National and regional prevalence of gestational diabetes mellitus in India: a systematic review and Meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. METHODS: We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. RESULTS: Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0-13.0%, I2=96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0-16.0%, I2 = 99%]. CONCLUSIONS: This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country.

Clinical Evaluation of a Novel, Patented Green Coffee Bean Extract (GCB70®), Enriched in 70% Chlorogenic Acid, in Overweight Individuals.

OBJECTIVE: Obesity and overweight are challenging health problems of the millennium that lead to diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis. Green coffee bean exhibited significant promise in healthy weight management, potentiating glucose-insulin sensitization and supporting liver health. The safety and efficacy of a novel, patented water-soluble green coffee bean extract (GCB70® enriched in 70% total chlorogenic acid and <1% caffeine) was investigated in 105 participants for 12 consecutive weeks. An institutional review board and Drugs Controller General (India) (DCGI) approvals were obtained, and the study was registered at ClinicalTrials.gov. METHOD: Body weight, body mass index (BMI), waist circumference, lipid profile, plasma leptin, glycosylated hemoglobin (HbA1c), and total blood chemistry were assessed over a period of 12 weeks of treatment. Safety was affirmed. RESULTS: GCB70 (500 mg BID) supplementation significantly reduced body weight (approximately 6%; p = 0.000**) in approximately 97% of the study population. About a 5.65% statistically significant reduction (p = 0.000**) in BMI was observed in 96% of the study volunteers. Waist circumference was significantly reduced by 6.77% and 6.62% in 98% of the male and female participants, respectively. Plasma leptin levels decreased by 13.6% in 99% of the study population as compared to the baseline value. Upon completion of 12 weeks' treatment, fasting glucose levels decreased by 13.05% (p = 0.000**) in 79% of the study population. There was a statistically significant decrease in HbA1c levels in both male and female participants (p = 0.000**), while 86.7% of the study participants showed a statistically significant decrease in thyroid-stimulating hormone (TSH) levels (p = 0.000**). The mean decrease in TSH levels on completion of the treatment was 14.07% in the study population as compared to baseline levels. Total blood chemistry analysis exhibited broad-spectrum safety. CONCLUSIONS: This investigation demonstrated that GCB70 is safe and efficacious in healthy weight management.

Honeymoon phase in type 1 diabetes mellitus: A window of opportunity for diabetes reversal?

The knowledge of the pathogenesis of type 1 diabetes mellitus (T1DM) continues to rapidly evolve. The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status. Not all individuals of T1DM progress in that specific sequence. We hereby present a case of T1DM with a classical third phase (honeymoon phase) and discuss the intricacies of this interesting phase along with a possible future promise of "cure" with the use of immunotherapies. We now know that the course of T1DM may not be in only one direction towards further progression; rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed. The third phase popularly called the "honeymoon phase", is of special interest as this phase is complex in its pathogenesis. The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive "diabetes reversal" in T1DM. Identifying this phase is therefore the key, with a lot of varying criteria having been proposed.

Quantitative Association of Platelet-Rich Fibrin (PRF) and Hyperacute Serum (HAS) with Glycemic Control (HbA1c) in Chronic Periodontitis Patients: An Ex vivo Study.

Aim: To evaluate correlation of PRF and HAS with glycemic control (HbA1c) and other systemic parameters amongst the chronic periodontitis patients. Materials and Methods: Twenty-seven non-smoker, non-tobacco users, non-alcoholic moderate chronic periodontitis volunteers (Stage II, Grade A or B), aging between 40 and 50 years of both genders with type 2 diabetes mellitus (T2DM, HbA1c >6.5%) or without T2DM (HbA1c <6.5%), were recruited. After recording vitals and demographic parameters, 20 ml of intravenous fasting blood was collected, of which 11 ml blood was used for investigating complete blood count, lipid profile, glycated hemoglobin (HbA1c), C-reactive protein, and fasting insulin level. As per the standard protocol, PRF and HAS was prepared from the 9-ml blood sample of the patients. PRF obtained was quantified using Wensar's analytical balance with a readability of 0.0001 g. Prepared HAS from the fibrin clot was quantified using a micropipette and stored in 2 ml Eppendorf vials. Results: Mean values of PRF and HAS obtained in the study were 2.0089 ± 0.844 g (ranged between 0.0 g and 3.968 g) and 1.540 ± 0.552 ml (ranged between 0.00 and 3.500 ml), respectively. The amount of PRF and HAS obtained were significantly higher in non-diabetic patients (mean 2.3093 g and 1.743 ml, respectively) as compared to diabetic patients (mean 1.5762 g and 1.266 ml, respectively). Results suggested a significant correlation between HbA1c level and quantification of PRF (P=0.007) and HAS (P=0.037), whereas no correlation was observed between HbA1c levels and hematologic, lipid, and demographic parameters. Conclusion: Within the limitation of the present study, it can be concluded that a significant correlation exists between the HbA1c level and quantification of PRF and HAS.

Technical considerations in obtaining platelet rich fibrin for clinical and periodontal research.

Autologous platelet rich fibrin (PRF), is currently being widely used and investigated across the globe by clinicians and periodontal research. The technical aspect required for the procurement of PRF includes revolution per minute (RPM), relative centrifugal force (RCF) or G-force, rotor radius, rotor angle, stability or vibration in the centrifugal machine and material of test-tube, besides the systemic health of the individual may influence the final outcome. Present technical note intends to compile these aspects for better understanding and appropriate outcome while preparing PRF in varying clinical scenarios.

Development process of a clinical guideline to manage type 2 diabetes in adults by Ayurvedic practitioners.

Background: Type 2 diabetes mellitus (T2DM), a common chronic health condition, has major health and socioeconomic consequences. In the Indian subcontinent, it is a health condition for which individuals commonly consult Ayurvedic (traditional medical system) practitioners and use their medicines. However, to date, a good quality T2DM clinical guideline for Ayurvedic practitioners, grounded on the best available scientific evidence, is not available. Therefore, the study aimed to systematically develop a clinical guideline for Ayurvedic practitioners to manage T2DM in adults. Methods: The development work was guided by the UK's National Institute for Health and Care Excellence (NICE) manual for developing guidelines, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, and the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. First, a comprehensive systematic review was conducted which evaluated Ayurvedic medicines' effectiveness and safety in managing T2DM. In addition, the GRADE approach was used for assessing the certainty of the findings. Next, using the GRADE approach, the Evidence-to-Decision framework was developed, and we focused on glycemic control and adverse events. Subsequently, based on the Evidence-to-Decision framework, a Guideline Development Group of 17 international members made recommendations on Ayurvedic medicines' effectiveness and safety in T2DM. These recommendations formed the basis of the clinical guideline, and additional generic content and recommendations were adapted from the T2DM Clinical Knowledge Summaries of the Clarity Informatics (UK). The feedback given by the Guideline Development Group on the draft version was used to amend and finalize the clinical guideline. Results: A clinical guideline for managing T2DM in adults by Ayurvedic practitioners was developed, which focuses on how practitioners can provide appropriate care, education, and support for people with T2DM (and their carers and family). The clinical guideline provides information on T2DM, such as its definition, risk factors, prevalence, prognosis, and complications; how it should be diagnosed and managed through lifestyle changes like diet and physical activity and Ayurvedic medicines; how the acute and chronic complications of T2DM should be detected and managed (including referral to specialists); and advice on topics like driving, work, and fasting including during religious/socio-cultural festivals. Conclusion: We systematically developed a clinical guideline for Ayurvedic practitioners to manage T2DM in adults.

Markers, Pathways, and Current Evidence for Periodontitis-associated Insulin Resistance: A Narrative Review.

Aims and Objectives: The aim of the present paper is to provide a narrative review of the markers and pathways of periodontitis-associated insulin resistance (IR). Materials and Methods: Research papers published in peer-reviewed scientific journals from 2000 to 2021 were searched systematically in Online Cochrane Library, Google Scholar, and MedLine/PubMed database. The medical subject headings (MeSH) terms used for literature search were "diabetes AND periodontal disease," "diabetes AND periodontitis," "inflammation AND insulin resistance," "Insulin resistance AND periodontal disease," and "insulin resistance AND periodontitis." Manual search for applicable work in review article peer-reviewed print journals, and latest editions of standard textbooks of pharmacology and pathology were searched for updated additional information. Relevant papers in English language on the topic and abstracts of pertinent articles after excluding the duplicates, animal studies, and in-vitro studies were also scrutinized thoroughly and finally included as required in this narrative review. Results: Literature search in MedLine/PubMed with MeSH words mentioned above revealed 4,621, 4,993, 19,349, 414, and 434 papers, respectively. Seven out of 13 systematic reviews and a total of 18 randomized clinical trials to evaluate periodontitis-induced IR were short-listed to update current evidences. The current literature in the past two decades has evaluated the effect of periodontal therapy on various type-2 diabetes (T2D) biomarkers following periodontal therapy. These indicators of periodontal disease activity and surrogate biomarkers of T2D in periodontitis may be an important diagnostic tool for the early prediction of complications due to IR. This increased systemic burden of proinflammatory cytokines by periodontitis can be reduced by periodontal therapy, thus improving the patient's overall systemic condition. Conclusion: The inflammatory response in periodontitis is characterized by dysregulated secretion of host-derived mediators of inflammation and tissue breakdown that may lead to IR. It can be comprehended that periodontal disease is a recognized amendable risk factor for T2D.

Non-medicalization of medical science: Rationalization for future.

As we delve into the intricacies of human disease, millions of people continue to be diagnosed as having what are labelled as pre-conditions or sub-clinical entities and may receive treatments designed to prevent further progression to clinical disease, but with debatable impact and consequences. Endocrinology is no different, with almost every organ system and associated diseases having subclinical entities. Although the expansion of these "grey" pre-conditions and their treatments come with a better understanding of pathophysiologic processes, they also entail financial costs and drug adverse-effects, and lack true prevention, thus refuting the very foundation of Medicine laid by Hippocrates "Primum non nocere" (Latin), i.e., do no harm. Subclinical hypothyroidism, prediabetes, osteopenia, and minimal autonomous cortisol excess are some of the endocrine pre-clinical conditions which do not require active pharmacological management in the vast majority. In fact, progression to clinical disease is seen in only a small minority with reversal to normality in most. Giving drugs also does not lead to true prevention by changing the course of future disease. The goal of the medical fraternity thus as a whole should be to bring this large chunk of humanity out of the hospitals towards leading a healthy lifestyle and away from the label of a medical disease condition.

Gout in Primary Hyperparathyroidism, Connecting Crystals to the Minerals.

Musculoskeletal manifestations in primary hyperparathyroidism (PHPT) range from 13% to 93% encompassing pseudogout, vertebral fracture, myopathy, and cord compression. Though pseudogout has been the most prevalent musculoskeletal condition in PHPT, rarely reports of acute gouty attacks in large joints including the knee have been reported in the literature. Here we detail a unique case of PHPT presenting with acute severe bilateral knee joint inflammatory arthritis accompanied by occasional abdominal pain. Joint aspiration fluid study revealed extracellular monosodium urate crystals exhibiting strong negative birefringence on polarized light microscopy suggestive of acute gouty arthritis. Hypercalcemia and hypophosphatemia with high intact parathyroid hormone (iPTH) confirmed the diagnosis of PHPT and a right inferior parathyroid adenoma was localized. Parathyroidectomy resulted in statistically significant clinical improvement of the debilitating joint manifestations, and the patient was able to walk again without support. Although the incidence of gout is increasing because of an overall increase in metabolic syndrome prevalence, a higher prevalence than in the general population is reported in PHPT. Serum uric acid levels positively correlate with serum iPTH levels in PHPT, and parathyroidectomy leads to a reduction in levels. Acute inflammatory joint pain due to urate crystal deposition in a large joint like the knee is an uncommonly reported condition in PHPT. Identifying the correct etiology in such a case can result in marked clinical improvement in the joint manifestations following surgical cure of hyperparathyroidism.

Diabetic ketoacidosis (DKA) in type 1 diabetes mellitus (T1DM) temporally related to COVID-19 vaccination.

SARS-CoV-2 pandemic has claimed millions of lives since its first identification in December 2019. Patients with diabetes are at a high risk of adverse outcomes after COVID-19 infection, whereas infection itself can be associated with severe hyperglycemia, including hyperglycemic emergencies. While the accelerated vaccine development and rollout have considerably decreased morbidity and mortality with reasonable safety, there are emerging reports of worsening of hyperglycemia in response to vaccination, with possible shared pathophysiology with COVID-19 infection-related hyperglycemia. We hereby report two young patients with type 1 diabetes (T1DM) who presented with severe diabetic ketoacidosis (DKA) after receiving second doses of COVISHIELD (ChAdOx1 nCoV-19) and COVAXIN (BBV152- inactivated whole virion) vaccines. Though a causal link cannot be established, post-vaccination immune response can potentially explain this transient worsening of hyperglycemia and hyperglycemic emergencies. We, hence report diabetic ketoacidosis (DKA) following COVID-19 vaccination in T1DM. We suggest that people with diabetes, particularly patients with T1DM with inadequate glycemic control should ideally be closely monitored for hyperglycemia and ketonemia for at least 2 weeks after receiving vaccination for COVID 19.

Effect of plasma glucose at admission on COVID-19 mortality: experience from a tertiary hospital.

OBJECTIVE: Plasma glucose has been correlated with in-hospital mortality among many diseases including infections. We aimed to study the plasma glucose at the admission of hospitalized patients with COVID-19 at a tertiary care referral hospital at Jodhpur, India and its relation with mortality. DESIGN: A hospital-based clinical study of plasma glucose of COVID-19 patients conducted from May 15 to June 30, 2020 after ethical approval. MEASUREMENTS: Random blood samples at admission were collected for plasma glucose, interleukin-6 (IL6) and high sensitivity C-reactive protein (hsCRP) after written informed consent was obtained. Plasma glucose was analyzed by the automated analyzer, IL6 by chemiluminescent immunoassay and hsCRP by immune-turbidimetric assay. RESULTS: A total of 386 patients were studied (female 39.6%); 11.1% had severe disease and 4.1% expired. There were 67 (17.4%) patients with known diabetes mellitus (DM). Patients with a history of DM had three times higher mortality (6/67, 9%) than those without DM (10/309, 3.1%). Patients with moderate and severe disease according to ICMR and WHO grading had higher plasma glucose than those with asymptomatic or mild disease (P < 0.0001). Plasma glucose levels at admission were significantly higher in non-survivors when compared to those who survived (297 ± 117 vs 131 ± 73; P < 0.0001). COVID-19 patients showed increased mortality with incremental plasma glucose levels. The hazard ratio for mortality was 1.128 (95% CI 0.86-14.860), 1.883 (95% CI 0.209-16.970), and 4.005 (95% CI 0.503-32.677) in random plasma glucose group of >100-200, >200-300 and >300 mg/dL, respectively, compared to those with random plasma glucose of <100 mg/dL at admission. Plasma glucose was strongly correlated with hsCRP (P < 0.001) and IL6 (P < 0.0001). CONCLUSIONS: Plasma glucose at admission in hospitalized COVID-19 patients is a strong predictor of mortality.

Short Stature: Understanding the Stature of Ethnicity in Height Determination.

Height is a polygenic trait with a high degree of heritability. Most (95%) children with short stature (defined as height below the third percentile) and poor growth (growth velocity <5 cm/year) do not have an endocrine disorder. The genetic basis for stature potential has been evaluated in recent years and is increasingly being recognized as a major basis for variation in height between different ethnic populations. Numerous genome-wide association studies have identified hundreds of loci linked to human growth. Apart from the genetic factors, various environmental, nutritional, hormonal, and socioeconomic factors also influence the height, and stature of individuals varies between different geographical locations and ethnic groups. Ethnically different populations might respond differently to the same environmental factors and thus the final height in different ethnic groups is different. This review covers in detail the short stature of African Pygmies and Andamanese Islanders along with the possible causative factors responsible for the variation in height in these ethnic groups.

Relation of Bone Mineral Density with Homocysteine and Cathepsin K levels in Postmenopausal Women.

BACKGROUND: Homocysteine (HCY) interferes with collagen cross-linking in bones and stimulates osteoclast activity. The activated osteoclasts secrete cathepsin K (CathK), a cysteine protease, in eminent quantity during bone resorption. Hyperhomocysteinemia may effect bone mineral density (BMD) through CathK. We, therefore, examined the relation between HCY and BMD along with CathK, 25-hydroxyvit-D (25[OH]D), intact parathyroid hormone (iPTH), and Vitamin B12. MATERIALS AND METHODS: We recruited a total of 93 postmenopausal women between the age group of 45-60 years, attending the Endocrinology outpatient department at King George's Medical University, Lucknow. BMD was done by DXA scan using Hologic QDR1000 system. Based on the WHO criteria, patients were segregated into three groups as follows; normal bone mass, osteopenia, and osteoporosis. All women underwent routine biochemical laboratory parameters, HCY, Vitamin B12, and CathK levels. RESULTS: Among 93 postmenopausal women, 56% (52) had osteoporosis. Nineteen percent (18) had normal BMD (mean age, 53.22 ± 8.5 years) and 23 (25%) had osteopenia (mean age 52.86 ± 6.67 years). The mean age in the osteoporetic group was 56.2 ± 6.9 years. The median (interquartile range) levels of HCY in the three groups were 14.5 µmol/L (12.2-24.7), 15.05 µmol/L (12.1-19.9) and 13.2 µmol/L (10.3-17.0), respectively. CathK levels were similar in three groups 7.6 ng/ml (7.0-80.5), 8.3 ng/ml (7.3-8.5), and 8.6 ng/ml (7.2-8.9). Both HCY and CathK were found positively associated with serum phosphorus (r = 0.584, P < 2.01 and r = 0.249, P < 0.05, respectively). Levels of HCY positively correlate with PTH (r = 0.303, P < 0.01) and inversely with Vitamin B12 (r = -0.248, P < 0.05). No significant association was seen between CathK level and 25(OH) D, iPTH, serum calcium. CONCLUSION: Low bone mass by DXA is a significant problem in postmenopausal females. HCY and CathK do not reliably correlate with bone loss in postmenopausal women although phosphorus metabolism may play a role.

A study of neuroendocrine dysfunction in patients of tuberculous meningitis.

BACKGROUND: Endocrine dysfunction is known to occur in various infectious diseases of the brain. The neuroendocrine dysfunction is not well studied in patients of Tuberculous meningitis (TBM). In this study, we aimed at knowing pattern of endocrine dysfunction in newly diagnosed patients of tuberculous meningitis, structural changes occurring in hypothalamic-pituitary region, assessing its predictors and correlative factors related to outcome. MATERIALS AND METHODS: This was a prospective observational study. All newly diagnosed patients of tuberculous meningitis were subjected to clinical, laboratory, and hormonal evaluation along with neuroimaging of hypothalamic-pituitary region. All the patients were treated with antituberculous drugs along with corticosteroids as per WHO guidelines. The clinical outcomes of the patients were assessed at the end of 3months. RESULTS: Out of 115 patients enrolled in the study, endocrine dysfunction was seen in 62 (53.9%) patients. Out of these 62 patients, single axis involvement was seen in 35 (30.4%) patients, while multiple axis dysfunction was observed in 27 (23.5%) patients. Most common hormonal axis involved was gonadotropic axis (33.9%) followed by hyperprolactinemia (22.6%), thyrotropic axis (17.4%), corticotropic axis (13%), SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion) (9.6%) and somatotropic axis (7.8%). None had diabetes insipidus. The presence of multiple cranial nerve palsies, hypotension, stage II and III of TBM, baseline MBI ≤12 and basal exudates were significantly higher in endocrine dysfunction group, while the presence of basal exudates independently predicted the occurrence of endocrine dysfunction on multivariate analysis. Though the poor outcome was significantly higher in endocrine dysfunction group at the end of 3months, on multivariate analysis factors independently associated with poor outcome were the presence of altered sensorium and stage III of TBM. CONCLUSION: Endocrine dysfunction occurs in a significant proportion of patients with tuberculous meningitis. The presence of basal exudates is significantly associated with the occurrence of endocrine dysfunction. Patients with endocrine dysfunction had a poorer outcome although it was not an independent predictor of the same nor associated with increased mortality.