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PubMed1992

Twenty-four-hour energy expenditure in Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus.

To assess the impact of Type 2 (non-insulin-dependent) diabetes mellitus on energy metabolism, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were measured in a respiratory chamber in 151 Pima Indians, 102 with normal glucose tolerance (67 male/35 female, (mean +/- SD) 28 +/- 7 years, 99 +/- 24 kg, 32 +/- 9% body fat) and in 49 with Type 2 diabetes (22 male/27 female, 35 +/- 11 years, 107 +/- 33 kg, 39 +/- 7% body fat), after at least 3 days on a weight maintaining diet. After adjustment for differences in fat-free mass, fat mass, age and sex, 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were significantly higher in diabetic patients than in control subjects (72 kcal/day, p less than 0.05; 99 kcal/day, p less than 0.005; 99 kcal/day, p less than 0.001 respectively). Spontaneous physical activity was similar in both groups whereas the thermic effect of food, calculated as the mean energy expenditure corrected for activity throughout the day above sleeping metabolic rate and expressed as a percentage of energy intake, was significantly lower in Type 2 diabetic patients (17.1 +/- 7.1 vs 19.8 +/- 5.6%, p less than 0.05). Adjusted values of 24-h energy expenditure, basal metabolic rate and sleeping metabolic rate were correlated with hepatic endogenous glucose production (r = 0.22, p less than 0.05; r = 0.22, p less than 0.05; r = 0.31, p less than 0.01 respectively). Therefore, increased basal and sleeping metabolic rates, resulting in increased 24-h sedentary energy expenditure may play a role in the weight loss so often observed in Type 2 diabetic subjects in addition to the energy loss from glycosuria.

Adult↗

PubMed1986

The cochlea of the spontaneously diabetic mouse. I. Electron microscopic observation of KK mice.

We examined the cochleae of the spontaneously diabetic KK mice by using transmission electron microscopy. At the age of 3 months, the mice started to show evidence for glycosuria and hyperglycemia, and tissue sections showed beginning cochlear pathology. The pathological changes present were found to be limited to the stria vascularis: protrusions of marginal cells, swellings of intermediate cells and widening of intercellular spaces were the main findings seen. These changes progressed with age, but were not observed in age-matched non-diabetic 57BL/6 mice. The possible mechanism of diabetes causing cochlear pathology is discussed.

Animals↗

PubMed1987

Increased urinary excretion of collagen metabolites in cadmium-metallothionein nephropathy.

In order to investigate the effect of cadmium-metallothionein (Cd-MT) on renal reabsorption of collagen metabolites, urinary excretion of hydroxylysine (Hyl), glucosyl-galactosyl-Hyl (Glc-Gal-Hyl), galactosyl-Hyl (Gal-Hyl), and hydroxyproline (Hyp), which are unique collagen metabolites, was determined in rats. Administration of Cd-MT resulted in acute renal failure in the form of proteinuria, aminoaciduria and glycosuria. Protein content in urine was greatly increased 1 day after injection of Cd-MT and decreased from 5 days, while the maximum levels of excretion of amino acids and glucose were observed at 6 days post-injection. The urinary excretion of total Hyp and Hyl, including Glc-Gal-Hyl, Gal-Hyl and free Hyl, were significantly increased at 3, 6 and 8 days after injection of Cd-MT with the maximum level at 6 days. Moreover, the molar ratio of Glc-Gal-Hyl/Gal-Hyl of urine in the Cd-MT-treated group was almost the same as that in the controls. These results suggest that a portion of Hyp, Hyl and its glycosides is normally reabsorbed from the renal tubule in the controls, and Cd-MT exposure caused an increase in urinary excretions of Hyp and Hyl, including its glycosides, through a renal tubular defect in reabsorption of Hyl in the same manner as with common amino acids.

Acute Kidney Injury↗

PubMed1985

Reduction of diabetes incidence of BB Wistar rats by early prophylactic insulin treatment of diabetes-prone animals.

A group of 36 diabetes-prone BB Wistar rats were given prophylactic insulin treatment with heat-treated bovine ultralente insulin (15 IU X kg-1 X day-1) from 50 to 142 days of age. The incidence of Type 1 (insulin-dependent) diabetes at the end of the treatment period was compared to that of 36 control animals given insulin only from the first day of glycosuria. At withdrawal of the prophylactic insulin treatment, 6 of 36 treated animals were insulin-dependent, while 15 of 36 control animals had developed diabetes (p less than 0.02). One control animal (day 153) and 2 insulin-treated animals (day 172 and 186) subsequently developed diabetes, yielding an overall diabetes incidence of 16 of 36 controls against 8 of 36 insulin treated (p less than 0.05). The finding that prophylactic insulin treatment of diabetes-prone BB Wistar rats reduced the incidence of diabetes suggests a relationship of the immune destruction of B cells to the endogenous insulin production/secretion rate.

Animals↗

PubMed1987

Ultrastructural alterations in cardiac muscle of diabetic BB Wistar rats.

The cardiac muscle of BB Wistar rats suffering from diabetes for 8 and 16 weeks (8-Wk and 16-Wk of DM) were examined by light and electron microscopy. The diabetic rats were kept alive by injections of small doses of insulin and exhibited severe hyperglycaemia, glycosuria and weight loss. The heart/body weight ratio of all diabetic groups was greater than that of age matched controls. Over the experimental period, the left ventricular myocardium of the diabetic BB rats sustained damage that was progressively more serious with the duration of the diabetic state. In BB rats after 8-wk of diabetes the myocardium contained large numbers of lipid droplets and glycogen granules around mitochondria which showed patchy swelling, and slight loss of myofilaments. Disruption of mitochondrial membranes and extensive loss of myofilaments were seen in rats diabetic for 16 wk. In addition, dilatation of the sarcoplasmic reticulum-transverse tubular system, formation of a contraction band and myelin bodies and widening of the intercellular space at the fasciae adherens of the intercalated disc were characteristically observed in BB rats after 16-wk of diabetes. However, there were no evident alterations in the capillaries of any diabetic BB rats. Morphometric analyses showed the volume percentage of myofibrils in diabetic rats to be significantly decreased when compared with controls. The loss of myofibrillar elements may be a primary damage induced by insulin deficiency. The formation of contraction bands suggests Ca2+ overload caused by diabetic metabolic disturbances.

Actin Cytoskeleton↗

PubMed1992

Acute tubulointerstitial nephritis with uveitis syndrome presenting as multiple tubular dysfunction including Fanconi's syndrome.

We describe an 11-year-old male patient with acute tubulointerstitial nephritis with uveitis (TINU) syndrome. He presented with easy fatigability, pallor, nocturia and weight loss. Laboratory examination disclosed anaemia, polyclonal hypergammaglobulinaemia, low molecular weight proteinuria, glycosuria, aminoaciduria, proximal and distal renal tubular acidosis, a urine concentration defect and decreased creatinine clearance. The multiple renal tubular dysfunction and slight glomerular dysfunction subsided spontaneously. Bilateral anterior uveitis was manifested 7 months after the onset of the disease. This is the first reported case of TINU syndrome with multiple proximal and distal tubular dysfunction including a complete type of Fanconi's syndrome.

Acidosis, Renal Tubular↗

PubMed1986

Distribution of endogenous albumin in the glomerular wall of streptozotocin-induced diabetic rats as revealed by high-resolution immunocytochemistry.

Endogenous albumin was revealed with high resolution in the glomerular wall of renal tissue from normoglycaemic and long-term streptozotocin-induced hyperglycaemic rats applying the protein A-gold immunocytochemical approach. In tissues from normal animals, albumin antigenic sites were detected at the level of the endothelial cell basal plasma membrane and in the subendothelial side of the lamina densa of the glomerular basal laminae. The epithelial side of the laminae was weakly labelled, while the urinary space was devoid of labelling. In the podocytes, labelling for albumin was confined to few lysosomal structures. In diabetic animals, concomitant with hyperglycaemy, low insulin levels, significant glycosuria, proteinuria and albuminuria, the glomerular basal laminae displayed the characteristic increase in thickness found in diabetic microangiopathy (404 +/- 45 nm versus 190 +/- 10 nm). Major basal laminae deposits were also found in the mesangial regions. Albumin antigenic sites were detected throughout the entire thickness of the glomerular basal laminae without any preferential accumulation at any particular site. Labelling was also found over flocculent material present in the urinary space. Numerous densely labelled lysosomal structures were present in the podocytes. The basal laminae deposits in the mesangial regions were labelled for albumin. Morphometrical evaluations made on the distribution of the labelling confirmed the qualitative observations. Two sites for albumin retention were revealed in the glomerular wall of the normal animal: the endothelial cell basal membrane (less than 10 nm) and the subendothelial side of the lamina densa (50 nm).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Longitudinal study of first phase insulin release in the BB rat.

First phase insulin release was measured in response to intravenous glucose given weekly from approximately day 40 in 6 BB rats which subsequently developed diabetes and in age-matched non-diabetic (n = 15) and normal Wistar rats (n = 8) until day 180. The mean sequential insulin responses in BB rats with and without diabetes were significantly lower (p = 0.008 and less than 0.0001, respectively) than in normal rats from an early age. Five diabetic BB rats showed a progressive decline in first phase insulin release immediately prior to glycosuria, with the impaired phases ranging from 25-50 days. However, protracted periods of low first phase responses were also seen in several aglycosuric BB rats, which showed histological evidence of insulitis and B-cell loss. Our findings demonstrate that, although most BB rats with diabetes show a progressive impairment of B-cell function preceding the disease, this aberrant phase can also be present in BB rats which remain aglycosuric. Impaired first phase insulin release in response to serial intravenous glucose tolerance tests may not be a reliable predictor of Type 1 (insulin-dependent) diabetes in this animal model.

Animals↗

PubMed1982

Use of intravenous immune globulin in patients receiving bone marrow transplants.

Patients undergoing bone marrow transplantation for acute leukemia or aplastic are a great risk for the development of interstitial pneumonia associated with the cytomegalovirus (CMV). Passive immunization with a CMV immune plasma has been found to be effective for the prevention of interstitial pneumonia after marrow transplantation. Because of the limited availability of high-titered CMV plasma, we studied the kinetics of CMV antibody in bone marrow transplant patients receiving immune globulin intravenous, 5%, in 10% maltose (IGIV). Several lots of IGIV had CMV radioimmunoassay (RIA) antibody titers (1:30,000) comparable to the CMV antibody titers in the CMV immune plasma. A single infusion of 20 cc/kg of IGIV produced a mean peak CMV RIA antibody titer of 1:9,500. This titer fell to 1:1,000 after seven days. These antibody titers were approximately two-to three-fold lower than the CMV RIA antibody titers achieved after a 10 cc/kg dose of the CMV immune plasma. Administration of IGIV at doses lower than 20 cc/kg produced correspondingly lesser increases in the CMV antibody titers of recipients. At all doses, IGIV was well tolerated and caused no significant biochemical abnormalities. Some patients experienced mild elevation of their serum glucose levels and asymptomatic glycosuria. We are presently evaluating the efficacy of IGIV (20 cc/kg given once every week) for the modification of CMV infection and prevention of interstitial pneumonia after bone marrow transplantation in a randomized, controlled study. The effects of IGIV on the incidence and outcome of bacterial, fungal, and other viral infections are also being analyzed.

Antibodies, Viral↗

PubMed1977

Clinical evaluation of somatostatin as a potential ajunct to insulin in the management of diabetes mellitus.

To determine whether somatostatin, an inhibitor of glucagon and growth hormone secretion, might be useful as an adjunct to insulin the management of diabetic hyperglycaemia, seven insulin-requiring diabetic men were given somatostatin (100 microgram/h, IV) continuously for 3 days after their diabetes had been treated intensively by diet and insulin on a metabolic ward. During infusion of somatostatin and despite reduction in average insulin dose exceeding 50%, there was improvement in diabetic control as assessed by postprandial hyperglycaemia, 24-h glycosuria and the average daily serum glucose level and its fluctuation; when somatostatin was discontinued, but insulin doses held constant, diabetic control rapidly worsened. No adverse effects were observed. These results indicate that somatostatin plus insulin can be a more effective regimen than insulin alone in controlling diabetic hyperglycaemia. A longer acting and more selective somatostatin preparation may prove useful as an adjunct to insulin in the management of diabetes.

Adult↗

PubMed1979

Chemical diabetes in the adult rat as the spontaneous evolution of neonatal diabetes.

Injection of streptozotocin in newborn rats induced a severe diabetic syndrome on day 4 after birth, with acute hyperglycaemia and glycosuria. Over the next 3 weeks spontaneous recovery occurred as attested by normal basal blood glucose and plasma insulin levels. Recovery was, however, incomplete in the adult since a definite impairment in insulin release and glucose disposal was observed. This state was characterized by the following features: 1) a 72% decrease in pancreatic insulin stores without change in pancreatic glucagon stores; 2) a slight but consistent elevation of blood glucose in the fasted and fed basal states and especially of blood glucose 90 min after an IV glucose load (2 g/kg) performed under pentobarbitone anaesthesia; 3) a considerable decline in the glucose-induced insulin release with a decrease in the maximal response. Both early and late phases of insulin release were impaired, as indicated by in vivo glucose infusion experiments. Basal plasma glucagon levels were normal. Over a period of 12 months with a normal laboratory diet no aggravation of the chemical diabetic state was observed. This new experimental syndrome is a potentially interesting model for the study of the influence of environmental factors on the development of overt diabetes.

Aging↗

PubMed1982

Pathophysiology of human proximal tubular transport defects.

The generalized proximal tubular transport abnormalities comprising the Fanconi syndrome (glycosuria, generalized aminoaciduria, the proximal form of renal tubular acidosis, and increased renal clearance of phosphate, urate, calcium, magnesium, and potassium) may be ascribed to interference with "sodiumlinked" active transport. Evidence is presented that the majority of conditions known to cause Fanconi syndrome in man or experimental animals are associated with inhibitors of the renal Na-K-ATPase-ATP transport system.

Adenosine Triphosphate↗

PubMed1989

Streptozotocin-induced diabetes is not a model for methylmalonic acidaemia.

The streptozotocin-treated diabetic rat was not found to be a suitable animal model for methylmalonic acidaemia as previously described. Urinary methylmalonic acid (MMA) was measured in adult Wistar rats prior to and following injection of streptozotocin (40 mg/kg). Plasma and tissue MMA levels were measured following the induction of diabetes and compared with data from control rats. MMA levels were determined by a gas chromatographic-mass spectrometric method (McMurray et al., 1986). Diabetes was confirmed by the 10 x increase in 24 h urine volume; glycosuria; glycaemia; and weight loss. Urinary MMA excreted did not change during the 11 week diabetic period and there was no difference between the pre- and post-diabetic phases (p less than 0.05). Plasma and tissue MMA concentrations were not elevated in this diabetic animal model. Also in contrast to earlier reports, the vitamin B12 levels of the diabetic rats were not elevated compared to controls (p less than 0.05).

Animals↗

PubMed1992

Cephaloridine-induced nephrotoxicity in the Fischer 344 rat: proton NMR spectroscopic studies of urine and plasma in relation to conventional clinical chemical and histopathological assessments of nephronal damage.

The acute toxicological effects of the nephrotoxic antibiotic cephaloridine (CPH, 0-1500 mg/kg) in male Fischer 344 (F344) rats, have been investigated over 48 h using clinical chemistry, histopathology and proton nuclear magnetic resonance (1H NMR) spectroscopy of urine and plasma. High field (400 and 600 MHz)1H NMR urinalysis revealed increased excretion of lactic acid, acetoacetate, alanine, valine, lysine, glutamine and glutamate and a severe, time-dependent glycosuria. A major change observed in urine of CPH-treated animals was the dose-dependent increase in HB which may relate to altered energy metabolism. CPH also caused dose-dependent decreases in the urinary excretion of hippurate, allantoin and protein (conventional assay). This abnormal metabolic profile is consistent with a functional defect in the S1/S2 regions of the proximal tubule, and was confirmed by histology post mortem. Functional changes observed included elevations in blood urea nitrogen (BUN) and urine flow rate (UFR) and dose-related decreases in urine osmolality. Spin-echo 1H NMR spectroscopic analysis of lyophilised plasma, reconstituted with 2H2O revealed an abnormal phase modulation of the methyl signal from free alanine and it is postulated that this is due to the release of transaminases from damaged tissue which via a reversible conversion to pyruvate, cause variable deuteration of alanine at the alpha-CH position. This observation suggests that 1H NMR spectral patterns are also dependent on the level of plasma transaminases and this may provide a novel indicator of tissue damage.

Animals↗

PubMed1981

The adult presenting idiopathic Fanconi syndrome.

The adult presenting Fanconi syndrome is a rare familial disorder. A 30-year follow-up of one of the original families in the literature is reported here. Two important points have emerged. Firstly, the inheritance in this family is dominant, not recessive as originally suggested, and there remains no good example in the literature of a recessive inheritance of this disorder. Second, in this family lactic aciduria and tubular proteinuria are probably the earliest manifestations of the disorder in childhood, with glycosuria and aminoaciduria developing in the second decade and osteomalacia from the start of the fourth decade. Glomerular function deteriorates slowly but is compatible with a normal lifespan.

Adult↗

PubMed1986

Multi-system coxsackievirus B-6 infection with findings suggestive of diabetes mellitus.

A fatal case of Coxsackievirus B-6 (CBV-6) infection in a 4 1/2-year-old girl is reported. The disease was initially characterized by a severe meningoencephalitis and, successively, by the appearance of hyperglycaemia and glycosuria, concomitantly with complement-fixing-islet cell antibodies (CF-ICA) and ICA, diarrhoea, electrolyte disorders, arrhythmia and decrease of the IgG levels, suggesting a multi-system involvement. CBV-6 was identified by isolation from stool and cerebrospinal fluid and by detection of specific IgM antibodies.

Child, Preschool↗

PubMedDate not supplied

Diabetic neuropathic cachexia.

A case of diabetic neuropathic cachexia is presented. This unusual syndrome within the broad group of diabetic neuropathies is characterized by extreme loss of body mass and severe neuropathic pain. The loss of body weight is unassociated with glycosuria or ketoacidosis. Initially, the patient may present a confusing picture suggestive of carcinomatous neuropathy.

Cachexia↗

PubMedDate not supplied

Remission from insulin dependence induced by continuous subcutaneous insulin infusion (CSII) in type I, newly diagnosed diabetics: role of some hormonal and immunologic factors.

Optimal and early control of recent onset, type I diabetes by intensive insulin therapy has been reported to allow insulin withdrawal in about two thirds of subjects treated. We used continuous s.c. insulin infusion (CSII) in the attempt to induce a temporary remission of insulin dependence in 18 newly diagnosed young adult diabetics. After 10 days of optimized glycometabolic control, insulin infusion was stopped and patients were switched to glibenclamide (15 mg/die) plus metformin (1 g/die). Diabetics were considered in remission of insulin dependence when their metabolic control fulfilled the following criteria for at least 3 months: absence of glycosuria, pre- and post-prandial blood glucose less than or equal to 120 and 180 mg/dl, respectively, HbA1c less than or equal to 7%. Insulin therapy could be discontinued for periods of over three months in 11 subjects (61%) and for as long as 18 months in one case. Insulin requirement during CSII was slightly higher in nonremitters (NR) than in remitters (R): 0.36-0.64 vs 0.26-0.41 U/kg/die. After 24 months from CSII, R still showed lower insulin requirement (0.35-0.42 U/kg/die) than NR (0.55-0.75 U/kg/die). Further, the role of some hormonal and immunologic factors was investigated. Plasma C-peptide and glucagon were measured, fasting and 2h after each meal, both on admission and immediately after CSII, when patients were switched to oral therapy. No difference in hormone levels could be detected on admission, whereas, after CSII, mean post-prandial increase of C-peptide over basal was significantly higher in R than in NR (1.18 +/- 0.37 vs 0.22 +/- 0.16 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗