The characteristics of blood glucose fluctuations in patients with fulminant type 1 diabetes mellitus in the stable stage

ABSTRACT Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). Subjects and methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. Conclusion: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.

Etiologia da hiperglicemia em crianças críticas e o impacto da disfunção de órgãos / Etiology of hyperglycemia in critically ill children and the impact of organ dysfunction

RESUMO Objetivo: Verificar a incidência da hiperglicemia de estresse em crianças em condição grave e investigar a etiologia da hiperglicemia com base em um modelo de avaliação da homeostasia. Métodos: Estudo prospectivo de coorte, conduzido em uma unidade de terapia intensiva pediátrica da Cairo University, que incluiu 60 crianças com doença grave e 21 controles saudáveis. Utilizaram-se os níveis séricos de glicose, insulina e peptídeo C, avaliados em até 24 horas após a admissão. O modelo de avaliação da homeostasia foi utilizado para analisar a função das células beta e a sensibilidade à insulina. Resultados: A hiperglicemia foi estimada em 70% dos pacientes. Valores de glicemia ≥ 180mg/dL se associaram com desfechos piores. Os níveis de glicemia se correlacionaram de forma positiva com o Pediatric Risk for Mortality (PRISM III) e o número de órgãos com disfunção (p = 0,019 e p = 0,022, respectivamente), enquanto os níveis de insulina se correlacionaram de forma negativa com o número de órgãos com disfunção (r = -0,33; p = 0,01). O modelo de avaliação da homeostasia revelou que 26 (43,3%) das crianças em condições graves tinham baixa função de células beta e 18 (30%) baixa sensibilidade à insulina. Detectou-se patologia combinada em apenas dois (3,3%) pacientes. Baixa função de células beta se associou de forma significante com a presença de disfunção de múltiplos órgãos, disfunção respiratória, cardiovascular e hematológica, e presença de sepse. Conclusões: A disfunção de células beta pareceu ser prevalente em nossa coorte e se associou com disfunção de múltiplos órgãos.

ABSTRACT Objective: This study aimed to study the incidence of stress hyperglycemia in critically ill children and to investigate the etiological basis of the hyperglycemia based on homeostasis model assessment. Methods: This was a prospective cohort study in one of the pediatric intensive care units of Cairo University, including 60 critically ill children and 21 healthy controls. Serum blood glucose, insulin, and C-peptide levels were measured within 24 hours of admission. Homeostasis model assessment was used to assess β-cell function and insulin sensitivity. Results: Hyperglycemia was estimated in 70% of patients. Blood glucose values ≥ 180mg/dL were associated with a poor outcome. Blood glucose levels were positively correlated with Pediatric Risk for Mortality (PRISM III) score and number of organ dysfunctions (p = 0.019 and p = 0.022, respectively), while insulin levels were negatively correlated with number of organ dysfunctions (r = −0.33, p = 0.01). Homeostasis model assessment revealed that 26 (43.3%) of the critically ill patients had low β-cell function, and 18 (30%) had low insulin sensitivity. Combined pathology was detected in 2 (3.3%) patients only. Low β-cell function was significantly associated with the presence of multi-organ dysfunction; respiratory, cardiovascular, and hematological dysfunctions; and the presence of sepsis. Conclusions: β-Cell dysfunction appeared to be prevalent in our cohort and was associated with multi-organ dysfunction.

Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene – KCNJ11:c1001G>7 (p.Gly334Val) – and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

An insulinoma with an aberrant feeder from the splenic artery detected by super-selective arterial calcium stimulation with venous sampling

No abstract available.

The association of vitamin D deficiency with non-alcoholic fatty liver disease

OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl). CONCLUSIONS: In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed. .

Hiperinsulinismo endógeno: dois desafios diagnósticos / Endogenous hyperinsulinism: two diagnostic challenges

A hipoglicemia em um adulto aparentemente saudável é um achado raro na prática clínica que exige uma investigação exaustiva da causa. A identificação de glicemia plasmática diminuída associada a concentrações plasmáticas de insulina e peptídeo-C não suprimidos deverá levar à exclusão de causas raras de hipoglicemia, entre elas, doença das células betapancreáticas e hipoglicemia autoimune. Neste artigo, descrevemos dois casos de hipoglicemia associada a hiperinsulinismo endógeno, cujas causas são pouco habituais na prática clínica. A propósito desses casos clínicos revemos aspectos importantes de diagnósticos e tratamento da hipoglicemia no contexto de hiperinsulinismo endógeno.

Hypoglycemia in apparently healthy adults is a rare finding in clinical practice requiring a thorough investigation of the cause. During the investigation, identification of hypoglycemia associated with inappropriately high levels of insulin and C-peptide should prompt the exclusion of rare causes of hypoglycemia, including pancreatic islet-cells disease and autoimmune hypoglycemia. In this paper, we describe two cases of hypoglycemia associated with endogenous hyperinsulinism, whose causes are uncommon in clinical practice, and review important aspects of the diagnosis and treatment of hyperinsulinemic hypoglycemia.

Factors associated with hyperglycemia and low insulin levels in children undergoing cardiac surgery with cardiopulmonary bypass who received a single high dose of methylprednisolone

OBJECTIVES: Administering steroids before cardiopulmonary bypass in pediatric heart surgery modulates systemic inflammatory response syndrome and improves postoperative recovery. However, the use of steroids aggravates hyperglycemia, which is associated with a poor prognosis. Adult patients with systemic inflammatory response syndrome usually evolve with hyperglycemia and high insulin levels, whereas >90% of pediatric patients exhibit hyperglycemia and low insulin levels. This study aims to determine: A) the metabolic and inflammatory factors that are associated with hyperglycemia and low insulin levels in children who underwent cardiac surgery with cardiopulmonary bypass and who received a single high dose of methylprednisolone and B) the best predictors of insulin variation using a mathematical model. METHODS: This preliminary study recruited 20 children who underwent heart surgery with cardiopulmonary bypass and received methylprednisolone (30 mg/kg) immediately after anesthesia. Among the 20 patients initially recruited, one was excluded because of the absence of hyperglycemia and lower insulin levels after surgery. However, these abnormalities were confirmed in the remaining 19 children. The C-peptide, CRP, IL-6, and adrenomedullin levels were measured before surgery, immediately after cardiopulmonary bypass, and on the first, second, and third days after cardiac surgery. RESULTS: IL-6, CRP, and adrenomedullin increments were observed, whereas the C-peptide levels remained within reference intervals. CONCLUSION: The multiple regression model demonstrated that in addition to age and glycemia (two well-known factors that are directly involved in glucose metabolism), adrenomedullin and IL-6 levels were independent factors associated with lower insulin concentrations. These four parameters were responsible for 64.7% of the observed insulin variances. In addition, the fact that C-peptide levels did not fall together with insulin could have grounded the medical decision not to administer insulin to patients.

The Clinical Measures Associated with C-peptide Decline in Patients with Type 1 Diabetes over 15 Years

This study was done to characterize the natural course of C-peptide levels in patients with type 1 diabetes and identify distinguishing characters among patients with lower rates of C-peptide decline. A sample of 95 children with type 1 diabetes was analyzed to retrospectively track serum levels of C-peptide, HbA1c, weight, BMI, and diabetic complications for the 15 yr after diagnosis. The clinical characteristics were compared between the patients with low and high C-peptide levels, respectively. The average C-peptide level among all patients was significantly reduced five years after diagnosis (P < 0.001). The incidence of diabetic ketoacidosis was significantly lower among the patients with high levels of C-peptide (P = 0.038). The body weight and BMI standard deviation scores (SDS) 15 yr after diagnosis were significantly higher among the patients with low C-peptide levels (weight SDS, P = 0.012; BMI SDS, P = 0.044). In conclusion, C-peptide level was significantly decreased after 5 yr from diagnosis. Type 1 diabetes patients whose beta-cell functions were preserved might have low incidence of diabetic ketoacidosis. The declines of C-peptide level after diagnosis in type 1 diabetes may be associated with changes of body weight and BMI.

Hypoglycemic effects of date seed extract. Possible mechanism of action, and potential therapeutic implications

To investigate the possible mechanism, by which an extract from date seeds exert its hypoglycemic effect. This study was performed at the Anatomy Department, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia from May to December 2012. Eighty rats were divided into 4 groups. Group 1 received no treatment. Group 2 received daily ingestions of 10 ml of date seed extract for 8 weeks. Animals of groups 3 and 4 were made diabetic by streptozotocin injection, and were given daily subcutaneous injections of 3 IU/day of insulin for 8 weeks. Group 4 received, in addition, daily ingestions of 10 ml of seed extracts. Rats were sacrificed, and the sera were separated for estimation of serum C-peptide levels. Pancreatic tissues were processed for histological study of the islet cells, immunohistochemical study for insulin secretion and image analysis for insulin quantification. Mean serum C-peptide level was significantly higher in group 4 compared to group 3. Pancreatic islets from rats of group 3 showed weak immunoreactivity for insulin, while those of group 4 showed strong immunoreactivity in some hypertrophied beta cells. Immunopositive cells were detected in the wall of interlobular ducts and in centroacinar cells of pancreas only in group 4. Quantification of insulin immunoreactivity showed a marked reduction in islet size and extent of insulin immunoreactivity in diabetic compared to control groups. Date seed extracts may stimulate endogenous insulin secretion through extra-islet sources

Associations between Hemoglobin Concentrations and the Clinical Characteristics of Patients with Type 2 Diabetes

BACKGROUND/AIMS: Many studies have demonstrated an association between hemoglobin levels and cardiovascular disease in diabetic patients. The aim of this study was to determine whether there is an association between hemoglobin concentrations and various clinical parameters, including metabolic factors, plasma C-peptide response after a meal tolerance test, and microvascular complications, in Korean patients with type 2 diabetes. METHODS: In total, 337 male patients with type 2 diabetes were recruited. All subjects were subjected to a meal tolerance test and underwent assessment of hemoglobin levels, fasting and postprandial beta-cell responsiveness, and microvascular complications. RESULTS: Patients with lower hemoglobin concentrations had a longer duration of diabetes, a lower body mass index, and lower concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. They also had lower levels of postprandial C-peptide, Delta C-peptide, and postprandial beta-cell responsiveness. They had a higher prevalence of retinopathy and nephropathy. In multivariate analyses, there was a significant association between nephropathy and hemoglobin concentration. Also, hemoglobin concentrations were independently associated with Delta C-peptide levels and postprandial beta-cell responsiveness. CONCLUSIONS: Hemoglobin concentrations are associated with postprandial C-peptide responses and diabetic nephropathy in patients with type 2 diabetes.

Two Novel Insulin Receptor Gene Mutations in a Patient with Rabson-Mendenhall Syndrome: The First Korean Case Confirmed by Biochemical, and Molecular Evidence

Rabson-Mendenhall syndrome (RMS) is a rare syndrome manifested by extreme insulin resistance with hyperinsulinemia, acanthosis nigricans, tooth dysplasia and growth retardation. Our patient was first noted at the age of 8 months due to pigmentations on skin-folded areas. Initial laboratory tests showed normal fasting glucose (69 mg/dL). Fasting insulin level was severely elevated, up to 554.6 microIU/mL, and c-peptide level was increased, up to 13.81 ng/mL. However, hemoglobin A1c was within normal range (4.8%). He is now 11 yr old. His growth development followed the 5-10th percentile and oral hypoglycemic agents are being administered. The last laboratory results showed insulin 364.1 microIU/mL, C-peptide 4.30 ng/mL, and hemoglobin A1c 7.6%. The boy was a compound heterozygote for the c.90C > A and c.712G > A mutations of the insulin receptor gene, INSR, which are nonsense and missense mutations. In summary, we report the first Korean case of RMS, which was confirmed by two novel mutations of the INSR.

Parameters Measuring Beta-Cell Function Are Only Valuable in Diabetic Subjects with Low Body Mass Index, High Blood Glucose Level, or Long-Standing Diabetes

PURPOSE: The aim of this study was to identify the most precise and clinically practicable parameters that predict future oral hypoglycemic agent (OHA) failure in patients with type 2 diabetes, and to determine whether these parameters are valuable in various subgroups. MATERIALS AND METHODS: We took fasting blood samples from 231 patients for laboratory data and standard breakfast tests for evaluation of pancreatic beta-cell function. Hemoglobin A1c (HbA1c) levels were tested, and we collected data related to hypoglycemic medications one year from the start date of the study. RESULTS: Fasting C-peptide, postprandial insulin and C-peptide, the difference between fasting and postprandial insulin, fasting beta-cell responsiveness (M0), postprandial beta-cell responsiveness (M1), and homeostasis model assessment-beta (HOMA-B) levels were significantly higher in those with OHA response than in those with OHA failure. The area under the curve (AUC) of the receiver operating characteristic (ROC) measured with postprandial C-peptide to predict future OHA failure was 0.720, and the predictive power for future OHA failure was the highest of the variable parameters. Fasting and postprandial C-peptide, M0, and M1 levels were the only differences between those with OHA response and those with OHA failure among diabetic subjects with low body mass index, high blood glucose level, or long-standing diabetes. CONCLUSION: In conclusion, postprandial C-peptide was most useful in predicting future OHA failure in type 2 diabetic subjects. However, these parameters measuring beta-cell function are only valuable in diabetic subjects with low body mass index, high blood glucose level, or long-standing diabetes.

Effect of chronic exposure to sulphur dioxide vapour and sulphur related compounds on serum levels of insulin, glucose, C-peptid, and zinc

Sulphur dioxide is emitted from the superphosphate factory in mankabad, Assiut province, Egypt with the possibility of environmental pollution, 28 male workers exposed to sulphur dioxide were included in the study, their ages ranged between 26 and 55years,the control insulin, C-peptide, Zinc levels and alkaline phosphatase. Workers of the exposed group had fasting blood glucose, insulin, C-peptide, serum zinc and alkaline phosphatase, level that were higher than control. Exposed group has hyperglycemina. Hyperglycemina, although their insulin levels and C-peptide are within the international rang

Hypoglycemic and anti apoptotic effect of garlic in streptozotocin induced diabetic rats

Diabetes mellitus is caused by many factor include oxidative stress that leads to apoptosis of beta cells of the pancreas and so the antioxidant therapy strongly correlated with decrease risk of diabetes mellitus. The aim of the present study was to investigate the efficacy of an aqueous extract of raw garlic in controlling serum glucose, plasma c peptide of insulin, level of reduced glutathione and catalase activity in pancreatic tissue, also to estimate caspase 3 activity expression in pancreatic tissue in streptozotocin induced diabetic rats treated daily with garlic extract intraperitoneally [IP] for 6 weeks. This study was carried on 30 rats: grouped into 3 group. Group 1, the control normal group, was injected IP daily with 0.5 ml saline and group 2; diabetic group was injected with streptozotocin, 60 mg/Kg body weight [BWt] IP in 0.5 ml saline once and group 3; garlic-treated group, was injected IP daily with 500 mg/kg of the garlic extract 2 weeks before streptozotocin and 4 week after streptozotocin injection. There was a significant increase in blood glucose in streptozotocin group II [p = 0.001] as compared with control groups [331.3 +/- 16.15 vs 101.8 +/- 4.02 mg/dl] respectively and significantly decreased after treatment with garlic extract [161.5 +/- 5.28 mg/dl]. C peptide was significantly decreased in streptozotocin group II [p = 0.001] as compared with control groups [0.034 +/- 0.003 vs 0.053 +/- 0.001 ng/ml] respectively and significantly increased after treatment with garlic extract [0.046 +/- 0.003]. Catalase activity of pancreatic tissue was significantly decreased in streptozotocin group [p = 0.001] as compared with control groups [11.10 +/- 0.73 vs 25.7 +/- 0.55 U/gm tissue] respectively and significantly increased after treatment with garlic extract [20.3 +/- 0.66]. Reduced glutathione content of pancreatic tissue was significantly decreased in streptozotocin group [p = 0.001] as compared with control groups [0.67 +/- 0.055 vs 1.23 +/- 0.076 mg/g tissue] respectively and significantly increased after treatment with garlic extract [0.89 +/- 0.080 mg/g tissue]. Also it was observed that the expression of caspase 3 protein in the pancreatic tissue was decreased after garlic treatment using western blot technique. These results revealed that aqueous extract of raw garlic may have antioxidant and antiapoptotic activity that could be used in treatment of diabetes mellitus

Influence of serum cortisol levels on glycemic control in children with type 1 diabetes

The association between plasma glucose [PG], HbAlc and serum cortisol levels in children with type 1 diabetes was investigated to determine the influence of serum cortisol on their glycemic control. A total of 45 children, aged 10-15 years, with type 1 diabetes for at least 3 years of diabetes were studied. Most of them did not have pancreatic beta-cell function. The cortisol levels among all patients were stratified according to fasting plasma glucose levels [50-99, 100-199, 200-299, and >/= 300mg/dL], and the HbAlc levels [<7.0, 7.0-7.9, 8.0-8.9, and >/= 9%]. The mean fasting PG, HbAlc and serum cortisol levels were 174 +/- 97mg/dL, 7.7 +/- 1.3% and 23.04 +/- 16.6 ug/dl, respectively. The cortisol levels were highly correlated with PG levels [r =0.553, P<0.0001] and mildly correlated with HbAlc levels [r = 0.301, P =0.0192]. Patients with high PG levels gave significantly higher cortisol levels as compared to those with lower PG levels [18.4 +/- 7.3, 26.8 +/- 18.3, 31.4 +/- 17.0 and 36.3 +/- 17.2ug/dl, P =0.0009]. There were no significant differences in serum cortisol levels among patients stratified according to HbAlc levels [P = 0.1566], however, patients with HbAlc levels >/= 9% had significantly higher cortisol levels than those with HbAlc levels <7% [32.6 +/- 14.4 vs. 21.8 +/- 11.3ug/dl,P=0.0291]

Classificação do diabete melito / Diabetes mellitus classification

A correta classificação do diabete melito (DM) permite o tratamento mais adequado e compreende quatro categorias: DM tipo 1; DM tipo 2; Outros tipos e Diabete Gestacional. Em alguns casos, pode ocorrer sobreposição de quadros, principalmente no DM que inicia no adulto jovem ou que se apresenta inicialmente com cetoacidose, intermediários ao DM 1 e DM 2. Assim, acréscimos ao sistema de classificação clássico têm sido propostos, avaliando a presença de autoimunidade (anticorpos) e a função de célula β (peptídeo-C) para definir mais precisamente os subtipos. O objetivo desta revisão foi de analisar o desempenho desses índices diagnósticos para a classificação do DM e descrever os subtipos em detalhe. Os anticorpos contra o pâncreas evidenciam a autoimunidade, sendo o anticorpo contra insulina o mais acurado antes dos 5 anos de idade e o anti-descarboxilase do ácido glutâmico para início da doença acima dos 20 anos, é esse o teste que permanece positivo por mais tempo. Já a medida do peptídeo-C avalia a reserva pancreática de insulina, e os métodos de estímulo mais usados são a medida após refeição ou após glucagon endovenoso. Valores de peptídeo-C < 1,5 ng/ml definem o paciente com função pancreática ausente, e acima desse valor, com função preservada. Combinando-se a presença de anticorpos (A+) dirigidos ao pâncreas e a sua capacidade secretória de insulina (β+), pode-se subdividir a classificação do DM em tipo 1A (A+β-) e 1B (A+ β-); e o DM tipo 2 em subgrupos de DM 2A (A+β+) e DM 2B (A-β+), o que permite uma classificação e tratamento mais precisos, além de abrir os horizontes para o entendimento da patogênese do DM.

The right classification for diabetes mellitus (DM) allows a more adequate treatment and comprises four categories: type 1 DM, type 2 DM, other types, and gestational diabetes. In some cases, there might be a superposition of situations, especially with regard to the DM that initiates in the young adult or is initially presented with diabetic ketoacidosis intermediately to type 1 and 2 DM. Thus, additions to the classic classification system have been proposed as assessing the presence of autoimmunity (antibody) and b cell function (C-peptide) to precisely define the subtypes. The aim of this literature review was to analyze these diagnostic indexes’ performance in the DM classification and to describe subtypes with details. The antibodies against pancreas confirm autoimmunity, and the antibody against insulin is more accurate before 5 years old, while the anti-glutamic acid decarboxylase is more accurate after 20 years old, a test which remains positive for a longer period. The measurement of C-peptide evaluates the pancreatic insulin reserve, and the most largely used methods of stimulation are the measurement after meals or after intravenous glucagon. C-peptide values < 1.5 ng/ml define a patient with absent pancreatic function and, above this value, patients with preserved function. When the presence of antibodies (A+) directed to the pancreas is combined to its insulin secretion capability (β+), it is possible to subdivide DM’s classification in type 1A (A+β-) and 1B (A+β-); and type 2A (A+β+) and 2B (A-β+), which allows a more precise classification and treatment besides opening horizons for the understanding of DM pathogenesis.

Implicações clínicas da persistência de anti-GAD positivo e peptídeo C detectável em pacientes com diabetes melito tipo 1 de longa duração / GADA persistence and detectable C peptide in patients with long standing diabetes mellitus type 1

OBJETIVO: Avaliar se anti-GAD positivo e PC detectável se correlacionam com a presença de outras doenças autoimunes, com controle glicêmico e com risco de retinopatia no diabetes melito tipo 1 (DMT1) > 3 anos de duração. PACIENTES E MÉTODOS: Cinquenta sujeitos com DMT1 foram entrevistados, realizaram fundoscopia e dosaram PC pré e pós-glucagon, HbA1C e anti-GAD. RESULTADOS: Pacientes anti-GAD+ (n = 17) apresentaram maior frequência de doenças autoimunes em relação aos demais (p = 0,02). PC detectável (n = 11) também foi associado ao aumento dessa prevalência (p = 0,03), porém nenhum dos dois parâmetros influenciou na presença de retinopatia diabética. PC detectável não influenciou no controle glicêmico (HbA1C média) (p = 0,28), porém as doses diárias de insulina foram mais baixas (0,62 vs. 0,91 U/kg/dia; p = 0,004) neste grupo. CONCLUSÃO: Apesar de não ser um marcador para outras doenças autoimunes, o anti-GAD+ parece ser não só um sinalizador de autoimunidade pancreática. PC detectável também parece ter papel promissor na detecção dessas comorbidades. Ambos não interferiram na presença de retinopatia, entretanto, o PC detectável se relacionou a menores necessidades de insulina.

OBJECTIVE: The aim of this study was to evaluate if GADA+ and detectable CP had any influence in other autoimmune diseases, glycemic control, and risks of retinopathy in diabetes mellitus type 1 (T1DM) lasting longer than 3 years of duration. SUBJECTS AND METHODS: Fifty T1DM subjects were interviewed, performed fundoscopic examination, and measured CP before and after glucagon, HbA1C, and GADA. RESULTS: GADA+ (n = 17) had a higher frequency of other autoimmune diseases when compared to GADA (p = 0.02). Detectable CP was also associated with a higher prevalence of these diseases (p = 0.03), although, retinopathy was not influenced by either one. Detectable CP had no influence in the glycemic control (mean HbA1C) (p = 0.28). However, insulin daily doses were lower in this group (0.62 vs. 0.91 U/kg/day; p = 0.004). CONCLUSION: Although not recommend as a marker of other autoimmune diseases, GADA+ seems to be not only a pancreatic autoimmunity signal. Detectable CP may also have some promising influence in detecting these diseases. Neither influenced the presence of retinopathy, but insulin daily requirements were smaller when CP was present.

Dysregulation of immune system in diabetic child

Diabetes is a chronic disease associated with selective destruction of the pancreatic B-cells. The exact etiology of the disease is unclear; however, insulin deficiency results from autoimmune destruction of B-cells. The appearance of auto antibodies to beta cell antigen, such as those against the 65-KDA isoform of glutamic acid decarboxylase GAD65 and the protein tyrosine phosphates in the peripheral circulation is a predictive sign of clinical disease in non diabetic individuals. Although GAD65 and IA-2 [insulin auto antibodies] may not be directly involved in the pathogenic processes in beta-cell destruction. They are good markers in assessing the risk of disease manifestation. This study aimed to evaluate GAD65 [glutamic acid decarboxylase] and ICA [islet cell auto antibodies] and IA-2 [insulin auto antibodies] auto antibodies as a disease markers and their relationship to certain residual beta cell function and glycemic control in type I diabetes and risk group, and assess the relation between CD4 [+] CD25 [+] [T-regulatory cells] and immune mediated diabetes. This study was conducted on 50 subjects randomly selected from those attending pediatrics outpatients clinics in the period of 2008. The subjects were classified into 3 groups: 1-Group A [patient group]: This group included 20 patients diagnosed as type I DM according to WHO classifications. Their ages ranging from 3-16 years with a mean age of 10.6 +/- 4.0. They were 11 males and 9 females. 2-Group B: [Risk group]: included 20 sibling of diabetic [type I DM] father, mother or both. They were 9 females and 11 males their ages ranging from 18 years to 25 years with a mean of age 21 +/- 2.5. 3-Group C: Control group, included 10 healthy children; they were 5 females and 5 males, their ages ranging from 5-16 years with a mean age of 10.8 +/- 2.8, with no family history of diabetes mellitus. All subjects are subjected to: Complete history taking, Full clinical examination, Complete blood picture, Glycosylated Hb using ion-exchane chromatography, C-peptide of insulin by-ELISA, determination of GAD 65, ICA and IA-2 auto antibodies by ELISA technique, Flowcytometric measurement of the expression of the CD4 [+] /CD25 [+] of T-regulatory cell. The most frequently encountered antibody in children group was GAD65 in 60% of cases, followed by ICA, 40%. When taken together, both GAD65 and ICA were detected in 30%. IA-2 was detectable only in 30% of cases. When both GAD65 and IA-2 were taken together, they were detected in 25% of cases also ICA and IA-2 were detected in 15% of cases. When GAD, ICA and IA-2 were taken together, they were detectable in 5% of cases. The most frequently encountered antibody in risk group was ICA in 15% of cases, followed by GAD, in 10%. When taken together, both GAD65 and ICA were detected in 10%. IA-2 was detectable only in 10% of cases. When both GAD65 and IA-2 were taken together. they were detected in 5% of cases also ICA and IA-2 were detected in 15% of cases. When GAD, ICA and IA-2 were taken together, they were detectable in 5% of cases. There was highly significant difference between 3 groups for prevalence of GAD65 autoantibody [p<0.001] and significant difference between 3 groups for prevalence of ICA autoantibody [p<0.005] and significant difference between 3 groups for prevalence of IA-2 autoantibody [p<0.003]. There were highly significant differences in the level of fasting C-peptide of insulin between patient and control groups. [p value<0.001]. There were significant difference between level of fasting Cpeptide and single and multiple autoantibody positivity [p<0.05]. In the children group the mean and SD of the percentage of CD4 [+] CD25 [+] from CD4 cells were 0.96, 0.46 respectively. In the control group the mean and SD of the percentage of CD4 [+] CD25 [+] from CD4 cells were 2.85, 0.92 respectively. The difference between control and study group according to the mean and SD of the percentage of CD4 [+] CD25 [+] from CD4 cells was statistically highly significant [p<0.001]. In the Risk group the mean and SD of the percentage of CD4 [+] CD25 [+] from CD4 cells were 0.99, 0.7 respectively. In the control group the mean and SD of the percentage of CD4 [+] CD25 [+] from CD4 cells were 2.96, 0.62 respectively. The difference between control and risk group according to the mean and SD of the percentage of CD4 [+] CD25 [+] from CD4 cells was statistically non significant. There was highly sig relation [p<0.001] between percent of CD4 [+] CD25 [+] out of CD4 cells and the presence and absence of auto antibodies in the children group. There was no sig relation between percent of CD4 [+] CD25 [+] out of CD4 cells and the presence and absence of auto antibodies in the in risk group. At the time of diagnosis almost all patients with type I diabetes have auto antibodies that are reactive to islet antigens and auto antibodies GAD, ICA, lA-2 are of' value for predicting IDDM in sibling of diabetic parents type I also CD4[+] CD25[+]T-regulatory cells actively suppress activation of the immune system and prevent pathological self-reactivity

A study on clinical and biochemical profile of low body weight type 2 diabetes mellitus.

Low body weight type2 diabetes mellitus (T2DM) is a distinct entity in T2DM having different clinical presentation, morbidity and mortality patterns as well as biochemical profile when compared with classical T2 DM. This study was aimed at comparing three subtypes of T2 DM-overweight (BMI>25), normal weight (BMI>18.5 but <25) and low body weight or lean type2 DM (BM1<18.5). Seventy-five cases of T2 DM (25-lean, 25-normal weight and 25-overweight) were selected. The present study revealed that normal C-peptide level with basal hyperglycaemia is an important characteristic of lean T2 DM. Lower prevalence of hypercholesterolaemia and higher level of triglycerides were found in low body weight T2 DM.Lower prevalence of macrovascular and higher prevalence of microvascular complications are also noted.