Significant Contributions in National and International Research
The focus of Dr. Misra’s research has been on obesity, metabolic syndrome (syndrome X), diabetes mellitus, hyperlipidemia and other cardiovascular risk factors in Asian Indians and rare disorders of adipose tissue.
Obesity, Diabetes, Insulin Resistance, and Cardiovascular Risk in the Underprivileged Population in India: Epidemiological Studies
For the first time, Dr. Misra’s team showed a high prevalence of Type 2 Diabetes Mellitus, abdominal obesity, dyslipidemia and metabolic syndrome in the underprivileged population living in urban resettlement colonies of New Delhi. Other previously unreported observations on the same population included a high prevalence of hyperhomocysteinemia, endothelial dysfunction and subclinical inflammation. His team also carried out epidemiological study of metabolic syndrome and cardiovascular risk factors of post-menopausal women belonging to low socio-economic stratum, and reported a marked clustering of cardiovascular risk factors. His team’s health awareness program in poor socio-economic stratum is based on the above findings.
Imbalanced Nutrition and Sedentary Lifestyle in The Underprivileged Population:Epidemiological Studies:
Dr. Misra and his team have reported markedly imbalanced nutrition among the underprivileged; high total and saturated fat, low intakes of fibre and ω-3 fatty acids, and low intakes of anti-oxidants in the people belonging to low socio-economic stratum in urban slums.
Adverse Nutrition Profile and Cardiovascular Risk Factors in Children:
In serial studies, Dr. Misra and his team recorded a rising prevalence of obesity among schoolchildren in Delhi. They have also reported a high intake of energy-dense food and carbonated beverages in children, resulting in a high prevalence of insulin resistance among them, which correlates to the intake of n-6 fatty acids. Other important findings include a high intake of saturated fat and trans fatty acids.
Based on high levels of C-reactive protein in children, Dr. Misra calculated that saturated fat intake in adolescents should be restricted to <7%. In a preliminary communication, they reported that ~ 65% of adolescent and young population in schools and colleges of New Delhi are sedentary.
Determinants of Diabetes and Cardiovascular Risk Factors in Asian Indians: A Multi-Site Epidemiological Study in USA and Urban and Rural Populations Residing in India in Collaboration With Texas AM University, USA:
This important study, carried out for the first time, aimed to assess the obesity, insulin resistance, diabetes, and other cardiovascular risk factors in Asian Indians at three sites: USA, urban and rural India. The study shows a stepwise increase in the prevalence of diabetes and cardiovascular risk factors in rural and urban populations in India, and migrant Asian Indians at 6 sites in USA. The study also highlights the high prevalence of abdominal obesity and metabolic syndrome in Asian Indians. An important finding is the rising prevalence of diabetes and obesity in rural populations as well.
High Prevalence of Diabetes, Other Cardiovascular Risk Factors and Imbalanced Nutrition in Women: A Country wide, Multi-site Study
This study, done on four urban and four rural centers in India, shows high prevalence of diabetes, hypertension, obesity and dyslipidemia in women >35 years of age, in addition of highly imbalanced dietary profile.
Study of Hepatic Gluconeogenesis Pathway in Patients with Fatty liver Using Proton MRS Spectroscopy
Dr. Misra and his team studied hepatic gluconeogenesis metabolism in non-diabetic Asian Indian males having non-alcoholic fatty liver disease (NAFLD) using in vivo (31P) phosphorous magnetic resonance spectroscopy (MRS). In this novel experiment, they observed derangements in hepatic gluconeogenesis in obese and non-obese Asian Indians with NAFLD.
This is a very important study. It shows that people with fatty liver are pre-disposed to develop diabetes. Further, this in vivo method holds promise as a non-invasive method for the prediction of diabetes.
A New Laboratory Measure for the Assessment of Long-Term Glycemia in Diabetes Mellitus:
In collaboration with Indian Institute of Technology, New Delhi, Dr. Misra and his team investigated intrinsic fluorescence property of hemoglobin-AGE as a simple, accurate and cost-effective method for the assessment of glycemic status and as an alternative to the current standard investigation of glycosylated hemoglobin. Experimental observations in male Wistar rats and human beings indicate that hemoglobin-AGE is an efficient fluorescence based biosensing molecule for the long-term monitoring of glycemic control in diabetes. These are hitherto unreported observations and provide a novel laboratory tool for the monitoring of diabetes mellitus.
Currently, as part of a new study, he and his team are testing Hb-AGE as a method for monitoring of glycemia in patients with diabetes mellitus.
Assessment of Phenotype and Insulin Sensitivity (Using Hyperinsulinemic Euglycemic Clamp) in Patients with Inherited and Acquired Lipodystrophies:
Lipodystrophies are rare disorders of adipose tissue. Investigations on this rare disorder may answer some complex questions pertaining to the pathogenesis of insulin resistance, diabetes and fatty liver. Dr. Misra has worked extensively on the clinical and pathophysiological correlates of Acquired Generalized Lipodystrophy and devised the classification and diagnostic criteria of these disorders; as also that an extensive study on Acquired Partial Lipodystrophy (Barraquer Simons Syndrome) leads to new diagnostic criteria and classification. He has also done research on Familial Partial Lipodystrophy, Dunnigan Variety, and lipodystrophy in HIV-infected patients.
Assessment of Cognitive Dysfunction, Neuronal Functions (Using Proton Nuclear Magnetic Resonance Spectroscopy) and Cerebral Blood Flow (Using PET Scan) in Young Patients with Diabetes and Hyperlipidemia:
Central nervous system has been rarely researched in patients with diabetes. For the first time, Dr. Misra and his team reported cognitive dysfunctions in young patients with type 2 diabetes, and further showed the relation of central neuropathy with NAT polymorphisms in Asian Indian patients. They have further shown cognitive and neuronal dysfunction in young patients with hypertension, hyperlipidemia etc.
In a recent investigation, they have investigated cognitive dysfunction, and cerebral blood flow using positron emission tomography scan and cerebral neuronal functions using proton magnetic resonance spectroscopy in young Asian Indian patients with hyperlipidemia. Importantly, these young patients have abnormal cerebral functions.
Progressive Resistance Exercise Training Protocol in Asian Indians with Type 2 Diabetes
This is the first study showing the usefulness of resistance muscle exercise in patients of diabetes. Not only resistance exercise (using small weights) improves blood glucose profile but also decreases subcutaneous fat, which does not decrease in a selective manner to any weight loss therapy. Based on this study, Dr. Misra and his team have proposed that the resistance should be included in the exercise advisory of Asian Indians with diabetes.
Novel Phenotypic Markers for the Metabolic Syndrome in Adult Asian Indians
In this study, new phenotypic markers (‘buffalo hump’ and ‘double chin’) for the prediction of metabolic syndrome has been investigated in Asian Indians for the first time in the world. The identification of these phenotypic markers in a person means that he/she is at a high risk for development of metabolic syndrome and diabetes. These simple physical signs could be used by any physician anywhere in India to identify those at risk of diabetes. This is a simple yet very useful research paper.
Simvastatin as a Novel Treatment for Non-Significant Macular Edema in Patients with Type 2 Diabetes
Though hyperlipidemia has been correlated to the occurrence of diabetic retinopathy, specifically hard exudates, no intervention study with lipid-lowering treatment was available. Dr. Misra and his team were the first to show that simvastatin use retards clinically significant macular edema in diabetic patients in a randomized double-blind controlled trial.
Artificial Neural Network (ANN) Analysis of Risk Factors for Diabetes
ANN is a new statistical method to analyze the relative importance of risk factors. In this study, variables according to their importance in predicting the diabetes outcome were: age, suprailiac skinfold, waist-hip-ratio (W-HR), subscapular skinfold, systolic blood pressure, body mass index (BMI), total cholesterol levels, diastolic blood pressure and serum triglyceride levels.
Phenotype and Genotype of Lean Diabetics (Non-type 1)
In this proposal, Dr. Misra aims to investigate the phenotype (anthropometry, body composition, pancreatic imaging, insulin resistance, lipids, other biochemical variables), auto-antibodies, and genetic (known mutations and polymorphisms) correlates of young (age 14-40 years) diabetic patients (non-type 1). Specifically, special investigations would include anti-GAD and anti-insulin auto antibodies, C-peptide, and genetic profiling in auto-antibody negative patients [(HNF-1 α, LMNA (R482W), PPAR γ (Pro 12 Ala) polymorphisms) and unknown mutations.
Metabolic and Genetic Investigations of Obstructive Sleep Apnea
Obstructive sleep apnoea (OSA) may be a risk factor for hypertension, diabetes and cardiovascular disease. For the first time, Dr. Misra and his team reported increased serum levels of TNF- in obese Asian Indians showing a strong association with OSA, and significant association of OSA with -308G/A promoter polymorphism of TNF- gene. Further, they also reported the association of PPAR (Pro12Ala) and Neuropeptide-Y (Leu7Pro) gene polymorphisms in OSA for the first time.
Fatty Liver, Characterization and Treatment with Monounsaturated Fatty Acid-Rich Oils
In a case controlled study, Dr. Misra and his team have demonstrated that people with fatty liver have a high predisposition to develop metabolic syndrome and diabetes.
In another randomized controlled trial, patients with fatty liver are being treated with MUFAs-rich oils. This a preliminary study to see dietary treatment to decrease hepatic triglycerides.
Assessment of Trans Fatty Acid (TFA) Contents of Indian Foods:
This proposal aims to assess the TFA content of commonly consumed fast foods by Urban Indians. It is also proposed to investigate the TFA content and the effect of frying temperatures and time on the quality of edible oils. Using these TFA values the study also proposes to assess the TFA consumption among different groups of population and to correlate it with the anthropometric measurements. The proposal also deals with identifying appropriate alternatives for reuse of degraded oils after mild treatment at home or commercial outlets and to formulate a strategy to limit/avoid TFA intake and to educate mothers/homemakers about the adverse effects of TFA.
Other Significant Research
- Taq 1B polymorphism and CETP activity with HDL-cholesterol in healthy normolipidemic Northern Asian Indians
- Implications of leptin with exocrine and endocrine pancreatic function in idiopathic chronic pancreatitis.