SGLT2i as a First-line Antihyperglycemic in the Management of Type 2 Diabetes in the Context of Indians: A Systematic Review and Consensus.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India. MATERIALS AND METHODS: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology. RESULTS: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (ß-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and ß-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus. CONCLUSION: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India.

Prescribing Patterns and Response to Antihyperglycemic Agents Among Novel Clusters of Type 2 Diabetes in Asian Indians.

Aim: To assess the prescribing patterns and response to different classes of antihyperglycemic agents in novel clusters of type 2 diabetes (T2D) described in India. Materials and Methods: We attempted to replicate the earlier described clusters of T2D, in 32,867 individuals with new-onset T2D (within 2 years of diagnosis) registered between October 2013 and December 2020 at 15 diabetes clinics located across India, by means of k-means clustering utilizing 6 clinically relevant variables. Individuals who had follow-up glycated hemoglobin (HbA1c) up to 2 years were included for the drug response analysis (n = 13,247). Results: Among the 32,867 participants included in the study, 20,779 (63.2%) were males. The average age at diagnosis was 45 years and mean HbA1c at baseline was 8.9%. The same four clusters described in India earlier were replicated. Forty percent of the study participants belonged to the mild age-related diabetes cluster, followed by insulin-resistant obese diabetes (27%), severe insulin-deficient diabetes (21%), and combined insulin-resistant and insulin-deficient diabetes (12%) clusters. The most frequently used antihyperglycemic agents were sulfonylureas, metformin, and dipeptidyl peptidase-4 inhibitors apart from insulin. While there were significant differences in HbA1c reduction between drugs across clusters, these were largely driven by differences in the baseline (pretreatment) HbA1c. Conclusions: In this new cohort, we were able to reliably replicate the four subtypes of T2D earlier described in Asian Indians. Prescribing patterns show limited usage of newer antihyperglycemic agents across all clusters. Randomized clinical trials are required to establish differential drug responses between clusters.

Gut microbiota and its mysteries.

Gut microbiota are microorganisms that inhabit the gut; they coexist peacefully with the host, thereby contributing to the health and well-being of individuals. Bacteroidetes and Firmicutes largely dominate the gut microbial flora. The intestinal flora promotes intestinal mucosal integrity, provides essential nutrients such as vitamins and enzymes, protects the body against pathogens and produces antimicrobial peptides such as defensins, C-type lectins, cathelicidins, they also play an active role in the innate and adaptive immune system. Gut microbial flora plays an active role in the synthesis of short-chain fatty acids such as butyrate, propionate and acetate. Gut microbiota also plays a significant role in the cognitive and behavioural functions of the host. A balanced gut microbiota shifts to dysbiosis, due to intake of high fat or sugar or other factors like sedentary lifestyle. The dysbiosis of the gut results in increased permeability, endotoxaemic, insulin resistant, systemic inflammation, adiposity and metabolic disorders such as type 2 diabetes mellitus, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, irritable bowel disorder, colorectal cancer, etc. A prudent lifestyle modification, added on with use of probiotics and prebiotic restore the normal flora of the gut, especially in patients with Clostridium difficle-associated diarrhoea, inflammatory bowel syndrome, liver disease and colon cancer. Faecal microbial transplant is an important therapeutic tool in many illness related with the gut. Thereby, understanding the gut microbial signatures in various diseases yields various novel therapeutic targets. Human gut microbiota has a prognostic, diagnostic and therapeutic potential which is recognised worldwide.

Sequencing of Porphyromonas gingivalis from saliva in patients with periodontitis and type 2 diabetes mellitus.

Background: Porphyromonas gingivalis is a major periodontal pathogen. Saliva is the most easy, non-invasive microbiological sample for detection of periodontal pathogens. Aim and Objectives: A prospective study on 37 diabetic patients was grouped into well-controlled diabetes with/without periodontitis and uncontrolled diabetic with periodontitis. PCR and sequencing of P. gingivalis was performed in saliva samples. Materials and Methods: DNA was extracted from saliva using Triton X-100 and 16s rRNA gene (404 bp) was amplified by polymerase chain reaction. DNA sequencing was performed for two samples. Results: P. gingivalis was detected in 27.03% (n = 10), of which 30% (n = 9) were diabetic with periodontal disease and 14.3% (n = 1) were diabetic without periodontal disease. The percentage of poor oral hygiene was 50% and 20% in uncontrolled and controlled glycaemic patients, respectively. DNA sequencing of two samples showed 100% identity with the sequences in the GenBank database (Gen Bank accession no: KX640913-KX640914). Conclusion: Type 2 diabetes mellitus and periodontitis are interlinked. Early detection of P. gingivalis and appropriate treatment with doxycycline will also assist in controlling the glycaemic status.

Correlation between Ultrasound-based TIRADS and Bethesda System for Reporting Thyroid-cytopathology: 2-year Experience at a Tertiary Care Center in India.

BACKGROUND: In recent times, high-resolution ultrasound thyroid imaging has paved the way for significant transformation in clinical approach to thyroid nodule. There are several risk stratification systems in thyroid imaging, developed with an aim, not only to reduce the inter-observer variability but also to establish effective communication system. Thyroid image reporting and data system (TIRADS) classification system, which is similar to breast imaging reporting and data system for breast lesion, is the most useful of all. To our knowledge, there is just a handful published research articles available based on Indian population in this regard. In this article, we study the thyroid nodules using high-resolution ultrasound in Indian population and we try to correlate the TIRADS and Bethesda system for reporting thyroid cytopathology. MATERIALS AND METHODS: This prospective study includes 184 patients studied over a period of 2 years (April 2015-April 2017). Patients having thyroid nodule in B-mode ultrasound and are scheduled to get a fine-needle aspiration cytology (FNAC) done. Bethesda classification of these nodules is tabulated in follow-up period simultaneously. By comparing these data, efficacy of TIRADS in differentiating benign from malignant nodules are assessed finally using accuracy, positive predictive value (PPV), cross-tabulation, and Chi-square tests. RESULTS: Out of the 117 TIRADS 2 nodules, none turned out to be Bethesda IV or higher, which means none of these nodules turned out to be malignant. The risk of malignancy for TIRADS 2, TIRADS 3, TIRADS 4, and TIRADS 5 was 0, 2.2, 38.5, and 77.8%, respectively. The risk of malignancy percentage in our study is similar to those values obtained in other prominent studies. CONCLUSION: The probability of a particular nodule being malignant can be effectively inferred from the ultrasound-based TIRADS system with a certain level of confidence. Considering our results and other literature reviews, it be can be safely assumed that FNAC can be at least deferred in patients having TIRADS 2 nodules, which contribute to majority of newly detected cases. In our experience, there is a remarkable correlation exists between TIRADS ultrasound classification and Bethesda cytology, especially for benign nodules.

Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome.

OBJECTIVES: The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low-density lipoprotein (LDL) size, before and after sustained release metformin (Met-SR) therapy in women with polycystic ovarian syndrome (PCOS). METHODS: Sixty women with PCOS and sixty age-matched controls in the age group 18-45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. RESULTS: Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. CONCLUSION: Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.

A Pragmatic Approach to the Indeterminate Thyroid Nodule.

Thyroid nodules are prevalent in upto 68% of randomly selected individuals in whom high resolution ultrasound is performed. The majority of nodules are benign. The use of ultrasound coupled with FNAC has dramatically reduced the number of patients who undergo surgery for nodules. The six tier Bethesda scoring system has reduced variability and increased the ability to clinicians to guide patients with thyroid nodules. There is good correlation between cytology and histopathologic outcomes. A significant proportion of patients will however fall into an indeterminate category. The availability of molecular markers enhanced with next generation sequencing technology and the expression classifier are added diagnostic aids that can help in management. However these are not available in many countries and in resource limited settings. A pragmatic approach to the diagnosis of indeterminate nodules includes utilising pre and post test probability, clinical acumen, correlation of ultrasound findings and expert opinion in some settings. Using this approach high risk patients can be appropriately chosen for surgery while relegating patients with lower risk to watchful followup.

Next generation sequencing of oral microbiota in Type 2 diabetes mellitus prior to and after neem stick usage and correlation with serum monocyte chemoattractant-1.

INTRODUCTION: Oral microbiome impacts health and disease. T2DM and periodontitis are associated. Neem (Azadiracta indica) has antibacterial activity against oral microbiota. OBJECTIVES: To characterize oral microbiota (OMB) in saliva samples of T2DM patients by Next generation sequencing. To analyze MCP-1 levels among the T2DM patients before and after a month of neem stick usage as a toothbrush. MATERIALS AND METHODS: Blood and saliva samples were collected from adult T2DM patients before and after the neem stick usage. Metagenomic sequencing was performed on saliva samples targeting V6 region of 16s rRNA. Serum MCP-1 levels were determined using a quantitative sandwich Human MCP-1 standard ABTS development kit (Peprotech, USA). RESULTS: The profile of oral microbiota of T2DM patients (n=24) consists of Streptococcus (95.8%) counts ranging from 2644 to 27,214, Veillonella (72.2%, counts 25-19,709, Neisseria (87.5%) 453-33,445), Rothia (63.6%, 233-6734), Actinomycetes (25%, 161-3730), Fusobacterium (21%, 2252-21,334), and Pigmentiphaga (12.5% 3-16,644). Oral microbiota in healthy controls (n=10), consists of Streptococcus (26.1%), Veillonella (21.9%), Neisseria (16.9%), Haemophilus (10.7%), Actinomycetes (2.6%), Rothia (3.1%), Oribacterium (1.7%). Post neem samples showed drastic reduction in the load of bacteria which was statistically significant. The mean serum MCP-1 before the use of neem stick was 265.18±79.44 (range 141.6-980.5pg/ml) and dropped to 33.6±7.35 after a month of neem stick usage (P value>0.001). CONCLUSION: OMB of T2DM patients and healthy controls were similar, however bacterial loads were significantly higher in T2DM patients. Use of neem stick has a statistically significant reduction on bacterial loads and MCP-1 levels in T2DM patients.

Reported hypoglycemia in Type 2 diabetes mellitus patients: Prevalence and practices-a hospital-based study.

INTRODUCTION: Hypoglycemia tops the list of hurdles in preventing tight glycemic control in diabetic patients. It is even considered as a cardiovascular risk factor. However, it continues to be a neglected complication with very limited epidemiological data in our country. AIM: To study the self-reported prevalence of hypoglycemia among type 2 diabetic patients and the practices adopted by them during and after the episodes to manage and avert future occurrences. MATERIALS AND METHODS: It is a questionnaire-based cross-sectional study done using systematic random sampling selecting every 5th patient attending the diabetic Out-Patient (OP) in a tertiary medical college hospital. RESULTS: There were 366 participants with median age of 60 years. Around 96% reported any one symptom of hypoglycemia, but 78% had eaten following the episode and got relieved of the symptoms. Weakness (76.2%) and dizziness (74%) were the most common symptoms reported by the patients. A quarter of them reported having severe attacks requiring somebody's assistance. Most patients resorted to timely meals (85%) to avert future attacks. Patients who took insulin along with oral hypoglycemic agents (OHAs) were at a higher risk (OR = 2.3) for hypoglycemia compared to patients taking only OHAs (P < 0.01). CONCLUSION: The reported prevalence of hypoglycemia among type 2 diabetes patients is quite high. This finding reiterates the importance of enquiring and educating every diabetic patient about hypoglycemic episodes during every health visit.

Gut Microbiota in Type 2 Diabetes Individuals and Correlation with Monocyte Chemoattractant Protein1 and Interferon Gamma from Patients Attending a Tertiary Care Centre in Chennai, India.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are associated with changes in gut microbiota and characterized by chronic low-grade inflammation. Monocyte chemoattractant protein-1 (MCP-1) and interferon gamma (IFNγ) are proinflammatory cytokines which play an important role in the development of T2DM. We undertook this study to analyze the gut microbiota of T2DM and nondiabetic subjects and to determine the profile of MCP 1 and IFNγ in the same subjects attending a tertiary care center in Chennai, Tamil Nadu, India. METHODS: The study included 30 subjects with clinical details. Stool and blood samples were collected from all the subjects. DNA was extracted from fecal samples and polymerase chain reaction was done using fusion primers. Metagenomic analysis was performed using ion torrent sequencing. The reads obtained were in FASTA format and reported as operational taxonomic units. Human MCP 1 and IFNγ enzyme linked immunosorbent assay (ELISA) were performed for 23 serum samples. RESULTS: The study consisted of 30 subjects; 17 were T2DM and 13 were nondiabetics. The gut microbiota among T2DM consisted predominantly of Gram negative bacteria; Escherichia and Prevotella, when compared with the nondiabetic group with predominantly Gram positive organisms suchas Faecalibacterium, Eubacterium, and Bifidobacterium. The mean MCP-1 values in the diabetic group were 232.8 pg/ml and in the nondiabetic group 170.84 pg/ml. IFNγ (mean 385.5 pg/ml) was raised in glycated hemoglobin (HbA1c) group of 6.5-7.5% which was statistically significant. Association of Escherichia with T2DM and association of Bifidobacteria in the nondiabetics were also statistically significant. CONCLUSION: Escherichia counts were elevated in T2DM with HbA1c of 6.5-8.5% which was statistically significant suggesting that lipopolysaccharides present in the cell wall of Gram-negative bacteria may be responsible for low-grade inflammation as evidenced by elevated MCP-1 and IFNγ levels in T2DM with the same HbA1c levels.

The neuroendocrinology of love.

Romantic love could be considered as a collection of activities associated with the acquisition and retention of emotions needed to survive and reproduce. These emotions change the individual's behavioural strategies in a way that will increase the likelihood of achieving these goals. Love may be defined as an emergent property of an ancient cocktail of neuropeptides and neurotransmitters. It appears that lust, attachment and attraction appear to be distinct but intertwined processes in the brain each mediated by its own neurotransmitters and circuits. These circuits feed on and reinforce each other. Sexual craving is mediated by testosterone and oestrogen and has the amygdala as an important centre. Attraction is mediated by hormones of stress and reward including dopamine, norepinephrine cortisol and the serotinergic system and has the nucleus accumbens the ventral tegmental area as key mediators.

The effect of prior antithyroid drug use on delaying remission in high uptake Graves' disease following radioiodine ablation.

Antithyroid drugs (ATDs) have been shown to attenuate the effectiveness of radioiodine (radioiodine ablation, RIA) therapy in Graves' disease. We undertook a study to look at the impact of iodine uptakes on the outcome of (131)I therapy. To determine the effect of prior ATD use on the duration of time to achieve cure in patients with high vs intermediate uptake Graves' disease who received a fixed dose (15 mCi) of (131)I radioiodine. In a retrospective study of patients with Graves' disease, 475 patients who underwent RIA were followed-up on a two-monthly basis with thyroid function tests. Of the 123 patients with a documented preablation RAIU and consistent follow-up it was observed that 40 patients had an intermediate RAIU (10-30%) and 83 subjects had a distinctly increased uptake (>30%). Successful cure was defined as the elimination of thyrotoxicosis in the form of low free thyroxin and rising TSH levels. When a standard dose of 15 mCi (131)I was administered, a cure rate of 93% was achieved. The median duration of time to cure (TC) was 129 days. Surprisingly, a direct proportional linear relationship (R(2)=0.92) was established between time to cure and radioiodine uptake (TC> 3 0%=172days, TC10 - 3 0%=105 days, P<0.001). Patients who used ATD medications took a proportionately longer duration to achieve remission (TCNO ATD=102days, TCATD=253days, P<0.001). The effect of prior ATD therapy in delaying remission was amplified in the subset of patients with higher uptakes (TC> 3 0% + ATD=310days, TC> 3 0% + NO ATD=102days, P<0.001) compared to those with the intermediate uptakes (TC10 - 3 0% + ATD=126 days, TC10 - 3 0% + NO ATD=99 days, P<0.001). RIA, using a dose of 15 mCi achieved a high cure rate. Higher uptakes predicted longer time to achieve remission, with prior ATD use amplifying this effect.

Knowledge of hypoglycemia and its associated factors among type 2 diabetes mellitus patients in a Tertiary Care Hospital in South India.

INTRODUCTION: Hypoglycemia being the rate limiting complication in the attainment of strict glycemic control in diabetes management, in this study, we intended to study the knowledge of its symptoms, target blood levels during treatment and ways of prevention among type 2 diabetes patients attending Outpatient Department (OPD) of a medical college hospital. MATERIALS AND METHODS: Every fifth patient attending the OPD during the 4 months between March and June 2013 was interviewed using a questionnaire. RESULTS: The study included 366 type 2 diabetic patients, of which 76.5% were females. The target fasting and postprandial blood glucose levels while on treatment was known to 135 (36.9%) and 126 (34.4%) patients, respectively. The common symptoms of hypoglycemia known to the study subjects were dizziness (81.4%), weakness (73.8%), and drowsiness (72.1%). Overall, 242 (66.1%) diabetic patients had good knowledge on hypoglycemia (knowledge of at least three symptoms of hypoglycemia together with at least one precipitating factor and at least one remedial measure). Higher age, illiteracy, low socioeconomic status were associated with poor knowledge whereas treatment with insulin along with oral hypoglycemic agents was associated with good knowledge on hypoglycemia. Sex and duration of disease were not associated with knowledge on hypoglycemia. CONCLUSION: Although the knowledge on symptoms of hypoglycemia, precipitating factors, remedial measures are high in this study, the target blood levels, complications were known to just a third of them. There is a knowledge gap on important aspects of hypoglycemia among type 2 diabetic patients.

Serum monocyte chemoattractant protein-1 is a biomarker in patients with diabetes and periodontitis.

INTRODUCTION: The role of serum Monocyte Chemoattractant Protein-1 (MCP-1) as a biomarker of periodontitis is well documented; however, its role in diabetic patients with periodontitis is unknown. AIM: This study was conducted to determine the presence and concentration of serum MCP-1 in diabetic patients with and without periodontitis and correlate it glycemic status with periodontitis. MATERIALS AND METHODS: Adult diabetic patients were enrolled and grouped into group I, II, and III based on their glycemic status and serum MCP-1 estimated by ELISA. Linear regression and correlation tests were performed using R statistical software, Medcalc software to observe correlation between the serum MCP-1 and glycated hemoglobin level among different groups. RESULTS: Serum samples obtained from 37 patients tested positive for MCP-1. Mean serum MCP-1 concentration was highest (482.3 pg/ml) in group III, lowest (149.3 pg/ml) in group I, and intermediate 398.8 pg/ml in group II. Correlation and regression analysis was done between HbA1c and serum MCP-1. A significant positive correlation (P < 0.001) was observed. Serum MCP-1 increased by 37.278 pg/ml for every 1% rise in HbA1c, and the levels were raised in group II and group III than in group I irrespective of their glycemic status. With an HbA1c range of 6.5-6.9% (group II), the serum MCP-1 values cluster around 380-410 pg/ml. Elevated levels of serum MCP-1 (>500 pg/ml) in three subjects corresponded to HbA1c values more than 12.2% (group III). CONCLUSION: To our knowledge, this is the first study to document serum MCP-1 levels in diabetic patients with periodontitis. Glycemic status influences serum MCP-1, and lack of glycemic control contributes to increased serum MCP-1 levels. Serum MCP-1 may thus serve as a biomarker of inflammation and disease progression in diabetes with periodontitis.

Circulating adiponectin levels in Indian patients with psoriasis and its relation to metabolic syndrome.

BACKGROUND: Adiponectin is a cytokine mainly secreted from the adipose tissue, which has insulin-sensitizing effects, antiatherosclerotic actions, and antiinflammatory properties. There are a few studies that have demonstrated that adiponectin is reduced in patients with psoriasis suggesting that this adipocytokine may have a role in the pathogenesis of psoriasis. There have been no studies so far on adiponectin in relation to psoriasis and metabolic syndrome (MetS). OBJECTIVES: This study was performed to analyze serum adiponectin and insulin levels in psoriasis patients with and without MetS and in controls with and without MetS. MATERIALS AND METHODS: We performed a case control study on 60 psoriasis patients, 29 with MetS and 31 without MetS and 40 controls, 20 with and 20 without MetS, matched for age, sex, and body mass index (BMI). Fasting serum insulin and adiponectin levels were measured in all groups. RESULTS: The overall serum adiponectin levels were significantly reduced in psoriasis patients when compared with controls (P = 0.000). A significant reduction was also observed in psoriasis patients with MetS than those without MetS in the same group (P = 0.000). Similar decrease was observed between those with MetS in the psoriasis and control groups (P = 0.001). The lowest mean value of serum adiponectin (6387.9 ng/ml) was observed in psoriasis with MetS group and highest value (12146.3 ng/ml) in controls without MetS. CONCLUSION: Adiponectin levels are decreased in psoriasis patients irrespective of MetS thus indicating a role in its pathogenesis. This study prompts future trials on drugs increasing adiponectin levels in patients with psoriasis.

Endocrinology and the arts at the feet of the dancing Lord: Parathyroid hormone resistance in an Indian icon.

The dance of Siva has a cosmic appeal. Nowhere has this dance been crystallised in its pristine form as in the Nataraja Bronzes from the Chola period. Mysticism surrounds the dancing form of the Nataraja. But does Nataraja dance upon an endocrine mystery. Does the demon under his feet Apasmara literally forgetfulness or epilepsy have an endocrine disorder. The short limbed stocky eye popping dwarf with possible mental retardation with a name that suggests epilepsy throws open a host of endocrine diagnoses. From cretinisim to the original descriptions of pseudohypoparathyroidism here is one view of the medical mystery under Shiva's dancing feet.