Metabolic syndrome as a risk indicator for periodontal disease and tooth loss.

OBJECTIVES: The aim of the present study was to evaluate the association of metabolic syndrome (MS) with periodontitis (PE) and tooth loss (TL). MATERIALS AND METHODS: A cross-sectional study was conducted with 363 individuals who underwent full-mouth periodontal examination, and the association between MS and PE was evaluated considering three outcomes: severe periodontitis, mean probing depth ≥2.4 mm, and mean clinical attachment loss ≥2.0 mm. The prevalence ratio (PR) between MS and PE was calculated using a model adjusted for gender, age, smoking, years of education, and socioeconomic status. RESULTS: The adjusted model showed a PR for severe periodontitis of 1.17 (95 % CI 0.83-1.65). There was no significant association between MS and PE defined as mean probing depth ≥2.4 mm. MS was significantly associated with PE defined as mean attachment loss ≥2 mm in individuals aged 41-60 years (PR 1.47, 95 % CI 1.05-2.06). In addition, MS was associated with TL (>6 teeth) (PR 1.23, 95 % CI 1.02-1.49) for all ages, both in crude and adjusted analyses. CONCLUSIONS: We concluded that there is a weak association of MS with both attachment loss and TL. CLINICAL RELEVANCE: Patients with MS seem to have a higher risk of attachment loss and tooth loss and should be screened for periodontal disease.

Increased protein intake is associated with uncontrolled blood pressure by 24-hour ambulatory blood pressure monitoring in patients with type 2 diabetes.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial.

BACKGROUND: Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population. METHODS: This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (≥1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight. RESULTS: A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5 to 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of placebo patients, with one related discontinuation (dapagliflozin 5 mg). Evidence suggestive of urinary tract infection was reported in 8.0% to 13.3% of dapagliflozin patients and 8.0% of placebo patients, with one related discontinuation (dapagliflozin 2.5 mg). CONCLUSIONS: Dapagliflozin added to metformin for 102 weeks enabled sustained reductions in HbA1c, FPG, and weight without increased risk of hypoglycemia in patients with type 2 diabetes who were inadequately controlled on metformin alone. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00528879.

The presence of the -866A/55Val/Ins haplotype in the uncoupling protein 2 (UCP2) gene is associated with decreased UCP2 gene expression in human retina.

Uncoupling protein 2 (UCP2) is a mitochondrial transporter present in the inner membrane of mitochondria, and it uncouples substrate oxidation from ATP synthesis, thereby dissipating the membrane potential energy and consequently decreasing ATP production by mitochondrial respiratory chain. As a consequence of the uncoupling, UCP2 decreases the reactive oxygen species (ROS) formation by mitochondria. ROS overproduction is related to diabetic retinopathy (DR), a chronic complication of diabetes mellitus (DM). Recently, our group reported that the -866A/55Val/Ins haplotype (-866G/A, Ala55Val and Ins/Del polymorphisms) of the UCP2 gene was associated with increased risk for DR in patients with DM. The purpose of this study was to analyze the effect of this haplotype on UCP2 gene expression in human retina. In addition, MnSOD2 gene expression was also investigated according to different UCP2 haplotypes. This cross-sectional study included 188 cadaveric cornea donors. In a subset of 91 retinal samples differentiated according to the presence of the mutated UCP2 haplotype and risk alleles of the -866G/A and Ins/Del polymorphisms, UCP2 and MnSOD2 gene expressions were measured by semi-quantitative RT-qPCR. Mutated UCP2 haplotype carriers (homozygous + heterozygous) had a lower UCP2 gene expression than reference haplotype carriers (8.4 ± 7.6 vs. 18.8 ± 23.7 arbitrary units; P = 0.046). Accordingly, UCP2 gene expression was decreased in -866A carriers when compared with G/G carriers (P = 0.010). UCP2 gene expression did not differ between Ins allele carriers and Del/Del carriers (P = 0.556). Interestingly, subjects carrying the heterozygous UCP2 haplotype showed increased MnSOD2 gene expression (P = 0.025). This is the first report suggesting that the presence of the -866A/55Val/Ins haplotype is associated with decreased UCP2 gene expression in human retina. Possibly, MnSOD2 expression might influence the UCP2 effect in the protection against oxidative stress.

Albuminuria is not associated with bacteriuria in patients with type 2 diabetes mellitus: a meta-analysis of observational studies.

BACKGROUND/AIMS: It has been recommended that urinary albumin be measured in sterile urine for the proper diagnosis of diabetic nephropathy. However, the association between bacteriuria and urinary albumin is controversial. METHODS: A systematic review and meta-analysis was performed to investigate the association of albuminuria and bacteriuria in patients with diabetes. Medline and Embase were searched (beginning in 1950 until November 2010). Data were extracted independently by two investigators. The pooled OR estimates were calculated using the random effects model. RESULTS: We identified 305 studies in the database searches. A total of seven studies were included, providing data from 1,552 patients (mean age 56.4 years). The OR of bacteriuria for the presence of micro- and/or macroalbuminuria was 1.60 (95% CI: 0.97-2.66, I(2) = 66.6%) as compared to patients without bacteriuria. Funnel plots and the Egger regression test suggested no significant asymmetry in the analysis (p = 0.21). In a sensitivity analysis including the five studies (1,197 participants) that evaluated microalbuminuria as the outcome, the OR of bacteriuria for microalbuminuria was 1.22 (95% CI: 0.68-2.19). CONCLUSION: In conclusion, no association was identified between albuminuria and bacteriuria considering the current literature. Further prospective studies of a large diabetic population are needed to clarify such an association.

Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis.

BACKGROUND: Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea. PURPOSE: To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases. STUDY SELECTION: Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A(1c) (HbA(1c)) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea. DATA EXTRACTION: Primary end points were change in HbA(1c) level, change in weight, and frequency of severe hypoglycemia. DATA SYNTHESIS: Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA(1c) level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents. LIMITATIONS: Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions. CONCLUSION: There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patient's clinical characteristics. PRIMARY FUNDING SOURCE: Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacao de Aperfeicoamento de Pessoal de Nível Superior.

Dose-ranging effects of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis.

The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI -0.66 to -0.59) and body weight by 0.60 kg (95% CI -0.64 to -0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Correction of hyperglycaemia and prevention of glucotoxicity are important objectives in the management of type 2 diabetes. Dapagliflozin, a selective sodium-glucose cotransporter-2 inhibitor, reduces renal glucose reabsorption in an insulin-independent manner. We assessed the efficacy and safety of dapagliflozin in patients who have inadequate glycaemic control with metformin. METHODS: In this phase 3, multicentre, double-blind, parallel-group, placebo-controlled trial, 546 adults with type 2 diabetes who were receiving daily metformin (>/=1500 mg per day) and had inadequate glycaemic control were randomly assigned to receive one of three doses of dapagliflozin (2.5 mg, n=137; 5 mg, n=137; or 10 mg, n=135) or placebo (n=137) orally once daily. Randomisation was computer generated and stratified by site, implemented with a central, telephone-based interactive voice response system. Patients continued to receive their pre-study metformin dosing. The primary outcome was change from baseline in haemoglobin A(1c)(HbA(1c)) at 24 weeks. All randomised patients who received at least one dose of double-blind study medication and who had both a baseline and at least one post-baseline measurement (last observation carried forward) were included in the analysis. Data were analysed by use of ANCOVA models. This trial is registered with ClinicalTrials.gov, number NCT00528879. FINDINGS: 534 patients were included in analysis of the primary endpoint (dapagliflozin 2.5 mg, n=135; dapagliflozin 5 mg, n=133; dapagliflozin 10 mg, n=132; placebo, n=134). At week 24, mean HbA(1c) had decreased by -0.30% (95% CI -0.44 to -0.16) in the placebo group, compared with -0.67% (-0.81 to -0.53, p=0.0002) in the dapagliflozin 2.5 mg group, -0.70% (-0.85 to -0.56, p<0.0001) in the dapagliflozin 5 mg group, and -0.84% (-0.98 to -0.70, p<0.0001) in the dapagliflozin 10 mg group. Symptoms of hypoglycaemia occurred in similar proportions of patients in the dapagliflozin (2-4%) and placebo groups (3%). Signs, symptoms, and other reports suggestive of genital infections were more frequent in the dapagliflozin groups (2.5 mg, 11 patients [8%]; 5 mg, 18 [13%]; 10 mg, 12 [9%]) than in the placebo group (seven [5%]). 17 patients had serious adverse events (four in each of the dapagliflozin groups and five in the placebo group). INTERPRETATION: Addition of dapagliflozin to metformin provides a new therapeutic option for treatment of type 2 diabetes in patients who have inadequate glycaemic control with metformin alone. FUNDING: Bristol-Myers Squibb and AstraZeneca.

High dietary glycemic index and low fiber content are associated with metabolic syndrome in patients with type 2 diabetes.

OBJECTIVE: To investigate possible associations of dietary glycemic index (GI) and fiber content with metabolic syndrome (MetS) in patients with type 2 diabetes. METHODS: In this cross-sectional study, 175 outpatients with type 2 diabetes (aged 61.1 ± 9.7 years; HbA(1c) 7.3% ± 1.4%; diabetes duration of 11 years [range, 5-17]) had food intake assessed by 3-day weighed-diet records. Dietary GI (according to FAO/WHO) and fiber content were categorized as high or low based on median values. MetS was defined according to the 2009 Joint Interim Statement. RESULTS: Patients with MetS (n = 109) had higher 24-hour GI (60.0% ± 6.3% vs 57.5% ± 6.4%), higher breakfast GI (59.8% ± 8.0% vs 55.0% ± 9.9%), and lower fiber intake at 24 hours (17.0 ± 6.6 g vs 21.2 ± 8.0 g), breakfast (1.9 [1.2-3.2] vs 3.1 [1.8-4.9] g), lunch (6.2 [3.9-8.0] vs 7.5 [4.7-9.4] g), and dinner (3.3 [2.1-5.2] vs 4.9 [3.1-6.4] g; p < 0.05 for all comparisons) than patients without MetS. In multivariate analyses, high GI (~60%) of 24 hours (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.10-4.11; p = 0.025), breakfast (OR, 2.20; 95% CI, 1.15-4.21; p = 0.017), and lunch (OR, 2.46; 95% CI, 1.28-4.74; p = 0.007) was associated with MetS. Breakfast (OR, 2.14; 95% CI, 1.04-4.41; p = 0.039) and dinner (OR, 2.27; 95% CI, 1.15-4.49; p = 0.019) with low fiber content were also associated with MetS. When high GI and low fiber intake were combined into the same variable, associations with MetS were maintained. CONCLUSIONS: Increased dietary GI and reduced fiber content were positively associated with MetS, mainly due to breakfast intake, in patients with type 2 diabetes.

Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis.

CONTEXT: Regular exercise improves glucose control in diabetes, but the association of different exercise training interventions on glucose control is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) assessing associations of structured exercise training regimens (aerobic, resistance, or both) and physical activity advice with or without dietary cointervention on change in hemoglobin A(1c) (HbA(1c)) in type 2 diabetes patients. DATA SOURCES: MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and SPORTDiscus databases were searched from January 1980 through February 2011. STUDY SELECTION: RCTs of at least 12 weeks' duration that evaluated the ability of structured exercise training or physical activity advice to lower HbA(1c) levels as compared with a control group in patients with type 2 diabetes. DATA EXTRACTION: Two independent reviewers extracted data and assessed quality of the included studies. DATA SYNTHESIS: Of 4191 articles retrieved, 47 RCTs (8538 patients) were included. Pooled mean differences in HbA(1c) levels between intervention and control groups were calculated using a random-effects model. Overall, structured exercise training (23 studies) was associated with a decline in HbA(1c) level (-0.67%; 95% confidence interval [CI], -0.84% to -0.49%; I(2), 91.3%) compared with control participants. In addition, structured aerobic exercise (-0.73%; 95% CI, -1.06% to -0.40%; I(2), 92.8%), structured resistance training (-0.57%; 95% CI, -1.14% to -0.01%; I(2), 92.5%), and both combined (-0.51%; 95% CI, -0.79% to -0.23%; I(2), 67.5%) were each associated with declines in HbA(1C) levels compared with control participants. Structured exercise durations of more than 150 minutes per week were associated with HbA(1c) reductions of 0.89%, while structured exercise durations of 150 minutes or less per week were associated with HbA(1C) reductions of 0.36%. Overall, interventions of physical activity advice (24 studies) were associated with lower HbA(1c) levels (-0.43%; 95% CI, -0.59% to -0.28%; I(2), 62.9%) compared with control participants. Combined physical activity advice and dietary advice was associated with decreased HbA(1c) (-0.58%; 95% CI, -0.74% to -0.43%; I(2), 57.5%) as compared with control participants. Physical activity advice alone was not associated with HbA(1c) changes. CONCLUSIONS: Structured exercise training that consists of aerobic exercise, resistance training, or both combined is associated with HbA(1c) reduction in patients with type 2 diabetes. Structured exercise training of more than 150 minutes per week is associated with greater HbA(1c) declines than that of 150 minutes or less per week. Physical activity advice is associated with lower HbA(1c), but only when combined with dietary advice.

Polymorphisms of the UCP2 gene are associated with proliferative diabetic retinopathy in patients with diabetes mellitus.

BACKGROUND AND OBJECTIVE: Uncoupling protein 2 (UCP2) plays a role in controlling reactive oxygen species (ROS) production by mitochondria. As ROS overproduction is related to diabetic retinopathy (DR), UCP2 gene polymorphisms might be involved in the development of this complication. We investigated whether the -866G/A (rs659366), Ala55Val (rs660339) and 45 bp insertion/deletion (Ins/Del) polymorphisms in the UCP2 gene might be associated with proliferative DR (PDR). DESIGN AND METHODS: In this case-control study, we analysed 501 type 2 diabetic patients (242 patients with PDR and 259 subjects without any degree of DR) and 196 type 1 diabetic patients (85 cases with PDR and 111 without DR). Haplotypes constructed from the combination of the three UCP2 polymorphisms were inferred using a Bayesian statistical method. RESULTS: In the type 2 diabetic group, multivariate analyses confirmed that the haplotype [A Val Ins] was an independent risk factor for PDR when present in one [adjusted odds ratio (aOR) = 2.12; P = 0.006], at least one (aOR = 2.75; P = 0.00001), or two copies (aOR = 5.30; P = 0.00001), suggesting an additive model of inheritance. Nevertheless, in type 1 diabetic patients, the association of this haplotype with PDR was confirmed only when it was present in at least one (aOR = 2.68; P = 0.014) or two copies (aOR = 6.02; P = 0.005). CONCLUSIONS: The haplotype [A Val Ins] seems to be an important risk factor associated with PDR in both type 2 and 1 diabetic groups.

Evaluating the maintenance of effect of duloxetine in patients with diabetic peripheral neuropathic pain.

BACKGROUND: To evaluate the maintenance of effect of duloxetine 60 mg QD over 26 weeks in patients with diabetic peripheral neuropathic pain (DPNP). METHODS: Adult patients with DPNP and Brief Pain Inventory (BPI) 24-h average pain >or=4 were treated in this open-label study with duloxetine 60 mg QD for 8 weeks. Responders (>or=30% pain reduction) continued on duloxetine 60 mg QD (maintenance arm) for 26 weeks while non-responders had duloxetine increased to 120 mg QD (rescue arm). The primary outcome measure was the mean change from baseline (Week 8) to endpoint (Week 34) in BPI average pain in the maintenance arm. A number of secondary efficacy measures, as well as safety and tolerability, were assessed. RESULTS: Two hundred and sixteen patients entered the study and their baseline BPI average pain was 5.9. Thirty-two patients (15%) discontinued during the acute phase. One hundred and fifteen (53%) patients were found to be responders to 60 mg dose and they entered the maintenance arm. During the maintenance period they reported a mean change of BPI average pain of 0.35, with 0.79 as the upper bound of the one-sided 97.5% CI, which was less than the pre-specified non-inferiority margin of 1.5 (p < 0.001). Non-responders, upon dose increase to 120 mg QD, reported a statistically significant pain reduction. Total of 119 patients completed either arm of the study. Twenty patients experienced 27 serious adverse events including one death. CONCLUSION: In this open-label study, the effect of duloxetine 60 mg QD in patients with DPNP was maintained over 6-month period.

Does bacteriuria interfere with albuminuria measurements of patients with diabetes?

BACKGROUND: Urinary albumin is the main parameter employed to diagnose diabetic nephropathy (DN). The exclusion of bacteriuria has been recommended at the time of DN diagnosis. This approach has been debated and information on this suggestion in patients with diabetes is scarce. The present case-control study was conducted to investigate the interference of bacteriuria in the interpretation of urinary albumin measurements in random urine samples of diabetic patients. METHODS: Urinary albumin concentration (UAC) was measured in random urine samples twice in diabetic patients with and without bacteriuria (> or =10(5) colony-forming units/mL). Cases (n = 81) were defined as patients who had baseline UAC measurement in the presence of bacteriuria and had the second UAC measured in a sterile urine sample. Controls (n = 80) had the two UAC measured in sterile urine specimens. RESULTS: Baseline UAC was not different between case [15.4 (1.5-2148) mg/L] and control groups [14.2 (1.5-1292) mg/L; P = 0.24], nor was the proportion of patients with normo-, micro- and macroalbuminuria. In cases, UAC measurements in the presence of bacteriuria and in sterile urine specimens were not different [15.4 (1.5-2148) versus 13.7 (1.5-2968) mg/L; P = 0.14)], nor was the proportion of normo- (51.9% versus 61.5%), micro- (40.7% versus 32.1%) and macroalbuminuria (7.4% versus 6.4%; P = 0.46). In the control group, UAC values were also not different in the two urine samples: [14.2 (1.5-1292) versus 9.7 (1.5-1049) mg/L, P = 0.22]. CONCLUSIONS: The presence of bacteriuria does not interfere significantly with urinary albumin measurements and its exclusion is not necessary to diagnose DN.

Glucagon-like peptide-1 receptor agonists and pancreatic cancer: a meta-analysis with trial sequential analysis.

We aimed to assess if GLP-1 agonists are associated with pancreatic cancer. Systematic review and meta-analysis of randomized trials with GLP-1 agonists as an intervention was performed. Trial sequential analysis (TSA) was performed to assess if the available information is sufficient to reject this association. Twelve trials met the study criteria, with a total of 36, 397 patients. GLP-1 analogues did not increase the risk for pancreatic cancer when compared to other treatments (OR 1.06; 95% CI 0.67 to 1.67; I2 14%). TSA confirmed that enough patients were randomized and again no association of the medications and pancreatic cancer was observed considering a NNH of 1000 and the short mean follow-up of the included trials (1.7 years). Larger studies with longer duration would be required to exclude a greater NNH and to aside concerns regarding possible influence of study duration and the outcome.

Sources of protein and polyunsaturated fatty acids of the diet and microalbuminuria in type 2 diabetes mellitus.

BACKGROUND: Albuminuria excretion rate above the reference range and below albustix positive proteinuria (20-199 microg/min) is known as microalbuminuria and has been associated with an increased risk of death and progression to renal failure. Besides hyperglicemia and high blood pressure levels, dietary factors can also influence albuminuria. OBJECTIVE: To evaluate possible associations of dietary components (macronutrients and selected foods) with microalbuminuria in type 2 diabetic patients. METHODS: In this cross-sectional study, 119 normoalbuminuric [NORMO; 24-h urinary albumin excretion (UAE) < 20 microg/min; immunoturbidimetry] and 62 microalbuminuric (MICRO; UAE 20-199 microg/min) type 2 diabetic patients, attending the Endocrine Division, Hospital de Clínicas de Porto Alegre (Brazil), without previous dietary counseling, underwent 3-day weighed-diet records, and clinical and laboratory evaluation. RESULTS: MICRO patients consumed more protein (20.5 +/- 4.4 vs. 19.0 +/- 3.5% of total energy; p = 0.01) with a higher intake from animal sources (14.5 +/- 4.7 vs. 12.9 +/- 3.8% of total energy; p = 0.015) than NORMO patients. The intakes of PUFAs (8.6 +/- 2.9 vs. 9.7 +/- 3.3% of total energy; p < 0.03), PUFAs from vegetable sources (7.3 +/- 3.4 vs. 8.6 +/- 3.7% of total energy; p = 0.029), plant oils [0.2 (0.1-0.6) vs. 0.3 (0.1-0.9) mg/kg weight; p = 0.02] and margarines [3.3 (0-75.7) vs. 7.0 (0-51.7) g/day; p = 0.01] were lower in MICRO than in NORMO. In multivariate logistic regression models, adjusted for age, gender, presence of hypertension and fasting plasma glucose, intake of total protein (% of total energy; OR 1.104; 95% CI 1.008-1.208; p = 0.032) was positively associated with microalbuminuria. The intakes of total PUFAs (% of total energy; OR 0.855; 95%CI 0.762-0.961; p = 0.008), PUFAs from vegetable sources (% of total energy; OR 0.874; 95%CI 0.787-0.971; p = 0.012) and plant oils (mg/kg weight; OR 0.036; 95% CI 0.003-0.522; p = 0.015) were negatively associated with microalbuminuria. CONCLUSIONS: In type 2 diabetic patients, the high intake of protein and the low intake of PUFAs, particularly from plant oils, were associated with the presence of microalbuminuria. Reducing protein intake from animal sources and increasing the intake of lipids from vegetable origin might-reduce the risk of microalbuminuria.

Long-term effect of a chicken-based diet versus enalapril on albuminuria in type 2 diabetic patients with microalbuminuria.

OBJECTIVE: In short-term studies, the replacement of red meat in the diet with chicken reduced the urinary albumin excretion rate (UAER) and improved lipid profile in type 2 diabetic patients with diabetic nephropathy. The present study sought to assess these effects over a long-term period, comparing the effects of a chicken-based diet (CD) versus enalapril on renal function and lipid profile in microalbuminuric type 2 diabetic patients. DESIGN: This was a randomized, open-label, controlled clinical trial with a follow-up of 1 year. SETTING: The trial involved outpatients with type 2 diabetes attending a clinic of the Division of Endocrinology at a tertiary-care hospital. PATIENTS: Twenty-eight microalbuminuric patients completed the study and were evaluated. INTERVENTIONS: Patients were randomized to an experimental diet (CD plus active placebo) or to treatment with enalapril (10 mg/day plus usual diet). MAIN OUTCOME MEASURES: The main outcome measure was UAER (according to immunoturbidimetry). Blood pressure, anthropometric indices, and compliance were also evaluated monthly. The glomerular filtration rate ((51)Cr-EDTA), and lipid, glycemic, and nutritional indices, were measured at baseline and quarterly. RESULTS: The UAER was reduced after CD (n = 13; from 62.8 [range, 38.4 to 125.1] to 49.1 [range, 6.2 to 146.5] microg/min; P < .001) and after enalapril (n = 15; from 55.8 [range, 22.6 to 194.3] to 23.1 [range, 4.0 to 104.9] microg/min; P < .001), and this was already significant at month 4. The reduction in UAER after CD (32%; 95% confidence interval, 6.7% to 57.6%) and after enalapril treatment (44.7%; 95% confidence interval, 28.3% to 61.1%; P = .366) were not significantly different. CONCLUSIONS: The CD and the angiotensin-converting enzyme inhibitor enalapril promoted a similar reduction of UAER in patients with type 2 diabetes and microalbuminuria in a 12-month follow-up period.

Dipeptidyl peptidase-4 inhibitors, pancreatic cancer and acute pancreatitis: A meta-analysis with trial sequential analysis.

The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with pancreatic cancer and acute pancreatitis. Recent meta-analyses have reported conflicting findings. Therefore, we performed a meta-analysis to assess the risk of both pancreatic cancer and acute pancreatitis associated with the use of DPP-4 inhibitors. We also used trial sequential analysis to evaluate whether the number of patients included was enough to reach conclusions. We included randomised controlled trials lasting 24 weeks or more that compared DPP-4 inhibitors with placebo or other antihyperglycaemic agents. A total of 59,404 patients were included. There was no relationship between the use of DPP-4 inhibitors and pancreatic cancer (Peto odds ratio 0.65; 95% CI 0.35-1.21), and the optimal sample size was reached to determine a number needed to harm (NNH) of 1000 patients. DPP-4 inhibitors were associated with increased risk for acute pancreatitis (Peto odds ratio 1.72; 95% CI 1.18-2.53), with an NNH of 1066 patients, but the optimal sample size for this outcome was not reached. In conclusion, there is no association between DPP-4 inhibitors and pancreatic cancer, and a small risk for acute pancreatitis was observed with DPP-4 inhibitor use, although the latter finding is not definitive.

Type 2 diabetic patients attending a nurse educator have improved metabolic control.

To investigate if routine education by nurses is associated with improved metabolic control in type 2 diabetic (DM2) outpatients, we randomly selected 143 patients (81 women), not using insulin, at the Endocrine or Internal Medicine clinics, to be interviewed and submitted to a clinical and laboratory evaluation. Age was 59.1+/-10.1 years; duration of DM2 7.5+/-6.3 years; BMI 29.7+/-5.2 kg/m(2). Patients were grouped according to HbA(1c) (<7.0% or > or =7.0%). Age, gender, DM2 duration, BMI, and lipid profile were not different. Patients with HbA(1c)> or =7.0% (n=49) were more likely to be taking oral agents, and to be treated by internists rather than endocrinologists (P=0.04). Nurse education was associated with a greater proportion of patients with HbA(1c)<7.0%, especially among those attending the Internal Medicine clinic. In logistic regression, education by nurses remained associated to HbA(1c)<7.0% (OR: 3.29, P=0.005), after controlling for use of oral agents (OR 0.067, P=0.01), attending the Endocrine clinic (OR 4.11, P=0.002), self-reported adherence to diet ("yes" or "no"), known DM duration, and instruction level (NS). Nurse education contributes significantly and independently for better metabolic control in DM2 outpatients in a teaching hospital.

[Dietary factors and metabolic syndrome]. / Fatores dietéticos e síndrome metabólica.

The role of diet in metabolic syndrome (MS) has been studied regarding each one of its components: obesity, high blood pressure, dyslipidemia, and abnormal glucose metabolism. However, few studies evaluated the effects of diet in the presence of MS as a unique independent disease. The aim of this manuscript was to review the role of dietary factors and dietary recommendations for MS. Recently some studies demonstrated that intake of whole-grain foods were negatively associated with MS. Foods with high glycemic index were positively associated with insulin resistance and the prevalence of MS. Following a Mediterranean-style diet caused a reduction in the number of MS components. Also, the adoption of the DASH diet improved the profile of all MS components. A total daily energy intake to obtain and/or to maintain a desirable weight is recommended for patients with MS. The fat content, especially from saturated fat, and cholesterol must be reduced and the intake of whole-grain foods, fruits, and vegetables must be increased. Probably, dietary fibers have an important role in the management of MS. New studies to evaluate the role of diet in the presence and development of MS are needed.

Screening for coronary artery disease in patients with type 2 diabetes: a meta-analysis and trial sequential analysis.

OBJECTIVE: To evaluate the efficacy of coronary artery disease screening in asymptomatic patients with type 2 diabetes and assess the statistical reliability of the findings. METHODS: Electronic databases (MEDLINE, EMBASE, Cochrane Library and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled trials evaluating coronary artery disease screening in asymptomatic patients with type 2 diabetes and reporting cardiovascular events and/or mortality were included. Data were summarised with Mantel-Haenszel relative risk. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 40% reduction in outcomes. Main outcomes were all-cause mortality and cardiac events (non-fatal myocardial infarction and cardiovascular death); secondary outcomes were non-fatal myocardial infarction, myocardial revascularisations and heart failure. RESULTS: One hundred thirty-five references were identified and 5 studies fulfilled the inclusion criteria and totalised 3315 patients, 117 all-cause deaths and 100 cardiac events. Screening for coronary artery disease was not associated with decrease in risk for all-cause deaths (RR 0.95(95% CI 0.66 to 1.35)) or cardiac events (RR 0.72(95% CI 0.49 to 1.06)). TSA shows that futility boundaries were reached for all-cause mortality and a relative risk reduction of 40% between treatments could be discarded. However, there is not enough information for firm conclusions for cardiac events. For secondary outcomes no benefit or harm was identified; optimal sample sizes were not reached. CONCLUSION: Current available data do not support screening for coronary artery disease in patients with type 2 diabetes for preventing fatal events. Further studies are needed to assess the effects on cardiac events. PROSPERO: CRD42015026627.