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1.
Folia Histochem Cytobiol ; 57(2): 74-83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31187872

RESUMO

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease which becomes a rapidly growing health problem in the Western countries. The development of the disease is most often connected to obesity. NAFLD is also considered as the hepatic manifestation of metabolic syndrome. Transforming growth factor b1 (TGF-b1) plays an important role in the pathogenesis of liver fibrosis, being involved in activation of hepatic stellate cells, stimulation of collagen gene transcription, and suppression of matrix metalloproteinase expression. The objective of the study was to evaluate by immunohistochemistry the expression of TGF-b1 in the liver tissue of NAFLD patients and correlate it with anthropometric, biochemical and routine histological parameters. MATERIAL AND METHODS: The study group consisted of 48 patients with diagnosed NAFLD. Liver steatosis, NAFLD Activity Score (NAS) and METAVIR score of fibrosis were evaluated in liver biopsies. The immunoreactivity of TGF-b1 was evaluated semi-quantitatively separately in portal, septal, lobular hepatocytic and lobular sinu-soidal liver compartments. The results were analyzed in regard to patients' clinical and biochemical parameters. RESULTS: Neither steatosis nor NAS correlated with TGF-b1 expression in any liver compartment, whereas METAVIR score of fibrosis was associated with increased immunoreactivity of TGF-b1 in most of the studied liver compartments. TGF-b1 immunoreactivity showed positive correlation with patients' age and its expression in septal compartment disclosed positive correlation with body mass index, and waist and hip circumference. Hyaluronic acid serum level was positively and iron concentration was negatively associated with TGF-b1 ex-pression in the selected consecutive liver compartments. CONCLUSIONS: The immunohistochemical expression of TGF-b1 may be complementary to routine methods of liver fibrosis evaluation.


Assuntos
Cirrose Hepática/imunologia , Fígado/imunologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Fator de Crescimento Transformador beta1/imunologia , Adulto , Peptídeo C/sangue , Fígado Gorduroso/patologia , Feminino , Hemoglobina A Glicada/análise , Haptoglobinas/análise , Humanos , Ácido Hialurônico/sangue , Imuno-Histoquímica , Ferro/sangue , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Fator de Crescimento Transformador beta1/sangue
2.
Crit Care Resusc ; 21(2): 87-95, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142238

RESUMO

OBJECTIVE: To assess the effects of sepsis and exogenous insulin on C-peptide levels and C-peptide to insulin ratios in intensive care unit (ICU) patients with type 2 diabetes mellitus (T2DM). DESIGN, SETTING AND PARTICIPANTS: In this prospective, observational, single-centre study, we enrolled 31 ICU-admitted adults with T2DM. We measured serum C-peptide and insulin levels during the first 3 days of ICU stay and recorded characteristics of exogenous insulin therapy. Patients were compared on the basis of the presence of sepsis, and their exposure to exogenous insulin therapy. C-peptide levels were also measured in eight healthy subjects. MAIN OUTCOME MEASURES: Serum insulin and C-peptide levels during the first 3 days in ICU. RESULTS: Median C-peptide levels were higher in the ICU population compared with healthy subjects (10.9 [IQR, 8.2 -14.1] v 4.8 [IQR, 4.6-5.1] nmol/L, P < 0.01). Sepsis was present in 25 ICU patients (81%). Among ICU patients unexposed to exogenous insulin, the 11 patients with sepsis had higher median C-peptide levels compared with the six non-septic patients (2.5 [IQR, 1.8-3.7] v 1.7 [IQR, 0.8-2.2] nmol/L, P = 0.04), and a threefold higher C-peptide to insulin ratio (45 [IQR, 37-62] v 13 [IQR, 11-17], P = 0.03). However, septic patients exposed to exogenous insulin had lower median C-peptide levels (1.2 [IQR, 0.7-2.3] nmol/L, P = 0.01) and C-peptide to insulin ratios (5 [IQR, 2-10], P < 0.01) compared with insulin-free septic patients. The C-peptide to insulin ratio was significantly associated with white cell count and severity of illness in insulin-free septic patients. CONCLUSION: C-peptide levels were elevated in critically ill patients with T2DM. In this population, sepsis increased C-peptide levels and uncoupled serum C-peptide and insulin levels. Exogenous insulin decreased both C-peptide levels and C-peptide to insulin ratios.


Assuntos
Peptídeo C/sangue , Estado Terminal , Diabetes Mellitus Tipo 2/complicações , Insulina/sangue , Unidades de Terapia Intensiva , Sepse/sangue , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Estudos Prospectivos , Sepse/etiologia
3.
Diabetes Res Clin Pract ; 152: 53-57, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31063857

RESUMO

BACKGROUND: T1DM is divided into 1A (immune-mediated), 1B (virus-triggered, genetic and idiopathic). Presence of auto-antibodies may be correlated to glycemic control. AIM: Assessment relation between the autoantibodies and the poor glycemic control in T1DM. METHODS: 60 patients T1DM 30 males, 30 females, subjected to full history, clinical, anthropometric assessment and laboratory assessment of fasting C-peptide, FBS, 2 h PP glucose, HbA1c, GADA, ICA and IAA level. Classified into two groups; Group I: negative auto-antibodies, Group II: positive auto-antibodies, Group II was further classified into 3 sub-groups, Group II a:1 positive autoantibody, Group II b: 2 positive autoantibodies and Group II c: 3 positive autoantibodies. RESULTS: HbA1c was significantly higher in group II than group I (11.85 ±â€¯1.61% vs. 8.52 ±â€¯0.41%, p = 0.000). HbA1c was highest in group IIc followed by IIb then IIa (12.25 ±â€¯1.48% vs. 11.57 ±â€¯1.59% vs. 10.78 ±â€¯1.73%, p = 0.038). Total insulin units per day was significantly higher in group II than group I (109.83 ±â€¯7.77 U/day vs. 100.83 ±â€¯1.83 U/day, p = 0.007). Duration of diabetes was significantly higher in group I than group II (10.17 ±â€¯1.94 years vs. 8.11 ±â€¯2.20 years, p = 0.033). HbA1c, total insulin units per day and duration of diabetes were independent predictive factors for presence of autoantibodies (p = 0.007, p = 0.033 and p = 0.043 respectively). CONCLUSION: Autoantibodies affect the glycemic control presented by high HbA1c; also it causes increase in total insulin units needed by patients; the more autoantibodies, the higher HbA1c, the more insulin units required to control glycemic state.


Assuntos
Autoanticorpos/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Adolescente , Adulto , Autoanticorpos/imunologia , Peptídeo C/sangue , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Egito/epidemiologia , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Insulina/imunologia , Anticorpos Anti-Insulina/sangue , Masculino , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/imunologia , Adulto Jovem
4.
Wiad Lek ; 72(4): 584-588, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055537

RESUMO

OBJECTIVE: Introduction: Atherosclerosis is a trigger in the development of cardiovascular disease. Complications of atherosclerosis give reason to search for new criteria, diagnostic concepts, treatment methods and active preventive measures. The aim of our work is to study of the structural changes in the intima-media complex of the common carotid artery, pro-inflammatory cytokines (TNF-α, IL-6) secreted by mononuclear cells; the level of the intercellular adhesion molecule (according to sICAM-1), the level of the C-peptide of the blood, as well as the study of the relationship between these factors affecting the development of atherosclerosis. PATIENTS AND METHODS: Materials and methods: In the group of 110 patients are studied the levels of secretion of TNF-α, IL-6, the soluble intercellular adhesion molecule-1, the level of blood C-peptide, performed of duplex scanning of the brachiocephalic vessels, studied of biopsy of the skin. RESULTS: Results and conclusions: In the group of patients with atherosclerosis and the accompanying metabolic syndrome, endothelial activation is noted under the influence of risk factors (hyperinsulinemia, arterial hypertension, hypercholesterolemia), accompanied with the activation of mononuclear cells (with marked hyperproduction of proinflammatory cytokines (IL-6) and thickening of the intima-media complex of the common carotid artery with an increase in body weight. Patients with metabolic syndrome develop microangiopathy (edema of endothelial cells, thickening and reduplication of the basement membranes, focal reaction of the pericytes).


Assuntos
Aterosclerose/patologia , Peptídeo C/sangue , Leucócitos Mononucleares/metabolismo , Aterosclerose/metabolismo , Biomarcadores , Artérias Carótidas , Espessura Intima-Media Carotídea , Citocinas/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Túnica Íntima
5.
J Pediatr Endocrinol Metab ; 32(5): 447-454, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31042641

RESUMO

Background Too much consumption of carbonated beverages increases the risk of diabetes. Insulin deficiency and the body's decreased sensitivity to insulin cause diabetes. C-peptide can assess a person's own insulin secretion. The decrease of C-peptide is closely related to the occurrence of diabetes and its chronic complications. The present study assessed the effect of carbonated beverages on C-peptide in adolescents and analyzed the correlation between C-peptide and the drinking index (DI). Methods The subjects investigated including 463 adolescents were divided into a carbonated beverages group, a non-carbonated beverages group and a control group. The general demographic characteristics, beverage consumption status, physical activity and family history of hypertension and diabetes were interviewed with a questionnaire designed by us. All the subjects maintained their original lifestyle and received the oral glucose tolerance test. Various biochemical indicators and C-peptides were detected in these three groups. The data were analyzed by statistical analysis, and multivariate logistic regression analysis was used to examine the risk factors related to C-peptide. Results Blood glucose, blood lipid, liver function and renal function had no statistically significant difference among the three groups. C-peptide levels were lower in the carbonated beverages group and the non-carbonated beverages group than in the control group. Compared to the non-carbonated beverages group, there was a significant decrease in C-peptide levels in the carbonated beverages group. Logistic analysis demonstrated that DI was negatively correlated with C-peptide levels when the physical activity was adjusted. The odds ratio (OR) (OR = 2.540, 95% confidence interval [CI] 1.121-5.752) value difference was statistically significant at a stratification level of DI ≥ 6. Conclusions The C-peptide of adolescents was affected by the long-term consumption of beverages, and the effect of carbonated beverages was even more obvious. DI ≥ 6 bottle-years was a risk factor for diabetes, and we can constitute prevention and control measures accordingly so as to reduce the incidence of diabetes.


Assuntos
Peptídeo C/sangue , Bebidas Gaseificadas/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Adolescente , Adulto , Estudos de Casos e Controles , Diabetes Mellitus/sangue , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Fatores de Risco , Adulto Jovem
6.
Saudi Med J ; 40(4): 353-359, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30957128

RESUMO

OBJECTIVES: To investigate the cord blood levels of adipokine and to assess their association with the fetal insulin resistance and fetal outcomes in newborns of gestational diabetic women (GDM). Methods: This cross-sectional study was performed in 40 GDM women and 40 healthy pregnant women (HPW) in the Department of Obstetrics and Gynecology at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) hospital in Puducherry, India, during the period from May 2016 to December 2017. Cord blood samples were collected at delivery from GDM and HPW groups. Cord plasma biochemical parameters such as insulin, C-peptide, adiponectin, leptin, resistin, and visfatin concentrations were measured. Leptin/adiponectin ratio (L/A), homeostasis model assessment of insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-%S) and beta cell function (HOMA2-%B) were calculated. The pregnancy outcomes such as birth weight (BW), Ponderal index and Apgar scores of the baby were measured. Results: The BW and Ponderal index of the baby were found to be significantly higher in GDM newborns compared to HPW newborns. Cord plasma insulin, C-peptide, HOMA2 -IR, visfatin, leptin, and L/A ratio were significantly higher whereas adiponectin level was lower in GDM compared to HPW. A significant positive correlation was observed between L/A ratio and fetal HOMA2-IR. Conclusion: Altered adipokine levels with increased L/A ratio was observed among the new-borns of Indian gestational diabetic mothers. There was an association between increased L/A ratio, insulin resistance and increased Ponderal index among the new-borns.


Assuntos
Adipocinas/sangue , Diabetes Gestacional/sangue , Diabetes Gestacional/fisiopatologia , Sangue Fetal/metabolismo , Resistência à Insulina , Resultado da Gravidez , Índice de Apgar , Biomarcadores/sangue , Peso ao Nascer , Peptídeo C/sangue , Estudos Transversais , Diabetes Gestacional/diagnóstico , Feminino , Humanos , Índia , Recém-Nascido , Insulina/sangue , Leptina/sangue , Nicotinamida Fosforribosiltransferase/sangue , Gravidez , Resistina/sangue
7.
Int J Mol Sci ; 20(8)2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31010033

RESUMO

Fish contains high quality proteins and essential nutrients including 25-hydroxyvitamin D (25(OH)D). Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and studies have shown an association between 25(OH)D deficiency, CVD and CVD risk factors, such as diabetes. This study investigated acute effects of a single dose of cholecalciferol (VitD3), bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. A randomized, crossover, placebo controlled trial was conducted in 22 adults. They ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3 g of BPH, a combination of both, or a placebo. A 180 min oral glucose tolerance test was performed. Differences in whole-genome expression levels after versus before each supplementation were computed for 18 subjects. We observed that 16, 1 and 5 transcripts were differentially expressed post- vs. pre-ingestion for VitD3, BPH or VitD3 + BPH treatments, respectively. VitD3-containing treatments affected the expression of the solute carrier family 25 member 20 (SLC25A20) gene involved in fatty acid oxidation, various transcription factors and genes related to glucose metabolism. These results suggest that VitD3 rapidly modulates genes related to CVD risk factors in blood while BPH seems to moderately modulate gene expression levels.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos/administração & dosagem , Vitamina D/administração & dosagem , Adulto , Idoso , Animais , Glicemia/metabolismo , Peptídeo C/sangue , Estudos de Coortes , Feminino , Peixes , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Vitamina D/farmacologia , Adulto Jovem
8.
Clin Chim Acta ; 495: 210-214, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30978327

RESUMO

BACKGROUND: C-peptide and insulin are widely used in clinical practice for the diagnosis for several conditions, including hypoglycaemia and diabetes. However, the lack of method harmonization represents an important analytical limitation. Aims of this study were to evaluate new Mindray CL-2000i C-peptide and insulin methods for precision and comparability with Tosoh AIA-CL2400 and Siemens Immulite 2000 systems. METHODS: Mindray CL-2000i precision was evaluated by the CLSI EP15-A3 protocol and compared with the manufacturer's claimed values. A series of one hundred sixty-five specimens were used for comparing C-peptide and immunoreactive insulin (IRI) between Mindray CL-2000i, Tosoh AIA-CL2400 and Siemens Immulite 2000. RESULTS: Mindray CL-2000i repeatability results were 1.7% and 1.35% for C-peptide and 2.1% and 1.2% for IRI. Intermediate precisions were 2.6% and 1.4% for C-peptide and 4.6% and 2.3% for IRI. For C-peptide, Mindray CL-2000i performed similarly to Tosoh AIA-CL2400; for IRI a good agreement between Mindray C-2001 and Siemens Immulite 2000was found. CONCLUSIONS: Mindray CL-2000i shows a low imprecision while a satisfactory for IRI between Mindray 2000i and Siemens Immulite 2000 was onbserved. Overall, results emphasize the need for standardization/harmonization efforts for both C-peptide and IRI measurement.


Assuntos
Análise Química do Sangue/métodos , Peptídeo C/sangue , Insulina/sangue , Humanos , Limite de Detecção
9.
PLoS One ; 14(3): e0213255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845211

RESUMO

Adolescence is the most critical phase of human growth that radically alters physiology of the body and wherein any inconsistency can lead to serious health consequences in adulthood. The timing and pace at which various developmental events occur during adolescence is highly diverse and thus results in a drastic change in blood biochemistry. Monitoring the physiological levels of various biochemical measures in ample number of individuals during adolescence can call up for an early intervention in managing metabolic diseases in adulthood. Today, only a couple of studies in different populations have investigated blood biochemistry in a small number of adolescents however, there is no comprehensive biochemical data available worldwide. In view, we performed a cross-sectional study in a sizeable group of 7,618 Indian adolescents (3,333 boys and 4,285 girls) aged between 11-17 years to inspect the distribution of values of common biochemical parameters that generally prevails during adolescence and we observed that various parameters considerably follow the reported values from different populations being 3.56-6.49mmol/L (fasting glucose), 10.60-199.48pmol/L (insulin), 0.21-3.22nmol/L (C-peptide), 3.85-6.25% (HbA1c), 2.49-5.54mmol/L (total cholesterol), 1.16-3.69mmol/L (LDL), 0.78-1.85mmol/L (HDL), 0.33-2.24mmol/L (triglycerides), 3.56-11.45mmol/L (urea), 130.01-440.15µmol/L (uric acid) and 22.99-74.28µmol/L (creatinine). Barring LDL and triglycerides, all parameters differed significantly between boys and girls (p< 0.001). Highest difference was seen for uric acid (p = 1.3 x10-187) followed by C-peptide (p = 6.6 x10-89). Across all ages during adolescence, glycemic and nitrogen metabolites parameters varied markedly with gender. Amongst lipid parameters, only HDL levels were found to be significantly associated with gender following puberty (p< 0.001). All parameters except urea, differed considerably in obese and lean adolescents (p< 0.0001). The present study asserts that age, sex and BMI are the essential contributors to variability in blood biochemistry during adolescence. Our composite data on common blood biochemical measures will benefit future endeavors to define reference intervals in adolescents especially when the global availability is scarce.


Assuntos
Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Peptídeo C/sangue , Insulina/sangue , Lipídeos/sangue , Obesidade/fisiopatologia , Adolescente , Criança , Estudos Transversais , Jejum , Feminino , Humanos , Masculino , Fatores Sexuais , Maturidade Sexual
10.
Diabetes Res Clin Pract ; 150: 174-183, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30878389

RESUMO

AIMS: To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes. METHODS: The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996-1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation. RESULTS: In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49-3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49-4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06-2.45, p = 0.027, n = 90). CONCLUSIONS: Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death.


Assuntos
Biomarcadores/sangue , Peptídeo C/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Causas de Morte , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Acidente Vascular Cerebral , Suécia/epidemiologia , Fatores de Tempo
11.
Mol Nutr Food Res ; 63(7): e1800967, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30763457

RESUMO

INTRODUCTION: The effect of whole-grain (WG) versus refined-grain (RG) diets on glucose-stimulated insulin secretion (GSIS) and ß-cell function is unclear. METHODS: In a double-blind crossover randomized controlled trial, 13 prediabetic adults (37.2 ± 1.8 y, BMI: 33.6 ± 1.4 kg m-2 , 2 h glucose: 146.9 ± 11.6 mg dL-1 ) are provided isocaloric-matched WG and RG diets for 8-weeks each, with an 8-10 week washout between diets. Glucose, insulin, and C-peptide are studied over 240 min following a 75 g OGTT. Incretins (GLP-1 and GIP), PYY, and total ghrelin are assessed at 0, 30, and 60 min. Mixed-meal diets for carbohydrate (54%), fat (28%), and protein (18%) contain either WG (50 g/1000 kcal) or equivalent RG. RESULTS: Both diets induce fat loss (≈2 kg). While neither diet impacts early phase GSIS, the WG diet increases total GSIS (iAUC of C-peptide0-240 /Glc0-240 , p = 0.02) and ß-cell function (disposition index; GSIS × insulin sensitivity, p = 0.02). GIP and PYY are unaltered by either diet, but GLP-1 is higher at 30 min following RG versus WG (p = 0.04). Ghrelin levels are higher at 60 min of the OGTT following both interventions (p = 0.01). CONCLUSION: A WG-rich diet increases ß-cell function independent of gut hormones in adults with prediabetes.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Hormônios Gastrointestinais/sangue , Secreção de Insulina , Estado Pré-Diabético/dietoterapia , Grãos Integrais , Adulto , Peptídeo C/sangue , Dieta , Método Duplo-Cego , Feminino , Glucose/metabolismo , Humanos , Incretinas/sangue , Insulina/sangue , Masculino , Estado Pré-Diabético/metabolismo
12.
Diabetes Res Clin Pract ; 150: 1-7, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30794834

RESUMO

INTRODUCTION: Accurate dosing of medications for glycemic control is a challenge for clinicians in diabetic patients with kidney disease. Diminishing glomerular filtration rates are associated with decreased renal clearance of insulin and increased prevalence of hypoglycemic episodes. Measurement of glucose/C peptide ratios may be useful to guide dosing in those patients who receive powerful insulin secretogogues as glomerular function decreases with age and disease. METHODS: In order to determine the relationship between glucose, C-peptide and renal function, we reviewed the records of patients with type 2 diabetes followed in our kidney hypertension clinic who met the following criteria: age 35-90 years, requirement of medications to control glycemia, at least 4 simultaneous measurements of C peptide, HbA1c, creatinine and blood glucose. RESULTS: 87 patients (67 males, 20 females), ages 67.1 ±â€¯10.6 years, BMI 32.5 ±â€¯5.2, A1c 8.2 ±â€¯1.2%, eGFR 73 ±â€¯27.2 ml/min, had glucose/C-peptide ratios 60.7 ±â€¯46.4. 59% of the total group were taking insulin secretogogues. Patients were divided into groups based upon mean eGFR and use or absence of insulin secretogogues. Glucose C-peptide ratios were lowest in the quartile of patients with the lowest eGFR (<50 ml/min). CONCLUSION: Diminished renal function and advanced age are associated with the lowest glucose/C-peptide ratios, independent of achieved glycemic control. With similar use of secretogogues, glucose/C-peptide ratio were lower when eGFR was ≤49 ml/min compared to >50-80 ml/min. Use of secretogogues was associated with decreased glucose/C-peptide levels. In patients with reduced renal function (eGFR < 50 ml/min), use of insulin secretogogues may be associated with lower glucose/C-peptide ratios associated with higher risks for hypoglycemic reactions.


Assuntos
Biomarcadores/sangue , Glicemia/metabolismo , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/diagnóstico , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico
13.
Diabetes Metab Syndr ; 13(1): 708-715, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641793

RESUMO

BACKGROUND AND OBJECTIVES: We aimed to compare C-peptide levels & measures of insulin resistance in non-lean & non-obese Asian Indian patients with type 2 diabetes (T2DM) vs. non-lean, non-diabetic controls and to correlate with anthropometric measures, volumes of abdominal adipose tissue depots, pancreas, & liver span. METHODS: Non-lean, non-obese (BMI >19 and < 25 kg/m2) Asian Indian patients with T2DM, (cases n, 87), diagnosed within one year, on metformin mono therapy, were compared to BMI-matched non-diabetic subjects (controls, n, 37). Measures of glycaemia, insulin and C-peptide levels (fasting and post-prandial), lipid profile, and hepatic transaminases were analysed. Abdominal adipose tissue volumes [subcutaneous & intra-abdominal], pancreatic volume and liver span were assessed using 1.5 Tesla MRI scan. RESULTS: In cases, the mean values of HbA1c, fasting and post prandial insulin and C-peptide levels, and 3 measures of insulin resistance were significantly higher than controls, but not for HOMA-B. Higher fasting C-peptide levels correlated significantly with HOMA-IR (r = 0.42, p < 0.001), Fasting Insulin Resistance Index (r = 0.42, p < 0.001), Bennett's Index (r = 0.38, p < 0.05), and volumes of SCAT and IAAT only in cases. The independent predictors of higher fasting C-peptide level were IAAT volume (ß = 0.057; p = 0.002), liver span (ß = 0.057, p = 0.005) and fasting insulin levels (ß = 0.35, p = 0.02). CONCLUSION: Higher fasting and post-prandial C-peptide levels and surrogate measures of insulin resistance in non-obese Asian Indian patients with T2DM are independently associated with IAAT volume and liver span.


Assuntos
Distribuição da Gordura Corporal , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Fígado/patologia , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Índia , Resistência à Insulina , Masculino
14.
Mol Nutr Food Res ; 63(7): e1800959, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30636184

RESUMO

SCOPE: Ingestion of rye bread leads to lower postprandial plasma insulin concentrations than wheat bread ingestion, but most often not too different glucose profiles. The mechanism behind this discrepancy is still largely unknown. This study investigates whether glucose kinetics may explain the observed discrepancy. METHODS AND RESULTS: Nine healthy men participated in a crossover study, eating 50 g of available carbohydrates as either refined wheat (WB) or traditional wholemeal rye bread (WMR) during d-[6,6-2 H2 ]glucose infusion. Labeled glucose enrichment is measured by an HPLC-TOF-MS method. The calculated rate of glucose appearance (RaE) is significantly lower after ingestion of WMR during the initial 15 min postprandial period. Additionally, the 0-90 min RaE area under the curve (AUC) is significantly lower after ingestion of WMR, as is plasma gastric inhibitory polypeptide (GIP) at 60 and 90 min. Postprandial glycemic responses do not differ between the breads. Postprandial insulin is lower after ingestion of WMR at 45 and 60 min, as is the 0-90 min AUC. CONCLUSION: Ingestion of WMR elicits a lower rate of glucose appearance into the bloodstream compared with WB. This may explain the lower insulin response observed after rye bread ingestion, commonly known as the rye factor.


Assuntos
Glicemia/metabolismo , Pão , Insulina/sangue , Secale , Triticum , Adolescente , Adulto , Glicemia/análise , Peptídeo C/sangue , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Polipeptídeo Inibidor Gástrico/sangue , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Masculino , Espectrometria de Massas , Período Pós-Prandial/fisiologia
15.
Int J Cancer ; 145(2): 360-369, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30614528

RESUMO

Several biological mechanisms linking physical activity with cancer have been proposed. However, the influence of specific components of physical activity (volume, type and intensity), and their interaction with adiposity and diet, on cancer-related biomarkers remain unclear. We used cross-sectional data on 7,219 men in the Health Professionals Follow-up Study (1992-1994) with C-reactive protein (CRP), interleukin-6 (IL6), tumor necrosis factor alpha receptor 2 (TNFαR2), adiponectin, C-peptide and triglycerides/high-density lipoprotein cholesterol ratio (TG/HDL). Details on physical activity, diet and adiposity were assessed by questionnaires. We used multivariable-adjusted linear regression analyses to estimate relative concentrations of biomarkers by physical activity. Total physical activity was favorably associated with all biomarkers in a fairly linear manner. Comparing the highest (63+ metabolic equivalent (MET)-hr/week) to the lowest (0-8.9 MET-hr/week) physical activity groups, the percent relative difference in concentration of biomarkers was -31% for CRP, -22% for IL6, -8% for TNFαR2, +9% for adiponectin, -22% for C-peptide, and -20% for TG/HDL. These differences were modestly attenuated after adjustment for adiposity. For the same total MET-hours of physical activity, the association was stronger for men engaging in both aerobic and resistance exercises compared to those engaging in aerobic only. However, no difference was found between those engaging in vigorous activities (≥20% of total MET-hours) compared to those who did smaller amount of vigorous activities. Physical activity showed similar associations for these biomarkers regardless of adiposity and dietary pattern. In conclusion, high physical activity, preferably aerobic plus resistance training, was associated with favorable cancer-related biomarkers.


Assuntos
Biomarcadores/sangue , Exercício/fisiologia , Inflamação/sangue , Insulina/sangue , Adiponectina/sangue , Adulto , Idoso , Peptídeo C/sangue , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , Estudos Transversais , Pessoal de Saúde , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Autorrelato , Triglicerídeos/sangue
16.
Pediatr Diabetes ; 20(3): 282-285, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30652426

RESUMO

AIMS: Residual beta-cell secretion in type 1 diabetes is commonly assessed by area-under-curve of plasma C-peptide concentration (AUCCpep ) following mixed-meal tolerance test (MMTT). We aimed to investigate alternative measures of beta-cell responsiveness. METHODS: We analyzed data from 32 youth (age 7 to 17 years) undergoing MMTT within 6 months of type 1 diabetes diagnosis. We related AUCCpep with (a) validated mechanistic index of postprandial beta-cell responsiveness MI accounting for glucose level during MMTT, and (b) pragmatic marker calculated as baseline plasma C-peptide concentration corrected for baseline plasma glucose concentration. RESULTS: Postprandial responsiveness MI was correlated with age and BMI SDS (Rs = 0.66 and 0.44, P < 0.01 and P < 0.05) and was more correlated with glycated hemoglobin than AUCCpep (Rs = 0.79, P = 0.04). The pragmatic marker was highly correlated with AUCCpep (Rs = 0.94, P < 0.01). CONCLUSIONS: Postprandial responsiveness MI may be more relevant to glucose control than AUCCpep . Baseline C-peptide corrected for baseline glucose appears to be a suitable surrogate of AUCCpep if MMTT is not performed.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 1/metabolismo , Técnicas de Diagnóstico Endócrino , Secreção de Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Refeições , Adolescente , Área Sob a Curva , Glicemia/metabolismo , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Estudos de Viabilidade , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Período Pós-Prandial
17.
J Affect Disord ; 243: 70-74, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30236760

RESUMO

BACKGROUND: Depression is a seriously disabling public health problem with very high world-wide prevalence. This study examined cross-sectional association between depression and both inflammatory markers and laboratory data involved in metabolic disturbance among Japanese subjects. METHODS: This cross-sectional study is a secondly analysis for the data of the Iwaki Health Promotion Project 2014 (1167 subjects). Plasma inflammatory markers and laboratory metabolic data involved were used. Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence and severity of depressive symptoms. Participants with CES-D scores ≥ 16 were assigned to the 'Depression' group (Group D). Differences between group Non-depression (ND) and D were estimated using χ2 test or Fisher's exact test for categorical variables and Student's t-test or Mann-Whitney test for continuous variables. Multivariate logistic regression analysis was also used to identify characteristics, co-morbidities, conditions and laboratory data associated with depression after adjusting for possible confounding factors. RESULTS: There were significant differences in sex, age, blood pressure, interleukin (IL)-6, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), and cortisol level using univariate analysis between the two groups. However, multivariate logistic regression analysis indicated that lower age, lower C-peptide, and higher leptin were associated with the depression. CONCLUSION: This study showed that higher plasma leptin and lower C-peptide levels were significantly associated with depressive symptoms. No significant association was found between plasma inflammatory markers and depressive symptoms after adjusting for possible confounding factors.


Assuntos
Peptídeo C/sangue , Depressão/sangue , Leptina/sangue , Adulto , Grupo com Ancestrais do Continente Asiático/psicologia , Biomarcadores/sangue , Glicemia/análise , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Jejum/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Interleucina-6/sangue , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Adulto Jovem
18.
J Nutr ; 149(2): 286-294, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590589

RESUMO

BACKGROUND: The dietary insulin index (II) directly quantifies dietary effects on postprandial insulin secretion, whereas the empirical dietary index for hyperinsulinemia (EDIH), based on fasting C-peptide concentrations, is primarily reflective of insulin resistance. How these scores are related to nonfasting C-peptide in cohort studies has not been examined. OBJECTIVE: We investigated the extent to which EDIH and II scores predict plasma C-peptide concentrations, in cross-sectional analyses by postprandial duration at blood collection from 1 to ≥15 h. METHODS: Both EDIH and II scores were calculated from food-frequency questionnaire data reported by 3964 men in the Health Professionals Follow-up Study (1993-1995) and 6215 women in the Nurses' Health Study (1989-1990) who were not diabetic. We constructed 12 multivariable-adjusted linear regression models separately in men and women, by postprandial duration, to calculate relative differences and absolute values of plasma C-peptide concentrations in dietary index quintiles. RESULTS: In both men and women, C-peptide concentrations were elevated 1-2 h after eating and declined with increasing postprandial duration. In men, percent differences in C-peptide concentration in the highest compared with lowest dietary index quintile were: EDIH: 0-1 h: 50%; 2 h: 22%; 14 h: 14%; ≥15 h: 30% (all P-trend< 0.05). II: 0-1 h: 19% (P-trend = 0.09); 2 h: 3% (P-trend = 0.09); 14 h: -6% (P-trend = 0.17); ≥15 h: -15% (P-trend = 0.02). Corresponding results among women were: EDIH: 0-1 h: 29% (P-trend = 0.002); 2 h: 33% (P-trend = 0.009); 14 h: 44% (P-trend < 0.0001); ≥15 h: 40% (P-trend < 0.0001). II: 0-1 h: -12% (P-trend = 0.09); 2 h: 17% (P-trend = 0.09); 14 h: -14% (P-trend = 0.009); ≥15 h: -3% (P-trend = 0.37). CONCLUSION: The EDIH was superior to the II in predicting both fasting and nonfasting C-peptide concentrations, suggesting that the EDIH may be better in assessing dietary effects of hyperinsulinemia on disease risk in adult men and women.


Assuntos
Peptídeo C/sangue , Insulina/metabolismo , Período Pós-Prandial , Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso
19.
Diabetes Care ; 42(2): 258-264, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30530850

RESUMO

OBJECTIVE: Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin. RESEARCH DESIGN AND METHODS: C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) C-peptide positive, with high stimulated values ≥0.2 nmol/L; 2) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and 3) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide-positive subjects with diabetes after 1, 2, and 4 years. RESULTS: Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L; n = 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide. CONCLUSIONS: In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Proinsulina/metabolismo , Adolescente , Adulto , Peptídeo C/sangue , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Jejum/metabolismo , Feminino , Humanos , Insulina/sangue , Masculino , Refeições , Pessoa de Meia-Idade , Proinsulina/sangue , Fatores de Tempo , Adulto Jovem
20.
Diabetes Obes Metab ; 21(1): 95-102, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30073765

RESUMO

AIM: To evaluate whether ß cells continue to undergo death in the later stages of type 1 diabetes (T1D). MATERIALS AND METHODS: Fasting banked sera from a cross-section of 90 participants in the T1D Exchange Registry with longstanding T1D (median duration of 9 years) were analysed. Subjects were determined to be C-peptide (-) or (+) based on mixed-meal tolerance testing. Results were compared with 54 adult non-diabetic controls. Stimulated samples were assayed in a subset of subjects. Levels of unmethylated and methylated preproinsulin (INS) DNA were analysed using digital droplet PCR. RESULTS: Fasting and stimulated circulating unmethylated INS DNA levels were increased among both C-peptide (-) and C-peptide (+) subjects with longstanding T1D compared with non-diabetic controls (P < 0.01). Consistent with prior reports, unmethylated INS DNA values correlated with methylated INS DNA values, which were also elevated among T1D subjects (P < 0.001). There was wide variation in the effects of mixed-meal stimulation on DNA levels, with fasting values in the highest quartiles decreasing with stimulation (P < 0.05). CONCLUSIONS: These results could reflect ongoing ß cell death in individuals with longstanding T1D, even in the absence of detectable C-peptide production, suggesting that therapies targeting ß cell survival could be beneficial among individuals with longstanding T1D.


Assuntos
DNA , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Insulina , Precursores de Proteínas , Adulto , Peptídeo C/sangue , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Metilação de DNA , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Insulina/sangue , Insulina/genética , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas/sangue , Precursores de Proteínas/genética , Adulto Jovem
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