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Variations in renal threshold for glucose in Type 1 (insulin-dependent) diabetes mellitus.

The blood glucose/urinary glucose relationship was studied in 23 patients with Type 1 (insulin-dependent) diabetes. Glucose was infused intravenously in order to increase blood glucose concentration slowly and gradually. The renal threshold was recorded at the slightest trace of glycosuria and varied by a factor of 2 (from 6.0 to 14.3 mmol/l). The rise in blood glucose required to change the urinary output (0-1.1 mmol glucose/20 min) varied by a factor of 7 (1.1-7.6 mmol/l). The maximal rate of tubular glucose reabsorption varied by a factor of 2 (0.93-1.98 mmol/min). The renal threshold was negatively correlated with the creatinine clearance (r = -0.052, p less than 0.05), but was not correlated with diabetic control, age or duration of diabetes. The maximal rate of glucose reabsorption was negatively correlated with age (r = 0.47, p less than 0.05) and duration of diabetes (r = -0.54, p less than 0.05). In conclusion, urinary glucose excretion is dependent on both renal threshold and the splay and the slope of the blood glucose/urinary glucose excretion curve. Thus, the degree of glycosuria is of value as an index of diabetic control only when the blood glucose/urinary glucose relationship is known. The inverse correlation between renal threshold and creatinine clearance limits the usefulness of measuring glycosuria in patients with nephropathy.

Adolescent↗

Proteinuria in the acutely diabetic rat and its response to insulin treatment.

The development of proteinuria and its response to insulin therapy in acute experimental diabetes was examined in 11 female rats by sequentially measuring 24 h excretion of glucose and total protein before diabetes, during 5-37 days of acute streptozotocin diabetes, during and after 7-14 days of continuous subcutaneous insulin administration. Induction of diabetes promptly resulted in marked polyuria (78 +/- 9 ml/24 h), and glycosuria (6.6 +/- 0.7 g/24 h), while proteinuria quadrupled (from 4.7 +/- 0.7 to 18.8 +/- 1.8 mg/24 h, p less than 0.001). Concurrent with amelioration of polyuria and glycosuria by insulin treatment, proteinuria decreased strikingly (8.5 +/- 1.2 mg/24 h, p less than 0.001) Polyuria and glycosuria resumed after discontinuing continuous subcutaneous insulin, and proteinuria promptly returned to pretreatment levels (19.0 +/- 2.5 mg/24 h). Similarly decreased proteinuria (8.8 +/- 0.9 mg/24 h) recurred in five rats retreated with insulin after 100 days of diabetes. Elevated proteinuria was not associated with lysozymuria or consistent changes in glomerular filtration rate. The rapid fluctuations in proteinuria attending acute diabetes and its effective treatment suggest that metabolic aberrations of diabetes may directly effect renal handling of proteins.

Acute Disease↗

Glycosylated hemoglobin (Hb AI) as an indicator of therapy effects in different clinical types of diabetes.

The levels of glycosylated hemoglobin (Hb AI), intermittent glycemia and glycosuria over 24 hr, Mw index, fasting serum cholesterol and triglycerides, and 24-hr proteinuria were determined in 20 healthy subjects and 88 diabetics representing different clinical types of diabetes mellitus. In each of the subjects all the tests were carried out on a single day. The other investigations included endogenous creatinine clearance, ECG and ophthalmoscopic examination of the eye-fundus. The mean Hb AI levels in the "A" control group (up to 40 yr of age) and in the "B" control group (41-60 yr) were mean +/- SD = 6.8 +/- 0.65% and mean +/- SD = 6.49 +/- 0.99% of the total hemoglobin concentration, respectively. A significant increase in Hb AI concentration was found in all the diabetic patients. The increase, independent of the subject's age, clinical type of diabetes and the therapy employed, was related to the degree of hyperglycemia. In Type I diabetes there was no positive correlation between Hb AI concentration on the one hand and fasting glycemia, the 24-hr profile of glycemia, glycosuria and Mw index on the other. The latter indices of diabetes mellitus control seem thus to differ in value and significance. In Type II diabetes, both newly-diagnosed and of long duration, treated with the sulfonylurea derivatives, a marked correlation was found between Hb AI level and fasting glycemia, the mean value of 8 glycemia determinations over 24-hr, Mw index and 24-hr glycosuria. In Type II diabetes treated with insulin a correlation was established between Hb AI and other findings, except fasting glycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Change of plasma 1,5-anhydro-D-glucitol levels after the onset of diabetes in spontaneous diabetes prone BB/Wor/(/)Tky rats.

Plasma 1,5-anhydro-D-glucitol (AG) is a marker of the diabetic state and also reflects the glycosuria induced by hyperglycemia but not by renal pathology. To investigate the benefits of the AG determination in order to diagnose diabetes in BB/Wor/(/)Tky rats, AG was measured in non-diabetic (n = 104) and diabetic (n = 113) BB/Wor/(/)Tky rats. AG was significantly higher in non-diabetic rats than in diabetic rats (25.2 +/- 9.3 vs 4.1 +/- 7.4 micrograms/ ml, mean +/- SD, p < 0.001). The best cut-off level for AG (8.5 micrograms/ml) was highly specific (100%) for ruling out diabetes and fairly sensitive (82.3%) to detect diabetes. Based on the AG cut-off levels, 90% of false-negative diabetic rats (18/20) were observed within 4 days after the onset of diabetes, which corresponded to 38.3% in diabetic rats (18/47) at that time. The false-negative diabetic rats and positive rats could be effectively distinguished based on the cumulative points given according to the urinary glucose after the onset of diabetes. 1 point for each cross [+] indicating glycosuria using the Testape, i.e. 2 or less points false negative and 4 or more points for diabetic rats in the first 4 days. In conclusion, there is a close inverse relation between the level of plasma AG and the amount of glycosuria detected just after the onset of overt diabetes in BB/Wor/(/)Tky rats.

Animals↗

Relationship between urinary and blood glucose in diabetic children.

The relationship of urine glucose concentration with 'average' blood glucose concentration for the corresponding period was investigated in 10 juvenile diabetics during the performance of 15 inpatient metabolic profiles. 0% glucosuria was associated with 'average' blood glucose concentrations less than 6.4 mmol/l (less than 115 mg/100ml), 2% glycosuria with concentrations greater than 8.6 mmol/l (greater than 154 mg/100ml), and over 5% glycosuria with concentrations greater than 11.3 mmol/l (greater than 204 mg/100ml). Urinary glucose loss was large (greater than 278 mmol; greater than 5g) when the 'average' blood glucose was greater than 11.1 mmol/l (greater than 200 mg/100ml). Because many diabetics have blood glucose concentrations up to 11.1 mmol/l, it is advantageous if glucosuria up to 5% is detectable by routine home urine tests. The 2-drop Clinitest method detects glycosuria up to 5% without significant loss of accuracy and is recommended in preference to the 5-drop method.

Adolescent↗

Glucose tolerance tests in 200 patients with senile cataract.

An account is given of asymptomatic diabetes mellitus. To determine the incidence in 200 patients with senile cataract 3 tests are described, namely, a modified standard glucose tolerance test, a provocative steroid glucose tolerance test, and a standard glucose tolerance test. Known diabetics and patients with a fasting blood glucose in excess of 5.5 mmol/l or glycosuria were excluded. Eighty-eight patients had an abnormal modified standard glucose tolerance test. Of these, 41 had an abnormal curve after a provocative steroid glucose tolerance test, and 30 had an abnormal curve after a standard glucose tolerance test. Forty-three of the 71 patients with abnormal curves had no glycosuria, although the blood glucose level exceeded an arbitrary renal threshold of 10 mmol/l. Asymptomatic diabetes was diagnosed in patients of all age groups. It is concluded that glucose intolerance is common in patients with senile cataract who show no glycosuria and have a normal fasting blood sugar on routine examination.

Aged↗

Self testing for diabetes mellitus.

OBJECTIVE: To develop a simple, economically viable, and effective means of population screening for diabetes mellitus. DESIGN: A postal request system for self testing for glycosuria with foil wrapped dipsticks. Preprandial and postprandial tests were compared with a single postprandial test. The subjects were instructed how to test, and a result card was supplied on which to record and return the result. All those recording a positive test result and 50 people recording a negative result were invited for an oral glucose tolerance test. SETTING: General practice in east Suffolk, list size 11534. PATIENTS: All subjects aged 45-70 years registered with the practice were identified by Suffolk Family Health Services Authority (n = 3057). The 73 subjects known to have diabetes from the practice's register were excluded, leaving 2984 subjects, 2363 (79.2%) of whom responded. 1167 subjects completed the single test and 1196 the two tests. MAIN OUTCOME MEASURES: Response rate and number of patients with glycosuria. Sensitivity, specificity, and positive predictive value of a single postprandial test and preprandial and postprandial tests. Number of new cases of diabetes identified and cost of screening. RESULTS: Of the patients completing the single postprandial test, 29 had a positive result, an oral glucose tolerance test showed that eight (28%) had diabetes, six (21%) impaired glucose tolerance, and 14 (48%) normal glucose tolerance. 44 of the group who tested before and after eating had a positive result; nine (20%) had diabetes, five (11%) impaired tolerance, and 26 (11%) normal tolerance. Screening cost 59p per subject and 81 pounds per case detected. Of the 17 people with previously undiagnosed diabetes, eight were asymptomatic and 11 had not visited their general practitioner in the past three months. CONCLUSIONS: A postal request system for self testing for postprandial glycosuria in people aged 45-70 is a simple and effective method of population screening for diabetes mellitus.

Aged↗

Accuracy and influence of ascorbic acid on glucose-test with urine dip sticks in prenatal care.

OBJECTIVE: In Germany, urine analysis with dip sticks are used for screening of gestational diabetes. Our goal was to find the cut-off levels of glucose dip sticks and evaluate the influence of ascorbic acid on the result. STUDY DESIGN: We took urine samples of 152 pregnant patients between 01/2004 and 10/2004. The glucose content of the urine was analyzed using several dip sticks (Combur10 Roche, Multistix 8SG Bayer, Diabur5000 Roche and by the hexokinase method. The ascorbic acid concentration of the specimen was determined. RESULTS: Glycosuria test dip sticks have a good sensitivity and specificity of the expected positive/negative-reaction compared with the hexokinase method but showed a significant reduction of the color reaction at high concentrations of ascorbic acid. CONCLUSION: High ascorbic acid concentrations cause a reduction in the color reaction of urine dip sticks. False-negative test stick measurements can appear in patients with low glycosuria. The rate of glycosuria shows high individual differences and dependent on the concentration of vitamin C. We conclude that dip sticks are not useful in prenatal management.

Adolescent↗

Diabetes mellitus in the guinea pig.

Spontaneous diabetes mellitus has been documented in a colony of guinea pigs. The contagious nature of the disease has been verified, but the nature of the infectious agent is not known. Animals from the original colony or animals exposed to the colony with normal glucose tolerance tests (GTT) became diabetic, as evidenced by elevated one- and four-hour GTT values, and in most cases have significant glycosuria. The severity of pathologic changes in the pancreatic islets parallel, in general, the severity of the clinical symptoms (glycosuria and abnormal GTT). Those animals with severe glycosuria and elevated FBS as well as one- and four-hour GTT values had the most pronounced degranulation and most prominent cytoplasmic inclusions in islet B cells. The severity of scarring in the islets can be correlated with the duration of the overt diabetic state. The other clinical parameters of note were elevated serum triglycerides, normal serum but elevated aortic cholesterol, and absence of ketonemia or ketonuria. The reproductive capacity of diabetic females was compromised. While the clinical manifestations are mild or variable, the presence of significant islet pathology is reminiscent of human juvenile diabetes mellitus. These findings lend support to the concept that infectious and/or immune mechanisms could be operative in the etiology and pathogenesis of human diabetes mellitus.

Animals↗

[Glomerular filtration and tubular reabsorption of glucose in insulin-dependent diabetes in children].

Although glycosuria is important in the control of diabetes in children, few studies clearly show its significance as compared to glycemia. The aim of the present study was therefore to determine the two parameters that control glucose presence in urine, i.e. glucose glomerular filtration rate (GFR) and tubular reabsorption (JrG). GFR was measured by using a 110 min polyfructosan perfusion in 96 diabetic children and adolescents. The results are as follows: 1) In this population there is a significant correlation (p less than 0.01) between the quantity of glucose in urine and mean glycemia during the test; 2) polyfructosan clearance that reflects GFR in diabetic children without renal complication is 2.11 +/- 0.04 ml/s 1.73 m2, or 126 +/- 2.4 ml/min 1.73 m2 (mean +/- SEM); it is higher than in the reference values already published; 3) JrG is correlated with glucose filtered load (p less than 0.01), GFR (p less than 0.01) and sodium reabsorption (p less than 0.01). The ratio JrG/GFR could be substituted for the classical concept of "renal threshold", as it can be easily measured and may help in interpreting glycosuria in some diabetic children. To conclude, in IDD children, the parameters controlling glycosuria may be studied by a simple method. The clinical value of such renal exploration has still to be determined.

Absorption↗

Differential response of urinary N-acetyl-beta-D-glucosaminidase to two osmotic diuretics in the dog.

Urinary N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal hydrolase located the proximal tubule of the kidney, has been used as a marker for subtle renal injury. In humans and other animals with diabetes mellitus, urinary NAG activity has been shown to increase within 12 hours of the onset of hyperglycemia and glycosuria. Whether the rise in urinary NAG activity is in response to the hyperglycemia or to the osmotic diuresis associated with glycosuria is not known, nor has the time course of the rise in enzyme activity been determined. A study was designed using four groups of dogs to examine these possibilities: group 1 (n = 5), control dogs; group 2 (n = 5), mannitol-infused dogs; group 3 (n = 5), low-glucose dogs; and group 4 (n = 5), high-glucose dogs. In groups 2 and 4, mannitol and glucose, respectively, were infused at a rate to double urine flow from the left ureter without altering the contralateral urine volume. In group 3, sufficient glucose was infused to elevate left renal vein glucose level without producing glycosuria. In the control dogs infused with normal saline solution at a constant rate throughout the control and study periods, no differences were found in urinary NAG excretion when data from individual clearance periods were compared for the right and left kidneys. In the low-glucose dogs, urinary NAG/creatinine ratios were significantly increased (P less than 0.01) when the left and right kidneys were compared for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

[Induction of dietetic diabetes in Microtus arvalis Pallas and its developmental mechanism].

In Microtus arvalis Pallas, new born voles were fostered to ICR mice and supplied with pellets for mice after weaning. A high concentration of glycosuria was shown in about 50% of the voles and continued for over ten weeks. Concentrations of blood glucose and plasma FFA iun glycosuric voles were three or four times as high as those in normal controls. The fermentation ability and pH lowered in the esophageal sac, and comparatively large amount of starch existed in the pyloric stomach of the glycosuric voles. This demonstrated that the dietary starch were tolerably transported to the pyloric stomach without being fermented in the esophageal sac. Glycosuria was also induced in about 50% of the voles supplied with an acidified water (0.02 N HCl, pH 1.7), and the glycosuric voles showed a low pH (1.4-4.2) and lowering of the fermentative ability in esophageal sac. Such an abnormal fermented conditions in the esophageal sac is considered to induce glycosuria in the voles. Glucose tolerance in the diabetic voles which were supplied with pellets for mice lowered considerably with the progress of the disease. On the other hand, plasma insulin levels in the slight diabetic cases rose to eight times as high as normal level, but they lowered considerably with the progress. In the serious cases, the voles fell into complete insulin deficiency. From the above results, the herbivorous Microtus species was considered to be useful as an "animal model" of the dietetic diabetes.

Animals↗

Detecting GD and preeclampsia. Effectiveness of routine urine screening for glucose and protein.

OBJECTIVE: To assess why urine collection and analysis for proteinuria and glycosuria is routinely performed during each antepartum visit at prenatal clinics. STUDY DESIGN: Six hundred ten antepartum medical records were reviewed. RESULTS: One hundred nine (18%) patients had proteinuria, while 17 patients (2.8%) developed preeclampsia. Fifteen patients (2.5%) had at least one episode of glycosuria (100 mg/dL), while 11 had gestational diabetes. Of those with gestational diabetes, four (36%) had glycosuria. Of those with preeclampsia, three (17.7%) had proteinuria that preceded the finding of hypertension. CONCLUSION: These results support our observation that routine oral 50-g glucose diabetes screening and careful monitoring of blood pressure are better screens for gestational diabetes and preeclampsia. The increased patient inconvenience and clinic staffing necessary for routine urinalysis may be avoided by eliminating that ritual.

Blood Glucose↗

Islet hyperplasia in callitrichids.

Five callitrichids (three common marmosets -Callithrix jacchus -, a black tufted-eared marmoset -C. penicillata-, and a saddle-back tamarin -Saguinus fuscicollis) were diagnosed with islet hyperplasia by histopathology and immunohistochemistry. All were privately-owned, unrelated callitrichids ranging from 2- to 4-year-old. Relevant findings were anorexia (3/5), vomiting (2/5), ptyalism (1/5), polyuria/polydipsia (1/5), respiratory distress (1/5), hyperglycemia (2/3) and glycosuria (1/1); hyperglycemia and glycosuria were associated with pregnancy in a common marmoset and resolved after reducing simple carbohydrates in diet. All five animals died, three of them after few premonitory signs; in two cases, other concurrent diseases unrelated to islet hyperplasia were considered the cause of death. Additional animals from two facilities had high weight (4), physical obesity (3), polyuria/polydipsia/polyphagia/uriposia (1), hyperglycemia (1), and/or glycosuria (2). Pathologic findings in the deceased callitrichids were: islet hyperplasia (5/5); hemosiderosis (5/5); lipomatosis (4/5) of several tissues (atria, 3/5; pancreas, gall bladder, intestine, esophagus, and thyroid, 2/5; liver, 1/5); pancreatic necrosis or steatonecrosis, and/or acute pancreatitis (3/5); and vacuolation of hepatocytes and renal tubular cells most likely consistent with hepatorenal lipidosis (2/5). The islets of Langerhans were more numerous and larger than in a control, and morphologically normal in all cases, except in a common marmoset that had a few cells with a foamy cytoplasm and shrunken hyperchromatic or picknotic nucleus. Insulin (5/5), glucagon (3/5), and somatostatin (3/5) immunohistochemistry revealed that most cells stained positively for insulin diffusely in their cytoplasm (5/5) (staining restricted to the vascular pole of b-cells in the control). These findings suggest that obesity, insulin resistance and/or type II diabetes may be implicated and thus a prospective study on these diseases in callitrichids is necessary to determine their etiopathogenesis.

Animals↗

Pancreatic beta-cell function in cirrhotic patients with and without overt diabetes. C-peptide response to glucagon and to meal.

To study the role of pancreatic beta-cell function in glucose intolerance and frank diabetes that sometimes develops in cirrhosis, the C-peptide response to a bolus IV injection of 1 mg of glucagon was measured in nine controls and in two groups of patients with cirrhosis. The first group comprised nine subjects with normal or high-normal fasting plasma glucose and no glycosuria; five of them had impaired glucose tolerance. The second group consisted of eight cirrhotics in whom frank diabetes had developed six to 48 months after the diagnosis of cirrhosis. They were characterized by fasting plasma glucose greater than 140 mg/dL and permanent glycosuria. No differences in the degree of liver impairment or portal-systemic shunting were observed between the two groups. Plasma glucose response to glucagon was similarly reduced in cirrhotic subjects. Basal C-peptide was high normal in patients with cirrhosis, and significantly increased in nondiabetic subjects. By contrast peak C-peptide levels and total C-peptide responses to glucagon were low normal in cirrhotics and significantly reduced in patients with cirrhosis and diabetes. In 14 patients the C-peptide response to a standard meal was also measured. It was significantly reduced in patients with cirrhosis and diabetes (six cases), as compared to cirrhotic subjects without diabetes. Peak C-peptide after IV glucagon significantly correlated with peak C-peptide after the meal (r = .927), or total C-peptide response to meal (r = .871). Impaired insulin secretion may add to insulin resistance in patients with liver cirrhosis, leading to the development of frank diabetes, characterized by fasting hyperglycemia and glycosuria.

Adult↗

Urinary glycosylated, free and total pyridinoline and free and total deoxypyridinoline in diabetes mellitus.

OBJECTIVE: Published data on bone metabolism in diabetes mellitus are conflicting. We have measured pyridinium crosslinks, biochemical markers of bone resorption, in order to evaluate bone resorption in diabetes mellitus. We also wished to investigate whether, as a consequence of chronic hyperglycaemia, pyridinoline is glycosylated to a greater extent in patients with diabetes mellitus. DESIGN AND PATIENTS: This cross sectional study included 142 patients (64 males, 78 females) with insulin dependent and non-insulin dependent diabetes mellitus (IDDM and NIDDM). These patients were compared to a healthy control group of 99 individuals (39 males and 60 females). MEASUREMENTS: Pyridinium crosslinks, glycosylated, free and total pyridinoline (gPYD, fPYD, tPYD) and free and total deoxypridinoline (fDPD, tDPD) were measured in a spot urine sample by high performance liquid chromatography (HPLC). Urinary creatinine, albumin and glucose were also measured. RESULTS: In the diabetic group, values of urinary gPYD and tDYD were significantly lower than in controls. gPYD excretion was lowest in patients with severe glycosuria. Free pyridinium crosslinks, both fPYD and fDPD, were excreted to a significantly lower extent. The molar ratio of tPYD to tDPD was significantly increased in diabetes mellitus. CONCLUSIONS: Decreased excretion of tDPD suggests low bone resorption in IDDM and NIDDM. Pyridinoline is not glycosylated to a greater extent in diabetes mellitus and tends to be decreased in proportion to the degree of glycosuria. Excretion of gPYD, fPYD and fDPD is depressed in severe glycosuria. Diminshed degradation to the final products, fPYD and fDPD, might represent increased resistance to enzymatic activity or diminished enzymatic activity. The increased molar ratio tPYD/tDPD in urine suggests an increased ratio in bone collagen in diabetes mellitus.

Adolescent↗

Dietary self-selection patterns of rats with mild diabetes.

Rats were allowed a free selection of a diet from among separate sources of protein, fat and carbohydrate or were fed a composite diet formulated to approximate the nutrient composition of a commonly used nonpurified diet. Immediately after streptozotocin injections, diabetic rats displayed polyuria, polydipsia and glycosuria as well as elevated fasting plasma glucose levels and glucose intolerance indicative of mild diabetes. Diabetic rats allowed a free choice tended to consume more protein and consumed significantly less carbohydrate than nondiabetics. This pattern of nutrient choice was associated with a reduction of diabetic signs including reduced polyuria, polydipsia and glycosuria. Diabetic rats permitted to choose their diets were not hyperphagic and maintained a slow but steady rate of body weight gain, accompanied by a sparing of body fat stores. In contrast, diabetic rats consuming the composite diet experienced no improvement in diabetic status; these rats displayed a deterioration of fasting plasma glucose, severe polydipsia, polyuria and glycosuria as well as hyperphagia and wasting of fat stores. These data demonstrate that when mildly diabetic rats are given the opportunity to select their own diets, they choose a diet that leads to improvement of their diabetic status.

Animals↗

A method for early detection of graft failure in pancreas transplantation.

Pancreatic transplantation is intended to normalize carbohydrate metabolism in insulin-dependent diabetics by restoring endogenous insulin release, and it is usually performed together with kidney transplantation in patients with end-stage renal failure. A major problem in these patients is the daily control of the grafted pancreas because traditional measurements do not appear to be adequate to evaluate pancreatic function. Aiming at early detection of graft failure, we have analyzed in 8 such patients and in 20 nondiabetic kidney-grafted patients (a control group) the following variables: 24-hr glycosuria (absolute values, or values after natural logarithmic transformation) and 24-hr urinary C-peptide excretion (corrected for 24-hr urinary creatinine). These measurements, considered alone, did not detect pancreatic graft failure; for instance, glycosuria can depend on immunosuppressive steroid treatment, and it was often found even in the control group. On the contrary, the ratio Ln 24-hr glycosuria: 24-hr urinary C-peptide varied from 0.00 to 0.18 in the control group and in normally working pancreatic grafts; when the pancreatic grafts failed, however, as confirmed by arteriographic evidence, histologic findings, or dynamic endocrine tests, this ratio rose far higher than 0.18, reaching values as high as 12.2. Use of this ratio provides a simple technique for daily evaluation of pancreatic graft function and for early detection of graft failure.

Diabetes Mellitus↗