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PubMed2000

Fibronectin and lipoprotein(a) are inversely related to plasminogen activator inhibitor type-1 levels in Type 2 diabetic patients without complications.

Plasminogen activator inhibitor type-1 (PAI-1), the most important physiological fibrinolysis inhibitor, is considered an independent factor of cardiovascular risk in Type 2 diabetes mellitus (T2DM). In previous papers we demonstrated that a T2DM population without complications presents: 1) PAI-1 not increased with respect to a control group; and 2) a negative correlation between PAI-1 and lipoprotein(a) [Lp(a)], suggesting that in these subjects PAI-1 levels could be modulated by the "endothelial stress" induced by Lp(a) and diabetes. This work has been performed in order to better verify this intriguing hypothesis, and the endothelial stress has been evaluated through a marker of endothelial damage, fibronectin (FNC). For this purpose we chose a T2DM population without complications (n=73) and a control group (n=46). Plasma concentrations of FNC, Lp(a), PAI-1 antigen and activity, and the main parameters of lipo- and glycometabolic balance were determined. Fibronectin was significantly higher in diabetics with respect to controls (p<0.01). As expected, significant correlation between PAI-1 antigen, PAI-1 activity and Lp(a) (r=-0.54,p<0.01 and r=-0.39,p<0.01, respectively) was found only in diabetic patients. In the same group FNC showed a significant correlation with PAI-1 antigen and activity (r=-0.49,p<0.01 and r=-0.47; p<0.01, respectively), while no relationship was found between Lp(a) and FNC. Multiple regression analysis showed statistically significant correlation between PAI-1 antigen and PAI-1 activity with FNC and Lp(a) in diabetic patients without complications (p<0.05). These data suggest that in absence of complications, the endothelium is able to modulate PAI-1 levels, favouring in that way the fibrinolytic pathway and, subsequently, the recovery of the endothelial integrity. This modulation seems to be related to parameters such as Lp(a) and FNC, although the mechanisms of the endothelial stress of these two molecules seem to be different.

Blood Glucose↗
PubMed1999

[Usefulness of current and retrospective markers of glycemia for early prognostication of ischemic stroke in diabetics and non-diabetics].

Diabetes mellitus is associated with an increased incidence of ischaemic stroke but it is not established whether it may exacerbate its clinical course and prognosis. In the study we have assessed relations of fasting (1st-2nd day of illness) and pre-stroke glycaemia (measured as HbA1 and FA) with recent clinical manifestation and outcome within one month in 22 diabetics and 37 non-diabetics with ischaemic brain infarction in the internal carotid territory. Merely enhanced HbA1 in the majority of non-diabetic stroke patients confirmed impaired pre-stroke glucose tolerance but did not influence severity of hemiparesis and further prognosis. Abnormally high both HbA1 and dFA in diabetics, reflecting non-sufficient metabolic control of illness did not exacerbate acute manifestation of stroke and outcome. Fasting post-stroke glycaemia that expresses a stress response of brain origin was determinative for clinical state but not for one-month prognosis in diabetics and non-diabetics with brain infarction.

Aged↗
PubMed2001

Glucose monitoring in type 2 diabetes.

A major goal in the treatment of type 2 diabetes is to maintain blood glucose values in the normal or near normal range. A system of monitoring glycemic control, which includes self-monitoring of blood glucose (SMBG) by the patient, and frequent glycated protein assays, is an important tool for achieving this goal. Optimal use of SMBG by the patient is best accomplished through comprehensive glucose monitoring education, which includes appropriate monitor selection and use and strategies to use monitoring results to improve glycemic control.

Bias↗
PubMed2001

The obese Göttingen minipig as a model of the metabolic syndrome: dietary effects on obesity, insulin sensitivity, and growth hormone profile.

The objective of the study reported here was to induce obesity in the female Göttingen minipig to establish a model of the human metabolic syndrome. Nine- to ten-month-old female Göttingen minipigs received a high-fat high-energy (HFE) diet or a low-fat, low-energy (LFE) diet. The energy contents derived from fat were 55 and 13 %, respectively. After 5 weeks, animals were subjected to dual energy x-ray absorptiometry (DEXA) scanning, intravenous glucose tolerance testing (IVGTT), and 6-h growth hormone profile recording. After treatment, mean body weight of pigs of the LFE group was 21.0 +/- 0.4 kg, and was 26.8 +/- 0.2 kg in pigs of the HFE group (P < 0.0001). The DEXA scanning indicated that the fat content of the LFE group was 10.0 +/- 1.2 % versus 15.2 +/- 0.7 % in the HFE group (P < 0.003). Triglycerides concentration was significantly (P < 0.05) increased in pigs of the HFE group (0.24 +/- 0.03 mM), compared with that in pigs of the LFE group (0.13 +/- 0.04 mM). Preprandial plasma glucose and insulin concentrations were not affected, but insulin area under the curve during IVGTT was significantly high in the obese animals. Growth hormone (GH) secretion was low in both groups of pigs. The obese minipig shares some of the metabolic impairments seen in obese humans, and may thus serve as a model of the metabolic syndrome.

Absorptiometry, Photon↗
PubMed2002

Fluidising effect of resorcylidene aminoguanidine on sarcolemmal membranes in streptozotocin-diabetic rats: blunted adaptation of diabetic myocardium to Ca2+ overload.

The "remodelling" of cardiac sarcolemma in diabetes is believed to underlie the reduced sensitivity of diabetic hearts due to their overload with extracellular calcium. Along with a non-enzymatic glycosylation and the free radical-derived glycoxidation of sarcolemmal proteins there is ongoing reduction in cardiomyocyte membrane fluidity, the modulator of cardiac sarcolemmal functioning. Aminoguanidine derivatives, that inhibit glycation and glycoxidation, might suppress myocardium "remodelling" occurring in diabetic heart. To verify this hypothesis, we studied physical parameters of cardiac sarcolemma from the streptozotocin-induced diabetic rats (45 mg.kg(-1) i.m.) treated with resorcylidene aminoguanidine (RAG, 4 or 8 mg.kg(-1) i.m.). The treatment with RAG not only completely abolished protein glycation and a generation of free oxygen species (p < 0.001) in treated diabetic animals, but also considerably attenuated the decrease in sarcolemmal membrane fluidity (p < 0.001). In diabetic animals the "normalization" of the sarcolemmal membrane fluidity was accompanied by the vastly increased susceptibility of diabetic hearts to be overload with external calcium. We concluded that the decreased fluidity of the sarcolemmal membrane, apparently linked to the excessive glycation of sarcolemmal membrane proteins, might be intimately connected with the adaptation mechanism(s) that are likely to develop in diabetic heart to protect it against the overload with external calcium.

Adaptation, Physiological↗
PubMedDate not supplied

[Glycosylation products in the early diagnosis and prognostic evaluation of carbohydrate metabolism disorders].

HbAIc and FA were investigated as markers in the diagnosis of early carbohydrate metabolic derangements. A group with normal TSH and a high concentration for glycosylation products was singled out. Carbohydrate metabolic derangements in 89 per cent showed a tendency to progression. Interrelationship between glycemia and PH was noted. The diagnostic and prognostic importance of HbAIc and FA was determined, and their combined use for single investigation of carbohydrate metabolism was recommended, making it possible to exclude "accidental" latent transitory hyperglycemia. TSH determination at early stages can be of low informative value, whereas HbAIc and FA measurements can detect disorders of carbohydrate metabolism early enough.

Adolescent↗
PubMed1992

Brain catecholamine concentrations in hyperosmolar diabetic and diabetic rats.

The concentration of brain catecholamines were measured and compared in the experimentally made hyperosmolar diabetic, diabetic and normal control rats in order to clarify the metabolic changes of the brain in these states. Diabetes was induced with streptozotocin and hyperosmolarity was achieved through deprivation of water for 50 hours prior to experimentation. Dopamine, norepinephrine and epinephrine concentrations were measured in the left cerebral cortex, hypothalamic-thalamic area, cerebellum and medulla oblongata. Dopamine and norepinephrine concentrations were significantly elevated in the cerebral cortex, hypothalamic-thalamic area and cerebellum of the dehydrated hyperosmolar-diabetic rats relative to those of normal controls (p < 0.01-0.05). In diabetes with high blood sugar level, the norepinephrine concentration was significantly elevated in the cerebral cortex, cerebellum and medulla oblongata, and these changes generally paralleled the increase in fasting blood glucose. It was concluded that hyperosmolarity due to dehydration contributed these changes. The findings of this study further suggest that changes in brain catecholamines may be involved in the nervous system disturbances that occur in the dehydrated hyperosmolar-diabetes and severe diabetes.

Animals↗
PubMed2004

Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer?

High levels of insulin have been associated with increased risk of breast cancer, and poorer survival after diagnosis. Data and sera were collected from 603 breast cancer patients, including information on diet and physical activity, medical history, family history, demographic, and reproductive risk factors. These data were analyzed to test the hypothesis that excess insulin and related factors are directly related to mortality after a diagnosis of breast cancer. The cohort was recruited from breast cancer patients treated at the British Columbia Cancer Agency between July 1991 and December 1992. Questionnaire and medical record data were collected at enrollment and outcomes were ascertained by linkage to the BC Cancer Registry after 10 years of follow-up. The primary outcome of interest was breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using Cox proportional hazards regression models to relate risk factors to outcomes, controlling for potential confounders, such as age and stage at diagnosis. Data for biological variables were analyzed as a nested case-control study due to limited serum volumes, with at least one survivor from the same cohort as a control for each breast cancer death, matched on stage and length of follow-up. High levels of insulin were associated with poorer survival for postmenopausal women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest to lowest tertile, P trend = 0.10], while high dietary fat intake was associated with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3-18.1, comparing highest to lowest quartile). Higher dietary protein intake was associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2-0.8, comparing highest to lowest quartile).

Adult↗
PubMed2006

[Dynamics of rat hepatocyte histone glycoxidation after general x-ray irradiation].

Dynamics of structural parameters of hepatocyte histone glucoxidative modification 3, 9 and 24 h after general X-ray irradiation of rats at dose 5 Gy was studied. Dynamics of these parameters (content of carbonyl groups, bityrosyl cross-linkings, pentosidines, advanced glycation end products) was compared with alterations in DNA structure (according to agarose gel electrophoresis) and lipid peroxidation extent (by malondialdehyde content). Oxidative stress induced by hepatocyte irradiation results in structural damage of DNA and histones accompanied by an increase of histone bityrosyl cross-linking and carbonyl content. The content of advanced glycation end products in histones corresponds to the extent to DNA damage and malondialdehyde content. The described postradiation modifications of histones may be important for regulation of chromatin function.

Animals↗
PubMed1991

Indications that branched chain amino acids, in addition to glucagon, affect the glomerular filtration rate after a high protein diet in insulin-dependent diabetes.

Hormonal changes and whole blood free amino acid levels and their relation to renal function were measured in 12 insulin-dependent diabetic patients after two 10-day periods with a diet consisting of 10% and 20% respectively of the energy as protein. The patients were 15-21 years old and mean duration of diabetes was 12 (5-20) years. Glomerular filtration rate, renal plasma flow, and albumin excretion rate were measured together with plasma concentrations of glucagon, growth hormone, insulin-like growth factor 1 (IGF-1), somatostatin, serum insulin and free amino acids in blood. Glomerular filtration rate was 123 +/- 3 ml/min/1.73 m2 on high protein diet and 113 +/- 3 ml/min/1.73 m2 on low protein diet (p = 0.02). Renal plasma flow was unchanged. Glucagon, IGF-1, branch chained amino acids (BCAA), tyrosine, phenylalanine, lysine, and methionine were increased after the high protein diet. Growth hormone, somatostatin, insulin, and other amino acids remained unchanged. The increase in glomerular filtration rate was significantly correlated to the increase in glucagon, isoleucine, and valine (glucagon r = 0.71, p = 0.01, isoleucine r = 0.59, p = 0.04, valine r = 0.62, p = 0.03). In a multiple regression model the increase in glomerular filtration correlated most strongly to the increase in isoleucine, followed by valine and glucagon. Together these variables explained 88% of the total variance of the change in glomerular filtration rate (r2 = 0.88, p = 0.001). Albumin excretion rate was correlated to IGF-1 (r = 0.86, p less than 0.001) on the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

[Multicenter study of the risk of infection in diabetics. I. Correlation between altered glucose metabolism and cutaneous reactivity to the Multitest IMC].

Within the framework of a multicentre study on the risk of infection in diabetes, organised to document the frequency of subjects predisposed to infoffion among the diabetic population and to evaluate the effects of Thymostimulin on the latter, 176 subjects (38%) with a deficient response (less than or equal to alarm score), of which 82 (18%) were totally anergic, were selected from a population of 460 diabetic subjects, both type I and type II, using the Multitest IMC multiantigenic delayed hypersensitivity test. It was not possible to establish any relationship between altered skin response and age, whereas males appeared to be more predisposed than females. The degree of metabolic compensation also influenced the degree of skin response, although this was not decisive. Hypergic and anergic responses were more frequent in type I diabetic subjects than in type II subjects, probably due to the greater immunological involvement of this type of diabetes.

Adolescent↗
PubMed1991

The detection of an early advanced glycation product which co-elutes with the Amadori product on aminophenylboronate affinity chromatography.

The production of an antiserum recognizing an early advanced glycation product of glycated human serum albumin (HSA) is reported. The antiserum was produced with the intention of recognizing the Amadori product, i.e. the monofructosamine derivative, of any glycated protein. In retrospect, however, the immunogen appears to have been transformed in vivo which led to the production of antibodies to an early advanced glycation product. Two-site immunometric and competitive ELISAs showed that the affinity-purified antibodies recognized glycated HSA only after it had been stored for several months. This recognition, by the antibody, was more specific for the transformed product than for the original hapten (1-amino-1-deoxy-D-fructose-6-aminohexanoic acid) used for immunization by a factor of more than 1,000. These antibodies also detected immunoreactive material present in the elution fraction after in vivo glycated HSA had been chromatographed on an aminophenylboronate affinity column, indicating that an early advanced glycation product can co-elute with the Amadori product of glycated HSA on aminophenylboronate affinity chromatography. This suggests that the antiserum recognized an early advanced glycation product that also contained cis-diols as does the Amadori product, and may prove useful in the early detection of clinical complications in diabetic patients.

Aminocaproic Acid↗