Real-world effectiveness and safety of insulin glargine 300 U/ml in insulin-naïve people with type 2 diabetes in the Latin America region: A subgroup analysis of the ATOS.

AIM: To evaluate the real-world effectiveness and safety of insulin glargine 300 U/ml (Gla-300) in achieving glycaemic goals in insulin-naïve people with type 2 diabetes (T2D) in Mexico, Colombia and Peru (Latin America region) in the A Toujeo Observational Study (ATOS). MATERIALS AND METHODS: ATOS was a multicentre, prospective, 12-month observational study, which included 4422 insulin-naïve adults (age ≥ 18 years) with T2D uncontrolled (HbA1c > 7% and ≤11%) on at least one oral antidiabetic drug (OAD) who initiated Gla-300 treatment as per routine practice. The primary endpoint was the percentage of participants achieving their predefined individualized HbA1c goal at month 6. Key secondary endpoints included change from baseline in HbA1c, fasting plasma glucose (FPG), fasting self-monitored blood glucose (SMBG), body weight and incidence of hypoglycaemia. RESULTS: In this subgroup analysis, a total of 314 participants with T2D received Gla-300. At baseline, mean ± SD age was 56.0 ± 11.6 years, duration of diabetes was 9.7 ± 6.6 years and 65.9% of participants were on at least two OADs. The individualized HbA1c target was achieved by 25.8% of participants (95% confidence interval [CI]: 20.3-31.9) at month 6 and by 35.3% (95% CI: 28.5-42.5) at month 12. Gla-300 treatment improved glycaemic control with meaningful reductions in mean HbA1c, FPG and fasting SMBG. The incidence of hypoglycaemia reported was low and body weight remained stable. CONCLUSIONS: In a real-world setting in the Latin America region, the initiation of Gla-300 in people with T2D uncontrolled on OADs resulted in improved glycaemic control with a low incidence of hypoglycaemia and no change in body weight.

Thyroid Dysfunction and Heart Failure: Mechanisms and Associations.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the current knowledge of the pathophysiology, the mechanisms, and the cardiovascular impact of the different stages of thyroid dysfunction (TD) in heart failure (HF) patients. RECENT FINDING: The influence of thyroid hormones (THs) on the cardiovascular system involves the regulation of key processes related to maintenance of cardiac function; however, there are no long-term studies available showing that intervening the TD changes the incidence or the prognosis in HF individuals. Future research shall focus on the effects of cardiovascular morbidity and mortality associated with different treatment modalities for hyper and hypothyroidism. TD has been associated with different clinical results in HF individuals; treatment with THs in patients with hypothyroidism improves cardiovascular risk factors, but the effect on cardiovascular events has not been assessed in randomized, controlled trials.

Autoimmune Thyroid Disease and Differentiated Thyroid Carcinoma: A Review of the Mechanisms That Explain an Intriguing and Exciting Relationship.

Autoimmune thyroid disease is a complex and highly frequent disease, where a wide variety of genetic, epigenetic and environmental factors (among others) come together and interact, and is characterized by the presence of two clinical outcomes: hypothyroidism (in Hashimoto's thyroiditis) and hyperthyroidism (in Graves-Basedow disease). For its part, differentiated thyroid carcinoma (mainly papillary carcinoma) is the most common type of cancer affecting the thyroid (and one of the most prevalent worldwide). An important co-occurrence between autoimmune thyroid disease and differentiated thyroid carcinoma has been documented. In this article, studies that have evaluated possible associations and relationships between autoimmune thyroid disease and differentiated thyroid cancer are systematically described and summarized. To date, the underlying mechanism that explains this association is inflammation; however, the characteristics and designs of the studies evaluated do not yet allow a causal relationship between the two entities to be established. These aspects have made it difficult to establish "causality" in the continuum of the pathogenesis between both conditions.

Molecular Mechanisms in Autoimmune Thyroid Disease.

The most common cause of acquired thyroid dysfunction is autoimmune thyroid disease, which is an organ-specific autoimmune disease with two presentation phenotypes: hyperthyroidism (Graves-Basedow disease) and hypothyroidism (Hashimoto's thyroiditis). Hashimoto's thyroiditis is distinguished by the presence of autoantibodies against thyroid peroxidase and thyroglobulin. Meanwhile, autoantibodies against the TSH receptor have been found in Graves-Basedow disease. Numerous susceptibility genes, as well as epigenetic and environmental factors, contribute to the pathogenesis of both diseases. This review summarizes the most common genetic, epigenetic, and environmental mechanisms involved in autoimmune thyroid disease.

Population status of selenium in Colombia and associated factors: a cross-sectional study.

OBJECTIVES: This study aims to investigate the population status of selenium in Colombia and other associated factors. METHODS: Cross-sectional study, in population of urban or rural origin (n=412). Main outcome measures were: median serum selenium, thyrotropin, the prevalence of and positivity of anti-thyroid peroxidase, anti-thyroglobulin, and anti-TSH receptor. RESULTS: This study found that 96.6% of the subjects had normal selenium levels, and no significant associations were found between the population median of selenium and overweight/obesity, sociodemographic variables, age, goiter, and thyroid antibody positivity. CONCLUSIONS: In Colombia, the population status of selenium is normal, and the geological characteristics may contribute to the state of selenium in this population. However, additional studies are required to evaluate the content of selenium in plants and other foods.

The Usefulness of Thyroid Antibodies in the Diagnostic Approach to Autoimmune Thyroid Disease.

Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto's thyroiditis (HT) and hyperthyroidism (Graves-Basedow disease (GBD)). Both conditions are characterized by presenting a cellular and humoral autoimmune reaction, with an increase in the synthesis and secretion of antibodies directed toward various thyroid antigens, together with a phenomenon of thyrocyte necrosis and apoptosis (in HT) and a persistent thyrotropin-receptor stimulation (in GBD). The diagnosis of both entities is based on clinical, laboratory, and imaging findings. Three major anti-thyroid antibodies have been described, those directed against the TSH receptor (TRAb), against thyroid peroxidase (TPOAb), and against thyroglobulin (TgAb). Each of these autoantibodies plays a fundamental role in the diagnostic approach of autoimmune thyroid disease. TRAbs are the hallmark of GBD, and additionally, they are predictors of response to disease treatment, among other utilities. Likewise, TPOAb and TgAb allow for identifying individuals with a higher risk of progression to hypothyroidism; the positivity of one or both autoantibodies defines the presence of thyroid autoimmunity. In this review, the usefulness of anti-thyroid antibodies in the diagnostic approach to autoimmune thyroid disease is described.

Fixed-ratio Combinations (basal Insulin Plus GLP-1RA) In Type 2 Diabetes. an Analytical Review Of Pivotal Clinical Trials.

In type 2 diabetes, therapeutic failure to the oral anti diabetics is frequent, the use of schemes with basal insulin or with multiple doses of insulin (basal insulin and short-acting insulins) are a widely accepted way to intensify therapy. The use of GLP-1 receptor agonists is another intensification strategy. The fixedratio combinations with molecules such as insulin degludec + liraglutide, and insulin glargine + lixisenatide have proven useful in intensifying treatment of individuals with type 2 diabetes. The purpose of this review was to evaluate and analyze the results of pivotal studies with both fixed-ratio combinations in individuals with type 2 diabetes, finding that, they are capable of achieving better glycemic control when compared with each of its components separately (with a lower risk of hypoglycemia vs basal insulin and lower risk of gastrointestinal adverse effects vs GLP-1 receptor agonists) in various clinical scenarios, especially in individuals who do not achieve control with oral antidiabetics or who do not achieve control with basal insulin (associated with oral antidiabetics) or in those under management with GLP-1RA plus oral antidiabetics.

Prevalence of Functional Alterations and the Effects of Thyroid Autoimmunity on the Levels of TSH in an Urban Population of Colombia: A Population-Based Study.

BACKGROUND: The population prevalence of functional alterations and thyroid autoimmunity is high, and numerous genetic and environmental aspects have been described as triggering factors. OBJECTIVES: The objective of this study was to determine the prevalence of functional alterations and thyroid autoimmunity in an urban population of Colombia. MATERIALS AND METHODS: It is a cross-sectional, population-based study (n = 9,638) conducted on an urban population of Popayán-Cauca-Colombia between February 5th, 2018, to December 11th, 2021. The variables evaluated were thyrotropin (TSH), free T4 (FT4), and anti-thyroid antibodies (thyroid peroxidase antibodies: TPOAb, and thyroglobulin antibodies: TgAb). RESULTS: TSH in men was significantly higher than in women. No differences were observed in the values of FT4, TPOAb, and TgAb (according to sex). The prevalence of normal thyroid function and subclinical hypothyroidism was significantly higher in men. The positivity of TPOAb and TgAb was 22.3% and 19.2%, respectively. TSH levels increased with age (both in men and in women). In participants with normal FT4 and negative TPOAb, the TSH was significantly higher. TSH was significantly higher in TPOAb-positive individuals and among those with TPOAb and TgAb positives, as well as in women with positive TPOAb and men with positive TPOAb and TgAb. CONCLUSION: In an urban population of Colombia, TSH was found to be higher than in populations of other geographical areas, especially in older individuals and in the presence of positive anti-thyroid antibodies, a high prevalence of functional alterations and thyroid autoimmunity was also found. These findings can be explained by excess iodine consumption and some environmental factors.

Population Status of Vitamin B12 Values in the General Population and in Individuals with Type 2 Diabetes, in Southwestern Colombia.

Vitamin B12 (B12) is necessary for the proper functioning of the central and peripheral nervous systems. Although there is no exact definition for B12 levels, a value of 200 pg/mL is compatible with deficiency, 200-299 pg/mL is considered borderline, and 300 pg/mL is considered normal. In population studies, the prevalence of B12 deficiency ranges between 2.9% and 35%. Furthermore, many medications, such as metformin [for type 2 diabetes mellitus (T2DM)], can cause B12 deficiency. The objectives of this study were to determine the population status of B12 in southwestern Colombia (and the status of B12 in subjects with T2DM). In the total population (participants with and without T2DM), the prevalence of B12 deficiency was 17.8%; that of borderline was 19.3%; and that of normal levels was 62.9%. The prevalence of deficiency increased with age and was significantly higher in those aged ≥60 years (p = 0.000). In T2DM subjects, the prevalence of deficiency was significantly higher concerning those without T2DM (p = 0.002) and was significantly higher in those who received >1 gm/day of metformin (p = 0.001). Thus, the prevalence of deficiency and borderline levels of B12 in our population was high, particularly in those >60 years of age. B12 deficiency was significantly higher in individuals with T2DM than in individuals without T2DM, especially among those receiving high doses of metformin.

Relationship of Subclinical Hypothyroidism on Epicardial Adipose Tissue: A Systematic Review and Meta-Analysis.

Accumulation of epicardial adipose tissue (EAT) and Subclinical hypothyroidism (SH) are associated with increased cardio-metabolic risk. The objective of this study was to quantitatively compare EAT thickening between patients with SH and healthy controls. Therefore, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases; we analyzed a group of observational studies who compare the EAT changes between SH vs control groups. A total of 9 studies were included in the final analysis, for a total of 424 patients with SH and 330 controls. Random or fixed effects models were used. Pooled analysis revealed that HS increased EAT (MD: 1.0 mm [0.40; 1.50]; P < 0.01). This meta-analysis suggests that the amount of EAT is significantly increased in SH patients. EAT might be a marker of cardiovascular risk in patients with SH.

Current State and Principles of Basal Insulin Therapy in Type 2 Diabetes.

Treatment with basal insulins is a fundamental part of management in many patients with type 2 diabetes mellitus. Multiple management schemes may be indicated in these individuals, for example, the use of oral antihyperglycemic agents with basal insulins (basal-supported oral therapy) or the combinations of basal insulins with glucagon-like peptide-1 receptor agonists; each of these strategies makes it easier to achieve glycemic control goals. A basic knowledge of the physiology, pharmacodynamic and pharmacokinetic aspects of the different basal insulins is essential to achieve treatment goals and compliance. This review addresses the principles of management with basal insulins.

Population Status of Iodine and Its Potential Effects on Thyroid Function and Autoimmunity in Southwestern Colombia.

Background: This study aimed to investigate the iodine status and its potential effects on thyroid function and autoimmunity in Colombia. Methods: This was a cross-sectional study, in population of urban and rural areas, from four geographic regions in the Department of Cauca, Colombia; the participants were 412 healthy adults, a third from rural areas. The following variables were evaluated: median urinary iodine concentration (mUIC), serum thyrotropin (TSH), clinical and ultrasonographic (US) goiter assessment, and anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg) and anti-TSH receptor (TRAb) concentrations. Results: The mUIC levels were 153.9 µg/L (interquartile range (IQR): 220.06); 30% had "excessive" mUIC and a quarter had "low" mUIC. The positivity of anti-Tg and anti-TPO was higher in subjects > 60 years (P = 0.017 and P ≤ 0.001, respectively). A high prevalence of "low" mUIC was found in the "low" socioeconomic status (SES) and of "more than adequate or excessive" in the "high" SES when compared with the "medium" SES (P ≤ 0.001). The prevalence of goiter by physical examination was 41.7% and 34% by US. The highest mUIC levels were significantly more prevalent in women, in subjects with elevated TSH and in those from rural areas. Conclusions: The population status of iodine in Colombia is U-shaped; the high prevalence of goiter, hypothyroidism, and thyroid autoimmunity can be explained by excess or deficit of iodine and by probable environmental goitrogens.

Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL in Insulin-Naïve People with Type 2 Diabetes: the ATOS Study.

INTRODUCTION: The clinical benefits of insulin glargine 300 U/mL (Gla-300) have been confirmed in randomised clinical trials (EDITION programme and BRIGHT) and real-world studies in the USA and Western Europe. ATOS evaluated the real-world effectiveness and safety of Gla-300 in wider geographic regions (Asia, the Middle East, North Africa, Latin America and Eastern Europe). METHODS: This prospective observational, international study enrolled adults (≥ 18 years) with type 2 diabetes mellitus (T2DM) uncontrolled [haemoglobin A1c (HbA1c) > 7% to ≤ 11%] on one or more oral anti-hyperglycaemic drugs (OADs) who had been advised by their treating physician to add Gla-300 to their existing treatment. The primary endpoint was achievement of a pre-defined individualised HbA1c target at month 6. RESULTS: Of the 4550 participants included, 4422 (51.8% female) were eligible for assessment. The mean ± standard deviation (SD) age was 57.2 ± 10.8 years, duration of diabetes was 10.2 ± 6.2 years and baseline HbA1c was 9.28 ± 1.0%. The proportion of participants reaching their individualised glycaemic target was 25.2% [95% confidence interval (CI) 23.8-26.6%] at month 6 and 44.5% (95% CI 42.9-46.1%) at month 12. At months 6 and 12, reductions were observed in HbA1c (-1.50% and -1.87%) and fasting plasma glucose (-3.42 and -3.94 mmol/L). Hypoglycaemia incidence was low, and body weight change was minimal. Adverse events were reported in 283 (6.4%) participants, with 57 (1.3%) experiencing serious adverse events. CONCLUSION: In a real-world setting, initiation of Gla-300 in people with T2DM uncontrolled on OADs resulted in improved glycaemic control and low rates of hypoglycaemia with minimal weight change. TRIAL REGISTRATION: Clinicaltrials.gov number NCT03703869.

Comparative efficacy and safety of basal insulins: A review.

BACKGROUND AND AIM: To provide an update on the usefulness of basal insulin in patients with type 2 diabetes mellitus. METHODS: We conducted a literature search using PubMed and MEDLINE, BIOSIS, Scopus, EMBASE, ClinicalTrials.gov, Google Scholar, and Springer Online Archives Collection until June 2021. RESULTS: All basal insulins are similar in efficacy, with only small differences among them in terms of the risk of hypoglycemia. CONCLUSIONS: For type 2 diabetes mellitus, all basal insulins have a similar efficacy, with some advantage of Glar-300 and Deg-100 in reducing the risk of hypoglycemia compared to Glar-100.

Challenges in familial chylomicronemia syndrome diagnosis and management across Latin American countries: An expert panel discussion.

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by extremely high triglyceride levels due to impaired clearance of chylomicrons from plasma. This paper is the result of a panel discussion with Latin American specialists who raised the main issues on diagnosis and management of FCS in their countries. Overall FCS is diagnosed late on the course of the disease, is characterized by heterogeneity on the occurrence of pancreatitis, and remains a long time in care of different specialists until reaching a lipidologist. Pancreatitis and secondary diabetes are frequently seen, often due to late diagnosis and inadequate care. Molecular diagnosis is unusual; however, loss of function variants on the lipoprotein lipase gene are apparently the most frequent etiology. A founder effect of the glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 gene has been described in the northeast of Brazil. Low awareness of the disease amongst health professionals contributes to inadequate care and an inadequate patient journey.

Dyslipidaemias and their treatment in high complexity centres in Colombia. / Las dislipidemias y su tratamiento en centros de alta complejidad en Colombia.

BACKGROUND AND OBJECTIVE: Data is scarce on the distribution of different types of dyslipidaemia in Colombia. The primary objective was to describe the frequency of dyslipidaemias. The secondary objectives were: frequency of cardiovascular comorbidity, statins and other lipid-lowering drugs use, frequency of statins intolerance, percentage of patients achieving c-LDL goals, and distribution of cardiovascular risk (CVR). MATERIALS AND METHODS: Cross-sectional study with retrospective data collection from 461 patients diagnosed with dyslipidaemia and treated in 17 highly specialised centres distributed into six geographic and economic regions of Colombia. RESULTS: Mean (SD) age was 66.4 (±12.3) years and 53.4% (246) were women. Dyslipidaemias were distributed as follows in order of frequency: mixed dyslipidaemia (51.4%), hypercholesterolaemia (41.0%), hypertriglyceridaemia (5.4%), familial hypercholesterolaemia (3.3%), and low c-HDL (0.7%). The most prescribed drugs were atorvastatin (75.7%) followed by rosuvastatin (24.9%). As for lipid control, 55% of all patients, and 28.6% of those with coronary heart disease, did not achieve their personal c-LDL goal despite treatment. The frequency of statin intolerance was 2.6% in this study. CONCLUSIONS: Mixed dyslipidaemia and hypercholesterolaemia are the most frequent dyslipidaemias in Colombia. A notable percentage of patients under treatment with lipid-lowering drugs, including those with coronary heart disease, did not achieve specific c-LDL goals. This poor lipid control may worsen patient's CVR, so that therapeutic strategies need to be changed, either with statin intensification or addition of new drugs in patients with higher CVR.

Blood pressure control and impact on cardiovascular events in patients with type 2 diabetes mellitus: A critical analysis of the literature. / Metas de control de la presión arterial e impacto sobre desenlaces cardiovasculares en pacientes con diabetes mellitus tipo 2: un análisis crítico de la literatura.

High blood pressure in individuals with type2 diabetes mellitus increases the risk of cardiovascular events. The international management guidelines recommend starting pharmacological treatment with blood pressure values >140/90mmHg. However, there is no optimal cut-off point from which cardiovascular events can be reduced without causing adverse events. A blood pressure range of >130/80 to <140/90mmHg seems to be adequate. These values can be achieved through non-pharmacological (diet, exercise) and pharmacological interventions (using drugs that have been shown to reduce cardiovascular events). The choice of one or several drugs must be individualised, according to factors including, ethnicity, age, and associated comorbidities, among others.

Iodine Status in the Colombian Population and the Impact of Universal Salt Iodization: A Double-Edged Sword?

Iodine deficiency and iodine excess have severe consequences on human health and have been associated with the presence of goiter, hypothyroidism, hyperthyroidism, thyroid cancer, thyroid nodules and thyroid autoimmunity, poor mental health, and impaired intellectual development. Universal salt iodization programs have been considered one of the most cost-effective interventions for the prevention of iodine deficiency-associated disorders, as evidenced over time since the implementation of such programs. However, these efforts have also led to an excessive consumption of iodine in certain geographical regions, due to salt overuse. Consequently, the amount of iodine derived from salt intake exceeds the established limits required for achieving the right balance between salt consumption and health benefits and leads to undesirable health effects. In Colombia, the recommendations and standards for the production and commercialization of iodized salt are fully complied with. Nevertheless, there is a remarkable rate of iodine excess among the country's population, which, at least hypothetically, represents a higher risk for developing functional and structural disorders of the thyroid gland. This review analyzes universal salt iodization programs worldwide, particularly their impact on the thyroid gland and the results of the studies conducted in Colombia following the implementation of such strategy.

Efficacy and Safety of Insulin Glargine 300 U/mL versus 100 U/mL in Diabetes Mellitus: A Comprehensive Review of the Literature.

To achieve good metabolic control in diabetes and maintain it in the long term, a combination of changes in lifestyle and pharmacological treatment is necessary. The need for insulin depends upon the balance between insulin secretion and insulin resistance. Insulin is considered the most effective glucose-lowering therapy available and is required by people with type 1 diabetes mellitus to control their blood glucose levels; yet, many people with type 2 diabetes mellitus will also eventually require insulin therapy, due to the progressive nature of the disease. A variety of long-acting insulins is currently used for basal insulin therapy (such as insulin glargine, degludec, and detemir), each having sufficient pharmacodynamic and pharmacokinetic profiles to afford lower intrapatient variability and an extended duration of action. The new glargine-300 formulation was developed to have a flatter and more extended time-action profile than the original glargine-100, and these characteristics may translate into more stable and sustained glycemic control over a 24 h dosing interval. The objective of this comprehensive review was to summarize the available evidence on the clinical efficacy and safety of glargine-300 versus glargine-100 from the EDITION clinical trial program, in patients with type 1 and type 2 diabetes mellitus.

Control of Blood Pressure and Cardiovascular Outcomes in Type 2 Diabetes.

High blood pressure in patients with diabetes mellitus results in a significant increase in the risk of cardiovascular events and mortality. The current evidence regarding the impact of intervention on blood pressure levels (in accordance with a specific threshold) is not particularly robust. Blood pressure control is more difficult to achieve in patients with diabetes than in non-diabetic patients, and requires using combination therapy in most patients. Different management guidelines recommend initiating pharmacological therapy with values >140/90 mm/Hg; however, an optimal cut point for this population has not been established. Based on the available evidence, it appears that blood pressure targets will probably have to be lower than <140/90mmHg, and that values approaching 130/80mmHg should be recommended. Initial treatment of hypertension in diabetes should include drug classes demonstrated to reduce cardiovascular events; i.e., angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, diuretics, or dihydropyridine calcium channel blockers. The start of therapy must be individualized in accordance with the patient's baseline characteristics, and factors such as associated comorbidities, race, and age, inter alia.