Achievement of Treatment Goals and Mortality in Individuals with Diabetes: The ELSA-Brasil Study.

BACKGROUND: To prevent diabetes complications, the American Diabetes Association (ADA) has recommended the treatment of blood glucose, blood pressure, and LDL-cholesterol (LDL-c) to target levels. Our aim is to characterize the risk of death according to the achievement of these goals in subjects with diabetes participating in the ELSA-Brasil study. METHODS: ELSA-Brasil is an occupational cohort study of middle-aged and elderly adults followed from a 2008-2010 baseline to 2019 by two additional clinic visits and annual telephone interviews. We ascertained known diabetes by self-reported diagnosis or anti-diabetic medication use. We used treatment targets based on the 2022 ADA guidelines. We ascertained deaths from any cause based on the annual surveillance confirmed by death certificates. RESULTS: After 11 (1.8) years of follow-up, 261 subjects had died among 2423 with known diabetes. Within-target HbA1c was associated with the greatest protection (HR = 0.66; 95%CI 0.50-0.88) against all-cause mortality. Achieving both glycemic and blood pressure targets conferred substantial protection (HR = 0.54; 95%CI 0.37-0.78). Within-target LDL-c, however, was associated with increased mortality (HR = 1.44; 95%CI 1.11-1.88). CONCLUSIONS: Glucose and blood pressure control, especially when concomitant, reduced mortality. The increased mortality associated with achieving the LDL-c target merits further investigation.

Levels and correlates of risk factor control in diabetes mellitus -ELSA-Brasil.

BACKGROUND: Control of glucose, blood pressure, cholesterol, and smoking improves the prognosis of individuals with diabetes mellitus. Our objective was to assess the level of control of these risk factors in Brazilian adults with known diabetes and evaluate correlates of target achievement. METHODS: Cross-sectional sample of the Brazilian Longitudinal Study of Adult Health, composed of participants reporting a previous diagnosis of diabetes or the use oof antidiabetic medication. We measured glycated hemoglobin (HbA1c) and LDL-cholesterol at a central laboratory and blood pressure following standardized protocols. We defined HbA1c < 7% as glucose control (target A); blood pressure < 140/90 mmHg (or < 130/80 mmHg in high cardiovascular risk) as blood pressure control (target B), and LDL-c < 100 mg/dl (or < 70 mg/dl in high risk) as lipid control (target C), according to the 2022 American Diabetes Association guidelines. RESULTS: Among 2062 individuals with diabetes, 1364 (66.1%) reached target A, 1596 (77.4%) target B, and 1086 (52.7%) target C; only 590 (28.6%) achieved all three targets. When also considering a non-smoking target, those achieving all targets dropped to 555 (26.9%). Women (PR = 1.13; 95%CI 1.07-1.20), those aged ≥ 74 (PR = 1.20; 95%CI 1.08-1.34), and those with greater per capita income (e.g., greatest income PR = 1.26; 95%CI 1.10-1.45) were more likely to reach glucose control. Those black (PR = 0.91; 95%CI 0.83-1.00) or with a longer duration of diabetes (e.g., ≥ 10 years PR = 0.43; 95%CI 0.39-0.47) were less likely. Women (PR = 1.05; 95%CI 1.00-1.11) and those with private health insurance (PR = 1.15; 95%CI 1.07-1.23) were more likely to achieve two or more ABC targets; and those black (PR = 0.86; 95%CI 0.79-0.94) and with a longer duration of diabetes (e.g., > 10 years since diabetes diagnosis, PR = 0.68; 95%CI 0.63-0.73) less likely. CONCLUSION: Control of ABC targets was poor, notably for LDL-c and especially when considering combined control. Indicators of a disadvantaged social situation were associated with less frequent control.

Diagnostic yield of multi-gene panel for muscular dystrophies and other hereditary myopathies.

Genetic testing is being considered the first-step in the investigation of hereditary myopathies. However, the performance of the different testing approaches is little known. The aims of the present study were to evaluate the diagnostic yield of a next-generation sequencing panel comprising 39 genes as the first-tier test for genetic myopathies diagnosis and to characterize clinical and molecular findings of families from southern Brazil. Fifty-one consecutive index cases with clinical suspicion of genetic myopathies were recruited from October 2014 to March 2018 in a cross-sectional study. The overall diagnostic yield of the next-generation sequencing panel was 52.9%, increasing to 60.8% when including cases with candidate variants. Multi-gene panel solved the diagnosis of 12/25 (48%) probands with limb-girdle muscular dystrophies, of 7/14 (50%) with congenital muscular diseases, and of 7/10 (70%) with muscular dystrophy with prominent joint contractures. The most frequent diagnosis for limb-girdle muscular dystrophies were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related; for congenital muscular diseases, RYR1-related-disorders; and for muscular dystrophy with prominent joint contractures, Emery-Dreifuss-muscular-dystrophy-type-1 and COL6A1-related-disorders. In summary, the customized next-generation sequencing panel when applied in the initial investigation of genetic myopathies results in high diagnostic yield, likely reducing patient's diagnostic odyssey and providing important information for genetic counseling and participation in disease-specific clinical trials.

A systematic review and evidence-based guideline for diagnosis and treatment of Menkes disease.

Menkes disease is a rare X-linked neurodegenerative disorder caused by defect in copper metabolism. Parenteral copper supplementation has been used as a potential disease-modifying treatment of Menkes disease for decades. However, recent evidence suggests its efficacy only when treatment is started within days after birth, which also has important implications related to the techniques that enable early diagnosis. We aim at proposing a guideline for prenatal and neonatal diagnosis and for disease-modifying treatment of Menkes disease, guided by a systematic review of the literature, and built in conjunction with medical experts, methodologists and patient representatives. Thirteen articles were used for our recommendations that were based on GRADE system. Reviewed evidence suggests that prenatal genetic diagnosis in families with previous diagnosis of Menkes disease is feasible; analysis of plasma catecholamine levels is accurate for neonatal diagnosis of Menkes disease; treatment with copper-histidine is effective to increase survival and reduce neurologic burden of the disease if initiated in the neonatal period; and, treatment indication should not be guided by patient's genotype. In conclusion, our guideline can contribute to standardize some aspects of the clinical care of patients with Menkes disease, especially reducing disease burden and mortality and providers' and families' anxiety.