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.
Body Composition of Asian Indians and New definitions of Obesity and Syndrome X
Importance of Body Fat Compartments, Cut-off Points of Body Fat Depots, for Asian Indians and Predictive Equations:
- As a World Health Organization fellow in 1996, Dr. Misra worked at the Center of Human Nutrition, University of Texas Southwestern Medical Center at Dallas. For the first time, he showed a strong relationship of subcutaneous abdominal fat, particularly in the posterior abdominal region, using magnetic resonance imaging of abdominal fat and made assessment of insulin sensitivity, using hyperinsulinemic euglycemic clamp technique
- In India, using the same technique, Dr. Misra reported body composition characteristics of Asian Indians residing in India. In adults, he analyzed cut-offs for subcutaneous and intra-abdominal fat for CV risk prediction. He also reported predictive equations for total fat, abdominal subcutaneous fat and intra-abdominal fat, using simple anthropometric measures. Further to that, he defined the body composition characteristics of adolescent population, especially body fat patterning.
New Waist Circumference Criteria for Indians and Correct Methodology for Measurement of Waist Circumference:
- Dr. Misra reported a new waist circumference criteria for abdominal obesity in Indians, which are different from the current international criteria. These criteria have been considered for revised criteria for the diagnosis of abdominal obesity in Asian Indians and for revised criteria for the metabolic syndrome.
- There are different methods for measurement of waist circumference and there is no consensus on this issue. Dr. Misra has tried to evolve a standard method for the measurement of waist circumference for worldwide use.
New Limits for Body Mass Index in Indians:
- According to Dr. Misra and his team’s data as well as that of others, Asian Indians develop diabetes and other co-morbidities at a lower BMI than white Caucasians. Dr. Misra proposed that the current limits of body mass index are not appropriate for the diagnosis of overweight and obesity in Asian Indians, based on the estimation of body fat and prevalence of cardiovascular morbidities. These observations have been debated at the International Congress of Obesity in Sao Paulo and Sydney and published repeatedly.
New Definitions of Syndrome X in Indians and Proposal for Improving International Definitions of Syndrome X:
- There is controversy about the correct definition of Syndrome X worldwide. Dr. Misra has proposed new definitions for syndrome X in Indians, both in adults and in children. In the definition for adults, he has included new criteria which are more appropriate for the Indian population. For children, he and his team are one of the four groups in the world who have attempted to define this syndrome.
- In addition Dr. Misra has published a number of papers, debated at international fora and suggested new ways to improve ethnic-specific diagnostic criteria for the metabolic syndrome.
Excess Muscle Lipids in Obese Indians:
- Using magnetic resonance spectroscopy, Dr. Misra and his team have shown high content of intra-myocellular lipids in obese and lean Asian Indians and its absence in correlation with insulin sensitivity. These findings have been reported for the first time in Asian populations and also emphasize the ethnic difference in the deposition of fat.
Adverse Profile of Nutrition and High Prevalence of Sub-clinical Inflammation in Adolescents and Young Asian Indians:
- A high prevalence of obesity, excess body fat, sedentary activity and imbalanced nutrition in adolescents has been reported by Dr. Misra and his team. High prevalence of hyperinsulinemia and sub-clinical inflammation (marker-C-reactive protein) and their strong correlations to generalized obesity, abdominal obesity and subcutaneous fat in young Asian Indians have also been recently reported by them. They have also shown low plasma adiponectin concentration and other novel cardiovascular risk factors in children. In these series of publications, they have adequately highlighted high future metabolic and cardiovascular risk in young, and prepared a platform for intensive intervention for risk reduction.
- Importantly, Dr. Misra and his team have reported a new cut off for intake of saturated fat and the importance of n-6 fatty acids in relation to insulin resistance in adolescent population. These findings have important implications for policies for prevention. Their public health awareness activities among children are based on these findings
Genetics of Obesity, Insulin Resistance, Subcutaneous Fat, and Fatty Liver
Genetics of Obesity, Insulin Resistance, Subcutaneous Fat, and Fatty Liver: Relationships of Apolipoproteins B, E, and C3 and PPAR-γ Gene Polymorphisms and Other Candidate Genes
- Dr. Misra and his team were first to show the negative association of apolipoprotein-B gene polymorphisms with generalized and regional obesity for Asian Indians in India. Recently, they reported a strong association of apolipoprotein-E4 allele with early-onset of coronary heart disease.
- They investigated genotype-phenotype correlations of peroxisome-proliferator receptor-α and γ genes with obesity, diabetes mellitus and hyperlipidemia in Asian Indians.
- Studies of polymorphisms of 13 genes as genetic determinants of insulin resistance and subcutaneous body fat are ongoing.
- d. Similarly, Dr. Misra and his team are also investigating the genetic association of fatty liver with peroxisome-proliferator receptor-α and γ genes.
- Collaborative Studies with Department of Cardiology, University of Maryland: In collaboration with Dr. Mike Miller (University of Maryland, MD, USA), Dr. Misra has investigated polymorphisms of APOC3 promoter (C-482T,T-455C), APOE genotypes (2/3/4), PPAR alpha (intron 7: G/C), PPAR gamma (Pro12Ala), GNB3 (C825T and G814A), B3AR (Trp64Arg), FABP2 (Ala54Thr) and LPL (-93 T/G) in Asian Indians in India and Caucasians in USA. These data demonstrate that the prevalence of the metabolic syndrome was particularly elevated in homozygotes with the APOC3 promoter polymorphism variants (C-482T, T-455C) and raises the possibility that alterations in a single-gene may contribute to the metabolic syndrome.
Contribution to National Health Policy and International Health Guidelines
- Dr Misra has been a member of a number of National and International policy and decision-making bodies in internal medicine, diabetes, obesity and cardiovascular diseases. He has been a member of WHO Expert Group for Childhood Obesity (2005), and in WHO Expert Committee for Appropriate Measures of Obesity in Asian Populations (2005). He has been a key member for National Control Programs for Diabetes and Cardiovascular disease, and in various National Committees set up by Health Ministry, Planning Commission, ICMR, Dept. of Biotechnology, DST, and the WHO. He has been in Committee for Indian Pharmacopoeia and is an advisor for monitoring committees for National Institute of Nutrition (Hyderabad) and Department of Biotechnology.
- Important contributions in guidelines of contraception
- For guidelines for National Diabetes Control Program
- For National Program for Cardiovascular Disease and Stroke
- For ICMR Committees on Obesity and Childhood obesity
- For ICMR programs on Diabetes in Young
- For ICMR guidelines on Fatty Liver
- ICMR guidelines of health effects of carbonated water
- For Nutrition as a member of Steering Committees of National Nutrition Monitoring Bureau and National Institute of Nutrition