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) 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% for GADAb, 62.9% for IA-2Ab and 82.9% for GADAb and/or IA-2Ab. The long-duration type 1 diabetes subjects presented frequencies of 54.1% for GADAb and IA-2Ab, and 67.5% 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.

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 normotensive 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 and 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 BP 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/24 h, 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%, P < 0.05) and this ratio turned out to be similar to that found in the control group (10.3 vs 16.3%). 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 sympathetic activity.

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.

Different urinary albumin responses to submaximal exercise by normoalbuminuric 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% 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/creatine ration was not significantly different between normal and diabetic subjects, but became different following exercise (6.6 +/- 4.1 vs 17.7 +/- 18.7 mg/g. P < 0.05). While this ratio decreased in the control group (14.8 +/- 11.1 to 6.6 +/- mg/g, P < 0.02), it increased (9.0 +/- 7.1 to 17.7 +/- 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 +/- 0.064 to 0.030 +/- 0.039 microgram/g, P = 0.05) and diabetic patients to an increase (0.116 +/- 0.125 to 0.247 +/- 0.247 microgram/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 require further investigation.

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.

Disturbances of glucose and lipid metabolism in first and second generation Japanese-Brazilians. Japanese-Brazilian Diabetes Study Group.

Increased prevalence of self-reported NIDDM in Japanese-Brazilians was reported when compared to Japan. This study aimed at determining the prevalence of NIDDM and IGT in Japanese-Brazilians living in the city of Bauru, São Paulo, Brazil. The impact of western environment on the frequency of obesity, dyslipidemia and hypertension was investigated. All Issei (first generation; n = 238) and a random sample of Nisei (second generation; n = 292), aged 40-79 years, were selected for clinical examination and OGTT (WHO criteria). Age-adjusted prevalence of NIDDM did not differ between men and women for Issei (12.4 vs. 11.6%, respectively), but it became different for Nisei (21.7 vs. 11.4%, P < 0.03) due to an increased rate among men. Increased IGT prevalence was also observed between Issei and Nisei men (8.5 vs. 19.3%, P < 0.03). Issei women had a higher IGT rate than Issei men (27. 3 vs. 8.5%, P < 0.0005). Body mass index (BMI) was higher in the second generation (24.1 +/- 3.6 vs. 23.3 +/- 3.1 kg/m2, P < 0.00005) and also the frequency of obesity, defined as BMI > 25 kg/m2. Comparison of waist/hip ratio by gender showed that only among women, Nisei had lower ratio than Issei (0.90 vs. 0.88, P < 0.05). Nisei had a lower total and LDL-cholesterol than Issei but triglyceride and HDL-cholesterol did not differ. Nisei women (younger than the Issei) had lower triglyceride and total cholesterol. This pattern was not seen between the two generations of men. Considering the mean blood pressure values, Issei and Nisei groups with normal glucose tolerance were not hypertensive. Systolic blood pressure was lower in Nisei and the inverse was found concerning diastolic levels. NIDDM prevalence in Japanese-Brazilians is higher than in Japan and in the general Brazilian population. Besides environment, genetic factors may confer susceptibility to NIDDM when they are exposed to a western environment. Before developing glucose intolerance, disturbances of lipid profile and blood pressure could be detected. Nisei may be more affected due to a longer exposure to an unfavorable environment and these changes seem to occur earlier among men than women.

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 +/- 2.7 years) and 45 matched control subjects (11.9 +/- 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 +/- 21 to 5 +/- 7 g/12 h, P < 0.01) and in insulin requirement (42 +/- 20 to 31 +/- 12 U/day, P < 0.01) in the diabetic group. The mean BP and AER of the diabetic patients fell from 74 +/- 11 to 69 +/- 11 mmHg, P < 0.001, and from 4.9 +/- 6.0 to 2.1 +/- 2.0 micrograms/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 +/- 2.1 years) was submitted to the same 9-day program and also to improved glycemic control (Study II). Changes in BP (79 +/- 11 to 76 +/- 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 +/- 99 to 127 +/- 42 ml min-1 (1.73 m2)-1, P < 0.05). Urinary aldosterone decreased from 5.3 +/- 3.9 to 3.4 +/- 2.4 micrograms/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 hyperfiltration 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.

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.

Familial hypertension and albuminuria in normotensive type I diabetic patients.

An inherited predisposition to hypertension may increase susceptibility to nephropathy in type I diabetes. We evaluated the influence of a family history of essential hypertension on albuminuria in normotensive, normoalbuminuric type I diabetic patients. Forty-two diabetics (12.9 +/- 2.04 years) were divided into three groups according to tertiles of albumin excretion rate (group 1, 1.27 +/- 0.35; group 2, 2.43 +/- 0.49; group 3, 6.37 +/- 3.43 micrograms/min; P < .001). Familial hypertension was considered to be present if the patient had one parent or grandparent on antihypertensive therapy. The three groups did not differ concerning age, diabetes duration, insulin requirement, body mass index, blood pressure, and urinary glucose excretion. Albumin excretion rate did not correlate with any parameter studied. The frequency of hypertension was significantly lower among the relatives of the patients from group 1 compared with those from groups 2 and 3 (28.6% versus 64.3% versus 78.6%, P < .03). Our data suggest that a familial antecedent of hypertension in normoalbuminuric type I diabetic patients is associated with a high normal albumin excretion rate not related to increases in blood pressure. Early changes in renal hemodynamics, seen in patients with a predisposition to hypertension, may contribute to increments in albuminuria even within the normal range.

Population-based incidence of IDDM in the state of São Paulo, Brazil.

OBJECTIVE: To study the incidence of IDDM among children, infants to 14 yr of age, in the state of São Paulo, Brazil, 1987-1991. RESEARCH DESIGN AND METHODS: A prospective population-based register was established, using physician reports of newly diagnosed IDDM patients < 15 yr of age as the primary source of case identification and school surveys as the main secondary source. Data were collected according to the methods recommended by the Diabetes Epidemiology Research International group. RESULTS: Case ascertainment was estimated at 95.0, 92.8, and 98.8% complete for each of the three cities studied. The average annual IDDM incidence was 7.6/100,000 inhabitants (95% confidence interval, 5.6-9.7). We found a higher incidence rate in girls than boys. CONCLUSIONS: The incidence of childhood IDDM in a tropical region in South America (São Paulo, Brazil) is in the middle incidence range observed in developed countries throughout the world. Increased incidence of IDDM in girls compared with boys will be tested by the ongoing Brazilian incidence study being developed in 18 other centers across the country.