COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Patterns of kidney function and risk assessment in a nationwide laboratory database: the Brazilian CHECK-CKD study.

BACKGROUND: Chronic kidney disease (CKD) is a global health problem with rising prevalence, morbidity, mortality, and associated costs. Early identification and risk stratification are key to preventing progression to kidney failure. However, there is a paucity of data on practice patterns of kidney function assessment to guide the development of improvement strategies, particularly in lower-income countries. METHODS: A retrospective observational analysis was conducted in a nationwide laboratory database in Brazil. We included all adult patients with at least one serum creatinine assessment between June 2018 and May 2021. Our primary objective was to determine the proportion of patients with estimated glomerular filtration rate (eGFR) evaluations accompanied by predicted levels of urinary albumin-to-creatinine ratio (pACR) assessments within 12 months. RESULTS: Out of 4,5323,332 serum creatinine measurements, 42% lacked pACR measurements within 12 months. Approximately 10.8% of tests suggested CKD, mostly at stage 3a. The proportion of serum creatinine exams paired with pACR assessment varied according to the CKD stage. Internal Medicine, Cardiology, and Obstetrics/Gynecology were the specialties requesting most of the creatinine tests. Nephrology contributed with only 1.1% of serum creatinine requests for testing. CONCLUSION: Our findings reveal that a significant proportion of individuals with a creatinine test lack an accompanying urinary albuminuria measurement in Brazil, contrary to the recommendations of the international guidelines. Non-Nephrologists perform most kidney function evaluations, even among patients with presumable advanced CKD. This highlights the urge to incorporate in clinical practice the early detection of CKD and to encourage more collaborative multidisciplinary care to improve CKD management.

Dysglycemias in patients admitted to ICUs with severe acute respiratory syndrome due to COVID-19 versus other causes - a cohort study.

BACKGROUND: Dysglycemias have been associated with worse prognosis in critically ill patients with COVID-19, but data on the association of dysglycemia with COVID-19 in comparison with other forms of severe acute respiratory syndrome are lacking. This study aimed to compare the occurrence of different glycemic abnormalities in patients with severe acute respiratory syndrome and COVID-19 admitted to intensive care units versus glycemic abnormalities in patients with severe acute respiratory syndrome from other causes, to evaluate the adjusted attributable risk associated with COVID-19 and dysglycemia and to assess the influence of these dysglycemias on mortality. METHODS: We conducted a retrospective cohort of consecutive patients with severe acute respiratory syndrome and suspected COVID-19 hospitalized in intensive care units between March 11 and September 13, 2020, across eight hospitals in Curitiba-Brazil. The primary outcome was the influence of COVID-19 on the variation of the following parameters of dysglycemia: highest glucose level at admission, mean and highest glucose levels during ICU stay, mean glucose variability, percentage of days with hyperglycemia, and hypoglycemia during ICU stay. The secondary outcome was the influence of COVID-19 and each of the six parameters of dysglycemia on hospital mortality within 30 days from ICU admission. RESULTS: The sample consisted of 841 patients, of whom 703 with and 138 without COVID-19. Comparing patients with and without COVID-19, those with COVID-19 had significantly higher glucose peaks at admission (165 mg/dL vs. 146 mg/dL; p = 0.002) and during ICU stay (242 mg/dL vs. 187md/dL; p < 0.001); higher mean daily glucose (149.7 mg/dL vs. 132.6 mg/dL; p < 0.001); higher percentage of days with hyperglycemia during ICU stay (42.9% vs. 11.1%; p < 0.001); and greater mean glucose variability (28.1 mg/dL vs. 25.0 mg/dL; p = 0.013). However, these associations were no longer statistically significant after adjustment for Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, and C-reactive protein level, corticosteroid use and nosocomial infection. Dysglycemia and COVID-19 were each independent risk factors for mortality. The occurrence of hypoglycemia (< 70 mg/dL) during ICU stay was not associated with COVID-19. CONCLUSION: Patients with severe acute respiratory syndrome due to COVID-19 had higher mortality and more frequent dysglycemia than patients with severe acute respiratory syndrome due to other causes. However, this association did not seem to be directly related to the SARS-CoV-2 infection.

Efficacy of liraglutide added to sodium-glucose cotransporter-2 inhibitors in type 2 diabetes, stratified by baseline characteristics: Post-hoc analysis of LIRA-ADD2SGLT2i.

AIMS: The LIRA-ADD2SGLT2i trial demonstrated that liraglutide + sodium-glucose cotransporter-2 inhibitors (SGLT2is) ± metformin significantly improved glycaemic control (not body weight) versus placebo in adults with type 2 diabetes (T2D). This post-hoc analysis assessed whether baseline characteristics influenced these findings. MATERIALS AND METHODS: LIRA-ADD2SGLT2i (NCT02964247) was a placebo-controlled, double-blind, multinational trial, wherein participants received liraglutide (≤1.8 mg/day) or placebo (randomized 2:1). Changes from baseline to week 26 in haemoglobin A1c (HbA1c), body weight and waist circumference stratified by HbA1c, body mass index (BMI), diabetes duration, duration of pre-trial SGLT2i use and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were analysed. These five baseline characteristics were divided into tertiles, and the treatment effect was evaluated using the trial product estimand. RESULTS: Data from all 303 participants were analysed. There was a significant interaction between baseline HbA1c tertiles (7.0%-<7.6%; 7.6%-8.1%; ≥8.2%-9.5%) and glycaemic control at week 26 (p[interaction]  = .011), with the lowest HbA1c estimated treatment difference (95% confidence interval) observed in patients with lowest baseline HbA1c [-0.20% (-0.59, 0.19); -0.68% (-1.03, -0.33); -0.98% (-1.33, -0.64), respectively]. There were no significant interactions in glycaemic control across baseline BMI, diabetes duration, insulin resistance determined by HOMA-IR or SGLT2i use duration (p[interaction] > .05, all). Across the five characteristics assessed, no significant interactions were found for body weight or waist circumference changes from baseline (p[interaction] > .05, all). CONCLUSION: For individuals with T2D and inadequate glycaemic control despite therapy with SGLT2is ± metformin, liraglutide 1.8 mg would provide an effective treatment intensification option, irrespective of HbA1c, BMI, diabetes duration, insulin resistance determined by HOMA-IR and SGLT2i use duration.

Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6).

AIM: To assess what drives change in health-related quality of life (HRQoL) in type 2 diabetes in the SUSTAIN 6 trial and identify potential mediators of the treatment effect of semaglutide on HRQoL scores. MATERIALS AND METHODS: The Short Form (SF)-36v2® questionnaire [comprising physical component summary (PCS) and mental component summary (MCS)] was used to assess changes in HRQoL from baseline to week 104, by treatment, in a prespecified analysis. This post-hoc analysis assessed change in PCS and MCS using the following factors as parameter/covariate, using descriptive statistics and linear regressions: major adverse cardiac events, hypoglycaemia, gastrointestinal adverse events, at least one episode of nausea, vomiting or diarrhoea, and change in glycated haemoglobin (HbA1c), body weight, blood pressure, heart rate and estimated glomerular filtration rate. RESULTS: Mean change in overall PCS score was +1.0 with semaglutide versus +0.4 with placebo, and +0.5 versus -0.2 for MCS. The treatment effect of semaglutide versus placebo (unadjusted estimate) was 0.7 [(95% confidence interval 0.1, 1.2); P = 0.018] on PCS and this was reduced when adjusted for change in HbA1c [0.4 (-0.2, 1.0), P = .167] and body weight [0.3 (-0.3, 0.9), P = .314]. The unadjusted treatment effect on MCS [0.7 (-0.0, 1.5), P = .054] was only reduced when adjusted for change in HbA1c [0.3 (-0.4, 1.1), P = .397]. When adjusting for all other parameters separately, the estimated effect of semaglutide on PCS and MCS qualitatively did not change. CONCLUSIONS: Semaglutide improved HRQoL versus placebo; greater improvements with semaglutide versus placebo were possibly mediated, in part, by change in HbA1c and body weight. Clinicaltrials.gov: NCT01720446 (SUSTAIN 6).

Liraglutide as add-on to sodium-glucose co-transporter-2 inhibitors in patients with inadequately controlled type 2 diabetes: LIRA-ADD2SGLT2i, a 26-week, randomized, double-blind, placebo-controlled trial.

AIM: To compare the effect of liraglutide or placebo added on to sodium-glucose co-transporter-2 inhibitor (SGLT2i) ± metformin on glycaemic control in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with type 2 diabetes on a stable SGLT2i dose ± metformin (with HbA1c 7.0%-9.5% and body mass index [BMI] ≥ 20 kg/m2 ) were randomized 2:1 to add-on liraglutide 1.8 mg/day or placebo in this parallel, double-blind, multinational trial. Primary and confirmatory secondary endpoints were changes in HbA1c and body weight from baseline to week 26, respectively. The proportions of patients achieving HbA1c (<7.0%) targets and safety events after week 26 were also assessed. RESULTS: Of 303 patients randomized (one in error), 280 completed treatment. Mean changes in HbA1c from baseline to week 26 with liraglutide (n = 202) and placebo (n = 100) were - 0.98% and - 0.30%, respectively (estimated treatment difference [ETD]: -0.68% [95% CI: -0.89, -0.48]; P < 0.001). Mean body weight changes from baseline were - 2.81 versus -1.99 kg, respectively (ETD: -0.82 kg [95% CI: -1.73, 0.09]; P = 0.077); 51.8% of liraglutide-treated patients achieved HbA1c < 7.0% versus 23.2% receiving placebo (odds ratio: 5.1 [95% CI: 2.67, 9.87]; P < 0.001). More patients treated with liraglutide reported ≥1 treatment-emergent adverse events (66.3%) versus placebo (47.0%). CONCLUSIONS: Liraglutide significantly improved glycaemic control compared with placebo in patients with type 2 diabetes, insufficiently controlled with SGLT2is with/without metformin, with no unexpected safety findings.

Relationship between adherence to diet, glycemic control and cardiovascular risk factors in patients with type 1 diabetes: a nationwide survey in Brazil.

BACKGROUND: To determine the relationship between adherence to the diet reported by patients with type 1 diabetes under routine clinical care in Brazil, and demographic, socioeconomic status, glycemic control and cardiovascular risk factors. METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data was obtained from 3,180 patients, aged 22 ± 11.8 years (56.3% females, 57.4% Caucasians and 43.6% non-Caucasians). The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: Overall, 1,722 (54.2%) of the patients reported to be adherent to the diet without difference in gender, duration of diabetes and socioeconomic status. Patients who reported adherence to the diet had lower BMI, HbA1c, triglycerides, LDL-cholesterol, non HDL-cholesterol and diastolic blood pressure and had more HbA1c at goal, performed more frequently self-monitoring of blood glucose (p < 0.001), and reported less difficulties to follow specific schedules of diet plans (p < 0.001). Less patients who reported to be adherent were obese or overweight (p = 0.005). The quantity of food and time schedule of the meals were the most frequent complaints. Logistic regression analysis showed that ethnicity, (Caucasians, (OR 1.26 [1.09-1.47]), number of medical clinical visits in the last year (OR 1.10 [1.06-1.15]), carbohydrate counting, (OR 2.22 [1.49-3.30]) and diets recommended by diabetes societies', (OR 1.57 [1.02-2.41]) were related to greater patients' adherence (p < 0.05) and age, [adolescents (OR 0.60 [0.50-0.72]), high BMI (OR 0.58 [0.94-0.98]) and smoking (OR 0.58 [0.41-0.84]) with poor patients' adherence (p < 0.01). CONCLUSIONS: Our results suggest that it is necessary to rethink medical nutrition therapy in order to help patients to overcome barriers that impair an optimized adherence to the diet.

Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE) activity and changes its relationship with lipids.

Many conditions interfere with butyrylcholinesterase (BChE) activity, e.g., pregnancy or presence of the BCHE gene variant -116A can decrease activity whereas obesity and types I and II diabetes mellitus can increase activity. In this study, we examined BChE activity, -116A and 1615A BCHE gene variants, and anthropometric and biochemical variables associated with diabetes in patients with gestational diabetes mellitus (GDM) and in healthy pregnant women. BChE activity was measured spectrophotometrically using propionylthiocholine as substrate and genotyping of the -116 and 1615 sites of the BCHE gene was done with a TaqMan SNP genotyping assay. Three groups were studied: 150 patients with GDM, 295 healthy pregnant women and 156 non-pregnant healthy women. Mean BChE activity was significantly lower in healthy pregnant women than in women from the general population and was further reduced in GDM patients. BChE activity was significantly reduced in carriers of -116A in GDM patients and healthy pregnant women. Although GDM patients had a significantly higher mean body mass index (BMI) and triglycerides than healthy pregnant women, they had lower mean BChE activity, suggesting that the lowering effect of GDM on BChE activity was stronger than the characteristic enhancing effect of increased BMI and triglycerides.

Effect of switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL (Gla-300) in Brazilian people with type 1 diabetes.

BACKGROUND: Low adherence to the number of insulin injections and glycemic variability are among the challenges of insulin therapy in type 1 diabetes (T1D). The TOP1 study investigated the effect of switching from twice-daily (BID) basal insulin to once daily (OD) insulin glargine 300 U/mL (Gla-300) on glycemic control and quality of life. METHODS: In this 28-week, phase 4 trial, people with T1D aged ≥ 18 years, who were treated with BID basal insulin in combination with prandial rapid-acting insulin for at least 1 year, and had HbA1c between 7.5% and 10.0%, were switched to Gla-300 OD as basal insulin. The present study aimed to evaluate the impact of this change on HbA1c, glycemic profile, treatment satisfaction and safety. The change in HbA1c from baseline to Week 24 was the primary endpoint. RESULTS: One hundred and twenty-three people with T1D (mean age 37 ± 11 years; 54.5% female) were studied. The disease duration was 20.0 ± 9.8 years, baseline HbA1c and fasting plasma glucose (FPG) were 8.6 ± 0.7% and 201 ± 80.3 mg/dL, respectively. After switching from BID to OD insulin regimen, no significant change in HbA1c was observed from baseline to Week 24 (p = 0.873). There were significant reductions in fasting self-monitoring blood glucose (SMBG) from baseline to Week 24 (175 ± 42 vs. 156 ± 38 mg/dL; p < 0.0001), and in glycemic profile (8-point SMBG) at several time points. There was a significant decrease in the proportion of patients with at least one hypoglycemic event (p = 0.025), in numbers of hypoglycemic events per patient-years of any type (p = 0.036), symptomatic (p = 0.007), and confirmed ≤ 70 mg/dL events (p = 0.049) from run-in to the last 4 weeks on treatment. There were significant improvements in treatment satisfaction (p < 0.0001), perceived hyperglycemia (p < 0.0001) scores and satisfaction with the number of injections between post-run-in and Week 24, and a significant decrease in fear of hypoglycemia. CONCLUSIONS: Switch from BID basal insulin to OD Gla-300 as part of basal bolus therapy in T1D resulted in similar glycemic control as measured by HbA1c, but provided significant improvements in SMBG, daily glucose profile, a lower incidence of hypoglycemia and increased patient satisfaction. TRIAL REGISTRATION: NCT03406000.

Telephone lifestyle intervention to prevent diabetes in women with recent gestational diabetes mellitus attending the national health system: the LINDA-Brasil clinical trial.

OBJECTIVES: To evaluate a postpartum telephone-based lifestyle intervention to prevent diabetes in high-risk women with recent gestational diabetes mellitus (GDM). DESIGN: Multicentre parallel randomised clinical trial. SETTING: Specialised antenatal clinics in the Brazilian National System. METHODS: Lifestyle Intervention for Diabetes Prevention After Pregnancy compared (1:1) postpartum telephone support for lifestyle changes with conventional care in women with recent GDM at substantial risk for diabetes. Randomisation started on 28 March 2015 and ended on 13 March 2020, with the onset of the COVID-19 pandemic. We used Cox regression to estimate HRs for diabetes and analysis of covariance adjusted for follow-up time to assess weight change. OUTCOMES: The primary outcome was incident diabetes ascertained with blinded measurements of oral glucose tolerance tests. The secondary outcome was a change in measured weight. RESULTS: We enrolled 5323 women with GDM, 2735 (51%) being at high risk. After invitations, baseline assessment and exclusions, we assigned 466 women to intervention (231) or control (235) groups. Attendance was satisfactory (≥7/20 phone sessions) in 75%. Over an average follow-up of 29.7 (15.6) months, 142 (30.5%) women progressed to diabetes, 75 (32%) in the control and 67 (29%) in the intervention group. There was no reduction in the incidence of diabetes (HR=0.84; 0.60-1.19) and only a non-significant 0.97 kg less weight gain (p=0.09). Among the 305 women randomised more than 1 year before the COVID-19 pandemic, the intervention did not reduce the incidence of diabetes (HR=0.71; 0.48-1.04) despite a 2.09 kg (p=0.002) lesser weight gain. CONCLUSION: The strategy to identify women with GDM at high risk proved valid, as women often gained weight and frequently developed diabetes. Over a 30-month follow-up, telephone support for lifestyle changes at postpartum did not reduce weight gain or diabetes incidence, although only 75% attended the minimum number of telephone sessions. The COVID-19 pandemic negatively impacted trial conduction. TRIAL REGISTRATION NUMBER: NCT02327286.

Association between HLA Class II Alleles/Haplotypes and Genomic Ancestry in Brazilian Patients with Type 1 Diabetes: A Nationwide Exploratory Study.

We aimed to identify HLA-DRB1, -DQA1, and -DQB1 alleles/haplotypes associated with European, African, or Native American genomic ancestry (GA) in admixed Brazilian patients with type 1 diabetes (T1D). This exploratory nationwide study enrolled 1599 participants. GA percentage was inferred using a panel of 46 ancestry informative marker-insertion/deletion. Receiver operating characteristic curve analysis (ROC) was applied to identify HLA class II alleles related to European, African, or Native American GA, and showed significant (p < 0.05) accuracy for identifying HLA risk alleles related to European GA: for DRB1*03:01, the area under the curve was (AUC) 0.533; for DRB1*04:01 AUC = 0.558, for DRB1*04:02 AUC = 0.545. A better accuracy for identifying African GA was observed for the risk allele DRB1*09:01AUC = 0.679 and for the protective alleles DRB1*03:02 AUC = 0.649, DRB1*11:02 AUC = 0.636, and DRB1*15:03 AUC = 0.690. Higher percentage of European GA was observed in patients with risk haplotypes (p < 0.05). African GA percentage was higher in patients with protective haplotypes (p < 0.05). Risk alleles and haplotypes were related to European GA and protective alleles/haplotypes to African GA. Future studies with other ancestry markers are warranted to fill the gap in knowledge regarding the genetic origin of T1D in highly admixed populations such as that found in Brazil.

HLA Genotypes and Type 1 Diabetes and Its Relationship to Reported Race/Skin Color in Their Relatives: A Brazilian Multicenter Study.

We aimed to investigate the relationship between HLA alleles in patients with type 1 diabetes from an admixed population and the reported race/skin color of their relatives. This cross-sectional, multicenter study was conducted in public clinics in nine Brazilian cities and included 662 patients with type 1 diabetes and their relatives. Demographic data for patients and information on the race/skin color and birthplace of their relatives were obtained. Typing of the HLA-DRB1, -DQA1, and -DQB1 genes was performed. Most studied patients reported having a White relative (95.17%), and the most frequently observed allele among them was DRB1*03:01. Increased odds of presenting this allele were found only in those patients who reported having all White relatives. Considering that most of the patients reported having a White relative and that the most frequent observed allele was DRB1*03:01 (probably a European-derived allele), regardless of the race/skin color of their relatives, we conclude that the type 1 diabetes genotype comes probably from European, Caucasian ethnicity. However, future studies with other ancestry markers are needed to fill the knowledge gap regarding the genetic origin of the type 1 diabetes genotype in admixed populations such as the Brazilian.

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus.

BACKGROUND: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. METHODS: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

IL18 Gene Polymorphism Influences Age of Onset of DM1 in African Ancestry Brazilians.

The aim of this study was to investigate the relationship of two single nucleotide polymorphisms (SNPs) in the interleukin-18 ( IL18 ) gene (rs187238, g.-137G > C; rs1946518, g.-607C > A) and one SNP of the IL12B gene (rs3212227 g.*159A > C, 3'UTR) with the age of onset for type 1 diabetes mellitus (DM1). A total of 1,101 patients with DM1 enrolled in 13 centers from different regions of Brazil were genotyped with TaqMan assay and classified according to the ancestry. Our results show that an SNP in IL18 gene could be associated with DM1 age onset, taking into account that this studied variation affects gene expression.

Insulin Injection Technique Questionnaire: results of an international study comparing Brazil, Latin America and World data.

BACKGROUND: In 2014-2015, the largest international survey of insulin injection technique in patients with diabetes taking insulin was conducted in 42 countries, totaling 13,289 participants. In Brazil, patients from five public health centers were included. This study aims to evaluate insulin injection technique in Brazilian patients and compare results with Latin America (LatAm) and World data. METHODS: The insulin Injection Technique Questionnaire (ITQ) survey consisted of an initial patient section (questions applied by an experienced nurse), followed by observation of injection technique and examination of the injection sites by the health care professional. RESULTS: In Brazil, 255 patients were evaluated: 25% had type 1 diabetes mellitus (T1DM) and 75% had T2DM. In this study, 79% of patients injected less than 4 times a day, and 17.3% used insulin pens, compared to 28% in LatAm and 86% worldwide. Syringes were used by 78% of patients in Brazil, compared to 65% in LatAm and 10% globally. Differences in needle length were substantial-nearly 64% in Brazil inject with 8 mm length needle compared to 48% in LatAm and 27% worldwide. Additionally, 48% of patients in Brazil skip doses, 80% reuse pen needles and 57% reuse syringes with 27% having lipohypertrophy by exam. CONCLUSION: Brazilian patients use syringes more and pens less, inject with larger needles and have more lipohypertrophy when compared to Latin America and World data. Their re-use of needles and syringes is also high. This study showed that in Brazil, teaching of proper injection technique has to be more widespread, and more intensive during diabetes educational sessions, and the type of delivered supplies must be updated to smaller, shorter needles preferred by patients, in order to facilitate adherence to treatment. From the ITQ, we conclude that there are many aspects of insulin injection technique that may be improved in Brazil.

[Prevalence of hepatitis C infection in patients with type 2 diabetes mellitus]. / Prevalência de infecção pelo vírus da hepatite C em pacientes com diabetes melito tipo 2.

BACKGROUND: Recently, a possible epidemiological association between hepatitis C virus infection and diabetes mellitus has been suggested and a higher prevalence of HCV antibodies has been found among type 2 diabetic when compared with normal controls. AIM: To evaluate the prevalence of hepatitis C infection in diabetic patients in Curitiba, PR, Brazil. PATIENTS AND METHODS: A total of 145 type 2 and 104 type 1 diabetic patients attending the outpatient diabetic unit of an university hospital were consecutively tested for anti-HCV, using a fourth-generation enzyme-linked immunosorbent assay (ELISA). The control group was constituted by 16,720 volunteer blood donors attending the blood bank of the same hospital during the period of the study. Diabetic patients were also evaluated for clinical, biochemical (aminotransferase levels) and demographic variables and previous exposure to risk factors for hepatitis C infection. RESULTS: A higher prevalence of hepatitis C infection was observed in type 2 diabetic patients in comparison with blood donors. Although anti-HCV prevalence in type 2 diabetic patients was higher than found in type 1, it did not reach statistical significance. Both diabetic groups were predominantly female, and as expected, type 2 diabetic were older than type 1. Race distribution, duration of the disease, and previous exposure to hepatitis C risk factors were similar in both groups, but type 2 diabetic subjects had higher median levels of alanine aminotransferase than type 1. CONCLUSIONS: A higher prevalence of hepatitis C infection was detected in type 2 diabetic patients in comparison with blood donors in our region, in accordance with study data from different populations. If all type 2 diabetic patients should undergo regular screening for hepatitis C infection remains a question.

[Nationwide multicenter study on the prevalence of overweight and obesity in type 2 diabetes mellitus in the Brazilian population]. / Prevalência de sobrepeso e obesidade em pacientes com diabetes mellitus do tipo 2 no Brasil: estudo multicêntrico nacional.

AIM: To evaluate the prevalence of overweight and obesity in type 2 diabetic (DM2) outpatients from different regions of Brazil. PATIENTS AND METHODS: We studied 2,519 randomly selected patients, from 11 hospitals, 2 endocrine and one general public care clinics from 10 cities. Overweight was defined as body-mass index (BMI) > 25 and obesity as BMI > 30 kg/m2. Glycemic control (GC) was evaluated by GC index (GCI = patient's HbA1 or HbA1c/upper limit of normal for the method x 100). RESULTS: 39% of the population studied was male, the mean age was 58.8 +/- 11.6 y, the duration from clinical diagnosis of DM2 was 9.0 +/- 7.3y, and BMI was 28.3 +/- 5.2 kg/m2. No measurements of BMI were recorded from 265 patients (10.5%). Patients from the Northeast presented lower BMI as compared with those from the Midwest, Southeast and South areas, respectively (26.4 +/- 4.7 vs. 27.9 +/- 4.8 vs. 29.2 +/- 5.1 vs. 29.4 +/- 5.4 kg/m2; p < 0.001). A greater prevalence of obesity was observed in the Southeast and South areas as compared to the Northeast (p < 0.001), as well as in the female group, respectively (69% vs. 31%; p < 0.001). Normal weight patients presented lower GCI. Patients being treated with two or more oral drugs and an association of insulin plus oral drug presented greater BMI values than those being treated with diet, oral hypoglycemic agents and insulin p < 0.001. The BMI of patients treated by a specialist did not differ from those treated by a generalist. CONCLUSIONS: 75% of our sample was out of adequate BMI and 30% was obese. The percentage of patients with overweight and obesity was comparable to those found in similar European studies but still lower than those found in the USA. The prevalence of obesity in diabetic patients was three times higher than in the overall Brazilian population according to data from the Brazilian Institute of Geography and Statistics (IBGE).

Postpartum Reclassification of Glycemic Status in Women with Gestational Diabetes Mellitus and Associated Risk Factors.

UNLABELLED: Objective The aims of the study were to evaluate, after pregnancy, the glycemic status of women with history of gestational diabetes mellitus (GDM) and to identify clinical variables associated with the development of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Methods Retrospective cohort of 279 women with GDM who were reevaluated with an oral glucose tolerance test (OGTT) after pregnancy. Characteristics of the index pregnancy were analyzed as risk factors for the future development of prediabetes (IFG or IGT), and T2DM. RESULTS: T2DM was diagnosed in 34 (12.2%) patients, IFG in 58 (20.8%), and IGT in 35 (12.5%). Women with postpartum T2DM showed more frequently a family history of T2DM, higher pre-pregnancy body mass index (BMI), lower gestational age, higher fasting and 2-hour plasma glucose levels on the OGTT at the diagnosis of GDM, higher levels of hemoglobin A1c, and a more frequent insulin requirement during pregnancy. Paternal history of T2DM (odds ratio [OR] = 5.67; 95% confidence interval [95%CI] = 1.64-19.59; p = 0.006), first trimester fasting glucose value (OR = 1.07; 95%CI = 1.03-1.11; p = 0.001), and insulin treatment during pregnancy (OR = 15.92; 95%CI = 5.54-45.71; p < 0.001) were significant independent risk factors for the development of T2DM. Conclusion A high rate of abnormal glucose tolerance was found in women with previous GDM. Family history of T2DM, higher pre-pregnancy BMI, early onset of GDM, higher glucose levels, and insulin requirement during pregnancy were important risk factors for the early identification of women at high risk of developing T2DM. These findings may be useful for developing preventive strategies.