Call to action for a life course approach.

Gestational diabetes remains the most common medical disorder in pregnancy, with short-term and long-term consequences for mothers and offspring. New insights into pathophysiology and management suggest that the current gestational diabetes treatment approach should expand from a focus on late gestational diabetes to a personalised, integrated life course approach from preconception to postpartum and beyond. Early pregnancy lifestyle intervention could prevent late gestational diabetes. Early gestational diabetes diagnosis and treatment has been shown to be beneficial, especially when identified before 14 weeks of gestation. Early gestational diabetes screening now requires strategies for integration into routine antenatal care, alongside efforts to reduce variation in gestational diabetes care, across settings that differ between, and within, countries. Following gestational diabetes, an oral glucose tolerance test should be performed 6-12 weeks postpartum to assess the glycaemic state. Subsequent regular screening for both dysglycaemia and cardiometabolic disease is recommended, which can be incorporated alongside other family health activities. Diabetes prevention programmes for women with previous gestational diabetes might be enhanced using shared decision making and precision medicine. At all stages in this life course approach, across both high-resource and low-resource settings, a more systematic process for identifying and overcoming barriers to preventative care and treatment is needed to reduce the current global burden of gestational diabetes.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Late-night salivary cortisol cut-offs for diagnosis of Cushing syndrome using second-generation electrochemiluminescence immunoassay kits.

CONTEXT: Late-night salivary cortisol (LNSC) is a simple and reliable screening test for Cushing syndrome (CS). With improved analytical performance of the current second-generation electrochemiluminescence immunoassay (ECLIA; Elecsys Cortisol-II; Roche Diagnostics), there is a need to revisit the LNSC cut-offs, especially in a South-Asian population. OBJECTIVE: To derive LNSC cut-offs for diagnosis of CS using second-generation ECLIA kits. DESIGN: Diagnostic accuracy study. METHODS: We prospectively recruited 155 controls aged 18-60 years, including, normal-weight (body mass index [BMI] < 25 kg/m2 and no hypertension or diabetes [n = 53]) and overweight/obese (BMI 25-30 kg/m2 and hypertension and/or diabetes [n = 52] or BMI ≥ 30 kg/m2 with/without comorbidities [n = 50]) participants. All participants submitted LNSC samples collected at home; overweight/obese controls additionally underwent dexamethasone suppression test to exclude CS. We also reviewed records of adults with endogenous CS (cases, n = 92) and a valid LNSC result using the same method. RESULTS: The 95th percentile for LNSC in controls was 6.76 nmol/L. The mean ± SD LNSC levels were 40.47 ± 49.63 nmol/L in cases and 3.37 ± 1.18 nmol/L in controls (p < 0.001). Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance of LNSC for CS, with area under curves (AUCs) of 0.994 (cases vs. all controls) and 0.993 (cases vs. overweight/obese controls), respectively. The best diagnostic performance was achieved at cut-offs ≥6.73 nmol/L (sensitivity: 97.8%, specificity: 94.8%) and ≥7.26 nmol/L (sensitivity: 97.8%, specificity: 95.1%), respectively. CONCLUSIONS: LNSC measured using second-generation ECLIA demonstrated high diagnostic accuracy for CS. Based on this study, we propose a LNSC cutoff ≥6.73 nmol/L to diagnose CS.

Bone microarchitecture, bone mineral density and bone turnover in association with glycemia and insulin action in women with prior gestational diabetes.

OBJECTIVE: The aim of this cross-sectional study was to comprehensively assess bone health in women with prior gestational diabetes mellitus, including bone microarchitecture (TBS), bone mineral density (BMD, DXA) and bone turnover (osteocalcin). DESIGN, PATIENTS AND MEASUREMENTS: Study participants underwent a detailed anthropometric, biochemical and hormone assessment, including insulin and osteocalcin measurement. BMD was measured at lumbar spine, femur neck and total hip using DXA and TBS derived from lumbar spine DXA images using TBS iNsight software. RESULTS: A total of 240 women (mean age: 33.3 ± 5.0 years; median postpartum duration: 34 [interquartile range 13.0-54.5] months were evaluated. At the current visit, 115 (47.9%) and 36 (15%) women had prediabetes and diabetes, respectively. Women with dysglycemia (diabetes/prediabetes) had a higher BMD at all three sites, compared to those with normoglycemia; however, the difference was not statistically significant. Women with dysglycemia had a significantly lower TBS (1.32 ± 0.09 vs. 1.35 ± 0.09; p = .038). In the fully adjusted model, the odds ratio for association between diabetes and low TBS was 2.92 (95% confidence interval: 1.20, 7.08; p = .018). Women with dysglycemia had significantly lower serum osteocalcin levels (18.6 ± 8.5 ng/ml vs. 21.5 ± 9.7 ng/ml; p = .018). HOMA-IR (r = -.285, p < .001) was negatively correlated, while Matsuda index (r = .274, p < .001) and disposition index (r = .159, p = .016) were positively correlated with serum osteocalcin levels. CONCLUSIONS: Bone health is affected early in the natural history of diabetes and is associated with an overall low bone turnover state.

SARS-CoV-2 Seroprevalence in Individuals With Type 1 and Type 2 Diabetes Compared With Controls.

OBJECTIVE: Data for the association between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility are conflicting. We aimed to evaluate this association using an analytical cross-sectional study design. METHODS: Study participants were recruited from endocrine clinics of our hospital and belonged to 3 groups: group 1 (type 1 diabetes mellitus [T1DM]), group 2 (type 2 diabetes mellitus [T2DM]), and group 3 (controls). All participants submitted blood samples for SARS-CoV-2 S1/S2 immunoglobulin G antibody test (LIAISON; DiaSorin) and were interviewed for a history of documented infection. RESULTS: We evaluated a total of 643 participants (T1DM, 149; T2DM, 160; control, 334; mean age, 37.9 ± 11.5 years). A total of 324 (50.4%) participants were seropositive for SARS-CoV-2. The seropositivity rate was significantly higher in the T1DM (55.7% vs 44.9%, P = .028) and T2DM (56.9% vs 44.9%, P = .013) groups than in the control group. The antibody levels in seropositive participants with T1DM and T2DM were not significantly different from those in seropositive controls. On multivariable analysis, low education status (odds ratio [OR], 1.41 [95% CI, 1.03-1.94]; P = .035), diabetes (OR, 1.68 [95% CI, 1.20-2.34]; P = .002), and overweight/obesity (OR, 1.52 [95% CI, 1.10-2.10]; P = .012) showed a significant association with SARS-CoV-2 seropositivity. The association between diabetes and SARS-CoV-2 seropositivity was found to further increase in participants with coexisting overweight/obesity (adjusted OR, 2.63 [95% CI, 1.54-4.47]; P < .001). CONCLUSION: SARS-CoV-2 seropositivity, assessed before the onset of the national vaccination program, was significantly higher in participants with T1DM and T2DM than in controls. The antibody response did not differ between seropositive participants with and without diabetes. These findings point toward an increased SARS-CoV-2 susceptibility for patients with diabetes, in general, without any differential effect of the diabetes type.

Improving care for hypertension and diabetes in india by addition of clinical decision support system and task shifting in the national NCD program: I-TREC model of care.

BACKGROUND: The growing burden of hypertension and diabetes is one of the major public health challenges being faced by the health system in India. Clinical Decision Support Systems (CDSS) that assist with tailoring evidence-based management approaches combined with task-shifting from more specialized to less specialized providers may together enhance the impact of a program. We sought to integrate a technology "CDSS" and a strategy "Task-shifting" within the Government of India's (GoI) Non-Communicable Diseases (NCD) System under the Comprehensive Primary Health Care (CPHC) initiative to enhance the program's impact to address the growing burden of hypertension and diabetes in India. METHODS: We developed a model of care "I-TREC" entirely calibrated for implementation within the current health system across all facility types (Primary Health Centre, Community Health Centre, and District Hospital) in a block in Shaheed Bhagat Singh (SBS) Nagar district of Punjab, India. We undertook an academic-community partnership to incorporate the combination of a CDSS with task-shifting into the GoI CPHC-NCD system, a platform that assists healthcare providers to record patient information for routine NCD care. Academic partners developed clinical algorithms, a revised clinic workflow, and provider training modules with iterative collaboration and consultation with government and technology partners to incorporate CDSS within the existing system. DISCUSSION: The CDSS-enabled GoI CPHC-NCD system provides evidence-based recommendations for hypertension and diabetes; threshold-based prompts to assure referral mechanism across health facilities; integrated patient database, and care coordination through workflow management and dashboard alerts. To enable efficient implementation, modifications were made in the patient workflow and the fulcrum of the use of technology shifted from physician to nurse. CONCLUSION: Designed to be applicable nationwide, the I-TREC model of care is being piloted in a block in the state of Punjab, India. Learnings from I-TREC will provide a roadmap to other public health experts to integrate and adapt their interventions at the national level. TRIAL REGISTRATION: CTRI/2020/01/022723.

The Integrated Tracking, Referral, and Electronic Decision Support, and Care Coordination (I-TREC) program: scalable strategies for the management of hypertension and diabetes within the government healthcare system of India.

BACKGROUND: Hypertension and diabetes are among the most common and deadly chronic conditions globally. In India, most adults with these conditions remain undiagnosed, untreated, or poorly treated and uncontrolled. Innovative and scalable approaches to deliver proven-effective strategies for medical and lifestyle management of these conditions are needed. METHODS: The overall goal of this implementation science study is to evaluate the Integrated Tracking, Referral, Electronic decision support, and Care coordination (I-TREC) program. I-TREC leverages information technology (IT) to manage hypertension and diabetes in adults aged ≥30 years across the hierarchy of Indian public healthcare facilities. The I-TREC program combines multiple evidence-based interventions: an electronic case record form (eCRF) to consolidate and track patient information and referrals across the publicly-funded healthcare system; an electronic clinical decision support system (CDSS) to assist clinicians to provide tailored guideline-based care to patients; a revised workflow to ensure coordinated care within and across facilities; and enhanced training for physicians and nurses regarding non-communicable disease (NCD) medical content and lifestyle management. The program will be implemented and evaluated in a predominantly rural district of Punjab, India. The evaluation will employ a quasi-experimental design with mixed methods data collection. Evaluation indicators assess changes in the continuum of care for hypertension and diabetes and are grounded in the Reach, Effectiveness, Adoption Implementation, and Maintenance (RE-AIM) framework. Data will be triangulated from multiple sources, including community surveys, health facility assessments, stakeholder interviews, and patient-level data from the I-TREC program's electronic database. DISCUSSION: I-TREC consolidates previously proven strategies for improved management of hypertension and diabetes at single-levels of the healthcare system into a scalable model for coordinated care delivery across all levels of the healthcare system hierarchy. Findings have the potential to inform best practices to ultimately deliver quality public-sector hypertension and diabetes care across India. TRIAL REGISTRATION: The study is registered with Clinical Trials Registry of India (registration number CTRI/2020/01/022723 ). The study was registered prior to the launch of the intervention on 13 January 2020. The current version of protocol is version 2 dated 6 June 2018.

Diabeto-theranostics.

This communication is an interesting and off-beat take on the concept of theranostics, as applied to diabetes care. It proposes the use of the term diabeto-theranostics, to define the combined use of diagnostic and therapeutic modalities, so as to create individualized or personalized treatment strategies in persons with diabetes. Historical examples such as the chlorpropamide challenge test and modern innovations such as genotyping are described. The rubrics of gluco-phenotype, endo-phenotype, metabolic phenotype, glucagon: insulin ratio, and adenosine monophosphate activated protein kinase (AMPK) status in planning glucose lowering therapy are explained. Novel concepts such as psycho-theranostics and electro-theranostics in diabetes are discussed.

Concordance of glycaemic and cardiometabolic traits between Indian women with history of gestational diabetes mellitus and their spouses: an opportunity to target the household.

AIMS/HYPOTHESIS: The aim of this study was to investigate the concordance of dysglycaemia (prediabetes or diabetes) and cardiometabolic traits between women with a history of gestational diabetes mellitus (GDM) and their spouses. METHODS: Using hospital medical records, women with GDM (diagnosed between 2012 and 2016) and their spouses were invited to participate in the study and to attend a scheduled hospital visit in a fasting state. Sociodemographic, anthropometric and medical data were collected, and a 75 g OGTT with serum insulin estimation, HbA1c measurement and fasting lipid profile were performed at the visit. Prediabetes and diabetes were defined using ADA criteria and the metabolic syndrome was defined using IDF criteria. RESULTS: A total of 214 couples participated in the study. Women were tested at a mean ± SD age of 32.4 ± 4.6 years and median (quartile [q]25-q75) of 19.5 (11-44) months following the index delivery, while men were tested at a mean ± SD age of 36.4 ± 5.4 years. A total of 72 (33.6%) couples showed concordance for dysglycaemia, while 99 (46.3%) and 51 (23.8%) couples were concordant for overweight/obesity and the metabolic syndrome, respectively. A total of 146 (68.2%) couples showed concordance for any of the above three factors. The presence of dysglycaemia in one partner was associated with an increased risk of dysglycaemia in the other partner (OR 1.80 [95% CI 1.04, 3.11]). Similarly, being overweight/obese (OR 2.19 [95% CI 1.22, 3.93]) and presence of the metabolic syndrome (OR 2.01 [95% CI 1.16, 3.50]) in one partner was associated with an increased risk of these conditions in the other partner. Both women and men were more likely to have dysglycaemia if they had a partner with dysglycaemia. Women with a partner with dysglycaemia had a significantly higher BMI, waist circumference and diastolic BP, and a significantly higher probability of low HDL-cholesterol (<1.29 mmol/l) and the metabolic syndrome compared with women with a normoglycaemic partner. No such differences were observed for men with or without a partner with dysglycaemia. CONCLUSIONS/INTERPRETATION: The high degree of spousal concordance found in this study suggests social clustering of glycaemic and cardiometabolic traits among biologically unrelated individuals. This provides us with an opportunity to target the behavioural interventions at the level of the 'married couple', which may be a novel and cost-effective method of combating the current diabetes epidemic.

Type 2 diabetes care and the law of endocrine parsimony.

Diabetes care has become more and more complex and challenging. For the practicing physician, advances in pathophysiology and diagnostic/ monitoring tools are welcome, as they enhance understanding of the syndrome, its causation, and its natural history. The surfeit of drug classes and drugs available today however, create confusion and chaos as well. The almost infinite number of permutations and combinations that these can be used, poses a dilemma for the diabetes care professional. This communication proposes the Law of Endocrine Parsimony, and relates it to therapeutic targets as well as strategies in type 2 diabetes care. The Law of Endocrine Parsimony assists in decision making by positing: Hormones which are secreted in excess must be reduced, before trying to increase hormones which are relatively deficient, while managing diabetes.

Osteovigilance in diabetes.

Osteovigilance is a state of clinical suspicion for abnormalities of bone and mineral metabolism , including efforts to optimize bone mineral health .In this article, we discuss various factors which contribute to coexistence of diabetes and bone mineral disease, the risk factors that they share, and iatrogenic and therapeutic considerations of importance. We highlight the need to practice osteovigilance as an integral part of diabetes management.

Glucocrinology.

Diabetes is a complex syndrome, with multiple pathophysiologic connections. While the vasculometabolic aspects are certainly important, current discourse tends to ignore the endocrine facets of diabetes. We propose the term 'glucocrinology', to define the study of medicine that relates to the relationship of glycaemia with the endocrine system. Glucocrinology includes in its ambit, endocrinopathies that may cause secondary diabetes, coexist with metabolic syndrome, precipitate hypoglycaemia, lead to refractory hyperglycaemia, or simply coexist with diabetes. The concept also covers the role of endocrinotropic drugs in unmasking latent diabetes, worsening hyperglycaemia, or managing diabetes in specific situations, as well as antidiabetic drugs in modulating endocrine disease. Highlighting glucocrinology as a distinct field will enhance the quality of diabetes care, by making it more holistic, comprehensive and clinically oriented. This article will be followed by gland-specific reviews of glucocrinology.

Prevention of hypoglycaemia, the ASAP (Anticipate, Suspect, Act, Prevent) strategy.

This article describes a simple framework to prevent hypoglycaemia. Four strategies of prevention are detailed, which correspond to four levels of prevention (primordial, primary, secondary and tertiary). This framework, given the mnemonic ASAP (As Soon As Possible) includes action to Anticipate and Avoid, and Suspect and Screen hypoglycaemia. It also enjoins us to Act and Assist persons with hypoglycaemia in a timely manner, while working to Prevent and Protect them by using safer glucose lowering drugs and insulins.

Preconception management of thyroid disorders.

Thyroid function is closely interlinked with pregnancy. Maternal and foetal outcomes can be improved if optimal thyroid function is achieved, and maintained prior to conception. This needs a systematic approach which includes rational screening, appropriate management, and pragmatic counseling. This review describes pre-conception management of thyroid disorders, and completes an earlier article on preconception management of other endocrine diseases.

Relationship Between BMD and Prevalent Vertebral Fractures in Indian Women Older Than 50 Yr.

The purpose of the study was to study the relationship of morphometric vertebral fractures with bone mineral density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip, and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment.

Choosing injectable therapy: The metabolic fulcrum.

This clinical decision making hypothesis utilizes the metabolic fulcrum based approach to classify persons with diabetes into three categories: predominantly catabolic, eubolic, and predominantly [maladaptive] anabolic. This systematic arrangement helps define choice of injectable therapy in type 2 diabetes mellitus. Patients with predominant catabolism, may respond better to intensive insulin therapy. Dual action insulin, including premixed insulin and I Deg Asp (insulin degludec aspart), may be an acceptable alternative. Uncomplicated, eumetabolic patients with type 2 diabetes may use any of the various drugs available. Patients classified as having maladaptive anabolism may benefit from a GLP1RA. If this does not suffice, a GLP1RA + basal insulin combination may be effective.