Consensus on pharmacological treatment of obesity in Latin America.

A panel of 10 experts in obesity from various Latin American countries held a Zoom meeting intending to reach a consensus on the use of anti-obesity medicines and make updated recommendations suitable for the Latin American population based on the available evidence. A questionnaire with 16 questions was developed using the Patient, Intervention, Comparison, Outcome (Result) methodology, which was iterated according to the modified Delphi methodology, and a consensus was reached with 80% or higher agreement. Failure to reach a consensus led to a second round of analysis with a rephrased question and the same rules for agreement. The recommendations were drafted based on the guidelines of the American College of Cardiology Foundation/American Heart Association Task Force on Practice. This panel of experts recommends drug therapy in patients with a body mass index of ≥30 or ≥27 kg/m2 plus at least one comorbidity, when lifestyle changes are not enough to achieve the weight loss objective; alternatively, lifestyle changes could be maintained while considering individual parameters. Algorithms for the use of long-term medications are suggested based on drugs that increase or decrease body weight, results, contraindications, and medications that are not recommended. The authors concluded that anti-obesity treatments should be individualized and multidisciplinary.

Low-Dose ACTH Stimulation Test in Obesity: A Randomized Dose Assessment.

Background: The short cosyntropin test is widely used for adrenal insufficiency screening and diagnosis. Lower cosyntropin doses may have greater sensitivity vs. the standard dose in detecting adrenal dysfunction. Obesity and overweight are increasing, impacting the clinical presentation of some diseases. Currently more than 50% of the subjects diagnosed with autoimmune adrenal insufficiency have a BMI greater than 25, and hence individuals living with overweight and obesity are more frequently requiring evaluation of the adrenal cortical function. Fixed-dose cosyntropin stimulation may not be appropriate for individuals with obesity. Objective: The primary objective was to compare cortisol response to a weight-adapted cosyntropin dose vs. a fixed low dose (1 µg) and a more physiologically fixed dose (10 µg). Methods: Twenty individuals with obesity and 20 age-matched healthy controls underwent in a randomized sequence at least one-week apart, to the The short cosyntropin test with three different doses, 0.2 µg/kg of body weight, 1 or 10 µg fixed dose stimuli. The assessment and data analysis were blinded to the individual and the investigator. Results: Cortisol response was reduced in the group with obesity with the 1 µg fixed dose stimuli at 30 minutes (median, IQR) 649.6 µg, 567.3-738.4 µg for the control group vs. 568.6 µg, 528.4-623.13 µg, p=0.04; there was a lower cortisol peak at 60' in all the three evaluated doses, with a dose-dependent trend. A weight-adapted cosyntropin dose of 0.2 µg in obesity produces a similar response to the one observed in individuals without obesity. The 1 µg ACTH test falls short on stimulating the cortisol adrenal response in individuals with obesity.

Impact of My Dose Coach App Frequency of Use on Clinical Outcomes in Type 2 Diabetes.

INTRODUCTION: My Dose Coach (MDC) is a US Food and Drug Administration-approved digital smartphone application designed to help users with type 2 diabetes (T2D) titrate their basal insulin (BI) according to a clinician-prescribed individualized titration plan. The aim of this analysis was to assess the impact of the frequency of MDC use on clinical outcomes. METHODS: This retrospective observational analysis included people with T2D who were registered for MDC (August 1st, 2018-April 30th, 2020) and received BI. Users with an activated care plan and ≥2 fasting blood glucose (FBG) observations spanning ≥2 weeks were defined as active. Outcomes included percentage achieving their individual FBG target, time to FBG target, change in FBG, change in insulin dose and hypoglycemia. Users were stratified into high (>3 days per week), moderate (>1- ≤3 days per week), and low (≤1 day per week) MDC usage groups. RESULTS: The analysis included 2517 active MDC users. Approximately 49% of users had high MDC usage. Overall, 44% of users across all usage frequencies achieved their individual FBG target. High MDC use was associated with significantly better FBG target achievement and less time to FBG target versus moderate- and low-usage groups (p≤0.01 for all). Insulin dose change was significantly greater in the high- versus moderate-usage group (p=0.01). There was no significant difference in hypoglycemia incidence among MDC usage groups (12%-16% of users in any usage group). CONCLUSIONS: More frequent MDC usage was associated with better FBG outcomes without increased hypoglycemia risk.

Epicardial adipose tissue thickness is associated with increased COVID-19 severity and mortality.

BACKGROUND: Increased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes. METHODS: We included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes. RESULTS: EAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95% CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4 C severity score, independent of obesity. EAT mediated 13.1% (95% CI 3.67-28.0%) and 5.1% (95% CI 0.19-14.0%) of the effect of age and 19.4% (95% CI 4.67-63.0%) and 12.8% (95% CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19. CONCLUSION: EAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.

The utility of the Edmonton Obesity Staging System for the prediction of COVID-19 outcomes: a multi-centre study.

BACKGROUND: Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. METHODS: 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. RESULTS: The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. CONCLUSIONS: EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.

Gestational diabetes mellitus and COVID-19, clinical characteristics and review of the literature.

There is a lack of information about the maternal-fetal outcomes in patients with gestational diabetes and concomitant COVID-19; and there is even less information about the outcomes of pregnant women with gestational diabetes and COVID-19. We present a case of a primigravidae of 20-year-old woman with gestational diabetes and COVID-19 and a review of the literature.

Perceptions, Attitudes, and Barriers to Obesity Care in Mexico: Data From the ACTION-IO Study.

OBJECTIVE: The Awareness, Care, and Treatment in Obesity Management-International Observation (ACTION-IO) study (ClinicalTrials.gov identifier NCT03584191) aimed to identify perceptions, attitudes, behaviors, and barriers to effective obesity care in people with obesity (PwO) and health care professionals (HCPs). This study presents the results from Mexico. METHODS: An online survey was conducted. In Mexico, eligible PwO were ≥18 years of age with BMI ≥30 kg/m2 based on self-reported height and weight. Eligible HCPs had direct patient care. RESULTS: The survey was completed by 2,000 PwO and 400 HCPs in Mexico. Many PwO (71%) and HCPs (94%) categorized obesity as a chronic disease. Sixty-three percent of PwO felt motivated to lose weight, but many HCPs perceived that PwO were not interested in losing weight (76%) or motivated to lose weight (69%). Lack of financial means to support weight-loss efforts was a barrier for PwO (34%) to discussing weight with HCPs. Sixty-five percent of PwO had discussed weight with HCPs in the past 5 years. PwO (80%) and HCPs (89%) considered lack of exercise as the main barrier to weight loss. Few PwO (34%) had successfully lost ≥5% of their body mass over the past 3 years. CONCLUSIONS: This ACTION-IO study in Mexico identified discrepancies in the perceptions of PwO and HCPs, highlighting opportunities for further education and patient-centered approaches.

Carotid Intima-Media Thickness in Patients with Subclinical Hypothyroidism: A Prospective Controlled Study.

PURPOSE: The association between subclinical hypothyroidism (SCH) and cardiovascular risk, particularly with a TSH <10 µIU/ml, remains controversial. The objective of our study was to assess the association between SCH and cardiovascular risk through carotid intima-media thickness, and alternatively, to evaluate its change after treatment with levothyroxine. METHODS: A total of 54 individuals were included in the study: 18 with SCH; 18 with overt hypothyroidism (OH); and 18 healthy controls (HC). The carotid intima-media thickness was measured in each group. In SCH, follow-up was performed at three and six months after the start of levothyroxine treatment. RESULTS: The mean age of the total population at baseline was 35.8 years. The median TSH in SCH was 6.15 µIU/ml. The carotid intima-media thickness (mean and standard deviation) was greater in SCH in comparison to the HC group: right common carotid artery (RCCA), 0.486 ± 0.106 mm and 0.413 ± 0.075 mm in SCH and HC, respectively, p=0.01 and left common carotid artery (LCCA), 0.511 ± 0.144 mm and 0.427 mm ± 0.090 in SCH and HC, respectively, p=0.03). In patients with SCH, there was a decrease in the carotid intima-media thickness after treatment with levothyroxine (RCCA and LCCA, p <0.05 at three and six months). CONCLUSIONS: There was an association between increased carotid intima-media thickness in patients with SCH in comparison with HC, even with a TSH <10 µIU/ml. The increase was reversed with levothyroxine therapy. The association of this increased thickness with important cardiovascular outcomes remains uncertain and should be evaluated in future studies.

Early triglyceride and glucose index as a risk marker for gestational diabetes mellitus.

OBJECTIVE: To assess the risk of gestational diabetes mellitus (GDM) according to the triglyceride and glucose (TyG) index values during the first trimester of pregnancy in Latin American women. METHODS: Pregnant women were enrolled at their first prenatal visit at the Obstetric Division in the University Hospital "Dr. José E. González". Triglycerides and fasting plasma glucose (FPG) were collected to determine the TyG index. GDM diagnosis was performed by a single-step 2-hour 75-g oral glucose tolerance test. Generalized linear models were used to determine risk ratios; pregnancy outcomes at delivery were collected from the hospital medical records. RESULTS: A total of 164 pregnant women were included. GDM was present in 29 (17.7%) women. No significant differences in age, first-trimester body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), family history of diabetes, and TyG index were observed between GDM cases and the reference group without GDM. The adjusted analysis showed no association between TyG and GDM (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.57-1.88]). Higher TyG index values between women with and without a diagnosis of GDM in the second trimester were observed. No significant differences were identified in pregnancy outcomes, although a trend was observed for hyperbilirubinemia in women with first-trimester TyG index values greater than 8.7. CONCLUSIONS: Our findings do not support the use of the TyG index for GDM prediction in Latin American women.

Recommendations for the care of patients with diabetes mellitus with risk factors or established cardiovascular disease and SARS-CoV-2mellitus con factores de riesgo o enfermedad cardiovascular establecida y SARS-CoV-2.

A review is carried out to examine the risk of patients suffering from diabetes mellitus in the context of general morbidity and mortality and related to infection by SARS-CoV-2. Likewise, the general recommendations for food and the prevention of comorbidities that most these patients suffer most frequently are also studied. Finally, a review of the pharmacological recommendations on both oral and parenteral treatment in the outpatient, in hospitalization and in critical states infected with SARS-CoV-2 is made.

Se realiza una revisión sobre el riesgo de los pacientes que padecen diabetes mellitus en el contexto de morbimortalidad general y relacionada a infección por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2). Así mismo se repasan las recomendaciones generales, de alimentación y de la prevención de las comorbilidades que más frecuentemente padecen dichos enfermos. Finalmente se hace una revisión de las recomendaciones farmacológicas sobre el tratamiento tanto oral como parenteral en el paciente ambulatorio, en la hospitalización y en estados críticos infectados por el SARS-CoV-2.

Diagnostic accuracy of the triglyceride-glucose index for gestational diabetes screening: a practical approach.

The oral glucose tolerance test (OGTT) remains as the gold standard to diagnose gestational diabetes mellitus (GDM); however, this test may be inconvenient and costly. Hence, other easy to perform and accurate diagnostic alternatives would be valuable for maternal care. The objective of the study was to assess the diagnostic performance of the TyG index to screen for GDM at 24-28 of pregnancy. A total of 140 pregnant women who received the one-step 2 h 75 g OGTT were included. Overall GDM prevalence was 27.1% according to IADSPG criteria. The mean TyG index value in the GDM group was significantly higher than the TyG index for the no GDM group (4.88 ± 0.70 versus 4.68 ± 0.19, p<.001). A sensitivity of 89% [95% CI 0.75-0.97] and a specificity of 50% [95% CI 0.39-0.60)], accompanied by a high negative predictive value of 93% was observed. No differences were found in maternal and neonatal outcomes irrespective of the TyG cutoff value for GDM. According to our results, the TyG index may be a highly sensitive and easy to perform screening test for GDM.

Diagnostic Accuracy of the Triglyceride and Glucose Index for Insulin Resistance: A Systematic Review.

Introduction. The triglyceride and glucose (TyG) index has been described as a biochemical marker of insulin resistance (IR); however, its diagnostic accuracy remains uncertain. OBJECTIVE: To summarize the evidence assessing the diagnostic accuracy of the TyG index regarding IR. METHODS: A comprehensive search in MEDLINE, EMBASE, Web of Science, and Scopus was performed without any language restriction. Studies assessing the diagnostic accuracy of the TyG index against the hyperinsulinemic-euglycemic clamp (HIEC) or any other IR biochemical were assessed independently and in duplicate. Diagnostic accuracy measures (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios) were extracted independently and in duplicate. The QUADAS-2 tool was used to assess the risk of bias of independent studies. RESULTS: We identified 15 eligible studies with 69,922 participants and an overall quality of low to moderate. The TyG index was evaluated by HIEC and HOMA as reference tests. The highest achieved sensitivity was 96% using HIEC, and the highest specificity was of 99% using HOMA-IR, with a cutoff value of 4.68. AUC values varied from 0.59 to 0.88. Cutoff values for IR were variable between studies, limiting its comparability. CONCLUSION: In this systematic review, we found moderate-to-low quality evidence about the usefulness of the TyG index as a surrogate biochemical marker of IR. Due to the lack of a standardized IR definition and heterogeneity between studies, further validation and standardized cutoff values are needed to be used in clinical practice.

SERUM MORNING CORTISOL AS A SCREENING TEST FOR ADRENAL INSUFFICIENCY.

Objective: To evaluate the performance of morning serum cortisol (MSC) compared to a 10 mg adrenocortico-tropic hormone (ACTH) stimulation test in the diagnosis of adrenal insufficiency (AI). Methods: A retrospective, cross-sectional analysis of ACTH stimulation tests were conducted. From a total of 312 potentially eligible ACTH stimulation tests, 306 met the inclusion criteria. The population was randomized into 2 groups: test (n = 159) and validation (n = 147). In the test group, the receiver operating characteristics curve test evaluated the diagnostic performance of MSC. Results: A subnormal cortisol response to ACTH was found in 25.8% of the test group. The area under the curve values of MSC to predict AI at +30 minutes, +60 minutes, or at maximal cortisol response were 0.874, 0.897, and 0.925 (95% confidence interval [CI] 0.81 to 0.92, 0.83 to 0.93, and 0.87 to 0.96). The Youden index was 234.2 mmol/L with a sensitivity of 83.3% (95% CI 65.2 to 94.3%), and a specificity of 89.1% (95% CI 82.4 to 93.9%). Positive and negative predictive values were 64.1% (95% CI 47.1 to 78.8%) and 95.8% (95% CI 90.5 to 98.6%). There was no difference in age, gender, AI prevalence, or mean serum cortisol at +30 or +60 minutes in the validation group; however, a lower mean MSC value was found. Lower sensitivity and specificity values (88.3% and 60%, respectively) were found for the 234.2 mmol/L cutoff value. Conclusion: This study supports the role of MSC as a first-step diagnostic test in patients with clinically suspected AI. The short stimulation test could be omitted in almost half of the cases. Prospective and longitudinal studies to reproduce and confirm the cutoff values proposed are warranted. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; AUC = area under the curve; CI = confidence interval; HPA = hypothalamic pituitary adrenal; ITT = insulin tolerance test; MSC = morning serum cortisol.

Acanthosis nigricans in middle-age adults: A highly prevalent and specific clinical sign of insulin resistance.

BACKGROUND: Insulin resistance (IR) precedes the diagnosis of many metabolic and non-metabolic illnesses, including type 2 diabetes mellitus (T2DM). Acanthosis nigricans (AN) is a clinical sign associated with IR. However, AN prevalence and diagnostic accuracy in middle-age adults before or at the time of prediabetes/diabetes diagnosis remain uncertain. METHODS: With the aim to define AN prevalence and diagnostic accuracy, adults between 40 and 60 years of age were consecutively invited to participate in the study. Participants were categorised into one of two main groups: individuals with normoglycaemia (group 1) and hyperglycaemia (group 2 [ie, prediabetes/diabetes]). Demographic, clinical, anthropometric characteristics, homeostasis model assessment of IR, homeostatic model assessment of ß-cell function, as well as the presence of AN on the neck, axillae, elbows and knuckles were assessed. RESULTS: A total of 320 consecutive participants with a mean age of 49.3 years (59.4% women) were included. Overall, AN prevalence was 46.3%, while AN in group 1 and group 2 was 36.3% and 49.6%, respectively (P = .04). The most common affected sites in group 1 (n = 80) were the knuckles (21.2%) and the neck (17.5%), while in group 2 (n = 240), the neck (29.6%) followed by the knuckles (26.7%). The specificity and positive predictive value of AN for IR were 0.85 and 0.86 in group 1 and 0.90 and 0.96 in group 2, respectively. CONCLUSIONS: In middle-age adults, within the entire spectrum of carbohydrate tolerance, AN is highly prevalent and specific. This finding supports its assessment as a reliable and convenient clinical sign of IR. The understanding of AN behaviour through different carbohydrate tolerance strata, and its different locations, could lead to early detection of individuals at high metabolic risk or help direct a more pathophysiological treatment approach in patients with T2DM.

Recomendaciones para la atención de pacientes con diabetes mellitus con factores de riesgo o enfermedad cardiovascular establecida y SARS-CoV-2 / Recommendations for the care of patients with diabetes mellitus with risk factors or established cardiovascular disease and SARS-CoV-2

Resumen Se realiza una revisión sobre el riesgo de los pacientes que padecen diabetes mellitus en el contexto de morbimortalidad general y relacionada a infección por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2). Así mismo se repasan las recomendaciones generales, de alimentación y de la prevención de las comorbilidades que más frecuentemente padecen dichos enfermos. Finalmente se hace una revisión de las recomendaciones farmacológicas sobre el tratamiento tanto oral como parenteral en el paciente ambulatorio, en la hospitalización y en estados críticos infectados por el SARS-CoV-2.

Abstract A review is carried out to examine the risk of patients suffering from diabetes mellitus in the context of general morbidity and mortality and related to infection by SARS-CoV-2. Likewise, the general recommendations for food and the prevention of comorbidities that most these patients suffer most frequently are also studied. Finally, a review of the pharmacological recommendations on both oral and parenteral treatment in the outpatient, in hospitalization and in critical states infected with SARS-CoV-2 is made.

Hypertriglyceridemia and Its Association with HbA1c Test: A Prospective In Vivo Controlled Study.

BACKGROUND: Hypertriglyceridemia and hyperglycemia coexist in 30-60% of patients with diabetes. The impact of hypertriglyceridemia regarding HbA1c assay reliability remains uncertain. Therefore, we conducted a prospective in vivo controlled study with the aim of defining the association between triglyceride levels and HbA1c. METHODS: A total of 44 patients with an index-hospital admission diagnosis of diabetic ketoacidosis or hypertriglyceridemia-induced pancreatitis, as a model for acute elevation of triglycerides, were recruited. Blood samples were drawn for the measurement of HbA1c, triglycerides, glucose, and hemoglobin at baseline and subsequently 24 and 48 hours after admission. HbA1c analysis was performed with high-performance liquid chromatography Bio-Rad D10 (NGSP approved). RESULTS: All patients completed the study protocol. A difference between mean triglycerides from day 0 (baseline) to day 2 of 1567.2 mg/dL was observed. We found a difference between mean serum HbA1c from days 0 to 2 of 0.09% [1 mmol/mol] (p = 0.004). Moreover, a weak correlation between the mean difference of HbA1c and triglycerides from baseline to day 2 was found to be statistically significant (r = 0.256, p = 0.015). None of these findings, however, are clinically significant. CONCLUSION: Triglycerides do not impair the interpretation of HbA1c assay. Patients and clinicians can now be confident that hypertriglyceridemia is not an important factor when interpreting HbA1c results.

A cost-utility analysis of dulaglutide versus insulin glargine as third-line therapy for Type 2 diabetes in Canada.

AIM: The prevalence of Type 2 diabetes in Canada is estimated to be 7.6% and rising. Given the substantial economic burden associated with Type 2 diabetes treatment, optimizing healthcare expenditure is extremely important. In the present analysis, we evaluated the cost-effectiveness of dulaglutide 1.5 mg, a once-weekly glucagon-like peptide 1 agonist as third-line therapy relative to insulin glargine from the perspective of a Canadian healthcare payer. METHODS: A patient-level cost-utility model of Type 2 diabetes was developed to capture seven microvascular and macrovascular complications and severe and nonsevere hypoglycemia. Cohort characteristics and the relative efficacy of dulaglutide 1.5 mg and insulin glargine were derived from the AWARD-2 head-to-head trial, which was identified by systematic literature review. Cost data were derived from Canadian sources and expressed in 2016 Canadian dollars (CAD), and future cost and quality-adjusted life expectancy (QALE) estimates were discounted at 1.5% per annum. One-way and probabilistic sensitivity analyses were conducted. RESULTS: Based on the AWARD-2 trial, relative to insulin glargine, dulaglutide 1.5 mg was projected to increase QALE by 0.38 quality-adjusted life years and increase costs by CAD 19,773, resulting in an incremental cost-effectiveness ratio of CAD 52,580 per quality-adjusted life year gained. CONCLUSION: A computer simulation analysis showed that dulaglutide 1.5 mg would likely be cost-effective relative to insulin glargine in patients with Type 2 diabetes inadequately controlled on metformin and sulfonylurea in Canada.