Amelioration of diabetic nephropathy by SGLT2 inhibitors independent of its glucose-lowering effect: A possible role of SGLT2 in mesangial cells.

Several clinical studies have shown the beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on diabetic nephropathy. The underlying mechanisms are not fully understood. We found that administration of canagliflozin at a low dose (0.01 mg/kg/day) did not affect either blood glucose levels or glycosuria, but it improved albuminuria and mesangial expansion in db/db mice to a similar extent as at a high dose (3.0 mg/kg/day) that lowered blood glucose levels. This indicated the existence of a tubular SGLT2-independent reno-protective mechanism. Here we focused on the potential role of SGLT2 in mesangial cells (MCs). Western blot analysis revealed the expression of SGLT2 in cultured mouse MCs. Exposure of MCs to high glucose levels for 72 h significantly increased the expression of SGLT2. Canagliflozin or ipragliflozin (both 100 nM) treatment inhibited glucose consumption in the medium under high-glucose conditions but not under normal-glucose conditions. Furthermore, canagliflozin inhibited high-glucose-induced activation of the protein kinase C (PKC)-NAD(P)H oxidase pathway and increases in reactive oxygen species (ROS) production. Thus, the inhibition of mesangial SGLT2 may cause an inhibition of PKC activation and ROS overproduction in diabetic nephropathy, and this may at least in part account for the reno-protective effect of SGLT2 inhibitors.

[Nutrition therapy for gestational diabetes]. / Ernährungstherapie bei Gestationsdiabetes.

Overweight and increased energy intake before conception are powerful risk factors in the development of gestational diabetes mellitus (GDM) and may also represent important determinants of the so-called fetal (mal-)programming, which may have long-term consequences for the health of the newborn. Thus, an adequate intake of energy and nutrients is of fundamental significance in the treatment of GDM, along with regular self-monitoring of blood glucose. This concept suffices in most cases to achieve the strict therapeutic goal of normoglycemia. However, because of a lack of data from interventional studies, there is uncertainty about the optimal macronutrient composition of the diet (carbohydrates, fat, protein) and meal distribution, as well as of the mode of calorie restriction in overweight and obese women with GDM. Varying the carbohydrate intake between 40 and 55 % of total energy intake appears to be acceptable and may be distributed across main meals and snacks. Thus, individualized nutritional treatment together with other specific lifestyle interventions are the principal components in the management of GDM.

Kidney toxicity of ingested uranium from drinking water.

BACKGROUND: In experimental settings, uranium is toxic to kidneys, but effects on humans are unclear. Ingestion of water from drilled wells is a source of high uranium exposure in some populations. METHODS: Uranium exposure was measured in 95 men and 98 women aged 18 to 81 years who had used drinking water from drilled wells for an average of 16 years. Urinary N-acetyl-gamma-d-glucosaminidase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, and glutathione-S-transferase; serum cystatin C; and urinary and serum calcium, phosphate, glucose, and creatinine were measured to evaluate possible toxic effects of uranium on kidney cells and renal function. In addition, supine blood pressure was measured. Associations between uranium exposure and the outcome variables were modeled by using linear regression with adjustment for age, sex, body mass index, smoking, and analgesic use. RESULTS: Median uranium concentration in drinking water was 25 microg/L (interquartile range, 5 to 148 microg/L; maximum, 1,500 microg/L). Indicators of cytotoxicity and kidney function did not show evidence of renal damage. No statistically significant associations with uranium in urine, water, hair, or toenails was found for 10 kidney toxicity indicators. Uranium exposure was associated with greater diastolic and systolic blood pressures, and cumulative uranium intake was associated with increased glucose excretion in urine. CONCLUSION: Continuous uranium intake from drinking water, even at relatively high exposures, was not found to have cytotoxic effects on kidneys in humans.

[Use of a specialized soft drink based on plant raw material in nutrition of patients with diabetes mellitus]. / Ispol'zovanie spetsializirovannogo bezalkogol'nogo napitka na osnove rastitel'nogo syr'ia v pitanii bol'nykh sakharnym diabetom.

The using of the low calorie soft drink "Forest gift" based on plant raw and enriched with vitamin C and iodine by patients with diabetes mellitus has resulted in the improvement of carbohydrates metabolism, provision of iodine and vitamin C and oxidant status of organism. Obtained data has promised to recommend this product for using in patient's ration.

A marvel of colors and ingredients. The story of urine test strip.

The history of the urinary test papers does not being in the post-war period. As early as the 1880's some practitioners and pharmacists tried to replace the complicated wet-chemical procedures and apparatus by "dry chemistry." The first popular test paper for sugar and albumin originated in England in 1883. Dry reagents for proving hematuria have been available since the beginning of this century. Until the 1930s a wide palette of commercial urine tests with "modern" brand names was established. A methodological breakthrough was created by the spot test chemistry inaugurated by the Austrian, Fritz Feigl, about 1920. Using the capillary properties of filter paper in enhancing color reactions he founded a new area of analytical chemistry. Many of the pioneers were recruited from Jewish scientists. In this lecture is proposed that their emigration and banishment as well as the Second World War have stopped the development of urinary diagnostics on the European continent. In the post-war period the American industry succeeded to the leading position in the researching and marketing of test papers. In 1956, the triumphal progress of the "stick tests" began with the "Clinistix" (Ames Company, today Bayer Diagnostic).

Ascorbic acid interference in reagent-strip reactions for assay of urinary glucose and hemoglobin.

Vitamin C (ascorbic acid), commonly taken as a dietary supplement and excreted in the urine, can interfere with peroxidase redox indicator systems such as those used in reagent-strip tests for urinary glucose and hemoglobin. We investigated whether the concentrations of ascorbic acid in urine after modest supplementary doses of vitamin C are high enough to interfere with such dipstick tests. After adding glucose or hemoglobin to urine collected from persons not taking vitamin C and from persons taking 350 to 1000 mg of vitamin C daily, we tested four reagent strips for interference and found that these commonly taken doses did frequently interfere with all test systems examined.

Effect of large-dose ascorbic acid on the two-drop clinitest determination.

A study was conducted to determine if high doses of ascorbic acid would affect the two-drop Clinitest determination for glucosuria in normal individuals. Numerous secondary literature sources indicate that large doses of ascorbic acid may cause a false positive Clinitest result. Three-gram and nine-gram doses of ascorbic acid following two dosing schedules (once daily and three times daily) were taken by nine normal individuals to determine if the renal excretion of large enough quantities of ascorbic acid or its metabolites would produce false positive results with the two-drop Clinitest procedure. Each dose was given for seven days in each schedule. There were only two (0.27%) trace positive Clinitest determinations reported out of 748 Clinitest determinations. High doses of ascorbic acid in normal individuals do not appear to affect the two-drop Clinitest determination for urinary glucose. The study indicates a need to be cautious about secondary literature references on drug-laboratory test interferences.

Urinary glucose and vitamin C.

The recent popularization of self-prescribed large doses of vitamin C has increased the possibility for erroneous conclusions to be drawn from standard clinical methods used in urinary glucose monitoring, due to interference with these methods by the greatly elevated excretion of vitamin C. The coupled-enzyme-chromogen strip tests showed erroneously negative glucose levels in urines of both a diabetic individual and a subject with a genetic low renal threshold for glucose when they were supplementing their normal diets with 1-2 g vitamin C per day. With this regimen, their urinary vitamin C levels reached 200 mg/dl (11.4 mmol/l). For normal urine with vitamin C added, false-positive tests for glucose were found using Benedict's reagent when vitamin C was present at 250 mg/dl (14.3 mmol/l) or higher concentrations. In diabetic individuals consuming large quantities of vitamin C, this interference with standard coupled-enzyme-chromogen strip tests or Benedict's test could present a significant problem in diagnosis and clinical management of the disease. A simple anion exchange method of treating the urine was used to correct the false results.