GLP-1 receptor agonists, SGLT2 inhibitors and noncardiovascular mortality in type 2 diabetes: Insights from a meta-analysis.

OBJECTIVE: Type-2 diabetes (T2D) poses a higher risk of noncardiovascular mortality in addition to the burden of cardiovascular mortality. The well-established cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) could solely explain their apparent effects on all-cause mortality in T2D. The present meta-analysis aims to pool their effects on noncardiovascular mortality in T2D and summarize the recent evidence on plausible pathways mediating these effects. METHODS: PubMed, Embase, Web of Science, and clinical trial registries were searched for randomized controlled trials (RCTs) with ≥1-year duration in adults with T2D reporting both cardiovascular and all-cause mortality in treatment versus placebo arms (PROSPERO: CRD42022337559). Noncardiovascular mortality was calculated by subtracting cardiovascular mortality events from all-cause mortality and risk ratios (RRs) were calculated. Random-effects meta-analysis was done. GRADE framework was used to assess evidence quality. RESULTS: We identified 17 eligible RCTs pooling data retrieved from 109,892 patients. Randomization to GLP-1 RA treatment versus placebo was associated with reduced noncardiovascular mortality (RR = 0.90; 95%CI: 0.81-0.99; I2 = 0 %; p < 0.05), consistent with their effects on cardiovascular mortality (RR = 0.88; 95%CI: 0.81-0.95; I2 = 0 %; p < 0.01) in T2D. Compared to placebo, SGLT2i significantly reduced noncardiovascular mortality (RR = 0.90; 95%CI: 0.82-0.99; I2 = 0 %; p < 0.05) along with cardiovascular mortality (RR = 0.84; 95%CI: 0.77-0.92; I2 = 28 %; p < 0.001). Subgroup analysis showed no significant effects of heart failure or renal function on treatment benefits of SGLT2i on noncardiovascular mortality (p value > 0.2 for subgroup differences). CONCLUSION: The impact of GLP-1RAs and SGLT2i on mortality in people with T2D extends beyond their cardiovascular benefits.

Renal Dysfunction in Primary Hyperparathyroidism is associated with nephrolithiasis, elevated serum calcium-phosphate product and parathormone levels.

PURPOSE: Baseline renal dysfunction predicts mortality in primary hyperparathyroidism (PHPT). However, it remains controversial whether renal insufficiency in PHPT is due to disease severity alone or other risk factors. This study aimed to explore the association of clinico-biochemical variables with renal dysfunction [estimated glomerular filtration rate (eGFR) < 60 ml/min/m2] in PHPT. METHODS: A total of 112 patients of PHPT were selected and divided into following subgroups: renal dysfunction (n = 28) and normal renal function (n = 84). Demographic characteristics, traditional risk factors, phenotypes of PHPT based on target organ involvement, and biochemical parameters were compared between these subgroups. RESULTS: Patient subgroups of PHPT with and without renal dysfunction had similar age, frequency of diabetes, and hypertension. Renal dysfunction was more prevalent in males (p < 0.05). Compared to normal renal function subgroup, individuals with renal dysfunction had higher serum levels of calcium, phosphate, alkaline phosphatase, intact parathormone (all p < 0.05), while having lower hemoglobin levels (p < 0.05) and higher nephrolithiasis rates (p < 0.05). Multiple regression analysis revealed that nephrolithiasis, serum calcium-phosphorous product (CaxP), parathormone levels were positively associated with baseline renal dysfunction (all p < 0.01). A baseline PTH > 456 pg/mL and CaxP > 30.0 mg2/dl2 could discriminate renal dysfunction from normal renal function with sensitivity and specificity of 75% and 74.5% and 92.6% and 74.4%, respectively. CONCLUSION: Renal dysfunction was associated with presence of nephrolithiasis, elevated serum CaxP and PTH levels in our cohort with predominantly symptomatic PHPT, indicating an association with the underlying disease itself. Serum CaxP may additionally be appraised during risk assessment in PHPT.

Integrated Care for Type 1 Diabetes: The West Bengal Model.

Introduction: A structured dedicated health programme for Type 1 diabetes mellitus (T1DM) has been initiated in the state of West Bengal, India. Aim: The aim is to provide comprehensive healthcare to all children, adolescents and young adults living with T1DM, along with the provision of free supply of insulin, glucose measuring devices, blood glucose test strips, and other logistics. The strategic framework for programme implementation is to utilise the infrastructure and manpower of the already existing non-communicable disease (NCD) clinic under National Health Mission. Methodology: Establishing dedicated T1DM clinics in each district hospital by utilising existing healthcare delivery systems, intensive training and hand-holding of named human resources; providing comprehensive healthcare service and structured diabetes education to all T1DM patients; and building an electronic registry of patients are important components of the programme. T1DM clinics run once a week on the same day throughout the state. All T1DM patients are treated with the correct dose of insulin, both human regular insulin and glargine insulin. Patients are routinely monitored monthly to ensure good glycaemic control and prevent complications of the disease. Routine anthropometric examination and required laboratory investigations are conducted in the set-up of the already existing NCD clinic. Ongoing monitoring and evaluation of the T1DM programme are being conducted in terms of glycated haemoglobin (HbA1c) values, growth and development, complication rates, psychological well-being, quality of life, and direct and indirect expenditure incurred by families. Through this programme, any bottlenecks or gaps in service delivery will be identified and corrective measures will be adopted to ensure better health outcomes for those living with T1DM.

Efficacy and Safety of Novel Thiazolidinedione Rivoglitazone in Type-2 Diabetes a Meta-Analysis.

No meta-analysis has analyzed the safety and efficacy of rivoglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for RCTs involving T2DM patients receiving rivoglitazone in the intervention arm, and placebo/active comparator in the control arm. The primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids, and adverse events. From initially screened 24 articles, data from 3 RCTs (3591 patients) that fulfilled all criteria was analzsed. HbA1c was significantly lower with standard-dose (1 mg/d) [MD-0.86% (95%CI:-1.11--0.61); P < 0.01; I2 = 87%] and high-dose (1.5-2 mg/d) [MD-0.97%(95%CI:-1.03--0.90); P < 0.01; I2 = 19%] rivoglitazone compared to placebo. When compared to pioglitazone (30-45 mg/d), HbA1c lowering was comparable with standard-dose [MD 0.05%(95%CI:-0.01 - 0.11); P = 0.08; I2 = 11%], but superior with high-dose [MD -0.11%(95%CI:-0.18- -0.04); P < 0.01; I2 = 0%] rivoglitazone. Triglycerides were significantly lower with standard-dose [MD-17.95 mg/dl (95%CI:-34.23--1.66); P = 0.03; I2 = 0%] and high-dose [MD-40.41 mg/dl (95%CI:-72.90- -7.93);P = 0.01;I2 = 71%] rivoglitazone compared to placebo. Adiponectin significantly improved with standard-dose [MD 7.94 ng/ml (95%CI: 5.48-10.39); P < 0.01;I2 = 98%] and high-dose [MD 13.82 ng/ml (95%CI: 8.16-19.48); P < 0.01; I2 = 100%] rivoglitazone compared to placebo. hsCRP was significantly lower with standard-dose [MD -1.00 mg/L (95% CI: -1.20 - -0.80); P < 0.01; I2 = 6%] and high-dose [MD -1.50 mg/L (95%CI:-1.59- -1.40); P < 0.01; I2 = 0%] rivoglitazone compared to placebo. Treatment-emergent adverse events with standard-dose [Risk ratio (RR) 1.16 (95%CI: 0.84 -1.60); P = 0.38; I2 = 0%] and high-dose [RR1.34 (95%CI: 0.99-1.83); P = 0.06; I2 = 0%] rivoglitazone was comparable to placebo. Severe adverse events with standard-dose [RR1.88 (95%CI: 0.69-5.12);P = 0.22;I2 = 0%] and high-dose [RR 1.27 (95% CI: 0.45 - 3.59); P = 0.68; I2 = 0%] rivoglitazone was comparable to placebo. This meta-analysis highlights the good glycaemic efficacy and safety of both standard and high-dose rivoglitazone, and appears to be better than lobeglitazone in T2DM.

Mineralocorticoid receptor antagonists with sodium-glucose co-transporter-2 inhibitors in heart failure: a meta-analysis.

BACKGROUND AND AIMS: To investigate the cardiovascular effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) with concomitant mineralocorticoid receptor antagonist (MRA) use in heart failure (HF) regardless of ejection fraction (EF) and explore the risk of MRA-associated adverse events in individuals randomized to SGLT2i vs. placebo. METHODS: PubMed/MEDLINE, Web of Science, Embase, and clinical trial registries were searched for randomized controlled trials/post-hoc analyses evaluating SGLT2i in HF with or without MRA use (PROSPERO: CRD42023397129). The main outcomes were composite of first hospitalization or urgent visit for HF/cardiovascular death (HHF/CVD), HHF, and CVD. Others were all-cause mortality, composite renal and safety outcomes. Hazard ratios (HR)/risk ratios were extracted. Fixed-effects meta-analyses and subgroup analyses were performed. RESULTS: Five eligible studies were included, pooling data from 21 947 people with HF (type 2 diabetes mellitus, n = 10 805). Compared to placebo, randomization to SGLT2i showed a similar reduction in HHF/CVD and HHF in people who were or were not using MRAs [HHF/CVD: hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.68-0.81 vs. HR 0.79; 95% CI 0.72-0.86; P-interaction = .43; HHF: HR 0.74; 95% CI 0.67-0.83 vs. HR 0.71; 95% CI 0.63-0.80; P-interaction = .53], with a suggestion of greater relative reduction in CVD in chronic HF people randomized to SGLT2i and using MRAs irrespective of EF (HR 0.81; 95% CI 0.72-0.91 vs. HR 0.98; 95% CI 0.86-1.13; P-interaction = .034). SGLT2i reduced all-cause mortality (P-interaction = .27) and adverse renal endpoints regardless of MRA use (P-interaction = .73) despite a higher risk of volume depletion with concomitant MRAs (P-interaction = .082). SGLT2i attenuated the risk of mild hyperkalaemia (P-interaction < .001) and severe hyperkalaemia (P-interaction = .051) associated with MRA use. CONCLUSIONS: MRAs did not influence SGLT2i effects on the composite of HHF/CVD, HHF or all-cause mortality; however, findings hinted at a more pronounced relative reduction in CVD in chronic HF patients regardless of EF who were randomized to SGLT2i and receiving an MRA compared to those randomized to SGLT2i and not receiving MRAs. SGLT2i attenuated the risk of MRA-associated treatment-emergent hyperkalaemia. These findings warrant further validation in well-designed randomized controlled trials.

Serum uric acid lowering and effects of sodium-glucose cotransporter-2 inhibitors on gout: A meta-analysis and meta-regression of randomized controlled trials.

AIMS: To pool the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on gout and to investigate the association of these effects with baseline serum uric acid (SUA), SUA lowering, and underlying conditions, such as type 2 diabetes mellitus (T2DM)/heart failure (HF). METHODS: PubMed, Embase, Web of Science, Cochrane Library and clinical trial registry websites were searched for randomized controlled trials (RCTs) or post hoc analyses (≥1-year duration; PROSPERO:CRD42023418525). The primary outcome was a composite of gouty arthritis/gout flares and commencement of anti-gout drugs (SUA-lowering drugs/colchicine). Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using a generic inverse-variance method with a random-effects model. Mixed-effects model univariate meta-regression analysis was performed. RESULTS: Five RCTs involving 29 776 patients (T2DM, n = 23 780) and 1052 gout-related events were identified. Compared to placebo, SGLT2 inhibitor use was significantly associated with reduced risk of composite gout outcomes (HR 0.55, 95% CI 0.45-0.67; I2 = 61%, P < 0.001). Treatment benefits did not differ between trials being conducted exclusively in baseline HF versus those conducted in patients with T2DM (P-interaction = 0.37), but were greater with dapagliflozin 10 mg and canagliflozin 100/300 mg (P < 0.01 for subgroup differences). Sensitivity analysis excluding trials that evaluated the effects of empagliflozin 10/25 mg (HR 0.68, 95% CI 0.57-0.81; I2 = 0%) accentuated the benefits of SGLT2 inhibitors with no between-trial heterogeneity (HR 0.46, 95% CI 0.39-0.55; I2 = 0%). Univariate meta-regression found no impact of baseline SUA, SUA lowering on follow-up, diuretic use, or other variables on their anti-gout effects. CONCLUSION: We found that SGLT2 inhibitors significantly reduced the risk of gout in individuals with T2DM/HF. Lack of an association with SUA-lowering effects suggests that metabolic and anti-inflammatory effects of SGLT2 inhibitors may predominantly mediate their anti-gout benefits.

Impact of Heart Failure History at Baseline on Cardiovascular Effects of GLP-1 Receptor Agonists in Type 2 Diabetes: a Meta-analysis.

PURPOSE: Effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type-2 diabetes mellitus (T2DM) with or without prior heart failure (HF) have been inconsistent across cardiovascular outcome trials. This study aimed to investigate the impact of HF history at baseline on cardiovascular effects of GLP-1 RAs in T2DM. METHODS: PubMed, Embase, Web of Science, and clinical trial registries were searched for randomized controlled trials (RCTs) or post hoc analyses (≥ 24 weeks) reporting HF hospitalizations and/or cardiovascular death (HHF/CVD), major adverse cardiovascular events (MACE) comprising of cardiovascular death, myocardial infarction, and stroke in adults with T2DM with or without HF history (PROSPERO:CRD42022367633). Hazard ratios (HRs) in GLP-1RAs versus placebo arms were pooled together using the generic inverse variance method in fixed-effects model. Subgroup analysis was performed. RESULTS: We identified 5 eligible studies, pooling data retrieved from six RCTs and 48,489 individuals with T2DM. On pooled analysis, GLP1RA treatment versus placebo significantly reduced risk of HHF/CVD in only T2DM without HF history (HR = 0.84; 95%CI, 0.77-0.91; I2 = 14%; p < 0.001), but not in those with HF history (HR = 0.96; 95%CI, 0.85-1.08; I2 = 14%; p = 0.4) (p-interaction < 0.1). GLP-1RAs reduced incident HHF in T2DM with or without HF history (HR = 0.89; 95%CI, 0.80-0.98; I2 = 41%; p < 0.05) (p-interaction = 0.28). Sensitivity analysis excluding REWIND trial accentuated the impact of baseline HF history on both HHF/CVD and HHF (p-interaction < 0.05). Benefits on MACE with GLP-1RAs were consistently seen in T2DM regardless of HF history (p-interaction = 0.8). CONCLUSION: GLP-1RAs consistently prevented HF hospitalizations and MACE in T2DM regardless of baseline HF history, whereas significant attenuation of benefits on composite HHF/CV death were observed in those with HF history.

Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Efficacy and Safety of the Novel Dipeptidyl Peptidase-4 Inhibitor Gemigliptin in the Management of Type 2 Diabetes: A Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarised the efficacy and safety of gemigliptin in type 2 diabetes. The meta-analysis addresses this knowledge gap. METHODS: Electronic databases were searched for randomised controlled trials (RCTs) involving diabetes patients receiving gemigliptin in the intervention arm and placebo/active comparator in the control arm. The primary outcome was change in haemoglobin A1c (HbA1c). The secondary outcomes were alterations in glucose, glycaemic targets, lipids, insulin resistance, and adverse events. RESULTS: Data from 10 RCTs involving 1,792 patients were analysed. Four had an active control group (ACG), with metformin/dapagliflozin/sitagliptin/glimepiride as the active comparator; six had a passive control group (PCG), with placebo/rosuvastatin as controls. HbA1c reduction by gemigliptin at 24 weeks was comparable to ACG (mean difference [MD], 0.09%; 95% confidence interval [CI], -0.06 to 0.23; P=0.24; I2=0%; moderate certainty of evidence [MCE]), but superior to PCG (MD, -0.91%; 95% CI, -1.18 to -0.63); P<0.01; I2=89%; high certainty of evidence [HCE]). Gemigliptin was superior to PCG regarding achieving HbA1c <7% (12 weeks: odds ratio [OR], 5.91; 95% CI, 1.34 to 26.08; P=0.02; I2=74%; 24 weeks: OR, 4.48; 95% CI, 2.09 to 9.60; P<0.01; I2=69%; HCE). Gemigliptin was comparable to ACG regarding achieving HbA1c <7% after 24 weeks (OR, 0.92; 95% CI, 0.52 to 1.63; P=0.77; I2=66%; MCE). Adverse events were similar between the gemigliptin and control groups (risk ratio [RR], 1.06; 95% CI, 0.82 to 1.36; P=0.66; I2=35%; HCE). The gemigliptin group did not have increased hypoglycaemia (RR, 1.19; 95% CI, 0.62 to 2.28; P=0.61; I2=19%; HCE). CONCLUSION: Gemigliptin has good glycaemic efficacy and is well-tolerated over 6 months of use.

Challenges in Women with Diabetes During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has created significant challenges for healthcare systems across the world. The disease seems to infect men and women in equal numbers, though trends suggest that men have greater morbidity. This has been attributed to differences in immunological response, expression of angiotensin-converting enzyme 2 (ACE2), prevalence of comorbidities, and health-related behaviours, such as smoking. However, this cannot be taken to mean that women are somehow protected. Advanced age, smoking, diabetes, hypertension, cardiovascular disease and chronic obstructive pulmonary disease have emerged as the leading contributors to increased morbidity and mortality from the disease. Women with diabetes form a vulnerable group as they often receive suboptimal diabetes care and support, even though they have a high burden of comorbidities and complications. While there are challenges in healthcare delivery during the pandemic, cardiometabolic care cannot be compromised, which calls for exploring new avenues of healthcare delivery, such as telemedicine. Pregnant women with diabetes should continue to receive quality care for optimal outcomes, and the psychological health of women also needs special consideration. The management of hyperglycaemia during COVID-19 infection is important to reduce morbidity and mortality from the infection. The gendered impact of outbreaks and quarantine goes beyond biomedical and psychological aspects, and the socioeconomic impact of the pandemic is likely to affect the long-term care of women with diabetes, which creates an urgent need to create effective policies and interventions to promote optimal care in this vulnerable group.

Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement.

Diabetic kidney disease (DKD) occurs in approximately 20-40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (- 21.0%, confidence interval [CI] - 34.1 to - 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52-0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48-0.64, p < 0.0001) with SGLT2i, irrespective of baseline estimated glomerular filtration rate. Thus, there is emerging evidence that SGLT2i may be used to curb the mortality and improve the quality of life in patients with DKD. However, clinicians need to effectively select candidates for SGLT2i therapy. In this consensus statement, we have qualitatively synthesized evidence demonstrating the renal effects of SGLT2i and proposed recommendations for optimal use of SGLT2i to effectively manage and delay progression of DKD.

IDEA Group Consensus Statement on Medical Management of Adult Gender Incongruent Individuals Seeking Gender Reaffirmation as Female.

Cross sex hormone therapy (CSHT) is a strongly desired medical intervention for gender incongruent individuals. The goal is to change secondary sex characteristics to facilitate gender presentation that is consistent with the desired sex. When appropriately prescribed CSHT can greatly improve mental health and quality of life for gender incongruent individuals. Appropriate care for gender incongruent individuals in India is almost absent due to lack of country specific guideline and lack of training amongst the medical professionals. This document is intended to assist endocrinologists and physicians whose adult gender incongruent client is seeking gender reaffirmation as female (transfeminine). These individuals require a safe and effective CSHT regimen that will suppress endogenous male hormone secretion and maintain physiologic levels of female sex hormone. In this document, we offer suggestions based on an in-depth review of Guidelines of Endocrine Society, The World Professional Association for Transgender Health guidelines, the Sappho Good Practice Guide of India and collegial meetings with expert Indian clinicians working in this field. Clinicians represented in our expert panel are not gender specialists by training but have developed expertise due to the volume of gender incongruent individuals they manage. This consensus statement on medical management provides protocols for the prescribing clinician relating to diagnosis, baseline evaluation and counselling, prescription planning for feminizing hormone therapy and anti-androgen therapy, targets for monitoring hormone therapy, choice of therapy, clinical and biochemical monitoring, recommending sex reaffirmation surgery and peri-operative hormone therapy. The recommendations made in this document should not be perceived as a rigid set of guidelines and the treating clinicians are encouraged to modify our suggested protocols to address emerging issues.

Clinical Profile of Asymptomatic Bacteriuria in Type 2 Diabetes Mellitus: An Eastern India Perspective.

INTRODUCTION: Asymptomatic bacteriuria (ASB), believed to precede symptomatic urinary tract infection (UTI) in diabetes mellitus, has geographical variation in microbial pattern and risk factors. However, data from the Eastern part of India are still lacking. MATERIALS AND METHODS: A prospective longitudinal study was performed over 80 otherwise healthy type 2 diabetes patients with a follow-up for one year to (1) estimate the prevalence of ASB and its association with age, gender, duration of diabetes, and renal and glycemic status; and (2) identify the antibiotic sensitivity pattern of uropathogens as well as evaluate the usefulness of microbial pattern as a predictor of symptomatic UTI. RESULTS: ASB was prevalent in 21.25% of type 2 diabetes population in our study. Klebsiella sp emerged as the commonest cause among males. The only risk factor for ASB was found to be long-standing type 2 diabetes. There was no association with age, gender, or recent glycemic status. Bacteriuric patients with worse baseline HbA1C values were at greater risk of UTI. Female diabetic patients with ASB due to Escherichia coli had significantly greater risk of developing UTI within one year. CONCLUSION: A large-scale prospective study reproducing similar findings will genuinely obviate the need to review recommendations on screening of ASB due to E. coli in females with long-standing diabetes and poor glycemic control. Early adoption of stringent HbA1C lowering strategy and measures to improve genital hygiene can help prevent symptomatic UTI in these patients.

Jaundice and anaemia as presenting features of an incomplete autoimmune polyglandular syndrome type II.

The coexistence of adrenal failure with either autoimmune thyroid disease and/or type 1 diabetes is defined as autoimmune polyglandular syndrome (APS) type 2 or Schmidt's syndrome. Vitiligo, hypergonadotropic hypogonadism, chronic autoimmune hepatitis, alopecia, pernicious anaemia and seronegative arthritis may also be present. We present a case of 45-year-old Indian man with progressive jaundice and asthenia for 3 months. He was also found to have pallor, icterus, dry coarse skin and delayed relaxation of ankle jerk. Investigations showed pancytopaenia with megaloblastic changes due to pernicious anaemia, autoimmune hypothyroidism and autoimmune adrenalitis with evolving adrenal insufficiency. Upper gastrointestinal endoscopy guided biopsy showed evidence of gastric mucosal atrophy. Patient responded well to hydroxocobalamin and thyroxine replacement. Detailed workup to check for evolving APS II is prudent in a hypothyroid patient presenting with pallor and jaundice. It may alert physicians to possible adrenal crisis in the future, especially after starting levothyroxine replacement in these patients.

Polypharmacy and comorbidity status in the treatment of type 2 diabetic patients attending a tertiary care hospital: An observational and questionnaire-based study.

PURPOSE/AIM: Diabetes mellitus is associated with several comorbid conditions. Thus, often, diabetic patients are prescribed multiple drugs. Although multiple drugs help to combat various diseases, they also increase the propensity of drug interactions and adverse drug reactions. The present study thus tried to evaluate the comorbid conditions and concurrent medications associated with type 2 diabetic patients. It also aimed to address patient compliance for the medications provided to them. MATERIALS AND METHODS: This was a cross-sectional observational study conducted for 2 months - January-February 2017. Data were collected from prescriptions of the patients and also by interviewing the willing patients, attending the Diabetic Clinic of R. G. Kar Medical College, Kolkata, India. RESULTS: During the study period, 150 patients were interviewed and their prescriptions were studied. Out of 150 patients, 69 (46%) were males and 81 (54%) were females. The mean age of the study population was 51.5 (±0.78) years. The present study evaluated that 83.3% (125) of the study population suffered from at least one comorbid conditions, the most common being hyperlipidemia (70.7%) and hypertension (47.3%). The average number of drugs prescribed is 4.72 (±0.11) per prescription. Metformin was prescribed to 96% of the patients. The concurrent medications recommended included hypolipidemics (72%), antihypertensives (68%), drugs for peptic ulcer (34.7%), and antiplatelets (10.7%). CONCLUSION: The present study thus concluded that diabetic patients suffer from a number of comorbid conditions, most commonly, cardiovascular problems. The comorbidity increased with the age. The level of polypharmacy was also high, thereby increasing the pill burden for the patients.

Occurrence of osteoporosis & factors determining bone mineral loss in young adults with Graves' disease.

BACKGROUND & OBJECTIVES: There is a paucity of data with conflicting reports regarding the extent and pattern of bone mineral (BM) loss in Graves' disease (GD), especially in young adults. Also, interpretation of BM data in Indians is limited by use of T-score cut-offs derived from Caucasians. This study was aimed to evaluate the occurrence of osteoporosis in active treatment naive patients with GD and determine the factors predicting BM loss, using standard T-scores from Caucasians and compare with the cut-offs proposed by the Indian Council of Medical Research (ICMR) for diagnosing osteoporosis in Indians. METHODS: Patients with GD, >20 yr age without any history of use of anti-thyroid drugs, and normal controls without fracture history, drugs use or co-morbidities underwent BM density (BMD) assessment at lumbar spine, hip and forearm, thyroid function and calcium profile assessment. Women with menopause or premature ovarian insufficiency and men with androgen deficiency were excluded. RESULTS: p0 atients with GD (n=31) had significantly lower BMD at spine (1.01±0.10 vs. 1.13±0.16 g/cm 2 ), hip (0.88±0.10 vs. 1.04±0.19 g/cm 2 ) and forearm (0.46±0.04 vs. 0.59±0.09 g/cm 2 ) compared with controls (n=30) (P<0.001). Nine (29%) and six (19.3%) patients with GD had osteoporosis as per T-score and ICMR criteria, respectively. None of GD patients had osteoporosis at hip or spine as per ICMR criteria. Serum T 3 had strongest inverse correlation with BMD at spine, hip and femur. Step-wise linear regression analysis after adjusting for age, BMI and vitamin D showed T 3 to be the best predictor of reduced BMD at spine, hip and forearm, followed by phosphate at forearm and 48 h I 131 uptake for spine BMD in GD. INTERPRETATION & CONCLUSIONS: Osteoporosis at hip or spine is not a major problem in GD and more commonly involves forearm. Diagnostic criterion developed from Caucasians tends to overdiagnose osteoporosis in Indians. T 3 elevation and phosphate are important predictors of BMD. Baseline I 131 uptake may have some role in predicting BMD.

Increased Soluble TNF Receptor-1 and Glutathione Peroxidase may Predict Carotid Intima Media Thickness in Females with Cushing Syndrome.

OBJECTIVE: Cardiovascular events are the most common cause of mortality in Cushing syndrome (CS). This study aimed to evaluate the impact of novel factors on atherosclerosis in endogenous CS. METHODS: A total of 22 female patients with CS and 33 normal female controls underwent evaluation of fibrinogen, high-sensitivity C-reactive protein (hsCRP), inflammatory cytokines (interleukin [IL]-6, IL-1ß, soluble tumor necrosis factor receptor [sTNFR]-1, and sTNFR2), glutathione peroxidase (GPx; measure of oxidative stress), carotid intima media thickness (CIMT; a measure of atherosclerosis), and percent change in flow-mediated vasodilation (%FMV) of the brachial artery, a measure of endothelial dysfunction. Stepwise multiple linear regressions were done after adjusting for variables in models 1 through 3 to evaluate their role in predicting CIMT and %FMV. Model 1 consisted of age and body mass index (BMI). Model 2 consisted of model 1 plus blood pressure (BP), fasting blood glucose (FBG), and 2-hour postglucose blood glucose (2hPGBG). Model 3 consisted of model 2 plus triglycerides and low- and high-density lipoprotein. RESULTS: Females with CS had significantly higher BMI, BP, FBG, 2hPGBG, total cholesterol, triglycerides, fibrinogen, IL-6, IL-1ß, sTNFR1, and GPx. CIMT and %FMV were significantly higher and lower, respectively, in CS patients. Regression analyses revealed sTNFR1 to be a consistent predictor of CIMT after adjusting for model 1 (ß = 0.656; P = .004), model 2 (ß = 0.571; P = .047), and model 3 (ß = 0.683; P =.026). GPx was a predictor of CIMT after adjusting for model 1 (ß = 0.565; P = .033) and model 3 (ß = 0.756; P= .038). CONCLUSION: This study highlights increased CIMT and endothelial dysfunction in CS, associated with an altered inflammatory milieu. sTNFR1 and GPx may predict CIMT in females with CS.

Percutaneous ethanol ablation in managing predominantly cystic thyroid nodules: An eastern India perspective.

AIMS: Percutaneous aspiration and ethanol injection (PEI) is effective in managing predominantly cystic (>50% cystic) thyroid nodules with efficacy ranging from 38-85%. We aimed to evaluate efficacy, safety, and factors determining outcomes of PEI in managing simple cystic (purely cystic) vs. complex cystic (having both cystic and solid components) thyroid nodules. MATERIALS AND METHODS: Predominantly cystic thyroid nodules, without any ultrasonography and/or fine needle aspiration, evidence of malignancy were aspirated ultrasonography guided. Sterile 100% ethanol (50-100% volume aspirated) was injected and reviewed monthly for 3 months and thereafter 3 monthly. Responders were defined as ≥ 50% reduction in nodule volume. RESULTS: Sixty-five patients out of 152 considered underwent PEI. Sixty patients [simple cystic (42) and complex cystic (18)] with mean follow-up of 12.3 ± 2.88 months were analyzed. Response rate of PEI was 78.33% [simple cystic (92.86%) and complex cystic (44.44%) nodules; P < 0.001]. Also, 31.67% patients achieved remission at 1(st) month. And, 46.67% patients achieved remission between 1-6-months follow-up. Kaplan Meier analysis showed significantly improved outcomes in patients with simple cystic nodules (P < 0.001). Cox-regression revealed type of nodule (simple cystic vs. complex cystic) to be predictive of outcome (P = 0.034). Complex cystic nodules were 67.6% less likely to go into remission, compared to simple cystic nodules. Baseline nodule size, aspirate, or volume of ethanol injected did not predict outcome. CONCLUSIONS: PEI is safe and should be treatment of choice for simple cystic thyroid nodules. PEI for complex cystic thyroid nodules are associated with lower response, increased recurrence, and need for repeated PEI.