The Relationship Between GAPDH Gene Polymorphism and Risk of Acute Coronary Syndrome in South Indians with Type 2 Diabetes Mellitus.

As glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the regulators of carbonyl stress, a pathogenic mechanism for diabetic complications like acute coronary syndrome (ACS), the study aimed to investigate the relationship between GAPDH gene polymorphism, GAPDH activity in red blood cell (RBC), methylglyoxal (MG) levels in plasma and ACS risk in South Indians with type 2 diabetes mellitus (T2DM). This study comprised 150 T2DM with ACS as cases and 150 T2DM without ACS as controls. The GAPDH rs1136666, rs1060620 and rs1060619 gene polymorphisms were identified by TaqMan probe assays. The RBC GAPDH activity and plasma MG levels were estimated. Cases had significantly higher plasma MG levels and lower RBC GAPDH activity than controls (P < 0.001). The distribution of rs1060620 or rs1060619 alleles and genotypes significantly differed between groups. The rs1060620 AG (OR 0.55; 95% CI 0.33-0.92; P = 0.022) or rs1060619 CT (OR 0.51; 95% CI 0.31-0.83; P = 0.007) genotype was associated with reduced ACS risk, confirmed in the over-dominant genetic model. Haplotype analyses revealed that the GAT and CGC haplotypes were associated with increased (OR 28.37; 95% CI 3.82-210.49; P = 8.51 × 10-7) and decreased (OR 0.45; 95% CI 0.24-0.86; P = 0.014) ACS risk in T2DM patients, respectively. Lower GAPDH activity was observed in the TT and CT genotypes compared to the CC genotype of rs1060619 (P < 0.001). This work established that the GAPDH rs1060620 or rs1060619 gene polymorphisms are associated with ACS risk in South Indians with T2DM.

GC-MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome.

Methylglyoxal (MG) is responsible for advanced glycation end-product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography-mass spectrometry (GC-MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC-MS. Validated GC-MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM.

Association of Tenascin-C Gene Polymorphisms with Risk of Acute Coronary Syndrome in South Indian Population: A Case-Control Genetic Association Study.

Background: The extracellular matrix (ECM) glycoprotein changes are associated with the pathogenesis and complications of atherosclerosis, leading to acute coronary syndrome (ACS). Tenascin-C (TNC), an ECM protein, has been implemented in the pathogenesis, diagnosis, and prognosis of patients with cardiovascular disease. Aim: The study aimed to compare the genetic variants of the TNC gene (rs13321, rs2104772, and rs12347433) between South Indians with ACS and healthy participants. Materials and Methods: This case-control study recruited 150 ACS patients as cases and 150 healthy participants as controls. TNC genotyping was performed using TaqMan 5'-exonuclease allele discrimination assay. Serum TNC levels were measured by enzyme-linked immunosorbent assay. Results: Serum TNC levels were significantly higher in cases compared with controls. No significant difference was observed in allele and genotype frequencies of rs13321, rs2104772, and rs12347433 between cases and controls, which was confirmed by dominant, recessive, codominant, and homozygotic genetic models. The patients with heterozygous genotypes of rs13321, rs2104772, and rs12347433 had significantly lower serum TNC levels than patients with respective homozygous genotypes. Haplotype analyses revealed that the C-T-A haplotype in the block of rs13321-rs12347433-rs2104772 was associated with lower ACS risk (OR = 0.33, 95% CI: 0.15 - 0.75; p = 0.005). Also, the C-T-T and G-T-A haplotypes of the TNC gene were associated with higher and lower serum TNC levels, respectively. Conclusion: Our study demonstrated no genetic association between single nucleotide polymorphisms of the TNC gene and ACS risk; however, the C-T-A haplotype of the TNC gene might be associated with reduced ACS risk in South Indians.

The genetic polymorphisms and activity of glyoxalase 1 as a risk factor for acute coronary syndrome in South Indians with type 2 diabetes mellitus.

OBJECTIVE: The individuals' genetic traits predispose them to a higher or lower risk of Type 2 diabetes mellitus (T2DM) and its complications, for example, acute coronary syndrome (ACS). As carbonyl stress is responsible for the pathogenesis and complications of T2DM, and glyoxalase 1 (GLO1) is the most crucial determinant of carbonyl stress, the study aimed to explore the association between GLO1 gene polymorphism, GLO1 activity in red blood cell (RBC), plasma methylglyoxal (MG) levels, and ACS risk in South Indian T2DM patients. METHODS: A total of 150 T2DM patients with ACS as cases and 150 T2DM patients without ACS as controls were recruited in a case-control study. The rs4746, rs1049346 and rs1130534 of the GLO1 gene were analysed using TaqMan allele discrimination assay. The RBC GLO1 activity and plasma MG levels were measured. RESULTS: Significantly lower RBC GLO1 activity and higher plasma MG levels were found in cases compared to controls (p < 0.001 and p = 0.008, respectively). The genotype and allele frequencies of rs1049346 significantly differed between cases and controls (p < 0.001). For rs1130534 and rs1049346, no significant difference was found. For rs1049346, the TT and CC genotypes were associated with higher (p = 0.002) and lower (p = 0.001) ACS risk, respectively, in various genetic models. The TT genotype of rs1049346 was associated with lower RBC GLO1 activity (p = 0.004) and higher MG level (p = 0.010). In haplotype analysis, higher ACS susceptibility with the TAT haplotype (p < 0.001) and lower ACS susceptibility with the TAC haplotype (p < 0.001) were observed. Also, lower RBC GLO1 activity was associated with the TAT haplotype (p = 0.002). CONCLUSIONS: The rs1049346 of the GLO1 gene may be associated with ACS risk in South Indian T2DM patients, and the T and C allele might be essential precipitating and protective factors, respectively.

Body Iron Store and its Association with Risk of First Episode of Spontaneous Lower Extremity Deep Vein Thrombosis/ Pulmonary Embolism: A Case-Control Study.

Background and objectives: The association between body iron stores and risk of deep vein thrombosis/ pulmonary embolism (DVT/ PE) has not been studied among Indian subjects. This study aimed to evaluate the same and also study the association between iron stores and recanalization of affected veins at week-12. Methods: This Case-Control with follow-up study enrolled 85 consecutive adult (≥ 18 years) cases presenting with first episode of spontaneous, proximal lower extremity DVT/ PE and 170 age (± 3 years) and sex matched adult controls without DVT/ PE. Those with haemoglobin(Hb) < 9 g/dl, malignancies, serum creatinine ≥ 2 mg/dL, heart failure and concurrent infections/ inflammatory disorders were excluded. All participants underwent iron profile, serum ferritin light-chain (FtL) and hepcidin testing. Results: Anaemia [OR = 2.3 (95% CI = 1.3-4.0), p = 0.001] and elevated RDW (RDW-CV > 15%) [OR = 2.3 (95% CI = 1.2-4.3), p = 0.012] were significantly associated with increased risk of DVT/ PE. Iron deficiency (ID, defined as serum ferritin < 30 µg/L, along with TSAT < 20%) was not associated with DVT/ PE risk [OR = 0.8 (95% CI = 0.4-1.7), p > 0.05]. Serum FtL in the highest quartile (> 75th centile) was associated with higher risk of DVT/ PE (OR = 5, 95% CI = 2.6-9.6) and levels < 25th centile with protection against DVT/ PE (OR = 0.1, 95% CI = 0.01-0.32), compared to levels between 25th and 75th centiles (referent range). Highest DVT/ PE risk was associated with FtL > 90th centile [OR≈12 (95% CI = 3.9-37.2)]. No associations were noted between serum hepcidin and DVT/ PE risk and ID and DVT recanalization at week-12. Conclusion: Higher iron stores, rather than ID, were associated with increased risk of DVT/ PE among those with Hb ≥ 9 g/dL. Anaemia and elevated RDW were also associated with risk of DVT/ PE. ID was not associated with poorer DVT recanalization at week-12.

Comparison of resting/postexercise ankle-brachial index and transcutaneous partial pressure of oxygen for noninvasive diagnosis of peripheral artery disease in type 2 diabetes mellitus.

Background Type 2 diabetes: Type 2 diabetes mellitus (T2DM) is a strong risk factor for peripheral artery disease (PAD) and PAD diagnosis in T2DM may indicate coexisting coronary artery disease as well. Postexercise ankle brachial index (ABI) and transcutaneous partial pressure of oxygen (TcPO2) have not been evaluated for PAD diagnosis among Indian T2DM patients. This study aimed to evaluate the performance of resting + postexercise(R + PE) ABI and R + PE-TcPO2 for PAD diagnosis among T2DM patients at increased PAD risk, using colour duplex ultrasound (CDU) as reference standard. Methods: This prospectively conducted diagnostic accuracy study involved T2DM patients at increased PAD risk. R-ABI≤0.9 or PE-ABI decline >20% from resting value in those with R-ABI between 0.91 and 1.4, R-TcPO2 <30 mm Hg or PE decline of TcPO2 to <30 mm Hg in those with R-TcPO2 ≥30 mm Hg, CDU showing >50% stenosis or complete occlusion of lower extremity arteries constituted PAD. Results: Among 168 patients enrolled, R + PE-ABI diagnosed PAD in 19(11.3%), R + PE-TcPO2 in 61 (36.3%) and 17 (≈10%) had PAD finally confirmed by CDU. Sensitivity, specificity, PPV and NPV of R + PE-ABI for PAD diagnosis were 82.3%, 96.7%, 73.7% and 98% and that of R + PE-TcPO2 were 76.5%, 68.2%, 21.3% and 96.2%, respectively. PE-ABI increased the sensitivity of ABI by ≈ 18% and had 100% PPV for PAD. When both ABI and TcPO2 (R + PE tests) were normal, PAD could be safely excluded in 88% of patients. Conclusion: PE-ABI should be routinely employed and TcPO2(R/PE) is unreliable as a stand-alone test for PAD detection among moderate to high risk T2DM patients.

Comparison of cardiac autonomic function across complete glycaemic spectrum.

OBJECTIVES: Autonomic imbalance is attributed as key mechanism altering metabolic regulation in diabetes mellitus. In view of controversial reports on autonomic function in FDRD and prediabetes, we aimed to assess and compare the autonomic function across the complete glycaemic spectrum in Indian population. METHODS: Short term heart rate variability and cardiac autonomic reactivity tests - blood pressure and heart rate response to orthostatic tolerance and deep breathing exercise, and diastolic response to isometric handgrip exercise were recorded in normoglycemic apparently healthy individual, normoglycemic first degree relatives of diabetes, prediabetes and diabetes individuals. RESULTS: Resting heart rate is significantly higher in FDRD, prediabetes and diabetes as compared to controls (control < FDRD = prediabetes = diabetes). Total power, LF power (control < FDRD < prediabetes = diabetes) and HF power (control < FDRD < prediabetes < diabetes) decreased along the glycaemic spectrum. Time-domain variables of HRV (SDNN, RMSSD, NN50, pNN50) were reduced as we move along the glycaemic spectrum (control < FDRD < prediabetes = diabetes). Cardiac autonomic function reactivity parameters such as 30:15 ratio and E:I ratio are decreased in prediabetes and diabetes group as compared to control and FDRD group (control = FDRD < prediabetes = diabetes). Diastolic response to isometric hand grip increases along the glycaemic spectrum starting from FDRD (control < FDRD < prediabetes = diabetes). CONCLUSIONS: Autonomic dysfunction is observed even in first degree relatives of diabetes. Autonomic dysfunction increases as we move along the glycaemic spectrum (control < FDRD < prediabetes < diabetes).

Altered expression of a disintegrin and metalloproteinase 10 in peripheral blood mononuclear cells in type 2 diabetes mellitus patients with the acute coronary syndrome: a pilot study.

PURPOSE: Advanced glycation end products (AGEs) are responsible for the complications in type 2 diabetes mellitus (T2DM) patients by acting via its receptor (RAGE). The soluble form of RAGE (sRAGE) prevents the harmful effects of AGE-RAGE signalling. The sRAGE is produced either by alternate splicing (esRAGE) or proteolytic RAGE cleavage by a disintegrin and metalloproteinase 10 (ADAM10). Hence, the study aimed to compare the expression of ADAM10 in peripheral blood mononuclear cell (PBMC), serum sRAGE and esRAGE levels in T2DM patients with and without acute coronary syndrome (ACS). METHODS: Forty-five T2DM patients with ACS and 45 age, gender and duration of DM-matched T2DM patients without ACS were recruited. Serum sRAGE and esRAGE levels were measured by enzyme-linked immunosorbent assay. The expression of ADAM10 in PBMC was determined by quantitative reverse transcription-polymerase chain reaction. RESULTS: The expression of ADAM10 in PBMC and serum sRAGE levels were significantly lower in T2DM patients with ACS than in T2DM patients without ACS (p < 0.001). Serum sRAGE levels and expression of ADAM10 in PBMC were positively correlated with each other and negatively correlated with markers of cardiac injury and glycaemic status (p < 0.05). Simple logistic regression showed that the models containing the expression of ADAM10 and serum sRAGE level could predict the ACS risk among T2DM patients. ROC analysis showed that both might be used for ACS diagnosis in T2DM patients. CONCLUSION: Reduced expression of ADAM10 in PBMC might be responsible for lower serum sRAGE levels, predisposing T2DM patients to high ACS risk.

Delayed Gastric Emptying among Indian Patients with Non-Diabetic Chronic Kidney Disease.

INTRODUCTION: Upper gastrointestinal symptoms such as nausea, vomiting, abdominal bloating, and poor appetite are more frequent among chronic kidney disease (CKD) patients and may contribute to poor nutritional intake and malnutrition. Delayed gastric emptying (GE), one of the important contributors to these symptoms, has not been evaluated systematically in different stages of non-diabetic CKD, among Indian patients. MATERIALS AND METHODS: This hospital-based, cross-sectional analytical study aimed to find out the frequency of delayed GE in non-diabetic CKD (stages: 3,4,5) patients and also to study the correlation between delayed GE and symptoms of gastroparesis, autonomic neuropathy and nutritional parameters. Patients were subjected to evaluation of symptoms of gastroparesis by standardized questionnaire (gastroparesis cardinal symptom index), nutritional status (by anthropometric measures and serum albumin), autonomic function by heart rate variability (HRV) and GE by gastric scintigraphy with a standardized solid rice idli (savory cake) meal labeled with technetium-99m sulfur colloid. RESULTS: Of the 89 non-diabetic CKD (stages-3,4,5) patients evaluated, 22 (≈25%) had delayed GE and 8 (≈9%) rapid GE. Prevalence of delayed GE was higher among stage 5 (15/49, 31%) compared to stages 3 and 4 (7/40, 17.5%), though the difference was statistically insignificant. There was no association between delayed GE and symptoms of gastroparesis and autonomic neuropathy. Though not statistically significant, nutritional parameters (body mass index, skinfold thickness, and serum albumin) were poorer in the delayed GE group compared to the rest. CONCLUSION: Delayed GE, irrespective of symptoms, may contribute to malnutrition and hence should be looked for in non-diabetic CKD patients with unexplained malnutrition.

Assessment of vascular function in complete glycaemic spectrum.

Purpose: The present study was conceived to delineate the point of vascular dysfunction along the glycemic spectrum (normoglycemic individuals with no family history of diabetes, normoglycemic individuals with family history of diabetes, prediabetic individuals, and diabetic individuals).Materials and Methods: In this cross-sectional comparative study, we enrolled 252 participants of both gender in the age group of 30-50 years. They were classified based on their family history of diabetes and glycemic status into four groups along the glycemic spectrum as mentioned above. We measured flow-mediated dilation (FMD) from brachial artery and vascular function biomarkers such as enthothelin-1 (ET-1), von Willbrand Factor (vWF), Vascular Endothelial Growth Factor (VEGF) to assess the vascular function. The comparison of data between groups were done using One Way ANOVA/Kruskal-Wallis followed by post-hoc analysis using LSD/Mann-Whitney U Test depending on the normality of the data. Spearman correlation was done between vascular function and plasma glucose levels to identify its relationship. Linear regression was carried out to identify the factors influencing the FMD across the glycemic spectrum.Results: We observed that vascular function negatively correlated with blood glucose levels. However, endothelin-1 and vWF derangement was there even in normoglycemic first degree relatives of diabetes (FDRD) and the derangement increased in prediabetes and diabetes. Physiological dysfunction in terms of decreased flow-mediated dilation starts from prediabetes only. VEGF derangement is found only in diabetic individuals.Conclusion: Vascular dysfunction is found even in normoglycemic FDRD and the derangement increased and compounded with the advancement of disease.

Assessment of serum tenascin-C and growth differentiation factor-15 among type 2 diabetes mellitus patients with and without acute coronary syndrome.

BACKGROUND: High prevalence of type 2 diabetes mellitus (T2DM) is associated with a higher prevalence of acute coronary syndrome (ACS). Inflammation is one of the important contributors to the pathogenesis and complications of coronary atherosclerotic plaque. Growth Differentiation Factor-15 (GDF-15) and Tenascin-C (TNC) play an important role in the initiation of atherosclerotic plaque as well as its rupture. The aim of the study was to evaluate the association between serum GDF-15, TNC, and the risk of ACS among T2DM patients. METHODS: Anthropometric parameters, routine biochemical investigations like liver and renal function tests, lipid profile, and Creatine Kinase-Total (CK-T), Creatine Kinase-MB (CK-MB) were measured in 42 T2DM patients with ACS and 42 T2DM patients. Serum GDF-15 and TNC were measured by Human Sandwich-ELISA kits. RESULTS: Serum GDF-15 and TNC levels were significantly higher in T2DM patients with ACS as compared to T2DM patients. Serum GDF-15 was significantly correlated with waist circumference, diastolic blood pressure, pulse, serum CK-T, and CK-MB. Serum TNC was significantly correlated with the pulse, serum CK-T, CK-MB, high-density lipoprotein-cholesterol, and blood urea nitro GEN. Multivariate linear regression analysis showed that waist circumference was independently positively associated with serum GDF-15. CONCLUSIONS: T2DM patients with higher serum GDF-15 and TNC levels were at higher risk of acute coronary syndrome independent of other cardiovascular risk factors.

Thyroid dysfunction in patients with type 2 diabetes mellitus and its association with diabetic complications.

BACKGROUND AND AIMS: Patients with type 2 diabetes mellitus are more prone to thyroid disorders. Hypothyroidism in them leads to an aggravation of microvascular complications. Diabetic patients with hypothyroidism also are at an increased risk of cardiovascular disease. Screening for thyroid dysfunction in diabetic patients will allow early treatment of hypothyroidism. The aim of this study was to assess the level of thyroid dysfunction in patients with type 2 diabetes mellitus and to identify the association of thyroid dysfunction with diabetic complications. METHODS: This is a cross-sectional study that was conducted at departments of Medicine & Endocrinology in JIPMER, Pondicherry, between June 2016 and May 2019. 331 patients with type 2 diabetes mellitus attending the out-patient department without any prior history of thyroid disease, chronic liver disease or acute illness were recruited for the study. All subjects were screened for diabetic complications (nephropathy, neuropathy, retinopathy & cardiovascular disease). Thyroid function test was done in all subjects using chemiluminescent immunoassay method. RESULTS: Hypothyroidism was seen in 13.9%, while hyperthyroidism was observed in 3.6% of the study subjects. Thyroid dysfunction was more common among females than males. No correlation was seen between thyroid dysfunction and diabetic complications in the study subjects. CONCLUSION: The prevalence of thyroid dysfunction is 17.5% in patients with type 2 diabetes mellitus. Thyroid dysfunction did not have any correlation with diabetic complications.

Comparison of anthropometric, cardiovascular, autonomic, baroreflex sensitivity, aerobic fitness, inflammatory markers and oxidative stress parameters between first degree relatives of diabetes and controls.

AIM: We aimed at assessing cardiovascular risk of first degree relatives of diabetes (FDRD). METHODS: A cross sectional study involving 90 apparently healthy normoglycemic volunteers aged between 15 and 50 years (45 FDRD and 45 FDRs of non-diabetics). We measured anthropometric parameters, baroreflex sensitivity, heart rate variability, cardiac autonomic function tests, and aerobic capacity, fasting blood glucose and insulin, lipid profile, inflammatory markers, nitric oxide and oxidative stress markers. RESULTS: FDRD had significantly higher hip circumference and BF%. Blood pressure, total peripheral resistance and cardiac output were comparable. FDRD had higher HR and rate pressure product. There were no significant differences in cardio-respiratory fitness (VO2max) and physical activity level. Time and Frequency domain parameters were comparable except for reduced NN50 and total power. Baroreflex sensitivity, 30:15 ratio and E: I ratio were significantly less in FDRD. Fasting glucose was comparable. Fasting Insulin, HOMA IR, HOMA %B and HOMA AD were higher while HOMA %S and QUICKI index were lower in FDRD. Lipid profile or lipid derived parameters were comparable except for higher non-HDLc in FDRD. Adiponectin was lower while Leptin and Leptin/apidonectin ratio was higher in FDRD. IL-6, hsCRP, TNF- alpha and MDA were significantly higher in FDRD, while TAS and nitric oxide were significantly lower in FDRD. CONCLUSION: Higher body fat percentage, with insulin resistance, deranged cardiac autonomic function, higher oxidative stress and inflammation, lower adiponectin and nitric oxide levels places FDRD at higher cardiovascular risk and necessitates early lifestyle modification/intervention.

Comparison of Hemoglobin A1c with Fasting and 2-h Plasma Glucose Tests for Diagnosis of Diabetes and Prediabetes among High-risk South Indians.

BACKGROUND: Glycosylated hemoglobin (HbA1c) has not been evaluated extensively for diabetes and prediabetes diagnosis and short-term variability of fasting plasma glucose (FPG), 2-h PG post-75 g glucose load (2 hPG) and HbA1c has not been studied among Indians. OBJECTIVES: The study aimed to compare the sensitivity of HbA1c, FPG and 2 hPG for diabetes and prediabetes diagnosis as per the American Diabetes Association criteria, assess short-term variability of three tests and determine optimal HbA1c cutoffs for diabetes and prediabetes diagnosis among high-risk south Indians. METHODS: This diagnostic accuracy study, conducted at a tertiary care teaching hospital located in South India, enrolled 332 adults at high risk for diabetes and subjected them to testing (FPG, 2 hPG, and HbA1c) twice at 2-3 weeks interval. Sensitivity of three tests for diagnosing diabetes and prediabetes was determined based on the final diagnosis of normoglycemia/prediabetes/diabetes made with six test results for each participant. Optimal HbA1c cutoffs for diabetes and prediabetes were determined based on the final diagnosis of glycemic status made with four test results of FPG and 2 hPG. RESULTS: FPG, 2 hPG, and HbA1c, at American Diabetes Association recommended values, had sensitivity of 84.4%, 97%, and 93.8% respectively for diabetes diagnosis. HbA1c had lowest short-term variability (CVw = 1.6%). Receiver operating characteristic curve plotted with mean (of two values) HbA1c for each participant showed optimal HbA1c cutoffs of 6.5% for diabetes (area under curve [AUC] =0.990, sensitivity = 95.8%, specificity = 96.2%, accuracy = 95.2%) and 5.9% for prediabetes (AUC = 0.893, sensitivity = 84.3%, specificity = 80%, accuracy = 75.6%) diagnosis respectively. HbA1c <5.6% had 100% negative predictive value to exclude prediabetes/diabetes. CONCLUSIONS: HbA1c ≥6.5% is a convenient and reliable alternative to plasma glucose tests to diagnose diabetes among high-risk South Indians. HbA1c ≥5.9% is optimal for prediabetes diagnosis and value <5.6% excludes prediabetes/diabetes.Abbreviations used in the manuscript: ADA: American Diabetes Association, AUC: Area under curve, CVw: Within-person coefficient of variation, FPG: Fasting plasma glucose, 2 hPG: Two-hour plasma glucose post-75 g oral glucose load, HbA1c: Glycosylated haemoglobin, IFG: Impaired fasting glucose, IGT: Impaired glucose tolerance, NPV: Negative predictive value, PPV: Positive predictive value; PG: Plasma glucose, ROC: Receiver operating characteristic.

Atorvastatin Induced Adverse Drug Reactions among South Indian Tamils.

INTRODUCTION: Atorvastatin is the most widely used statin world-over. Although atorvastatin is beneficial in reducing cardiovascular morbidity and mortality, they are associated with Adverse Drug Reactions (ADRs) which are under-recognized as well as under-reported. There is no data on safety of atorvastatin in ethnic populations like South Indian Tamils and hence the need for this study. AIM: To report the Adverse Events (AEs) associated with atorvastatin use, their causality and severity in dyslipidemic south Indian Tamils. MATERIALS AND METHODS: This cross-sectional study was carried out on 304 dyslipidemic Tamils. Those on any lipid lowering therapy within one month before study enrolment, those with contraindications to statin therapy, hypothyroid patients, those with LDL cholesterol >250 mg/dL or serum triglycerides >400 mg/dL and patients who were on drugs which modulate Cytochrome P 450 3A4/5 (CYP3A4/5) activity were excluded from the study. Causality assessment for atorvastatin induced AEs were done using Naranjo adverse drug reaction probability scale criteria and severity assessment was done using Hartwig scale. AEs which were causally related to atorvastatin use were reported as ADRs. RESULTS: One hundred and eighty three AEs were noted among 145 (47.7%) patients, during the course of first 45 days of atorvastatin therapy. AEs were probably due to atorvastatin in 11% of the patients and possibly due to atorvastatin in 89%. Most common ADRs were myalgia (41%), followed by nervous system ADRs (35.5%) and gastrointestinal ADRs (14%). CONCLUSION: Myalgia was the most common cause for atorvastatin discontinuation which might place these individuals at an increased risk of cardiovascular morbidity and mortality. Measures to identify and address atorvastatin induced myalgia should be given priority.

Prevalence and predictors of delayed gastric emptying among Indian patients with long-standing type 2 diabetes mellitus.

BACKGROUND AND AIMS: Upper gastrointestinal symptoms are more prevalent among type 2 diabetes mellitus (T2DM) patients. The prevalence of delayed gastric emptying (GE) and factors predictive of it have not been studied in Indian T2DM patients and the present study aimed to study the same. METHODS: This hospital-based cross-sectional study involved adult (age between 18 and 65 years) outpatients with T2DM of ≥5-year duration. Measurements of GE of a labelled standardized solid rice idli meal by gastric emptying scintigraphy (GES), symptoms of delayed GE (by standardized questionnaire) and autonomic function by cardiovascular autonomic function tests (AFTs) were carried out. Thirty healthy subjects served as controls for GES and AFTs. RESULTS: One hundred and forty T2DM patients (age range: 32-65 years) were studied. Delayed GE was documented in ≈29 % (40/140) and rapid GE in 2 % (3/140) of T2DM patients. Univariate analysis showed significant positive association between delayed GE and duration of DM, body mass index (BMI), HbA1c, retinopathy, peripheral neuropathy, autonomic dysfunction and coronary artery disease (p < 0.05 for all). However, there was no significant correlation of age, sex, symptoms suggestive of gastroparesis and nephropathy with delayed GE. Hypoglycemic episodes were significantly more frequent in those with delayed GE (p < 0.05). Multiple logistic regression analysis revealed only BMI and HbA1c to be significant independent predictors of delayed GE. CONCLUSION: Presence and severity of symptoms of gastroparesis did not predict delayed GE. Delayed GE, irrespective of symptoms, was associated with microvascular and macrovascular diabetic complications and increased risk of hypoglycemic episodes. HbA1c and BMI were independent predictors of delayed GE.