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- Asymptomatic bacteriuria and urinary tract infections in special patient groups: women with diabetes mellitus and pregnant women. [JOURNAL ARTICLE]
- Curr Opin Infect Dis 2013 Nov 27.
Asymptomatic bacteriuria (ASB) and urinary tract infections (UTIs) in women with diabetes mellitus and during pregnancy are common and can have far-reaching consequences for the woman and neonate. This review describes epidemiology, risk factors, complications and treatment of UTI and ASB according to recent developments in these two groups.Most articles addressing the epidemiology and risk factors of ASB and UTI in diabetic and pregnant women confirmed existing knowledge. New insights were obtained in the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors, as medication for diabetes mellitus type 2, and a small increased risk for UTI due to glucosuria and the possible negative effects of UTI, including urosepsis,on bladder and kidney function in diabetic women. Predominantly, potential long-term effects of antibiotic treatment of ASB or UTI during pregnancy on the neonate have received attention, including antibiotic resistance and epilepsy.SGLT2 inhibitors were associated with a small increased risk for UTI, UTI in diabetic women may lead to bladder and kidney dysfunction, and antibiotic treatment of ASB and UTI during pregnancy was associated with long-term effects on the neonate. Up-to-date research on the effectiveness and long-term effects of ASB screening and treatment policies, including group B Streptococcus bacteriuria in pregnancy, is warranted to inform clinical practice.
- The latest pharmacotherapy options for type 1 diabetes. [Journal Article]
- Expert Opin Pharmacother 2014 Jan; 15(1):37-49.
Introduction: Pharmacotherapy of type 1 diabetes (T1D) is mainly restricted to insulin treatment. Insulin analogues have replaced human insulin sometimes without reason. A broader approach is needed. Areas covered: Insulin and insulin analogues, but also other available hormone therapies and drugs, based on literature in PubMed are included in this study. Expert opinion: At diagnosis, T1D patients should, when resources allow, participate in clinical trials aiming at preservation of beta cell function, for example, with combination therapies involving auto-antigen/s. In very young children insulin pump is recommended, when enough resources for ALL patients; in older patients pump or multiple insulin therapy is recommended. Human insulin still has a place, with insulin analogues on special indications. Patients with pronounced insulin resistance might need Metformin, and Glitazones need more studies. Incretins, for example, GLP-1 may be of interest in patients with residual C-peptide. Amylin will probably be restricted to highly motivated patients. IGF-1 also requires more studies. C-peptide may be a hormone, probably part of future treatment. Glucosoxidase inhibitors might be considered in obese patients. Whether drugs increasing glucosuria will be of clinical value in T1D remains to be shown. In summary, insulin replacement is not enough for several patients. A broader pharmacotherapy is needed, at onset, and later when metabolic control needs improvement.
- The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype. [JOURNAL ARTICLE]
- J Med Genet 2013 Nov 27.
Mutation specific effects in monogenic disorders are rare. We describe atypical Fanconi syndrome caused by a specific heterozygous mutation in HNF4A. Heterozygous HNF4A mutations cause a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Autosomal dominant idiopathic Fanconi syndrome (a renal proximal tubulopathy) is described but no genetic cause has been defined.We report six patients heterozygous for the p.R76W HNF4A mutation who have Fanconi syndrome and nephrocalcinosis in addition to neonatal hyperinsulinism and macrosomia. All six displayed a novel phenotype of proximal tubulopathy, characterised by generalised aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypouricaemia, and additional features not seen in Fanconi syndrome: nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcaemia, and hypermagnesaemia. This was mutation specific, with the renal phenotype not being seen in patients with other HNF4A mutations. In silico modelling shows the R76 residue is directly involved in DNA binding and the R76W mutation reduces DNA binding affinity. The target(s) selectively affected by altered DNA binding of R76W that results in Fanconi syndrome is not known.The HNF4A R76W mutation is an unusual example of a mutation specific phenotype, with autosomal dominant atypical Fanconi syndrome in addition to the established beta cell phenotype.
- Association between urine osmolality and specific gravity in dogs and the effect of commonly measured urine solutes on that association. [Journal Article]
- Am J Vet Res 2013 Dec; 74(12):1542-5.
Objective-To determine the association between urine osmolality and specific gravity (USG) in dogs and to evaluate the effect of commonly measured urine solutes on that association. Animals-60 dogs evaluated by an internal medicine service. Procedures-From each dog, urine was obtained by cystocentesis and USG was determined with a refractometer. The sample was divided, and one aliquot was sent to a diagnostic laboratory for urinalysis and the other was frozen at -80°C until osmolality was determined. Urine samples were thawed and osmolality was measured in duplicate with a freezing-point depression osmometer. The correlation between mean urine osmolality and USG was determined; the effect of pH, proteinuria, glucosuria, ketonuria, bilirubinuria, and hemoglobinuria on this relationship was investigated with multiple regression analysis. Results-The Pearson correlation coefficient between urine osmolality and USG was 0.87. The final multivariable regression model for urine osmolality included USG and the presence of ketones; ketonuria had a small negative association with urine osmolality. Conclusions and Clinical Relevance-Results indicated a strong linear correlation between osmolality and USG in urine samples obtained from dogs with various pathological conditions, and ketonuria had a small negative effect on that correlation.
- Canagliflozin, a Novel SGLT2 Inhibitor for Treatment of Type 2 Diabetes. [Journal Article]
- Ann Pharmacother 2013 Oct; 47(10):1301-11.
To evaluate the available clinical data on canagliflozin and provide formulary considerations as to its place in the current treatment approach of type 2 diabetes mellitus (T2DM).A systematic review of the literature in MEDLINE and Web of Science was performed through July 2013 using the key words and medical subject headings canagliflozin, JNJ-28431754, TA-7284, and sodium-glucose co-transporter 2 inhibitor. A manual search of references from reports of clinical trials or review articles was performed to identify additional relevant studies.Citations eligible for inclusion were in vitro or in vivo evaluations of canagliflozin with no restrictions on patient population or indication used. Data related to the patient populations and outcomes of interest were extracted from each citation.Five clinical trials (n = 2775 subjects) have been published evaluating canagliflozin in patients with T2DM. A single study evaluated canagliflozin monotherapy, while the others included various add-on therapies. Four studies included placebo groups with 2 others using sitagliptin as an active control. Compared with placebo (+0.14%), canagliflozin monotherapy at doses of 100 to 300 mg/d decreases hemoglobin A1c by -0.77% to -1.03% from baseline. Reductions in fasting plasma glucose, body weight, and systolic blood pressure were seen. Because of the increase in glucosuria with the drug, patients (especially females) are at increased risk of genital mycotic infections. The overall safety of canagliflozin (eg, cardiovascular, oncologic, pancreatic, bone) is also yet to be fully elucidated.Canagliflozin is comparable to second-line oral medications in terms of effectiveness but has limitations in affordability and long-term safety data.
- Sodium-glucose linked transporter-2 inhibitors: potential for renoprotection beyond blood glucose lowering? [JOURNAL ARTICLE]
- Kidney Int 2013 Nov 20.
The proximal tubule's sodium-glucose linked transporter-2 (SGLT2) accounts for the vast majority of glucose reabsorption by the kidney. Its selective inhibition, accordingly, leads to substantial glycosuria, lowering blood glucose, and facilitating weight loss in individuals with diabetes. During the past year, two SGLT2 inhibitors, canagliflozin and dapagliflozin, have been approved for the treatment of type 2 diabetes. Beyond their anti-hyperglycemic properties, however, this new class of drugs has several other attributes that provide a theoretical basis for kidney protection. Like agents that block the renin-angiotensin system, SGLT2 inhibitors also reduce single-nephron glomerular filtration rate (SNGFR) in the chronically diseased kidney, though by quite different mechanisms. Additional potentially beneficial effects of SGLT2 inhibition include modest reductions in blood pressure and plasma uric acid. Finally, cell culture studies indicate that glucose uptake from the tubular lumen, as well as from the basolateral compartment, can contribute to proximal tubular production of extracellular matrix proteins. Whether such attributes will translate into reducing the progression of chronic kidney disease will require the undertaking of long-term, dedicated studies.Kidney International advance online publication, 20 November 2013; doi:10.1038/ki.2013.451.
- Clinical and genetic analysis in a patient with primary renal glucosuria: Identification of a novel mutation in the SLC5A2 gene. [JOURNAL ARTICLE]
- Exp Ther Med 2013 Dec; 6(6):1532-1534.
Primary renal glucosuria (PRG; OMIM #233100) is characterized by persistent glucosuria due to a reduction in the renal tubular reabsorption of glucose in the presence of a normal concentration of serum glucose and the absence of any other impairment of tubular function. The SLC5A2 gene is the causative gene, which codes for the low-affinity sodium/glucose co-transporter SGLT2. In the present study, the case of a patient with PRG associated with a novel mutation of the SLC5A2 gene is reported. The patient visited hospital for the evaluation of glucosuria in the absence of hyperglycemia, a condition that had been present for >20 years. The patient showed a fasting blood sugar level of 104 mg/dl, a 2-h postprandial sugar level of 101 mg/dl, a sodium level of 144 mmol/l, a potassium level of 3.7 mmol/l and a chloride level of 106 mmol/l in serum. Urine chemistry revealed that the amount of glucose excreted was 10.8 g/1.73 m(2)/24 h; however, the levels of the other parameters were unremarkable. Polymerase chain reaction (PCR) sequencing analysis of the SLC5A2 gene from the patient revealed a novel 1 bp deletion mutation, which altered the coding sequence of exon 10 in the transmembrane domain (c.1162delG; Ala388ProfsX48), suggesting an autosomal dominant inheritance pattern. This study identified a novel mutation in the SLC5A2 gene related to a benign clinical characteristic and suggests that the molecular diagnosis of the SLC5A2 gene may be useful for diagnosing renal glucosuria in patients and for deciding intervention measures for their family members.
- Influence of Successive Badminton Matches on Muscle Strength, Power, and Body Fluid Balance in Elite Players. [JOURNAL ARTICLE]
- Int J Sports Physiol Perform 2013 Nov 13.
The aim was to analyze the influence of the competitive round on muscle strength, body fluid balance, and renal function in elite badminton players during a real competition. Body mass, jump height during a countermovement jump (CMJ), hand grip force and urine samples were obtained from 13 elite badminton players (6 men and 7 women) before and after the 2nd round and quarter-final matches of the National Spanish badminton championship. Sweat rate was determined by using pre-to-post match body mass change and by weighing individually labelled fluid bottles. Sweat rate was 1.04±0.62 L/h and 0.98±0.43 L/h while rehydration rate was 0.69±0.26 L/h and 0.91±0.52 L/h for the 2nd round and quarter-finals, respectively. Thus, dehydration was 0.47±1.03% after the 2nd round and 0.23±0.43% after the quarter-finals. There were no differences in pre-to-post match jump height but jump height was reduced from 37.51±8.83 cm after the 2nd round game to 34.82±7.37 cm after the quarter-finals (P<0.05). No significant differences were found in hand grip force when comparing pre-post matches or rounds, although there were significant differences between dominant and non-dominant hands (P<0.05). The succession of rounds caused the appearance of proteinuria, haematuria, glycosuria, and higher nitrite and ketone concentrations in urine. Rehydration patterns during a real badminton competition were effective to prevent dehydration. A badminton match did not affect jump height or handgrip force but jump height was progressively reduced by the competitive round. Badminton players' renal responses reflected the diminished renal flux due to the high-intensity nature of this racket sport.
- Recommendations for self-monitoring in pediatric diabetes: a consensus statement by the ISPED. [JOURNAL ARTICLE]
- Acta Diabetol 2013 Oct 27.
A panel of experts of the Italian Society of Pediatric Endocrinology and Diabetology comprehensively discussed and approved the Italian recommendations regarding self-monitoring of blood glucose, continuous glucose monitoring and other measures of glycemic control in children and adolescents with type 1 diabetes. After an extensive review of the literature, we took these issues into account: self-monitoring blood glucose, continuous glucose monitoring, glycemic variability, glycosuria, ketonuria, ketonemia, glycated hemoglobin, fructosamine and glycated albumin, logbook, data downloading, lancing devices, carbohydrate counting, and glycemic measurements at school. We concluded that clinical guidelines on self-management should be developed in every country with faithful adaptation to local languages and taking into account specific contexts and local peculiarities, without any substantial modifications to the international recommendations. We believe that the National Health Service should provide all necessary resources to ensure self-monitoring of blood glucose and possibly continuous glucose monitoring of all children and adolescents with type 1 diabetes, according to the standards of care provided by these recommendations and internationally.
- Clinicopathologic and atypical features of naturally occurring leptospirosis in dogs: 51 cases (2000-2010). [Journal Article]
- J Am Vet Med Assoc 2013 Nov 1; 243(9):1316-22.
To determine clinicopathologic features, percentage of atypical abnormalities, antibody titers against Leptospira serogroups, and importance of convalescent titers in dogs with leptospirosis.Retrospective case series.51 dogs with leptospirosis.Criteria for inclusion were at least 1 positive microscopic agglutination test (MAT) result (titer ≥ 1:1,600 in vaccinated dogs, titer ≥ 1:800 in nonvaccinated dogs, or ≥ 4-fold increase in convalescent titer), a complete medical record (including leptospirosis vaccination date, reason for initial evaluation, and CBC, serum biochemical analysis, and urinalysis results), and clinical signs or laboratory findings consistent with leptospirosis.Initial clinical signs, temporal distribution, and signalment were similar to previous reports. Convalescent MAT titers were necessary for diagnosis in 45% of cases. Atypical abnormalities included radiographic evidence of pulmonary disease in 10 of 23 dogs and hepatic involvement alone in 7 of 51 dogs. Other abnormalities included proteinuria in 34 of 51 dogs, thrombocytopenia in 26 of 51, coagulopathy in 7 of 24 dogs, hypoalbuminemia in 14 of 51 dogs, and glucosuria in 9 of 51 dogs. Significant associations were found between antibodies against serogroup Grippotyphosa and renal involvement and serogroup Icterohaemorrhagiae and hepatic involvement.Increased awareness of atypical abnormalities may decrease misdiagnosis of leptospirosis in dogs. Results of concurrent infectious disease testing should be interpreted with caution; misdiagnosis of leptospirosis could pose a public health risk. Convalescent titers were necessary to identify infection when acute testing results were negative. Further research is needed to determine the true associations between antibodies against identified serogroups and clinical features.