Diabetes Mellitus Activity Research Articles

The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Increased Glomerular Production or Permeability in Diabetes Mellitus?

Background: A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-CoV-2 infection was increased as a sign of glomerular dysfunction. The aim of this report was to investigate the relation of the urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations, i.e., the ULSAM and PIVUS cohorts. Methods: HPLBII-P was measured by an ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in the urine of a community-based cohort of 75-year-old men, n = 387, and women, n = 401 (PIVUS). KIM-1, NGAL, and albumin were measured in urine and cathepsin S and cystatin C in serum. Results: HPLBII-P was significantly raised among males with diabetes in the ULSAM (p < 0.0001) and PIVUS cohorts (p ≤ 0.02), but not in the female cohort of PIVUS. In the female subpopulation of insulin-treated diabetes, HPLBII-P was raised (p = 0.02) as compared to women treated with oral antidiabetics only. In the ULSAM cohort, HPLBII-P was correlated to NGAL, KIM-1, and albumin in urine both in non-DM (all three biomarkers; p < 0.0001) and in DM (NGAL; p = 0.002, KIM-1; p = 0.02 and albumin; p = 0.01). Plasma glucose and HbA1c in blood showed correlations to U-HPLBII-P (r = 0.58, p < 0.001 and r = 0.42, p = 0.004, respectively). U-HPLBII-P and cathepsin S were correlated in the ULSAM group (r = 0.50, p < 0.001). No correlations were observed between U-HPLBII-P and serum creatinine or cystatin C. Conclusions: The urine measurement of HPLBII-P has the potential to become a novel and useful biomarker in the monitoring of glomerular activity in diabetes mellitus.

Anemoside B4 Exerts Hypoglycemic Effect by Regulating the Expression of GLUT4 in HFD/STZ Rats.

Anemoside B4 (B4) is a saponin that is extracted from Pulsatilla chinensis (Bge.), and Regel exhibited anti-inflammatory, antioxidant, antiviral, and immunomodulatory activities. However, its hypoglycemic activity in diabetes mellitus has not been evaluated. Here, we explored the effect of B4 on hyperglycemia and studied its underlying mechanism of lowering blood glucose based on hyperglycemic rats in vivo and L6 skeletal muscle cells (L6) in vitro. The rats were fed a high-fat diet (HFD) for one month, combined with an intraperitoneal injection of 60 mg/kg streptozotocin (STZ) to construct the animal model, and the drug was administrated for two weeks. Blood glucose was detected and the proteins and mRNA were expressed. Our study showed that B4 significantly diminished fasting blood glucose (FBG) and improved glucose metabolism. In addition, B4 facilitated glucose utilization in L6 cells. B4 could enhance the expression of glucose transporter 4 (GLUT4) in rat skeletal muscle and L6 cells. Mechanistically, B4 elevated the inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Furthermore, we confirmed the effect of B4 on glucose uptake involved in the enhancement of GLUT4 expression in part due to PI3K/AKT signaling by using a small molecule inhibitor assay and constructing a GLUT4 promoter plasmid. Taken together, our study found that B4 ameliorates hyperglycemia through the PI3K/AKT pathway and promotes GLUT4 initiation, showing a new perspective of B4 as a potential agent against diabetes.

Analysis of Foot Sensation and Physical Activity in Diabetes Mellitus

Neuropathy is a condition in which the patient experiences a decreased sensation of pain in the legs that can affect the physical activity of diabetic patients mellitus, until work productivity decreases. This pain is often disturbing, limiting activity and decreasing the work productivity of diabetic patients. The aim of this study was to identify a correlation between foot sensation and physical activity of diabetic mellitus patients. cross-sectional was used in this study. Data collection uses instruments in the form of observation sheets to assess the results of foot sensation examination with a 10 gr monofilament test and IPAQ-SF (International Physical Activity Questionnaire Short Form) questionnaire sheet on 70 respondents with a purposive sampling technique. The data was processed using Kendall's Tau statistical test. A total of 70 respondents obtained an average age of 57 years, long-suffering from diabetes mellitus for an average of 4 years. 39 people received normal test results and 31 experienced decreased leg sensation and an average score of 5 with moderate physical activity categories. Gamma statistical test results p-value value 0.0001 or (p≤0.05) with a positive relationship direction and strangeness (r = -0.706). There is a relationship between decreased leg sensation and physical activity of diabetic mellitus patients at Bangetayu Health Center Semarang

Periodontal risk assessment in a teaching hospital population in Saudi Arabia’s Eastern Province

ObjectiveWith this cross-sectional study, we aimed to evaluate factors associated with moderate and high risk of periodontal disease (PD) progression in the Saudi population. MethodsWe reviewed 281 patients’ clinical charts from predoctoral periodontal clinics at the dental teaching hospital in the College of Dentistry (COD) at Imam Abdulrahman Bin Faisal University (IAU) in Dammam, Saudi Arabia. After obtaining ethical approval, we determined the Periodontal Risk Assessment (PRA) of the included patients based on the modified criteria developed by Lang and Tonetti (2003). We used logistic regression on stratified data and divided the results into two categories (low-moderate and high risk) to assess the effect modifier for potential risk factors. We used SPSS version 22 for data analysis, and considered a P-value ≤ 0.05 to be statistically significant. ResultsOut of the 281 patients, 104 (37.0%) were male and 177 (63.0%) were female, with a mean age of 39.9 ± 14.0 years; 78.1% were Saudi nationals, 77% were married, and 44.6% were in the age group of 30 to 49. The PRA revealed 86 (30.5%) to represent high risk, 108 (38.3%) denoted moderate risk, and 88 (31.2%) signaled low risk for periodontitis. Logistic regression analysis showed that males were three times more likely to have high PRA (OR = 3.24) and to be married (OR = 2.77), as well as to be active smokers (OR = 8.87). The highest predictive factors of high PRA were 8 or more pockets ≥ 5 mm (OR = 29.0), those with active diabetes mellitus (DM; OR = 10.2), and those with 8 or more missing teeth (OR = 9.15). ConclusionSaudi males who are married and have residual periodontal pockets, are actively diabetic, and with missing teeth are at high risk of PD. Further research is needed with a larger sample size comparing the general population with and without PD.

Effects of respiratory muscle training on parasympathetic activity in diabetes mellitus.

This study verified the effects of respiratory muscle training (RMT) on hemodynamics, heart rate (HR) variability, and muscle morphology in rats with streptozotocin-induced diabetes mellitus (DM). Thirty-six male Wistar rats were randomized into 4 groups and 34 completed the study: i) sham-sedentary (Sham-ST; n=9); ii) sham-RMT (Sham-RMT; n=9); iii) DM-sedentary (DM-ST; n=8); and iv) DM-RMT (DM-RMT; n=8). Hemodynamics were assessed by central cannulation, and R-R intervals were measured by electrocardiogram. In addition, the effects of RMT on the cross-sectional area of the diaphragm, anterior tibial, and soleus muscles were analyzed. The induction of DM by streptozotocin resulted in weight loss, hyperglycemia, reduced blood pressure, and attenuated left ventricular contraction and relaxation (P<0.05). We also observed a decrease in root mean square of successive differences between adjacent RR intervals (RMSSD) index and in the cross-sectional area of the muscles assessed, specifically the diaphragm, soleus, and anterior tibial muscles in diabetic rats (P<0.05). Interestingly, RMT led to an increase in RMSSD in rats with DM (P<0.05). The induction of DM produced profound deleterious changes in the diaphragmatic and peripheral muscles, as well as impairments in cardiovascular hemodynamics and autonomic control. Nevertheless, RMT may beneficially attenuate autonomic changes and improve parasympathetic modulation.

Protective effect of exogenous hydrogen sulfide on diaphragm muscle fibrosis in streptozotocin-induced diabetic rats.

Diabetes mellitus is a group of chronic metabolic disorders, which causes serious damage to a variety of organs, such as the retina, heart, and skeletal muscle. The diaphragm is an important skeletal muscle involved in respiration in mammals. Fibrosis of the diaphragm muscle affects its contractility, which in turn impairs respiratory function. Accumulating evidence suggests that exogenous hydrogen sulfide (H2S) exhibits anti-fibrotic activity in diabetes mellitus, but whether and how H2S exerts this anti-fibrotic effect in the diabetic diaphragm remains unclear. The current work for the first time reveals that exogenous H2S attenuates hyperglycemia-induced fibrosis of the diaphragm muscle and strengthens diaphragmatic biomechanical properties in diabetes mellitus, and the mechanism may involve the alleviation of collagen deposition by suppression of the nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-mediated inflammatory reaction. Therefore, H2S supplementation could be used as an efficient targeted therapy against the NLRP3 inflammasome in the diabetic diaphragm.

Macrophylloflavone: A New Biflavonoid from Garcinia macrophylla Mart. (Clusiaceae) for Antibacterial, Antioxidant, and Anti-Type 2 Diabetes Mellitus Activities.

Investigations of antibacterial, antioxidant, and anti-type 2 diabetes mellitus activities have been carried out on Garcinia macrophylla Mart. plant extract fractions. An isolate from a fraction of ethyl acetate extract was characterized with spectroscopic data. A new biflavonoid compound was found to have a skeleton of 5,7,4′,5″,7″,3‴,4‴-heptahydroxyflavanone[3-6″] flavones which was named macrophylloflavone (1). The compound was evaluated for its antibacterial activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 with cephazolin as a positive control, antioxidant assay against 2,2 diphenyl-1-picrylhydrazyl (DPPH) with ascorbic acid as the positive control, and anti-type 2 diabetes mellitus treatment with metformin as a positive control. The biflavonoid compound exhibited a good inhibition for bacteria and free radical DPPH. Furthermore, biflavonoid compound treatment on the diabetic rats suggested its ability to decrease the blood glucose level. This study provided evidence that the plant has antibacterial, antioxidant, and antidiabetic properties.

Dietary supplementation of jute leaf (Corchorus olitorius) modulates hepatic delta-aminolevulinic acid dehydratase (δ-ALAD) activity and oxidative status in high-fat fed/low streptozotocin-induced diabetic rats.

Impaired liver function is associated with decreased hepatic delta-aminolevulinic acid dehydratase (δ-ALAD) activity in diabetes mellitus. Hence, this study described the effect of dietary jute leaf (Corchorus olitorius) on hepatic δ-ALAD activity in high-fat fed combined with low-dose streptozotocin administered diabetic rats. Animals were fed diets containing 35% fat for 14days prior to a single administration of low-dose (35mg/kg body weight) streptozotocin to induce diabetes. Thereafter, the animals were randomly placed in groups and fed 100mg/g jute leaf-supplemented diets for 30days. The result showed that jute leaf supplementation significantly (p<0.05) reversed the decreased hepatic δ-ALAD activity, increased hepatic catalase and SOD activity accompanying the decrease in serum AST and AST activities. This finding suggests that restoration of hepatic δ-ALAD activity, modulation of hepatic function biomarkers, and increase in antioxidant status could be possible underlying events mediating the hepatoprotective effect of jute leaf in diabetic conditions. PRACTICAL APPLICATIONS: Decrease in hepatic δ-ALAD activity has been associated with diabetes-induced hepatotoxicity arising from prolonged and uncontrolled hyperglycemia. Therefore, increased δ-ALAD activity represents improved hepatic function in diabetic situations. Antidiabetic properties of jute leaf have been demonstrated but information on its effect on hepatic δ-ALAD is lacking. Thus, this study revealed that dietary supplementation of jute leaf restored hepatic δ-ALAD activities and improved liver antioxidant status in diabetic rats which is an indication of its hepatoprotective properties.

AKTIVITAS FISIK PADA PASIEN DIABETES MELITUS TIPE 2 DENGAN NEUROPATI PERIFER : TINJAUAN LITERATUR

Type 2 diabetes mellitus is a chronic disease that could cause damage to foot peripheral nerves, namely peripheral neuropathy. Diabetic peripheral neuropathy is a damage and inability to regenerate nerve cells due to exposure of chronic hyperglycemia which can lead to various symptopms and complications. Therapy is aimed at improving symptoms and delaying development of peripheral neuropathy, one of which is physical activity which is one of the cornerstones of management of diabetes mellitus. An explanation of the benefits of physical activity in diabetes mellitus has been widely discussed, but nore in peripheral neuropathy. This literature review aims to explain the types and benefits of physical activity in peripheral neuropathy. Seven literature reviewed were obtained through electronic database search EBSCOHost, Proquest, and Clinical Key with key words physical activity, exercise intervention, diabetic peripheral neuropathy, and type 2 diabetes mellitus. Peripheral neuropathy patients can carry out various types of physical activity, either weight bearing or non-weight bearing exercise. Patients with ulcers, wounds and severe foot deformity can do non-weight bearing exercise such as static cycling and upper body ergometer. Another can do walking, aerobics, balance exercises, stretching, tai chi, resistance training, and foot ankle exercises. Aerobics is a physical activity that can prevent and delay development of peripheral neuropathy. Balance training can improve sensory and motor neuropathy. In general, physical activity can improve innervation in the cutaneous tissue, regenerate nerve cells, improve the symptoms of neuropathy in the form of pain, balance disorders, risk of falls, and obstacles to physical mobility.

Пути защиты организма от повреждения клеток при сахарном диабете

Recognition hyperinsulinemia as the root cause of type 2 diabetes mellitus is becoming more supporters. The overload nutrition cell and insulin resistance is developing as a result of hyperinsulinemia. Insulin resistance is not the only one protection mechanism. Functional system to limited excessive insulin action includes other mechanisms. This review describes the reactions that develop in the tissues in diabetic patients and their relationship with excessive exposure to insulin. Negative feedback mechanism under excessive stimulation of insulin action includes action contrainsular hormones, no β-cell response on increasing the glucose in the extracellular medium, reduction of C-peptide, induction of β-cell apoptosis. The compensation mechanisms includes the restriction of consumption of substances and flow of information, the redirecting excess in the adi-pose tissue, the glycogen synthesis and the activation of kinase-3 synthase glycogen. The conditions GI insulin is able to bind and activate receptors IGF-type 1 to a greater extent than insulin receptors. At diabetes the repro-duction, the growth and the differentiation of cells are accelerated, leading to tumor growth, the accumulation of senescent cells. The depletion and reduction of telomerase activity in diabetes mellitus also have an adaptive value. Contact with receptors undifferentiated cells caused by their high sensitivity and low capacity for insulin resistance, operates referral mechanism power is the same as for obesity. Young cells of functionally active or-gans die, some cells accelerate differentiation and less active peripheral located in hypoxic conditions, may be-come cancerous. The author believes that the growth of tumors after intensive treatment of diabetes is associated with excess insulin action.

Inhibition of mTOR activity in diabetes mellitus reduces proteinuria but not renal accumulation of hyaluronan

Objectives. Accumulation of extracellular matrix (ECM) components is an early sign of diabetic nephropathy. Also the glycosaminoglycan hyaluronan (HA) is elevated in the renal interstitium during experimental diabetes. The mammalian target of rapamycin (mTOR) pathway participates in the signaling of hyperglycemia-induced ECM accumulation in the kidney, but this has not yet been investigated for HA. We hypothesized that interstitial HA accumulation during diabetes may involve mTOR activation.Methods. Diabetic rats (6 weeks post-streptozotocin (STZ)) were treated with rapamycin to inhibit mTOR or vehicle for 2 additional weeks. Kidney function (glomerular filtration rate, renal blood flow, urine output) and regional renal HA content were thereafter analyzed. The ability of the animals to respond to desmopressin was also tested.Results. Diabetic animals displayed hyperglycemia, proteinuria, hyperfiltration, renal hypertrophy, increased diuresis with reduced urine osmolality, and reduced weight gain. Cortical and outer medullary HA was elevated in diabetic rats. Urine hyaluronidase activity was almost doubled in diabetic rats compared with controls. The ability to respond to desmopressin was absent in diabetic rats. Renal blood flow and arterial blood pressure were unaffected by the diabetic state. In diabetic rats treated with rapamycin the proteinuria was reduced by 32%, while all other parameters were unaffected.Conclusion. Regional renal accumulation of the ECM component HA is not sensitive to mTOR inhibition by rapamycin, while proteinuria is reduced in established STZ-induced diabetes. Whether the diabetes-induced renal accumulation of HA occurs through different pathways than other ECM components, or is irreversible after being established, remains to be shown.

The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients.

Diabetic neuropathy (DN) represents the main cause of morbidity and mortality among diabetic patients. Clinical data support the conclusion that the severity of DN is related to the frequency and duration of hyperglycemic periods. The presented experimental and clinical evidences propose that changes in cellular function resulting in oxidative stress act as a leading factor in the development and progression of DN. Hyperglycemia- and dyslipidemia-driven oxidative stress is a major contributor, enhanced by advanced glycation end product (AGE) formation and polyol pathway activation. There are several polymorphous pathways that lead to oxidative stress in the peripheral nervous system in chronic hyperglycemia. This article demonstrates the origin of oxidative stress derived from glycation reactions and genetic variations within the antioxidant genes which could be implicated in the pathogenesis of DN. In the diabetic state, unchecked superoxide accumulation and resultant increases in polyol pathway activity, AGEs accumulation, protein kinase C activity, and hexosamine flux trigger a feed-forward system of progressive cellular dysfunction. In nerve, this confluence of metabolic and vascular disturbances leads to impaired neural function and loss of neurotrophic support, and over the long term, can mediate apoptosis of neurons and Schwann cells, the glial cells of the peripheral nervous system. In this article, we consider AGE-mediated reactive oxygen species (ROS) generation as a pathogenesis factor in the development of DN. It is likely that oxidative modification of proteins and other biomolecules might be the consequence of local generation of superoxide on the interaction of the residues of L-lysine (and probably other amino acids) with α-ketoaldehydes. This phenomenon of non-enzymatic superoxide generation might be an element of autocatalytic intensification of pathophysiological action of carbonyl stress. Glyoxal and methylglyoxal formed during metabolic pathway are detoxified by the glyoxalase system with reduced glutathione as co-factor. The concentration of reduced glutathione may be decreased by oxidative stress and by decreased in situ glutathione reductase activity in diabetes mellitus. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of DN. In this work, the supporting data about the association between the -262T > C polymorphism of the catalase (CAT) gene and DN were shown. The -262TT genotype of the CAT gene was significantly associated with higher erythrocyte catalase activity in blood of DN patients compared to the -262CC genotype (17.8 ± 2.7 × 10(4) IU/g Hb vs. 13.5 ± 3.2 × 10(4) IU/g Hb, P = 0.0022). The role of these factors in the development of diabetic complications and the prospective prevention of DN by supplementation in formulations of transglycating imidazole-containing peptide-based antioxidants (non-hydrolyzed carnosine, carcinine, n-acetylcarcinine) scavenging ROS in the glycation reaction, modifying the activity of enzymic and non-enzymic antioxidant defenses that participate in metabolic processes with ability of controlling at transcriptional levels the differential expression of several genes encoding antioxidant enzymes inherent to DN in Type I Diabetic patients, now deserve investigation.

Improving Patients' Adherence to Physical Activity in Diabetes Mellitus: A Review

Regular physical activity (PA) is a key element in the prevention and management of type 2 diabetes mellitus (T2DM). Participation in regular PA improves blood glucose control and can prevent or delay T2DM and its complications, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. However, most people with T2DM are not active and show poor adherence. This paper reviews the possible barriers to PA and strategies to improve the adherence to PA. Based on the currently available literature, it is concluded that self-efficacy and social support from family, friends, and health care providers play the important role in adoption and maintenance of regular PA. Here we also highlight some new modern and innovative interventions that facilitate exercise participation and improve the adherence.

当科における喉頭全摘術後の合併症の検討

Introduction: We examined post-total laryngectomy complications. By using PGE1 during the perioperative period, we made it possible to achieve complication-free laryngeal surgery for patients with radiation failure. We now present our evaluation of complication frequencies of patients with radiation failure and those without it.Patients and Methods: Our work was a retrospective chart review of 37 patients who underwent total laryngectomy in our hospital from 2001 to 2008. These included 24 patients who underwent surgery for primary treatment and 12 patients who underwent salvage surgery due to radiation failure. The remaining one patient had laryngo-pharyngeal stenosis after radiation therapy for hypopharyngeal cancer and underwent total laryngectomy as a salvage surgery. One T2, 9 T3 and 14 T4 cases underwent surgery for primary treatment and 2 T2, 5 T3 and 5 T4 cases underwent salvage surgery. Closure of the hypopharyngeal mucosa was performed using 4-0 silk and no other procedures were conducted to reinforce the wound.Results: As for 24 patients who underwent primary treatment, a minor leakage and a pharyngo-cutaneous fistula were observed in two patients who had active diabetes mellitus and their initiation of oral intake were on the 17th post-operative day (POD) and the 34th POD, respectively. Their days of discharge were also prolonged to the 30th POD and the 50th POD, respectively. One patient had a subcutaneous abscess around his tracheostoma and the commencement of his oral intake and day of discharge were prolonged to the 13th POD and the 28th POD. Another patient also had a subcutaneous abscess and his day of discharge was prolonged to the 36th POD. The average number of days to begin oral intake after surgery was 9.1 days and the average number of days until discharge after surgery were 23.3 days. However, with 13 patients who underwent salvage surgery and had no leakage or other wound complications the average number of days to discharge after surgery was 20.8 days.Discussion: According to our protocols for laryngectomies, the administration of PGE1 during the perioperative period, even for patients with radiation failure that had no wound complication, shortened the time to discharge from the hospital. Since diabetes mellitus seemed to be a key factor in wound complication after laryngectomies, even for patients undergoing primary treatment, we must consider new methods for treating them.

Factor VIIa and tissue factor procoagulant activity in diabetes mellitus after acute ischemic stroke: Impact of hyperglycemia

Alterations in blood coagulation may explain the poorer neurological outcome with diabetes mellitus and hyperglycemia after acute ischemic stroke. We studied the relationships between diabetes mellitus, hyperglycemia, whole blood tissue factor procoagulant activity (TF-PCA) and plasma factorVIIa (FVIIa) in ten patients with type 2 diabetes mellitus and 11 non-diabetic patients at baseline and 6, 12, 24, and 48 hours (h) after presentation for acute stroke. In addition, we examined plasma prothrombin fragment 1+2 (F1.2) and thrombin-antithrombin complexes (TAT) as markers of thrombin generation. Stroke severity, assessed by National Institute of Health Stroke Scale (NIHSS), was similar at baseline (p=0.26) but worse in diabetic (8.20+/-4.3) than nondiabetic patients (2.67+/-2.1, p=0.023) at 48 h. At presentation, diabetic patients had higher FVIIa (p=0.004) and lower TF-PCA (p=0.027) than non-diabetic patients but both were higher than in normal control subjects. FVIIa levels remained higher in diabetic patients at 6, 12 and 24 h after stroke. In diabetic patients, FVIIa (r=0.40, p=0.02) and TF-PCA (r=0.50, p=0.02) correlated with blood glucose; and, FVIIa correlated with plasma F1.2 (r=0.34, p=0.002) and TAT levels (r=0.62, p<0.0001). In non-diabetic patients, TF-PCA, but not FVIIa, correlated with F1.2 (r=0.402, p=0.010) and TAT (r=0.39, p=0.011). Combining both groups, NIHSS scores were positively related to FVIIa levels (r=0.50, p=0.021) and inversely related to TF-PCA levels (r=-0.498, p=0.02). Acute ischemic stroke patients with diabetes and hyperglycemia have a more intense procoagulant state compared with nondiabetic patients. This is related to glucose levels and provides a potential mechanism for the observed worse prognosis in such patients after acute stroke.

Paraoxonase activity and lipid peroxidation in female patients with type 2 diabetes mellitus and without coronary heart disease

The rate of lipid peroxidation and the parameters of antioxida- tive defense, including the activity of paraoxonase that is essen­tial for the prevention of low-density lipoprotein oxidation, was studied in 229female patients with type 2 diabetes mellitus with and without coronary heart disease (CHD) under varying glyc­emic control. Carbohydrate and lipid metabolisms were explored by unified biochemical studies, blood insulin levels were meas­ured by radioimmunological assay. The activity of paraoxonase associated with high-density lipoproteins of ester hydrolase was spectrophotometrically determined by using paraoxan as a sub­strate. Along with dyslipoproteinemia and insulin resistance, there was a drastically reduced paraoxonase activity that was as­sociated with the high-density lipoproteins of the antioxidant en­zyme and more pronounced in diabetics with CHD. A highly sig­nificant inverse correlation of the activity of the enzyme with the rate of lipid peroxidation and a less close relationship to basal glycemia have been verified, which substantiates the polygenic nature of decreased paraoxonase activity in diabetes mellitus.

Impaired endogenous fibrinolysis in diabetes mellitus: mechanisms and therapeutic approaches.

In type II diabetes mellitus the activity of the endogenous fibrinolytic system is reduced secondary to increased plasma activity of the plasminogen activator inhibitor type 1 (PAI-1). Because PAI-1 is considered an independent risk factor for cardiovascular disease, increased PAI-1 activity in diabetes mellitus may partly explain the increased susceptibility to both primary atherosclerosis and restenosis after angioplasty in this disease. The factors contributing to increased PAI-1 expression in diabetes mellitus are reviewed as well as possible therapeutic approaches to normalize increased PAI-1 expression.

The relationship between glycated hemoglobin and polymorphonuclear leukocyte leukotriene B4 release in people with diabetes mellitus

In order to evaluate polymorphonuclear leukocyte (PMN) activity in diabetes mellitus, leukotriene B4 (LTB 4) levels were measured in sixty patients, 31 affected with Type 1 diabetes mellitus and 29 affected with Type 2 diabetes mellitus. The LTB 4 levels (12.1+0.2 pg/100 μl) in diabetic patients were higher compared to those of the control group (7.9+0.1 pg/100 μl) ( P<0.001), and remained significantly higher ( P<0.001) (12.8+0.2 pg/100 μl) than in the control group (11.0+0.2 pg/100 μ1) after stimulation with calcium ionophore. A significant and positive correlation between glycated hemoglobin and LTB 4 was demonstrated ( P<0.001, r=0.80). This study demonstrates that in diabetic patients there is a PMN activation and that this activation is correlated to glycated hemoglobin level.

Negative association between erythrocyte reduced glutathione concentration and diabetic complications.

1. Multiple logistic regression analysis of biochemical and clinical variables in diabetic patients was performed to identify those associated with the presence of diabetic complications (retinopathy, neuropathy and nephropathy). 2. The presence of diabetic complications correlated positively with duration of diabetes and patients age and negatively with the concentration of reduced glutathione in erythrocytes. Individually, retinopathy, neuropathy and nephropathy correlated with duration of diabetes, but retinopathy also correlated positively with haemoglobin A1C in diabetic patients. In insulin-dependent patients, the concentration of methylglyoxal was also in the logistic model for retinopathy and diabetic complications, but the logistic regression coefficient was not significant. 3. Multiple linear regression analysis indicated that erythrocyte reduced glutathione concentration correlated negatively with D-lactate concentration and positively with duration of diabetes in insulin-dependent patients and correlated negatively with glucose concentration in non-insulin-dependent diabetic patients. 4. In non-diabetic subjects, erythrocyte glyoxalase I activity correlated positively with methylglyoxal concentration. There was no similar correlation in diabetic patients. In insulin-dependent patients, methylglyoxal concentration correlated positively with duration of diabetes. 5. Glyoxal and methylglyoxal are detoxified by the glyoxalase system with reduced glutathione as co-factor. The concentration of reduced glutathione may be decreased by oxidative stress and by decreased in situ glutathione reductase activity in diabetes mellitus. A reduced concentration of reduced glutathione may predispose diabetic patients to oxidative damage and to alpha-oxoaldehydemediated glycation by decreasing the in situ glyoxalase I activity. Recent studies of vascular endothelial cells in vitro have suggested that alpha-oxoaldehydes detoxified by glyoxalase I are the major precursors of advanced glycation end products implicated in the development of diabetic complications. The role of these factors in the development of diabetic complications and the prospective prevention of diabetic complications by supplementation of reduced glutathione and/or alpha-oxoaldehyde-scavenging agents now deserve investigation.

Decreased susceptibility of glycated very low density lipoproteins to lipoprotein lipase in vitro and prevention by glutathione.

In vitro glycation of very low density lipoprotein (VLDL) reduced the susceptibility to lipoprotein lipase (LPL) as the level of glycation increased. Addition of reduced glutathione to an incubation medium of serum and glucose interfered with glycation of serum proteins when the concentration of reduced glutathione was higher than 10 mM. At concentrations higher than 25 mM, it also significantly prevented the glycation induced reduction of fatty acid releases from VLDL by LPL. There were no such effects on glycation of serum protein and the fatty acid release from the addition of aminoguanidine. By contrast, addition of D-lysine enhanced glycation of serum proteins by glucose and further decreased fatty acid release from VLDL by LPL. From these results, it is suggested that glycation of VLDL decreases the susceptibility of VLDL to LPL. Delayed catabolism of VLDL in diabetic patients is considered partly caused by glycation of apoproteins, which renders VLDL less sensitive to LPL, in addition to the decreased LPL activity in diabetes mellitus.