Heterogeneous response of estimated insulin sensitivity indices to metformin in young individuals with type 1 diabetes and different phenotypes.

AIMS: This study aimed to investigate whether the response to adding metformin to insulin in young adults with type 1 diabetes (T1D) differs according to weight phenotype and insulin sensitivity index. METHODS: A prospective pilot study was conducted over 26 weeks in which insulin plus metformin (2 g/day) was administered to 35 individuals, ranging from normal weight (NW) to overweight (OW) to obese (OB) T1D individuals, to correlate insulin sensitivity indices and other clinical variables. RESULTS: At the end of the follow-up period, all groups showed an increase in the eGDR (NW: 7.37 vs 8.16, p = 0.002; OW: 7.28 vs 8.24, p < 0.001; OB: 6.33 vs 7.52 p < 0.001). KITT and SEARCH SCORE improved only in the OB group (2.15 vs 3.14, p < 0.001 and 5.26 vs 5.72, p = 0.007, respectively). Furthermore, HbA1c and BMI were significantly greater in the OB group (- 0.62%, p < 0.001; - 1.12 kg/m2, p = 0.031, respectively). Regression analysis revealed that the serum levels of triglycerides and uric acid were significantly (0.059, p = 0.013; 0.076, p = 0.001) associated with insulin sensitivity indices. CONCLUSIONS: The study showed that eGDR improved independently of basal weight after metformin treatment. However, the KITT and SEARCH indices improved only in the obese group. Triglycerides and uric acid are associated with insulin sensitivity indices. These results highlight the heterogeneity of the mechanisms underlying insulin resistance and its response to metformin in individuals with T1D.

High-Density Lipoproteins-Cholesterol (HDL-C) in Women With Gestational Diabetes (GDM): A Predictor for Large Gestational Age (LGA) Babies.

Introduction The present study aimed to evaluate the associations between the clinical and biochemical characteristics of women with gestational diabetes (GDM) and the incidence of large for gestational age (LGA) babies. Methods This cohort study included data collected during prenatal follow-up of GDM women from January 2008 to August 2022. Clinical and biochemical variables were compared among small (SGA), adequate (AGA), or large for gestational age (LGA) babies. Associations of the main variables with the incidence of LGA were determined by multiple regression analysis. Results Out of 659 women, 56 had LGA, 547 had AGA, and 56 had SGA babies. We observed differences in the means of age, pregestational body mass index (BMI), high-density lipoproteins-cholesterol (HDL-C) levels, gestational weight gain (GWG), and gestational age at birth according to LGA, AGA, and SGA (p < 0.05). All other variables were not different between the groups. The frequencies (%) and relative risk (RR) of LGA babies were evaluated according to HDL-C in the first tertile and/or obesity, with 12.2% and risk ratio (RR)=2.77 (95% confidence interval (CI) 1.35-5.69, p=0.005) if the women had obesity and HDL in the first tertile, 11.3% and RR=2.27 (95% CI 1.03-5.03, p=0.042) if only HDL in the first tertile was present, 10.9% and RR=2.68 (95% CI 1.31-5.48, p=0.007) if the women had only obesity, using as a reference group those women without obesity or HDL-C in the first tertile (4.6% and RR=1) adjusted for age, age at birth and GWG. Conclusion In women with GDM, lower levels of HDL-cholesterol during pregnancy, as well as pregestational obesity, seem to be good predictors of the occurrence of LGA babies.

Dietary intake of pregnant women with non-alcoholic fatty liver disease: A case-control study.

BACKGROUND AND AIMS: Findings on the role of diet in non-alcoholic fatty liver disease (NAFLD) pathogenesis are inconsistent. There are few studies on the dietary habits of pregnant women with NAFLD. Our primary aim was to compare the dietary intakes of pregnant women with and without NAFLD. METHODS: This case-control study recruited 60 women (26-34 weeks' gestation) with recently diagnosed gestational diabetes (GDM) before any treatment was implemented. At recruitment, all participants underwent B-mode hepatic ultrasound. We included 30 women with sonographic NAFLD (cases) and 30 women without NAFLD (controls) matched for age, skin color, and pre-pregnancy body mass index. We assessed participants' dietary intakes in the last six months using a validated food frequency questionnaire. Mann-Whitney´s test was used to compare differences in median macro and micronutrient intakes between cases and controls. RESULTS: Total median daily energy (1965.1 × 1949.2 calories) and lipid (25.1% × 28.3%) intakes were similar in women with and without NAFLD and fell within recommended ranges. Participants with NAFLD reported significantly higher median daily intakes of carbohydrates (59.4% × 53.1% p = 0.003), and significantly lower protein (15.6% × 17.0% p = 0.005), fiber (10.7 × 13.3 g/day p = 0.010), and vitamin C (151.8 × 192.6 mg/day p = 0.008) intakes than those without NAFLD. CONCLUSIONS: Pregnant women with NAFLD ingest more carbohydrates and less protein, fiber, and vitamin C than those without NAFLD. Our findings contribute to understanding the role of diet in the development of NAFLD in pregnant women.

Increased risk of death following recurrent ketoacidosis admissions: a Brazilian cohort study of young adults with type 1 diabetes.

BACKGROUND: Recurrent DKA (rDKA) remains an acute type 1 diabetes complication even in post-insulin era. This study aimed to analyze the predictors and effects of rDKA on the mortality of patients with type 1 diabetes. METHODS: Patients hospitalized (n = 231) wih diabetic ketoacidosis (between 2007 and 2018) were included. Laboratorial and clinical variables were collected. Mortality curves were compared in four groups: diabetic ketoacidosis as a new-onset type 1 diabetes (group A), single diabetic ketoacidosis episode after diagnosis of type 1 diabetes (group B), 2-5 diabetic ketoacidosis events (group C), and > 5 diabetic ketoacidosis events during follow-up period (group D). RESULTS: During the follow-up period (approximately 1823 days), the mortality rate was 16.02% (37/231). The median age at death was 38.7 years. In the survival curve analysis, at 1926 days (5 years), the probabilities of death were indicated by ratios of 7.78%, 4.58%, 24.40%, and 26.63% in groups A, B, C, and D, respectively. One diabetic ketoacidosis episode compared with ≥ 2 events had a relative risk of 4.49 (p = 0.004) of death and > 5 events had 5.81 (p = 0.04). Neuropathy (RR 10.04; p < 0.001), retinopathy (relative risk 7.94; p < 0.01), nephropathy (RR 7.10; p < 0.001), mood disorders (RR 3.57; p = 0.002), antidepressant use (RR 3.09; p = 0.004), and statin use (RR 2.81; p = 0.0024) increased the risk of death. CONCLUSIONS: Patients with type 1 diabetes with > 2 diabetic ketoacidosis episodes have four times greater risk of death in 5 years. Microangiopathies, mood disorders, and use of antidepressants and statins were important risk factors for short-term mortality.

Father's weight could contribute to large babies in overweight and obese mothers with and without gestational diabetes.

We evaluated whether there was an association between fathers' nutritional status and children's birth weight (BW) considering weight-matched mothers with and without gestational diabetes mellitus (GDM). In total, 86 trios of women, infants, and fathers were evaluated. BW was not different between the groups of obese and non-obese parents, frequency of maternal obesity, or GDM. The percentage of infants who were large for gestational age (LGA) was 25% in the obese group and 14% in the non-obese group (p = 0.44). There was a borderline significance for higher body mass index (p = 0.09) of the father in the LGA group compared with the adequate for gestational age group. These results corroborate the hypothesis that the father's weight can also be relevant for the occurrence of LGA.

Gut Microbiota across Normal Gestation and Gestational Diabetes Mellitus: A Cohort Analysis.

The prevalence of gestational diabetes mellitus (GDM) is a global public health concern. The mechanism that leads to glucose tolerance beyond normal physiological levels to pathogenic conditions remains incompletely understood, and it is speculated that the maternal microbiome may play an important role. This study analyzes the gut microbiota composition in each trimester of weight-matched women with and without GDM and examines possible bacterial genera associations with GDM. This study followed 56 pregnant women with GDM and 59 without admitted to the outpatient clinic during their first/second or third trimester of gestation. They were submitted to a standardized questionnaire, dietary recalls, clinical examination, biological sample collection, and molecular profiling of fecal microbiota. Women with GDM were older and had a higher number of pregnancies than normal-tolerant ones. There was no difference in alpha diversity, and the groups did not differ regarding the overall microbiota structure. A higher abundance of Bacteroides in the GDM group was found. A positive correlation between Christensenellaceae and Intestinobacter abundances with one-hour post-challenge plasma glucose and a negative correlation between Enterococcus and two-hour plasma glucose levels were observed. Bifidobacterium and Peptococcus abundances were increased in the third gestational trimester for both groups. The gut microbiota composition was not dependent on the presence of GDM weight-matched women throughout gestation. However, some genera abundances showed associations with glucose metabolism. Our findings may therefore encourage a deeper understanding of physiological and pathophysiological changes in the microbiota throughout pregnancy, which could have further implications for diseases prevention.

Sodium-glucose cotransporter-2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews.

AIMS: To summarize the evidence from systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors versus placebo or active comparators for type 2 diabetes mellitus. MATERIALS AND METHODS: We searched six databases between 2014 and 2021. We assessed the quality of evidence using Assessment of Multiple Systematic Reviews (AMSTAR 2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) and summarized the main outcome results according to their evidence of benefit (PROSPERO ID: CRD42019132431). RESULTS: We included 46 SRs, comprising 175 RCTs and 136 096 participants. The results showed "clear evidence of benefit" in relation to: myocardial infarction (odds ratio [OR]/hazard ratio [HR] 0.85 to 0.91); cardiovascular mortality (OR/HR 0.67 to 0.86); heart failure (OR/HR 0.64 to 0.69); albuminuria progression and composite renal outcome (relative risk [RR]/HR 0.55 to 0.63); glycated haemoglobin (HbA1c) versus placebo (mean difference [MD] -0.49% to -0.77% [5.4 to 8.4 mmol/mol]); and weight versus placebo (MD -1.09 kg to -2.99 kg). "Possible benefit" was observed in relation to major adverse cardiovascular events (OR/HR 0.80 to 0.89), all-cause mortality and nonalcoholic fatty liver disease. SGLT2 inhibitors showed "clear evidence of no effect or equivalence" in relation to stroke and fractures. "Clear evidence of harm" was observed in relation to genital infections (RR/OR 2.06 to 5.25) and ketoacidosis (HR/OR 1.36 to 2.20). Regarding amputation risk and urinary tract infections, we found "no conclusions possible due to lack of evidence". CONCLUSIONS: Our results showed that SGLT2 inhibitors have beneficial effects in relation to renal and cardiovascular outcomes (except for stroke), HbA1c and weight. Further studies are needed to assess urinary infections and amputation risk.

Branched-chain amino acids predict incident diabetes in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

AIMS: To evaluate the role of branch chain amino acid (BCAA) concentrations as a predictor for incident type 2 diabetes (DM). METHODS: Participants from ELSA-Brasil without diabetes at baseline and followed for 3.9 ± 0.6 years were included in the analysis. The determinations of BCAA (valine, leucine, isoleucine) were performed by proton nuclear magnetic resonance spectroscopy. Cardiometabolic profile and incidence of DM were evaluated according to quartiles of BCAA at baseline, stratified by sex. RESULTS: From 3,828 participants (56% female, 50.5 ± 8.7 years) 299 (8.5%) were diagnosed with DM. For both sexes, a worsening of cardiometabolic profile was observed across increasing BCAA quartiles. In survival analysis, incidence rates of DM for the entire period were highest in participants in the third and fourth quartile of BCAA (log Rank analysis < 0.001 for both sexes). In Cox regression analysis, for men, the HR (95%CI) for risk of DM was 2.24 (1.24-4.03) for those from the fourth quartile of BCAA, while in women it was 1.94 (1.07-3.50), comparing to first quartile of BCAA after adjustments for age, BMI, physical activity, family history of DM, pre-diabetes, blood pressure, total cholesterol and HOMA-IR. CONCLUSIONS: Higher levels of BCAA were independently predictors of DM.

Severity and mortality of COVID 19 in patients with diabetes, hypertension and cardiovascular disease: a meta-analysis.

BACKGROUND: The aim of this study is to evaluate the impact of diabetes, hypertension, cardiovascular disease and the use of angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) with severity (invasive mechanical ventilation or intensive care unit admission or O2 saturation < 90%) and mortality of COVID-19 cases. METHODS: Systematic review of the PubMed, Cochrane Library and SciELO databases was performed to identify relevant articles published from December 2019 to 6th May 2020. Forty articles were included involving 18.012 COVID-19 patients. RESULTS: The random-effect meta-analysis showed that diabetes mellitus and hypertension were moderately associated respectively with severity and mortality for COVID-19: Diabetes [OR 2.35 95% CI 1.80-3.06 and OR 2.50 95% CI 1.74-3.59] Hypertension: [OR 2.98 95% CI 2.37-3.75 and OR 2.88 (2.22-3.74)]. Cardiovascular disease was strongly associated with both severity and mortality, respectively [OR 4.02 (2.76-5.86) and OR 6.34 (3.71-10.84)]. On the contrary, the use of ACEI/ARB, was not associate with severity of COVID-19. CONCLUSION: In conclusion, diabetes, hypertension and especially cardiovascular disease, are important risk factors for severity and mortality in COVID-19 infected people and are targets that must be intensively addressed in the management of this infection.

Neonatal Near Miss among Newborns of Women with Type 1 Diabetes Mellitus.

OBJECTIVE: To investigate the frequency of neonatal near miss (NNM) and associate it with maternal morbidity in newborns of women with type 1 diabetes mellitus (T1DM). METHODS: This was a cross-sectional retrospective study from a secondary analysis of data retrieved from medical records of pregnant women with T1DM cared at a Brazilian university hospital between 2005 and 2015. Maternal near miss (MNM) and potentially life-threatening conditions (PTLC) were classified according to the World Health Organization criteria. NNM was classified according to the Pan American Health Organization Neonatal Near Miss Working Group criteria. Association of maternal morbidity with NNM was assessed using chi-square test. RESULTS: There were 122 newborns (NB) among 137 T1DM pregnancies. Thirty-seven NB presented NNM-incidence of 303 NNM per 1000 live births (37/122). NNM was associated with MNM (P < 0.001, OR (95% CI): 17.15 (1.85-159.12)). PLTC did not increase the odds of NNM (P=0.07; OR (95% CI): 2.1281 (0.92-4.91)). Seven newborns died, six of them from pregnancies without severe maternal morbidity. 71% of the neonatal death (5/7) occurred in malformed neonates. CONCLUSION: MNM was associated with NNM among women with T1DM, and PLTC, paradoxically, did not increase NNM.