Rogério Friedman

Five-Year Prospective Study of Glomerular Filtration Rate and Albumin Excretion Rate in Normofiltering and Hyperfiltering Normoalbuminuric NIDDM Patients

OBJECTIVE To evaluate the evolution of glomerular filtration rate (GFR) and albumin excretion rate (AER) of normofiltering (NF) and hyperfiltering (HF) normoalbuminuric NIDDM patients. RESEARCH DESIGN AND METHODS A longitudinal study of 32 normoalbuminuric (AER < 20 μg/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals was done. Subjects had their GFR (51Cr-labeled EDTA single-injection method) measured at entry and after 40 and 60 months. At entry, 13 NIDDM patients had GFR values above the upper limit of the normal range in our laboratory (> 137 ml · min−1 x 1.73 m−2) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA1c, urinary urea, and mean arterial blood pressure (MBP) were analyzed at entry and after 40 and 60 months. RESULTS There was a significant decline of GFR in NIDDM patients and normal subjects at 60 months. The decline was significantly greater in HF patients (−0.61 ml · min−1.month−1; P = 0.001) than in NF (−0, 18) and control subjects (−0, 14); the rate of change in NF and control subjects was the same (P > 0.05). In stepwise multiple regression analysis, with GFR decline as the dependent variable and GFR and AER at baseline, age and change in MBP, change in urinary urea, change in HbA1c, and change in therapy as independent variables, only baseline GFR (R2 = 0.19, P = 0.002) and age (R2 = 0.31, P = 0.048) were significantly related to the outcome. At 60 months, AER raised > 20 μg/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although still in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of microalbuminuria. CONCLUSIONS The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to baseline GFR and age. HF NIDDM patients show a faster decline in GFR than NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The development of microalbuminuria is related to higher baseline AER and to increases in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NIDDM patients (P > 0.05).

Glomerular hyperfiltration in NIDDM patients without overt proteinuria

Objective— To evaluate the frequency and correlates of glomerular hyperfiltration in NIDDM patients without overt proteinuria. Research Design and Methods— A cross-sectional study was conducted. Seventy-one consecutive NIDDM patients attending an outpatient clinic, with Albustix-tested negative urine and a 24-h AER <200 μgrams/min, were examined for long-term complications of diabetes. We measured their GFR (51Cr-EDTA single-injection method), 24-h AER (RIA), plasma creatinine, HbA1c, total cholesterol, triglycerides, urinary glucose, and urea. Results— GFR above the upper limit of the normal range for age-matched control subjects (137.1 ml·min−1 · 1.73 m2) was present in 15 of 71 (21%) NIDDM patients. Subjects with normal and hyperfiltration did not differ in terms of age, sex distribution, BMI, duration of NIDDM, BP, AER, or frequency of long-term complications. Plasma glucose was significantly higher in subjects with hyperfiltration (mean [range]: 12.8 [4.3–18.7] vs. 8.7 [2.6–17.5] mM). HbA1c failed to reach statistical significance, although it tended to be higher in the group with hyperfiltration (10.4 [6.7–13.9] vs. 9.4 [4.2–16.5]%, P = 0.10). Age (rS −0.37, P = 0.002), FPG (rS 0.45, P < 0.0005), total cholesterol (rS −0.31, P = 0.008), and glycosuria (rS 0.40, P = 0.001) correlated significantly with GFR. In a stepwise multiple regression analysis, FPG, age, and total cholesterol emerged as significant correlates of the dependent variable GFR. Conclusions— Hyperfiltration occurred in 21% of NIDDM patients without overt proteinuria. FPG and age significant correlates of the GFR in these patients. Cholesterol is significantly (although only modestly) correlated with the GFR.

Nitric oxide system and diabetic nephropathy

About 30% of patients with type 2 diabetes mellitus develop clinically overt nephropathy. Hyperglycemia is necessary, but not sufficient, to cause the renal damage that leads to kidney failure. Diabetic nephropathy (DN) is a multifactorial disorder that results from interaction between environmental and genetic factors. In the present article we will review the role of the nitric oxide synthase (NOS) in the pathogenesis of DN.Nitric oxide (NO) is a short-lived gaseous lipophilic molecule produced in almost all tissues, and it has three distinct genes that encode three NOS isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS).The correct function of the endothelium depends on NO, participating in hemostasis control, vascular tone regulation, proliferation of vascular smooth muscle cells and blood pressure homeostasis, among other features. In the kidney, NO plays many different roles, including control of renal and glomerular hemodynamics. The net effect of NO in the kidney is to promote natriuresis and diuresis, along with renal adaptation to dietary salt intake.The eNOS gene has been considered a potential candidate gene for DN susceptibility. Three polymorphisms have been extensively researched: G894T missense mutation (rs1799983), a 27-bp repeat in intron 4, and the T786C single nucleotide polymorphism (SNP) in the promoter (rs2070744). However, the potential link between eNOS gene variants and the induction and progression of DN yielded contradictory results in the literature.In conclusion, NOS seems to be involve in the development and progression of DN. Despite the discrepant results of many studies, the eNOS gene is also a good candidate gene for DN.

Caregivers' attitudes and practices: Influence on childhood body weight

Childhood excess weight is probably associated with, or reflected in, parental attitudes. The objective of this study was to study the relationships between childhood excess weight and parental attitudes. The study subjects were 53 boys and 56 girls, aged 6-10, regularly attending schools in Porto Alegre, south Brazil, and one of their parents or caregivers. Attitudes of the parents or caregivers were assessed by the Child Feeding Questionnaire (CFD). Weight and height of the children were measured, parents self-reported their weight and height and body mass indexes were calculated for both. The WHO criteria for overweight and obesity were used for the adults. The CDC criteria for overweight and risk for overweight were used for the corresponding children. Boys presented excess weight more often than girls. The parents of children with excess weight showed higher scores for perceived child weight, concern about child weight, restriction and monitoring. In logistic regression, excess weight in children was associated with perceived child weight, restriction and male sex; pressure to eat was negatively associated with excess BMI. In Porto Alegre, south Brazil, excess body weight in children aged 6-10 is associated with parental perceived child weight and concern about it, monitoring and restriction; being a boy increases the odds of being overweight.

Impact of weight loss with or without exercise on abdominal fat and insulin resistance in obese individuals: a randomised clinical trial.

Evidence supports an important contribution of abdominal obesity and inflammation to the development of insulin resistance (IR) and CVD. Weight loss in obese individuals can reduce inflammation and, consequently, IR, but the role of training remains unclear. The aim of this study was to evaluate the effects of body weight reduction with and without exercise over abdominal fat tissue (primary outcome) and IR. In this randomised clinical trial, forty-eight obese individuals (age 31·8 (SD 6·0) years, BMI 34·8 (SD 2·7) kg/m2) were randomised to either a diet-only group (DI) or a diet and exercise group (DI þ EXE). Treatment was maintained until 5% of the initial body weight was lost. At baseline and upon completion, the following parameters were analysed: biochemical parameters such as glycaemia and insulin for the determination of homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP) and abdominal computed tomography for the determination of visceral and subcutaneous adipose tissue. A total of thirteen individuals dropped out before completing the weight-loss intervention and did not repeat the tests. In both the DI (n 18) and DI þ EXE (n 17) groups, we observed significant and similar decreases of visceral adipose tissue (difference between means: 7·9 (95% CI 29·5, 25·2) cm2, P¼0·36), hs-CRP (difference between means: 20·06 (95% CI 20·19, 0·03) mg/l, P¼0·39) and HOMA (difference between means: 20·04 (95% CI 20·17, 0·08), P¼0·53). In the present study, 5% weight loss reduced abdominal fat and IR in obese individuals and exercise did not add to the effect of weight loss on the outcome variables.

Nefropatia diabética e doença cardíaca

Patients in different stages of diabetic nephropathy (DN) frequently present cardiac disease expressed by myocardial ischemia and/or diabetic cardiomyopathy. These changes are already present at early stages of DN, probably even before urinary albumin excretion (UAE) reaches the traditionally diagnostic levels of microalbuminuria. The cardiac changes are responsible for a significant proportion of the increased death rates in patients with DN and can be reduced through multiple intervention on the several risk factors present in these patients. Cardiac disease assessment should ideally be performed in every patient, irrespective of renal status, through specific methods to detect ischemia and myocardial dysfunction, besides routinely performing 24-h ambulatory blood pressure monitoring. In patients with advanced atherosclerosis, other arteries (aorta, carotid, renal) should be evaluated as well. Intensive treatment of arterial hypertension, and use of cardioprotective drugs, correction of the associated dyslipidemia and anemia, and use of antiplatelet agents can reduce the elevated cardiovascular mortality in patients with DN.

Obesity coexists with malnutrition? adequacy of food consumption by severely obese patients to dietary reference intake recommendations

To assess the adequacy of food intake in severely obese patients and describe their main nutritional deficiencies on the basis of Dietary Reference Intakes (DRIs). Patients on a waiting list for bariatric surgery were sequentially recruited from March 2010 to November 2011. All subjects underwent nutritional status assessment (anthropometry, dietary recall and semi-structured interview), socioeconomic evaluation (Brazilian Association of Research Companies criteria) and laboratory testing (glucose/hormone/lipid panel). A total of 77 patients were assessed, 50 of whom (76.6%) were female. Mean age was 44.48 ± 12.55 years. The most common comorbidities were hypertension (72.4%), binge eating disorder (47.4%), type 2 diabetes mellitus (32.9%), sleep apnea (30.3%) and dyslipidemia (18.4%). Macronutrient intake was largely adequate, in view of the high calorie intake. However, some micronutrient deficiencies were present. Only 19.5% of patients had an adequate intake of potassium, 26.0% of calcium, and 66.2% of iron. All subjects consumed more than the minimum recommended intake of sodium, with 98.7% reaching the upper limit. Bcomplex vitamin intake was satisfactory (adequate in >80% of subjects), but lipid-soluble vitamin (A, D, E) intake often fell short of the RDI. The diet of severely obese patients is unbalanced, with high calorie intake paralleled by insufficient micronutrient intake. When these patients are assessed and managed, qualitative dietary changes should be considered in addition to routine caloric restriction.

Evolution of Glomerular Filtration Rate in Proteinuric NIDDM Patients

Objective To evaluate, by means of a precise method, the rate of decline of glomerular filtration rate in proteinuric non-insulin-dependent diabetic (NIDDM) patients. Research Degisn and Methods The study was comprised of seven NIDDM patients who visited an outpatient clinic and had a 24-h urinary protein excretion rate ≥500 mg in the absence of heart failure, urinary tract infection, or other nephropathies. Results Glomerular filtration rate (51Cr-labeled EDTA, single-injection protocol) and 24-h proteinuria (turbidimetric method) were assessed at periodic intervals (2–6 mo). Correlation of the measurements with time (Pearsons r, with Students t test used to assess the significance, α = 0.05) was used to evaluate the trend of evolution of glomerular filtration rate. Renal biopsies were performed in four patients. In three of four patients, renal histopathology was consistent with the diagnosis of diabetic nephropathy (in the 4th patient measurements were not satisfactory). Neither glomerular filtration rate nor proteinuria correlated significantly with time, except in one patient who had multiple myeloma. Conclusions The decline of glomerular filtration rate in proteinuric NIDDM patients is different from that observed in insulin-dependent diabetic patients, which is probably much slower.

Efeito da suplementação de L-arginina sobre a secreção de hormônio do crescimento e fator de crescimento semelhante à insulina em adultos

Based on presumptions that the infusion of amino acids can augment the release of human growth hormone (hGH) and that this metabolism is related with secretion of insulin-like growth factor I (IGF-I), the purpose of this study was to verify the effect of L-arginine supplementation on GH and IGF-I in adults. Seventeen male individuals participated on the study and were randomized to receive L-arginine (n= 10) or placebo (n= 7), seven grams per day for seven days. Before and after the supplementation period, the volunteers realized blood collection in fasting to verify both GH and IGF-I levels, as well as urine collection to verify urea excretion. At the end of the experimental period, it was verified that the group that received L-arginine augmented the urea in urine excretion (to 2684.1 ± 475.2 mg/dl from 2967.2 ± 409.7 mg/dl, p= 0.002), therefore it did not alter significantly the release of hormones evaluated. The group which received placebo did not alter significantly any evaluated parameters. The L-arginine supplementation during seven days was ineffective to augment both GH and IGF-I release in individual male adults.

RISK FACTORS FOR DECREASED BONE DENSITY IN PREMENOPAUSAL WOMEN

Osteoporosis is a major health problem. Little is known about the risk factors in premenopause. Sixty 40-50-year old patients with regular menses were studied cross-sectionally. None of the patients were on drugs known to interfere with bone mass. Patients answered a dietary inquiry and had their bone mineral density (BMD) measured. The Z scores were used for the comparisons. A blood sample was taken for the determination of FSH, SHBG, estradiol, testosterone, calcium and alkaline phosphatase. Calcium and creatinine were measured in 24-h urine. A Z score less than -1 was observed for the lumbar spine of 14 patients (23.3%), and for the femur of 24 patients (40%). Patients with a Z score less than -1 for the lumbar spine were older than patients with a Z score > or = -1 (45.7 vs 43.8 years) and presented higher values of alkaline phosphatase (71.1 +/- 18.2 vs 57.1 +/- 14.3 IU/l). Multiple regression analysis showed that a lower lumbar spine BMD was associated with higher values of alkaline phosphatase, lower calcium ingestion, a smaller body mass index (BMI), less frequent exercising, and older age. The patients with a Z score less than -1 for the femur were shorter than patients with a Z score > or = -1 (158.2 vs 161.3 cm). Multiple regression analysis showed that a lower femoral BMD was associated with lower BMI, higher alkaline phosphatase and caffeine intake, and less frequent exercising. A lower than expected BMD was observed in a significant proportion of premenopausal women and was associated with lower calcium intake, relatively lower physical activity and lower BMI. We conclude that the classical risk factors for osteoporosis may be present before ovarian failure, and their effect may be partly independent of estrogen levels.