Atherosclerosis and Associated Cardiovascular Risk Factors in Nonalcoholic Fatty Liver Disease and Metabolic Syndrome.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a well-known contributor for the development of cardiovascular disease (CVD). Nonalcoholic fatty liver disease is considered as the liver component of metabolic syndrome (MetS). This study aimed to assess the influence of NAFLD and MetS on markers of subclinical atherosclerosis, including carotid intima-media thickness (CIMT), ankle-brachial pressure index (ABI), and to investigate the impact of NAFLD and MetS on left ventricular (LV) diastolic and systolic function. STUDY DESIGN: A case-control study. MATERIALS AND METHODS: In this case-control study, 120 cases and 90 healthy controls in the age group ranging from ≥18 to ≤65 years were included. Metabolic syndrome was assessed using International Diabetes Federation (IDF) criteria. Height, weight, waist circumference, body mass index (BMI), and blood pressure were measured. Liver ultrasonographic scanning was used for assessing fatty liver. To assess atherosclerosis, CIMT and ABI were used. RESULTS: The prevalence of NAFLD was 66.7%. As compared with control subjects, patients with NAFLD had a significantly greater (p = 0.02) mean CIMT while in patients with MetS, it was not significant. Left ventricular diastolic and systolic function were significantly impaired (p = 0.03, p = 0.04, respectively) in NAFLD while only LV diastolic function was significantly (p = 0.04) impaired in MetS. There was a strong positive correlation between CIMT and triglyceride (TG) (r = 0.46, p = 0.0001), total cholesterol (TC) (r = 0.47, p = 0.0001), low density lipoprotein cholesterol (LDL-C) (r = 0.46, p = 0.0001), very low density lipoprotein cholesterol (VLDL-C) (r = 0.259, p = 0.001), BMI (r = 0.21, p = 0.003), and age (r = 0.22, p = 0.002). CONCLUSIONS: Carotid intima-media thickness, ABI, and LV diastolic function were affected in patients with NAFLD and MetS.

Clinical Evidence of Evogliptin plus Metformin in Management of Type 2 Diabetes mellitus.

Achieving adequate glycemic control in type 2 diabetes mellitus (T2DM) remains a difficult but achievable goal. Oral agents (OADs) are important option for management of T2DM. Most T2DM patients require more than one medication for adequate glycemic control. Metformin based combination therapy is recommended when monotherapy is insufficient. Evogliptin is a recently developed dipeptidyl peptidase-4 (DPP-4) inhibitor, which can to be combined with metformin for treating T2DM. Combination therapy of Evogliptin and Metformin lowers blood glucose via augmentation of insulin secretion, suppression of glucagon secretion, and insulin sensitization. Co-administration of Evogliptin and Metformin showed no clinically relevant pharmacokinetic differences compared to the administration of each drug alone. Combination therapy of Evogliptin and Metformin also provides significantly better glycemic control compared to the respective monotherapies. Efficacy and safety of Evogliptin and Metformin had been demonstrated in several multicentre randomized clinical trials conducted in various countries like South Korea, Russia and India. Consequently, fixed dose combination (FDC) of Evogliptin and Metformin is approved in South Korea and India. Complexity of the treatment regimen and polypharmacy are well-known factors of poor medication adherence and FDCs have the potential to improve adherence by reducing the pill burden. Adoption of this combination therapy in clinical practice for management of T2DMs will provide a greater degree of HbA1c reduction than that observed with the use of either drug as monotherapy, and is unlikely to cause significant hypoglycemia. Combination therapy of Evogliptin and Metformin is a promising strategy in the treatment of T2DM.

Metabolic Diseases and Associated Complications in Patients with Psoriasis.

BACKGROUND: Psoriasis patients are at increased risk of developing metabolic diseases. Proinflammatory cytokines such as IFN-γ, IL-17, IL-23, and TNF-α,IGF that are increased in psoriasis play an important role in the development of diabetes mellitus(DM), hypertension, dyslipidemia, obesity, insulin resistance and their complications. AIMS: To study prevalence of insulin resistance (IR) using HOMA-IR index in psoriasis patients and its association with severity of psoriasis. To study prevalence of metabolic diseases, macro and microvascular complications of these diseases in psoriasis. MATERIALS AND METHODS: A hospital based case control study was conducted involving 102 psoriasis patients and 102 age and sex matched controls. All patients were analysed for the presence of metabolic diseases and their complications. RESULTS: Mean age of cases was 38.41±16.37 years. Majority of cases(58.8%) as well as controls (55.9%) were males. Prevalence of hypertension, prediabetes, DM, raised TG, low HDL, MetS and IR was 46.1%, 28.4%, 27.5%, 42.2%, 31.4%, 31.4% and 48% respectively in cases as compared to 26.5%, 13.7%, 11.8%, 24.3%, 16.7%, 10.8% and 26.5% respectively in controls. However there was no significant difference in obesity (29.4% vs 21.6%, p=0.2024) and LDL among the cases and controls(14.7 %vs 10.8%,p= 0.4). Prevalence of all the metabolic disorders except LDL was significantly higher in cases as compared to that in controls. Prominent complications noted were retinopathy, neuropathy and CVD. With increased psoriasis severity insulin resistance increased. CONCLUSION: There is a positive correlation of psoriasis with IR and it is associated with increased risk of metabolic diseases and their complications.

Assessment of Glycemic status, Insulin Resistance and Hypogonadism in HIV Infected Male Patients.

OBJECTIVES: The aim of the present study was to assess the glycemic status measured as Fasting Plasma Glucose (FPG) and glycosylated haemoglobin (A1C); prevalence of Insulin Resistance (IR), hypogonadism and to study their correlation with CD4 (CD4 lymphocyte) counts in HIV infected patients receiving ART. Correlation between percentage android fat and IR was also studied. METHODS AND MATERIALS: 84 HIV male patients as diagnosed by ELISA test aged 18 to 70 years were included in this case control study. Software IBM SPSS 20.1 and Microsoft Excel 2013 was used for analysis of data. The numerical data was compared using two tailed student t-test. Log transformation was used for the conversion of qualitative data (% android fat) to quantitative data so that it can be correlated to HOMA-IR. The level of significance was considered 0.05. RESULTS: Out of total 84 patients, 19 had FPG ≥ 100. 11(13%) had Impaired Fasting Glucose (IFG) and 8 (9.5%) had Diabetes Mellitus (DM). 20 patients had A1C > 5.6. Nine (10.7%) patients had Impaired Glucose Tolerance (IGT) and 11 (13.1%) patients had DM on the basis of A1C. 11 (13.1%) patients had DM based on either FPG or A1C criteria. Patients with higher percentage android fat had significantly higher IR. 33 (39%) patients had hypogonadism, six patients (7.1%) had primary hypogonadism; 24 (28.6%) had secondary hypogonadism and 3 (3.6 %) had compensatory hypogonadism. CONCLUSION: Patients with lower CD4 counts had significantly higher dysglycemia and IR. Serum testosterone levels were progressively lower (insignificant) with decreasing CD4 counts.

Uttar Pradesh Association of Physicians of India Position Statement: Betel Quid (Paan) and Diabetes.

Betel quid (paan) chewing is common in India, especially in Uttar Pradesh. Betel quid has multifaceted relationship with health, including metabolic and psychosocial health. The current recommendations have been released keeping in view the public health and clinical importance of this addictive behavior. The objective of this document is to offer clinical guidance for screening, diagnosis and management of co-occurring betel quid chewing among persons with Diabetes Mellitus (DM). The document aims to provide education and guidance to clinicians engaged in care and management of persons with DM, and improve access to treatment for co-occurring betel quid chewing among persons with DM. The current recommendation grades are based on published evidence, and categorized as strong, intermediate, weak and no evidence. The strength of these recommendations is based on the level of evidence.

Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

Uttar Pradesh Association of Physicians of India Position Statement: Tobacco Use and Metabolic Syndrome.

Tobacco use is one of the main preventable causes of mortality and morbidity worldwide. The global disease burden due to tobacco use is huge with projected mortality of eight million lives per year by 2030. Metabolic syndrome (MS) is defined as a constellation of cardiovascular and endocrine risk factors such as insulin resistance, obesity, raised blood pressure, and abnormal lipid profile. The relationship between tobacco use and MS has been well established. Also, the causal association between tobacco use and development of individual components of MS is well established. The Uttar Pradesh Association of Physicians of India (UP API) has drafted this position statement on managing tobacco use among persons with or at risk of developing Metabolic Syndrome (MS). This position statement presents evidence-based recommendations as described below. Scope and purpose The objective of this position statement is to offer clinical recommendations for screening, diagnosis and management of tobacco use among persons with or at risk of developing Metabolic Syndrome (MS). The purpose of this document is to aid in identification and treatment of maladaptive patterns of tobacco use i.e. tobacco use disorder (tobacco dependence, harmful use, abuse) in person with or at risk of developing MS. Intended Audience The position statement is targeted at the clinicians engaged in care and management of person with or at risk of developing Metabolic Syndrome (MS). This might also be of relevance to the policy makers considering the public health burden of both MS and tobacco use disorders.

A Clinico-Epidemiological Profile of Neuroparalytic Snake Bite: Using Low Dose ASV in a Tertiary Care Centre from North India.

OBJECTIVE: Snake bite in India is a common medical emergency and an occupational hazard for majority of Indian population especially farmers. Epidemiological data on snake bite from the North India is sparse. Hence we conducted this study to find clinico-epidemiological profile of neuroparalytic snake bite. METHODS: This is a record-based, descriptive study carried out at the Department of Medicine, M.L.N. Medical College and associated Swaroop Rani Nehru Hospital, Allahabad, U.P. (India) which is a tertiary care hospital of north India.. This study describes the epidemiology, arrival delays and the outcome of neuroparalytic snakebites with low dose ASV along with ventilatory support. RESULTS: Among the total 113 cases of neuroparalytic snake bite victims (56.63%) were males aged 21-40 years. Majorities of the victims were bitten outdoor (63.71%) and most of the bites occurred on the lower limbs (83%). The highest number of cases occurred during the monsoon season of July-September. Most of the victims were farmers (53.44%) and labourers (30.55%), which suggested that snake bite was an occupational hazard. Mean dose of ASV administered was 16.99 vials. The percentage of patients requiring intensive care and ventilatory support were (40.70%) and the total percentage of patients showing recovery was (84.07%). The most important positive prognostic factor was reaching hospital within 7 hours. CONCLUSIONS: Snake bite can be viewed as an occupational hazard among farmers and labourers. Delay in reaching hospital in time where definite treatment and care can be done was identified as the most important cause of mortality. Low dose ASV administration and ventilatory support can provide sufficient cure if patients reach on time. Public health programs regarding the prevention and the importance of the early arrival to the hospital should be emphasized.

Non-insulin pharmacological therapy in pregnancy.

During pregnancy, when glycaemic levels remain uncontrolled, despite lifestyle modification, pharmacotherapy is advised, usually insulin which has been the gold standard for treatment. Recent studies however suggest that certain oral anti diabetic agents (OADs) may be safe and acceptable alternatives. There may be potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and foetus. Glibenclamide, a second generation sulfonylurea, more effective in glycaemic control in women with GDM has a lower treatment failure rate than metformin but there is lack of long term follow up data. Even though generally well tolerated, some studies report higher rates of preeclampsia, macrosomia, neonatal jaundice, neonatal hypoglycaemia and longer stay in neonatal care unit.

Consensus Statement on Management of Post-Prandial Hyperglycemia in Clinical Practice in India.

Postprandial hyperglycemia (PPHG) is a detrimental factor in the evolution of diabetes related complications. Numerous studies have established the role of PPHG in development of atherosclerosis and associated cardiovascular conditions. It is seen that management of PPHG can be more troublesome than fasting plasma glucose (FPG). Currently, there are various strategies both monitoring as well as therapeutic to control PPHG but there is no uniformity in practicing these strategies. In the absence of any standard guidelines, widespread variations in the management of PPHG are observed among physicians and diabetologists. The objective of this document is to set forth uniform guidelines to manage PPHG. This will not only result in optimal management and prevention of long term complications of diabetes but also better co-ordination and collaboration among the care providers. Moreover, an Indian perspective that can take into consideration the issues relevant to Indian patient pool will be effective. An expert committee comprising of prominent physicians and researchers associated with diabetes care provided their inputs to provide a basic platform for the formulations of guidelines. Their inputs were supplemented by extensive literature search to collect the relevant evidences. An initial draft was prepared which was reviewed by the core committee. Inputs from other experts were also sought and an initial guideline version was formulated that was presented in a conference, discussed and debated among experts. The guidelines on PPHG were then finalized and published.

Newer antidiabetic drugs in Ramadan.

The management of diabetes in the month of Ramadan can be very challenging. On one hand there is the issue of fasting associated hypoglycaemia, and on the other, fasting as well as post prandial hyperglycaemia. Under such circumstances, a planned regimen needs to be followed to keep the blood glucose levels under control. The same oral antidiabetic agents that were used prior to the fast are used during Ramadan with modification in dosage and timing. With the advent of newer anti-diabetic agents, there is a good scope for better control and reduced complications.

Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).

BACKGROUND: Non-communicable disease (NCD) rates are rapidly increasing in India with wide regional variations. We aimed to quantify the prevalence of metabolic NCDs in India and analyse interstate and inter-regional variations. METHODS: The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a cross-sectional population-based survey, assessed a representative sample of individuals aged 20 years and older drawn from urban and rural areas of 31 states, union territories, and the National Capital Territory of India. We conducted the survey in multiple phases with a stratified multistage sampling design, using three-level stratification based on geography, population size, and socioeconomic status of each state. Diabetes and prediabetes were diagnosed using the WHO criteria, hypertension using the Eighth Joint National Committee guidelines, obesity (generalised and abdominal) using the WHO Asia Pacific guidelines, and dyslipidaemia using the National Cholesterol Education Program-Adult Treatment Panel III guidelines. FINDINGS: A total of 113 043 individuals (79 506 from rural areas and 33 537 from urban areas) participated in the ICMR-INDIAB study between Oct 18, 2008 and Dec 17, 2020. The overall weighted prevalence of diabetes was 11·4% (95% CI 10·2-12·5; 10 151 of 107 119 individuals), prediabetes 15·3% (13·9-16·6; 15 496 of 107 119 individuals), hypertension 35·5% (33·8-37·3; 35 172 of 111 439 individuals), generalised obesity 28·6% (26·9-30·3; 29 861 of 110 368 individuals), abdominal obesity 39·5% (37·7-41·4; 40 121 of 108 665 individuals), and dyslipidaemia 81·2% (77·9-84·5; 14 895 of 18 492 of 25 647). All metabolic NCDs except prediabetes were more frequent in urban than rural areas. In many states with a lower human development index, the ratio of diabetes to prediabetes was less than 1. INTERPRETATION: The prevalence of diabetes and other metabolic NCDs in India is considerably higher than previously estimated. While the diabetes epidemic is stabilising in the more developed states of the country, it is still increasing in most other states. Thus, there are serious implications for the nation, warranting urgent state-specific policies and interventions to arrest the rapidly rising epidemic of metabolic NCDs in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India.

A Practitioner's Toolkit for Polycystic Ovary Syndrome Counselling.

Polycystic ovary syndrome (PCOS), a frequently occurring health issue, has a significant effect on the cosmetic, metabolic, psychosocial and fertility aspects of women. A multidisciplinary team approach based on the core pillars of screening, assessment and counselling to detect, prevent and treat physiological and psychological issues in PCOS is very essential. Women are treated medically, but the psychosocial part is often forsaken. Hence, counselling forms an integral part of PCOS management that enables enhanced clinical outcomes and patient satisfaction. Digital tools and PCOS support groups have built an opportunity for physicians to create awareness, help timely diagnosis and overcome PCOS symptoms. The absence of clear guidelines to tackle the often less discussed aspects of PCOS warrants the need for consensus on PCOS counselling. This review summarizes the biopsychosocial health, clinical assessment and treatment strategies of PCOS and associated co-morbidities. The review article will discuss the clinician's role in patient education with the special focus on counselling of females with PCOS regardless of age group.

Variations in glycated haemoglobin with age among individuals with normal glucose tolerance: Implications for diagnosis and treatment-Results from the ICMR-INDIAB population-based study (INDIAB-12).

AIM: To report on glycated haemoglobin (HbA1c) values among individuals with normal glucose tolerance (NGT) at different age groups, using data acquired from a large national survey in India. MATERIALS AND METHODS: Data on glycaemic parameters at different age groups were obtained from the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study, in adults aged ≥ 20 years representing all parts of India. Age-wise distribution of HbA1c was assessed among individuals with NGT (n = 14,222) confirmed by an oral glucose tolerance test using the World Health Organization (WHO) criteria. Results were validated in another large epidemiological study (n = 1077) conducted in Chennai, India. RESULTS: Among NGT individuals, HbA1c increased gradually with age from 5.16 ± 0.71% (33 mmol/mol) in the age group of 20-29 years to 5.49 ± 0.69% (37 mmol/mol) in those aged 70 + years. In the validation study, conducted in another study population, HbA1c was 5.35 ± 0.43% (35 mmol/mol) in age group of 20-29 years and 5.74 ± 0.50% (39 mmol/mol) in those aged 70 and above. In the INDIAB study, for every decadal increase in age, there is a 0.08% increase in HbA1c and this increase was more significant in females (females: 0.10% vs. males: 0.06%) and in urban (urban: 0.10% vs. rural: 0.08%) population. CONCLUSIONS: HbA1c levels increase steadily with age. This suggests that age-specific cutoffs be used while utilizing HbA1c to diagnose diabetes and prediabetes, so as to minimize the risk of overdiagnosis and unnecessary initiation of treatment in elderly people who could have physiological increase in HbA1c levels.

Achievement of guideline recommended diabetes treatment targets and health habits in people with self-reported diabetes in India (ICMR-INDIAB-13): a national cross-sectional study.

BACKGROUND: There is little information on comprehensive diabetes care comprising glycaemic, lipid, and blood pressure control in India; therefore, we aimed to assess the achievement of treatment targets among adults with self-reported diabetes. METHODS: The Indian Council of Medical Research (ICMR)-India Diabetes (INDIAB) study is a cross-sectional, population-based survey of adults aged 20 years or older in all 30 states and union territories of India. We used a stratified multistage sampling design, sampling states in a phased manner, and selected villages in rural areas and census enumeration blocks in urban areas. We used a three-level stratification method on the basis of geography, population size, and socioeconomic status for each state. For the outcome assessment, good glycaemic control was defined as HbA1c of less than 7·0% (A), blood pressure control was defined as less than 140/90 mm Hg (B), and the LDL cholesterol target was defined as less than 100 mg/dL (C). ABC control was defined as the proportion of individuals meeting glycaemic, blood pressure, and LDL cholesterol targets together. We also performed multiple logistic regression to assess the factors influencing achievement of diabetes treatment targets. FINDINGS: Between Oct 18, 2008, and Dec 17, 2020, 113 043 individuals (33 537 from urban areas and 79 506 from rural areas) participated in the ICMR-INDIAB study. For this analysis, 5789 adults (2633 in urban areas and 3156 in rural areas) with self-reported diabetes were included in the study population. The median age was 56·1 years (IQR 55·7-56·5). Overall, 1748 (weighted proportion 36·3%, 95% CI 34·7-37·9) of 4834 people with diabetes achieved good glycaemic control, 2819 (weighted proportion 48·8%, 47·2-50·3) of 5698 achieved blood pressure control, and 2043 (weighted proportion 41·5%, 39·9-43·1) of 4886 achieved good LDL cholesterol control. Only 419 (weighted proportion 7·7%) of 5297 individuals with self-reported diabetes achieved all three ABC targets, with significant heterogeneity between regions and states. Higher education, male sex, rural residence, and shorter duration of diabetes (<10 years) were associated with better achievement of combined ABC targets. Only 951 (weighted proportion 16·7%) of the study population and 227 (weighted proportion 36·9%) of those on insulin reported using self-monitoring of blood glucose. INTERPRETATION: Achievement of treatment targets and adoption of healthy behaviours remains suboptimal in India. Our results can help governments to adopt policies that prioritise improvement of diabetes care delivery and surveillance in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare.

Macronutrient Recommendations for Remission and Prevention of Diabetes in Asian Indians Based on a Data-Driven Optimization Model: The ICMR-INDIAB National Study.

OBJECTIVE: To derive macronutrient recommendations for remission and prevention of type 2 diabetes (T2D) in Asian Indians using a data-driven optimization approach. RESEARCH DESIGN AND METHODS: Dietary, behavioral, and demographic assessments were performed on 18,090 adults participating in the nationally representative, population-based Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study. Fasting and 2-h postglucose challenge capillary blood glucose and glycosylated hemoglobin (HbA1c) were estimated. With HbA1c as the outcome, a linear regression model was first obtained for various glycemic categories: newly diagnosed diabetes (NDD), prediabetes (PD), and normal glucose tolerance (NGT). Macronutrient recommendations were formulated as a constrained quadratic programming problem (QPP) to compute optimal macronutrient compositions that would reduce the sum of the difference between the estimated HbA1c from the linear regression model and the targets for remission (6.4% for NDD and 5.6% for PD) and prevention of progression in T2D in PD and NGT groups. RESULTS: Four macronutrient recommendations (%E- Energy) emerged for 1) diabetes remission in NDD: carbohydrate, 49-54%; protein, 19-20%; and fat, 21-26%; 2) PD remission to NGT: carbohydrate, 50-56%; protein,18-20%; fat, 21-27%; 3 and 4) prevention of progression to T2D in PD and NGT: carbohydrate, 54-57% and 56-60%; protein, 16-20% and 14-17%, respectively; and fat 20-24% for PD and NGT. CONCLUSIONS: We recommend reduction in carbohydrates (%E) and an increase in protein (%E) for both T2D remission and for prevention of progression to T2D in PD and NGT groups. Our results underline the need for new dietary guidelines that recommend appropriate changes in macronutrient composition for reducing the burden due to diabetes in South Asia.