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1.
Diabet Med ; 27(5): 563-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20536953

ABSTRACT

AIMS: The efficacy of two basal insulins, insulin lispro protamine suspension (ILPS) and insulin detemir, was compared in basal-bolus regimens in Type 1 diabetes. METHODS: In this 32-week, multinational, parallel-group, randomized, controlled trial, adult patients with Type 1 diabetes received ILPS or insulin detemir, injected twice daily (before breakfast and bedtime) and prandial insulin lispro three times daily. The primary outcome was change in glycated haemoglobin (HbA(1c)) from baseline to endpoint. RESULTS: Least squares mean (+/-se) changes in HbA(1c) were similar between groups, meeting non-inferiority (margin, 0.4%): -0.69 +/- 0.07% for ILPS and -0.59 +/- 0.07% for insulin detemir [between-treatment difference -0.10%; 95% confidence interval (CI) -0.29, 0.10]. Standard deviation of fasting blood glucose was similar (non-inferiority margin 0.8 mmol/l): 2.74 +/- 0.14 mmol/l for ILPS and 2.38 +/- 0.14 mmol/l for insulin detemir (CI -0.03, 0.75). Patients on ILPS gained more weight (1.59 +/- 0.23 kg vs. 0.62 +/- 0.24 kg; CI 0.34, 1.60; margin 1.5 kg). Weight-adjusted daily total and prandial insulin doses were lower for ILPS (prandial insulin, 0.38 +/- 0.01 U/kg/day for ILPS, 0.44 +/- 0.01 U/kg/day for insulin detemir; P = 0.004); daily basal insulin dose was similar. All hypoglycaemia incidence and rate and nocturnal hypoglycaemia incidence were similar between groups; nocturnal hypoglycaemia rate was lower for insulin detemir (mean +/- sd 0.79 +/- 1.23 for ILPS, 0.49 +/- 0.85 for insulin detemir; P = 0.001). Severe hypoglycaemia rate was 0.03 +/- 0.11 for ILPS and 0.02 +/- 0.10 for insulin detemir (P = 0.37). CONCLUSIONS: ILPS-treated patients with Type 1 diabetes achieved similar glycaemic control as insulin detemir-treated patients after 32 weeks. Glucose variability was similar. While weight gain and nocturnal hypoglycaemia rate were statistically higher with ILPS, the clinical relevance is unclear.


Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/drug effects , Hypoglycemic Agents/therapeutic use , Insulin/analogs & derivatives , Adult , Analysis of Variance , Blood Glucose/metabolism , Body Weight/drug effects , Dose-Response Relationship, Drug , Fasting , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/administration & dosage , Injections, Subcutaneous , Insulin/administration & dosage , Insulin/adverse effects , Insulin Detemir , Insulin Lispro , Insulin, Long-Acting , Male , Middle Aged
2.
Diabet Med ; 27(1): 109-12, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20121897

ABSTRACT

AIMS: The objective of this cost-of-illness analysis was to quantify the annual costs associated with hospital admission for people with diabetes and foot ulcers in Brazil. METHODS: A hypothetical cohort was simulated using a decision tree model. Prevalence and incidence rates and clinical outcomes were estimated from published studies and applied to the general Brazilian population over 30 years. Costs were quoted in Brazilian real (BRL) and converted to US dollars ($US) at the 2008 currency exchange rate ($US1 = BRL 1.64). In the sensitivity analysis, we reduced and increased rates to assess the robustness of the cost estimates. RESULTS: In this hypothetical cohort there are 6.48 million (95% confidence interval 4.47-7.12) Brazilians citizens with Type 2 diabetes. Each year, approximately 323,000 (89,500-484,500) of these people develop foot ulcers and almost 97,200 (17,900-169,600) require hospital admission as a result. Each year, almost 46,300 (8500-80,900) limb amputations and 12,400 (2300-21,700) deaths occur as a result of diabetic foot disease in Brazil. The annual cost associated with these hospital admissions is estimated to be almost $US264m ($US51m-461m). The estimated cost for patients with amputation is nearly $US128m ($US24.5m-222.3m). CONCLUSIONS: Our model shows that the social and economic impact of diabetic foot disease in Brazil is high. Government decision makers should reflect on the current situation and provide organized foot care throughout the whole country.


Subject(s)
Amputation, Surgical/economics , Diabetes Mellitus, Type 2/economics , Diabetic Foot/economics , Brazil/epidemiology , Cost-Benefit Analysis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/surgery , Diabetic Foot/surgery , Female , Humans , Male , Prevalence
3.
Int J Clin Pract ; 63(9): 1395-406, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19614786

ABSTRACT

AIMS: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy. METHODS AND PATIENTS: A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to

Subject(s)
Adamantane/analogs & derivatives , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , Dipeptides/therapeutic use , Hypoglycemic Agents/therapeutic use , Sulfonylurea Compounds/therapeutic use , Adamantane/therapeutic use , Adolescent , Adult , Aged , Analysis of Variance , Double-Blind Method , Drug Therapy, Combination , Humans , Middle Aged , Treatment Outcome , Young Adult
4.
Diabetes Obes Metab ; 7(2): 148-60, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15715888

ABSTRACT

Diabetes is a principal and growing health concern in Latin America, accounting for significant mortality and morbidities. Large, randomized, prospective trials of various interventional therapies in patients with both type 1 and type 2 diabetes have demonstrated that reductions in hyperglycaemia and management of diabetes-related risk factors can significantly reduce the micro- and macrovascular complications of diabetes. Therefore, patients with type 2 diabetes will benefit from more aggressive treatment regimens to help decrease the occurrence and rate of progression of diabetic complications. Given the many complexities of diabetes management, it is often difficult for general practice physicians to stay abreast of emerging treatment strategies and therapies. Owing to the high prevalence of type 2 diabetes in Latin America, the majority of patients with diabetes are treated by generalists rather than specialists. This article was intended to assist physicians and other healthcare professionals in developing and using effective treatment strategies to stem the growing epidemic of diabetes and its complications in Latin America.


Subject(s)
Algorithms , Diabetes Mellitus, Type 2/therapy , Adult , Age Factors , Blood Glucose/analysis , Diabetes Complications/epidemiology , Diabetes Complications/therapy , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/therapy , Exercise Therapy/methods , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Resistance/physiology , Latin America/epidemiology , Life Style , Microcirculation/physiopathology , Nutritional Physiological Phenomena/physiology , Risk Assessment/methods , Risk Factors , Urban Health , Weight Loss/physiology
5.
Braz. j. med. biol. res ; 36(10): 1301-1309, Oct. 2003. ilus, tab
Article in English | LILACS | ID: lil-346501

ABSTRACT

Pancreatic ß cell function and insulin sensitivity, analyzed by the homeostasis model assessment, before and after 24 weeks of insulin therapy were studied and correlated with the presence of autoantibodies against ß cells (islet cell and anti-glutamic acid decarboxylase antibodies), in a group of 18 Brazilian lean adult non-insulin-dependent diabetes mellitus (NIDDM) patients with oral hypoglycemic agent failure (OHAF). Median fasting plasma glucose before and after insulin treatment was 19.1 and 8.5 mmol/l, respectively (P < 0.001); median HbA1c was 11.7 percent before vs 7.2 percent after insulin treatment (P < 0.001). Forty-four percent of the patients were positive (Ab+) to at least one autoantibody. Fasting C-peptide levels were lower in Ab+ than Ab- patients, both before (Ab+: 0.16 ± 0.09 vs Ab-: 0.41 ± 0.35 nmol/l, P < 0.003) and after insulin treatment (Ab+: 0.22 ± 0.13 vs Ab-: 0.44 ± 0.24 nmol/l, P < 0.03). Improvement of Hß was seen in Ab- (median before: 7.3 vs after insulin therapy: 33.4 percent, P = 0.003) but not in Ab+ patients (median before: 6.6 vs after insulin therapy: 20.9 percent). These results show that the OHAF observed in the 18 NIDDM patients studied was due mainly to two major causes: autoantibodies and ß cell desensitization. Autoantibodies against ß cells could account for 44 percent of OHAF, but Ab- patients may still present ß cell function recovery, mainly after a period of ß cell rest with insulin therapy. However, the effects of ß cell function recovery on the restoration of the response to oral hypoglycemic agents need to be determined


Subject(s)
Humans , Male , Female , Adult , Autoantibodies , Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Insulin , Islets of Langerhans , Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Insulin , Islets of Langerhans , Treatment Failure
6.
Braz J Med Biol Res ; 36(10): 1301-9, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14502361

ABSTRACT

Pancreatic beta cell function and insulin sensitivity, analyzed by the homeostasis model assessment, before and after 24 weeks of insulin therapy were studied and correlated with the presence of autoantibodies against beta cells (islet cell and anti-glutamic acid decarboxylase antibodies), in a group of 18 Brazilian lean adult non-insulin-dependent diabetes mellitus (NIDDM) patients with oral hypoglycemic agent failure (OHAF). Median fasting plasma glucose before and after insulin treatment was 19.1 and 8.5 mmol/l, respectively (P < 0.001); median HbA1c was 11.7% before vs 7.2% after insulin treatment (P < 0.001). Forty-four percent of the patients were positive (Ab+) to at least one autoantibody. Fasting C-peptide levels were lower in Ab+ than Ab- patients, both before (Ab+: 0.16+/-0.09 vs Ab-: 0.41+/-0.35 nmol/l, P < 0.003) and after insulin treatment (Ab+: 0.22+/-0.13 vs Ab-: 0.44+/-0.24 nmol/l, P < 0.03). Improvement of H was seen in Ab- (median before: 7.3 vs after insulin therapy: 33.4%, P = 0.003) but not in Ab+ patients (median before: 6.6 vs after insulin therapy: 20.9%). These results show that the OHAF observed in the 18 NIDDM patients studied was due mainly to two major causes: autoantibodies and beta cell desensitization. Autoantibodies against beta cells could account for 44% of OHAF, but Ab- patients may still present beta cell function recovery, mainly after a period of beta cell rest with insulin therapy. However, the effects of beta cell function recovery on the restoration of the response to oral hypoglycemic agents need to be determined.


Subject(s)
Autoantibodies/immunology , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Islets of Langerhans/immunology , Adult , Diabetes Mellitus, Type 2/immunology , Female , Humans , Hypoglycemic Agents/immunology , Insulin/immunology , Islets of Langerhans/physiology , Male , Treatment Failure
8.
Braz J Med Biol Res ; 34(4): 479-87, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11285459

ABSTRACT

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 +/- 6 years, BMI 31.1 +/- 2.5 kg/m(2), %fat 40.3 +/- 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 +/- 12.3 vs 51.4 +/- 23.3 ng/ml, P<0.05). Weight loss (86.1 +/- 15.1 vs 80.6 +/- 14.2 kg, P<0.05) led to a reduction in leptin levels (25.13 +/- 12.8 vs 15.9 +/- 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.


Subject(s)
Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Leptin/blood , Obesity/metabolism , Weight Loss/physiology , Adult , Biomarkers/blood , Clinical Protocols , Energy Intake , Female , Humans , Leptin/metabolism , Male
9.
Braz. j. med. biol. res ; 34(4): 479-87, Apr. 2001. tab, graf
Article in English | LILACS | ID: lil-282613

ABSTRACT

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


Subject(s)
Humans , Male , Female , Adult , Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Leptin/blood , Obesity/metabolism , Weight Loss/physiology , Clinical Protocols , Energy Intake , Leptin/metabolism
10.
Sao Paulo Med J ; 119(2): 84-5, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11276172

ABSTRACT

CONTEXT: Latent autoimmune diabetes of the adult (LADA) as originally described represents perhaps as many as 10 - 20% of adult-onset patients with diabetes. DESIGN: case report. CASE REPORT: A 38-year-old Brazilian Xavante-Jê Indian with Latent Autoimmune Diabetes of the Adult (LADA) is described, coming from the Sangradouro community in Poxoréu, Mato Grosso. The onset of diabetes after reaching 25 years of age, the evolution to insulin deficiency after a period of insulin-independence and the presence of auto-antibodies to glutamic acid decarboxylase (GAD) characteristic of LADA were present. This patient may represent the first case of LADA in a Brazilian with full Indian heritage. Further studies are necessary to verify the prevalence of this new type of diabetes in this population that does not have Caucasoid admixture and has a particular environmental background.


Subject(s)
Diabetes Mellitus, Type 1/ethnology , Indians, South American , Adult , Brazil , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/therapy , Humans , Male
11.
Braz. j. med. biol. res ; 31(12): 1545-51, Dec. 1998.
Article in English | LILACS | ID: lil-224839

ABSTRACT

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic ß-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic ß-cell secretion in men with different body compositions. Eighteen young men (30.0 ± 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P<0.05), proinsulin (r = -0.47, P<0.05), C-peptide (r = -0.55, P<0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P<0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P<0.05). When subjects were divided into obese (BMI >28 kg/m2, N = 8) and nonobese (BMI £25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic ß-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic ß-cell demand


Subject(s)
Adult , Humans , Male , Hyperinsulinism/blood , Islets of Langerhans/metabolism , Proinsulin/blood , Sex Hormone-Binding Globulin/deficiency , Absorptiometry, Photon , Biomarkers , Body Mass Index , C-Peptide/blood , Glucose Tolerance Test , Hyperinsulinism/complications , Insulin/blood , Islets of Langerhans/chemistry , Islets of Langerhans/physiopathology
12.
Braz J Med Biol Res ; 31(12): 1545-51, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9951550

ABSTRACT

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic beta-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic beta-cell secretion in men with different body compositions. Eighteen young men (30.0 +/- 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P < 0.05), proinsulin (r = -0.47, P < 0.05), C-peptide (r = -0.55, P < 0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P < 0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P < 0.05). When subjects were divided into obese (BMI > 28 kg/m2, N = 8) and nonobese (BMI < or = 25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic beta-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic beta-cell demand.


Subject(s)
Hyperinsulinism/blood , Islets of Langerhans/metabolism , Proinsulin/blood , Sex Hormone-Binding Globulin/deficiency , Adult , Biomarkers , Body Mass Index , C-Peptide/blood , Glucose Tolerance Test , Humans , Hyperinsulinism/complications , Insulin/blood , Islets of Langerhans/chemistry , Islets of Langerhans/physiopathology , Male
13.
J Pediatr (Rio J) ; 72(4): 221-4, 1996.
Article in Portuguese | MEDLINE | ID: mdl-14688931

ABSTRACT

We have followed eight first-degree relatives of IDDM patients (insulin-dependent, type I diabetes) attending the outpatient diabetes clinic at the State University of Rio de Janeiro for three years, all of them with positive islet cell antibodies (ICA and/or ICA-CF). Three out of eight relatives less than fifteen years old have subsequently progressed to overt Insulin-Dependent Diabetes Mellitus (IDDM) 12, 21 and 8 months after the first positive autoantibodies detection. Four relatives have remained with ICA and/or ICA-CF positive, and in another one the reaction became negative during the observation period. A positive correlation has been found between high titles of ICA (> or = 1/16) and development of IDDM. We have concluded from our prospective study during three years that of our antibody-positive relatives, 37.5 % have developed overt diabetes, all of them being less than fifteen years old, with high titles of ICA and ICA-CF positive.

14.
Rev Invest Clin ; 47(3): 173-9, 1995.
Article in Spanish | MEDLINE | ID: mdl-7569360

ABSTRACT

A multicentric, comparative, single-blind, randomized, prospective study was designed to evaluate the efficacy and safety of the transference from animal source insulins to rDNA human insulin in Latinamerican insulin-requiring diabetic patients. All the patients were on animal insulin for at least two months before inclusion. The patients were evaluated at the beginning, and at two and six weeks after inclusion. A total 198 patients completed the study and were considered evaluable: 94 were assigned to the animal insulin group, and 104 to the human insulin group. There were no statistically significant baseline differences between groups. The only statistically significant difference, detected at the end of the study, was a reduction in fasting blood glucose level in the human insulin group (animal insulin 212 +/- 95.3 initial vs 193 +/- 78.3 mg/dL final, p = 0.18; human insulin 198 +/- 86.8 vs 169 +/- 71.7, p = 0.025). There were no statistically significant initial-final changes in the rest of the parameters evaluated although a trend of reduction in glycohemoglobin levels was observed in both groups. There were more episodes of mild hipoglycemia in the human insulin group, and only one episode of severe unwarned hypoglycemia in the same group. We conclude that the transference of insulins in Latinamerican diabetic patients is effective and reasonably safe (with a dose adjustment when the change is made).


Subject(s)
Diabetes Mellitus/therapy , Insulin/therapeutic use , Adolescent , Adult , Aged , Animals , Cattle , Female , Humans , Latin America , Male , Middle Aged , Prospective Studies , Recombinant Proteins/therapeutic use , Single-Blind Method
15.
Braz J Med Biol Res ; 28(4): 433-8, 1995 Apr.
Article in English | MEDLINE | ID: mdl-8520540

ABSTRACT

Nocturnal urinary growth hormone (U-hGH) levels measured by a sensitive immunoenzymometric assay were compared with hGH levels in serum before and after a clonidine test in healthy children and in children with short stature to determine whether U-hGH measurement is useful for the screening of hGH deficiency. The study was carried out on 19 healthy children (10 prepubertal and 9 pubertal subjects) and on 20 children with short stature, 10 with growth hormone deficiency (hGHD) and 10 with constitutional growth retardation. The diagnosis of hGHD was based on a blunted response to two provocative hGH tests in the appropriate clinical setting. Overnight urinary hGH secretion (mean of 3 collections) was measured by an immunoenzymometric assay. The best discrimination was obtained when the results were expressed as ng/h. Only one individual in the prepubertal group (U-hGH, 0.05 ng/h) and one patient in the growth retardation group (U-hGH, 0.08 ng/h) had a urinary hGH value below the highest value (0.17 ng/h) observed in the growth hormone deficiency group. The coefficient of correlation between urinary hGH in ng/h and post-clonidine peak was 0.50 (P = 0.0015), between urinary hGH in ng/l and post-clonidine peak was 0.48 (P = 0.0025), between urinary hGH in ng/l per hour and post-clonidine peak was 0.47 (P = 0.0027). The highest specificity (0.93), sensitivity (0.90), false negative rate (0.96) and false positive rate (0.82) were obtained when U-hGH was expressed as ng/h per night. Measurement of urinary nocturnal hGH excretion is a useful, simple, noninvasive method for the diagnosis of hGH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Circadian Rhythm , Growth Hormone/deficiency , Growth Hormone/urine , Adolescent , Age Determination by Skeleton , Child , Clonidine , Female , Growth Disorders , Growth Hormone/blood , Humans , Male , Predictive Value of Tests , Puberty
16.
Braz. j. med. biol. res ; 28(4): 433-8, Apr. 1995. tab, graf
Article in English | LILACS | ID: lil-154844

ABSTRACT

Nocturnal urinary growth hormone (U-hGH) levels measured by a sensitive immunoenzymometric assay were compared with hGH levels in serum before and after a clonidine test in healthy children and in children with short stature to determine whether U-hGH measurement is useful for the screening of hGH deficiency. The study was carried out on 19 healthy children (10 prepubertal and 9 pubertal subjects) and on 20 children with short stature, 10 with growth hormone deficiency (hGHD) and 10 with constitutional growth retardation. The diagnosis of hGHD was based on a blunted response to two provocative hGH tests in the appropriate clinical setting. Overnight urinary hGH secretion (mean of 3 collections) was measured by an immunoenzymometric assay. The best discrimination was obtained when the results were expressed as ng/h. Only one individual in the prepubertal group (U-hGH, 0.05 ng/h) and one patient in the growth retardation group (U-hGH, 0.08 ng/h) had a urinary hGH value below the highest value (0.17 ng/h) observed in the growth hormone deficiency group. The coefficient of correlation between urinary hGH in ng/h and post-clonidine peak was 0.50 (P = 0.0015), between urinary hGH in ng/l and post-clonidine peak was 0.48 (P = 0.0025), between urinary hGH in ng/l per hour and post-clonidine peak was 0.47 (P = 0.0027). The highest specificity (0.93), sensitivity (0.90), false negative rate (0.96) and false positive rate (0.82) were obtained when U-hGH was expressed as ng/h per night. Measurement of urinary nocturnal hGH excretion is a useful, simple, noninvasive method for the diagnosis of hGH deficiency. However, the day-to-day variability and wide normal range limit its usefulness in mild forms of hGH insufficiency


Subject(s)
Humans , Male , Female , Child , Adolescent , Circadian Rhythm , Growth Hormone/deficiency , Growth Hormone/urine , Age Determination by Skeleton , Body Height , Body Mass Index , Clonidine , Growth Disorders , Growth Hormone/blood , Predictive Value of Tests , Puberty , Sensitivity and Specificity
17.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 41(1): 37-42, jan.-fev. 1995. tab, graf
Article in Portuguese | LILACS | ID: lil-153314

ABSTRACT

A cetoacidose diabética (CAD) é a emergência endocrinológica mais freqüente e de boa evoluçäo, na maior parte dos casos. Os autores apresentam evoluçäo atípica de três casos de CAD precipitada por resistência imunológica à insulina (RII). RELATO DE CASO. Três pacientes: H.M.L. (46 anos, diabetes mellitus (DM) tipo II, há 6 anos), D.R.J (39 anos, DM, secundário à pancreatopatia, há 11 anos) e D.L.S. (54 sanos, DM tipo II, há 9 anos) foram admitidos na Unidade de primeiro Atendimento do Hospital Säo Paulo em CAD: H.M.L. (glicemia: 716mg/dL, pH: 6,8), D.R.J. (glicemia: 684mg/dL, pH 6,.9) e D.L.S. (glicemia: 384mg/dL, pH: 7,2), todos apresentavam cetonúria. As necessidades de insulina para o controle metabólico foram: H.M.L.: 1.369UI, D.R.J.: 1.496UI, D.I.S. 1.369UI em, respectivamente: 212, 206 e 72 horas. Os anticorpos antiinsulina (AI) foram dosados por RE e ELISA: H.M.L.: 7.186nU/ml, 3,6IE; D.R.J.: 7,879nU/mL, 3,24IE; D.I.S: 8.377nU/mL, 2,88IE. O seguimento ambulatorial revelou queda progressiva dos níveis de AI:H.M.L.: 3.393nU/mL, 1,39, após dez meses da CAD; d.r.j.: 4,673Nu/Ml, 2,34 E d.i.s.: 1,510nU/mL, ambos após 18 meses da CAD. A queda nos níveis de anticorpos foi significativa nos três pacientes e foi acompanhada de melhor controle metabólico. Discussäo. A ausência de fator desencadeante, o elevado tempo, as altas doses de insulina empregadas para a compensaçäo metabólica levaram os autores à suspeita diagnóstica de RII. O diagnóstico foi confirmado pelos altos níveis séricos dos AI. O controle metabólico nestes pacientes foi obtido somente após a introduçäo de insulina na humanizada. CONCLUSAO. A resistência imunológica à insulina pode ser uma das causas de CAD sem fator precipitante aparente e má resposta às medidas terapêuticas habituais


Subject(s)
Humans , Male , Female , Middle Aged , Insulin/administration & dosage , Diabetic Ketoacidosis/etiology , Insulin Resistance , Enzyme-Linked Immunosorbent Assay , Radioimmunoassay , Follow-Up Studies , Insulin/immunology , Insulin/blood , Insulin Antibodies/analysis , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/immunology , Diabetic Ketoacidosis/drug therapy
18.
Rev Assoc Med Bras (1992) ; 41(1): 37-42, 1995.
Article in Portuguese | MEDLINE | ID: mdl-7550412

ABSTRACT

Although rare, ketoacidosis may be induced by the occurrence of antibody mediated insulin resistance. Cases of 3 patients with ketoacidosis precipitated by immunologic insulin resistance (IIR) are reported. CASE REPORT--Three patients were admitted to the primary care unit of Hospital São Paulo in Diabetic Ketoacidosis. Demographic data of the patients (HML, DRJ and DIS) included: age (46.39 and 54 y.o.); sex (2F, 1M); diabetes mellitus (2 DM II and 1 pancreatic); duration of diabetes (6, 11 and 9 years) and BMI (17.5; 25.5 and 24.3 kg/m2. Admission laboratory data were: glucose (40, 38 and 22 mmol/L); pH (7.2; 6.9 and 7.2) and all had ketonuria. Insulin requirements for metabolic control were: HML: 1494U; DRJ: 1496U; DIS: 450U in a period of: 212, 206 and 72h. The plasmatic leves of Anti insulin antibodies (IA) measured by RIA (nU/mL) and ELISA (EI), where: HML: 7186, 3.26; DRJ: 7879, 3.42 and DIS: 8377, 2.88. HI was associated with marked decrease of both, insulin requirements and IA (HML: 3393, 1.39 after 10 months and DRJ: 4673, 2.34; DIS: 1510, after 18 months) at follow-up. DISCUSSION--The High Insulin requirements and time necessary to achieve the metabolic control guided us to the diagnosis of IIR. It was confirmed by high levels of AI and by the improvement in the metabolic control after the introduction of HI. CONCLUSION--The physician must be alert to severe IIR if there is no response after standard therapy to ketoacidosis. HI can be considered a valid alternative of treatment for IIR.


Subject(s)
Diabetic Ketoacidosis/etiology , Insulin Resistance/immunology , Insulin/administration & dosage , Diabetic Ketoacidosis/drug therapy , Diabetic Ketoacidosis/immunology , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Insulin/blood , Insulin Antibodies/analysis , Male , Middle Aged , Radioimmunoassay
19.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 39(1): 48-52, jan.-mar. 1993. tab
Article in Portuguese | LILACS | ID: lil-123288

ABSTRACT

Trata-se de um caso de diabetes mellitus do tipo I(DMI) no qual tivemos a oportunidade de diagnosticá-lo 23 meses antes das suas manifestaçöes clínicas mais freqüentes. Durante esse período foram observadas alteraçöes como o retorno de enurese, diminuiçäo na velocidade de crescimento e episódios de hiperglicemia e/ou glicosúria transitórios, apresentadas pela paciente, que podem näo ser devidamente valorizadas, na rotina clínica. Como, também, o aparecimento de marcadores imunológicos (ICA) e alteraçöes precoces na secreçäo de insulina (diminuiçäo na sua primeira fase de liberaçäo) vários meses antes do DMI manifesto. Esses marcadores imunológicos e essas alteraçöes endócrinas deveriam, se possível, ser pesquisados em pacientes com o quadro clínico inicial aqui apresentado, e em parentes jovens de DMI, no sentido de se detectar indivíduos com elevado risco de evoluírem para a fase manifesta dessa moléstia. O seguimento desses pacientes possibilitaria o diagnóstico precoce do DMI e a aplicaçäo de medidas no sentido de impedir a deteriorizaçäo total das células beta-pancreáticas e a evoluçäo para distúrbios metabólicos mais graves, como a cetoacidose diabética, com morbidade e mortalidade reconhecida


Subject(s)
Humans , Female , Child , Diabetes Mellitus, Type 1/diagnosis , Follow-Up Studies , Diabetes Mellitus, Type 1/therapy , Biomarkers
20.
Rev Assoc Med Bras (1992) ; 39(1): 48-52, 1993.
Article in Portuguese | MEDLINE | ID: mdl-8220508

ABSTRACT

Case report on a child whose type I diabetes mellitus was diagnosed 23 months before the appearance of overt glucose intolerance. In this pre-IDDM stage of DMI were observed secondary enuresis, decreased growth speed, transient hyperglycemia and asymptomatic glycosuria. These alterations may represent the earliest clinical manifestation of impaired beta cell function. Immunologic markers (ICA and/or AAI) of DMI and abnormalities of the first-phase insulin secretion in response to intravenous glucose also may precede by several months the most common clinical picture of type I diabetes as they were detected in this child. If possible, markers and alterations should be tested in such patients and their young relatives with DMI in order to detect high risk individuals who may develop DMI. Such and accurate predictive ability should be a prerequisite to institution of appropriate therapy to preventing further beta cell destruction and severe metabolic decompensation, thus having the potential to reduce morbidity and mortality from new onset DMI.


Subject(s)
Diabetes Mellitus, Type 1/diagnosis , Biomarkers , Child , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/therapy , Female , Follow-Up Studies , Humans
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