC, Maddi, R
Intensive care medicine. 2000;:S443-51
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Abstract
OBJECTIVE To determine the effect of the addition of disodium edetate (EDTA) to propofol on haemodynamics, ionised calcium and magnesium serum concentrations, and adverse events during cardiac surgery. DESIGN Double-blind, randomised, multicenter trial. SETTING Operating room and intensive care unit of 5 academic health centres. PATIENTS A total of 102 evaluable patients, aged 34 to 85 years, undergoing first-time, elective coronary artery bypass graft surgery. INTERVENTIONS Comparison of propofol with EDTA and propofol without EDTA, each in conjunction with the opioid sufentanil, for intraoperative anaesthesia and postoperative sedation. MEASUREMENTS AND RESULTS There were no significant differences at any time between the two formulations in any clinical chemistry measurements, including ionised calcium, ionised magnesium, total calcium, parathyroid hormone, blood urea nitrogen, creatinine, sodium, potassium, and phosphate. During bypass, the mean concentration of ionised calcium decreased to below the normal range, but the decrease was similar in both groups (propofol with EDTA, 0.98 +/- 0.07 mmol/L [N = 51]; propofol, 0.99 +/- 0.10 mmol/ L [N = 51]; p = NS). Calcium concentration returned to normal after rewarming. Mean ionised magnesium concentrations remained within normal limits in both groups. Similarly, there were no clinically meaningful differences between treatments with respect to haemodynamic variables, efficacy variables, or incidence of adverse events. CONCLUSIONS The inclusion of EDTA in the current formulation of propofol appears to have no significant effects on calcium and magnesium profiles, renal function, haemodynamic variables, or other indicators of safety and efficacy during intraoperative anaesthesia and postoperative sedation in patients undergoing cardiac surgery.