Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy.

BACKGROUND: Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS: We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS: A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, -0.04 kg; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS: Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.).

Glycaemic control is still central in the hierarchy of priorities in type 2 diabetes management.

A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes.

Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality.

BACKGROUND: Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population. METHODS: This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause. RESULTS: In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease. CONCLUSIONS: In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death. (Funded by the Population Health Research Institute and others.).

Factors influencing diabetes treatment satisfaction in the INtegrating DEPrEssioN and Diabetes treatmENT randomized clinical trial: A multilevel model analysis.

AIMS: Patient satisfaction is associated with positive diabetes outcomes. However, there are no identified studies that evaluate both patient- and clinic-level predictors influencing diabetes care satisfaction longitudinally. METHODS: Data from the INtegrating DEPrEssioN and Diabetes treatmENT trial was used to perform the analysis. We used fixed and random effects models to assess whether and how changes in patient-level predictors (treatment assignment, depression symptom severity, systolic blood pressure, body mass index, LDL cholesterol, and haemoglobin A1C) from 0 to 24 months and clinic-level predictors (visit frequency, visit cost, number of specialists, wait time, time spent with healthcare provider, and receiving verbal reminders) measured at 24 months influence diabetes care satisfaction from 0 to 24 months. RESULTS: Model 1 (patient-level predictors) accounted for 7% of the change in diabetes satisfaction and there was a significant negative relationship between change in depressive symptoms and care satisfaction (ß = -0.23, SE = 0.12, p < 0.05). Within Model 1, 2% of the variance was explained by clinic-level predictors. Model 2 included both patient- and clinic-level predictors and accounted for 18% of the change in diabetes care satisfaction. Within Model 2, 9% of the variance was attributed to clinic-level predictors. There was also a cross-level interaction where the change in depression had less of an impact on the change in satisfaction for those who received a verbal reminder (ß = -0.11, SE = 0.21, p = 0.34) compared with those who did not receive a reminder (ß = -0.62, SE = 0.08, p < 0.01). CONCLUSIONS: Increased burden of depressive symptoms influences diabetes care satisfaction. Clinic-level predictors also significantly influence diabetes care satisfaction and can reduce dissatisfaction in primary care, specifically, reminder calls from clinic staff.

Effect of treatment for early gestational diabetes mellitus on neonatal respiratory distress: A secondary analysis of the TOBOGM study.

OBJECTIVE: To identify factors associated with neonatal respiratory distress (NRD) in early Gestational diabetes mellitus (eGDM). DESIGN: Nested case-control analysis of the TOBOGM trial. SETTING: Seventeen hospitals: Australia, Sweden, Austria and India. POPULATION: Pregnant women, <20 weeks' gestation, singleton, GDM risk factors. METHODS: Women with GDM risk factors completed an oral glucose tolerance test (OGTT) before 20 weeks: those with eGDM (WHO-2013 criteria) were randomised to immediate or deferred GDM treatment. Logistic regression compared pregnancies with/without NRD, and in pregnancies with NRD, those with/without high-dependency nursery admission for ≤24 h with those admitted for >24 h. Comparisons were adjusted for age, pre-pregnancy body mass index, ethnicity, smoking, primigravity, education and site. Adjusted odds ratios (95% CI) are reported. MAIN OUTCOME MEASURES: NRD definition: ≥4 h of respiratory support (supplemental oxygen or supported ventilation) postpartum. Respiratory distress syndrome (RDS): Supported ventilation and ≥24 h nursery stay. RESULTS: Ninety-nine (12.5%) of 793 infants had NRD; incidence halved (0.50, 0.31-0.79) if GDM treatment was started early. NRD was associated with Caesarean section (2.31, 1.42-3.76), large for gestational age (LGA) (1.83, 1.09-3.08) and shorter gestation (0.95, 0.93-0.97 per day longer). Among NRD infants, >24 h nursery-stay was associated with higher OGTT 1-h glucose (1.38, 1.08-1.76 per mmol/L). Fifteen (2.0%) infants had RDS. CONCLUSIONS: Identifying and treating eGDM reduces NRD risk. NRD is more likely with Caesarean section, LGA and shorter gestation. Further studies are needed to understand the mechanisms behind this eGDM complication and any long-term effects.

Construct validity of the 12-item Short Form Health Survey (SF-12) version 2 and the impact of lifestyle modifications on the health-related quality of life among Indian adults with prediabetes: results from the D-CLIP trial.

PURPOSE: This study aimed to validate the factor structure of the 12-item Short-Form (SF-12) health-related quality of life (HRQOL) survey for Indian adults and assess the impact of lifestyle modification on the SF-12 of Indian adults with prediabetes. METHODS: To validate the context-specific construct of the SF-12, two-factor confirmatory factor analysis (CFA) was performed using data from 1285 adults residing in Chennai, India, who screened for the Diabetes Community Lifestyle Improvement Program (D-CLIP). D-CLIP was a randomized controlled trial of 578 participants with prediabetes (283 treatment, 293 control), focusing on the effect of lifestyle modifications on the prevention of diabetes. Physical and mental component scores (PCS and MCS) were computed by using CFA standardized factor loadings. Multiple linear regression was subsequently conducted to estimate the effect of lifestyle modification on post-study changes of PCS and MCS among D-CLIP participants. RESULTS: Cronbach's alpha and CFA fit indices demonstrated acceptable reliability and model fit of the SF-12 for Indian adults. The intervention group showed greater mean change in PCS after study participation compared to the controls (1.63 ± 0.82, p = 0.046); no significant difference was observed for MCS between two groups (1.00 ± 0.85, p = 0.242). CONCLUSION: The study confirmed that the SF-12 is suitable for assessing the physical and mental health dimensions of HRQOL for Indian adults. Our findings suggest that the benefits of diabetes prevention lifestyle modification strategies may primarily enhance the physical well-being of adults with prediabetes. Further studies validating the SF-12 in a broader Asian Indian population are needed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01283308.

Circulatory levels of lysophosphatidylcholine species in obese adolescents: Findings from cross-sectional and prospective lipidomics analyses.

BACKGROUND AND AIMS: Obesity has reached epidemic proportions, emphasizing the importance of reliable biomarkers for detecting early metabolic alterations and enabling early preventative interventions. However, our understanding of the molecular mechanisms and specific lipid species associated with childhood obesity remains limited. Therefore, the aim of this study was to investigate plasma lipidomic signatures as potential biomarkers for adolescent obesity. METHODS AND RESULTS: A total of 103 individuals comprising overweight/obese (n = 46) and normal weight (n = 57) were randomly chosen from the baseline ORANGE (Obesity Reduction and Noncommunicable Disease Awareness through Group Education) cohort, having been followed up for a median of 7.1 years. Plasma lipidomic profiling was performed using the UHPLC-HRMS method. We used three different models adjusted for clinical covariates to analyze the data. Clustering methods were used to define metabotypes, which allowed for the stratification of subjects into subgroups with similar clinical and metabolic profiles. We observed that lysophosphatidylcholine (LPC) species like LPC.16.0, LPC.18.3, LPC.18.1, and LPC.20.3 were significantly (p < 0.05) associated with baseline and follow-up BMI in adolescent obesity. The association of LPC species with BMI remained consistently significant even after adjusting for potential confounders. Moreover, applying metabotyping using hierarchical clustering provided insights into the metabolic heterogeneity within the normal and obese groups, distinguishing metabolically healthy individuals from those with unhealthy metabolic profiles. CONCLUSION: The specific LPC levels were found to be altered and increased in childhood obesity, particularly during the follow-up. These findings suggest that LPC species hold promise as potential biomarkers of obesity in adolescents, including healthy and unhealthy metabolic profiles.

Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: a cross-sectional analysis across 11 prospective studies.

BACKGROUND: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. METHODS: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. RESULTS: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. CONCLUSIONS: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.

Diet, cardiovascular disease, and mortality in 80 countries.

AIMS: To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. METHODS AND RESULTS: A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). CONCLUSION: A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

Assessment of microplastics in highland rock salts of Northern Borneo.

Mountain salts produced from the highland region in NE Sarawak have a market value and also provide basic income to the communities. During the salt-making process, microplastics (MPs) may enter into commercial table salts from various sources, which has not been explored yet. Hence, the current research investigates the presence of MPs in the rock salts produced from the highland saline water in two different locations (L1 and L2) in NE Sarawak. Among the brine water and rock salt samples analysed, the highest concentrations of MPs were detected from the salt samples. It has been revealed that both the water and salt samples have the highest concentration of MPs occurring within the size range of 1-1000 µm. Transparent MPs are the most common colour observed in both salt and water samples, followed by white, blue, red, and black. The most prevalent shapes of MPs are fibers, which account for almost 47% in water samples and 87% in salt samples. Based on the ATR-FTIR study, polyethylene (PE) is the most prevalent polymer observed in salt samples, followed by polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET). In water samples, PP is the most dominating polymer, followed by PE and PS. Through SEM microphotographs, fiber-type MPs have smooth surfaces, fragment-type MPs have rough edges, and sheet-type MPs have layered surfaces. EDX analysis revealed that carbon (C) and oxygen (O) are the most abundant elements, followed by aluminium (Al) and sodium (Na) in MPs. Based on the results, it is inferred that the MPs in the rock salts are mainly sourced from the different stages of salt-making production. This preliminary study shed light on the presence and characteristics of MPs in rock salts in this region. The research outcomes could support sustainable management plans to improve the salt quality and enhance the market value.

Diabetes Mellitus and Fluid Imbalance: The Need for Adequate Hydration.

The effect of hydration in modulating metabolic disease risk is a comparatively recent concept. Diabetic patients are at increased risk of dehydration due to osmotic diuresis. Undiagnosed or undertreated hyperglycemia may lead to electrolyte imbalance and elevated renal burden of glucose excretion, which may alter fluid reabsorption in the kidney. Also, the presence of one or more contributory factors, such as inadequate fluid intake, strenuous exercise, high temperatures, alcohol consumption, diarrhea, acute illnesses, fever, nausea, and vomiting, may put diabetic patients at increased risk of dehydration and electrolyte imbalance. Certain antidiabetic agents used by diabetic patients may cause fluid retention/deficits and/or electrolyte abnormalities in a few patients. Thus, drinking ample amounts of water and fluids with appropriate electrolyte composition is important to prevent dehydration. Successful management of dehydration in patients with diabetes is an unmet need and can best be accomplished by maintaining adequate hydration status.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

Competing risks analysis for neutrophil to lymphocyte ratio as a predictor of diabetic retinopathy incidence in the Scottish population.

BACKGROUND: Diabetic retinopathy (DR) is a major sight-threatening microvascular complication in individuals with diabetes. Systemic inflammation combined with oxidative stress is thought to capture most of the complexities involved in the pathology of diabetic retinopathy. A high level of neutrophil-lymphocyte ratio (NLR) is an indicator of abnormal immune system activity. Current estimates of the association of NLR with diabetes and its complications are almost entirely derived from cross-sectional studies, suggesting that the nature of the reported association may be more diagnostic than prognostic. Therefore, in the present study, we examined the utility of NLR as a biomarker to predict the incidence of DR in the Scottish population. METHODS: The incidence of DR was defined as the time to the first diagnosis of R1 or above grade in the Scottish retinopathy grading scheme from type 2 diabetes diagnosis. The effect of NLR and its interactions were explored using a competing risks survival model adjusting for other risk factors and accounting for deaths. The Fine and Gray subdistribution hazard model (FGR) was used to predict the effect of NLR on the incidence of DR. RESULTS: We analysed data from 23,531 individuals with complete covariate information. At 10 years, 8416 (35.8%) had developed DR and 2989 (12.7%) were lost to competing events (death) without developing DR and 12,126 individuals did not have DR. The median (interquartile range) level of NLR was 2.04 (1.5 to 2.7). The optimal NLR cut-off value to predict retinopathy incidence was 3.04. After accounting for competing risks at 10 years, the cumulative incidence of DR and deaths without DR were 50.7% and 21.9%, respectively. NLR was associated with incident DR in both Cause-specific hazard (CSH = 1.63; 95% CI: 1.28-2.07) and FGR models the subdistribution hazard (sHR = 2.24; 95% CI: 1.70-2.94). Both age and HbA1c were found to modulate the association between NLR and the risk of DR. CONCLUSIONS: The current study suggests that NLR has a promising potential to predict DR incidence in the Scottish population, especially in individuals less than 65 years and in those with well-controlled glycaemic status.

Long-term Effects of a Collaborative Care Model on Metabolic Outcomes and Depressive Symptoms: 36-Month Outcomes from the INDEPENDENT Intervention.

BACKGROUND: Collaborative care (CC) is a multicomponent team-based approach to providing mental health care with systematic integration into outpatient medical settings. The 12-month INDEPENDENT CC intervention improved joint disease control measures in patients with both depression and diabetes at 12 and 24 months following randomization. OBJECTIVE: This study investigated the durability of intervention effects on patient outcomes at 36 months following randomization. PARTICIPANTS: Adult patients with poorly controlled T2D and depression in India randomized to CC or usual care. DESIGN: Post hoc analyses of between-group differences in patient outcomes at 36 months post-randomization (N = 331) and maintenance of outcomes from 12 to 36 months (N = 314). MAIN MEASURES: We evaluated combined risk factor improvement since baseline, defined as ≥ 50.0% reduction in Symptom Checklist Depression Scale (SCL-20) scores along with reduction of at least 0.5 percentage point hemoglobin A1C, 5 mmHg systolic blood pressure, or 10 mg/dL low-density lipoprotein cholesterol. Improvements in single risk factors were also examined. KEY RESULTS: There were no between-group differences in improvements since baseline in multiple or single risk factors at 36 months. Patients in the CC group with improved outcomes at 12 months were more likely to maintain a ≥ 50.0% reduction since baseline in SCL-20 scores (CC [54.9%] vs. UC [40.9%]; RR: 1.27 [95% CI: 1.04, 1.56]) and 0.5 percentage point reduction since baseline in hemoglobin A1C (CC [31.9%] vs. UC [19.5%]; RR: 1.64 [95% CI: 1.11, 2.41]) at 36 months. CONCLUSIONS: While improvements since baseline in patient outcomes did not differ between the collaborative care and usual care groups at 36 months, patients who received CC were more likely to maintain improvements in depressive symptoms and glucose levels at 36 months if they had achieved these improvements at the end of active intervention. TRIAL REGISTRATION NUMBER: NCT02022111.

Are Unhealthy Diets Contributing to the Rapid Rise of Type 2 Diabetes in India?

The prevalence of diabetes is increasing at an alarming rate globally, particularly in India. In the urban areas, the prevalence of diabetes among adults aged ≥20 y, which was around 2% in the early 1970's, has increased by >20% in 50 y. The rapid nutrition transition due to high economic growth rates increased urbanization and globalization has resulted in higher intakes of processed refined grain staples, mainly white rice in Southern and Eastern India and refined wheat in Northern and Western India. This coupled with inadequate quantity and quality of protein; unhealthy fats; lower intake of vegetables, fruits, and fiber; and a sedentary lifestyle are the main drivers of the diabetes epidemic in India. This review attempts to discuss both the quality and quantity of Indian diets with specific reference to macronutrients. This review also outlines some of the strategies that can be employed to slow down the diabetes epidemic in this region. We believe that the lessons learned from India would be applicable to other developing nations as well, particularly to the South East Asian region.

Burden of undiagnosed and suboptimally controlled diabetes in selected regions of India: Results from the SMART India population-level diabetes screening study.

AIMS: To estimate the prevalence of undiagnosed diabetes and suboptimally controlled diabetes and the associated risk factors by community screening in India. METHODS: In this multi-centre, cross-sectional study, house-to-house screening was conducted in people aged ≥40 years in urban and rural areas across 10 states and one union territory in India between November 2018 and March 2020. Participants underwent anthropometry, clinical and biochemical assessments. Capillary random blood glucose and point-of-care glycated haemoglobin (HbA1c ) were used to diagnose diabetes. The prevalence of undiagnosed diabetes and suboptimal control (HbA1c ≥53 mmol/mol [≥7%]) among those with known diabetes was assessed. RESULTS: Among the 42,146 participants screened (22,150 urban, 19,996 rural), 5689 had known diabetes. The age-standardised prevalence of known diabetes was 13.1% (95% CI 12.8-13.4); 17.2% in urban areas and 9.4% in rural areas. The age-standardised prevalence of undiagnosed diabetes was 6.0% (95% CI 5.7-6.2); similar in both urban and rural areas with the highest proportions seen in the East (8.0%) and South (7.8%) regions. When we consider all people with diabetes in the population, 22.8% of individuals in urban areas and 36.7% in rural areas had undiagnosed diabetes. Almost 75% of the individuals with known diabetes had suboptimal glycaemic control. CONCLUSIONS: High prevalence of undiagnosed diabetes and suboptimally controlled diabetes emphasises the urgent need to identify and optimally treat people with diabetes to reduce the burden of diabetes.

Evaluation of Madras Diabetes Research Foundation-Indian Diabetes Risk Score in detecting undiagnosed diabetes in the Indian population: Results from the Indian Council of Medical Research-INdia DIABetes population-based study (INDIAB-15).

Background & objectives: Screening of individuals for early detection and identification of undiagnosed diabetes can help in reducing the burden of diabetic complications. This study aimed to evaluate the performance of Madras Diabetes Research Foundation (MDRF)-Indian Diabetes Risk Score (IDRS) to screen for undiagnosed type 2 diabetes in a large representative population in India. Methods: Data were acquired from the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study, a large national survey that included both urban and rural populations from 30 states/union territories in India. Stratified multistage design was followed to obtain a sample of 113,043 individuals (94.2% response rate). MDRF-IDRS used four simple parameters, viz. age, waist circumference, family history of diabetes and physical activity to detect undiagnosed diabetes. Receiver operating characteristic (ROC) with area under the curve (AUC) was used to assess the performance of MDRF-IDRS. Results: We identified that 32.4, 52.7 and 14.9 per cent of the general population were under high-, moderate- and low-risk category of diabetes. Among the newly diagnosed individuals with diabetes [diagnosed by oral glucose tolerance test (OGTT)], 60.2, 35.9 and 3.9 per cent were identified under high-, moderate- and low-risk categories of IDRS. The ROC-AUC for the identification of diabetes was 0.697 (95% confidence interval: 0.684-0.709) for urban population and 0.694 (0.684-0.704) for rural, as well as 0.693 (0.682-0.705) for males and 0.707 (0.697-0.718) for females. MDRF-IDRS performed well when the population were sub-categorized by state or by regions. Interpretation & conclusions: Performance of MDRF-IDRS is evaluated across the nation and is found to be suitable for easy and effective screening of diabetes in Asian Indians.

Cardiovascular disease, mortality, and their associations with modifiable risk factors in a multi-national South Asia cohort: a PURE substudy.

AIM: To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia. METHODS AND RESULTS: Prospective study of 33 583 individuals 35-70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%). CONCLUSION: In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants.

Early Gestational Diabetes Mellitus: An Update.

Hyperglycemia occurring in pregnancy is a growing burden worldwide. It is now standard of care to screen all women during pregnancy, both to detect preexisting diabetes as well as gestational diabetes mellitus (GDM). Traditionally, GDM was diagnosed at 24-28 weeks. However, with many international bodies recommending screening at first contact or booking, we are now diagnosing GDM earlier on in pregnancy. Based on the time of gestation at which it is diagnosed, GDM can be classified as conventional gestational diabetes mellitus (cGDM) or early gestational diabetes mellitus (eGDM). The cGDM is diagnosed between 24 and 28 weeks of gestation while eGDM is diagnosed in early pregnancy (<20 weeks). Till recently, there was little and conflicting evidence, on whether diagnosing and treating eGDM was beneficial or safe. The recent Treatment of BOoking Gestational diabetes Mellitus (ToBOGM) study, was a randomized control trial, showing clear benefits of diagnosing and treating eGDM. ToBOGM also showed that the best results were seen in those screened before 14 weeks of pregnancy and those in the higher band of glucose levels (FPG 95-109 mg/dL, 1-hour >191 mg/dL, and 2-hour glucose 162-199 mg/dL). In India, where the burden of hyperglycemia in pregnancy is high, the findings from the ToBOGM study further emphasize the need for screening for GDM at the time of first booking of the pregnancy followed by appropriate treatment for those detected to have eGDM. How to cite this article: Hannah W, Pradeepa R, Anjana RM, et al. Early Gestational Diabetes Mellitus: An Update. J Assoc Physicians India 2023;71(9):101-103.

Association of POC-based Measurement of Skin AGEs with Serum AGEs as well as AGE Biomarkers in Individuals with and without Glucose Intolerance.

Accumulation of advanced glycation end products (AGEs) occurs with aging and in various disease states. There are no reliable screening techniques to measure AGEs in clinical settings. In this study, a point-of-care (POC) device was used to validate skin AGE measurements with serum AGE levels and to assess its usefulness to identify individuals with abnormal glucose tolerance (AGT). MATERIALS AND METHODS: The study group comprised individuals with normal glucose tolerance (NGT: n = 47) and with AGT, that is, either diabetes or prediabetes (n = 68). Intrinsic AGE fluorescence was measured spectrofluorimetrically using multimode plate reader in the serum by exciting the samples at 370 nm and emission readouts at 440 nm. Skin AGEs were acquired using a CE-marked Scout DS commercial device. Serum levels of biomarkers carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and pentosidine were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: In subjects with AGT, the skin AGEs [61.3 vs 53.7 arbitrary units (AU), p<0.0001] and serum AGEs (3.5 vs 2.8 AU, p<0.0001) were significantly higher than in individuals with NGT. The levels of CML, CEL, and pentosidine were also significantly higher in the subjects with AGT when compared with NGT (138 vs 89 pg/mL; 2.4 vs 1.4 nmol/mL, and 64 vs 48 pmol/mL, p<0.0001), respectively. Pearson correlation analysis showed a significant positive association of skin AGEs with serum AGEs (r = 0.344) (p<0.001), CML (r = 0.323) (p<0.001), CEL (r = 0.308) (p<0.001), and pentosidine (r = 0.251) (p<0.001). In addition, it also showed a positive correlation with fasting plasma glucose (FPG) (p<0.001), 2-hour post-glucose (p<0.001), glycated hemoglobin (HbA1c) (p<0.001), and body mass index (BMI) (p<0.05). Multiple logistic regression analysis using AGT as a dependent variable showed that skin AGE scores were significantly (p<0.001) associated with AGT (odds ratio: 1.133, confidence intervals: 1.067-1.203). CONCLUSION: This study shows that the measurement of skin AGEs using a POC device may be suitable for mass screening of AGT even in low-resource settings.