Abnormalities In Diabetes Mellitus Research Articles

Barrier Abnormalities in Type 1 Diabetes Mellitus: The Roles of Inflammation and Ceramide Metabolism

Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation-mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.

Diabetes without Overt Cardiac Disease Is Associated with Markers of Abnormal Repolarization: A Case-Control Study.

Patients with diabetes mellitus (DM) are prone to advanced atherosclerosis, microvascular disease, and tissue fibrosis. Despite the increased risk for arrhythmias, little is known about cardiac repolarization abnormalities in DM. We aimed to determine whether abnormal T-wave morphology markers are common among patients with DM and no known cardiac disease. Patients were recruited and classified as having DM or impaired fasting glucose (IFG) according to accepted guidelines. Total cosine R to T (TCRT) and T-wave morphology dispersion (TMD) were computed with custom-designed software for randomly selected and averaged beats. Among 124 patients recruited; 47 were diagnosed with DM and 3 IFG. DM patients and the control group had similar clinical characteristics, other than statins and anti-diabetic drugs, which were more common among DM patients. Patients with DM/IFG had decreased TCRT values computed from a random beat (0.06 ± 0.10 vs. 0.43 ± 0.07, p < 0.01) and an average beat (0.08 ± 0.09 vs. 0.44 ± 0.06, p < 0.01), when compared with the control group. TMD parameters did not differ. In conclusion, TCRT is reduced in patients with DM and no known cardiac diseases. Further research is required to investigate whether repolarization-associated changes in DM are the consequence of subclinical atherosclerosis, diabetic cardiomyopathy, or a combination of the two.

Hyperglycaemia-Induced Contractile Dysfunction and Apoptosis in Cardiomyocyte-Like Pulsatile Cells Derived from Mouse Embryonic Stem Cells.

Hyperglycaemia, a key metabolic abnormality in diabetes mellitus, is implicated in pathological cardiogenesis during embryological development. However, the underlying mechanisms and potential therapeutic targets remain unknown. We, therefore, studied the effect of hyperglycaemia on mouse embryonic stem cell (mESC) cardiac differentiation. The mESCs were differentiated via embryoid body (EB) formation and cultured under conditions with baseline (25 mM) or high (50 mM) glucose. Time-lapse microscopy images of pulsatile mESCs and Ca2+ transients were recorded. Biomarkers of cellular changes were detected using immunocytochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and Western blot analyses. Differentiated, spontaneously beating mESCs stained positive for cardiac troponin T, α-actinin 2, myosin heavy chain, and connexin 43. Hyperglycaemia decreased the EB diameter and number of beating EBs as well as the cellular amplitude of contraction, the Ca2+ transient, and the contractile response to caffeine (1 mM), but had no effect on the expression of the sarco-endoplasmic reticulum calcium transport ATPase 2 (SERCA 2). Furthermore, hyperglycaemia decreased the expression of B cell lymphoma 2 (Bcl-2) and increased the expression of cytoplasmic cytochrome c and the number of TUNEL-positive cells, but had no effect on the expression of one of the mitochondrial fusion regulatory proteins, optic atrophy protein 1 (OPA1). Overall, hyperglycaemia suppressed the mESC cardiomyocyte-like differentiation and induced contractile dysfunction. The results are consistent with mechanisms involving abnormal Ca2+ handling and mitochondrial-dependent apoptosis, factors which represent potential therapeutic targets in developmental diabetic cardiac disease.

Incidence of Diabetes Mellitus Type II and Pre-Diabetes among Hand Nerves Entrapment Neuropathy Patients: Epidemiological Study

Objective: Measure the incidence of Diabetes Mellitus (DM)/pre-diabetes among patients with hand nerves entrapment syndromes. Design: Prospective cross sectional. Settings: Outpatient. Participants: 412 patients presented with unilateral or bilateral hand numbness suspecting Carpal Tunnel Syndrome (CTS). Exclusion criteria: Cervical spine or hand trauma history, nerve injury history. Interventions: Each patient was subjected to the following; demographic data including occupation, body mass index, detailed medical history including DM history. Neck exam including Spurling test. Full neurological exam. Main outcome measures: Upper extremities Nerve conduction studies and electromyography of segment pointing muscles. Laboratory testing including glycosylated hemoglobin (HgA1c), liver and kidney functions. Cervical spine MRI if possible. Results: Mean age 59.4 ± 11.123. All patients were right-handed, Male 37.1%, female 62.9%, Mean body mass index (BMI) 32.2 ± 8.2. majority were manual workers (55.1%). HgA1c <5.5 has the fewest patients (7.3%), highest number of patients with HgA1c 5.5-6.0. significant relation between HgA1c categories and sensory CTS p=0.001 and sensory motor CTS p=0.001. No significant relation between HgA1c categories and demyelinating pathology p=0.123 but significant with demyelinating axonal pathology p=0.017. Significant relation between HgA1c and Guyon canal syndrome p=0.001 and polyneuropathy p=0.001. No significance between HgA1c and cervical radiculopathy p=0321. Conclusions: High incidence of DM and pre-diabetes among patients with hand nerve entrapment: CTS, Guyon syndrome together with polyneuropathy. EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels.

Assessment of endogenous fibrinolysis using a point-of-care assay to identify increased cardiovascular risk in patients with diabetes and ACS

Abstract Introduction Patients with diabetes mellitus (DM) are increased risk of myocardial infarction (MI) and following a MI, patients with DM have an increased risk of recurrent MI and cardiovascular (CV) death. Plasma turbidimetry studies show that hypofibrinolysis is a key abnormality in DM that may drive increased ischaemic risk. Such assays are cumbersome, require specialist expertise and do not provide information in a clinically-relevant timeframe. Assessment of fibrinolysis in whole blood, using a point-of-care assay, has revealed that in ACS patients, impaired fibrinolysis is predictive of adverse CV events. Whether this technique can identify residual risk in patients with DM, is unclear. Purpose It was our aim to compare thrombotic and endogenous fibrinolytic status between patients with and without DM, presenting with ACS. Methods We conducted a prospective, observational study of consecutive patients admitted with ACS. Venous blood was taken to assess thrombotic and thrombolytic status using the point-of-care Global Thrombosis Test, assessing time to occlusive thrombus formation under high shear (occlusion time, OT) and time taken for spontaneous lysis of the thrombus (lysis yime, LT). Blood was taken after dual antiplatelet therapy (DAPT) loading, but before administration of fondaparinux or low molecular weight heparin. Patients with renal or hepatic impairment, known bleeding diathesis, thrombocytopenia and those taking anticoagulation were excluded. Results A total of 775 patients were included, of whom 158 (20%) had DM. Patients with DM, compared to those without DM, more frequently had hypertension (70% vs. 39%, p&amp;lt;0.001), hyperlipidaemia (65% vs. 29%, p&amp;lt;0.001), higher BMI (28.6 [25.3–32.0] vs. 26.6 [23.7–29.8] kg/m2, p&amp;lt;0.001) and prior MI (28% vs 9%, p&amp;lt;0.001), but were less often smokers (23% vs. 34% p=0.007). In all other clinical characteristics DM and non-DM patients were matched. Time to occlusive thrombus formation was similar in patients with and without DM (OT 401 (284–519) s vs. 391 (289–514) s, p=0.603). There was a trend for longer LT in patients with DM compared to those without DM (LT 1634 (130–2321) s vs. 1562 (1247–2147) s, p=0.080). After propensity score matching to adjust for baseline differences in clinical characteristics, we observed a highly significant difference in LT between DM and non-DM patients (LT 1634 [1306–2321] s vs. 1387 [1109–1740] s, p&amp;lt;0.001). Patients with DM also had higher fibrinogen level (4.4 [3.5–5.4] vs. 4.1 [3.5–4.8] g/l, p=0.012) and higher C-reactive protein (5 [2–12] vs. 3 [1–8] mg/l, p=0.002). CRP correlated with LT (r=0.2, p=0.016), but no correlation was observed between fibrinogen and LT (r=0.069, p=0.424). Conclusions Amongst patients with ACS, those with DM exhibit markedly impaired endogenous fibrinolysis compared to those without DM, and this can be detected with a bedside assay using whole blood. This may explain the increased risk of secondary events in patients with ACS and DM. Funding Acknowledgement Type of funding source: None

Electrolyte abnormalities in diabetes mellitus in the presence of normal serum creatinine

Aim: Diabetes mellitus is a metabolic disorder that causes disturbances in the electrolyte regulating mechanisms of our body. The purpose of the study was to determine the pattern of electrolyte imbalance in patients with diabetes mellitus and compare with healthy individuals; and to correlate the degree of electrolyte imbalance with control and duration of diabetes. Methods: This cross-sectional study was conducted over a period of 6 months. It included 90 cases with diabetes mellitus and 50 cases without diabetes mellitus. All subjects had normal serum creatinine level. Serum electrolytes (sodium, potassium, chloride and bicarbonate) were measured in each subject by automated methods. The normal levels of sodium, potassium, chloride and bicarbonate were taken as 136-146, 3.5-5, 102-109 and 22-30 mmol/L respectively. Levels above or below this reference were taken as abnormal. Control of diabetes was determined by measuring HbA1c using high-performance liquid chromatography. Result: The most common abnormalities in patients with diabetes mellitus were hypochloraemia (48.89%), low serum bicarbonate (23.33%) and hyponatraemia (11.11%), though the mean values of serum electrolytes were within the normal reference range. Serum bicarbonate level was significantly lower in the group with diabetes mellitus (p = 0.010). There were a significantly greater number of cases with hyponatraemia and hypochloraemia among cases with diabetes mellitus (p < 0.016). Serum sodium was negatively correlated with glycaemic control (r = -0.39; p <0.001) and duration of diabetes (r = -0.31; p = 0.003). Conclusion: Electrolyte abnormalities are more common in patients with diabetes mellitus even with normal serum creatinine, and this correlates with control and duration of diabetes.

糖尿病行为学异常及STZ糖尿病小鼠模型

糖尿病行为学异常及STZ糖尿病小鼠模型

SERUM CONCENTRATION OF THYROID HORMONES AND THYROID STIMULATING HORMONE IN ALLOXAN-INDUCED TYPE 1 DIABETIC WISTAR ALBINO RATS

Background: Literature has reported thyroid functional abnormalities in diabetes mellitus. The objectives of this study were to determine and compare the serum concentrations of T3, T4 and TSH in alloxan-induced type 1 diabetic and control Wistar albino rats. Materials &amp; Methods: It was an experimental animal study on 20 Wistar albino rats, extending over a period of eight weeks. Alloxan, a diabetogenic agent, was used to produce animal models of type 1 diabetes. Animals were divided equally into two groups: control and diabetic. The animals in the diabetic group were injected intraperitoneally with 150 mg/kg body weight of 10% alloxan to induce diabetes. After 72 hours, diabetes was confirmed with glucometer (glucose &gt;350mg/dl). During the course of experiment, one rat in control group and 2 rats in diabetic group died. Blood was collected for estimation of serum concentrations of thyroid hormones, thyroid stimulating hormone at the end of experimental period. Serum T3, T4, and TSH were measured using ELISA kits. Results: At the end of eight weeks, the mean concentration of serum T3 was 0.69 ±0.29 ng/ml and 0.44±0.02 ng/ml in control and diabetic groups, respectively. The mean concentration of T4 was 3.78±1.16 μg/dl and 2.24±0.86 μg/dl in control and diabetic groups respectively. The mean concentration of TSH was 0.77±0.20 μU/ml and 1.41±0.23 μU/ml in control and diabetic groups respectively. The mean serum concentrations of T3 (p=.0025) and T4 (p=&lt;.00001) were significantly lower in diabetic and that of TSH (p=&lt;.00001) were significantly higher in diabetic than control group. Conclusion: This study concludes that the serum concentrations of both T3 and T4 are significantly lower and that of TSH is significantly higher in alloxan-induced type 1 diabetic as compared to control group in Wistar albino rats.

Angiogenic Abnormalities in Diabetes Mellitus: Mechanistic and Clinical Aspects

Diabetes causes severe pathological changes to the microvasculature in many organs and tissues and is at the same time associated with an increased risk of coronary and peripheral macrovascular events. We herein review alterations in angiogenesis observed in human and experimental diabetes and how they contribute to diabetes onset and development of vascular complications. The English language medical literature was searched for articles reporting on angiogenesis/vasculogenesis abnormalities in diabetes and their clinical manifestations, mechanistic aspects, and possible therapeutic implications. Angiogenesis is a complex process, driven by a multiplicity of molecular mechanisms and involved in several physiological and pathological conditions. Incompetent angiogenesis is pervasive in diabetic vascular complications, with both excessive and defective angiogenesis observed in various tissues. A striking different angiogenic response typically occurs in the retina vs the myocardium and peripheral circulation, but some commonalities in abnormal angiogenesis can explain the well-known association between microangiopathy and macroangiopathy. Impaired angiogenesis can also affect endocrine islet and adipose tissue function, providing a link to diabetes onset. Exposure to high glucose itself directly affects angiogenic/vasculogenic processes, and the mechanisms include defective responses to hypoxia and proangiogenic factors, impaired nitric oxide bioavailability, shortage of proangiogenic cells, and loss of pericytes. Dissecting the molecular drivers of tissue-specific alterations of angiogenesis/vasculogenesis is an important challenge to devise new therapeutic approaches. Angiogenesis-modulating therapies should be carefully evaluated in view of their potential off-target effects. At present, glycemic control remains the most reasonable therapeutic strategy to normalize angiogenesis in diabetes.

ATP-binding cassette sub-family a member1 gene mutation improves lipid metabolic abnormalities in diabetes mellitus

BackgroundPatients with diabetes mellitus were often accompanied with hyperlipidemia. ATP-binding cassette sub-family A member1 (ABCA1) promotes the efflux of lipids and thereby mediates the metabolism of cholesterol. The aim of our study was to determine the associations of ABCA1 gene polymorphisms with the risks of diabetes mellitus and dyslipidemia in diabetic patients.MethodsWe retrieved literature about the relationship between ABCA1 gene polymorphisms (C69T and R230C) and the risk of diabetes through PubMed, Web of Science, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Cochrane database. Weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively, accompanied by their 95% confidence interval (CI).ResultsA total of 1746 diabetic patients and 1292 non-diabetic controls were enrolled. All subjects were Caucasians. ABCA1 R230C T allele was significantly associated with reduced the risk of diabetes (OR = 0.75, 95% CI = 0.57–0.98, P = 0.04). There was no association of ABCA1 C69T gene polymorphisms with the risk of diabetes. However, subgroup analyses showed that the ABCA1 C69T gene mutation significantly reduced the risk of hypertriglyceridemia in diabetic patients as compared with that in non-diabetic subjects (dominant model: WMD =0.66, 95% CI = 0.52–0.8, P < 0.0001; recessive model: WMD = 0.47, 95%CI = 0.11–0.83, P = 0.01).ConclusionsABCA1 R230C T allele gene mutation is a protective in decreasing the risk of diabetes in Caucasians and ABCA1 C69T gene mutation markedly influences the level of lipid metabolism in diabetic patients.

The Role of Serum Alpha-Amylase and Glycogen Synthase in the Anti-Diabetic Potential of Terminalia catappa Aqueous Leaf Extract in Diabetic Wistar Rats

Background: The endocrinal abnormalities in diabetes mellitus as one of the numerous metabolic disorders is associated with derangement in exocrine functions of the pancreas and ultimately influences blood glucose regulation.&#x0D; Aim: The study was aimed at assessing the role of alpha-amylase and glycogen synthase in anti-diabetic potential of Terminalia catappa in diabetic rats. &#x0D; Materials and Methods: Thirty five (35) Wistar rats were assigned to 5 groups of 7 animals each. Group 1 served as the control administered distilled water at 5ml/kg bodyweight and group 2 was a non diabetic group given orally, 130/kg body weight of aqueous leaf extract of Terminalia catappa. Groups 3, 4 and 5 received a single dose of 150mg/kg body weight of alloxan solution intraperitoneally to induce diabetes and rats with blood glucose levels ≥200mg/dl after 72 hours were considered diabetic. This was followed by oral administration of 5ml/kg bodyweight of distilled water, 130mg/kg body weight of Terminalia catappa leaf extract orally and subcutaneous administration of insulin, 0.75U/kg body weight to groups 3 (diabetic), 4(diabetic + extract) and 5 (diabetic + insulin) respectively.&#x0D; Results: The results showed significant (P&lt;.05) increase in serum level of alpha-amylase and glycogen synthase in both non-diabetic extract treated and diabetic groups when compared to control. But these enzymes significantly (P&lt;.05) reduced in diabetic extract and insulin treated groups when compared to the diabetic group. &#x0D; Conclusion: Therefore the hypoglycaemic potential of Terminalia catappa leaf extract could be attributed to its ability to reduce alpha-amylase level while lowered glycogen synthase might be secondary to reduction in blood glucose.

FUNCTIONAL STUDIES ON BLOOD MICROCIRCULATION SYSTEM WITH LASER DOPPLER FLOWMETRY IN CLINICAL MEDICINE: PROBLEMS AND PROSPECTS

The paper presents a review of the research update on the blood microcirculation system assessed with laser Doppler flowmetry (LDF). Specific procedures for measurement of the microcirculation index by LDF and individual variability of microcirculation parameters during their real time assessment in vivo are discussed. In physiological conditions, a relative deviation of the results of measurements by LDF is within the range±35% and above from the mean value of the microcirculation index. This imposes certain limitations on the interpretation of the diagnostic results in terms of the “normal or pathologic”. Specifics of performance of functional stress tests on the microcirculation system are reviewed. Diagnostic criteria based on functional stress testing of the microcirculation system, which can be implemented with methodologically strict normatives and regulations, for examples, those for the occlusion test, are more reliable from metrologic perspective and significant compared to the results obtained without stress testing. Problems of implementation of the functional tests into clinical practice are discussed. It was shown that they may have a potentially wide spectrum of clinical indications, from functional diagnostics and early detection of microcirculatory abnormalities in diabetes mellitus, arterial hypertension and other diseases associated with microcirculatory disorders, to the physical rationale of exposure parameters, as well as objectification of efficiency of medical procedures aimed to stimulation of the microcirculatory functions in a patient's tissues and organs.

Entrapment neuropathies in diabetes mellitus.

Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.

Pattern Visual Evoked Potential in Non Diabetic offspring‘s of Type II Diabetes

Metabolic abnormalities in diabetes mellitus involves ganglionic and preganglionic elements in the entire retina and macular region causing visual disturbances. Subclinical central nervous system (CNS) dysfunctions have been reliably detected by visual evoked potentials in patients with uncomplicated diabetes and normal brain Computed tomography (CT) scan. The offspring of diabetic parents have a higher risk of diabetes and a possibility of diabetic retinopathy. The study aims at evaluating visual evoked potential in asymptomatic, non-diabetic offspring of diabetic parents. A total of 150 individuals in each group (case and controls) were enrolled after Written and informed consent. Institutional ethical Committee approval was obtained. Visual evoked potential (VEP) recordings were done using the standard procedure given in Recommended Standards for VEP, Guidelines 9B. The statistical analysis revealed significant difference in controls and offspring of diabetic parents in terms of P100 latency in both left and right eye (P&lt;0.05). The offspring of diabetic parents may be screened with VEP, as, prolongation of P100 latency a direct sign of retinal damage and demyelination could add the risk to the fact that they may be in a pre-diabetic stage without clinical manifestation, but there may be subclinical optic pathway involvement which mandates active intervention to reduce the co-morbidly associated with diabetes.

Role of angiostatins in diabetic complications

Angiogenesis is a process through which new blood vessels form from pre-existing vessels. Angiogenesis is regulated by a number of factors of peptide nature. Disbalance of angiogenic system appears to be the major causative factor contributing vascular abnormalities in diabetes mellitus, resulting in various complications. Angiostatins, which are kringle-containing fragments of plasminogen/plasmin, are known to be powerful physiological inhibitors of neovascularization. In the present review, current literature data on peculiarities of production of angiostatins and their functioning at diabetes mellitus are summarized and analyzed for the first time. Also, role of angiostatins in the pathogenesis of typical diabetic complications, including retinopathies, nephropathies and cardiovascular diseases, is discussed. Data presented in this review may be useful for elaboration of novel effective approaches for diagnostics and therapy of vascular abnormalities in diabetes mellitus.

Case Control Study on Platelet Aggregation, Fibrinogen and Von Willebrand Factors in Diabetis Patients

Vascular complications are common in diabetes mellitus and are leading causes of morbidity and mortality due to the disease. Platelet hyper-aggregation and coagulation factor abnormalities have been implicated in the increased prevalence of vascular complications. The cross sectional analytical study was done on 50 young, non-obese, normo-to hypoinsulinemic normotensive and untreated Bangladeshi diabetic patients to help in understanding the pathogenesis of platelet hyper-aggregation and coagulation factor abnormalities in diabetes mellitus for their platelet aggregation response to ADP, plasma fibrinogen and Von Willebrand Factors (vWF). Mean age was 23.7 ± 2.26 years in control and 24.33 ± 3.29 years in patients. The lipid profile, C-peptide, C-peptide: glucose and other anthropometric measurements of the diabetic and control subjects were also measured to find out any possible correlation. Platelet aggregation was measured by optical aggregometry, plasma vWF and plasma fibrinogen were measured by radial immuno-diffusion method. The platelet aggregation with ADP in diabetics was found to be significantly higher in diabetics 76.56 ± 16.92 compared to controls 62.90 ± 12.35 (P&lt; 0.27). Plasma fibrinogen were found to be significantly higher in young diabetics 1075.90 mg/L compared to the non-diabetic counterparts and plasma vWF 1.372 iu/ml in diabetic patients. In young diabetics, platelet hyperaggregation and coagulation factor abnormalities appear quite early and seem to play important role in the natural history of vasculopathy in diabetes mellitus. Diabetic condition (as evidenced by hyperglycemia), by itself, may create platelet hyperaggregation and coagulation factor abnormalities, however, there seems to be no straightforward relationship between those abnormalities and the degree of hyperglycemia.

The Angiotensin-Melatonin Axis

Accumulating evidence indicates that various biological and neuroendocrine circadian rhythms may be disrupted in cardiovascular and metabolic disorders. These circadian alterations may contribute to the progression of disease. Our studies direct to an important role of angiotensin II and melatonin in the modulation of circadian rhythms. The brain renin-angiotensin system (RAS) may modulate melatonin synthesis, a hormone with well-established roles in regulating circadian rhythms. Angiotensin production in the central nervous system may not only influence hypertension but also appears to affect the circadian rhythm of blood pressure. Drugs acting on RAS have been proven effective in the treatment of cardiovascular and metabolic disorders including hypertension and diabetes mellitus (DM). On the other hand, since melatonin is capable of ameliorating metabolic abnormalities in DM and insulin resistance, the beneficial effects of RAS blockade could be improved through combined RAS blocker and melatonin therapy. Contemporary research is evidencing the existence of specific clock genes forming central and peripheral clocks governing circadian rhythms. Further research on the interaction between these two neurohormones and the clock genes governing circadian clocks may progress our understanding on the pathophysiology of disease with possible impact on chronotherapeutic strategies.

The efficacy and safety of Simvastatin in the treatment of lipid abnormalities in diabetes mellitus

Introduction:Notable lipid abnormalities in DM include elevated LDL-C which have been reported to be the prevalent lipid abnormality in DM and elevated total cholesterol levels. Although the Statins are widely used in the management of lipid abnormalities, their effects on the lipid abnormalities in Nigerians with DM has not been extensively evaluated.Objective:This report sets out to determine the effect of Simvor, a brand of Simvastatin in Nigerians with DM and abnormal lipid profiles.Materials and Methods:A total of 300 diabetic patients with abnormal lipid profile who were treatment naοve for lipid disorders were longitudinally recruited for the study. They were managed with Simvastatin (Simvor) in doses ranging from 20-40 mg alongside dietary counseling and exercise recommendation.Results:The mean age (SD) of the study subjects was 58.4 (10 years). The male; female ratio was 99:211. The proportions of lipid abnormalities for LDL-C, TCHOL, HDL-C and TG were 87%, 45%, 53% and 7% respectively. Following Simvastatin (Simvor) treatment, the mean LDL-C value was reduced by 16%, TCHOL by 23%, TG by 6% and HDL-C increased by 10%. Simvastatin (Simvor) was generally well tolerated and no cardiovascular events were noted in the study subjects during the period of the study.Conclusion:Simvastatin (Simvor) was effective and well tolerated in the management of lipid disorders in Nigerians with DM.

Atrial fibrillation is associated with increased mean platelet volume in patients with type 2 diabetes mellitus

Platelet abnormalities in diabetes mellitus (DM) and atrial fibrillation (AF) may underline the etiology of a prothrombotic state in these conditions. Increased mean platelet volume (MPV) is a marker of abnormal platelet function and activation. We aimed to investigate the possible association of chronic AF with MPV in patients who have type 2 DM. Patients who had type 2 DM with either chronic (≥6 months) AF or normal sinus rhythm (NSR) were included in the study. A total of 162 patients (aged 38–89 years) were divided into 2 groups according to the presence of either AF or NSR. Group 1 consisted of 81 diabetic patients with AF, and group 2 consisted of 81 diabetic patients with NSR. The two groups were not significantly different in terms of age, and gender, as well as in hypertension, smoking, history of coronary artery disease, previous cerebrovascular accidents, microalbuminuria, retinopathy, duration of DM, body mass index, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride (p > 0.05 for all variables). Although no significant difference was present between groups concerning platelet count; for patients with AF, MPV was higher compared with patients with NSR (9.0 ± 0.2 fl vs. 8.4 ± 0.2 fl; p = 0.001). Furthermore, no significant difference was noted between groups regarding routine medications received by patients. In multivariate logistic regression analysis, MPV was the only variable independently related to AF (OR = 2.659; 95% CI, 1.286–5.498; p = 0.008). Consequently, it is concluded that AF is associated with increased MPV in patients with type 2 DM, suggesting the presence of tentatively related processes leading to reciprocal interaction.

628 EVALUATION OF THE ASSOCIATION BETWEEN COMMON VARIANTS AT THE GCK, GCKR, MTNR1B, AND G6PC2 LOCI WITH ANGIOGRAPHICALLY CHARACTERIZED CORONARY ATHEROSCLEROSIS

Apolipoprotein A5 (APOA5) −1131C allele is associated with higher triglyceride, an independent cardiovascular risk factor and a commonly recognized lipid abnormality in diabetes mellitus (DM). We investigated the association of APOA5 −1131T>C or S19W with DM. Study subjects were all women and categorized into metabolically healthy controls (n = 2033) and DM subjects (n = 304). Association of APOA5 −1131T>C with DM was calculated by odds ratio (OR). Anthropometric parameters, fasting glucose, and lipid profiles were measured. C carriers, particularly those with CC homozygote, had higher triglyceride and lower high-density lipoprotein cholesterol in both healthy controls (P < .001 and P < .001) and DM patients (P = .002 and P = .006) after the adjustment for age, body mass index, menopause, smoking, and drinking. APOA5 −1131C allele was associated with an increased risk of DM (OR, 1.61 [95% confidence interval {CI}, 1.23-2.10]; P < .001) after adjustment for the above confounders. Further adjustment for fasting triglyceride or/and high-density lipoprotein cholesterol attenuated a little bit, but still significantly increased the risk of DM in C carriers (OR2, 1.36 [95% CI, 1.02-1.80]; P = .035 and OR3, 1.36 [95% CI, 1.032-1.79]; P = .029, respectively). Interestingly, C allele carriers in DM patients showed a positive correlation between fasting glucose and triglyceride after the adjustment (r = 0.172, P = .035). On the other hand, this significant correlation was not observed in healthy women. Regarding S19W, minor allele was not found in our study population from prescreening test. In conclusion, APOA5 −1131C allele may contribute to the increased susceptibility of DM in Korean women. In addition, positive correlation between fasting glucose and triglyceride in C carriers of DM patients suggested that C allele in hyperglycemic states may be more susceptible to the risk of cardiovascular disease.