Risk Of Cardiovascular Disease In Type Research Articles

Serum bicarbonate concentration and the risk of cardiovascular disease and death in type 2 diabetes: the Fremantle Diabetes Study.

BackgroundSerum bicarbonate is associated with mortality, heart failure (HF) and progression of renal failure in studies of healthy people and patients with chronic kidney disease, but the significance of these observations in unselected patients with diabetes in the general population is unknown. The aim of this study was to determine whether serum bicarbonate was associated with mortality and cardiovascular disease risk in type 2 diabetes.MethodsBaseline serum bicarbonate was available for 1283 well-characterized community-based patients (mean ± SD age 64.1 ± 11.3 years, 48.7 % males) from the longitudinal observational Fremantle Diabetes Study followed for a mean of 12 years. Associations between serum bicarbonate and mortality, coronary heart disease (CHD) and incident HF were analysed using Cox proportional hazards regression.ResultsSerum bicarbonate was independently and negatively associated with incident CHD. For each 1 mmol/L increase in bicarbonate, the hazard ratio for CHD was 0.95 (95 % confidence interval 0.92–0.99) after adjustment for age as time scale, age at baseline, sex, English fluency, diabetes duration, loge(serum triglycerides), loge(urinary albumin: creatinine ratio), peripheral sensory neuropathy and peripheral arterial disease. There were no independent associations between serum bicarbonate and all-cause mortality [0.98 (0.95–1.004)] or incident HF [0.99 (0.95–1.03)].ConclusionsSerum bicarbonate was a significant independent predictor of incident CHD but not death or HF in community-based patients with type 2 diabetes. This supports intervention trials of bicarbonate replacement in type 2 patients at risk of CHD and who have a low serum bicarbonate concentration.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0462-x) contains supplementary material, which is available to authorized users.

Evaluation of Non-HDL Cholesterol and Total Cholesterol/HDL-C Ratio, LDL-C/HDL-C Ratio as Cumulative Marker of Cardiovascular Disease risk in Type 2 Diabetes Mellitus Patients

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide with an estimated 17.3 million deaths from CVDs in 2008, representing 30% of all global deaths. The main cause of CVD development is atherosclerosis and among the various factors for developing increased cardiovascular risk in diabetes; lipid abnormalities, the dyslipidemia is the major contributor. The common type of dyslipidemia in diabetes is characterized by elevated triglyceride (TG), low levels of high density lipoprotein cholesterol (HDL-C) and typically has a preponderance of smaller, denser low density lipoprotein cholesterol (LDL-C) particles, which possibly increases atherogenicity even if the absolute concentration of LDL cholesterol (LDL-C) is not significantly increased. Materials & Methods: Total of 100 diagnosed type 2 diabetes mellitus ambulatory patients of both sexes were taken as cases. Their age ranged between 30 to 70 years. 100 healthy subjects, with their age ranging between 30 to 70 years were selected as control group. Serum sample was used for the estimation of study parameters such as FBS, PPBS, Total Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol. Results: In this study, total cholesterol, triglycerides, LDL-C, Non-HDL-C, TC/HDL-C and LDL-C/HDL-C were found to be statistically significantly increased in type 2 diabetes mellitus patients when compared to controls. HDL-C was significantly decreased in type 2 diabetes mellitus patients when compared to controls ( p -value 0.001). Conclusion: In this study, type 2 diabetes mellitus is associated with dyslipidemia with increased levels of TC, TG, LDL-C, Non-HDL-C, TC/HDL-C and LDL-C/HDL-C ratio, but a lower levels of HDL-C compared to that of controls. Increased levels of Non-HDL-C, TC/HDL-C and LDL-C/HDL-C ratio which indicates increased impending cardiovascular disease risk in type 2 diabetes mellitus.

Body mass index and adiposity indicators associated with cardiovascular biomarkers in youth with type 1 diabetes followed prospectively.

The impact of excess weight on cardiovascular disease risk in type 1 diabetes patients is unclear. This study examined associations of BMI and body composition with cardiovascular risk factors in youth followed prospectively for 18 months. The sample includes youth with type 1 diabetes (N = 136, baseline age = 12.3 ± 2.5y, glycated hemoglobin = 8.1 ± 1.1%) participating in an 18-month behavioral nutrition intervention trial. BMI, body composition (by dual energy x-ray absorptiometry), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C); triglycerides (TG), c-reactive protein (CRP), 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), adiponectin and systolic and diastolic blood pressure (SBP and DBP, respectively) were assessed at clinic visits every 6 months. Random effects regression models for repeated measures estimated associations of time-varying BMI and body composition with time-varying cardiovascular risk factors, adjusted for treatment assignment and covariates. There was no intervention effect on cardiovascular risk factors. Percent body fat was positively associated with TG, LDL-C, CRP, SBP and DBP, while trunk fat mass and trunk %fat were associated positively with TG, LDL-C, CRP, SBP and DBP, and inversely with HDL-C. Higher BMI was associated with greater TG, CRP, SBP and DBP and lower HDL-C. BMI and body composition indicators were unrelated to 8-iso-PGF2α and adiponectin. Excess adiposity is associated with increased cardiovascular risk factors in this sample of youth with type 1 diabetes. Non-significant associations with adiponectin and 8-iso-PGF2α suggest potential differences from the general population in the role of adiposity in cardiovascular health.

PWE-032 Fatty Liver Index (FLI), Which is An Accurate Predictor of Nonalcoholic Fatty Liver Disease (NAFLD), Is A Better Predictor of Cardiovascular Disease Risk in Type 2 Diabetic Patients than The UK Prospective Diabetes Study (UKPDS Risk Engine V 2.0)

Introduction NAFLD, which is increasingly and rapidly becoming the cause of liver disease in Western countries, is characterised by higher serum triglyceride and LDL levels, lower HDL levels, insulin resistance, and glucose intolerance, all crucial risk factors for the development of atherogenesis. The UK Prospective Diabetes Study (UKPDS risk engine v 2.0) and the Fatty liver index (FLI) are both validated prognostic scores for cardiovascular disease (CVD) risk and NAFLD in diabetic patients. Methods We retrospectively analysed 1902 patients attending our Diabetes Ambulatory in 2012–2013. The UKPDS risk engine and the FLI were calculated for each of these patient. Ninety-nine (19.2%) of these patients resulted at high CVD risk according to their UKPDS evaluation and underwent a complete CVD assessment (ergometric/ecostress test (EET), coronarography (CORO)). A two tailed t-test, Person’s Chi square test, and analysis of variance (ANOVA) were carried out. Results Sixty-six (59 M, mean age 68.1 y, mean disease duration 16.1 y, HbA1c > 7 prevalent) pts presented UKPDS positive/FLI > 60, 8/66 CORO+ (5 percutaneous transluminal coronary angiopathy-PTA, 3 cardiac bypass sugery-CABG, 1 peripheral transluminal angioplasty-PTA AAII) and 5 (4 M, mean age 68.6 y, mean duration disease 18.4 y, HbA1c > 7 prevalent) pts presented UKPDS positive/FLI 52 detected 9/14 pts positive at CORO with p 69/99) (100% > 14/14 CORO+) vs 81 pts FLI > 52 (EET negative 92.5% > 75/81) (64.2% > 9/14 CORO+). As expected, we found a significant association between CORO+ and FLI+ patients and microalbuminuria (p Conclusion Study results demonstrate that FLI can be used as a marker to predict CVD risk in patients with FLI > 52. The number of patients who undergo CVD screening with a low percentage of positivity can thus be reduced. An early and aggressive treatment and monitoring program can instead be begun for type 2 diabetic patients with FLI > 52 and a reasonable suspicion of NAFLD because this population has higher risk of developing CVD events with respect to patients with FLI Disclosure of Interest None Declared

ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels and predicts cardiovascular disease risk in Type 2 diabetic Tunisian population.

BackgroundAngiopoietin-like protein 4 (ANGPTL4) is a metabolic factor that increases plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). The objective of this study was to investigate the association of ANGPTL4 variants (E40K and T266M) with triglyceride levels and with cardiovascular risk factors, such as metabolic syndrome (MetS) and obesity in type 2 diabetic Tunisian population.MethodsWe investigated the effect of the tagging single nucleotide polymorphisms (SNPs) rs1044250 (T266M) and rs116843064 (E40K) with triglyceride (TG) levels and CAD risk factors in a cohort of 220 patients undergoing coronary angiography for the evaluation of stable CAD, all of whom had (type 2 diabetes) T2D and were at least overweight. Multivariate logistic regressions were performed on association studies.ResultsTT genotype of rs1044250 (T266M variant) showed a protective effect on CVD risk in CAD group patients (OR 1.92, 95 % CI 0.601.42, p =0.05) compared with control Group patients (OR 1.17, 95 % CI 0.70–1.66, p = 0.72). Likewise, GA genotype of rs116843064 (E40K variant): (OR 0.74, 95 % CI 0.54–1.65, p =0.01) for the CAD group compared with control Group patients (OR 1.12, 95 % CI 0.68–1.74, p = 0.074).ConclusionsANGPTL4 variants are associated with, not only lower fasting triglyceride levels, but also a decreased cardiovascular risk in T2D Tunisian patients. So, T266M and E40K polymorphism predicts cardiovascular disease risk in Type 2 diabetic Tunisian population

Evaluation of arterial stiffness in children with type 1 diabetes using the oscillometric method

AimsPulse wave velocity (PWV) is an accepted evaluation method to assess vascular changes and determine cardiovascular disease risk in type 1 diabetes (T1D) patients. The aim of this study was to identify atherosclerosis risk by using oscillometric device in pediatric patients who had T1D but no end organ impairment and no cardiovascular disease findings. Materials and methodsPediatric patients with T1D and no determined end organ impairment and cardiovascular disease were involved in the study. ResultsA total of 72 patients with T1D containing 32 males and 40 females were included in the study. A total of 77 patients including 39 males and 38 females were evaluated as healthy control group. The average age of patients with T1D was 12.8±3.7years, their average weight was established as 43.8±16.7kg. The average age of control group was 12.3±1.6years and average weight was determined as 46.8±12.8kg. When the results obtained by pulse wave method were compared; PWV and Alx_75 values in T1D patients (respectively, 4.63±0.40 and 22.9±6.7) were determined significantly higher than those of control group (respectively, 4.42±0.34 and 16.6±6.6). A positive correlation was identified between diabetes duration and HbA1c (instant and mean) levels in patients with T1D with respect to PWV and Alx_75 values. ConclusionsArterial stiffness was impaired in children with T1D with no end organ impairment using oscillometric method. This impairment was related to high HbA1c levels and diabetes duration.

Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus: The Steno Type 1 Risk Engine.

Patients with type 1 diabetes mellitus are at increased risk of developing cardiovascular disease (CVD), but they are currently undertreated. There are no risk scores used on a regular basis in clinical practice for assessing the risk of CVD in type 1 diabetes mellitus. From 4306 clinically diagnosed adult patients with type 1 diabetes mellitus, we developed a prediction model for estimating the risk of first fatal or nonfatal CVD event (ischemic heart disease, ischemic stroke, heart failure, and peripheral artery disease). Detailed clinical data including lifestyle factors were linked to event data from validated national registers. The risk prediction model was developed by using a 2-stage approach. First, a nonparametric, data-driven approach was used to identify potentially informative risk factors and interactions (random forest and survival tree analysis). Second, based on results from the first step, Poisson regression analysis was used to derive the final model. The final CVD prediction model was externally validated in a different population of 2119 patients with type 1 diabetes mellitus. During a median follow-up of 6.8 years (interquartile range, 2.9-10.9) a total of 793 (18.4%) patients developed CVD. The final prediction model included age, sex, diabetes duration, systolic blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, glomerular filtration rate, smoking, and exercise. Discrimination was excellent for a 5-year CVD event with a C-statistic of 0.826 (95% confidence interval, 0.807-0.845) in the derivation data and a C-statistic of 0.803 (95% confidence interval, 0.767-0.839) in the validation data. The Hosmer-Lemeshow test showed good calibration (P>0.05) in both cohorts. This high-performing CVD risk model allows for the implementation of decision rules in a clinical setting.

Assessment of Cardiovascular Disease Risk in Type 2 Diabetic Patients: A Comparison of Risk Indices

Diabetes mellitus is a major public health problem; it is synchronized with the development of many complications of which cardiovascular disease is the most prevalent and detrimental. This study aimed at comparing the strength of various cardiovascular risk indices among diabetes type 2 patients. The risk indices evaluated were: Apoprotein A1, Apoprotein B1, lipoprotein (a), total cholesterol, (TCHOL), Triglyceride (TG), low density lipoprotein (HDL), TC/HDL, pentad and tetrad. Two hundred and four (204) subjects were studied comprising of 152 diabetes subjects and 52 non-diabetics as control. The result shows significantly higher values in the mean blood pressure of diabetic subjects when compared with the control at (p < 0.05. Mean HbA1C and total cholesterol values for diabetes subjects were significantly higher when compared with the control. However, the HDL-cholesterol of the diabetes subjects was significantly lower when compared to the control subjects. There was no significant difference in triglyceride level of both groups. The mean values of Apo A, Apo B and lipoprotein a, were higher in diabetic subjects compared to the control subjects at (p < 0.05). Comparison of the liporprotein induces in terms of sensitivity, specificity and accuracy, Lpa had a sensitivity of 97.3%, specificity of 100% and accuracy of 95.7%, next was pentad with sensitivity of 91.45%, specificity of 100% and accuracy of 95.73%. Tetrad had a sensitivity of 81.05%, specificity of 100% and accuracy of 90.5%, the TC/HDL ratio and the least accuracy of 75.76%. Based on the overall accuracy Lpa tend to display highest accuracy followed by PENTAD and TETARD.

Association of Type II 5¢ Monodeiodinase Thr92Ala Polymorphism and Cardiovascular disease risk in Type 2 Diabetes Mellitus

Background: The physiological ratio of T3:T4 is essential to trigger the biological action since it is efficiently regulated by extrathyroidal selenodeiodinases. Thr92Ala is a common variant in the DIO2 gene which may have implication in decreased phenotypic expression. This study intends to find the effect of the SNP on CVD risk in type 2 diabetes. Materials and Methods: We included 130 T2DM patients without signs of CVD as controls and 106 CVD patients with T2DM as cases. All were genotyped for Thr92Ala of DIO2 gene. Fasting blood glucose lipid and thyroid profile, HDL subfractionations, type II deiodinase, malondialdehyde, paraoxonase, and superoxide dismutase were measured Results: The mean D2 level in Ala/Ala individuals was significantly lower than in Thr/Thr or Thr/Ala genotypes (122±39 VS 161±32ng/ml). The thyroid profile was significantly altered among Ala/Ala genotypes when compared with Thr/Thr and Thr/ Ala genotypes. There is a significant decrease in T3:T4 ratio, HDL3:HDL2 ratio and paraoxonase activity among Ala/Ala homozygote’s when compared with the/Thr+Thr/Ala genotypes. HDL3:HDL2 ratio is positively correlated with paraoxonase activity among Thr/Thr+Thr/Ala genotypes (r=0.36, p<0.05). Conclusion: Ala/Ala genotype plays a key role in thyroid dysfunction, dyslipidemia and the development of CVD risk in those which type 2 diabetes. Key-words: DIO2 Thr92Ala; Thyroid hormones; Dyslipidemia; Oxidative stress; Type 2 diabetes mellitus; CVD risk

Relation of Combined Non–High-Density Lipoprotein Cholesterol and Apolipoprotein B With Atherosclerosis in Adults With Type 1 Diabetes Mellitus

Apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are cardiovascular disease risk markers, although data in adults with type 1 diabetes mellitus (DM) are limited. We hypothesized that elevated apoB and non-HDL-C would be associated with greater odds of coronary artery calcification progression (CACp), a measure of coronary atherosclerosis, than either category alone in adults with type 1 DM. We grouped subjects with type 1 DM (n= 652) into 4 groups: elevated apoB (≥90mg/dl) and elevated non-HDL-C (≥130mg/dl), elevated non-HDL-C alone, elevated apoB alone, and normal apoB and non-HDL-C. We used logistic regression to examine the associations between the groups and CACp for a period of 6 years. We performed sensitivity analyses with elevated apoB and non-HDL-C redefined as at or more than the cohort means (91.4 and 119.0mg/dl, respectively). Subjects with elevated apoB and non-HDL-C had greater odds of CACp compared with those with normal apoB and non-HDL-C (odds ratio 1.90, 95% confidence interval 1.15 to 3.15) and compared with subjects with elevated apoB alone (odds ratio 2.86, 95% confidence interval 1.43 to 5.74) adjusting for age, gender, duration, hemoglobin A1c, and statins. Similar results were obtained with elevated apoB and non-HDL-C defined as at or more than the cohort means. In conclusion, elevated apoB and non-HDL-C carry a greater risk of atherosclerosis than elevated apoB in the absence of elevated non-HDL-C in adults with type 1 DM. These data suggest that apoB and non-HDL-C should be viewed as complementary rather than competitive indexes of cardiovascular disease risk in type 1 DM.

Matrix metalloproteinase-2 (MMP-2) gene polymorphism and cardiovascular comorbidity in type 2 diabetes patients

ObjectiveMatrix metalloproteinases (MMPs) play an important role in pathogenesis of atherosclerosis and vascular disease. We hypothesized that MMP-2 might be a susceptibility gene for cardiovascular disease (CVD) in diabetes. The aim of this study was to evaluate the association between C(−1306)T functional polymorphism in the MMP-2 gene and risk of CVD in type 2 diabetes patients. MethodsWe examined 1090 patients with T2DM and 612 controls. All subjects were genotyped for the C(−1306)T polymorphism by polymerase chain reaction (PCR) and restriction analysis. ResultsA significant decrease of T allele frequency was observed in patients with CVD versus those with no CVD (OR 0.44, 95% CI 0.36–0.52, p<0.0001). In contrast, OR for CC genotype was 2.19 (1.79–2.68, p<0.0001), conferring 2-fold greater odds for CVD. When the distribution of C(−1306)T was compared in subgroups with different clinical phenotypes of CVD, patients with stroke had the lowest frequency of T allele (6% vs. 11%), compared to entire CVD+ group (p<0.05). ConclusionsT2DM patients carrying the T allele of MMP-2 C(−1306)T polymorphism have a significantly reduced risk of CVD. The C(−1306)T polymorphism is associated with susceptibility to stroke in T2DM patients.

Insulin therapy in insulin resistance: Could it be part of a lethal pathway?

Insulin therapy in insulin resistance: Could it be part of a lethal pathway?

High daily insulin exposure in patients with type 2 diabetes is associated with increased risk of cardiovascular events

AimsIntensive glucose control, often involving insulin treatment, failed to improve cardiovascular outcomes in several clinical trials. Observational studies reported an association between insulin use and cardiovascular disease (CVD) risk. It has therefore been suggested that insulin adversely affects CVD risk. To investigate the feasibility of this hypothesis, we studied the association between insulin dose and CVD risk in type 2 diabetes. MethodsA case-control study was conducted of new users of oral antidiabetics who were prescribed insulin, using the Dutch Pharmo database. Cases were hospitalized for a cardiovascular event (CVE) and matched 1:2 to patients who were not hospitalized for a CVE, by sex, age, duration of diabetes and type of oral antidiabetic. Patients were divided into tertiles according to mean daily insulin dose. Conditional logistic regression analyses were used to explore the association between insulin exposure and CVE risk. ResultsWe included 836 patients (517 (62%) male, mean age 66 years). After adjusting for available potential confounders, including HbA1c and triglycerides, insulin exposure was positively related to CVE risk (odds ratios for high (≥53.0 U/day) and intermediate (24.3–52.9 U/day) vs. low exposure (≤24.2 U/day): 3.00 [95% confidence interval (CI) 1.70 to 5.28] and 2.03 [95% CI 1.17 to 3.52]. ConclusionOur findings are in line with the suggestion that high-dose insulin therapy adversely affects CVD risk, but need to be interpreted with caution due to the observational nature of the study. The role of particularly high-dose insulin in the progression of CVD warrants further investigation.

Lecithin: Cholesterol Acyltransferase Activity and Homocysteine Levels are Better Associated with Lipid Profile Indices Compared to Glycemic Control Indices in Patients with Diabetes Mellitus

Aims: Homocysteine (Hcy) level, LCAT activity, and HDL-C concentration and oxidative/antioxidative capacities are well-established factors in determining cardiovascular disease risk in Type 2 diabetes mellitus. However, the association between these factors and lipid profile and glycemic control variables remains to be unveiled. We aimed to assess accuracy of LCAT activity and Hcy Original Research Article Nakhjavani et al.; AIR, 3(1): 49-59, 2015; Article no. AIR.2015.005 50 for dyslipidemia and poor glycemic control screening in patients with type 2 diabetes mellitus. Study Design: This case control study was conducted in Vali-Asr hospital affiliated with Tehran University of Medical Sciences. Methodology: We quantified FBS, HDL-C, HbA1c, Hcy, LCAT activity and other lipid profiles markersin a total of 41 patients with type 2 diabetes mellitus along with 41 matched healthy subjects. Results: Linear regression and correlation analysis revealed that Hcy had a positive correlation with LCAT activity only in HDL levels above 40 mg/dl. Receiver operating characteristics (ROC) curves testing LCAT activity in prediction of hyperhomocysteinemia as the state variable for both control subjects and patients, showed the one for patients with diabetes being more shifted up and to the left than for control subjects. In addition, both Hcy and LCAT activity predicted lipid profile variables more precisely than glycemic control variables. Conclusion: LCAT activity could be considered as one of the factors predicting hyperhomocysteinemia and therefore indirectly associated with cardiovascular events and it is more specific and sensitive in patients with diabetes compared to control subjects. However neither Hcy and nor LCAT activity, are able to predict diabetes and/or diabetes associated oxidative stress. These factors might be more associated with diabetes related dyslipidemia.

Association of apolipoprotein B, LDL-C and vascular stiffness in adolescents with type 1 diabetes.

LDL cholesterol (LDL-C) is the current lipid standard for cardiovascular disease (CVD)-risk assessment in type 1 diabetes. Apolipoprotein B (apoB) may be helpful to further stratify CVD risk. We explored the association between apoB and pulse wave velocity (PWV) to determine if apoB would improve CVD-risk stratification, especially in type 1 diabetes adolescents with borderline LDL-C (100-129mg/dL). We hypothesized that type 1 diabetes adolescents with borderline LDL-C and elevated apoB (≥90mg/dL) would have increased PWV compared to those with borderline LDL-C and normal apoB (<90mg/dL), and that apoB would explain more of the variability of PWV than alternative lipid indices. Fasting lipids, including apoB, were collected in 267 adolescents, age 12-19years, with diabetes duration >5years and HbA1c 8.9±1.6%. Triglyceride to HDL-C ratio (TG/HDL-C) and nonHDL-cholesterol (nonHDL-C) were calculated. PWV was measured in the carotid-femoral segment. ApoB, nonHDL-C and TG/HDL-C correlated with PWV (p<0.0001). ApoB, nonHDL-C and TG/HDL-C remained significantly associated with PWV in fully adjusted models. In adolescents with borderline LDL-C (n=61), PWV was significantly higher in those with elevated apoB than in those with normal apoB (5.6±0.6 vs. 5.2±0.6m/s, p<0.01) and also remained significant after adjustment for CVD-risk factors (p=0.0002). Moreover, in those with borderline LDL-C, apoB explained more of the variability of PWV than nonHDL-C and TG/HDL-C. Elevated apoB is associated with increased arterial stiffness in type 1 diabetes adolescents. Measurement of apoB in addition to LDL-C may be helpful in stratifying CVD risk in type 1 diabetes adolescents, especially in those with borderline LDL-C.

Does the MTHFR C677T gene polymorphism indicate cardiovascular disease risk in type 2 diabetes mellitus patients?

Objective:Diabetes mellitus is a major risk factor for cardiovascular disease (CVD). We investigated the relationship among biochemical and cardiac risk parameters with the methylenetetrahydrofolate reductase (MTHFR) C677T genotype in type 2 diabetes mellitus (T2DM) patients.Methods:One hundred seven T2DM subjects with severe CVD diagnosed by angiography were included consecutively in this cross-sectional study. Biochemical and clinical parameters were obtained from patients who were not positive for nephropathy and retinopathy. MTHFR C677T genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Normally and abnormally distributed continuous variables were analyzed using student t- and Mann-Whitney U tests. Categorical variables were analyzed using chi-square test.Results:In the study, 31 T2DM subjects had the CC (29.0%), 62 had the CT (57.9%), and 14 had the TT (13.1%) genotypes. There were no significant differences between subjects with wild-type (677CC) and with mutant (677CT+677TT) alleles in terms of diabetes duration, visceral fat area, total cholesterol, triglyceride, fasting plasma glucose, systolic blood pressure, diastolic blood pressure, high-sensitivity C-reactive protein, homocysteine (Hcy), and carotid intima-media thickness values.Conclusion:This study suggests that MTHFR gene polymorphisms can not be used as a marker for the assessment of cardiovascular risk in T2DM patients.

Visfatin and adiponectin as early markers of atherosclerosis in type 2 diabetes mellitus

Abstract Introduction As cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus, new markers for early detection and risk stratification of diabetic macroangiopathy and microangiopathy are highly desired. Adipocytokines were considered to lead to an increased risk of vascular complications in patients with type 2 diabetes by modulating vascular function and affecting the inflammatory process, thus enhancing atherosclerosis. Two of these were of particular interest, namely, visfatin and adiponectin. Aim The aim of this study was to evaluate serum visfatin, serum, and urinary adiponectin as early, sensitive surrogate markers of vascular atherosclerosis. We also correlated the levels of these markers to the degree of carotid intimal medial thickness (reflecting the atherosclerotic burden) in type 2 diabetic patients. Results Sixty diabetic patients were subdivided into two groups: group I (30 patients with carotid atherosclerosis as assessed by carotid Doppler) and group II (30 patients without carotid atherosclerosis). Twenty healthy volunteers participated as controls. Serum visfatin as well as serum and urinary adiponectin were assessed in all the study groups. We found significantly higher levels of serum visfatin among diabetics compared with the control group. Visfatin was also significantly higher in group I diabetics with atherosclerosis than those without (P&lt;0.05). Similarly, urinary adiponectin was significantly higher in group I than in group II and in diabetics than in the control group. Serum adiponectin was higher in the control group than both the study groups. Using a regression model, visfatin proved to be the only significant predictor in the model (ß = 0.03, P&lt;0.001). In fact, visfatin alone proved significant, explaining 63% of the variability in carotid intima-media thickness (P&lt;0.001). Conclusion Serum visfatin is highly correlated with macrovascular complications in diabetic patients. Serum visfatin may emerge as a valuable and cheaper surrogate marker for the prediction of prevalent macrovascular complications in a type 2 diabetic population. It is a novel and easy-to-obtain method for the clinical assessment of vascular stress and cardiovascular disease risk in type 2 diabetes. Future prospective studies are needed to confirm our results.

Association between serum cystatin C levels and cardiovascular disease in type 2 diabetic patients

Serum cystatin C concentration was recently reported as a marker of cardiovascular disease (CVD). In the present study, we evaluated the association between the increase of serum cystatin C levels and the risk of CVD in type 2 diabetes. 42 patients with type 2 diabetes were included in the present study; 27 of them have CVD. The control group consisted of 30 healthy adults. Cystatin C, creatinine, microalbuminuria and CRP were measured on Cobas 6000(TM). Cystatine C level was significantly higher in patients with CVD. A significant difference in serum cystatin C was found in patients with and without CVD among albuminuria. No difference in serum cystatin C levels was found according to number of affected vessels. A cystatin C level above 1.10 mg/L was associated with increase of risk of CVD with significant difference (OR = 42.52; IC 95% 1.455 to 1242.827 and p = 0.029). Our results suggested that the increase of serum cystatin C concentrations is a potential marker for CVD in diabetes.

Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients

Osteoprotegerin (OPG) gene polymorphisms (T245G, T950C and G1181C) have been associated with osteoporosis and early predictors of cardiovascular disease. The aim of this study was to evaluate whether these polymorphisms contribute to cardiovascular disease (CVD) in type 2 diabetic patients. We performed a case-control study with 178 CVD subjects with diabetes and 312 diabetic patients without CVD to assess the impact of variants of the OPG gene on the risk of CVD. The OPG gene polymorphisms were analyzed by using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). There was no significant association between the T245G and G1181C polymorphisms and CVD in the additive genetic model (OR = 0.96, 95% CI 0.64–1.45, p = 0.79; OR = 1.06, 95% CI 0.81–1.39, p = 0.65, respectively). However, the C allele of the T950C polymorphism was independently associated with a risk of CVD in type 2 diabetic patients in this genetic model (OR = 1.38, 95% CI 1.07–1.80, p = 0.01). This study provides evidence that the C allele of the T950C polymorphism is associated with increased risk of CVD in diabetic patients. However, well-designed prospective studies with a larger sample size are needed to validate these results.

Assessing Framingham cardiovascular risk scores in subjects with diabetes and their correlation with diabetic retinopathy

Sir, I read with interest the article entitled “Assessing Framingham cardiovascular risk scores in subjects with diabetes and their correlation with diabetic retinopathy” by Damkondwar, et al.[1] I want to raise certain issues concerning the validity of the results obtained in the said study. Sir, say, A (Framingham scores in type II diabetics), B [Cardiovascular Disease (CVD) risks in type II diabetics] and C (diabetic retinopathy) are three entities and if one wants to correlate B with C by measuring A, then A and B must have undoubted pre-existing correlation. But in the said study, it was admitted “There is no longitudinal study from India which can suggest whether the scores underestimate or overestimate the CVD risk among subjects with type II diabetes”. It was even not mentioned whether the cross-sectional data obtained in the study were in conformity with the Framingham study or not. Therefore when the standard (Framingham scores) was not standardized (validated) for CVD risks in Indian diabetic population, how can Framingham scores and/or CVD risks be correlated to diabetic retinopathy? Framingham cardiovascular risk score is notoriously known for its high interethnic variability.[2,3] In fact it is often said that Framingham cardiovascular risk score correlates well only in the race from where it is actually evolved. The authors themselves mentioned that in the United Kingdom Prospective Diabetic Study (UKPDS), the Framingham scores underestimated the 10-year risk of CVD in type II diabetics by 32%. Therefore, the said scores though being globally investigated are not globally accepted for application. Hence mentioning Framingham scoring as ‘global risk assessment tool’ and advocating interaction between treating physician/cardiologist and the ophthalmologist on its basis (in the ‘Abstract’ of the said article) is probably not warranted. The results of the study were not compared with other compatible Indian cross-sectional study, in which Framingham scoring was used. Authors’ estimation of 10-year CVD risks in Sankara Nethralaya – Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN – DREAMS 1) i.e., in the study in question was 33.5%, whereas that estimated by The Indian Atherosclerosis Research Study (IARS) group was only 5.32%.[3] Although the inclusion criteria of the two studies were different (type II diabetes in SN – DREAMS 1 and genetic predisposition in IARS), however, both the criteria were found to have similar CVD risk potentials in the Framingham's cohort and hence tend to be compatible.[4,5] Correlating CVD risks with risks of diabetic retinopathy lacks biological plausibility. While cardiovascular diseases in diabetes are macrovascular in origin, retinopathy is microvascular, and each has distinct and different set of major etiological factors. While cardiovascular diseases are predominantly due to atherosclerosis, retinopathy is predominantly due to glucose dysregulation. That diabetes increases the risk of atherosclerotic diseases by two to three folds is an established fact[5] but the reverse, that is, role of atherosclerotic factors like cholesterol, LDL etc., in the causation of retinopathy is not as clear. Neither any article showing such correlation was cited in the ‘discussion’ section. Therefore, while investigation to this effect is laudable, a hypothetical explanation of this association was expected, and in the absence of explanation, needless to say, the strength of association had been weakened further.