WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.

Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome

AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.

Metabolic syndrome:A review of the role of vitamin D in mediating susceptibility and outcome

Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption.While generally not at the very low levels associated with rickets,hypovitaminosis D has been implicated in various very different,pathophysiological processes.These include putative effects on the pathogenesis of neoplastic change,inflammatory and demyelinating conditions,cardiovascular disease(CVD) and diabetes.This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity,glucose homeostasis,insulin resistance,hypertension and atherogenic dyslipidaemia.We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD,diabetes and non-alcoholic fatty liver disease.We structure this review into 3 distinct sections; the metabolic syndrome,vitamin D biochemistry and the putative association between hypovitaminosis D,the metabolic syndrome and cardiovascular risk.

Evaluation of oxidative stress levels in obesity and diabetes by the free oxygen radical test and free oxygen radical defence assays and correlations with anthropometric and laboratory parameters

BACKGROUND Obesity and diabetes are associated with high levels of oxidative stress.In Romanian patients with obesity and(or)diabetes,this association has not been sufficiently explored.AIM To evaluate oxidative stress in obese and(or)diabetic subjects and to investigate the possible correlations between oxidative stress and anthropometric/biochemical parameters.METHODS Oxidative stress was evaluated from a single drop of capillary blood.Reactive oxygen species(ROS)were evaluated using the free oxygen radical test(FORT).The free oxygen radical defence(FORD)assay was used to measure antioxidant levels.RESULTS FORT levels were higher in obese subjects(3.04±0.36 mmol/L H2O2)vs controls(2.03±0.14 mmol/L H2O2)(P<0.0001).FORD levels were lower in obese subjects(1.27±0.13 mmol/L Trolox)vs controls(1.87±1.20 mmol/L Trolox)(P=0.0072).Obese diabetic subjects had higher FORT values(3.16±0.39 mmol/L H2O2)vs non-diabetic counterparts(2.99±0.33 mmol/L H2O2)(P=0.0233).In obese subjects,FORT values correlated positively with body mass index(BMI)(r=0.48,P=0.0000),waist circumference(WC)(r=0.31,P=0.0018),fasting plasma glucose(FPG)(r=0.31,P=0.0017),total cholesterol(TC)(r=0.27,P=0.0068)and uric acid(r=0.36,P=0.0001).FORD values correlated negatively with BMI(r=-0.43,P=0.00001),WC(r=-0.28,P=0.0049),FPG(r=-0.25,P=0.0130),TC(r=-0.23,P=0.0198)and uric acid(r=-0.35,P=0.0002).In obese diabetic subjects,FORT values correlated positively with BMI(r=0.49,P=0.0034)and TC(r=0.54,P=0.0217).FORD values were negatively associated with BMI(r=-0.54,P=0.0217)and TC(r=-0.58,P=0.0121).CONCLUSION Oxidative stress levels,as measured by the FORT and FORD assays,were higher in obese subjects vs controls.ROS levels were elevated in diabetic obese patients vs obese non-diabetic patients and controls.

Antioxidant Effect of Atorvastatin in Type 2 Diabetic Patients

Evidence has long been existed regarding the relationship between oxidative stress and diabetes. The present study was conducted to assess the effect of atorvastatin on selected oxidative stress parameters and its effect on lipid profile parameters in dyslipidaemic type 2 diabetic patients. Fifty nine dyslipidaemic type 2 diabetic patients were included in this study. A full history was taken and general examination was performed. The patients were taking an oral hypoglycaemic drug (glibenclamide) during the study. The patients were followed up for 60 days and divided randomly into 2 groups. Group I (n = 31) received no drug and served as dyslipidaemic diabetic control. Group II (n = 28) received atorvastatin tablets 20 mg once daily at night. Blood samples were drawn from the patients at the beginning and after 60 days of follow up between 8:30 and 10:30 am after at least 12-14 hours fasting. Fasting blood glucose, lipid profile, selective oxidative stress parameters, glutathione S reductase (GSH), malondialdehyde (MDA) levels, glutathione S transferase (GST) and catalase (CAT) activities were measured. Renal and hepatic functions were also assessed. The results showed that atorvastatin treatment produced significant increase in serum levels of GSH and High Density Lipoprotein (HDL), while serum levels of MDA, Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C) and Very Low Density Lipoprotein (VLDL) were significantly decreased. However, no significant effect was observed regarding CAT and GST activity. There were insignificant correlations between atorvastatin induced changes in the oxidation markers and the observed changes of the lipid profile. In conclusion, the antioxidant effect of atorvastatin could be unrelated to its hypolipidemic action as there was insignificant correlation between changes in lipid profile and oxidative stress in this study.

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

Antiretroviral therapy in HIV patients is known for its negative effect on the cardiovascular system. One of the major adverse events in patients on lopinavir is increasing lipids. Hyperlipidaemia together with chronic inflammation by HIV-infection itself makes these patients prone for cardiovascular diseases.The purpose of this study (a sub study within the FREE-study) was to determine if higher plasma lopinavir (LPV) concentrations lead to increase of serum lipids. Plasma drug concentrations were analysed up to week 24 in a prospective cohort of HIV antiretroviral therapy naive patients who started on a regimen of zidovudine, lamivudine and ritonavir-boosted lopinavir (FREE study). Prospectively we measured plasma lopinavir concentrations from baseline to week 24 in 72 naive HIV-patients starting on lopinavir (59 males and 13 females). A total of 210 samples were analysed, with at least 2 samples in every patient. Mean LPV trough concentration was 4.3 mg/L (± 2.1). The median intra-subject variation in LPV level was 38% (range 4% - 111%). Serum lipids were not correlated to LPV plasma concentrations possibly due to the wide intra-individual variability in LPV trough levels. Monitoring of plasma lopinavir and subsequent dose adjustment of LPV will not be useful to prevent hyperlipidaemia in HIV-patients treated with lopinavir.

Association of Hyperhomocysteinaemia with Hyperglycaemia, Dyslipidaemia, Hypertension and Obesity

There is conflicting scientific data about the link between, high homocysteine (Hcy) levels in the general population, and obesity. This is a case-control study aimed to assess the role of hyperhomocysteinemia in obesity and its associated illnesses, including hypertension, dyslipidemia, and hyperglycemia in Gezira state, Sudan. Two hundred and eleven participants were included in the study, 140 were obese (117 females and 23 males) and 71 were normal weight control, the obese median age was 49.49 ± 12.2 years. The control group consisted of 71 individuals with an average age of 45.78 ± 17.67 years. Among those who were already known to be obese, 67 (47.9%) reported having type II diabetes mellitus, 71 (50.7%) reported having hypertension, and 35 (25%) were obese without having either diabetes or hypertension. Three mls of venous blood from each participant were collected in the morning after a 12 h overnight fasting in Lithium heparin containers then the plasma was separated and stored at -80&deg;C for analysis. Serum Hcy and lipid profile were measured using the enzymatic method by Cobas C 411 analyzer. In comparison to obese non-hypertensive, the results showed that obese hypertensive with Hcy levels > 15 mol/L had a considerably increased risk (OR 1.12). When Hcy levels > 15 mol/L were compared to obese diabetics and obese non-diabetics, insignificant difference was shown (P: 0.345). Males had a higher likelihood of having hyperhomocysteinemia than females did (OR 1.2). Homocysteine, cholesterol triglyceride, LDL, and HDL mean values were compared between case and control groups using the independent sample t-test, and the results revealed statistically significant (P: <0.05). Relationships between hyperhomocysteinaemia and cholesterol, triglycerides, LDL, and HDL in the group of obese individuals were not statistically significant (P: 0.574, 0.265, 0.748, and 0.14), respectively. Obesity and Hcyconcentrations were shown to be substantially correlated. However, there was no statistically significant association between baseline plasma Hcy levels and hyperglycemia, hypertension, or dyslipidemia.

Evaluation of Lipid Profile in Obese and Non-Obese Hypertensive Adult Patients Attended in Medicine Department of a Medical College Hospital of Bangladesh

Background: By the dawn of this modern era of science, the prime challenge of physician is cardiovascular disease (CVD). The most important modifiable risk factors of CVDs are unhealthy diet, physical inactivity and tobacco use. The effects of unhealthy diet and physical inactivity include abnormal blood lipid, obesity and hypertension. We tried to evaluate and correlate the pattern of lipid profile in obese and non-obese hypertensive patients. Objectives: This study was conducted at medicine department of Cumilla Medical College Hospital. The principal aim was to evaluate the lipid profile in obese and non-obese adult hypertensive patients. Methodology: During this cross sectional analytical study, a total of 100 adult hypertensive patients were taken by purposive sampling. Among them 50 (group 1) patients were taken those were obese and 50 (group 2) patients taken those were non-obese according to BMI measurement on operational definition. Diagnosis of hypertension would be established with the help of ambulatory BP measurements two occasions few minutes apart. The staging of hypertension was done according to JNC7 Criteria. Morning blood samples were taken after 8 - 12 hours of fasting and lipid profiles were done on authentic laboratories. The laboratory values were interpreted according to the operational definition of dyslipidaemia. The ethical research and review committee approved the study protocol and signed informed consent was obtained from the participants. The statistics was analyzed using the IBM SPSS software of version 19.0. Statistical significance was set at p < 0.05. Results: Among the two groups, there were 56 (56%) males and 44 (44%) females. The mean age of group 1 (46.10 ± 11.09) was compared to that of group 2 (45.5 ± 10.6). Lipid profile abnormalities were significantly higher in the stage 2 hypertension (59.62%) and stage 3 hypertension (66.66%), higher in class 2 obese (100%) and class 3 obese subjects (100%), female hypertensive patients had significantly higher BMI than their male counterparts (27.24 ± 3.63 kg/m2 versus 29.29 ± 3.99 kg/m2), lipid profiles were higher in the female than male hypertensive patients (63.33% vs 55.35%) but only TC was statistically significant (4.45 ± 1.19 mmol/l versus 4.86 ± 1.29 mmol/l, p < 0.05). Those who were obese had significant high TG (p < 0.001), high TC (p < 0.001) and high LDL-C (p < 0.001). 38 (76%) of the obese hypertensive patients had dyslipidaemia whereas 21 (42%) of non-obese hypertensive patients had dyslipidaemia. In multivariate regression, TG was significantly and directly associated with BMI of subjects. Dyslipidaemia was more prevalent in the age group 30 - 59 of adult hypertensive patients. It showed that obese hypertensive patients had significantly higher SBP (p < 0.001), DBP (p < 0.001) than non-obese subjects. The mean TC (4.83 ± 0.95 mmol/l versus 4.15 ± 0.57 mmol/l, t = -9.70, p < 0.001), TG (2.64 ± 0.67 mmol/l versus 2.10 ± 0.45 mmol/l, t = -5.37, p < 0.001) and LDL-C (3.00 ± 0.82 mmol/l versus 2.44 ± 0.53 mmol/l, t = -9.11, p < 0.001) were also significantly higher among the hypertensive obese subjects. The mean HDL-C was however comparable in the two groups (1.25 ± 0.27 mmol/l versus 1.24 ± 0.57 mmol/l, t = -0.25, p = 0.08)...

Hydro-Ethanol Extract of Persea americana Fruit Pulp Ameliorates Dyslipidaemia and Cardiotoxicity Exerted by Alloxan-Induced Diabetes Mellitus

Diabetes-induced dyslipidaemia has been associated with an increased risk of atherosclerosis and coronary heart diseases. Persea americana fruit has been reported to possess anti-diabetic properties. Therefore, this study assessed the lipid profile and likely cardio-protective effects of hydroethanolic extracts of P. americana fruits in alloxan-induced diabetic Wistar rats. Thirty-five male rats (150 ± 30 g) were divided into 5 groups (n = 7) and treated orally as follows;groups I-II were normal animals treated with distilled water (0.3 ml/day) and P. americana (300 mg/kg) only respectively. Animals in groups III-V were made diabetic using alloxan monohydrate (100 mg/kg i.p.) and treated orally with distilled water (0.3 ml/day), P. americana (300 mg/kg) and glibenclamide (5 mg/kg) respectively for 21 days. Fasting blood glucose level was monitored prior to, after induction of diabetes mellitus, and on day 21 post-treatment, respectively. Thereafter, retro-orbital blood samples were collected after anaesthesia and analysed for insulin, total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) levels, apolipoproteins A1 and B, superoxide dismutase (SOD) and catalase activities, reduced glutathione (GSH), Vitamin C and malondialdehyde levels, respectively. VLDL, atherogenic index (AI) and ApoB/A1 ratio were estimated mathematically. Pancreatic and cardiac structures were also investigated using Haematoxylin and Eosin stains. Treatment with P. ameriacana extracts reduced (p P. americana treated diabetic group. The hydro-ethanol fruit extract of Persea americana attenuates diabetes induced dyslipidaemia and reduces the susceptibility to cardiac impairment in experimental diabetes mellitus.

Apolipoprotein B Is a Good Tool for Screening Dyslipidaemia in Apparently Healthy Population

Dyslipidaemia is the major risk factor for cardiovascular disease (CVD) which is the leading cause of death in the world. Even though several lipid parameters are used, currently apolipoprotein B (apoB) is considered as the best predictor of CVD. Thus this study was carried out to find out the association between conventional lipid parameters and apoB in apparently healthy subjects. A descriptive cross-sectional study was carried out in 170 apparently healthy volunteers who were not diagnosed with dyslipidaemia. After 12 hours overnight fast venous blood was obtained and Total cholesterol (TC), Triglyceride (TG), High density lipoprotein cholesterol (HDL-C) were measured by enzymatic kit method. Low density lipoprotein cholesterol (LDL-C) was calculated by Friedewald formula and apoB was analyzed by immune turbid metry using a Konelab® auto analyzer. Among the participants, majority (63.5%) were females. The mean value of apoB concentration of the population was 103 ± 42 mg/dL which was similar and not significantly different between the genders (Males, 102 ± 37 mg/dL and Females, 104 ± 45 mg/dL). All lipid parameters showed a positive correlation with apoB concentration whereas HDL-C had a negative correlation (r = -0.165). HDL-C significantly (p < 0.05) decreased with increase in apoB concentration while LDL-C, TC/HDL-C and non-HDL-C significantly (p < 0.05) increased with an increase in apoB concentration. Present study suggests that serum apoB has better correlations and associations with the parameters that are used in conventional lipid profile and with markers recommended for diagnosing dyslipidaemia. Hence apoB could be used as a single marker for screening dyslipidaemia in apparently healthy people.

Potential role of vitamin D in patients with diabetes,dyslipidaemia,and COVID-19

Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2 has become a worldwide public health crisis.Studies have demonstrated that diabetes and dyslipidaemia are common comorbidities and could be high-risk factors for severe COVID-19.Vitamin D,a group of fatsoluble compounds responsible for intestinal absorption of calcium,magnesium,and phosphate,has been widely used as a dietary supplement for the prevention and treatment of numerous diseases,including infectious and non-infectious diseases,due to its high cost-effectiveness;safety;tolerability;and anti-thrombotic,anti-inflammatory,antiviral,and immunomodulatory properties.In this letter to the editor,we mainly discuss the potential role of vitamin D in patients with diabetes,dyslipidaemia,and COVID-19.

Dyslipidaemia among diabetic patients with ischemic stroke in a Chinese hospital

Background Dyslipidaemia is a potential independent The aim of this study was to investigate dyslipidaemia, with ischemic stroke in a Chinese hospital. risk factor for cerebrovascular disease in patients with diabetes. treatment and control of dyslipidaemia among diabetic patients Methods A total of 1046 type 2 diabetic patients were assigned to diabetes with （n=-522） and diabetes without stroke groups. The two groups were matched by gender, age and diabetes duration. Lipid and lipoprotein profile were measured. Serum level and control of lipids were assessed and classified according to American Diabetes Association （ADA） guidelines and an intensified low density lipoprotein-cholesterol （LDL-C） target recommended in Chinese dyslipidaemia control criteria. Results Diabetic patients suffering stroke displayed not only poorly-controlled lipid and lipoprotein profiles, including the significantly lower proportion of patients achieving intensified LDL-C target of 〈2.07 mmol/L （80 mg/dl）, and high density lipoprotein-cholesterol （HDL-C） target （14.4% vs 21.0%, P=0.005; 45.8% vs 51.9%, P=0.048 respectively）, but also less adherence to therapy prescribed for dyslipidaemia （30.8% vs 41.0%, P=0.001）, when compared with diabetic patients without stroke. For the diabetic women with stroke, situation of dyslipidaemia was worse, with significantly lower serum level of HDL-C and apoA1, higher LDL-C level and higher ratio of apoB/apoA1 when compared with diabetic counterparts without stroke. Conclusions Many diabetic patients with ischemic stroke remain uncontrolled for dyslipidaemia. Intensified LDL-C and overall lipid lowering clinical goals are potential precautions taken against ischemic stroke among diabetic patients in China.