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At least 775 records · Page 43Linked to original sources
PubMed1994

Osteopenia associated with non-insulin-dependent diabetes mellitus: what are the causes?

This study investigated whether alterations in bone mineral content (BMC) and/or in the phosphate-calcium metabolism exist in non-insulin-dependent diabetes mellitus (NIDDM); whether they are linked to glycaemic control and whether antidiabetic therapy--oral agents or insulin--influences BMC and mineral metabolism. A cross-section assessment compared BMC and mineral metabolism in 60 well-controlled and 50 poorly controlled diabetic patients under oral hypoglycaemic therapy with 50 healthy controls. A longitudinal assessment improved the high glucose levels of the poorly controlled diabetic group either by increasing oral treatment or by adding a bedtime NPH insulin. Glycaemic control, BMC and mineral metabolism were followed-up for 1 year. In NIDDM patients BMC is reduced. This reduction is more marked in poorly controlled diabetic patients. In well-controlled diabetes osteocalcin levels are low. In poorly controlled patients glycosuria, hypercalcuria and parathyroid hyperactivity are present. In both groups vitamins 25(OH)-D, 1,25(OH)2-D and calcitonin levels are normal. Improving metabolic control increased BMC, normalized urinary calcium excretion and parathyroid activity and reduced osteocalcin levels. The type of anti-diabetic therapy does not have any significant effect upon BMC or upon phosphate-calcium metabolism. In conclusion, in NIDDM a hard-to-define osteoblast deficit appears to exist. In poorly controlled diabetes the loss of BMC is aggravated by the negative calcium balance caused by the renal calcium leak. This is due to glucosuric-induced osmotic diuresis and is maintained by parathyroid activation.

Adult↗
PubMed1986

Short-term control of feeding: limitation of the glucostatic theory.

In the rat, the short-term effect on spontaneous feeding of intravenous administration of either glucose or glucose plus insulin was investigated. The infusions lasted 4 hours and covered 170% of rats's previously measured spontaneous caloric intake, while control infusions of saline and saline plus insulin were also made. Feeding patterns in subjects' home cages were recorded. Glycaemia and glycosuria were measured in order to asses glucose utilization. When it was infused alone, glucose was utilized at 95% and so covered 160% of oral caloric requirements, while the reduction of oral intake was only 40%. When insulin was co-infused with glucose, utilization reached 100% and oral feeding was reduced by 70%. Saline infusions did not affect oral feeding, and insulin brought about the expected increase in feeding. It is proposed that the mechanism which sustains feeding should depend on multiple macronutrients utilization rather than on one specific chemical family. Furthermore, the fact that insulin has a clear-cut effect, despite its lipogenetic, i.e., metabolite-sequestering properties, favors the ischymetric hypothesis (based on cellular power-production), rather than the energostatic one (based on yields of nutrients).

Animals↗
PubMed1975

Amniotic fluid glucose: a maternal, fetal, and neonatal correlation.

While it has been noted that amniotic fluid glucose is increased in patients withdiabetes mellitus, the exact significance of this finding is not known. Our study of amniotic fluid glucose in 53 amniotic fluid samples from 41 patients shows a high correlation of amniotic fluid glucose levels of 30 mg. per 100 ml. or greater with neonatal hypoglycemia. We have also found elevated amniotic fluid glucose levels in patients whose onlyother indication of abnormal glucose metabolism was recurrent glycosuria. Thepossible significance of these findings is discussed.

Amniotic Fluid↗
PubMed1975

The influence of chronic uremia on hepatic glycogen in the rat.

Long term maintenance of male Wistar rats following sub-total nephrectomy has been shown to alter carbohydrate metabolism. These rats frequently became hypoglycemic and concurrently demonstrated increased hepatic glycogen stores. Chemical analysis of glycogen revealed a significant increase in branching, with a concomitant decrease in glucose residues per segment. The influence of food intake and glycosuria are discussed. Decreased glycogen autolysis is attributed to increased glycogen branching in the uremic liver.

Animals↗
PubMed1998

A new spontaneous animal model of NIDDM without obesity in the musk shrew.

The EDS (early-onset diabetes in suncus) colony has been developed as a new closed breeding colony of the musk shrew (Suncus murinus, Insectivora) exhibiting a high incidence of spontaneous diabetes mellitus. We investigated the characteristic features of diabetic shrews in this colony. All diabetic shrews are characterized by glycosuria (Tes-tape value > or = 3+), hyperglycemia (23.3 +/- 0.8 mmol/l) and polyuria, and they were affected by the age of 3 months. Cumulative incidence (64.1% in males and 27.8% in females) was kept intact after the age of 3 months. The growth pattern of diabetic shrews was similar to that of non-diabetic shrews, and obesity was not consistent in diabetic shrews. The intraperioneal glucose tolerance test revealed both impaired glucose tolerance and impaired insulin secretion in diabetic shrews. Insulin sensitivity of diabetic shrews decreased in the intraperioneal insulin tolerance test. Neither severe hypertrophy nor lymphocytic infiltration was observed in pancreatic islets of diabetic shrews. These facts suggested that diabetic shrews in the EDS colony should be classified as early-onset non-insulin dependent diabetes mellitus (NIDDM) without obesity. Early-onset of severe hyperglycemia with impaired glucose tolerance is a distinctive character compared with other non-obese NIDDM models in rodents. We concluded that the diabetic shrews in the EDS colony are a new animal model of human NIDDM without obesity.

Age of Onset↗
PubMed1977

Glycosylated haemoglobin concentrations and clinitest results in insulin-dependent diabetes.

In 11 insulin-dependent diabetic outpatients, haemoglobin AIc (HbAIc) was measured by an electrofocusing method. Diabetic control was evaluated by the semiquantitative urine test for sugar, 'Clinitest', three times a day every day in the 8 weeks before the HbAIc determination. 24-hour glycosuria and fasting and postprandial blood-glucose levels were measured one to five times during this period. The HbAIc concentration correlated highly with the semi-quantitative urinary-sugar-concentration index but not with the other parameters.

Blood Glucose↗
PubMed1983

Cyclosporin prevents diabetes in BB Wistar rats.

Cyclosporin (U.S.A.N. cyclosporine) was used prophylactically to suppress the development of insulin-dependent diabetes mellitus in BB Wistar rats. In this rat strain diabetes spontaneously develops between 60 and 120 days of age and this condition resembles human type 1 diabetes. In 30 (75%) out of 40 control rats glycosuria and hyperglycaemia developed and these rats became insulin-dependent. Their pancreases showed partial to complete destruction of the islets of Langerhans by lymphocytic infiltration. None of the 40 cyclosporin-treated rats became diabetic and their pancreases were histologically normal. Serum cyclosporin was monitored in a subgroup and the dosage was adjusted accordingly; neither hepatotoxicity nor nephrotoxicity was seen in the treated animals.

Animals↗
PubMed1984

The effect of covert bacteriuria in schoolgirls on renal function at 18 years and during pregnancy.

Schoolgirls shown to have covert bacteriuria (CB) by a screening programme and followed up for 5 years to assess whether chemotherapy had any beneficial effect, underwent a further assessment of renal function at the age of 18 years and during subsequent pregnancies. At age 18, glomerular filtration rate (GFR) and urine concentrating ability were the same as in controls, but fractional reabsorption of glucose was significantly reduced in those who had previously been prescribed chemotherapy because of renal scarring or who had been randomly allocated not to receive prophylactic chemotherapy. Those who had had CB as schoolgirls had a higher frequency of CB in pregnancy than did controls, whether or not prophylactic chemotherapy had been given to the subjects when they were schoolgirls. Furthermore, compared with girls who had had such treatment, untreated patients had smaller increments in GFR, reduced fractional reabsorption of glucose, and more than usual degree of glycosuria during pregnancy. This suggests that subclinical renal damage may be prevented by prophylactic chemotherapy but this advantage is unmasked only by the physiological demands of pregnancy.

Adolescent↗
PubMed1997

Renal threshold for glucose in non-insulin-dependent diabetic patients.

Measurement of glycosuria is still widely used for home monitoring of glycaemia control in non-insulin-dependent diabetes (NIDDM). This method has been criticized because the renal threshold for glucose (RTglu) varies between subjects. In order to evaluate the validity of RTglu by measuring corresponding measurements of blood and urine glucose in NIDDM patients, we studied the blood/urine glucose relationship in 24 NIDDM patients. RTglu estimated from 75 contemporary blood and urine glucose concentrations measured at home by each patient (h-RTglu) was compared with RTglu measured by a hyperglycaemic glucose clamp (c-RTglu). H-RTglu and c-RTglu, being 7.6 mmol/1 (range 5.5-12.4) and 10.3 mmol/1 (6.2-12.3) respectively (P < 0.005), were weakly correlated (R(S) = 0.35, P = 0.15). In conclusion, c-RTglu varies two-fold between NIDDM patients. RTglu detected by home monitored urine and blood glucose determinations underestimates the true RTglu, probably due to the splay phenomenon. However, the method for detection of RTglu used by us seems of clinical relevance, since it reflects the individual blood glucose level at which glucose is detectable in the urine.

Aged↗
PubMed1983

Glomerular alterations in experimental diabetes of the rat.

To detect structural glomerular alterations in the early stages of diabetes mellitus glomeruli from young streptozotocin diabetic rats were studied by light microscopy with morphometric methods 2, 8, 12 and 24 weeks after induction of diabetes. It was found that there is a marked increase in the percentage mesangial surface as compared with the control animals already two weeks after induction of diabetes. The relative mesangial surface fraction was greater in the diabetic animals than in the controls at all test times. It was also demonstrated that the endothelial cell count was reduced in the diabetic animals in the first few weeks of the study. High-grade glycosuria and proteinuria were likewise observed in the diabetic animals. Hence the mesangium appears to be one of the glomerular structures which shows the first changes in the initial stages of diabetes mellitus. Possibly the most likely cause of the changes based on the present study is the diabetic metabolic state (or the insulin deficiency).

Animals↗
PubMed2003

NMR spectroscopic-based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats.

Understanding metabolic variation in "normal" animals is critical to the evaluation of drug-induced metabolic perturbation related to toxicity or pharmacology. NMR spectroscopic-based metabonomic methods were used to evaluate the acclimatization pathways of germ-free (axenic) rats to standard laboratory conditions concomitant with the associated development of gut microfloral communities. Urine samples from male Fischer 344 germ-free rats were collected over 21 days following introduction to a standard laboratory environment and analyzed using NMR spectroscopy. NMR spectra were data-reduced and analyzed using principal component analysis to visualize the changes in the host metabolic trajectory over the course of the study. At days 2 and 6 of the acclimatization process, there were marked episodes of glycosuria. In comparison to the concentrations in the 0-6 h samples, there was a reduction in the level of the tricarboxylic acid cycle intermediates (citrate, 2-oxoglutarate, and succinate) from 6 h to day 6, after which there was a sustained increase until the end of the study. The concentrations of hippurate and trimethylamine N-oxide increased over the course of the study in comparison to the levels at 0-6 h, with the most pronounced increase in the former between days 17 and 21. Phenylacetylglycine levels increased after 6 h whereas 3-hydroxypropionic acid was observed at day 12 and increased up to day 17. By day 21, the urinary metabolic profile was within the control range when compared to historical data, implying the establishment of a stable gut microflora. Although the metabolic alterations caused by the microbial alterations were not as substantial as those from metabolic dysfunction, their presence does have an effect on the interpretation of the profiles, the state of the animal, and the mechanism for the cause of such alterations. Furthermore, the use of oral drug delivery will have an effect on the microbial state, not only as a direct influence of the drug but also from it's associated vehicle. Such effects are likely to be observed particularly in the area of preclinical investigation where the data from these studies are of particular relevance.

Acclimatization↗
PubMed2000

Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG).

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to oxidative stress and if SDG can prevent the incidence of diabetes. The rats were divided into three groups: Group I, BioBreeding normal rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was determined by measuring lipid peroxidation product malondialdehyde (MDA) an index of level of reactive oxygen species in blood and pancreas; and pancreatic chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by glycosuria and hyperglycemia. SDG prevented the development of diabetes by approximately 71%. Development of diabetes was associated with an increase in serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in development of diabetes by SDG was associated with a decrease in serum and pancreatic-MDA and an increase in antioxidant reserve. These results suggest that IDDM is mediated through oxidative stress and that SDG prevents the development of diabetes.

Animals↗
PubMed2001

Renal handling of zinc in insulin-dependent diabetes mellitus patients.

Hyperzincuria is a common feature in diabetic patients, which is still not understood. Based on the above consideration, the aim of the present study was to investigate the renal handling of zinc in insulin-dependent diabetes mellitus (IDDM) patients. The glomerular filtration rate, urinary zinc excretion, zinc clearance, zinc clearance/creatinine clearance ratio, zinc tubular reabsorption, glycosuria, plasma glucose, C-peptide, glucagon, and cortisol were investigated in 10 normal individuals (Group C1 and Group C2, respectively) and 10 IDDM patients (Group E1: hyperglycemic and glycosuric and Group E2: normoglycemic and aglycosuric) during placebo or venous zinc tolerance test. The results showed that urinary zinc excretion and renal zinc clearance were increased after zinc injection in normal individuals (Group C2) and IDDM patients (Groups E1 and E2) when compared with normal individuals-placebo (Group C1). However, these renal parameters were statistically more significant in the hyperglycemic and glycosuric diabetics (Group E1). Because patients in Group E1 had the lowest plasma C-peptide levels and showed a strong negative correlation between CZn++/Ccr ratio and this hormone, we suggest that in this setting insulin inhibits urinary zinc excretion.

Adult↗
PubMed1976

Renal hypertrophy in streptozotocin-diabetic rats.

1. Kidney weight and content of protein, RNA and DNA were measured in rats with streptozotocin diabetes of varying duration. 2. Diabetic rats had larger kidneys than control rats: after 3 days of diabetes the weight increase was 15 per cent and after 42 days of diabetes it was 90 per cent. The protein content rose in parallel to the weight. 3 RNA content was already increased after 36 h of glycosuria, whereas DNA content was unchanged for the first 3 days of diabetes, and increased thereafter. The protein/DNA ratio increased rapidly during the first 3 days but remained constant thereafter. 4. Insulin treatment decreased the renal weight gain by about 67 per cent during the first 8 days of diabetes, but did not prevent the increase in DNA. When insulin was started after 25 days of diabetes there was only a slight regression of kidney growth.

Animals↗
PubMed1978

An interpretation of the intravenous glucose tolerance test in the light of recent findings on the kinetics of glucose and insulin in man.

1. A theoretical investigation of the intravenous glucose tolerance test has been carried out based on recent findings on the kinetics in man of insulin production, distribution, disposal and action, and of glucose turnover and distribution. 2. A good fit to published data on four groups of subjects required a scheme that includes two extravascular glucose spaces and separate venous, arterial and capillary volumes. The fit to the data was little affected by variations within the physiological range of venous and arterial volumes, cardiac output, glycosuria and the properties of the less-accessible glucose pool. 3. The only variables needed to account for the differences between the groups were kinsulin (a measure of the mean sensitivity of insulin-dependent tissues to insulin action) and the readily accessible glucose space. 4. Three published schemes for insulin kinetics were used. They were all consistent with the data and gave very similar relative values for kinsulin in the four groups. 5. It is shown that a rigorous interpretation of the test requires a knowledge of the hepatic response to the glucose load during the test. These effects are not well characterized in pathological states, e.g. diabetes and injury. Consequently conclusions about insulin resistance in these states drawn only from the test are doubtful.

Blood Glucose↗
PubMed1987

Abnormal diurnal urinary sodium and water excretion in diabetic autonomic neuropathy.

1. Diurnal patterns of urine output and sodium and potassium excretion were studied in 10 diabetic patients with and 10 without autonomic neuropathy, and in 10 normal subjects. 2. The diurnal patterns of excretion in the diabetic patients with autonomic neuropathy differed significantly from the two other groups, as a smaller proportion of the 24 h output of urine, sodium and potassium was excreted during the day and a larger proportion was excreted at night. 3. Similar changes were noted in the diurnal patterns of urinary kallikrein excretion in diabetic patients with autonomic neuropathy, and urinary kallikrein output correlated significantly with urine volume but not with urinary sodium excretion. 4. The diurnal patterns of excretion of urinary prostaglandin E2 and 6-keto-PGF1 alpha were not significantly different in diabetic patients with autonomic neuropathy. 5. Nocturia was a common complaint in this group, and the number of nocturnal voidings correlated with night urine volume. There was no evidence of premature bladder emptying. 6. The changes observed in the day/night urine output and sodium excretion could not be explained by glycosuria, insulin regimens, impaired renal function or abnormal diurnal prostaglandin excretion; their possible relevance to the diurnal changes of urinary kallikrein excretion is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Plasma 1,5-anhydroglucitol concentrations are influenced by variations in the renal threshold for glucose.

AIMS: Measurement of serum 1,5-anhydroglucitol (1,5AG) concentrations has been proposed as an alternative to HbA1c as both a marker of diabetic glycaemic control and as a screening test for diabetes. The sugar competes with glucose for renal tubular reabsorption, so hyperglycaemia leads to reduced serum 1,5AG concentrations through increased urinary loss. This study has sought to establish whether plasma 1,5AG can be influenced by not only hyperglycaemia, but by variations in renal threshold for glucose. METHODS: Thirty-eight pregnant women (median age 30 years, range 20-43) found to be normoglycaemic after a 75-g carbohydrate load had plasma 1,5AG and urine glucose measured. RESULTS: Using multivariate analysis, the presence and degree of detectable glycosuria at 2 h post glucose load was strongly predictive of a low plasma 1,5AG concentration (P=0.0012) independently of fasting plasma glucose (P=0.96), 2 h glucose (P=0.029), subject age (P=0.97) and gestation (P=0.36). Thus, when matched for plasma glucose areas under the glucose load curve, 16 glycosuric subjects had significantly lower 1,5AG concentrations compared to 16 nonglycosuric ones (median 1,5AG 46 micromol/l (IQR 30-56) vs. 72 micromol/l (IQR 55-79, P=0.017). CONCLUSIONS: People with the same glucose tolerance may demonstrate variable plasma 1,5AG concentrations depending on their renal threshold for glucose. This inherent characteristic is likely to limit the usefulness of the test when monitoring or screening for diabetes.

Adult↗
PubMed2000

Type 2 diabetes mellitus in UK children--an emerging problem.

AIMS: Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester. METHODS: Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma. RESULTS: Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin. CONCLUSIONS: These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.

Acanthosis Nigricans↗