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Objective: This work aimed to investigate the effect of the SGLT2 inhibitor, dapagliflozin (DAPA), on cardiac function and the metabolic and hormonal response to moderate exercise in people with type 2 diabetes. Methods: This was a double-blind, placebo-controlled crossover study with a 4-week washout period. Nine participants were randomly assigned to receive either 4 weeks of DAPA or 4 weeks of placebo. After each treatment, they underwent an exercise protocol with 2 consecutive 10- minute stages at a constant load corresponding to 40% and 70% maximal oxygen consumption (VO2max), coupled with hormonal and metabolic analysis. A blinded transthoracic echocardiogram was performed 3 days later. Results: During the exercise protocol, glucose and lactate were lower (P<.0001 and P<.05, respectively) and β-hydroxybutyrate (BOBH) and growth hormone (GH) were higher (P<.0005 and P= .01) following DAPA treatment compared to placebo. There was a trend for lower insulin with DAPA. Adrenalin, noradrenalin, and glucagon were not different. Following DAPA participants demonstrated an increased mean peak diastolic mitral annular velocity (e') in comparison to placebo (P=.03). The indexed left atrial volume and right ventricular e" were reduced following DAPA compared with placebo (P=.045 and P=.042, respectively). Arterial stiffness was not different between treatments (DAPA 9.35±0.60 m/s; placebo 9.07±0.72 m/s). Conclusion: During exercise, GH may be more important than catecholamines in driving the shift from glucose to fatty acid metabolism by SGLT2 inhibitors. The 4-week crossover design showed changes in cardiac function were rapid in onset and reversible. [ABSTRACT FROM AUTHOR]

Protein loss leading to reduced lean body mass is recognized to contribute to the high levels of morbidity and mortality seen in critical illness. This prospective, randomized, controlled study compared the effects of conventional parenteral nutrition (TPN), glutamine-supplemented (0.4 g * [kg.sup.-1] * [day.sup.-1]) TPN (TPNGLN), and TPNGLN with combined growth hormone (GH, 0.2 IU * [kg.sup.-1] * [day.sup.-1]) and IGF-I (160 [micro]g * [kg.sup.-1] * [day.sup.-1]) on protein metabolism in critical illness. Nineteen mechanically ventilated subjects [64 [+ or -] 3 yr, body mass index (BMI) 23.8 [+ or -] 1.3, kg/[m.sup.2]] were initially studied in the fasting state (study 1) and subsequently after 3 days of nutritional with/without hormonal support (study 2). All had recently been admitted to the ICU and the majority were postemergency abdominal surgery (APACHE II 17.5 [+ or -] 1.0). Protein metabolism was assessed using a primed constant infusion of [1-[sup.13]C]leucine. Conventional TPN contained mixed amino acids, Intralipid, and 50% dextrose. TPNGLN, unlike TPN alone, resulted in an increase in plasma glutamine concentration (~50%, P < 0.05). Both TPN and TPNGLN decreased the rate of protein breakdown (TPN 15%, P < 0.002; TPNGLN 16%, P < 0.05), but during these treatments the patients remained in a net negative protein balance. Combined treatment with TPNGLN + GH/IGF-I increased plasma IGF-I levels (10.3 [+ or -] 0.8 vs. 48.1 [+ or -] 9.1 nmol/l, study 1 vs. study 2, P < 0.05), and in contrast to therapy with nutrition alone, resulted in net protein gain (-0.75 [+ or -] 0.14 vs. 0.33 [+ or -] 0.12 g protein * [kg.sup.-1] * [day.sup.-1], study 1 vs. study 2, P < 0.05). Therapy with GH/IGF-I + TPNGLN, unlike nutrition alone, resulted in net positive protein balance in a group of critically ill patients. metabolism; leucine; humans; intensive care; total parenteral nutrition

Abnormal lipid metabolism may be related to the increased cardiovascular risk in type I diabetes. Secretion and clearance rates of very low density lipoprotein (VLDL) apolipoprotein B100 (apoB) determine plasma lipid concentrations. Type 1 diabetes is characterized by increased growth hormone (GH) secretion and decreased insulin-like growth factor (IGF) I concentrations. High-dose IGF-I therapy improves the lipid profile in type 1 diabetes. This study examined the effect of low-dose (40 [micro]g * [kg.sup.-1] * [day.sup.-1]) IGF-I therapy on VLDL apoB metabolism, VLDL composition, and the GH-IGF-I axis during euglycemia in type 1 diabetes. Using a stable isotope technique, VLDL apoB kinetics were estimated before and after 1 wk of IGF-I therapy in 12 patients with type 1 diabetes in a double-blind, placebo-controlled trial. Fasting plasma triglyceride (P < 0.03), VLDL-triglyceride concentrations (P < 0.05), and the VLDL-triglyceride-to-VLDL apoB ratio (P < 0.002) significantly decreased after IGF-I therapy, whereas VLDL apoB kinetics were not significantly affected by IGF-I therapy. IGF-I therapy resulted in a significant increase in IGF-I and a significant reduction in GH concentrations. The mean overnight insulin concentrations during euglycemia decreased by 25% after IGF-I therapy. These results indicate that low-dose IGF-I therapy restores the GH-IGF-I axis in type 1 diabetes. IGF-I therapy changes fasting triglyceride concentrations and VLDL composition probably because of an increase in insulin sensitivity. type 1 diabetes mellitus; insulin-like growth factor I; growth hormone secretion; very low density lipoprotein apolipoprotein B turnover study; stable isotope technique

The method developed by Biolo et al is used in measuring whole body leucine transport across the cell membranes under steady-state conditions in 10 healthy human subjects. It uses an arteriovenous balance technique of stable-label amino acid tracers. Measurements are given in terms of the ratio of u with deltaTTR, where u is the infusion rate of leucine tracer and deltaTTR is the difference between the tracer-to-tracee ratio of extracellular and intracellular leucine.

Research was conducted on the pharmacokinetics of recombinant human insulin-life growth factor I (IGF-I) in four healthy human subjects by a 3-h infusion at a rate of 20 micron g.kg-1.h-1. To simulate the plasma 'free' IGF-I and IGF-I associated with the 50- and 150-kDa plasma protein fractions, a compartmental model was used. Results indicate that higher concentrations of IGFBP-3 would increase the estimate of metabolic clearance rate for free IGF-I by reducing free IGF-I concentration. The model will be valuable for simulation of dynamic profiles of IGF-I.

Abstract Background Psychometric properties of two measures of psychological well-being were evaluated for adults with growth hormone deficiency (GHD): the General Well-being Index, (GWBI) – British version of the Psychological General Well-being Index, and the 12-item Well-being Questionnaire (W-BQ12). Methods Reliability, structure and other aspects of validity were investigated in a cross-sectional study of 157 adults with treated or untreated GHD, and sensitivity to change in a randomised placebo-controlled study of three months' growth hormone (GH) withdrawal from 12 of 21 GH-treated adults. Results Very high completion rates were evidence that both questionnaires were acceptable to respondents. Factor analyses did not indicate the existence of useful GWBI subscales, but confirmed the validity of calculating a GWBI Total score. However, very high internal consistency reliability (Cronbach's alpha = 0.96, N = 152), probably indicated some item redundancy in the 22-item GWBI. On the other hand, factor analyses confirmed the validity of the three W-BQ12 subscales of Negative Well-being, Energy, and Positive Well-being, each having excellent internal reliability (alphas of 0.86, 0.86 and 0.88, respectively, N from 152 to 154). There was no sign of item redundancy in the highly acceptable Cronbach's alpha of 0.93 (N = 148) for the whole W-BQ12 scale. Whilst neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations (for GH-treated patients) with duration of GH treatment for GWBI Total (r = -0.36, p = 0.001, N = 85), W-BQ12 Total (r = 0.35, p = 0.001, N = 88) and for all W-BQ12 subscales: thus the longer the duration of GH treatment (ranging from 0.5 to 10 years), the better the well-being. Both questionnaires found that men had significantly better overall well-being than women. The W-BQ12 was more sensitive to change than the GWBI in the GH-Withdrawal study. A significant between-group difference in change in W-BQ12 Energy scores was found [t(18) = 3.25, p = 0.004, 2-tailed]: patients withdrawn from GH had reduced energy at end-point. The GWBI found no significant change. Conclusion The W-BQ12 is recommended in preference to the GWBI to measure well-being in adult GHD: it is considerably shorter, has three useful subscales, and has greater sensitivity to change.