[Show abstract][Hide abstract] ABSTRACT: Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil.
[Show abstract][Hide abstract] ABSTRACT: To analyze possible associations of dietary components, especially protein intake, with blood pressure (BP) during ambulatory BP monitoring (ABPM) in patients with type 2 diabetes.
In this cross-sectional study, BP of outpatients with type 2 diabetes was evaluated by 24-hour ABPM (Spacelabs 90207) and usual diet by 3-day weighed diet records. Patients were divided into 2 groups according to their daytime ABPM: uncontrolled BP (systolic BP ≥ 135 mmHg or diastolic BP ≥ 85 mmHg) and controlled BP (systolic BP < 135 mmHg and diastolic BP < 85 mmHg). Logistic regression models unadjusted and adjusted for possible confounders (covariates) were used to analyze the association of protein and uncontrolled BP.
A total of 121 patients with type 2 diabetes aged 62.3 years, 54.5% of whom were women, were studied. The uncontrolled BP group had higher glycated hemoglobin (HbA1C) values (8.4 ± 2.0 vs 7.6 ± 1.3%; p = 0.04) and consumed more protein (20.0 ± 3.8 vs 18.2 ± 3.6% of energy; p = 0.01) and meat, (2.6 [1.45, 2.95] vs 2.0 [1.49, 2.90] g/kg weight; p = 0.04) than the controlled BP group. In a multivariate analysis, protein intake (% of energy) increased the chance for uncontrolled BP (odds ratio [OR] = 1.16; 95% confidence interval [CI], 1.02, 1.30; p = 0.02), adjusted for body mass index (BMI), HbA1C, low-density lipoprotein (LDL) cholesterol, number of antihypertensive medications, and ethnicity. Meat consumption higher than 3.08 g/kg weight/day more than doubled the chance for uncontrolled BP (OR = 2.53; 95% CI, 1.01, 7.60; p = 0.03).
High protein intake and meat consumption were associated with high daytime ABPM values in patients with type 2 diabetes. Reducing meat intake might represent an additional dietary intervention in hypertensive patients with type 2 diabetes.
Journal of the American College of Nutrition 03/2015; 34(3):1-8. DOI:10.1080/07315724.2014.926155 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Thyroid nodules are a common finding in the general population and their detection is increasing with the widespread use of ultrasound (US). Thyroid cancer is found in 5-15% of cases depending on sex, age, and exposure to other risk factors. Some US parameters have been associated with increased risk of malignancy, however, no characteristic seems sufficiently reliable in isolation to diagnose malignancy. The objective of this meta-analysis was to evaluate the diagnostic performance of US features for thyroid malignancy in patients with unselected thyroid nodules and nodules with indeterminate FNA cytology. Methods: Electronic databases were reviewed for studies published prior to July 2012 for studies that evaluated US features of thyroid nodules and reporting postoperative histopathologic diagnosis. A manual search of references of review and key articles, and previous meta-analyses was also performed. A separate meta-analysis was performed including only nodules with indeterminate cytology. Analyzed features were: solid structure, hypoechogenicity, irregular margins, absence of halo, microcalcifications, central vascularization, solitary nodule, heterogeneity, taller than wide shape, and absence of elasticity. Results: 52 observational studies (12,786 nodules) were included. Nine studies included nodules with indeterminate cytology as separate category, comprising 1851 nodules. In unselected nodules, all US features were significantly associated with malignancy with an OR varying from 1.78 to 35.7, and, microcalcifications, irregular margins and a taller than wide shape had high specificities (Sp) (87.8%, 83.1%, 96.6%) and positive likelihood ratios (LHR) (3.26, 2.99, 8.07). Absence of elasticity was the single feature with the best diagnostic performance (sensitivity 87.9%, Sp 86.2% and positive LHR 6.39). The presence of central vascularization was the most specific US feature in nodules with indeterminate cytology (Sp 96% and positive LHR 2.13). Conclusions: US features in isolation do not provide reliable information to select nodules that should have a fine-needle aspiration performed. Combination of US characteristics with higher likelihood ratios and, consequently with higher post test probabilities of malignancy - microcalcifications, or a taller than wide shape, or irregular margins, or absence of elasticity -probably will identify nodules with an increased risk for malignancy. Further studies are required to standardize elastography techniques and evaluate outcomes, especially in nodules with an indeterminate cytology.
Thyroid: official journal of the American Thyroid Association 03/2015; 25(5). DOI:10.1089/thy.2014.0353 · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: To evaluate associations of dietary fat composition with the development of cardiac events in patients with type 2 diabetes, without ischemic heart disease who were followed for at least 12 months. Methods: In this prospective cohort study the usual diet of patients was retrospectively assessed by a 3-day weighed diet record (WDR). Compliance with the WDR technique was assessed by comparing protein intake estimated from 3-day WDR and 24-h urinary nitrogen output. The following were considered cardiac events: myocardial infarction, myocardial revascularization procedures, congestive heart failure, new-onset angina pectoris, and sudden death. Results: A total of 227 patients with type 2 diabetes (aged 59 +/- 10 years; 46.0% male), were followed during 4.6 years. In a multivariate Cox regression analysis, the intake of polyunsaturated fatty acids had a protective effect for cardiac events (HR = 0.31, 95% CI: 0.11-0.89; P = 0.03) adjusted for age, gender, duration of diabetes, smoking, compliance with WDR, using hypolipidemic agents, and the presence of hypertension and diabetic nephropathy. When the fat intake was divided into quartiles, the highest intake of a-linolenic acid (>1.25% of energy) was negatively associated with cardiac events (HR = 0.58, 95% CI: 0.39-0.85; P = 0.006), adjusted for the same covariates. Conclusion: In patients with type 2 diabetes without ischemic heart disease, a high intake of polyunsaturated fatty acids, especially alpha linolenic acid, was protective for the development of cardiac events.
[Show abstract][Hide abstract] ABSTRACT: Background
Obesity and diabetes mellitus are well-defined risk factors for cardiovascular mortality. The impact of antecedent hyperglycemia and body size on mortality in critical ill patients in intensive care units (ICUs) may vary across their range of values. Therefore, we prospectively analyzed the relationship between in-hospital mortality and preexisting hyperglycemia and body size in critically ill ICU patients to understand how mortality varied among normal, overweight, and obese patients and those with low, intermediate, and high glycated hemoglobin (HbA1c) levels.
Medical history, weight, height, physiologic variables, and HbA1c were obtained during the first 24 h for patients who were consecutively admitted to the high complexity ICU of Hospital de Clínicas de Porto Alegre, Brazil, from April to August 2011. The relationships between mortality and obesity and antecedent hyperglycemia were prospectively analyzed by cubic spline analysis and a Cox proportional hazards model.
The study comprised 199 patients. The overall hospital mortality rate was 43.2% during a median 16 (8–28) days of follow-up. There was a progressive risk of in-hospital mortality with higher HbA1c levels, with the relationship becoming significant at HbA1c >9.3% compared with lower levels (hazard ratio 1.74; 95% confidence interval with Bonferroni correction 1.49–2.80). In contrast, mean body mass index (BMI) was higher in survivors than in nonsurvivors (27.2 kg/m2 ± 7.3 vs. 24.7 kg/m2 ± 5.0 P = 0.031, respectively). Cubic spline analysis showed that these relationships differed nonlinearly through the spectrum of BMI values. In a Cox proportional hazards model adjusted for Acute Physiology and Chronic Health Evaluation II score and HbA1c, the risk of in-hospital mortality progressively decreased with increasing BMI (BMI <20 vs. 20–23.9 kg/m2, P = 0.032; BMI <20 vs. 24–34.9 kg/m2, P = 0.010; BMI <20 vs. ≥35 kg/m2, P = 0.032).
Our findings suggest that significant hyperglycemia prior to ICU admission is a risk factor for in-hospital mortality. Conversely, increasing BMI may confer an advantageous effect against mortality in critical illness independently of previous glycemic control.
[Show abstract][Hide abstract] ABSTRACT: GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine.RESEARCH DESIGN AND METHODS: Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26.RESULTS: At week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 ± 0.19 kg vs. +0.81 ± 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%).CONCLUSIONS: Weekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk.
Diabetes Care 06/2014; 37(8). DOI:10.2337/dc14-0001 · 8.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Higher intake of dietary fiber is associated with lower risk of coronary heart disease, the leading cause of mortality among people with type 1 diabetes. The protective effect includes the anti-inflammatory properties of some foods. Population-based studies have shown an inverse association between some nutritional habits and high sensitive -C-reactive protein (hs-CRP). This study aimed to ascertain the association between fiber intake and hs-CPR levels in patients with type 1 diabetes.
This cross-sectional study was conducted with 106 outpatients with type 1 diabetes; age 40 ± 11 years; diabetes duration of 18 ± 8.8 years. Dietary intake was evaluated by 3-day weighed-diet records. Patients were categorized in 2 groups, according to fiber intake (>20 g/day and <20 g/day).
The group with fiber intake > 20 g/day had lower hs-CRP levels [median (25th-75th) 0.7 mg/dl (0.4-2.4) vs. 1.9 mg/dl (1.0-4.4); P = 0.002], than the other group. Controlled for HbA1c and energy intake, an inverse relation was observed between hs-CRP levels and total fiber [ß = − 0.030 (SE: 0.0120), P = 0.02], soluble fiber [ß = − 0.078 (SE: 0.0421), P = 0.06] and insoluble fiber [ß = − 0.039 (SE: 0.01761), P = 0.026]. Even, after additional adjustment fibers remained associated with lower hs-CRP levels. Total fibers were stratified in 4 groups: < 10 g/day, from 10 to < 20 g/day, from 20 to 30 g/day and > 30 g/day. Compared to the group who ingested < 10 g/day of total fiber (referent group), the group who consumed > 30 g/d had significantly lower hs-CRP levels [−2.45 mg/L, P = 0.012] independent of the HbA1c values.
The present study suggests that an increased consumption of dietary fiber > 30 g/day may play a role in reducing inflammation in individuals with type 1 diabetes.
[Show abstract][Hide abstract] ABSTRACT: AimsTo compare the efficacy and safety of two insulin intensification strategies in patients with type 2 diabetes inadequately controlled on basal insulin glargine with metformin and/or pioglitazone.Materials And MethodsA multinational, randomized, open-label trial that compared insulin lispro low mixture twice daily (LM25; n = 236) with a basal-prandial regimen of insulin glargine once daily and insulin lispro once daily (IGL; n = 240) over 24 weeks in patients with HbA1c 7.5%–10.5% and fasting plasma glucose ≤6.7 mmol/L. The primary objective was to assess noninferiority [per-protocol (PP) population], and then superiority [intention-to-treat (ITT) population], of LM25 versus IGL according to change in HbA1c at 24 weeks (noninferiority margin 0.4%, two-sided significance level 0.05).ResultsEstimated change [least squares (LS) mean (95% CI)] in HbA1c at 24 weeks: -1.30 (-1.44, -1.16)% with LM25 and -1.08 (-1.22, -0.94)% with IGL. Noninferiority was shown [LS mean (95% CI) HbA1c treatment difference -0.21 (-0.38, -0.04) (PP population)]; gated superiority assessment showed a statistically significant advantage for LM25 (P = 0.010; ITT population). Mean blood glucose, glycemic variability, overall tolerability, and hypoglycemic episodes per patient-year did not show significant differences between treatments during the study.Conclusions
In patients with type 2 diabetes inadequately controlled on once-daily basal insulin glargine and metformin and/or pioglitazone, intensification with LM25 was superior to a basal-prandial approach in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycemia episodes.
[Show abstract][Hide abstract] ABSTRACT: This systematic review with meta-analysis of randomized controlled trials (RCT) aimed to analyze the effect of fiber intake on glycemic control in patients with type 2 diabetes. Databases were searched up to November 2012 using the following medical subject headings: diabetes, fiber, and randomized controlled trial. Absolute changes in glycated hemoglobin and fasting plasma glucose were reported as differences between baseline and end-of-study measures. Pooled estimates were obtained using random-effects models. Of the 22,046 articles initially identified, 11 (13 comparisons; range of duration, 8-24 weeks) fulfilled the inclusion criteria, providing data from 605 patients. High-fiber diets, including diets with foods rich in fiber (up to 42.5 g/day; four studies) or supplements containing soluble fiber (up to 15.0 g/day; nine studies), reduced absolute values of glycated hemoglobin by 0.55% (95% CI -0.96 to -0.13) and fasting plasma glucose by 9.97 mg/dL (95% CI -18.16 to -1.78). In conclusion, increased fiber intake improved glycemic control, indicating it should be considered as an adjunctive tool in the treatment of patients with type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Long-term insulin independence after islet transplantation depends on engraftment of a large number of islets. However, the yield of pancreatic islets from brain-dead donors is negatively affected by the up-regulation of inflammatory mediators. Brain death is also believed to increase tissue factor (TF) expression, contributing to a low rate of engraftment.
We conducted a case-control study to assess brain death-induced inflammatory effects in human pancreas. Seventeen brain-dead patients and 20 control patients undergoing pancreatectomy were studied. Serum tumor necrosis factor (TNF), interleukin (IL) 6, IL-1β, interferon (IFN) γ, and TF were measured using enzyme-linked immunosorbent assay kits. Gene expressions of these cytokines and TF were evaluated by reverse transcriptase quantitative polymerase chain reaction. Protein quantification was performed by immunohistochemistry in paraffin-embedded pancreas sections.
Brain-dead patients had higher serum concentrations of TNF and IL-6 and increased TNF protein levels compared to controls. The groups had similar TNF, IL-6, IL-1β, and IFN-γ messenger RNA levels in pancreatic tissue. Reverse transcriptase quantitative polymerase chain reaction revealed TF messenger RNA up-regulation in controls. Immunohistochemical analyses showed that brain-dead patients had increased TNF protein levels compared to controls.
Brain death induces inflammation evidenced by the up-regulation of TNF in serum and pancreatic tissue. Blocking the expression of key inflammatory mediators in brain-dead donors should be evaluated as a new approach to improve the outcomes of islet transplantation.
[Show abstract][Hide abstract] ABSTRACT: To evaluate possible associations between cardiovascular autonomic dysfunction and peripheral artery disease (PAD) in patients with type 2 diabetes mellitus.
In this cross-sectional study, 67 patients with type 2 diabetes were included. PAD was identified by Doppler ultrasonography: systolic ankle-brachial pressure index <0.9. Cardiovascular autonomic function, besides five conventional cardiovascular autonomic function tests, was assessed by heart rate variability (HRV; 24-h ambulatory ECG recording) in time and frequency domains (spectral analyses) and three dimensional return maps. Power spectral analyses (PSA) were quantified in low frequency (LF), high frequency (HF), and very low frequency.
Patients with PAD (n = 30) had longer diabetes duration, higher systolic blood pressure (BP), waist-to-hip ratio, HbA1C test, and urinary albumin excretion (UAE) than patients without PAD. Most HRV indices in time domain were lower in patients with than without PAD. These patients also had lower PSA indices (LF=0.19±0.07 vs. 0.29±0.11 n.u.; LF/HF ratio=1.98±0.9 vs. 3.35±1.83; P< 0.001) and indices of sympathetic (three-dimensional return map: P1-night 61.7±9.4 vs. 66.8±9.7; P=0.04) and vagal (24-h P2 54.5±15.2 vs. 62.7±2.9; P< 0.02) activities (arbitrary units) than patients without PAD. Multivariate logistic regression analyses, adjusted for systolic BP, DM duration, HbA1C test, and UAE, confirmed the associations between impaired autonomic modulation and PAD, except for P1 index.
In conclusion, patients with type 2 diabetes with PAD had lower HRV indices than patients without PAD, reflecting a dysfunction of cardiovascular autonomic modulation.