Laser acupuncture to reduce temporomandibular disorder (TMD) symptoms: systematic review and meta-analysis.

The application of low-level laser therapy (LLLT) to acupuncture points may produce effects similar to that of needle stimulation in patients with temporomandibular disorders (TMD). This systematic review was conducted according to the Cochrane Collaboration guidelines and aimed to address clinical questions using the following strategy: Patient/Problem, Intervention, Comparison, and Outcome (PICO). A comprehensive literature search was performed upto April 26, 2023, across nine electronic databases (BVS, PubMed, Scopus, Embase, Web of Science, ScienceDirect, Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), and Google Scholar) supplemented with gray literature. The risk of bias in randomized and nonrandomized clinical trials was assessed using two tools: risk-of-bias (RoB) 2 and Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I). Meta-analysis involved the extraction of mean and standard deviation values for spontaneous pain and mouth opening levels. Seven studies were included in this review, all of which used LLLT. The applied wavelengths ranged from 690 to 810 nm without significant variations in light emission patterns. LLLT demonstrated a significant reduction in instantaneous pain levels (standard mean difference [SMD] = 3.85; 95% confidence interval [CI] = 2.09, 5.62; p < 0.003) and an improvement in instantaneous mouth opening ability (mean difference [SMD] = -7.15; 95% CI = -11.73, -2.58; p < 0.002), with low certainty of evidence. LLLT may alleviate symptoms in patients with TMD; however, caution should be exercised when interpreting the results because of protocol variations among studies and the limited number of studies included in the meta-analysis.

HbA1c trajectories over 3 years in people with type 2 diabetes starting second-line glucose-lowering therapy: The prospective global DISCOVER study.

AIM: To identify distinct HbA1c trajectories in people with type 2 diabetes (T2D) starting second-line glucose-lowering therapy. MATERIALS AND METHODS: DISCOVER was a 3-year observational study of individuals with T2D beginning second-line glucose-lowering therapy. Data were collected at initiation of second-line treatment (baseline) and at 6, 12, 24 and 36 months. Latent class growth modelling was used to identify groups with distinct HbA1c trajectories. RESULTS: After exclusions, 9295 participants were assessed. Four distinct HbA1c trajectories were identified. Mean HbA1c levels decreased between baseline and 6 months in all groups; 72.4% of participants showed stable good levels of glycaemic control over the remainder of follow-up, 18.0% showed stable moderate levels of glycaemic control and 2.9% showed stable poor levels of glycaemic control. Only 6.7% of participants showed highly improved glycaemic control at month 6 and stable control over the rest of follow-up. For all groups, dual oral therapy use decreased over time, compensated for by the increasing use of other treatment regimens. Use of injectable agents increased over time in groups with moderate and poor glycaemic control. Logistic regression models suggested that participants from high-income countries were more probable to be in the stable good trajectory group. CONCLUSIONS: Most people receiving second-line glucose-lowering treatment in this global cohort achieved stable good or highly improved long-term glycaemic control. One-fifth of participants showed moderate or poor glycaemic control during follow-up. Further large-scale studies are required to characterize possible factors associated with patterns of glycaemic control to inform personalized diabetes treatment.

Treatment patterns and glycated haemoglobin levels over 36 months in individuals with type 2 diabetes initiating second-line glucose-lowering therapy: The global DISCOVER study.

AIMS: To describe glucose-lowering treatment regimens and glycated haemoglobin (HbA1c) trajectories in individuals with type 2 diabetes (T2D) over 36 months of follow-up from the start of second-line therapy. MATERIALS AND METHODS: This data analysis from the 3-year, observational DISCOVER study programme included 14 687 participants from 37 countries with T2D initiating second-line glucose-lowering therapy. Treatment and HbA1c data were collected at baseline (start of second-line therapy) and at 6, 12, 24 and 36 months. Treatment regimen changes over follow-up were analysed using the McNemar test, with carry-forward imputation for intermediate missing values. RESULTS: A total of 11 592 participants had treatment data at baseline and 36 months, and 11 882 had HbA1c data at baseline. At baseline and 36 months, respectively, rates of oral monotherapy use were 12.1% and 12.4% (P = 0.22), rates of dual oral therapy use were 63.4% and 47.6% (P < 0.0001), rates of ≥ triple oral therapy use were 17.5% and 25.4% (P < 0.0001), and rates of injectable treatment use were 7.0% and 13.7% (P < 0.0001). Use of injectable drugs was most common among participants with an HbA1c level ≥64 mmol/mol (≥8.0%). Overall, 42.9% of participants changed treatment during follow-up. Mean HbA1c levels at baseline and 6 months were 67 mmol/mol (8.3%) and 55 mmol/mol (7.2%), respectively, remaining stable thereafter. CONCLUSIONS: Dual oral therapy was the most common treatment regimen at the start of second-line treatment, and over half of the participants remained on the same treatment during follow-up.

The Challenging Management of Acute Thrombotic Microangiopathy in Pregnancy.

Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ injury. Pregnancy-associated thrombotic microangiopathy is a severe disorder with a high risk of maternal mortality and poor fetal outcomes. Preeclampsia/eclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are the most common causes, and hemolytic uremic syndrome or thrombotic thrombocytopenic purpura are rare causes. Due to overlapping clinical findings, the differential diagnosis is challenging and should be managed by a multidisciplinary team. We present a case of a 38-year-old woman at 40 weeks of second gestation, admitted with thrombotic microangiopathy being the final diagnosis not immediately clear.

Incidence rates and predictors of microvascular and macrovascular complications in patients with type 2 diabetes: Results from the longitudinal global discover study.

BACKGROUND: Micro- and macrovascular complications are a major cause of morbidity and mortality in people with type 2 diabetes (T2D). We sought to understand the global incidence rates and predictors of these complications. METHODS: We examined the incidence of vascular complications over 3 years of follow-up in the DISCOVER study-a global, observational study of people with T2D initiating second-line glucose-lowering therapy. Hierarchical Cox proportional hazards regression models examined factors associated with development of micro- and macrovascular complications during follow-up. RESULTS: Among 11,357 people with T2D from 33 countries (mean age 56.9 ± 11.7 years, T2D duration 5.7 ± 5.1 years, HbA1c 8.4 ± 1.7%), 19.0% had a microvascular complication at enrolment (most commonly neuropathy), and 13.2% had a macrovascular complication (most commonly coronary disease). Over 3 years of follow-up, 16.0% developed an incident microvascular complication, and 6.6% had an incident macrovascular complication. At the end of 3 years of follow-up, 31.5% of patients had at least one microvascular complication, and 16.6% had at least one macrovascular complication. Higher HbA1c and smoking were associated with greater risk of both incident micro- and macrovascular complications. Known macrovascular complications at baseline was the strongest predictor for development of new microvascular complications (HR 1.40, 95% CI 1.21 -1.61) and new macrovascular complications (HR 3.39, 95% CI 2.84 -4.06). CONCLUSIONS: In this global study, both the prevalence and 3-year incidence of vascular complications were high in patients with relatively short T2D duration, highlighting the need for early risk-factor modification.

Factors associated with weight loss in people with overweight or obesity living with type 2 diabetes mellitus: Insights from the global DISCOVER study.

AIMS: To estimate real-world change in weight over 3 years and the factors influencing it in participants who are overweight and live with type 2 diabetes. MATERIALS AND METHODS: DISCOVER is a multinational prospective observational study that enrolled participants with type 2 diabetes between December 2014 and June 2016 at the time of initiation of a second-line glucose-lowering medication (GLM). Demographic, anthropometric, and quality-of-life data were collected at baseline, and after 6, 12, 24 and 36 months of follow-up. Using a hierarchical, repeated-measures linear regression model, we examined factors associated with weight change over time. RESULTS: Of 10 675 participants with type 2 diabetes who were overweight/obese (mean age 57.1 ± 11.1 years, 46% women), 21% lost ≥5% weight over 3 years, which was associated with modestly improved physical and mental health. Advancing age, female sex, and higher baseline weight were associated with weight loss. Most importantly, the type of GLM prescribed at previous visit had the strongest impact on weight change over time independent of participant factors, with use of a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist associated with 1.0% weight loss versus a 0.6% weight gain with sulphonylureas, thiazolidinediones, meglitinides or insulin. CONCLUSION: In this large contemporary prospective study, approximately one in five participants with early-stage type 2 diabetes and overweight/obesity lost ≥5% weight over 3 years. The type of GLM has the most impact on weight loss over time, highlighting the need for a careful selection of agents that takes baseline weight into consideration.

Global use of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes. Results from DISCOVER.

BACKGROUND: Despite strong evidence of benefit, uptake of newer glucose-lowering medications that reduce cardiovascular risk has been low. We sought to examine global trends and predictors of use of SGLT2i and GLP-1 RA in patients with type 2 diabetes. METHODS: DISCOVER is a global, prospective, observational study of patients with diabetes enrolled from 2014-16 at initiation of second-line glucose-lowering therapy and followed for 3 years. We used hierarchical logistic regression to examine factors associated with use of either an SGLT2i or GLP-1 RA at last follow-up and to assess country-level variability. RESULTS: Among 14,576 patients from 37 countries, 1579 (10.8%) were started on an SGLT2i (1275; 8.7%) or GLP-1 RA (318; 2.2%) at enrollment, increasing to 16.1% at end of follow-up, with large variability across countries (range 0-62.7%). Use was highest in patients treated by cardiologists (26.1%) versus primary care physicians (10.4%), endocrinologists (16.9%), and other specialists (22.0%; p < 0.001). Coronary artery disease (OR 1.29, 95% CI 1.08-1.54) was associated with greater use of SGLT2i or GLP-1 RA while peripheral artery disease (OR 0.73, 95% CI 0.54-1.00) and chronic kidney disease (OR 0.73, 95% CI 0.58-0.94) were associated with lower use (OR 0.73, 95% CI 0.54-1.00). The country-level median odds ratio was 3.48, indicating a very large amount of variability in the use of SGLT2i or GLP-1 RA independent of patient demographic and clinical factors. CONCLUSIONS: Global use of glucose-lowering medications with established cardiovascular benefits has increased over time but remains suboptimal, particularly in sub-groups most likely to benefit. Substantial country-level variability exists independent of patient factors, suggesting structural barriers may limit more widespread use of these medications.

Pragmatic Clinic-Based Investigation of Glycemic Variability in Patients With Type 1 Diabetes in Routine Clinical Practice and Its Association With Cardiovascular Autonomic Neuropathy: A Pilot Study.

OBJECTIVE: To evaluate the relationship between markers of glycemic variability (GV), assessed by blinded continuous glucose monitoring (CGM), and cardiovascular autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D). METHODS: GV indices, such as SD and coefficient of variation were obtained by blinded CGM through an electrode inserted into the subcutaneous tissue for at least 3 consecutive days. CAN was assessed by cardiovascular reflex tests and HRV. RESULTS: Fifteen T1D patients were included: 7 (46.7%) women, aged 47.1 ± 11.6 years, with a diabetes duration of 26 years (20 to 29.5 years). Five patients (25%) were excluded from our study. The majority of our patients presented glycated hemoglobin (60%), SD (86.3%), and coefficient of variation (60%) above the established goals. Patients with defined CAN had a longer diabetes duration, higher glycated hemoglobin levels, lower glomerular filtration rate, lower prevalence of indices related to hypoglycemic stress, and short-term GV indices compared with patients without CAN. CONCLUSION: Our study showed an inverse association between GV and CAN. The most important risk factors associated with CAN were age, diabetes duration, and markers of chronic hyperglycemia. Furthermore, the difficulty in the interpretation of data extracted from the blinded CGM system, which also requires a minimum of 3 capillary blood glucose measurements for calibration, should be carefully analyzed to ensure the accuracy and usefulness of the blinded CGM system as a tool for diabetes management in developing countries. Further studies are necessary to establish the role of GV in the development of CAN in patients with T1D.

[Reregistration of the population residing in Foz do Iguaçu, Brazil, in compliance with the Primary Health Care PolicyReinscripción de la población residente en Foz do Iguaçu, Brasil, en cumplimiento de la Política de atención primaria de salud]. / Recadastramento da população residente em Foz do Iguaçu, Brasil, em atendimento à Política de Atenção Primária à Saúde.

Objective: To present the experience and results of the reregistration of residents in Foz do Iguaçu, a border town located in the state of Paraná, Brazil, to meet the guidelines of the national Primary Health Care (PHC) Policy and its new financing model (Programa Previne Brasil). Method: A scanning strategy (convenience sample) was used for data collection, with 52 263 households visited and 22 710 interviews conducted from September to November 2019. The interviews were conducted face-to-face by 54 community health workers. Data were collected on the household (ownership status, urban or rural location, type of household, construction material, availability of electrical and sewage networks, water supply and waste disposal). Demographic and health information on the residents was also collected. Results: The reregistration process revealed that most residents were home owners and lived in well-constructed homes, located mostly in urban areas, served by electricity, with access to water supply and garbage collection. Of the reregistered population, 52.8% were women, 62.5% were aged between 15 and 59 years and 60.0% declared themselves white. Among respondents aged 15 or over, 90.0% had completed elementary school. The main occupation was "formal salaried job". Additionally, 18.6% of the interviewees declared themselves to be hypertensive and 7.0%, diabetic. Conclusions: The reregistration process uncovered relevant information to support both PHC planning as well as social assistance, work and housing initiatives; it was also fundamental to define health care strategies in this border town during the COVID-19 pandemic.

Objetivo: Presentar la experiencia y los resultados de la reinscripción de la población residente en Foz do Iguaçu, un municipio fronterizo ubicado en el estado de Paraná (Brasil), en cumplimiento de las directrices de la Política de atención primaria de salud y su nuevo modelo de financiamiento (Programa Previne Brasil). Métodos: Utilizando una estrategia de barrido (muestreo de conveniencia) para la recolección de datos, se visitaron 52 263 hogares y se realizaron 22 710 entrevistas entre septiembre y noviembre de 2019. Las entrevistas fueron presenciales y estuvieron a cargo de 54 trabajadores comunitarios de salud. Se recopilaron datos sobre el hogar (régimen de propiedad de la vivienda, ubicación en una zona urbana o rural, tipo de vivienda, material de construcción, disponibilidad de redes de energía eléctrica y alcantarillado, abastecimiento de agua y eliminación de desechos) e información sobre la composición demográfica y la salud de los residentes. Resultados: La reinscripción reveló que los residentes eran propietarios de sus viviendas y que estas se encontraban ubicadas en zonas urbanas, estaban bien construidas y tenían servicios de energía eléctrica, abastecimiento de agua y recolección de basura. El 52,8% de la población registrada correspondió a mujeres, el 62,5% tenía entre 15 y 59 años y el 60,0% declaró que era de raza blanca. El 90,0% de los entrevistados mayores de 15 años había terminado la escuela primaria. La ocupación principal era "persona asalariada con carnet de trabajo". Además, el 18,6% de los entrevistados indicó que tenía hipertensión y el 7,0%, diabetes. Conclusiones: La reinscripción aportó información relevante para apoyar la planificación de la atención primaria de salud , así como las iniciativas en materia de asistencia social, trabajo y vivienda; también fue fundamental para definir las estrategias de atención de salud en ese municipio fronterizo durante la pandemia de COVID-19.

Associations between second-line glucose-lowering combination therapies with metformin and HbA1c, body weight, quality of life, hypoglycaemic events and glucose-lowering treatment intensification: The DISCOVER study.

AIM: To explore the effects of second-line combination therapies with metformin on body weight, HbA1c and health-related quality of life, as well as the risks of hypoglycaemia and further treatment intensification in the DISCOVER study, a 3-year, prospective, global observational study of patients with type 2 diabetes initiating second-line glucose-lowering therapy. MATERIALS AND METHODS: Adjusted changes from baseline in weight, HbA1c and 36-item Short Form Health Survey version 2 (SF-36v2) summary scores at 6, 12, 24 and 36 months were assessed using linear mixed models. Risk of hypoglycaemia and further intensification were assessed using interval censored analyses. RESULTS: At baseline, 7613 patients received metformin in combination with a sulphonylurea (SU; 40.9%), a dipeptidyl peptidase-4 (DPP-4) inhibitor (48.3%), a sodium-glucose co-transporter-2 (SGLT-2) inhibitor (8.3%) or a glucagon-like peptide-1 (GLP-1) receptor agonist (2.4%). After 36 months, all combinations showed similar reductions in HbA1c (0.8%-1.0%), however, metformin plus a DPP-4 inhibitor, an SGLT-2 inhibitor or a GLP-1 receptor agonist was associated with greater weight loss (1.9, 2.9 and 5.0 kg, respectively) than metformin plus an SU (1.3 kg, P < .0001). Proportions of further treatment intensification were similar across combinations (19.9%-26.2%). Patients prescribed metformin plus an SU more often reported one or more hypoglycaemic events (11.9%) than other combinations (3.9%-6.4%, P < .0001). SF-36v2 summary scores were typically lowest among patients prescribed metformin and an SU. CONCLUSIONS: Combinations of metformin with an SU were associated with the lowest weight reduction, highest risk of hypoglycaemia and lower SF-36v2 scores.

What are the factors associated with long-term glycaemic control in patients with type 2 diabetes and elevated glycated haemoglobin (≥7.0%) at initiation of second-line therapy? Results from the DISCOVER study.

AIMS: Glycaemic control is a cornerstone of type 2 diabetes (T2D) management. We assessed factors associated with good long-term glycaemic control in patients with glycated haemoglobin (HbA1c) ≥7.0% at initiation of second-line glucose-lowering therapy, using data from DISCOVER, a global, prospective, 3-year observational study of patients with T2D. MATERIALS AND METHODS: This analysis included patients with HbA1c ≥7.0% at baseline (initiation of second-line therapy). Multivariable regression models assessed factors associated with having HbA1c <7.0% at 3 years in two distinct groups: patients with (a) HbA1c ≥7.0% and <9.0%, and (b) HbA1c ≥9.0% at baseline. RESULTS: In total, 7575 patients with baseline HbA1c ≥7.0% were included (2233 with baseline HbA1c ≥9.0%). At 6 months, 43.7% and 24.2% of patients had an HbA1c level <7.0% in groups a and b, respectively; the corresponding proportions at 3 years were 45.8% and 29.3%. Having HbA1c <7.0% at 6 months (vs. ≥7.0%) was the strongest predictor of having HbA1c <7.0% at 3 years in both group a and group b [odds ratio (95% confidence interval): 2.01 (1.77-2.27) and 2.68 (2.10-3.41), respectively]. Longer T2D duration was associated with a decreased likelihood of having HbA1c <7.0% at 3 years. CONCLUSIONS: In patients with poor glycaemic control at initiation of second-line therapy, early attainment of HbA1c <7.0% appears predictive of long-term glycaemic control, suggesting that timely modification of treatment strategies in patients with elevated HbA1c after 6 months is important to minimize therapeutic inertia.

Global patterns of comprehensive cardiovascular risk factor control in patients with type 2 diabetes mellitus: Insights from the DISCOVER study.

AIM: To investigate global patterns of cardiovascular risk factor control in patients with type 2 diabetes mellitus (T2D). METHODS: DISCOVER is an international, observational cohort study of patients with T2D beginning second-line glucose-lowering therapy. Risk factor management was examined among eligible patients (ie, those with the risk factor) at study baseline. Inter-country variability was estimated using median odds ratios (MORs). RESULTS: Among 14 343 patients with T2D from 34 countries, the mean age was 57.4 ± 12.0 years and the median (interquartile range) duration of T2D was 4.2 (2.0-8.0) years; 11.8% had documented atherosclerotic cardiovascular disease (ASCVD). Among eligible patients, blood pressure was controlled in 67.5% (9284/13756), statins were prescribed in 43.7% (5775/13208), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers were prescribed in 55.6% (5292/9512), aspirin was prescribed in 53.3% of those with established ASCVD (876/1645), and 84.4% (12 102/14343) were non-smoking. Only 21.5% of patients (3088/14343) had optimal risk factor management (defined as control of all eligible measures), with wide inter-country variability (10%-44%), even after adjusting for patient and site differences (MOR 1.47, 95% confidence interval 1.24-1.66). CONCLUSION: Globally, comprehensive control of ASCVD risk factors is not being achieved in most patients, with wide variability among countries unaccounted for by patient and site differences. Better country-specific strategies are needed to implement comprehensive cardiovascular risk factor control consistently in patients with T2D to improve long-term outcomes.

Prevalence and progression of chronic kidney disease among patients with type 2 diabetes: Insights from the DISCOVER study.

We report the prevalence and change in severity of chronic kidney disease (CKD) in DISCOVER, a global, 3-year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy. CKD stages were defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m2 ), baseline prevalence estimates for stage 0-1, 2, 3 and 4-5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow-up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9-3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/1.73 m2 over follow-up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second-line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment.

Glycaemic control in patients with type 2 diabetes initiating second-line therapy: Results from the global DISCOVER study programme.

AIM: To assess glycaemic control and factors associated with poor glycaemic control at initiation of second-line therapy in the DISCOVER programme. MATERIALS AND METHODS: DISCOVER (NCT02322762 and NCT02226822) comprises two similar prospective observational studies of 15 992 people with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy in 38 countries across six regions (Africa, Americas, South-East Asia, Eastern Mediterranean, Europe and Western Pacific). Data were collected using a standardized case report form. Glycated haemoglobin (HbA1c) levels were measured according to standard clinical practice in each country, and factors associated with poor glycaemic control (HbA1c >8.0%) were evaluated using hierarchical regression models. RESULTS: HbA1c levels were available for 80.9% of patients (across-region range [ARR] 57.5%-97.5%); 92.2% (ARR 59.2%-99.1%) of patients had either HbA1c or fasting plasma glucose levels available. The mean HbA1c was 8.3% (ARR 7.9%-8.7%). In total, 26.7% of patients had an HbA1c level ≥9.0%, with the highest proportions in South-East Asia (35.6%). Factors associated with having HbA1c >8.0% at initiation of second-line therapy included low education level, low country income, and longer time since T2D diagnosis. CONCLUSIONS: The poor levels of glycaemic control at initiation of second-line therapy suggest that intensification of glucose-lowering treatment is delayed in many patients with T2D. In some countries, HbA1c levels are not routinely measured. These findings highlight an urgent need for interventions to improve monitoring and management of glycaemic control worldwide, particularly in lower-middle- and upper-middle-income countries.

Genomic ancestry and glycemic control in adolescents with type 1 diabetes: A multicenter study in Brazil.

OBJECTIVE: To determine the influence of genomic ancestry (GA) and self-reportedcolor-race (SRCR) on glycemic control in adolescents with type 1 diabetes (T1D) in an admixed population. RESEARCH DESIGN AND METHODS: This multicenter nationwide study was conducted in 14 public clinics in 10 Brazilian cities. We estimated global and individual African, European, and Native Amerindian GA proportions using a panel of 46 AIM-INDEL markers. From 1760 patients, 367 were adolescents (20.9%): 184 female (50.1%), aged 16.4 ± 1.9 years, age at diagnosis 8.9 ± 4.3 years, duration of diabetes 8.1 ± 4.3 years, years of study 10.9 ± 2.5 and HbA1c of 9.6 ± 2.4%. RESULTS: Patients SRCR as White: 176 (48.0%), Brown: 159 (43.3%), Black: 19(5.2%), Asians: 5 (1.4%) and Amerindians: 8 (2.2%). The percentage of European GA prevailed in all groups: White (71.1), Brown (58.8), Black (49.6), Amerindians (46.1), and Asians (60.5). Univariate correlation was noted between A1c and African GA, r = 0.11, P = .03; years of study, r = -0.12 P = .010, and having both private and public health care insurance (r = -0.20, P < .001). After adjustments, the multivariate logistic analysis showed that SRCR or GA did not influence glycemic control. CONCLUSIONS: A high percentage of European GA was noted in our patients, even in those who self-reported as non-White, confirming the highly admixed ethnicity of the Brazilian population. Better glycemic control was associated with having both types of health care; however, there was no association between glycemic control with GA or SRCR. Future prospective studies with other admixed populations are necessary to confirm our findings.

Relationship between Proliferative Diabetic Retinopathy and Inflammatory Markers in Patients with Type 1 Diabetes in Brazil: A Nested Case Control Study.

INTRODUCTION: This study examined the relationship between proliferative diabetic retinopathy (PDR) and serum levels of C-reactive protein, VEGF, TNF-α, and IL-6 inflammatory biomarkers, related to the pathophysiology of diabetic retinopathy. METHODS: This cross-sectional, case control study comprised 240 patients with type 1 diabetes (80 cases with PDR and 160 controls without diabetic retinopathy) who were matched for gender and duration of diabetes. RESULTS: C-reactive protein was the only inflammatory biomarker that was positively related to PDR (OR 1.96; 95% CI 1.01-3.78, p = 0.0045). We also noted an association between high glycated hemoglobin levels, the use of angiotensin-converting enzyme inhibitor, low glomerular filtration rate, and PDR. CONCLUSION: Patients with higher levels of C-reactive protein are more likely to present with PDR. We did not find a link between serum levels of VEGF, TNF-α, or IL-6 and PDR. The function of inflammatory biomarkers in PDR must be addressed in further studies.

Treatment patterns and associated factors in 14 668 people with type 2 diabetes initiating a second-line therapy: Results from the global DISCOVER study programme.

AIM: To evaluate treatment data from DISCOVER (NCT02322762 and NCT02226822), a global, prospective, observational study programme of patients with type 2 diabetes initiating a second-line glucose-lowering therapy. MATERIALS AND METHODS: Data were collected using a standardized case report form. First- and second-line treatments were assessed in 14 668 patients from 37 countries across six regions. Among patients prescribed first-line metformin monotherapy, Firth logistic regression models were used to assess factors associated with second-line treatment choices. RESULTS: The most common first-line therapies were metformin monotherapy (57.9%) and combinations of metformin with a sulphonylurea (14.6%). The most common second-line therapies were combinations of metformin with other agents (72.2%), including dipeptidyl peptidase-4 (DPP-4) inhibitors (25.1%) or sulphonylureas (21.3%). Among patients prescribed first-line metformin monotherapy, the most common second-line therapies were combinations of metformin with a DPP-4 inhibitor [32.8%; across-region range (ARR): 2.4%-51.3%] or a sulphonylurea (30.0%; ARR: 18.3%-63.6%); only a few patients received combinations of metformin with sodium-glucose co-transporter-2 inhibitors (6.7%; ARR: 0.0%-10.8%) or glucagon-like peptide-1 receptor agonists (1.9%; ARR: 0.1%-4.5%). Both clinical and non-medical factors were associated with choice of second-line therapy after metformin monotherapy. CONCLUSIONS: Fewer patients than expected received metformin monotherapy at first line, and the use of newer therapies at second line was uncommon in some regions of the world. Patients' socioeconomic status was associated with treatment patterns, suggesting that therapy choices are influenced by cost and access.

Vascular complications in patients with type 2 diabetes: prevalence and associated factors in 38 countries (the DISCOVER study program).

BACKGROUND: The global prevalence of type 2 diabetes-related complications is not well described. We assessed prevalence of vascular complications at baseline in DISCOVER (NCT02322762; NCT02226822), a global, prospective, observational study program of 15,992 patients with type 2 diabetes initiating second-line therapy, conducted across 38 countries. METHODS: Patients were recruited from primary and specialist healthcare settings. Data were collected using a standardized case report form. Prevalence estimates of microvascular and macrovascular complications at baseline were assessed overall and by country and region, and were standardized for age and sex. Modified Poisson regression was used to assess factors associated with the prevalence of complications. RESULTS: The median duration of type 2 diabetes was 4.1 years (interquartile range [IQR]: 1.9-7.9 years), and the median glycated hemoglobin (HbA1c) level was 8.0% (IQR: 7.2-9.1%). The crude prevalences of microvascular and macrovascular complications were 18.8% and 12.7%, respectively. Common microvascular complications were peripheral neuropathy (7.7%), chronic kidney disease (5.0%), and albuminuria (4.3%). Common macrovascular complications were coronary artery disease (8.2%), heart failure (3.3%) and stroke (2.2%). The age- and sex-standardized prevalence of microvascular complications was 17.9% (95% confidence interval [CI] 17.3-18.6%), ranging from 14.2% in the Americas to 20.4% in Europe. The age- and sex-standardized prevalence of macrovascular complications was 9.2% (95% CI 8.7-9.7%), ranging from 4.1% in South-East Asia to 18.8% in Europe. Factors positively associated with vascular complications included age (per 10-year increment), male sex, diabetes duration (per 1-year increment), and history of hypoglycemia, with rate ratios (95% CIs) for microvascular complications of 1.14 (1.09-1.19), 1.30 (1.20-1.42), 1.03 (1.02-1.04) and 1.45 (1.25-1.69), respectively, and for macrovascular complications of 1.41 (1.34-1.48), 1.29 (1.16-1.45), 1.02 (1.01-1.02) and 1.24 (1.04-1.48), respectively. HbA1c levels (per 1.0% increment) were positively associated with microvascular (1.05 [1.02-1.08]) but not macrovascular (1.00 [0.97-1.04]) complications. CONCLUSIONS: The global burden of microvascular and macrovascular complications is substantial in these patients with type 2 diabetes who are relatively early in the disease process. These findings highlight an opportunity for aggressive early risk factor modification, particularly in regions with a high prevalence of complications. Trial registration ClinicalTrials.gov; NCT02322762. Registered 23 December 2014. https://clinicaltrials.gov/ct2/show/NCT02322762 . ClinicalTrials.gov; NCT02226822. Registered 27 August 2014. https://clinicaltrials.gov/ct2/show/NCT02226822.

Sensibility and specificity of laser speckle contrast imaging according to Endo-PAT index in type 1 diabetes.

OBJECTIVES: To find out an normality value for microvascular response (physiological and pharmacological) assessed through laser speckle contrast imaging (LSCI) based on Endo-PAT, which identifies the ones with Endothelial Dysfunction (ED) in patients with Type 1 Diabetes (T1D). METHODS: Patients with T1D, aged ≥12years underwent a clinical-epidemiological questionnaire. Fasting blood samples were obtained (lipid profile, glycemic control and levels of C-reactive protein). Vascular reactivity was assessed in the forearm through the technique of LSCI at baseline, during post occlusive reactive hyperemia (PORH) and during iontophoresis of acetylcholine (ACh) and peripheral arterial tonometry was performed by supplying the RHI through Endo-PAT device. RESULTS: 189 patients were evaluated, 97 women (51.3%) with T1D, aged 32±13years and with a disease duration of 16 (6-21) years and mean A1c of 9.2% (±2.2). Receiver Operating Characteristics curve (ROC) analysis according to RHI showed that the Area under curve (AUC) of ACh of 10,369 Laser Speckle Perfusion Unit (LSPU) presented sensitivity and specificity of 65% and 87,5%, respectively, (p=0.002) in those patients with T1D's duration <5years. Overall, no test of vascular reactivity was able to distinguish the ideal cuttoff based on RHI. CONCLUSION: In the present study, we could find an ideal cut off value of microcirculation assessment through endothelium-dependent vasodilation to ACh using LSCI according to Endo-PAT's score, only in those under 5years of disease duration. Further prospective studies shall be conducted to evaluate its predictive cardiovascular value.

Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: A systematic review.

AIMS: Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner according to evidence-based clinical guidelines, is a key reason for uncontrolled hyperglycaemia in patients with type 2 diabetes. The aims of this systematic review were to identify how therapeutic inertia in the management of hyperglycaemia was measured and to assess its extent over the past decade. MATERIALS AND METHODS: Systematic searches for articles published from January 1, 2004 to August 1, 2016 were conducted in MEDLINE and Embase. Two researchers independently screened all of the titles and abstracts, and the full texts of publications deemed relevant. Data were extracted by a single researcher using a standardized data extraction form. RESULTS: The final selection for the review included 53 articles. Measurements used to assess therapeutic inertia varied across studies, making comparisons difficult. Data from low- to middle-income countries were scarce. In most studies, the median time to treatment intensification after a glycated haemoglobin (HbA1c) measurement above target was more than 1 year (range 0.3 to >7.2 years). Therapeutic inertia increased as the number of antidiabetic drugs rose and decreased with increasing HbA1c levels. Data were mainly available from Western countries. Diversity of inertia measures precluded meta-analysis. CONCLUSIONS: Therapeutic inertia in the management of hyperglycaemia in patients with type 2 diabetes is a major concern. This is well documented in Western countries, but corresponding data are urgently needed in low- and middle-income countries, in view of their high prevalence of type 2 diabetes.