Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (β = 1.416, P = 0.039) and body mass index (β = 0.390, P < 0.001), and was also inversely associated with adiponectin (β = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.

Impact of a 2-year intervention program on cardiometabolic profile according to the number of goals achieved

We investigated the impact of lifestyle goal achievement on cardiovascular risk factors after a 2-year behavioral intervention program applied to 394 adults (113 with diabetes, mean age 60.2 ± 11.4 years, 56 percent women) and targeting four goals: ≥5 percent weight loss; ≥150 min/week physical activities; <10 percent saturated fat intake/day; ≥400 g fruit and vegetable intake/day. Baseline characteristics and changes in variables after intervention among the four categories of number of goals achieved (none, 1, 2, and ≥3) were compared by independent ANOVA or the Kruskal-Wallis test. Individuals without diabetes achieving a higher number of goals were more likely to be older (3 or 4 goals: 61.8 ± 12.6 years vs none: 53.3 ± 10.3 years, P < 0.05) and to have a lower mean BMI (3 or 4 goals: 21.7 ± 2.6 kg/m² vs none: 29.0 ± 4.8 kg/m², P < 0.05), diastolic blood pressure (3 or 4 goals: 77.3 ± 2.1 mmHg vs none: 85.4 ± 9.6 mmHg, P < 0.05), triglyceride (3 or 4 goals: 116.1 ± 95.1 mg/dL vs none: 144.8 ± 65.5 mg/dL, P < 0.05) and insulin levels (3 or 4 goals: 3.6 ± 2.4 μU/L vs none: 5.7 ± 4.0 μU/L, P < 0.05) than those achieving fewer goals. The absolute changes in cardiovascular risk factors tended to be more pronounced with increasing number of goals achieved in individuals without diabetes. The intervention had a beneficial impact on the cardiometabolic profile of individuals with normal or altered glucose metabolism. The number of goals achieved in this lifestyle intervention was associated with the magnitude of improvement of cardiovascular risk factors in individuals without diabetes. Participants with a better cardiometabolic profile seemed to be more likely to have a healthy lifestyle.

Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?

In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP) levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m² and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20) or metformin, 1.7 g/day (N = 21) for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 ± 0.04 mg/dL (P = 0.002) over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.

Leptin is not associated independently with hypertension in Japanese-Brazilian women

We evaluated the relationship of leptin with hypertension adjusted for body mass index (BMI) and/or waist circumference in a population of Japanese-Brazilian women aged > or = 30 years with centrally distributed adiposity. After excluding diabetic subjects, the study subjects - who participated in a population-based study on the prevalence of metabolic syndrome - showed prevalence rates of obesity (BMI > or = 25 kg/m²) and central adiposity (waist > or = 80 cm) of 32.0 and 37.8 percent, respectively. The hypertensive group (N = 162) was older, had higher BMI (24.9 ± 4.2 vs 23.3 ± 3.4 kg/m², P < 0.001), waist circumference (81.1 ± 10.1 vs 76.3 ± 8.2 cm, P < 0.001) and insulin levels (8.0 ± 6.2 vs 7.1 ± 4.9 æU/mL, P < 0.05) than the normotensive group (N = 322) and showed an unfavorable metabolic profile (higher 2-h plasma glucose, C-reactive protein and non-HDL cholesterol levels). Leptin did not differ between groups (8.2 ± 6.8 vs 7.2 ± 6.6 ng/mL, P = 0.09, for hypertensive vs normotensive, respectively) and its levels correlated significantly with anthropometric variables but not with blood pressure. Logistic regression analysis indicated that age and waist were independently associated with hypertension but not with homeostasis model assessment of insulin resistance or leptin levels. The lack of an independent association of hypertension with metabolic parameters (2-h glucose, C-reactive protein and non-HDL cholesterol) after adjustment for central adiposity suggested that visceral fat deposition may be the common mediator of the disturbances of the metabolic syndrome. Our data indicate that age and waist are major determinants of hypertension in this population of centrally obese (waist > or = 80 cm) Japanese-Brazilian women, but do not support a role for leptin in the elevation of blood pressure.

Improved glycemic control by acarbose therapy in hypertensive diabetic patients: effects on blood pressure and hormonal parameters

A double-blind, randomized, placebo-controlled study was carried out on 44 hypertensive type 2 diabetic subjects previously treated by diet associated or not with sulfonylurea to assess the effects of acarbose-induced glycemic control on blood pressure (BP) and hormonal parameters. Before randomization and after a 22-week treatment period (100 to 300 mg/day), the subjects were submitted to a standard meal test and to 24-h ambulatory BP monitoring (ABPM) and had plasma glucose, glycosylated hemoglobin, lipid profile, insulin, proinsulin and leptin levels determined. Weight loss was found only in the acarbose-treated group (75.1 ± 11.6 to 73.1 ± 11.6 kg, P<0.01). Glycosylated hemoglobin decreased only in the acarbose group (6.4 ± 1.7 to 5.6 ± 1.9 percent, P<0.05). Fasting proinsulin decreased only in the acarbose group (23.4 ± 19.3 to 14.3 ± 13.6 pmol/l, P<0.05), while leptin decreased in both (placebo group: 26.3 ± 6.1 to 23.3 ± 9.4 and acarbose group: 25.0 ± 5.5 to 22.7 ± 7.9 ng/ml, P<0.05). When the subset of acarbose-treated patients who improved glycemic control was considered, significant reductions in diurnal systolic, diastolic and mean BP (102.3 ± 6.0 to 99.0 ± 6.6 mmHg, P<0.05) were found. Acarbose monotherapy or combined with sulfonylurea was effective in improving glycemic control in hypertensive diabetic patients. Acarbose-induced improvement in metabolic control may reduce BP in these patients. Our data did not suggest a direct action of acarbose on insulin resistance or leptin levels

Comparison of methods for urinary albumin determination in patients with type 1 diabetes

We tested the correlation of the albumin-to-creatinine ratio (A/C) in an early-morning urine sample, measured with a commercial kit (DCA 2000®), with the conventional immunoturbidimetric determination in the laboratory and with overnight albumin excretion rate (reference method). Fifty-five type 1 diabetic adolescents had their first-morning urine collected on the 1st and 8th day of the period. Urinary albumin and creatinine were determined immediately using the DCA 2000® kit. Samples were also stored for laboratory analysis. To evaluate the correlation between early-morning urinary A/C ratio and overnight albumin excretion rate, 16 subjects had a timed overnight urine collection. A/C ratios determined with the DCA 2000® kit and by the laboratory method were 13.1 ± 20.5 and 20.4 ± 46.3 mg/g, respectively. A/C results by both methods proved to be strongly correlated (r = 0.98, P<0.001). DCA 2000®-determined A/C showed 50 percent sensitivity and 100 percent specificity when compared to the reference method. Spot urinary A/C of the subset of 16 subjects significantly correlated with their overnight albumin excretion rate (r = 0.98, P<0.001). Intraindividual variation ranged from 17 to 32 percent and from 9 to 63 percent for A/C and overnight albumin excretion rate, respectively. In conclusion, an early-morning specimen should be used instead of timed overnight urine and the A/C ratio is an accurate, reliable and easily determined parameter for the screening of diabetic nephropathy. Immediate measurement of the A/C ratio is feasible using the DCA 2000® kit. Intraindividual variability indicates the need for repeated determinations to confirm microalbuminuria and the diagnosis of incipient diabetic nephropathy

Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals

The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 + or - 6 years, BMI 31.1 + or - 2.5 kg/m², percentfat 40.3 + or - 8.3) and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily) for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001). After dexamethasone, there was a significant increase in serum leptin levels (22.9 + or - 12.3 vs 51.4 + or - 23.3 ng/ml, P<0.05). Weight loss (86.1 + or - 15.1 vs 80.6 + or - 14.2 kg, P<0.05) led to a reduction in leptin levels (25.13 + or - 12.8 vs 15.9 + or - 9.1 ng/ml, P<0.05). We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels

Frequency of islet cell autoantibodies (IA-2 and GAD) in young Brazilian type 1 diabetes patients

Type 1 diabetes, as an autoimmune disease, presents several islet cell-specific autoantibodies such as islet cell antibody (ICA), anti-insulin, anti-glutamic acid decarboxylase (GAD) and the antibody (Ab) against tyrosine phosphatase (PTP)-like protein known as ICA-512 (IA-2). In order to determine the frequency of the anti-GAD and anti-IA-2 autoantibodies in Brazilian type 1 diabetes patients we studied 35 diabetes mellitus (DM) type 1 patients with recent-onset disease 12 months and 37 type 1 diabetes patients with long-duration diabetes 12 months who were compared to 12 children with normal fasting glucose. Anti-GAD65 and anti-IA-2 autoantibodies were detected with commercial immunoprecipitation assays. The frequency of positive results in recent-onset DM type 1 patients was 80.0 percent for GADAb, 62.9 percent for IA-2Ab and 82.9 percent for GADAb and/or IA-2Ab. The long-duration type 1 diabetes subjects presented frequencies of 54.1 percent for GADAb and IA-2Ab, and 67.5 percent for GAD and/or IA-2 antibodies. The control group showed no positive cases. Anti-GAD and IA-2 assays showed a high frequency of positivity in these Brazilian type 1 diabetes patients, who presented the same prevalence as a Caucasian population

Abnormal nocturnal blood pressure fall in normmotensive adolescents with insulin-dependent diabetes is ameliorated following glycemic improvement

Lack of the physiological nocturnal fall in blood pressure (BP) has been found in diabetics an it seems to be related to the presence of diabetic complications. The present study examined the changes in the nocturnal BP pattern of 8 normotensive insulin-dependent diabetic adolescents without nephropathy following improvement in glycemic control induced by an 8-day program of adequate diet and exercise. The same number of age- and sex-matched control subjects were studied. During the first and eighth nights of the program, BP was obtained by ambulatory monitoring. After a 10-min rest, 3 BP and heart rate (HR) recordings were taken and the mean values were considered to represent their awake values. The monitor was programmed to cuff insufflation every 20 min from 10:00 p.m. to 7:00 a.m. The glycemic control of diabetics improved since glycemia (212.0+ 91.5 to 140.2+69.1 mg/dl, P<0.03), urine glucose (12.7+11.8 to 8.6+6.4 g/24h, P=0.08) and insulin dose (31.1+7.7 to 16.1+9.7 U/day, P<0.01) were reduced on the last day. The mean BP of control subjects markedly decreased during the sleeping hours of night 1 (92.3+6.4 to 78.1+5.0 mmHg, P<0.001) and night 8 (87.3+6.7 to 76.9+3.6 mmHg, P<0.001). Diabetic patients showed a slight decrease in mean BP during the first night. However, the fall in BP during the nocturnal period increased significantly on the eighth night. The average awake-sleep BP variation was significantly higher at the end of the study (4.2 vs 10.3 percent, P<0.05) and this ratio turned out to be similar to that found in the control group (10.3 vs 16.3 percent). HR variation also increased on the eighth night in the diabetics. Following the metabolic improvement obtained at the end of the period, the nocturnal BP variation of diabetics was close to the normal pattern. We suggest that amelioration of glycemic control may influence the awake-sleep BP and HR differences. This effect may be due at least in part to an attenuated insulin stimulation of sympthetic activity.

Factors associated with the development of renal complications of diabetes mellitus in Säo Paulo city

The incidence of diabetic end-stage renal failure (ESRF) varies world wide and risk factors have been demonstrated in several populations. The objective of the present study was to identify possible factors associated with the risk of development of ESRF in patients with diabetes mellitus (DM). Two groups of diabetic subjects were included in a case-control study: 1) one group was submitted to renal replacement therapies, attending dialysis centers in Spo Paulo city and 2) the same number of controls without clinical nephropathy (two negative dipstick tests for urine protein), matched for duration of DM, were obtained from an outpatient clinic. A standardized questionnaire was used by a single investigator and additional data were obtained from the medical records of the patients. A total of 290 diabetic patients from 33 dialysis centers were identified, and 266 questionaires were considered to contain reliable information. Male/female rations were 1.13 for ESRF and 0.49 for the control group. A higher frequency of men was observed in the ESRF group when compared with controls (53 vs 33 percent, P<0.00001), although logistic regression analysis did not confirm an association of gender and diabetic nephropathy (DN). Similar proportions of non-white individuals were found for both groups. Patients with insulin-dependent diabetes mellitus (IDDM) were less common than patients with non-insulin-dependent diabetes mellitus (NIDDM), particulary in the control group (3.4 vs 26.3 percent, P<0.00001, for controls and ESRF patients, respectively); this type of DM was associated with a higher risk of ESRF than NIDDM, as determined by univariate analysis or logistic regression (OR = 4.1). Hypertension by the time of the DM diagnosis conferred a 1.4-fold higher risk of ESRF (P = 0.04), but no difference was observed concerning the presence of a family history. Association between smoking and alcohol habits and increased risk was observed (OR = 4.5 and 5.9, respectively, P<0.001). A 2.4-fold higher risk of ESRF was demonstrated in patients with multiple hospitalizations due to DM decompensation, which suggested poor metabolic control. Photocoagulation and neuropathy were found to be strongly associated with ESRF but not with macrovascular disease. Data collected in our country reinforce the higher risk attributable to IDDM and the association between hypertension and the progression of DN.Indirect evidence for an association with metabolic control is also suggested.

Different urinary albumin responses to submaximal exercise by normoalbumin-uric diabetic children and controls

It is not clear if exercise could be useful to identify diabetic patients at risk for the development of nephropathy. We evaluated the responses of blood pressure (BP) and urinary albumin (Alb) and retinol-binding protein (RBP) excretion to standardized sub-maximal exercise in 17 normoalbuminuric normotensive children with IDDM and 17 matched normal subjects. RBP was used as an index of tubular function. Standardization of exercise load was based on heart rate (HR) which was maintained at 70 per cent of the maximum calculated to age. A step exercise test lasted for 35 min; baseline BP and HR were taken at midtime and during cooling down. Pre- and postexercise urines were obtained for Alb, RBP and creatinine determinations. Both groups showed a significantly increased systolic BP at the midpoint but the percent variations were not different. HR responses did not differ and demonstrated the exercise effectiveness. Great variability in Alb excretion was observed within the normal range for both groups. The baseline Alb/creatinine ratio was not significantly different between normal and diabetic subjects, but became different following exercise (6.6 ñ 4.1 vs 17.7 ñ 18.7 mg/g, P<0.05). While this ratio decreased in the control group (14.8 ñ 11.1 to 6.6 ñ 4.1 mg/g, P<0.02), it increased (9.0 ñ 7.1 to 17.7 ñ 18.7 mg/g, P = 0.05) in diabetic patients. Percent variations in the two groups occurred in opposite directions and were significantly different. RBP/creatinine followed the same pattern within each group; normals showed a tendency to a decrease (0.058 ñ 0.064 to 0.030 ñ 0.039 mug/g, P = 0.05) and diabetic patients to an increase (0.116 ñ 0.125 to 0.247 ñ 0.247 mug/g, P = 0.06). We conclude that there was a variable proteinuric response to exercise among diabetic subjects with normal renal function as evaluated by albumin excretion. A subset of IDDM patients responded abnormally to the exercise stress, increasing albumin excretion to levels compatible with microalbuminuria. Whether this heterogeneity reflects individual risk for diabetic renal disease requires further investigation.

Effect of improved glycemic control on blood pressure and albuminuria of insulin-dependent diabetes without nephropathy

To assess the effect of glycemic control on blood pressure (BP) and albumin excretion rate (AER) in insulin-dependent diabetes, 35 patients (age 12.6 ñ 2.7 years) and 45 matched control subjects (11.9 ñ 1.8 years) were studied at an educational camp (Study I). They were evaluated at the beginning and at the end of a 9-day program of adequate diet and exercise twice daily, which induced statistically significant reductions in urinary glucose (18 ñ 21 to 5 ñ 7 g/12 h, P<0.01) and in insulin requirement (42 ñ 20 to 31 ñ 12 U/day, P<0.01) in the diabetic group. The mean BP and AER of the diabetic patients fell from 74 ñ 11 to 69ñ 11 mmHg,P<0.001, and from 4.9ñ 6.0 to 2.1 ñ 2.0 mug/min, P<0.01, and a correlation was found between AER and urinary glucose. In contrast, controls showed a lower reduction in BP and no change in AER. To evaluate the mechanisms involved in BP fall another group of 39 diabetics (age 12.7 ñ 2.1 years) was submitted to the same 9-day program and also to improved glycemic control (Study II). Changes in BP (79 ñ 11 to 76 ñ 11 mmHg, P<0.05) were slighter than in the previous study. Initial creatinine clearance was high and fell to the normal range at the end of the study (159 ñ 99 to 127 ñ 42 ml min(-1)(1.73 M2) (-1), P<0.05). Urinary aldosterone decreased from 5.3 ñ 3.9 to 3.4 ñ 2.4 mug/24 h (P<0.05), and fractional Na+ excretion tended to increase. Initial and final metanephrine values did not differ. Changes in mean BP did not correlate with changes in aldosterone, insulin requirement or urinary glucose. The decreases in hyperflltration and AER may have been due to the improved glycemic control induced by this educational program. Exercise may be responsible for BP reduction in diabetics and controls. BP changes particularly in diabetics could be attributed to the inhibition of the renin-angiotensin-aldosterone system and/or to decreased insulin requirement. The contribution of a negative Na+ balance consequent to decreased plasma insulin levels to the BP fall cannot be excluded.

Exercício físico e diabete melito / Physical exercise and diabetes mellitus

O diabete melito acomete 7,6 por cento da populaçäo brasileira entre 30 e 69 anos. O exercício tem sido recomendado como parte do tratamento. Estudos recentes têm contribuído para a compreensäo dos seus efeitos metabólicos e hormonais, tanto em indivíduos normais como em diabéticos. nos indivíduos com diabete melito dependente de insulina, o exercício näo apresenta efeito importante sobre o controle glicêmico. Deve, no entanto, ser estimulado em relaçäo aos seus demais benefícios, näo diretamente racionados à glicemia . O principal risco associado ao exercício nesses indivíduos é a hipoglicemia, que pode ser reduzido com adequado ajuste de dieta e dose de insulina decorrentes das informaçöes obtdias por emio da adequada automonitorizaçäo da glicemia. Por outro lado, nos portadores de diabete melito näo-depende de insulina, a atividade física propricia melhora em vários aspectos relacionados a sua fisiopatogênese decorrentes de resistência insulínica, sendo, portanto, um importante fator no tratamno juntamente com dienta e/ou terapêutica medicamentosa indicada. Além dos benefícios diretos relacionados com o controle glicêmico, o exercício para o diabete melito näo-dependente de insulina traz outros pontos positivos. A subpopulaçäo de portadores de diabete melito näo-dependente de insulina com intolerância moderada à glicose é a que mais parece se beneficiar da atividade física. tanto no diabete melito dependente de insulina com intorlerância moderada à glicose é a que mais parece se beneficiar d aividade física. Tanto no diabete melito dependente de insulina como no diabete melito näo-dependente de insulina, deve ser realizada availaçäo médica inicial e educaçäo específica para que sejam atingidos os resultados esperados em relaçäo ao controle metabólico e à melhora na qualidade de vida. A atividade física é um importante fator adjuvante no tratamento diabete melito, com papel bastante distinto no diabete melito dependente de insulina e no diabete melito näo-dependente de insulina.

Radioimmunoassay of carboxyl and amino terminal fragments of parathyroid hormone for the evaluation of secondary hyperparathyroidism in chronic renal failure

1. Some parameters of calcium and phosphorus metabolism and the radioimmunoassay of plasma concentrations of both the carboxyl (COOH) (residues 53-84) and amino (NH2) terminal (residues 1-34) fragments of parathyroid hormone (PTH) were measured to evaluate secondary hyperparathyroidism in 68 patients with chronic renal falure (CRF), 34 of whon were on hemodialysis therapy. 2. The upper limits of the normal values for serum PTH-NH2 and PTH-COOH concentrations were 28 and 146 pmol/l, respectively. Patients with mild CRF (plasma creatinine (CRp) 1.2-2 mg/dl) hadh normal mean serum total calcium, low mean phosphorus, undetectable plasma levels of PTH-COOH concentration and normal fractional excretion of phosphorus (FEP). Patients with moderate CRF (CRp2.1-4 mg/dl) had normal mean serum concentrations of both total calcium and phosphorus, and elevated mean levels of both plasma PTH-COOH and PTH-NH2 associated with increased FEP. Patients with end-stage CRF (CRp > 4mg/dl) and those on hemodialysis had elevated mean serum phosphorus levels and decreased mean serum total calcium concentrations compared with those with mild and modetate CRF, and more pronounced, increases in both mean plasma PTH-COOH and PTH-NH2. 3. The logarithm of plasma PTH-NH2, but not PTH-COOH, concentration correlated positively with FEP and serum phosphorus concentration and negatively with total serum calcium concentration, while the logarithms of both PTH-NH2 and PTH-COOH levels correlated positively with CRp. 4. Calcium infusion (2 mg Kg-1 h-1 for 90 min) in eight patients with high plasma levels of PTH-NH2, and PTH-COOH resulted in a significant decrease of plasma PTH-NHL but not of plasma PTH-COOH concentration. 5. These data demonstrate increased plasma PTH levels in moderate renal failure and suggest that the assay of plasma PTH-NH2 rather than PTH-COLL is more appropriate for the evaluation of secondary hyperparathyroidism in chronic renal failure