The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.

Glycated Hemoglobin and Blood Pressure Levels in Adults With Type 2 Diabetes: How Many Patients Are on Target?

OBJECTIVES: Achieving glycated hemoglobin (A1C) and blood pressure targets is an important strategy for preventing chronic vascular complications in diabetes. Our aim in this study was to determine the proportion of type 2 diabetes patients who meet the recommended A1C and arterial blood pressure targets and to identify the determinants of failure to do so. METHODS: A cross-sectional study was conducted in an outpatient endocrine clinic at a university hospital. The A1C goal was 7% in general and 8% for patients with advanced chronic complications. Regarding blood pressure, the overall expected target was 140/90 mmHg. RESULTS: A total of 602 type 2 diabetes patients were analyzed: 62% were female, 14% self-reported as black, mean age was 63±11 years, mean diabetes duration was 17±9 years and median A1C was 8.0% (interquartile range, 7.0% to 9.5%). Macrovascular disease was present in 33% of the patients, diabetic retinopathy in 47%, peripheral neuropathy in 43% and diabetic kidney disease in 56%. Regarding metabolic control, 403 (67%) patients were not at the adjusted target A1C level, and being female, black, young and an insulin user were the main determinants of poor glycemic control. Regarding blood pressure, 348 (58%) patients were not at the recommended targets, and a more advanced age was the main associated factor. CONCLUSIONS: Because more than half of type 2 diabetes outpatients do not meet the recommended A1C and blood pressure target values, there is a major call to overcome the therapeutic inertia and target treatment of patients on an individual basis.

Dietary source of saturated fat and percentage body fat of patients with type 2 diabetes mellitus: A cross-sectional study.

BACKGROUND: The influence of dietary fat on the body fat of patients with diabetes is not well established. This cross-sectional study aimed to analyze the association between percentage body fat (PBF) and dietary sources of fat from the usual diet of patients with type 2 diabetes. METHODS: Outpatients were submitted to PBF evaluation estimated by bioelectrical impedance. The patient's usual diet was assessed by a 3-day weighed diet record (WDR), and compliance was analyzed by comparing the protein intake estimated from the WDR and that from 24-hr urinary nitrogen output. RESULTS: A total of 188 patients with type 2 diabetes (aged 62.5 ± 8.8 years; 57% female, body mass index [BMI] 29.3 ± 3.8 kg/m²) were analyzed and divided into groups with high and low PBF according to mean PBF (men: 26.6 ± 7.1%; women: 39.8 ± 5.9%). Patients with high PBF consumed an increased proportion of red meat (52.0% of total meat), processed meat (5.4%), and saturated fat from red meat (2.1% of energy) compared to low PBF individuals (42.3% [p = 0.036]; 3.0% [p = 0.010]; 1.5% of energy [p = 0.032], respectively). According to Poisson's regression, the consumption of red meat (PR = 1.008 [95% CI = 1.002-1.013]; p = 0.006) and the reuse of frying oil (PR = 1.670 [95% CI = 1.240-2.249]; p = 0.001) were associated with higher PBF. In the adjusted analysis, the upper tertile of processed meat intake was associated with higher PBF (PR = 1.522 [95% CI = 1.226-1.891]; p = 0.001) compared to the lower tertile. CONCLUSIONS: The present study suggested that a higher ingestion of dietary sources of saturated fat was associated with high PBF in patients with type 2 diabetes.

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.

Protein intake estimated by weighed diet records in patients with type 2 diabetes: misreporting and intra-individual variability using 24-hour nitrogen output as criterion standard.

In patients with type 2 diabetes mellitus (DM), the factors associated with under- or overreporting of protein intake in nutrition assessment tools, as well as the variability of diet records, have not been fully established. The aim of this cross-sectional study was to evaluate factors associated with under- or overreporting of protein intake and its variability in patients with type 2 DM. Protein intake was estimated in 205 patients (aged 59.8+/-9.6 years) using 3-day weighed diet records and 24-hour nitrogen output (criterion standard). Twenty-three patients repeated the 3-day weighed diet records three times. Clinical, nutrition, and lifestyle evaluations were performed. Coefficients of variation were calculated for protein intake. Factors associated with under- and overreporting were assessed using multivariate logistic regression models. Coefficients of variation for protein intake estimated by weighed diet records or nitrogen output were similar (11.9% vs 11.3%; P>0.05). Using Beaton's formula, a difference of 16.5% in protein intake between two 3-day weighed diet records was acceptable. The lowest A1c test tertile (< or =6.9%) was associated with protein intake underreporting (odds ratio [OR]=0.40; 95% confidence interval [CI]=0.16 to 0.99; P=0.046] after adjustment for sex, age, employment status, and living alone. Male sex (OR=6.66; 95% CI: 2.08 to 22.07; P=0.002), A1c test (OR=1.29; 95% CI: 1.02 to 1.64; P=0.036), and body mass index (OR=0.89; 95% CI: 0.80 to 0.994; P=0.039), adjusted for physical and employment status, education, and preparing one's own meals, were associated with overreporting. In conclusion, in patients with type 2 DM, a difference >16.5% in protein intake between two 3-day weighed diet records should be interpreted as a true discrepancy. Poor glucose control and male sex increase the chance of inaccurate 3-day weighed diet records.

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.

Low linolenic and linoleic acid consumption are associated with chronic kidney disease in patients with type 2 diabetes.

AIM: This cross-sectional study aimed to assess the association of the fat content in the diet with Diabetic Kidney Disease (DKD) in patients with type 2 diabetes. METHODOLOGY: Patients from the Diabetes research clinic at Hospital de Clínicas de Porto Alegre (Brazil) were consecutively recruited. The inclusion criterion was the diagnosis of type 2 diabetes. The exclusion criteria were as follows: body mass index >40 kg/m2, heart failure, gastroparesis, diabetic diarrhea, dietary counseling by a registered dietitian during the previous 12 months, and inability to perform the weighed diet records (WDR). The dietary fatty acids (saturated, monounsaturated and polyunsaturated) consumption was estimated by 3-day WDR. Compliance with the WDR technique was assessed by comparison of protein intake estimated from the 3-day WDR and from the 24-h urinary nitrogen output performed on the third day of the WDR period. The presence of DKD was defined as urinary albumin excretion (UAE) ≥ 30 mg / 24 h or/and glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Urinary albumin was measured twice and eGFR was estimated by using the CKD-EPI equation. RESULTS: A total of 366 patients were evaluated; of these, 33% (n = 121) had DKD. Multivariate analysis showed that the intake of linolenic acid was negatively associated with DKD (OR = 0.57; 95% CI 0.35-0.93; P = 0.024), adjusted for gender, smoking, cardiovascular disease, ACE inhibitors and/or angiotensin receptor blocker use, systolic blood pressure, fasting plasma glucose and HDL cholesterol. In a separate model, similar results were observed for linoleic acid, adjusting to the same co-variables (OR = 0.95; 95% CI 0.91-0.99; P = 0.006). CONCLUSION: The lower intake of polyunsaturated fatty acids, especially linolenic and linoleic acid, is associated with chronic kidney disease in patients with type 2 diabetes.

Withdrawal of red meat from the usual diet reduces albuminuria and improves serum fatty acid profile in type 2 diabetes patients with macroalbuminuria.

BACKGROUND: Replacement of red meat in the diet with chicken has reduced the urinary albumin excretion rate (UAER) and serum cholesterol in microalbuminuric type 2 diabetes patients. The effects of withdrawing red meat are unknown in the more advanced stages of diabetic nephropathy. OBJECTIVE: Our objective was to assess the effects of replacing red meat in the usual diet (UD) with chicken (CD) and of consuming a lactovegetarian low-protein diet (LPD) on renal function, fatty acid, and lipid profile in macroalbuminuric type 2 diabetes patients. DESIGN: A crossover controlled trial was conducted in 17 type 2 diabetes patients with macroalbuminuria (24-h UAER > or = 200 microg/min). Each patient followed the UD, CD, and LPD in a random order for 4 wk. After each diet, glomerular filtration rate, UAER, serum fatty acid, lipid profile, glycemic control, anthropometric indexes, and blood pressure were measured. RESULTS: UAER [median CD: 269.4 (range: 111-1128) microg/min; LPD: 229.3 (76.6-999.3) microg/min; UD: 312.8 (223.7-1223.7) microg/min; P < 0.01] and mean (+/-SD) non-HDL cholesterol (CD: 3.92 +/- 0.99 mmol/L; LPD: 3.92 +/- 0.93 mmol/L; UD: 4.23 +/- 1.06 mmol/L; P = 0.042) were lower after CD and LPD than after UD. Compared with the UD, an increase in serum total polyunsaturated fatty acids was also observed (CD: 39.8 +/- 2.6%; LPD: 39.7 +/- 4.4%; UD: 37.3 +/- 3.1%; P = 0.029). CONCLUSION: In macroalbuminuric patients with type 2 diabetes, withdrawing red meat from the diet reduces the UAER.

Diabetic nephropathy: diagnosis, prevention, and treatment.

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects approximately 40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 microg/min and < or =199 microg/min) and macroalbuminuria (UAE > or =200 microg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c <7%), treating hypertension (<130/80 mmHg or <125/75 mmHg if proteinuria >1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.

[Analysis of the criteria used for the definition of metabolic syndrome in patients with type 2 diabetes mellitus]. / Análise dos critérios de definição da síndrome metabólica em pacientes com diabetes melito tipo 2.

The aim was to compare in patients with type 2 diabetes mellitus (DM2) the prevalence of the metabolic syndrome according to the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP) definitions, and to analyze the association between them and the complications of DM2. Patients with DM2 (n= 753) were evaluated for ethnics, anthropometrics and laboratory parameters and for the presence of DM2 complications: diabetic nephropathy, coronary artery disease, stroke, diabetic retinopathy and peripheral vascular disease. Insulin resistance was estimated using the HOMA index. Metabolic syndrome was found in 671 (89%) and 657 (87%) patients using the WHO definition and the NCEP definition, respectively. In the total group, there was a moderate agreement between the two definitions (k= 0.54; 95% CI 0.49-0.59), although, it was better for black patients (k= 0.69; 95% CI 0.60-0.78) than white (k= 0.54; 95% CI 0.48-0.6) or mulattos patients (k= 0.26; 95% CI 0.09-0.43). Patients with metabolic syndrome using the NCEP criteria had higher HOMA-IR values compared to those without metabolic syndrome (p= 0.001). This differentiation was not seen using the WHO definition (p= 0.152). The proportion of diabetic complications was similar for both definitions. In conclusion, regarding the risk of diabetic complications both definitions are equivalent. However, there are some ethnic differences in the agreement between the two definitions.

Abnormal captopril scintigraphy in Bartter syndrome.

A 37-year-old patient with severe hypokalemia (approximately 1.7 mEq/L) and muscular weakness had a very high serum renin level. No renin-producing tumor was found and she was diagnosed with Bartter Syndrome The parathyroid hormone level was high due to concomitant renal calcium loss. Tc-99m-DTPA captopril scintigraphy was performed to confirm the diagnosis.

Effect of a chicken-based diet on renal function and lipid profile in patients with type 2 diabetes: a randomized crossover trial.

OBJECTIVE: To assess the effect of replacing red meat with chicken in the usual diet and the effect of a low-protein diet on glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and lipid levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized, crossover, controlled trial was conducted with 28 patients with type 2 diabetes (seven women; mean age 58.1 years): 15 patients were normoalbuminuric (UAER <20 microg/min), and 13 patients were microalbuminuric (UAER 20-200 microg/min). A chicken-based diet (red meat replaced with chicken) and a low-protein diet were compared with the patients' usual diet. Patients followed each diet for 4 weeks with a 4-week washout period between. GFR ((51)Cr-EDTA single-injection technique), 24-h UAER (immunoturbidimetry), apolipoprotein B, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured after each diet. RESULTS: Normoalbuminuric and microalbuminuric patients with diabetes were analyzed separately. In normoalbuminuric patients, GFR after the chicken (101.3 +/- 22.9 ml x min(-1) x 1.73 m(-2)) and low-protein diets (93.8 +/- 20.5 ml x min(-1) x m(-2)) was lower than after the usual diet (113.4 +/- 31.4 ml x min(-1) x 1.73 m(-2); P < 0.05). In microalbuminuric patients, apolipoprotein B levels were lower after the chicken (113.5 +/- 36.0 mg/dl) and low-protein diets (103.5 +/- 40.1 mg/dl) than after the usual diet (134.3 +/- 30.7 mg/dl; P < 0.05). Only the chicken diet reduced UAER (median 34.3 microg/min) compared with the low-protein (median 52.3 microg/min) and usual (median 63.8 microg/min) diets (P < 0.05). Glycemic control and blood pressure did not change after the diets. CONCLUSIONS: A normoproteic diet with chicken as the only source of meat may represent an alternative strategy for treatment of patients with type 2 diabetes and microalbuminuria.

Fatty acid composition of serum lipid fractions in type 2 diabetic patients with microalbuminuria.

OBJECTIVE: To determine the fatty acid composition of serum phospholipid, triglyceride, and cholesterol ester fractions and to analyze the lipid profile of microalbuminuric type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A case-control study was conducted with 72 patients: 37 were normoalbuminuric (urinary albumin excretion rate [UAER] <20 microg/min), and 35 were microalbuminuric (UAER 20-200 microg/min). After 4 weeks of a standardized diet, the fatty acid composition of phospholipid, triglyceride, and cholesterol ester fractions was determined by gas chromatography. Total cholesterol and triglycerides were measured by enzymatic-colorimetric methods; cholesterol HDL by double precipitation with heparin, MnCl(2), and dextran sulfate; and apolipoprotein B by immunoturbidimetry. RESULTS: Microalbuminuric patients showed a lower proportion of polyunsaturated fatty acids (24.8 +/- 11.0%), especially of the n-6 family (21.7 +/- 10.5%), in triglyceride fraction than normoalbuminuric patients (34.1 +/- 11.3%, P = 0.001 and 31.4 +/- 11.5%, P < 0.001, respectively). Patients with microalbuminuria also presented higher levels of saturated fatty acids in triglyceride fraction (43.4 +/- 18.0% vs. 34.7 +/- 13.1%, P = 0.022). In the logistic regression analysis, only the proportion of polyunsaturated fatty acids in triglyceride fraction remained significantly associated with microalbuminuria (odds ratio [OR] 0.92, 95% CI 0.85-0.98, P = 0.019). Total cholesterol, HDL cholesterol, triglyceride, and apolipoprotein B levels were similar in normo- and microalbuminuric patients. CONCLUSION: Microalbuminuria in type 2 diabetic patients is associated with low polyunsaturated fatty acid contents in serum triglyceride fraction. This association may represent a risk factor for cardiovascular disease and may contribute to the progression of renal disease.

[The role of the diet as a risk factor for the development and progression of diabetic nephropathy]. / Papel da dieta como fator de risco e progressão da nefropatia diabética.

Diabetic nephropathy (DN) is the leading cause of kidney disease in patients starting renal replacement therapy, and affects up to 40% of type 1 and type 2 diabetic patients. Diet seems to play an important role in the development of the disease. There are evidences supporting the concept that not only the amount but also the origin of dietary protein are associated with DN. Few studies analyzed the role of dietary lipids. A low-protein diet slows down the decline of renal function and ameliorates the DN prognosis and death in patients with type 1 diabetes with micro- and macroalbuminuria. Studies in type 2 diabetic patients are scanty but short-term studies suggest that this approach decreases albuminuria. However, the use of low-protein diet for long periods is compromised by poor compliance and its long-term safety is not firmly established. Enthusiastic results come up when comparing the effect of different sources of animal protein on renal function and lipid profile in patients with DN, which may represent an alternative strategy for low-protein diet on medical nutritional therapy in patients with DN and in cardiovascular risk factors and endothelial function.

Dietary fat composition and cardiac events in patients with type 2 diabetes.

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 α-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..

Prediction of cardiovascular events, diabetic nephropathy, and mortality by albumin concentration in a spot urine sample in patients with type 2 diabetes.

AIMS: To analyze in a random urine spot the predictive value of urinary albumin concentration (UAC) for cardiovascular events, diabetic nephropathy (DN), and death in patients with type 2 diabetes. METHODS: In this cohort, urinary albumin (immunoturbidimetry) was measured as 24-h urinary albumin excretion (UAE) and, in a random spot urine, as UAC and albumin:creatinine ratio (ACR). Primary outcomes were: 1) cardiovascular events, 2) DN defined as a composite outcome [macroalbuminuria and/or decreased glomerular filtration rate (GFR) <60 ml/min/1.73 m²], and 3) death. RESULTS: A total of 199 type 2 diabetic patients, aged 59.9 ± 9.9 years, were followed for 6.1 ± 2.7 years. UAC ≥14.4 mg/l, as determined by ROC curve, predicted DN and prediction for this and other outcomes were compared with traditional microalbuminuria cutoffs for ACR and UAE. The outcomes frequency was: cardiovascular events = 26.4%, DN = 31.7% (23.5% decreased GFR; 13.6% macroalbuminuria) and death = 8.50%. In Cox analyses, UAC ≥14 mg/l increased the risk (hazard ratio, HR) for cardiovascular events 3.25 times (95% CI 1.43-7.38; P = 0.005), 4.30 for DN composite outcome (95% CI 2.22-8.32; P <0.001), and 5.51 for death (95% CI 1.16-26.22; P = 0.032). Corresponding HRs of ACR ≥30 mg/g were: 2.89 (95% CI 1.29-6.45; P = 0.009) for cardiovascular events, 4.67 (95% CI 2.34-9.34; P <0.001) for DN composite outcome and 5.07 (95% CI 1.01-24.88; P = 0.049) for death. HRs of UAE ≥30 mg/24-h were: 2.20 (95% CI 2.08-2.49; P = 0.030) for cardiovascular events, 6.76 (95% CI 3.32-13.77; P <0.001) for DN composite outcome, and 2.47 (95% CI 0.72-8.42; P = 0.150) for death. CONCLUSIONS: In conclusion, random UAC ≥14 mg/l predicted cardiovascular events, diabetic nephropathy, and mortality just as well as ACR. UAC may be used to assess cardiovascular and renal risks in patients with type 2 diabetes.

The Ala54Thr polymorphism of the FABP2 gene influences the postprandial fatty acids in patients with type 2 diabetes.

CONTEXT: The Ala54Thr polymorphism of FABP2 gene increases affinity of intestinal fatty acid-binding protein 2 for long-chain dietary fatty acids (FA) in subjects without diabetes. OBJECTIVE: Our objective was to evaluate whether the Ala54Thr polymorphism of the FABP2 gene influences the FA composition in chylomicrons after a standard meal in patients with type 2 diabetes. METHODS: This clinical trial studied 11 patients with TT and 15 patients with AA genotypes for Ala54Thr polymorphism of FABP2 gene selected from a Brazilian type 2 diabetic cohort. FA in chylomicrons (gas chromatography), plasma glucose, and serum triglycerides were measured after an overnight fast at baseline and, after a standard test meal, at 2-h intervals during 8 h. RESULTS: During the test meal, the curves response of unsaturated FA of patients with TT genotype were different from patients with AA genotype: only patients with TT genotype exhibited an increase, with a postprandial peak at 6 h in monounsaturated FA [0.479 (0.248-0.709) to 1.674 (0.698-2.650) g/liter], polyunsaturated FA [0.338 (0.154-0.522) to 1.827 (0.389-3.265) g/liter], and trans-unsaturated FA [0.025 (0.013-0.037) to 0.122 (0.040-0.205) g/liter] (generalized estimating equations for repeated measurements: P<0.05 for all). The increase of saturated FA did not reach statistical significance. Diabetes treatment, previous diet, FA at baseline, and the increase of plasma glucose and triglycerides during the test meal were not different between TT and AA genotypes. CONCLUSIONS: The TT genotype in Ala54Thr polymorphism of FABP2 gene in patients with type 2 diabetes increased dietary FA absorption, and this might increase the susceptibility to the effects of dietary lipids.

[Critical analysis of the American Diabetes Association dietary recommendations for cardiovascular disease in diabetes mellitus]. / Análise crítica das recomendações da Associação Americana de Diabetes para doença cardiovascular no diabetes melito.

Cardiovascular disease (CVD) is the main cause of mortality among patients with diabetes mellitus (DM), and dietary intervention is an essential measure to prevent and treat this complication. The aim of this manuscript was to review scientific evidence that underlies the dietetic recommendations of the American Diabetes Association (ADA) for prevention and treatment of CVD in patients with DM. The ADA guidelines are mostly based on studies performed on patients with CVD and without DM. The evidence-based dietary recommendations for patients with DM are to increase the intake of fish and soluble fibers. Although DM has been considered as an equivalent of established CVD, the adoption of the same dietary recommendations for patients without DM and with CVD for all patients with DM is still questionable -- especially considering the peculiarities of CVD in DM. Randomized clinical trials including patients with DM should provide further information regarding the benefits of these dietary interventions for CVD.

Diabetic nephropathy.

Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality. Diabetic nephropathy has been categorized into stages: microalbuminuria and macroalbuminuria. The cut-off values of micro- and macroalbuminuria are arbitrary and their values have been questioned. Subjects in the upper-normal range of albuminuria seem to be at high risk of progression to micro- or macroalbuminuria and they also had a higher blood pressure than normoalbuminuric subjects in the lower normoalbuminuria range. Diabetic nephropathy screening is made by measuring albumin in spot urine. If abnormal, it should be confirmed in two out three samples collected in a three to six-months interval. Additionally, it is recommended that glomerular filtration rate be routinely estimated for appropriate screening of nephropathy, because some patients present a decreased glomerular filtration rate when urine albumin values are in the normal range. The two main risk factors for diabetic nephropathy are hyperglycemia and arterial hypertension, but the genetic susceptibility in both type 1 and type 2 diabetes is of great importance. Other risk factors are smoking, dyslipidemia, proteinuria, glomerular hyperfiltration and dietary factors. Nephropathy is pathologically characterized in individuals with type 1 diabetes by thickening of glomerular and tubular basal membranes, with progressive mesangial expansion (diffuse or nodular) leading to progressive reduction of glomerular filtration surface. Concurrent interstitial morphological alterations and hyalinization of afferent and efferent glomerular arterioles also occur. Podocytes abnormalities also appear to be involved in the glomerulosclerosis process. In patients with type 2 diabetes, renal lesions are heterogeneous and more complex than in individuals with type 1 diabetes. Treatment of diabetic nephropathy is based on a multiple risk factor approach, and the goal is retarding the development or progression of the disease and to decrease the subject's increased risk of cardiovascular disease. Achieving the best metabolic control, treating hypertension (<130/80 mmHg) and dyslipidemia (LDL cholesterol <100 mg/dl), using drugs that block the renin-angiotensin-aldosterone system, are effective strategies for preventing the development of microalbuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with diabetes.

Endothelial dysfunction and serum fatty acid composition in patients with type 2 diabetes mellitus.

The aim of this study was to evaluate the possible association between serum fatty acids composition and endothelial dysfunction in patients with type 2 diabetes mellitus. A cross-sectional study was conducted with 125 normo- or microalbuminuric type 2 diabetes mellitus patients with serum creatinine <1.5 mg/dL. Serum fatty acids composition (gas chromatography), serum levels of endothelin-1 (ET-1) (enzyme-linked immunosorbent assay), fibrinogen, serum C-reactive protein, lipids, homeostasis model assessment resistance index (HOMA-R), and 24-hour urinary albumin excretion rate were measured. Serum levels of ET-1 were positively correlated with saturated fatty acids (r = 0.257, P = .025) and negatively correlated with polyunsaturated fatty acids (PUFAs) (r = -0.319, P = .005). Serum ET-1 levels were also positively correlated with systolic blood pressure, waist circumference, total cholesterol levels, triglycerides, and HOMA-R. In multiple linear regression models, only saturated fatty acids (R(2) = 0.317, P = .002) or PUFAs (R(2) = 0.314, P = .001) remained associated with ET-1 levels. Models were adjusted for systolic blood pressure, HOMA-R, waist circumference, triglycerides, body mass index, and smoking habit. The serum total PUFA levels showed an inverse correlation with urinary albumin excretion rate (r = -0.248, P = .012). In conclusion, in type 2 diabetes mellitus patients, the serum fatty acids composition was independently related to endothelial function evaluated by serum ET-1. Saturated fatty acids were associated with endothelial dysfunction (high levels of ET-1), whereas PUFAs had a protective role in endothelial function.