Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes.

BACKGRUOUND: This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c). METHODS: Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence. RESULTS: During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53). CONCLUSION: HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Prognostic Impact of On-Treatment Cumulative Ambulatory Blood Pressures for Adverse Macro- and Microvascular Outcomes in Individuals With Type 2 Diabetes: The Rio de Janeiro Type 2 Diabetes Cohort.

BACKGROUND: The prognostic value of on-treatment mean cumulative ambulatory blood pressures (BPs) in type 2 diabetes has never been investigated. We aimed to assess it in a prospective cohort of 647 individuals with type 2 diabetes. METHODS: Clinic-office and ambulatory BPs were measured at baseline and serially during follow-up. Multivariable Cox analyses assessed the associations between baseline and mean cumulative BPs with the occurrence of cardiovascular events, major adverse cardiovascular events, all-cause and cardiovascular mortality, and microvascular outcomes (microalbuminuria, renal failure, retinopathy, and peripheral neuropathy). C statistics and the integrated discrimination improvement (IDI) index evaluated the improvement in risk discrimination by using cumulative ambulatory BPs instead of baseline BPs. RESULTS: Over a median follow-up of 10.6 years, there were 202 cardiovascular events (163 major adverse cardiovascular events), 254 all-cause deaths (118 cardiovascular); 125 individuals had microalbuminuria development/progression, 104 developed advanced renal failure, 159 had retinopathy, and 174 individuals had peripheral neuropathy development/progression. The risks associated with mean cumulative ambulatory BPs were in general higher than those associated with baseline BPs, particularly for cardiovascular (HR, 1.42 versus 1.25 for increments of 1 SD in 24-hour systolic blood pressure) and mortality outcomes (1.56 versus 1.26). Compared with cumulative clinic BPs, mean cumulative ambulatory BPs improved risk discrimination for most outcomes, with IDIs from 11% to 14% for major adverse cardiovascular events and mortality up to 24% to 26% for microalbuminuria and neuropathy. CONCLUSIONS: Compared with clinic-office BPs, mean cumulative ambulatory BPs during follow-up improve risk discrimination for most complications and mortality in individuals with type 2 diabetes. Serial ambulatory BP monitoring shall be more widely used in clinical management.

Diabetes in a hospital cohort of persons living with HIV: a descriptive and comparative study in French Guiana.

BACKGROUND: In French Guiana (population 294,000) the prevalence of type 2 diabetes (10%) and of HIV(1.1%) are very high. Our objective was to determine the prevalence of diabetes and its complications in a HIV cohort. MATERIALS AND METHODS: We enrolled HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals between January 1, 1992 and December 31, 2021 in the French Hospital Database for HIV (FHDH) a national database compiling data from all French regions. RESULTS: There was no difference of diabetes prevalence between men (8.2%) and women (8.8%), P = 0.4. Patients with diabetes were older (56 years ± 13.4) than those without diabetes (44.7 years ± 13.6) and prevalence increased with age. The proportion of persons with diabetes was greater among virologically suppressed persons (10%) than those with a detectable viral load under antiretroviral treatment (5.8%). Persons with diabetes had substantially greater CD4 counts at diagnosis than persons without diabetes. The majority of macro and microvascular complications were observed in people with diabetes. Persons with diabetes and HIV were significantly less likely to have had AIDS (1.6 versus 2.2 per 100 person-years, respectively). Overall, 374 persons living with HIV of 4167 had died (9%) the proportion of persons with diabetes among the dead was greater than those who did not die 11.7% versus 8.1%, respectively, p = 0.017. However, persons with diabetes were older and hence died older, 62.3 years (SD = 1.9) for deceased persons with diabetes versus 50.4 years (SD = 0.8), P < 0.0001. However, using Cox regression to adjust for age, initial CD4 count, country of birth there was no significant difference in the Hazard for death between persons with diabetes and persons without diabetes (aHR = 0.99, 95%CI = 0.65-1.5), P = 0.9. CONCLUSIONS: The prevalence of diabetes in our HIV cohort was high. Persons with diabetes had greater CD4 counts, earlier care, and greater virological suppression than persons without diabetes. There were no significant differences between persons with diabetes and without diabetes in terms of survival.

Residual ß-cell function in Brazilian Type 1 diabetes after 3 years of diagnosis: prevalence and association with low presence of nephropathy.

BACKGROUND: Persistence of ß cell-function in Type 1 diabetes (T1D) is associated with glycaemia stability and lower prevalence of microvascular complications. We aimed to assess the prevalence of residual C- peptide secretion in long-term Brazilian childhood onset T1D receiving usual diabetes care and its association to clinical, metabolic variables and microvascular complications. METHODS: A cross-sectional observational study with 138 T1D adults with ≥ 3 years from the diagnosis by routine diabetes care. Clinical, metabolic variables and microvascular complications were compared between positive ultra-sensitive fasting serum C-peptide (FCP +) and negative (FCP-) participants. RESULTS: T1D studied had ≥ 3 yrs. of diagnosis and 60% had FCP > 1.15 pmol/L. FCP + T1D were older at diagnosis (10 vs 8 y.o; p = 0.03) and had less duration of diabetes (11 vs 15 y.o; p = 0.002). There was no association between the FCP + and other clinical and metabolic variable but there was inversely association with microalbuminuria (28.6% vs 13.4%, p = 0.03), regardless of HbA1c. FCP > 47 pmol/L were associated with nephropathy protection but were not related to others microvascular complications. CONCLUSION: Residual insulin secretion is present in 60% of T1D with ≥ 3 years of diagnosis in routine diabetes care. FCP + was positively associated with age of diagnosis and negatively with duration of disease and microalbuminuria, regardless of HbA1c.

Correlation Between Hemoglobin Glycation Index Measured by Continuous Glucose Monitoring With Complications in Type 1 Diabetes.

OBJECTIVE: HbA1C is the "gold standard" parameter to evaluate glycemic control in diabetes; however, its correlation with mean glucose is not always perfect. The objective of this study was to correlate continuous glucose monitoring (CGM)-derived hemoglobin glycation index (HGI) with microvascular complications. METHODS: We conducted a cross-sectional study including permanent users of CGM with type 1 diabetes mellitus or latent autoimmune diabetes of the adult. HGI was estimated, and presence of microvascular complications was compared in subgroups with high or low HGI. A logistic regression analysis to assess the contribution of high HGI to chronic kidney disease (CKD) was performed. RESULTS: In total, 52 participants who were aged 39.7 ± 14.7 years, with 73.1% women and 15.5 years (IQR, 7.5-29 years) since diagnosis, were included; 32.7% recorded diabetic retinopathy, 25% CKD, and 19.2% neuropathy. The median HbA1C was 7.6% (60 mmol/mol) and glucose management indicator (GMI) 7.0% (53 mmol/mol). The average HGI was 0.55% ± 0.66%. The measured HbA1C was higher in the group with high HGI (8.1% [65 mmol/mol] vs 6.9% [52 mmol/mol]; P < .001), whereas GMI (7.0% [53 mmol/mol] vs 7.0% [53 mmol/mol]; P = .495) and mean glucose were similar in both groups (153 mg/dL vs 153 mg/dL; P = .564). In the high HGI group, higher occurrence of CKD (P = .016) and neuropathy were observed (P = .025). High HGI was associated with increased risk of CKD (odds ratio [OR]: 5.05; 95% CI: 1.02-24.8; P = .04) after adjusting for time since diagnosis (OR: 1.09; 95% CI: 1.02-1.16; P = .008). CONCLUSION: High HGI measured by CGM may be a useful marker for increased risk of microvascular diabetic complications.

The rs705708 A allele of the ERBB3 gene is associated with lower prevalence of diabetic retinopathy and arterial hypertension and with improved renal function in type 1 diabetic patients.

INTRODUCTION: The Erb-b2 receptor tyrosine kinase 3 (ERBB3) is involved in autoimmune processes related to type 1 diabetes mellitus (T1DM) pathogenesis. Accordingly, some studies have suggested that single nucleotide polymorphisms (SNPs) in the ERBB3 gene confer risk for T1DM. Proliferation-associated protein 2G4 (PA2G4) is another candidate gene for this disease because it regulates cell proliferation and adaptive immunity. Moreover, PA2G4 regulates ERBB3. To date, no study has evaluated the association of PA2G4 SNPs and T1DM. AIM: To evaluate the association of ERBB3 rs705708 (G/A) and PA2G4 rs773120 (C/T) SNPs with T1DM and its clinical and laboratory characteristics. METHODS: This case-control study included 976 white subjects from Southern Brazil, categorized into 501 cases with T1DM and 475 non-diabetic controls. The ERBB3 and PA2G4 SNPs were genotyped by allelic discrimination-real-time PCR. RESULTS: ERBB3 rs705708 and PA2G4 rs773120 SNPs were not associated with T1DM considering different inheritance models and also when controlling for covariables. However, T1DM patients carrying the ERBB3 rs705708 A allele developed T1DM at an earlier age vs. G/G patients. Interestingly, in the T1DM group, the rs705708 A allele was associated with lower prevalence of diabetic retinopathy and arterial hypertension as well as with improved renal function (higher estimated glomerular filtration rate and lower urinary albumin excretion levels) compared to G/G patients. CONCLUSIONS: Although no association was observed between the ERBB3 rs705708 and PA2G4 rs773120 SNPs and T1DM, the rs705708 A allele was associated, for the first time in literature, with lower prevalence of diabetic retinopathy and arterial hypertension. Additionally, this SNP was associated with improved renal function.

Differential effects of treatment targets on risks of adverse outcomes according to diabetes duration, age and complications: Can these characteristics be used to individualize diabetes treatment? The Rio de Janeiro type 2 diabetes cohort.

AIMS: To investigate interactions between more/less strict treatment targets (HbA1c, systolic blood pressure, LDL-cholesterol) and clinical characteristics (age, diabetes duration and presence of complications) for occurrence of cardiovascular/microvascular complications and mortality in type 2diabetes. METHODS: 690 individuals were followed-up for 10 years (median). Interactions between treatment targets, estimated as mean values during the first 2-years, and clinical characteristics were tested in multivariable Cox regressions adjusted for other risk factors. Hazard ratios (HRs) were estimated in stratified analyses for cardiovascular/microvascular outcomes and mortality. RESULTS: During follow-up, 214 patients had a cardiovascular event (175 MACEs); and 265 died (132 cardiovascular deaths); there were 206 renal, 161 retinopathy and 181 peripheral neuropathy events. There were interactions between treatment parameters and clinical characteristics, in most of them the HRs were higher in older individuals, in those with longer diabetes durations and with complications, particularly for the cardiovascular outcomes and mortality. For microvascular outcomes the opposite was observed. For cardiovascular mortality, the HRs of higher HbA1c were 1.31 (1.08-1.58) and 1.09 (0.88-1.34), respectively with longer/shorter diabetes duration (p-for-interaction 0.11); and 1.43 (1.14-1.79) and 1.02 (0.85-1.23) in older/younger individuals (p-for-interaction 0.019). CONCLUSIONS: Our findings do not support less strict treatment targets for older individuals, with longer diabetes duration or with complications, particularly for cardiovascular and mortality prevention.

A systematic review of preclinical animal studies on fenofibrate's potential role in type 1 diabetic micro-vascular complications

Abstract Fenofibrate is a peroxisome-proliferator-activator α agonist and it is a widely used drug for hyperlipidemia since its approval in 2004. So, in this review we are focusing on the effect of fenofibric acid's mechanism to alleviate type 1 diabetic micro vascular complications like diabetic retinopathy, diabetic cardiomyopathy in animal models, since the drug is safe, efficacious and more economical when compared with the currently available treatment strategies for juvenile diabetic complications and also a profound observation is needed due to the rarity of research in these therapeutic areas. Important preclinical animal studies published from January 2001 to June 2020 were recognised from databases like PubMed and Cochrane central register of controlled trials. Reviewers screened the articles based on the selection criteria and risk of bias was determined using Systematic Review Centre for Laboratory animal Experimentation risk of bias tool for animal studies. Our literature search yielded a total of 5 studies and after pooling up the data from the 5 preclinical studies, we found that Fenofibrate have the efficacy to prevent type 1 diabetic complications, chiefly diabetic retinopathy and those mechanisms are dependent on peroxisome-proliferator-activator and fibroblast growth factor-21 pathways. Fenofibrate is a well safe and moreover, cost effective medication in preventing type 1 diabetic micro vascular complications especially diabetic retinopathy and also in maintaining the glucose homeostasis in apart from its anti-dyslipidemic effect.

Type 2 diabetes mellitus in Peru: A literature review including studies at high-altitude settings.

We performed a comprehensive review of recent publications about type 2 diabetes mellitus (T2DM) in Peru, including studies among people living at high altitude above the sea level. An increase in the prevalence of T2DM in Peru has been reported, the reasons are multifactorial and coinciding with the strong economic growth that our country has experienced over the last 20 years along with migration from the Andean regions to the coast and the adoption of a lifestyle that is a known to be a risk factor for obesity and insulin resistance. Scarce information is available in Peru about the prevalence of chronic complications of T2DM such as retinopathy, neuropathy, and nephropathy. There is a need for a health care plan based on early diagnosis of T2DM to reduce social and economic problems, as recommended by the WHO and the United Nations.

Cost of microvascular complications in people with diabetes from a public healthcare perspective: a retrospective database study in Brazil.

AIM: To evaluate direct medical costs incurred by patients with diabetes in the periods before and after experiencing a microvascular complication from a Brazilian public healthcare system perspective. MATERIALS AND METHODS: This was a retrospective, observational study using the Brazilian Unified Health System (DATASUS) database. Direct medical costs (hospitalization and outpatient) were extracted for patients with evidence of diabetes and a microvascular complication (January 2012-December 2018) and converted to 2019 US Dollars (USD). Length of hospital stays was also extracted. Mixed-effects logistic regression explored associations between demographic/clinical characteristics and incurrence of high direct medical costs (defined as the highest tertile of the annual costs ranked by median cost in the total population). RESULTS: In total, 2,096 patients with diabetes experienced a microvascular complication and met study inclusion/exclusion criteria. Median [interquartile range] annual costs (USD/patient) were 176.3 [91.0; 481.2] at baseline, increasing to 1,678.5 [287.0; 6,908.4] and 5,172.4 [274.8; 7,395.9] in the first and second year after the complication, respectively. Median hospital stay was 2.0 and 3.0 days at baseline and in the first year, respectively. The odds of incurring high costs were substantially elevated in the first and second years (odds ratios of 69.9 and 84.7, respectively, vs. baseline, both p < .001). LIMITATIONS: The DATASUS database covers secondary and tertiary care (not primary), adding selection bias to our sample. Additionally, our findings may not apply to the entire Brazilian population, as around 25% have some access to private healthcare. CONCLUSIONS: This study demonstrates a large increase in costs, from the perspective of the Brazilian public healthcare system, in patients with diabetes after experiencing a microvascular complication compared with pre-complication costs. In addition to providing up-to-date cost estimates, our findings highlight the need to appraise the cost-effectiveness of evidence-based strategies that reduce the risk of diabetes-related microvascular complications in Brazilian patients.

Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

BACKGROUND: The prognostic importance of several hematological parameters has been scarcely investigated in type 2 diabetes. So, we aimed to evaluate their prognostic importance for development of complications in a cohort of type 2 diabetes. METHODS: In a prospective study, 689 individuals with type 2 diabetes had blood red cell, platelet and leukocyte parameters obtained at baseline. Multivariate Cox analyses examined the associations between several hematological parameters (including neutrophyl-to-lymphocyte, lymphocyte-to-monocyte, platelet-to-lymphocyte, and monocyte-to-HDL ratios) and the occurrence of microvascular (retina, renal and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs], and major adverse CVEs [MACEs]), and all-cause and cardiovascular mortality. Improvements in risk discrimination were assessed by C-statistics and Integrated Discrimination Improvement (IDI) index. RESULTS: During a median follow-up of 10.5 years, 212 patients had a CVE (174 MACEs), 264 patients died (131 cardiovascular deaths); 206 had a renal, 161 a retinopathy and 179 patients had a neuropathy outcome. In multivariate-adjusted analyses, the lymphocytes count and lymphocyte-to-monocyte ratio were protective (hazard ratios [HRs]: 0.77 and 0.72, respectively), whereas the neutrophyl-to-lymphocyte and platelet-to-lymphocyte ratios were associated with increased risks (HRs: 1.19 and 1.17) for all-cause mortality. For cardiovascular mortality, the monocytes count, the neutrophyl-to-lymphocyte and monocyte-to-HDL ratios were associated with increased risks and the lymphocyte-to-monocyte ratio was protective. Higher lymphocyte-to-monocyte ratio was protective for renal failure outcome. However, none of them improved risk discrimination. CONCLUSIONS: Low lymphocytes count and leukocyte ratios that mainly included lymphocytes were predictors of macrovascular complications and mortality in individuals with type 2 diabetes. However, they did not improve risk prediction over traditional risk factors.

Ferritin levels in children and adolescents with type 1 diabetes mellitus: relationship with microvascular complications and glycemic control.

OBJECTIVE: Evaluate ferritin levels in children and adolescents with type 1 diabetes mellitus and its relation to diabetic microvascular complications, and metabolic control. METHODS: This study included 180 children and adolescents with type 1 diabetes mellitus (T1DM) with a mean age of 14.9 ± 3.1 years and 180 apparently normal children matched for age and sex (control group). All children were evaluated with full history taking, thorough clinical examination, laboratory assessment of high-sensitivity C-reactive protein and hemoglobin A1c (HbA1c), and evaluation of the presence of microvascular complications. Serum ferritin levels were measured using electrochemiluminescence immunoassay. The patients were divided into two groups according to the presence or absence of microvascular complications. RESULTS: Serum ferritin levels were significantly higher in patients with T1DM in both groups compared with healthy controls (p < 0.001). Additionally, patients with microvascular complications had higher serum ferritin concentrations than those without microvascular complications (p < 0.001). Patients with microalbuminuria showed higher ferritin levels compared with patients without microalbuminuria (p < 0.05). Stepwise regression analysis revealed that levels of HbA1c and urinary albumin excretion were independently related to ferritin levels (p < 0.001 for both). On receiver operating characteristic (ROC) curve analysis, a ferritin cutoff value of 163.6 ng/mL differentiated patients with microvascular complications from those without microvascular complications with a sensitivity of 92.1% and specificity of 93.4%. CONCLUSION: Serum ferritin levels are elevated in T1DM, particularly in patients with microvascular complications.

Quality of life and self-efficacy in patients with type 2 diabetes mellitus in a Peruvian public hospital.

Quality of life and self-efficacy assessments are increasingly applied in research with type 2 diabetes mellitus patients due to the impact of the disease on their lives. This study aimed to describe the quality of life and self-efficacy in type 2 diabetes mellitus patients and describe the association of quality of life and self-efficacy with demographic, metabolic, and clinical variables. This is a secondary data analysis from a cross-sectional study: Metabolic control in patients with type 2 diabetes mellitus in a public hospital in Peru: a cross-sectional study in a low-middle income country. Data were obtained by standardized interviews and evaluation of medical records. The evaluation tools used were the Diabetes 39 questionnaire (D-39) to measure the quality of life and the General Self-Efficacy scale (GSE) for self-efficacy. The median scores of the D-39 and GSE were 34.6 and 34, respectively. The D-39 dimension with the highest score was anxiety and concern. Better quality of life was associated with being older than 65 years old, not having complications, and the absence of depression. No significant association was found between self-efficacy and the quality of life score. Results suggest patients with type 2 diabetes mellitus have a poor quality of life. Patient-centered strategies for type 2 diabetes mellitus care must consider these psychosocial factors to improve disease control and quality of life.

La calidad de vida y la evaluación de autoefiacia se aplican cada vez más en la valoración de los pacientes con diabetes mellitus tipo 2 debido al alto impacto de la enfermedad en sus vidas. Este estudio tiene como objetivo describir la calidad de vida y autoeficacia en pacientes con diabetes mellitus tipo 2 y describir la asociación de calidad de vida y autoeficacia con variables demográficas, metabólicas y clínicas. Este estudio es un análisis secundario del estudio transversal: “Control metabólico en pacientes con diabetes mellitus tipo 2 en un hospital público del Perú: estudio de corte transversal en un país de bajos y medianos ingresos”. Los datos se obtuvieron mediante cuestionarios estandarizadas y evaluación de historias clínicas. Las herramientas de evaluación utilizadas fueron el cuestionario Diabetes -39 (D-39) para medir la calidad de vida y la escala de autoeficacia general para medir autoeficacia (GSE). Las medias del D-39 y GSE fueron 34,6 y 34, respectivamente. La dimensión con la puntuación más alta del D-39 fue "ansiedad y preocupación". Una mejor calidad de vida estuvo asociada con ser mayor de 65 años, no tener complicaciones microvasculares y la ausencia de depresión. No se encontró una asociación significativa entre la autoeficacia y calidad de vida. Los resultados sugieren que los pacientes con diabetes mellitus tipo 2 tienen una pobre calidad de vida. Las estrategias centradas en el cuidado del paciente con diabetes mellitus tipo 2 deben considerar estos factores psicosociales para mejorar el control de la enfermedad y la calidad de vida.

Variants in HSD11B1 gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes.

BACKGROUND AND AIM: 11ß-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. MATERIALS AND METHODS: Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). RESULTS: The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96; P = .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37; P = .028). A follow-up study revealed that 29% of the individuals lost ≥5 mL min-1 × 1.73 m2 per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89; P = .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42; P = .004). CONCLUSION: SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals.

Ferritin levels in children and adolescents with type 1 diabetes mellitus: relationship with microvascular complications and glycemic control

ABSTRACT Objective: Evaluate ferritin levels in children and adolescents with type 1 diabetes mellitus and its relation to diabetic microvascular complications, and metabolic control. Subjects and methods: This study included 180 children and adolescents with type 1 diabetes mellitus (T1DM) with a mean age of 14.9 ± 3.1 years and 180 apparently normal children matched for age and sex (control group). All children were evaluated with full history taking, thorough clinical examination, laboratory assessment of high-sensitivity C-reactive protein and hemoglobin A1c (HbA1c), and evaluation of the presence of microvascular complications. Serum ferritin levels were measured using electrochemiluminescence immunoassay. The patients were divided into two groups according to the presence or absence of microvascular complications. Results: Serum ferritin levels were significantly higher in patients with T1DM in both groups compared with healthy controls (p < 0.001). Additionally, patients with microvascular complications had higher serum ferritin concentrations than those without microvascular complications (p < 0.001). Patients with microalbuminuria showed higher ferritin levels compared with patients without microalbuminuria (p < 0.05). Stepwise regression analysis revealed that levels of HbA1c and urinary albumin excretion were independently related to ferritin levels (p < 0.001 for both). On receiver operating characteristic (ROC) curve analysis, a ferritin cutoff value of 163.6 ng/mL differentiated patients with microvascular complications from those without microvascular complications with a sensitivity of 92.1% and specificity of 93.4%. Conclusion: Serum ferritin levels are elevated in T1DM, particularly in patients with microvascular complications.

Parámetros clínicos, bioquímicos y metabólicos predictores de complicaciones micro y macrovasculares en diabéticos tipo 2 / Clinical, biochemical and metabolic parameters predictive of micro and macrovascular complications in type 2 diabetics / Parâmetros clínicos, bioquímicos e metabólicos preditivos de complicações micro e macrovasculares em diabéticos tipo 2

RESUMEN Introducción: la diabetes mellitus (DM) es una enfermedad endocrino - metabólica, vascular, crónica, producida por una interacción variable de factores genéticos y ambientales. Actualmente la DM2 es considerada por algunos autores como pandémica, sin la existencia de signos de reducción de las tasas de incidencia. Objetivo: identificar los parámetros clínicos, bioquímicos y metabólicos predictores de complicaciones micro y macrovasculares en personas con diabetes mellitus tipo 2. Método: se realizó un estudio analítico de tipo casos y controles con pacientes ingresados en el Centro de Atención al Diabético de Bayamo (CAD), Granma, desde el año 2010 al 2017, 81 con alguna complicación microvascular, 40 con alguna complicación macrovascular y 162 sin ninguna complicación. Resultados: en el análisis univariado se observó que el tiempo de evolución de la enfermedad y la HTA descontrolada fueron los factores de riesgo para el desarrollo de una complicación microvascular, mientras que a estas se le unieron el tabaquismo y le hipercolesterolemia como factores de riesgo para el desarrollo de complicaciones macrovasculares. Las variables que mostraron una relación independiente con el riesgo de desarrollar alguna complicación microvascular fueron el tiempo de evolución de la enfermedad y la HTA descontrolada, mientras que para el desarrollo de complicaciones macrovasculares fueron el tiempo de evolución de la enfermedad y el tabaquismo. Conclusiones: el tiempo de evolución de la diabetes y la HTA descontrolada y el tiempo de evolución de la enfermedad y el tabaquismo se asocian de forma independiente con la aparición de complicaciones microvasculares y macrovasculates respectivamente.

ABSTRACT Introduction: diabetes mellitus (DM) is an endocrine-metabolic, vascular, chronic disease, produced by a variable interaction of genetic and environmental factors. Currently DM2 is considered by some authors as pandemic, without the existence of signs of reduction of incidence rates. Objective: to identify clinical, biochemical and metabolic parameters predictors of micro and macrovascular complications in people with type 2 diabetes mellitus. Method: an analytical case and control study was conducted with patients admitted to the Bayamo Diabetic Care Center (CAD), Granma, from 2010 to 2017, 81 with some microvascular complications, 40 with some macrovascular complications and 162 without any complications. Results: the univariate analysis found that disease progression time and uncontrolled HTA were the risk factors for the development of a microvascular complication, while these were joined by smoking and hypercholesterolemia as risk factors for the development of macrovascular complications. The variables that showed an independent relationship with the risk of developing some microvascular complications were the time of disease evolution and uncontrolled HTA, while for the development of macrovascular complications were the time of disease evolution and smoking. Conclusions: the time of evolution of diabetes and uncontrolled HTA and the time of disease and smoking evolution are independently associated with the emergence of microvascular and macrovasculate complications respectively.

RESUMO Introdução: diabetes mellitus (DM) é uma doença endócrina-metabólica, vascular, crônica, produzida por uma interação variável de fatores genéticos e ambientais. Atualmente o DM2 é considerado por alguns autores como pandemia, sem a existência de sinais de redução das taxas de incidência. Objetivo: identificar preditores de parâmetros clínicos, bioquímicos e metabólicos de complicações micro e macrovasculares em pessoas com diabetes mellitus tipo 2. Método: estudo analítico de caso e controle foi realizado com pacientes internados no Centro de Atendimento Diabético Bayamo (CAD), Granma, de 2010 a 2017, 81 com algumas complicações microvasculares, 40 com algumas complicações macrovasculares e 162 sem complicações. Resultados: a análise univariada constatou que o tempo de progressão da doença e o HTA descontrolado foram os fatores de risco para o desenvolvimento de uma complicação microvascular, enquanto estes foram acompanhados pelo tabagismo e hipercolesterolemia como fatores de risco para o desenvolvimento de complicações macrovasculares. As variáveis que apresentaram relação independente com o risco de desenvolver algumas complicações microvasculares foram o tempo de evolução da doença e HTA descontrolada, enquanto para o desenvolvimento de complicações macrovasculares foi o tempo de evolução da doença e tabagismo. Conclusões: o tempo de evolução do diabetes e do HTA descontrolado e o tempo de evolução da doença e do tabagismo estão independentemente associados ao surgimento de complicações microvasculares e macrovasculadas, respectivamente.

Prognostic importance of visit-to-visit blood pressure variability for micro- and macrovascular outcomes in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study.

BACKGROUND: The prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes. METHODS: BP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index. RESULTS: Over a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03-1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%). CONCLUSIONS: Systolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis.

PURPOSE: The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. METHODS: A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). RESULTS: A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54-0.79), renal death (0.57; 95% CI 0.49-0.65), and progression of albuminuria (0.69; 95% CI 0.66-0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI - 0.74 to 1.41) or reducing serum creatinine (- 0.07; 95% CI - 0.26 to 0.11), whereas urine albumin-creatinine ratio (- 23.4; 95% CI - 44.6 to - 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93-1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. CONCLUSION: SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.

Lower Insulin-Dose Adjusted A1c (IDAA1c) Is Associated With Less Complications in Individuals With Type 1 Diabetes Treated With Hematopoetic Stem-Cell Transplantation and Conventional Therapy.

Objective: To evaluate the association between insulin-dose adjusted A1C (IDAA1c) and microvascular complications (MC) and hypoglycemia in a representative Brazilian population of Type 1 diabetes mellitus (T1DM) patients. Research Design and Methods: This was a cross-sectional study based on a previous study, "Microvascular Complications in Type 1 Diabetes: a comparative analysis of patients treated with autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) and conventional medical therapy (CT)". The 168 patients in that study (144 from CT plus 24 from AHST) were re-subdivided into two groups, according to their IDAA1c values (30 patients had IDAA1c ≤ 9; 138 had IDAA1c > 9). Then, the prevalence of MC (diabetic renal disease, neuropathy, and retinopathy), hypoglycemia (blood glucose <60 mg/dL), and severe hypoglycemic (episode of hypoglycemia that required the assistance of another person to treat) events were compared between the groups. The groups were well-matched on these factors: duration of disease, sex, and age at the time of diagnosis of T1DM. Results: After an average of 8 years after diagnosis, only 6.6% (2/30) of the patients from IDAA1c ≤ 9 group developed any MC, whereas 21.0% (29/138) from the IDAA1c > 9 group had at least one complication (p = 0.044). Regarding hypoglycemic events, the proportion of individuals who reported at least 1 episode of hypoglycemia in the last month was 43.3 and 64.7% from the IDAA1c ≤ 9 and IDAA1c > 9 groups, respectively (p = 0.030). Regarding severe hypoglycemia, the proportion of patients presenting at least one episode in the last month and the rate of episode/patient/month were similar between groups (6.7 vs. 13.2%; p = 0.535; and 0.1/patient/month vs. 0.25/patient/month; p = 0.321). Conclusion: In a representative Brazilian population of T1DM patients, those with IDAA1c ≤ 9 presented a lower frequency of MC, as well as fewer episodes of hypoglycemia, in the month prior to the analysis.

HbA1c variability and long-term glycemic control are linked to diabetic retinopathy and glomerular filtration rate in patients with type 1 diabetes and multiethnic background.

AIM: To evaluate the associations between HbA1c variability and long-term glycemic control with microvascular complications in type 1 diabetes (T1D) patients and multiethnic background. METHODS: T1D adults with ≥10 years of follow-up and ≥ 2 HbA1c measurements were included. Glycemic variability was evaluated by the standard deviation (HbA1c-SD), and coefficient of variation (HbA1c-CV), and glycemic control by mean HbA1c over 10 years. Diabetic retinopathy (DR), increased urinary albumin excretion rate (UAER) and reduced glomerular filtration rate (eGFR) were diagnosed. Cardiac autonomic neuropathy (CAN) was diagnosed by cardiac reflex tests. Associations between glycemic parameters with complications were assessed by multivariate logistic regressions. RESULTS: 220 patients were included. Simultaneously adjusted for each other, mean HbA1c was independently associated with DR (OR: 2.82; 95%CI: 1.45-5.50), increased UAER (OR: 1.97; 95%CI: 1.14-3.09) and CAN (OR: 4.42; 95%CI: 1.45-13.51); whereas HbA1c-CV was independently associated with DR (OR: 8.93; 95%CI: 1.86-42.87) and reduced eGFR (OR: 7.02; 95%CI: 1.47-35.55). CONCLUSIONS: Long-term glycemic control was associated with DR, increased UAER and CAN, while glycemic variability was additionally associated with DR and impaired renal function; suggesting that both good and stable glycemic status might be important to prevent microvascular complications in T1D patients and multiethnic background.