The Adaptive Renal Response for Volume Homeostasis During 2 Weeks of Dapagliflozin Treatment in People With Type 2 Diabetes and Preserved Renal Function on a Sodium-Controlled Diet

Introduction: Proximal tubule sodium uptake is diminished following sodium glucose cotransporter 2 (SGLT2) inhibition. We previously showed that during SGLT2 inhibition, the kidneys adapt by increasing sodium uptake at distal tubular segments, thereby maintaining body sodium balance. Despite continuous glycosuria, we detected no increased urine volumes. We therefore assessed the adaptive renal responses to prevent excessive fluid loss. Methods: We conducted a mechanistic open-label study in people with type 2 diabetes mellitus with preserved kidney function, who received a standardized sodium intake (150 mmol/d) to evaluate the effects of dapagliflozin on renin-angiotensin-aldosterone system (RAAS) hormones, volume-related biomarkers, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), at start of treatment (day 4), end of treatment (day 14), and follow-up (day 18). Results: A total of 14 people were enrolled. Plasma renin and angiotensin II and urinary aldosterone and angiotensinogen were acutely and persistently increased during treatment with dapagliflozin. Plasma copeptin level was numerically increased after 4 days (21%). Similarly, fractional urea excretion was significantly decreased at start of treatment (−17%). Free water clearance was significantly decreased after 4 days (−74%) and 14 days (−41%). All changes reversed after dapagliflozin discontinuation. Conclusion: Dapagliflozin-induced osmotic diuresis triggers kidney adaptive mechanisms to maintain volume and sodium balance in people with type 2 diabetes and preserved kidney function. ClinicalTrials.gov (identification: NCT03152084)

What do young athletes implicitly understand about psychological skills?

One reason sport psychologists teach psychological skills is to enhance performance in sport; but the value of psychological skills for young athletes is questionable because of the qualitative and quantitative differences between children and adults in their understanding of abstract concepts such as mental skills. To teach these skills effectively to young athletes, sport psychologists need to appreciate what young athletes implicitly understand about such skills because maturational (e.g., cognitive, social) and environmental (e.g., coaches) factors can influence the progressive development of children and youth. In the present qualitative study, we explored young athletes’ (aged 10–15 years) understanding of four basic psychological skills: goal setting, mental imagery, self-talk, and relaxation. Young athletes (n = 118: 75 males and 43 females) completed an open-ended questionnaire to report their understanding of these four basic psychological skills. Compared with the older youth athletes, the younger youth athletes were less able to explain the meaning of each psychological skill. Goal setting and mental imagery were better understood than self-talk and relaxation. Based on these findings, sport psychologists should consider adapting interventions and psychoeducational programs to match young athletes’ age and developmental level

“It’s my dream to work with Olympic athletes”: Neophyte sport psychologists’ expectations and initial experiences regarding service delivery

We examined trainee practitioners' initial experiences of applied sport psychology practice. Semi-structured interviews (4) were conducted over 6 months with 7 full-time MSc students before, during, and after the applied sport psychology module, when they were working with clients. Participants also kept reflective diaries over an 8-week period whilst working with clients. Findings included: (a) motivations and expectations of an ASP practice career, (b) perceptions of service delivery, (c) emotional demands, and (d) pivotal experiences. Findings extend previous literature on the initial stages of practitioner development, providing micro-level detail on aspects of the intense development process during this pivotal perio

Irish athletes’ attitudes towards seeking sport psychology consultation

The aim of this study was to replicate previous research examining attitudes to sport psychology consultation conducted in the United States, Germany, and United Kingdom (Martin, Lavallee, Kellmann & Page, 2004), and New Zealand (Anderson, Hodge, Lavallee, & Martin, 2004). The study employed the Sport Psychology Attitudes-Revised (SPA-R) questionnaire (Martin, Kellman, Lavallee & Page, 2002) in order to develop an understanding of the attitudes elite Irish athletes (N=240) hold toward sport psychology and also compare these attitudes with those found in other countries. Irish athletes in this study reported a generally positive attitude toward sport psychology provision overall, and also were identified as being open to receiving sport psychology assistance, reported moderately high levels of confidence in sport psychology, and indicated the lack of accessibility and availability to these services as distinguishing factors. Comparison of results with athletes from other countries suggested that positive attitudes toward sport psychology may be based on factors not directly associated with personal experiences of sport psychology. As the provision of sport psychology increases, practitioners need to better understand athletes' attitudes toward sport psychology so they can tailor their services to best meet the needs of athletes. In order to do this, further research related to cultural and national differences is required

Effect of exenatide twice daily and dapagliflozin, alone and in combination, on markers of kidney function in obese patients with type 2 diabetes: A prespecified secondary analysis of a randomized controlled clinical trial

Aims: To evaluate the effects of separate and combined use of the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin and the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on measures of kidney function. Methods: In this prespecified secondary analysis of the DECREASE trial, we enrolled 66 obese patients with type 2 diabetes in a 16-week randomized double-blind placebo-controlled clinical trial to investigate the effects of dapagliflozin and exenatide twice daily, alone or in combination, versus placebo on 24-hour urinary albumin:creatinine ratio (UACR), creatinine and cystatin C-estimated glomerular filtration rate (GFR) and kidney injury molecule-1:creatinine ratio (KIM-1:Cr). Results: At week 16, the mean UACR change from baseline was −39.6% (95% confidence interval [CI] −58.6, −11.9; P = 0.001) in the combined exenatide-dapagliflozin group, −18.1% (95% CI −43.1, 18.0; P = 0.278) in the dapagliflozin group, −15.6% (95% CI −41.4, 21.6; P = 0.357) in the exenatide group and − 11.0% (95% CI −39.8, 31.5; P = 0.552) in the placebo group. Compared to placebo, UACR difference at week 16 in the exenatide-dapagliflozin group was −32.2% (95% CI −60.7, 16.9; P = 0.159). Effects were similar in 37 participants who were using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at baseline. Compared to placebo, in the exenatide-dapagliflozin group, an acute dip in estimated GFR was observed with creatinine-estimated GFR (−4.0 mL/min/1.73 m2 [95% CI −9.3, 1.2]; P = 0.129) and cystatin C-estimated GFR (−10.4 mL/min/1.73 m2 [95% CI −14.9, −5.8]; P < 0.001). The mean KIM-1:Cr difference in the combined treatment arm versus placebo was −43.8% (95% CI −73.5, 18.9; P = 0.129). Conclusion: This prespecified secondary analysis suggests that combined therapy with exenatide and dapagliflozin may have synergistic effects on markers of kidney function compared to either therapy alone or placebo in obese patients with type 2 diabetes

SGLT2 inhibition versus sulfonylurea treatment effects on electrolyte and acid-base balance: secondary analysis of a clinical trial reaching glycemic equipoise: Tubular effects of SGLT2 inhibition in Type 2 diabetes

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Exenatide once weekly decreases urinary albumin excretion in patients with type 2 diabetes and elevated albuminuria: Pooled analysis of randomized active controlled clinical trials

Aims: To examine the albuminuria-lowering effect of exenatide once weekly (EQW) compared with active glucose-lowering comparators in patients with type 2 diabetes and elevated urinary albumin-to-creatinine ratio (uACR). Methods: Six randomized double-blind and open-label phase III studies were pooled in a post hoc, exploratory analysis to evaluate the efficacy and safety of EQW versus non-glucagon-like peptide-1 receptor agonist comparators in patients with type 2 diabetes and baseline uACR ≥30 mg/g. Treatment groups were EQW versus all comparators pooled. Efficacy outcomes were percent change from baseline to week 26/28 in uACR and absolute change in glycated haemoglobin (HbA1c), systolic blood pressure (SBP), body weight and estimated glomerular filtration rate (eGFR). Results: Baseline characteristics were generally similar between the two treatment groups (EQW: N = 194, all comparators: N = 274). Relative to the comparator group, EQW changed albuminuria by −26.2% (95% confidence interval [CI] −39.5 to −10). Similar improvements were observed with EQW versus oral glucose-lowering drugs (−29.6% [95% CI −47.6 to −5.3) or insulin (−23.8% [95% CI −41.8 to −0.2]). The effect of EQW on uACR was independent of baseline renin-angiotensin system inhibitor usage. Adjusted mean decreases in HbA1c, SBP and body weight were more pronounced in the EQW versus the comparator group. Adjustment for changes in HbA1c, eGFR and SBP did not substantially affect the uACR-lowering effect of EQW. When also adjusting for changes in body weight, the uACR-lowering effect was reduced to (−13.0% [95% CI −29.9 to 7.8]). Conclusion: Exenatide once weekly reduced uACR in patients with type 2 diabetes and elevated albuminuria compared to commonly used glucose-lowering drugs

Exenatide once weekly decreases urinary albumin excretion in patients with type 2 diabetes and elevated albuminuria: Pooled analysis of randomized active controlled clinical trials

Aims: To examine the albuminuria-lowering effect of exenatide once weekly (EQW) compared with active glucose-lowering comparators in patients with type 2 diabetes and elevated urinary albumin-to-creatinine ratio (uACR). Methods: Six randomized double-blind and open-label phase III studies were pooled in a post hoc, exploratory analysis to evaluate the efficacy and safety of EQW versus non-glucagon-like peptide-1 receptor agonist comparators in patients with type 2 diabetes and baseline uACR ≥30 mg/g. Treatment groups were EQW versus all comparators pooled. Efficacy outcomes were percent change from baseline to week 26/28 in uACR and absolute change in glycated haemoglobin (HbA1c), systolic blood pressure (SBP), body weight and estimated glomerular filtration rate (eGFR). Results: Baseline characteristics were generally similar between the two treatment groups (EQW: N = 194, all comparators: N = 274). Relative to the comparator group, EQW changed albuminuria by −26.2% (95% confidence interval [CI] −39.5 to −10). Similar improvements were observed with EQW versus oral glucose-lowering drugs (−29.6% [95% CI −47.6 to −5.3) or insulin (−23.8% [95% CI −41.8 to −0.2]). The effect of EQW on uACR was independent of baseline renin-angiotensin system inhibitor usage. Adjusted mean decreases in HbA1c, SBP and body weight were more pronounced in the EQW versus the comparator group. Adjustment for changes in HbA1c, eGFR and SBP did not substantially affect the uACR-lowering effect of EQW. When also adjusting for changes in body weight, the uACR-lowering effect was reduced to (−13.0% [95% CI −29.9 to 7.8]). Conclusion: Exenatide once weekly reduced uACR in patients with type 2 diabetes and elevated albuminuria compared to commonly used glucose-lowering drugs

The Adaptive Renal Response for Volume Homeostasis During 2 Weeks of Dapagliflozin Treatment in People With Type 2 Diabetes and Preserved Renal Function on a Sodium-Controlled Diet

Introduction: Proximal tubule sodium uptake is diminished following sodium glucose cotransporter 2 (SGLT2) inhibition. We previously showed that during SGLT2 inhibition, the kidneys adapt by increasing sodium uptake at distal tubular segments, thereby maintaining body sodium balance. Despite continuous glycosuria, we detected no increased urine volumes. We therefore assessed the adaptive renal responses to prevent excessive fluid loss. Methods: We conducted a mechanistic open-label study in people with type 2 diabetes mellitus with preserved kidney function, who received a standardized sodium intake (150 mmol/d) to evaluate the effects of dapagliflozin on renin-angiotensin-aldosterone system (RAAS) hormones, volume-related biomarkers, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), at start of treatment (day 4), end of treatment (day 14), and follow-up (day 18). Results: A total of 14 people were enrolled. Plasma renin and angiotensin II and urinary aldosterone and angiotensinogen were acutely and persistently increased during treatment with dapagliflozin. Plasma copeptin level was numerically increased after 4 days (21%). Similarly, fractional urea excretion was significantly decreased at start of treatment (−17%). Free water clearance was significantly decreased after 4 days (−74%) and 14 days (−41%). All changes reversed after dapagliflozin discontinuation. Conclusion: Dapagliflozin-induced osmotic diuresis triggers kidney adaptive mechanisms to maintain volume and sodium balance in people with type 2 diabetes and preserved kidney function. ClinicalTrials.gov (identification: NCT03152084)