- Effect of a SGLT2 inhibitor on the systemic and intrarenal renin-angiotensin system in subtotally nephrectomized rats. [Journal Article]
- JPJ Pharmacol Sci 2017 Oct 28
- We aimed to examine the effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor on systemic and intrarenal renin-angiotensin system (RAS) in subtotally nephrectomized non-diabetic rats, a mode...
We aimed to examine the effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor on systemic and intrarenal renin-angiotensin system (RAS) in subtotally nephrectomized non-diabetic rats, a model of chronic kidney disease (CKD). Oral administration of the selective SGLT2 inhibitor, TA-1887 (10 mg/kg/day), for 10 weeks induced glycosuria. However, plasma renin activity, plasma angiotensinogen levels, kidney angiotensin II contents and renal injury were not significantly affected by TA-1887. These data indicate that chronic treatment with an SGLT2 inhibitor does not activate the systemic and intrarenal RAS in subjects with non-diabetic CKD.
- Glycosuria amount in response to hyperglycaemia and risk for diabetic kidney disease and related events in Type 1 diabetic patients. [Journal Article]
- NDNephrol Dial Transplant 2018 Jul 05
- CONCLUSIONS: Reduced tubulo-glomerular feedback and glycosuria during hyperglycaemia indicate high renal risk for Type 1 diabetic patients. Inter-individual variability in tubulo-glomerular feedback activity determines renal risk in Type 1 diabetes.
- A Positive Urine Alcohol with Negative Urine Ethyl-Glucuronide. [Journal Article]
- LMLab Med 2018 Jul 05; 49(3):276-279
- Urine ethanol is a common finding in urine drug-screening results. An unexpected finding of alcohol in urine can have serious implications for patients who have committed to pain-management contracts...
Urine ethanol is a common finding in urine drug-screening results. An unexpected finding of alcohol in urine can have serious implications for patients who have committed to pain-management contracts or are being counseled for substance abuse. Although laboratory screening for urine ethanol is highly specific and sensitive, the source of the ethanol can sometimes be unclear. This case report describes a 44-year-old Caucasian man with positive urine ethanol results who reported having abstained from alcohol. A test for urine ethyl-glucuronide and ethyl sulfate was used to validate the information in the patient history stating that the patient had not consumed alcohol for 1 year. Evaluation of the urinalysis results from the patient revealed fermentation in the context of glucosuria as the source of the urine ethanol.
- Dual inhibition of sodium-glucose linked cotransporters 1 and 2 exacerbates cardiac dysfunction following experimental myocardial infarction. [Journal Article]
- CDCardiovasc Diabetol 2018 Jul 07; 17(1):99
- CONCLUSIONS: The exacerbation of post myocardial infarction cardiac dysfunction with T-1095 in the experimental setting suggests the need for caution with the use of dual SGLT1/2 inhibitors in humans.
- Detection of carnosinase-1 in urine of healthy individuals and patients with type 2 diabetes: correlation with albuminuria and renal function. [Journal Article]
- AAAmino Acids 2018 Jun 30
- Low serum carnosinase (CN-1) concentrations are associated with low risk for development of diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Although CN-1 is expressed in the kidney,...
Low serum carnosinase (CN-1) concentrations are associated with low risk for development of diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Although CN-1 is expressed in the kidney, urinary CN-1 (CNU) excretion and its pathological relevance in patients with T2D have not been investigated to date. The present study therefore assessed the extent of CNU excretion in healthy subjects (n = 243) and in patients with T2D (n = 361) enrolled in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1) in relation to functional renal parameters. CNU was detected in a high proportion of healthy individuals, 180 (74%); median CNU excretion was 0.25 mg/24 h [(IQR 0-0.65 mg/24 h]. In patients with T2D the prevalence and extent of CNU increased in parallel with albuminuria (r = 0.59, p < 0.0001; median CNU 0.1 vs 0.2 vs 1.5 mg/24 h, p < 0.0001; prevalence of CNU 61 vs. 81 vs. 97% p < 0.05 in normo- (n = 241), micro- (n = 80) and macroalbuminuria (n = 40), respectively). Patients with estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 displayed higher median CNU excretion rates in comparison to patients with preserved eGFR (> 90 ml/min/1.73 m2) (1.36 vs 0.13 mg/24 h, p < 0.05). Backward stepwise multivariate linear regression analysis revealed albuminuria, eGFR and glycosuria to be independent factors of CNU excretion rates, all together explaining 37% of variation of CNU excretion rates (R2 = 0.37, p < 0.0001). These results show for the first time that CN-1 can be detected in urine and warrants prospective studies to assess the relevance of CNU for renal function deterioration in diabetes patients.
- Optimizing SGLT inhibitor treatment for diabetes with chronic kidney diseases. [Journal Article]
- BCBiol Cybern 2018 Jun 28
- Diabetes induces glomerular hyperfiltration, affects kidney function, and may lead to chronic kidney diseases. A novel therapeutic treatment for diabetic patients targets the sodium-glucose cotranspo...
Diabetes induces glomerular hyperfiltration, affects kidney function, and may lead to chronic kidney diseases. A novel therapeutic treatment for diabetic patients targets the sodium-glucose cotransporter isoform 2 (SGLT2) in the kidney. SGLT2 inhibitors enhance urinary glucose, [Formula: see text] and fluid excretion and lower hyperglycemia in diabetes by inhibiting [Formula: see text] and glucose reabsorption along the proximal convoluted tubule. A goal of this study is to predict the effects of SGLT2 inhibitors in diabetic patients with and without chronic kidney diseases. To that end, we applied computational rat kidney models to assess how SGLT2 inhibition affects renal solute transport and metabolism when nephron population are normal or reduced (the latter simulates chronic kidney disease). The model predicts that SGLT2 inhibition induces glucosuria and natriuresis, with those effects enhanced in a remnant kidney. The model also predicts that the [Formula: see text] transport load and thus oxygen consumption of the S3 segment are increased under SGLT2 inhibition, a consequence that may increase the risk of hypoxia for that segment. To protect the vulnerable S3 segment, we explore dual SGLT2/SGLT1 inhibition and seek to determine the optimal combination that would yield sufficient urinary glucose excretion while limiting the metabolic load on the S3 segment. The model predicts that the optimal combination of SGLT2/SGLT1 inhibition lowers the oxygen requirements of key tubular segments, but decreases urine flow and [Formula: see text] excretion; the latter effect may limit the cardiovascular protection of the treatment.
- A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss. [Journal Article]
- DTDiabetes Ther 2018 Jun 13
- CONCLUSIONS: Metabolic effects with DAPA + ExQW included less FFA suppression versus placebo during the OGTT, suggesting compensatory lipid mobilization for energy production when glucose availability was reduced because of glucosuria. The expected increase in glucagon with DAPA did not occur with DAPA + ExQW coadministration. Bodyweight loss with DAPA + ExQW was associated with the SNP variant rs10010131 A allele, lower baseline adiposity (BMI), and lower baseline insulin secretion (IGI). These findings require further validation.
- Accuracy of glycosuria, random blood glucose and risk factors as selective screening tools for gestational diabetes mellitus in comparison with universal diagnosing. [Journal Article]
- BOBMJ Open Diabetes Res Care 2018; 6(1):e000493
- CONCLUSIONS: Selective screening using glycosuria and random blood glucose is unnecessary due to its low sensitivity. Fasting glucose ≥5.1 mmol/L could be applicable for screening at the population level. Where 2-hour OGTT is not available, FPG ≥5.6 mmol/L, complemented by the presence of risk factors, could be useful in making therapeutic decision.
- Switching to abacavir versus use of a nucleoside-sparing dual regimen for HIV-infected patients with tenofovir-associated renal toxicity. [Journal Article]
- HMHIV Med 2018 Jun 22
- CONCLUSIONS: Tenofovir disoproxil fumarate discontinuation was associated with a rapid and significant improvement in eGFR and tubular abnormalities, regardless of whether abacavir or dual therapy was chosen. Switching to a regimen that included dolutegravir and/or rilpivirine was associated with a eGFR decrease without differences in the rate of tubular dysfunction improvement in comparison with the rest of patients who discontinued tenofovir.
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- Prolonged diabetic ketoacidosis associated with canagliflozin. [Journal Article]
- EDEndocrinol Diabetes Metab Case Rep 2018; 2018
- We report a case of a 63-year-old man who developed diabetic ketoacidosis (DKA) associated with canagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor. He presented acutely unwell with a...
We report a case of a 63-year-old man who developed diabetic ketoacidosis (DKA) associated with canagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor. He presented acutely unwell with a silent myocardial infarction, diverticulitis and DKA with a minimally raised blood glucose level. Standard therapy for DKA was initiated. Despite this, ketonaemia persisted for a total of 12 days after discontinuation of canagliflozin. Glucosuria lasting for several days despite discontinuation of the medications is a recognised phenomenon. However, this is the longest duration of ketonaemia to be reported. The cause of prolonged SGLT-2 inhibition remains uncertain. Deviation from the normal DKA treatment protocol and use of personalised regimens may be required in order to prevent relapse into ketoacidosis while avoiding hypoglycaemia in those that develop this condition.