Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001) after the addition of metformin (1404.4 ± 565.5 mg/day), with 14 percent of the 57 patients reaching A1C levels up to 7 percent, and 53 percent reaching values up to 8 percent. There was a statistically significant reduction (P < 0.05) of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/dL), BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m²), waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm), and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01 percent) and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

Diet plus insulin compared to diet alone in the treatment of gestational diabetes mellitus: a systematic review

Fetuses of mothers with gestational diabetes mellitus are at increased risk to develop perinatal complications mainly due to macrosomia. However, in view of the marked heterogeneity of this disease, it seems difficult to set guidelines for diagnosis and treatment. This complicates the choice of assigning patients either to diet or to insulin therapy. Also of concern is how much benefit could be expected from insulin therapy in preventing fetal complications in these patients. In a systematic review of the literature assessing the efficacy of insulin in preventing macrosomia in fetuses of mothers with gestational diabetes, we found six randomized controlled trials comparing diet alone to diet plus insulin. The studies included a total of 1281 patients (644 in the diet plus insulin group and 637 in the diet group), with marked differences among trials concerning diagnostic criteria, randomization process and treatment goals. Meta-analysis of the data resulted in a risk difference of -0.098 (95 percentCI: -0.168 to -0.028), and a number-necessary-to-treat of 11 (95 percentCI: 6 to 36), which means that it is necessary to treat 11 patients with insulin to prevent one case of macrosomia. This indicates a potential benefit of insulin, but not significantly enough to set treatment guidelines. Because of the heterogeneous evidence available in the literature about this matter, we conclude that larger trials addressing the efficacy of these two therapeutic modalities in preventing macrosomia are warranted

Non-obese adult onset diabetes with oral hypoglycemic agent failure: islet cell autoantibodies or reversible beta cell refractoriness?

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

Development according to pubertal stage in Brazilian children and adolescents with short-term diabetes

The anthropometric status and metabolic control of 51 recently diagnosed Brazilian schoolchildren with type 1 diabetes (DM1), during the first 5 years of the disease, were compared with those of normal children (60 girls and 132 boys) belonging to the same environmental condition and pubertal stage. Metabolic control was evaluated on the basis of fasting plasma glucose (FPG) and HbA1c levels. The criteria of the National Center for Health Statistics were used for anthropometric evaluation. FPG (205 + or - 51 mg/dl for girls vs 200 + or - 34 mg/dl for boys) and percent above upper normal limit of median HbA1c (1.8 percent for girls vs 2.5 percent for boys with diabetes) were not significantly different during follow-up. The Z-score of the last height evaluation was lower in the girls' group (-0.14 vs -0.53, P<0.05). By forward stepwise analysis, the Z-score of the initial height was statistically significant as a determinant factor for height at the end of the study in both girls and boys with DM1. The Z-score of weight at last evaluation was not different from that at diagnosis in either sex. However, analysis according to pubertal stage showed a tendency to a weight increase in the girls. The weight recovery and height loss in girls with DM1 follows the trend of the normal Brazilian population

Detection of adrenocortical autoantibodies in Addison's disease with a peroxidase-labelled protein A technique

Adrenocortical autoantibodies (ACA), present in 60-80 percent of patients with idiopathic Addison's disease, are conventionally detected by indirect immunofluorescence (IIF) on frozen sections of adrenal glands. The large-scale use of IIF is limited in part by the need for a fluorescence microscope and the fact that histological sections cannot be stored for long periods of time. To circumvent these restrictions we developed a novel peroxidase-labelled protein A (PLPA) technique for the detection of ACA in patients with Addison's disease and compared the results with those obtained with the classical IIF assay. We studied serum samples from 90 healthy control subjects and 22 patients with Addison's disease, who had been clinically classified into two groups: idiopathic (N = 13) and granulomatous (N = 9). ACA-PLPA were detected in 10/22 (45 percent) patients: 9/13 (69 percent) with the idiopathic form and 1/9 (11 percent) with the granulomatous form, whereas ACA-IIF were detected in 11/22 patients (50 percent): 10/13 (77 percent) with the idiopathic form and 1/9 (11 percent) with the granulomatous form. Twelve of the 13 idiopathic addisonians (92 percent) were positive for either ACA-PLPA or ACA-IIF, but only 7 were positive by both methods. In contrast, none of 90 healthy subjects was found to be positive for ACA. Thus, our study shows that the PLPA-based technique is useful, has technical advantages over the IIF method (by not requiring the use of a fluorescence microscope and by permitting section storage for long periods of time). However, since it is only 60 percent concordant with the ACA-IIF method, it should be considered complementary instead of an alternative method to IIF for the detection of ACA in human sera

Cetoacidose diabética desencadeada por resistência imunológica à insulina / Diabetic ketoacidosis induced by immunologic insulin resistance

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

Detection of insulin antibodies by radioassay and ELISA: interrelation and correlation with metabolic control in type I diabetes

1. The literature suggests that the radioassay (RA) and ELISA detect different types of insulin antibodies (IA) (Wilkin et al., 1989. Diabetes, 38: 172-181). 2. In the present study we evaluated the relationship between these two antibodies and their involvement in the metabolic control of Type I diabetic (DMI) patients. 3. IA were measured by RA and ELISA in sera obtained from 34 patients (age: 9-16 years, median = 12.5 years; clinical duration of DMI: 0.1-11.0 years, median = 1.7 years) treated with different types of insulin [purified (bovine + porcine) N = 18, and monocomponent (porcine or human) N = 16] and submitted to various degrees of metabolic control as assessed by glycosylated serum protein (GSP) levels: range, 3.4-13.5; median = 8.7; normal value, 0.8-2.4. 4. Insulin antibody levels measured by RA were: 3264 +/- 300 nU/ml (mean +/- SEM, normal value < 60 nU/ml) and by ELISA: 0.74 +/- 0.11 ELISA index (EI) (normal value, < 0.53). No correlation was found between IA levels measured by RA and ELISA, or between duration of the disease or insulin daily necessity and IA by either method. GSP was positively correlated with IA determined by ELISA (rS = 0.43, P < 0.01) but not with IA determined by RA. 5. The patients on purified bovine + porcine insulin had higher titers of IA by ELISA, compared to those of patients on monocomponent (0.96 +/- 0.15 vs 0.50 +/- 0.13 EI, P < 0.03, while IA levels measured by RA did not differ between groups. 6. These data show that RA or ELISA assays provide different serum titers of IA in insulin-treated diabetics and data obtained with ELISA correlated best with the metabolic control of Type I diabetic patients.

Aspectos da fase näo-insulinodependente do diabetes mellitus do tipo I / Aspects of non-insulin-dependent phase of type I diabetes mellitus

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

Insulin autoantibodies in first degree relatives of type I diabetic patients

Insulin autoantibodies (IAA) of first-degree relatives of type diabetic patient and recent-onset type I diabetics were measured by radioimmunoassay. A cut-off of 60 nU/ml was established on the basis of the values of normal control individuals. The intra-assay coefficient of variation was 9.2% for a moderately positive serum (1908 ñ 176 nU/ml (mean ñ SD), N=7; range, 1708 to 2158 nU/ml). The interassay coefficient of variation was 23.8% for a negative (normal control) serum (28.1 ñ 6.7 nU/ml, N=6; range, 22 to 39 nU/ml) and 14.5% in a highly positive serum (6185 ñ 899 nU/ml, N=7; range, 5053 to 7009 nU/ml). Insulin autoantibody levels (mean ñ SEM) were 19.3 ñ 2.8 nU/ml (range, =-19 to 40 nU/ml) in 25 controls, 24.8 ñ 3.4 nU/ml (range, -17 to 59 nU/ml) in 41 type II diabetic patients, 18.5 ñ 2.4 nU/ml (range, -58 to 268 nU/ml) in 171 first-degree relatives of type I diabetic patients and 208.9 ñ 87.0 nU/ml (range, 10 to 1101 nU/ml) in 16 recent-onset type I diabetic patients. IAA levels were significantly higher in the last group compared with the other groups (P<0.01). None of the controls or type II diabetics exceeded the upper limit of normalyity. In contrast, 9 of 171 (5.3%) first-degree relatives and 9 of 16 (56.0%) recent-onset type I diabetic patients had IAA levels above the 60 nU/ml cut-off point. These data indicate that this method is effective for the detection of individuals who are at high risk to develop type I diabetes

Do impaired glucose tolerance and diabetes mellitus interfere with the interpretation of the growth hormone response to the oral glucose tolerance test ?

The ability of glucose to suppress growth hormone (GH) secretion is well known and the glucose test is widely used for the diagnosis of acromegaly. However when suspected acromegaly is associaterd with diabetes mellitus (DM) or impaired glucose tolerance (IGT) the interpretation of the GH response to the oral glucose tolerance test (OGTT) may be difficult. Recently, Haltori et al. (Journal of clinical endocrinology and metabolism, 70: 771-778, 1990), using a highly sensitive (1.5 ng/l) polyclonal antibody-based immunoenzymometric assay, found no differences in the GH response to glucose load among control, IGT and DM patients. We employed a less sensitive (100 ng/l) but monoclonal antibody-based immunoenzymometric assay to measure the serum GII levels of 19 normal subjects, 11 patients with DM and 11 patients with IGT to determine the effect of glucose intolerance on the GH response to the OGTT. Complete suppression of GH (<0.1 ug/l) was achieved in 73% o9f the controls with a mean nadir of 0.17 ñ 0.16 ug/l (range, <0.1-0.6 ug/l). GH was completely suppressed in 82% of the the diabetes with a mean nadir of 0.58 ñ 1.21 ug/l (range, <0.1-4.0 ug/l). However, complete suppression occurred in only 27% of the IGT patients with a nadir of 1.09 ñ 2.08 ug/l (range, 0.1-7.0 yg/l), which was statisticaly higher than observed for controls and diabetics. We conclude that plasma GH plasma GH levels after glucose loading of IGT patients should be interpreted with caution because an abnormal response can be detected when some sensitive immunometric assays are employed

Estudo do valor diagnostico da glicemia de jejum, da curva glicemica e da hemoglobina glicosilada (HbA1) no "diabetes mellitus". / Diagnostic value of fasting glycemia, blood glucose curve and glycosylated hemoglobin (HbA1) in diabetes mellitus

Os autores compararam a dosagem da hemoglobina glicosilada (HbA1) e o teste oral de tolerancia a glicose em 437 individuos com suspeita de diabetes mellitus. Analisaram a sensibilidade, especificidade e o valor preditivo positivo de cada teste, e sugerem um protocolo para o diagnostico de diabetes mellitus. Neste esquema diagnostico recomendam, inicialmente, a realizacao da dosagem da glicemia de jejum, afastando nos pacientes com valores inferiores a 100mg/dl e estabelecendo o diagnostico quando a glicemia for maior ou igual a 125mg/dl. Em pacientes com valores intermediarios recomendam uma sobrecarga de glicose e dosagem de glicemia 2 horas apos, afastando diabetes nos valores de glicemia inferiores a 140mg/dl e estabelecendo o diagnostico com valores maiores ou iguais a 200mg/dl. A HbA1 esta indicada nos valores intermediarios

Tratamento do coma diabetico: experiencia em um hospital geral. / Treatment of diabetic coma: experience in a general hospital

O presente estudo mostrou que em nosso hospital o principal fator precipitante das descompensacoes diabeticas e a infeccao. Ressaltamos o baixo indice de mortalidade (1,4% nas cetoacidoses diabeticas e 8,8 no coma hiperosmolar nao cetotico) obtido com o esquema utilizado.Todos os nossos pacientes foram tratados a nivel de PS por uma equipe de residentes de Clinica Geral. Em nosso pais, onde centros endocrinologicos especializados se restringem as grandes concentracoes urbanas e de gran de importancia a divulgacao de esquemas terapeuticos de orientacao simples e que possam ser utilizados sem necessidade de grandes recursos materias, por clinicos gerais

Sindrome do T3 baixo com eutiroidismo em doenca sistemica severa. / Low T3 syndrome with euthyroidism in severe systemic diseases

Os autores analisam os testes de funcao tiroidiana num grupo de 50 pacientes eutiroidianos portadores de doencas sistemicas graves. Verificaram uma alta incidencia de T3 diminuido e T3 reverso elevado (56 e 50% respectivamente) e uma moderada casuitica de T4 baixo (20%). Todavia, todos os pacientes apresentavam-se clinicamente em eutiroidismo, alem de possuirem os valores de TSH dentro da normalidade.Em consequencia, demonstrou-se a dificuldade da analise do estado tiroidiano em pacientes portadores de doencas sistemicas e evidenciou-se que o encontro de T3 e T4 diminuidos, nesse grupo de doentes, nao significa obrigatoriamente hipotiroidismo

Tirotoxicose por T4: entidade nosologica independente ou efeito de alteracao na conversao periferica de T4? / T4 thyrotoxicosis: an independent disease or the effect of a change in the peripheral conversion of T4?

Em 250 pacientes com diagnostico de hipertiroidismo, observamos 6 casos de tirotoxicose por T4, doenca caracterizada por tirotoxicose acompanhada de valores elevados de T4 e niveis normais de T3. Em 5 episodios, o hipertiroidismo estava associado a doenca sistemica grave (insuficiencia respiratoria por doenca pulmonar obstrutiva cronica, arteriosclerose obliterante, politraumatismo com perfuracoes intestinais, carcinomatose generalizada e arritmia cardiaca), enquanto que o paciente restante estava sendo medicado com propranolol, droga bloqueadora da conversao periferica de T4 a T3. Esses dados indicam que a tirotoxicose por T4 nao e uma forma especial de hipertiroidismo, mas reflete apenas uma alteracao do metabolismo periferico do T4 induzido pelas doencas sistemicas associadas ou por drogas

HbA1: metodologia, fatores de erro, padronizacao de valores normais e niveis encontrados em diabeticos. / HbA1: methodology, error factors, normal values standardization and levels in diabetics

O presente trabalho descreve uma metologia para dosagem da HbA1,(a+b+c) baseada em cromatografia em coluna com resina de troca ionica. Discute os fatores criticos de erro, avaliando ainda a possivel influencia da idade, sexo, obesidade e gestacao no nivel da HbA1. Foram padronizados os valores normais em individuos com TOTG normal. Os dados demonstram que os valores normais variam de 5,5 a 9,5%, nao havendo influencia do sexo, peso corporeo, faixa etaria e gestacao. Foram tambem estudados os niveis de HbA1 em pacientes diabeticos insulino-dependentes e insulino-independentes