Onset Of Diabetic Complications Research Articles

Gastrointestinal Symptoms in Diabetes Occur Long before Diabetic Complications

Background/Aims: Gastrointestinal (GI) manifestations are common in patients with diabetes complications, such as autonomic neuropathy. However, the prevalence of GI symptoms before the development of diabetes complications is unclear.Methods: We conducted an interview survey of functional GI disorders among patients with diabetes visiting the endocrinology clinic of a general hospital using the Rome III criteria. The survey consisted of questions regarding functional dyspepsia, irritable bowel syndrome, and functional constipation, including functional defecation disorder.Results: In total, 509 patients were included in the analysis. The patients were divided into three groups: prediabetes (n = 115), diabetes without neuropathy (n = 275), and diabetes with neuropathy (n = 119). With regard to GI symptoms, the prevalences of functional dyspepsia in the prediabetes, diabetes without neuropathy, and diabetes with neuropathy groups were 16.52%, 27.27%, and 23.53%, respectively; those of irritable bowel syndrome were 8.70%, 11.68%, and 16.81%, respectively, and those of functional constipation were 8.85%, 11.85%, and 15.25%, respectively. In the subgroup analysis, symptoms of postprandial distress syndrome (e.g., postprandial fullness and early satiety) were more prevalent than symptoms of epigastric pain. In the constipation group, symptoms of pelvic outlet obstruction (such as the sensation of anorectal obstruction or blockage and the need for manual maneuvers to facilitate defecation) were more prevalent than symptoms of slow-transit constipation.Conclusions: The prevalence of functional GI disorders increases with diabetes severity. Diabetes-related GI symptoms appear long before the onset of diabetes complications.

IDF21-0124 Relationship between Serum Zinc Status and Diabetic Nephropathy in Algerian Patients with Type 2 Diabetes

Background: Diabetic nephropathy is a microvascular complication associated with diabetes that causes the kidneys to slowly deteriorate, leading to end-stage renal disease. Nephropathy associated with diabetes has been attributed to oxidative stress. Chronic zinc deficiency generally results in an increased sensitivity to the effects of oxidative stress. Zinc deficiency is often seen in diabetic patients. This alteration in zinc status appears to be involved in the development of microvascular complications of diabetes. Aim: The objective of this study will be to explore the relationship between zinc status and the progression of nephropathy in type 2 diabetes. Method: The study involved 80 normotensive diabetic patients with positive microalbuminuria and 60 healthy non-diabetic subjects of corresponding age. For all subjects, a serum zinc assay was performed on the ICE 3300 atomic absorption spectrometer from Thermo Fisher, a serum creatinine assay on Cobas 501 from Roche Diagnostic with evaluation of GFR, as well as a microalbuminuria assay. on the DCA Vantage from Siemens. Results: Serum zinc levels were low (p <0.001) in diabetic patients compared to non-diabetic control subjects. Elevated levels of microalbuminuria (p <0.001) were observed in diabetic patients with low serum zinc levels compared to those with normal serum zinc levels. Serum zinc level in diabetic patients was inversely correlated with serum creatinine (r = −0.51, p <0.001), microalbuminuria (r = −0.587, p <0.001) and positively with GFR (r = 0.24, p <0.01). Discussion: The results of our study support the observation that diabetes affects zinc status with a significant decrease in serum zinc levels at the onset of diabetic complications. During progression to the stages of diabetic nephropathy, morphological and structural changes occur in the glomerular and basal membrane of the kidneys, hyperfiltration, thickening of the glomerular basement membrane. All of these changes will cause albumin with trace metals to leak into the urine. Therefore, the hypozincemia seen in diabetics can be attributed to hyperzincuria. The results of this study are consistent with results reported by others.

In Search of Differential Inhibitors of Aldose Reductase

Aldose reductase, classified within the aldo-keto reductase family as AKR1B1, is an NADPH dependent enzyme that catalyzes the reduction of hydrophilic as well as hydrophobic aldehydes. AKR1B1 is the first enzyme of the so-called polyol pathway that allows the conversion of glucose into sorbitol, which in turn is oxidized to fructose by sorbitol dehydrogenase. The activation of the polyol pathway in hyperglycemic conditions is generally accepted as the event that is responsible for a series of long-term complications of diabetes such as retinopathy, cataract, nephropathy and neuropathy. The role of AKR1B1 in the onset of diabetic complications has made this enzyme the target for the development of molecules capable of inhibiting its activity. Virtually all synthesized compounds have so far failed as drugs for the treatment of diabetic complications. This failure may be partly due to the ability of AKR1B1 to reduce alkenals and alkanals, produced in oxidative stress conditions, thus acting as a detoxifying agent. In recent years we have proposed an alternative approach to the inhibition of AKR1B1, suggesting the possibility of a differential inhibition of the enzyme through molecules able to preferentially inhibit the reduction of either hydrophilic or hydrophobic substrates. The rationale and examples of this new generation of aldose reductase differential inhibitors (ARDIs) are presented.

Recipient age and outcome after pancreas transplantation: a retrospective dual-center analysis.

With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death‐censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.

Lycopene Improves the Metformin Effects on Glycemic Control and Decreases Biomarkers of Glycoxidative Stress in Diabetic Rats.

IntroductionOxidative stress and exacerbated generation of advanced glycation end products (AGEs) participate in the onset of diabetic complications. Lycopene is a potent antioxidant; evidence accounts for its ability to mitigate diabetic disturbances, including the deleterious events of advanced glycation. Therefore, this carotenoid has emerged as a candidate to be used in combination with antidiabetic drugs, such as metformin, attempting to counteract the glycoxidative stress. This study investigated the effects of the treatments with lycopene or metformin, alone or in combination, on glycoxidative stress biomarkers and antioxidant defenses in diabetic rats.MethodsStreptozotocin-induced diabetic rats were treated for 35 days with lycopene (45 mg/kg) or metformin (250 mg/kg), alone or as mixtures in yoghurt. Plasma levels of glucose, triglycerides, cholesterol, thiobarbituric acid reactive substances and protein carbonyl groups (biomarkers of oxidative damage), fluorescent AGEs (biomarkers of advanced glycation), and paraoxonase 1 activity (antioxidant enzyme) were assessed. Changes in the hepatic and renal levels of glycoxidative damage biomarkers and the activities of antioxidant enzymes were investigated.ResultsThe combination of lycopene with metformin maintained the beneficial effects of the isolated treatments, improving the glucose tolerance and lipid profile, lessening biomarkers of oxidative damage, and increasing the paraoxonase 1 activity. Besides, the combined therapy caused further decreases in postprandial glycemia, plasma levels of cholesterol and AGEs, avoided lipid peroxidation (plasma, kidney), and increased antioxidant defenses, mainly the activity of superoxide dismutase (liver, kidney), indicating the maintenance of the lycopene effects.ConclusionLycopene combined with metformin may act synergistically in the control of postprandial glycemia, dyslipidemia and glycoxidative stress, as well as increased antioxidant defenses, arising as a promising therapeutic strategy to mitigate diabetic complications.

Aldose Reductase Differential Inhibitors in Green Tea.

Aldose reductase (AKR1B1), the first enzyme in the polyol pathway, is likely involved in the onset of diabetic complications. Differential inhibition of AKR1B1 has been proposed to counteract the damaging effects linked to the activity of the enzyme while preserving its detoxifying ability. Here, we show that epigallocatechin gallate (EGCG), one of the most representative catechins present in green tea, acts as a differential inhibitor of human recombinant AKR1B1. A kinetic analysis of EGCG, and of its components, gallic acid (GA) and epigallocatechin (EGC) as inhibitors of the reduction of L-idose, 4-hydroxy2,3-nonenal (HNE), and 3-glutathionyl l-4-dihydroxynonanal (GSHNE) revealed for the compounds a different model of inhibition toward the different substrates. While EGCG preferentially inhibited L-idose and GSHNE reduction with respect to HNE, gallic acid, which was still active in inhibiting the reduction of the sugar, was less active in inhibiting HNE and GSHNE reduction. EGC was found to be less efficient as an inhibitor of AKR1B1 and devoid of any differential inhibitory action. A computational study defined different interactive modes for the three substrates on the AKR1B1 active site and suggested a rationale for the observed differential inhibition. A chromatographic fractionation of an alcoholic green tea extract revealed that, besides EGCG and GA, other components may exhibit the differential inhibition of AKR1B1.

Effect of socioeconomic deprivation on outcomes of diabetes complications in patients with type 2 diabetes mellitus: a nationwide population-based cohort study of South Korea

IntroductionThis study aimed to examine the effect of socioeconomic deprivation on the outcomes of diabetes complications in patients with type 2 diabetes mellitus (T2DM).Research design and methodsWe conducted a cohort...

Gender differences in self care in type 2 diabetes in rural Kerala

Background: Noncommunicable Diseases (NCDs) were estimated to have contributed to almost 60% of deaths in the world and 43% of the global burden of disease in 1999. NCDs are rapidly becoming a major public health threat in the developing world. The W.H.O fact file on NCDs states that healthy diet, regular physical activity, maintaining a normal body weight (self-care) are ways to prevent or delay the onset of type 2 diabetes or its complications. Thus, self-care in diabetes is the corner stone in achieving good glycemic control, thereby preventing the onset of diabetes complications which increases the morbidity and mortality of the disease. This study was undertaken to understand the effect of self-care on HbA1C (blood sugar control) among males and females with Type -2 diabetes in a rural population in Kerala. The study tries to draw out the differences in self-care among males and females taking into consideration the patriarchal nature of the society and to understand the gender differences in approaches to self-care. Sex- based differences should be considered when developing awareness and treatment programs for people with diabetes, more precisely in NCD preventive measures specifically for the Indian subcontinent.&#x0D; Materials and methods: A cross sectional study was conducted in a stratified random sample of diabetes patients belonging to the three religious groups found in the study area, in a diabetes treatment center in Kanjirapally taluk of Kottayam district. Based on pilot study, a sample of 300 is chosen with 138 males and 162 females. For part 1 of the questionnaire, demographic details were entered by the researcher and the medical records were accessed to record the relevant details like height, weight, A1C, B.M.I., F.B.S. and chronic conditions of the patients. The selfcare activity of the patients were assessed with the SDSCAS (Summary of diabetes self-care activity scale). It&#x0D; consists a core set of 12 questions to assess the dietary habits, exercise regimen, blood sugar testing, foot care and smoking status for the past 7 days. &#x0D; Results: Since the representative sample is not made of equal number of males and females, comparison of blood sugar control (HbA1C) based on self-care activities for males and females were calculated. The independent sample t-test is highly significant at 0.01 level with respect to general diet, specific diet, dietary adherence and podiatric care. The t-test again shows significance at 0.05 level with respect to physical activities on comparison. &#x0D; Conclusions: The self-care activities varied greatly between males and females. The self-care activities of the females were very poor when compared with the males. The poor self-care activities of the females could be attributed to behaviour conditioned by gender relations prevalent in the society. Women seem to assimilate or internalize the patriarchal subjectivity of the society. But this is a feature of most households not only in the study area but of the country as a whole. This gender difference in self-care can be annihilated by stringent awareness and health education campaigns. NCD prevention strategies should include gender sensitive health promotion measures to achieve the WHO Global Strategy for the Prevention and Control of Noncommunicable Diseases (NCD Action Plan).

Synthesis and Aldose Reductase Inhibitory Activity of Botryllazine A Derivatives.

Aldose reductase (AR) is associated with the onset of diabetic complications. Botryllazine A and its analogues were synthesized and evaluated for human AR inhibitory activity. Analogues possessing aromatic bicyclic systems at the C5 position of the central pyrazine ring exhibited superior AR inhibiting activity relative to the parent botryllazine A. In addition, the benzoyl groups at positions C2 and C3 of the pyrazine ring were dispensable for this improved inhibitory activity. Conversely, a benzoyl group-containing phenolic hydroxyl groups-at either position C2 or C3 of the pyrazine ring was essential for attainment of high inhibitory activity approaching that of sorbinil (a highly effective AR inhibitor).

2438-PUB: Adherence to Hypoglycemic Agents among Type 2 Diabetes Patients with Claims Database in Japan

Several studies have been conducted to understand adherence and to identify the determinants associated with it showing that medication adherence is influenced by numerous factors that may be related to patients and medication. There are no data of large-scale medication adherence originating in Japan. In this study, we examined non-adherence and predictive factors of T2DM patients in Japan. This was a retrospective cohort study using a Japanese claims database of patients with type 2 diabetes. Adherence to therapy was measured using the proportion of days covered (PDC) method over a fixed period of 3 years. If PDC &amp;lt;80%, patients were considered non-adherent, a commonly used standard. To assess the odds ratio (OR) of non-adherence, we performed a logistic regression analysis, having adjusted for patient characteristics. The final sample contained 885 patients. The mean PDC was 79.6%, with 50.2% of patients classified as non-adherence. The mean number of medicines was 2.4, with 11.1% of patients classified as polypharmacy. According to the inflection point of the ROC curve, the cut-off value of the number of outpatient visits associated with adherence was 17 times. In the multivariate logistic regression analysis, polypharmacy (OR:0.18), the older age (60y∼ OR:0.37, 50y∼OR:0.39) showed lower odds ratio. Men (OR:2.20), 17 or less times of outpatient visits in 3 years (OR:27.1) showed higher odds ratio. In this study, we investigated medication non-adherence in 3 years and showed adherence adequacy a little lower to that reported previously, which is one year observation period. Also, medication adherence tended to be lower in younger ages and cases with fewer drugs. Maintaining good medication adherence and achieving the targeted HbA1c in these cases are important for suppressing the onset of diabetic complications. We think that it is necessary to consider methods of intervention aimed at maintaining good medication adherence, such as by utilizing on-line medical treatment. Disclosure T. Horii: None. K. Momo: None. T. Yasu: None. Y. Kabeya: None. K. Atsuda: None. Funding Japan Association for Diabetes Education and Care

Diabetes-mediated IL-17A enhances retinal inflammation, oxidative stress, and vascular permeability

Diabetic retinopathy is a prevailing diabetes complication, and one of the leading causes of blindness worldwide. IL-17A is a cytokine involved in the onset of diabetic complications. In the current study, we examined the role of IL-17A in the development of retinal inflammation and long-term vascular pathology in diabetic mice. We found IL-17A expressing T cells and neutrophils in the retinal vasculature. Further, the IL-17A receptor was expressed on Muller glia, retinal endothelial cells, and photoreceptors. Finally, diabetes-mediated retinal inflammation, oxidative stress, and vascular leakage were all significantly lower in IL-17A−/− mice. These are all clinically meaningful abnormalities that characterize the onset of diabetic retinopathy.

Effects of flash glucose-sensing technology-based continuous glucose monitoring on compliance of patients with type 2 diabetes mellitus: study protocol for a randomized controlled trial

Background and objectives: Multiple insulin injection therapy has been widely used in the intensive treatment of diabetes mellitus and enabled more patients to obtain good glycemic control. Intensive insulin treatment such as multiple insulin injection every day had been proven to have effects on the protection of islet and delay the onset of diabetic complications. However, during the insulin intensive therapy, severe hypoglycemia must be avoided by intensive glucose monitoring because it can increase the risks of stroke and cardiovascular disease. Conventional invasive intensive blood glucose monitoring is limited in clinical practice because it can cause patient pain and inconveniences. Patient's poor compliance in blood glucose monitoring would restrict the application of insulin intensive therapy in patients outside the hospital. The latest method of flash glucose-sensing technology-based continuous glucose monitoring (CGM) made insulin intensive therapy safer and less painful for a patient with diabetes mellitus. However, little is reported on the effects of flash glucose-sensing technology based CGM in patients receiving multiple daily injections of insulin. This study will provide evidence to validate whether flash glucose-sensing technology-based CGM can increase the behavioral self-monitoring and compliance with self-management of a Chinese patient with diabetes mellitus receiving multiple daily injections of insulin compared with conventional invasive blood glucose monitoring. Subjects and methods: This is a prospective, single-center, open-label, randomized controlled trial. Forty patients with type 2 diabetes mellitus who receive multiple daily injections of insulin at the Department of Endocrinology, Northern Jiangsu People's Hospital, Yangzhou University, China between August 2018 and December 2019 are included in this study. These patients are randomly divided to undergo conventional blood glucose monitoring (n = 20) or a flash glucose-sensing technology-based CGM group (n = 20). Patient recruitment began in August 2018 and will end in June 2019. Analysis of primary outcome measure will be completed in June 2019. The study will end in December 2019. Study protocol: 1.0. The protocol was approved by the Medical Ethics Committee of Northern Jiangsu People's Hospital (approval No. 2018045) and is performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. All participants provide written informed consent. Outcome measures: The primary outcome measure is the compliance of glycemic monitoring. The secondary outcome measures include the time taken for reaching the goal of glycemic control, HbA1c, self-management scores, the number of hypoglycemia attacks, and Hamilton Anxiety Scale score. Discussion: This study will provide evidence to validate whether flash glucose-sensing technology can increase patient's compliance of intensive insulin treatments, control blood glucose, and improve quality of life. Trial registration: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800017456) on July 31, 2018.

Enzymological Studies on the Mechanisms of Pathogenesis of Diabetic Complications

Aldose reductase (AR) is involved in the pathogenesis of complications in diabetes. In this study, the enzymatic properties of AR isolated from various sources and a recombinant human AR (rh-AR) were analyzed in detail. The sensitivity of different forms of AR to several AR inhibitors (ARIs) was compared. Our findings enabled us to propose that human AR should be used as the target enzyme in the development of ARIs. An enzyme-linked immunosorbent assay (ELISA) for human AR which employed monoclonal antibodies against rh-AR was created, and this method was used to demonstrate the distribution of AR in human tissues. AR was widely distributed in various organs and blood cell components. The levels of erythrocyte AR (e-AR) were 10.1±1.9 ng/mg Hb and 10.5±3.0 ng/mg Hb in healthy volunteers and diabetic patients, respectively, and thus there was no significant difference between them. The e-AR levels of diabetic patients were assayed using the ELISA developed to investigate the potential correlation between AR levels and the onset of diabetic complications. There were significant correlations between the incidence of diabetic neuropathy and e-AR levels in patients with disease duration of less than 10 years, and between the incidence of diabetic retinopathy and e-AR levels in patients with disease duration of 10-20 years. Our results suggest that measurement of e-AR levels in patients could help optimize drug therapy with ARIs and be a useful method to predict the onset of complications due to the upregulation of the polyol pathway.

Investigation of Pharmacological Responses to an Anti-Diabetic Drug Pioglitazone in Female Spontaneously Diabetic Torii (SDT) Fatty Rats, A New Obese Type 2 Diabetic Rat

Rigorous glycemic control is essential to prevent the development of diabetes and onset of diabetic complications. Peroxisome proliferator-activated receptor (PPAR) γ activator pioglitazone is an anti-diabetic drug that exhibits glucose-lowering effects by enhancing insulin sensitivity in peripheral tissues. However, increases in body weight are a concerning finding associated with treatment with pioglitazone. In this study, the pharmacological effects of pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats, a new obese type 2 diabetic rat, to verify utility of this model.

Secretory glands and microvascular systems imaged in aqueous solution by atmospheric scanning electron microscopy (ASEM).

Exocrine glands, e.g., salivary and pancreatic glands, play an important role in digestive enzyme secretion, while endocrine glands, e.g., pancreatic islets, secrete hormones that regulate blood glucose levels. The dysfunction of these secretory organs immediately leads to various diseases, such as diabetes or Sjögren's syndrome, by poorly understood mechanisms. Gland-related diseases have been studied by optical microscopy (OM), and at higher resolution by transmission electron microscopy (TEM) of Epon embedded samples, which necessitates hydrophobic sample pretreatment. Here, we report the direct observation of tissue in aqueous solution by atmospheric scanning electron microscopy (ASEM). Salivary glands, lacrimal glands, and pancreas were fixed, sectioned into slabs, stained with phosphotungstic acid (PTA), and inspected in radical scavenger d-glucose solution from below by an inverted scanning electron microscopy (SEM), guided by optical microscopy from above to target the tissue substructures. A 2- to 3-µm specimen thickness was visualized by the SEM. In secretory cells, cytoplasmic vesicles and other organelles were clearly imaged at high resolution, and the former could be classified according to the degree of PTA staining. In islets of Langerhans, the microvascular system used as an outlet by the secretory cells was also clearly observed. Microvascular system is also critically involved in the onset of diabetic complications and was clearly visible in subcutaneous tissue imaged by ASEM. The results suggest the use of in-solution ASEM for histology and to study vesicle secretion systems. Further, the high-throughput of ASEM makes it a potential tool for the diagnosis of exocrine and endocrine-related diseases.

Lack of p47phox in Akita Diabetic Mice Is Associated with Interstitial Pneumonia, Fibrosis, and Oral Inflammation

Excess reactive oxygen species production is central to the development of diabetic complications. The contribution of leukocyte reactive oxygen species produced by the NADPH oxidase to altered inflammatory responses associated with uncontrolled hyperglycemia is poorly understood. To get insight into the role of phagocytic superoxide in the onset of diabetic complications, we used a model of periodontitis in mice with chronic hyperglycemia and lack of leukocyte p47(phox) (Akita/Ncf1) bred from C57BL/6-Ins2(Akita)/J (Akita) and neutrophil cytosolic factor 1 knockout (Ncf1) mice. Akita/Nfc1 mice showed progressive cachexia starting at early age and increased mortality by six months. Their lungs developed infiltrative interstitial lesions that obliterated air spaces as early as 12 weeks when fungal colonization of lungs also was observed. Neutrophils of Akita/Ncf1 mice had normal degranulation and phagocytic efficiency when compared with wild-type mice. Although Akita/Ncf1 mice had increased prevalence of oral infections and more severe periodontitis compared with wild-type mice, bone loss was only marginally higher compared with Akita and Ncf1 null mice. Altogether these results indicate that lack of leukocyte superoxide production in mice with chronic hyperglycemia results in interstitial pneumonia and increased susceptibility to infections.

Low-dose Insulin Treatment Ameliorate Glucose Metabolism in Type 1 Diabetic Rats

Study background: Type 1 diabetes is an insulin-dependent diabetes mellitus (IDDM) because the body does not produce sufficient insulin for daily need. Persistent high glucose level in the blood circulation can stimulate the advanced glycation end products/receptor for AGEs (AGE/RAGE) pathway leading to diabetic complications. Currently, there is no preventive measure for IDMM with only treatment focusing on delaying the onset of diabetic complications. This study aimed to investigate how the different insulin regimens given affect the glycemic control and glucose metabolism in type 1 diabetes. The effects on the AGE/RAGE axis were determined as well. Methods: Twenty-one male Sprague-Dawley rats were randomly assigned into three groups (Group A: streptozotocin-induced diabetic rats given high-dose insulin [5-7U per day], Group B: streptozotocin-induced diabetic rats given low-dose insulin [0-3U per day], Group C: non-diabetic control). Throughout the eight-week treatment, the body weight, systolic blood pressure and non-fasting blood glucose concentration were monitored. After eight weeks of treatment, fasting blood glucose concentration, glycated haemoglobin (HbA1c), nuclear factor kappa B (NF-κB), AGE level and RAGE expression were measured. Results: High-dose insulin treatment impaired glucose metabolism. On the contrary, diabetic rats receiving lowdose insulin showed reduced glucose level and improved insulin sensitivity towards the end of experiment. HbA1c level was significantly lower in low-dose insulin treated rats while NF-κB level was significantly lower in high-dose insulin treated rats (p ≤ 0.05). There was no significant difference in AGE levels in all the groups (p>0.05) and only the heart tissues from the low-dose insulin treated group showed significant down regulation of the RAGE gene expression (p ≤ 0.05). Conclusion: Low-dose insulin treatment was shown to be a better therapeutic intervention for type 1 diabetes.

Monitoring of Glycation, Oxidative Stress and Inflammation in Relation to the Occurrence of Vascular Complications in Patients With Type 2 Diabetes Mellitus

The study aimed to evaluate if the monitoring of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), lipoperoxides (LPO) and interleukin-6 (IL-6) in plasma could help to predict development of diabetic complications (DC). Clinical and biochemical parameters including AGEs, AOPP, LPO and IL-6 were investigated in patients with type 2 diabetes mellitus (DM2) with (+DC) and without (-DC) complications. AGEs were significantly higher in both diabetic groups compared to controls. AGEs were also significantly higher in group +DC compared to -DC. AGEs significantly correlated with HbA1c. We observed significantly higher AOPP in both diabetic groups in comparison with controls, but the difference between -DC and +DC was not significant. LPO significantly correlated with BMI. IL-6 were significantly increased in both diabetic groups compared to controls, but the difference between -DC and +DC was not significant. There was no significant correlation between IL-6 and clinical and biochemical parameters. These results do not exclude the association between IL-6 and onset of DC. We suggest that the measurement of not only HbA1c, but also AGEs may be useful to predict the risk of DC development in clinical practice. Furthermore, the measurement of IL-6 should be studied as adjunct to HbA1c monitoring.

Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats.

Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes.

Insights From Monogenic Diabetes and Glycemic Treatment Goals for Common Types of Diabetes

The “glucose hypothesis,” which held that bringing ambient glucose levels into the near-normal range would help prevent the onset of diabetic complications, was first supported by findings from the Diabetes Control and Complications Trial.1 Intensive glucose control resulting in a mean glycated hemoglobin (HbA1c) level near 7% had discernible and sustained effects on both microvascular2- 4 and macrovascular5 end points. An appeal of type 1 diabetes as a model for studying hyperglycemic effects is its clear-cut phenotype, in which autoimmune destruction of pancreatic beta cells causes hyperglycemia as the main triggering vascular insult at disease onset, typically unconfounded by other potential or established cardiovascular risk factors such as hyperinsulinemia, hyperlipidemia, and hypertension.